<?xml version="1.0" encoding="UTF-8"?>
<feed xml:lang="en" xmlns="http://www.w3.org/2005/Atom" xmlns:opensearch="http://a9.com/-/spec/opensearch/1.1/" xmlns:s="http://jadedpixel.com/-/spec/shopify">
  <id>https://comparativeguide.com/blogs/news.atom</id>
  <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news"/>
  <link rel="self" type="application/atom+xml" href="https://comparativeguide.com/blogs/news.atom"/>
  <title>NutriSearch - Supplements in the News</title>
  <updated>2026-03-24T14:13:00-07:00</updated>
  <author>
    <name>NutriSearch</name>
  </author>
  <entry>
    <id>https://comparativeguide.com/blogs/news/protective-vitamin-shots-for-newborns-on-decline</id>
    <published>2026-03-24T14:13:00-07:00</published>
    <updated>2026-03-24T14:14:38-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/protective-vitamin-shots-for-newborns-on-decline"/>
    <title>Protective vitamin shots for newborns on decline</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<div style="width: fit-content;">
<p style="padding: 0.5rem; border-top: 3px solid darkblue; border-bottom: 1px solid darkblue;">from National Institutes of Health Research Matters<br>January 13, 2026</p>
</div>
<div style="padding: 1rem; margin-top:3rem; margin-bottom: 1rem; background-color: #ffebcd; 2%; border-left: 2rem solid #F4A460;">
<h2>At a Glance</h2>
<ul>
<li>An analysis of more than 5 million births nationwide identified an ongoing drop in newborns receiving a vitamin shot that helps to prevent dangerous bleeding.</li>
<li>Further analysis is needed to determine the reasons behind this decline in a preventive treatment for newborns.</li>
</ul>
</div>
<p>Babies at birth lack an important substance called vitamin K. This vitamin doesn’t readily pass from mother to child via the placenta. And breast milk contains only small amounts. Babies need vitamin K because it helps the body form blood clots that stop bleeding. When blood does not clot well, small injuries such as a bruise can continue bleeding much longer than normal. Lack of vitamin K puts infants at risk of bleeding in the brain and throughout the body during the first six months of life. Although this bleeding condition is rare, it can be severe and even deadly.</p>
<p>In the 1960s, the U.S. began to routinely give newborns a single vitamin K shot into the thigh muscle. Injections of the nutrient are preferred over oral delivery, because a baby’s developing gut can’t readily absorb vitamin K. The vitamin shots essentially eliminated cases of bleeding from vitamin K deficiency nationwide. But in recent years some small studies have found evidence that more U.S. parents may be refusing vitamin K shots for their newborns.</p>
<p>An NIH-supported research team decided to take a broader look at the use of vitamin K shots. Led by Dr. Kristan Scott of the Children’s Hospital of Philadelphia, the scientists analyzed information from a nationwide database of electronic health records. They focused on babies born during the eight-year period from January 2017 to December 2024. Their analysis included data from 403 hospitals across all 50 states and the District of Columbia. Results were reported in JAMA on December 8, 2025.</p>
<p>Of the more than 5 million newborns included in the analysis, the researchers found that almost 200,000 (3.92%) did not receive the vitamin K shot. Over time, the number of babies that did not receive the shot rose from 2.92% in 2017 to 5.18% in 2024. That’s a 77% increase in infants not receiving the shot over the eight-year period.</p>
<p>In assessing other traits of newborns, the team found that non-Hispanic White newborns were most likely not to receive the vitamin shot (4.3%). In contrast, only 3.4% of non-Hispanic Black and 3.3 of Hispanic newborns didn’t receive the shot. Babies born via vaginal delivery were also more likely not to receive the vitamin K shot (4.2%) compared to those born via caesarean delivery (3.2%).</p>
<p>The researchers note that the available data could not distinguish the reasons behind the decline in vitamin K shots. But based on previous studies, they suggest that parent refusal is likely a significant factor. The scientists also note that further study is needed to determine if this trend leads to an uptick in serious health problems for newborns.</p>
<p>“There may be a growing perception among parents that vitamin K is unnecessary,” Scott says. “Unfortunately, opting out of vitamin K for a newborn is akin to gambling with a child’s health, forgoing a straightforward and safe measure that effectively prevents severe complications.”</p>
<h2>References</h2>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/41359326/">Trends in Vitamin K Administration Among Infants.</a> Scott K, Miller E, Culhane JF, Greenspan J, Handley SC, Lo JY, Knake LA, McKenney KM, Burris HH, Dysart K. <em>JAMA.</em> 2025 Dec 8:e2521460. doi: 10.1001/jama.2025.21460. Online ahead of print. PMID: 41359326.</p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/why-vitamin-d-fails-to-rise-in-many-people-new-evidence-and-how-orthomolecular-medicine-solves-it</id>
    <published>2025-12-10T16:21:49-08:00</published>
    <updated>2025-12-10T16:21:55-08:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/why-vitamin-d-fails-to-rise-in-many-people-new-evidence-and-how-orthomolecular-medicine-solves-it"/>
    <title>Why Vitamin D Fails to Rise in Many People: New Evidence - and How Orthomolecular Medicine Solves It</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p style="font-size: large; font-weight: 600;">FOR IMMEDIATE RELEASE<br>Orthomolecular Medicine News Service, December 7, 2025</p>
<p><span class="author-byline" style="padding: 0.25rem; border-top: #3c7680 solid; border-bottom: #3c7680 solid; border-bottom-width: 1px; line-height: 2rem;">by Richard Z. Cheng, M.D., Ph.D.</span><br><span style="font-size: small;">Editor-in-Chief, </span><span style="font-size: small; font-style: italic;">Orthomolecular Medicine News Service</span></p>
<h2>Introduction</h2>
<p>Millions of people take Vitamin D or spend time in the sun, yet their blood Vitamin D levels barely improve. Others supplement modestly and reach optimal levels quickly.</p>
<p>This long-standing clinical puzzle is finally gaining scientific clarity.</p>
<p>A major 2025 Nature Communications study [1] identified over 160 genetic variants that affect Vitamin D status. Combined with research on micronutrient cofactors, metabolic health, and inflammation, the evidence points to a key conclusion:</p>
<p style="font-weight: 600;">Vitamin D deficiency is rarely a "single-nutrient problem." It is a systems-biology problem.</p>
<p>Orthomolecular Medicine offers a complete solution.</p>
<hr>
<h2>1. Genetics Explains Why People Respond So Differently</h2>
<p>Shraim et al. (Nature Communications, 2025) [1] found 162 variants affecting:</p>
<ul>
<li>UVB → Vitamin D production in skin</li>
<li>Liver conversion (25-hydroxylase)</li>
<li>Kidney conversion (1α-hydroxylase)</li>
<li>Vitamin D binding protein</li>
<li>Vitamin D receptor (VDR) sensitivity</li>
</ul>
<p style="font-weight: 600;">Implications:</p>
<ul>
<li>Two individuals taking the same dose can have vastly different blood levels.</li>
<li>Some people require higher intake to reach physiological levels.</li>
<li>Genetics sets the baseline - but genes alone do not determine outcomes.</li>
</ul>
<p>Genetics sets the baseline - but genes are not the full story.</p>
<hr>
<h2>2. "Vitamin D Resistance": The Missing Diagnosis</h2>
<p>In my 2024 OMNS review, I proposed that many individuals exhibit acquired Vitamin D resistance [2]:</p>
<p>Vitamin D is present, but cannot activate or function properly.</p>
<p>Drivers include:</p>
<ul>
<li>Chronic inflammation</li>
<li>High cortisol and chronic stress</li>
<li>Circadian disruption</li>
<li>Fatty liver and insulin resistance</li>
<li>Leaky gut &amp; dysbiosis</li>
<li>Environmental toxins</li>
<li>Cofactor deficiencies (Mg, C, K<sub>2</sub>, B vitamins, Zn, Se)</li>
</ul>
<p>This explains why many people experience: "Vitamin D doesn't work for me."</p>
<p>The problem is not the Vitamin D - it is the <strong>internal metabolic environment.</strong></p>
<hr>
<h2>3. Vitamin D Needs Its Team: The Essential Cofactors</h2>
<p>Vitamin D metabolism and receptor activity depend on:</p>
<ul>
<li>
<strong>Magnesium</strong> - enzymatic activation</li>
<li>
<strong>Vitamin K<sub>2</sub></strong> - directs calcium into bone</li>
<li>
<strong>Vitamin C</strong> - modulates inflammation &amp; steroid hormone pathways</li>
<li>
<strong>B Vitamins</strong> - methylation &amp; energy metabolism</li>
<li>
<strong>Zinc &amp; Selenium</strong> - antioxidant &amp; immune regulation</li>
<li>
<strong>Omega-3s</strong> - membrane function &amp; inflammation balance</li>
</ul>
<p>Without these cofactors, functional Vitamin D deficiency develops - even with "normal" blood levels.</p>
<p style="font-size: large; font-weight: 600; font-style: italic;">General Cofactor Ranges</p>
<p style="font-style: italic;">(Individual needs vary, but the following ranges apply to most adults.)</p>
<ul>
<li>
<strong>Magnesium:</strong> 200-400 mg/day</li>
<li>
<strong>Vitamin K<sub>2</sub> MK-7:</strong> 90-200 mcg/day</li>
<li>
<strong>Vitamin C:</strong> 1,000-3,000 mg/day</li>
<li>
<strong>Zinc:</strong> 15-30 mg/day</li>
<li>
<strong>Selenium:</strong> 100-200 mcg/day</li>
<li>
<strong>Omega-3s (EPA &amp; DHA):</strong> 1-2 g/day</li>
</ul>
<p>This is a core principle of Orthomolecular Medicine.</p>
<hr>
<h2>4. How Much Vitamin D Is Safe? The Evidence Is Clear</h2>
<p style="font-weight: 600;">Optimal Range</p>
<ul>
<li>40-80 ng/mL (100-200 nmol/L)</li>
</ul>
<p style="font-weight: 600;">Safety Profile</p>
<p>VITAL (2,000 IU/day) and ViDA (monthly 100,000 IU) trials:</p>
<ul>
<li>No increase in hypercalcemia</li>
<li>No increase in kidney stones</li>
<li>Toxicity rare below 150 ng/mL</li>
<li>Real toxicity occurs only &gt;200 ng/mL</li>
</ul>
<p style="font-weight: 600;">Vitamin D remains one of the safest nutrients in modern medicine.</p>
<hr>
<h2>5. A Real-World Case: When Higher Doses Are Necessary</h2>
<h3>Case 1: Husband-Wife GrassrootsHealth Cohort</h3>
<p>A woman maintained 40-60 ng/mL on 2,000 IU/day.</p>
<p>Her husband, a Type 2 diabetic, taking the same amount:</p>
<ul>
<li>Could not surpass 20 ng/mL</li>
<li>Needed 10× her dose to reach 30-40 ng/mL</li>
</ul>
<p><strong>Lesson:</strong> metabolic inflammation and genetics radically alter dose requirements.</p>
<p>Some individuals - particularly those with inflammation, obesity, or genetic variations - simply require higher doses.</p>
<h3>Case 2: High-Dose Individual</h3>
<p>A man in his 60s took 30,000 IU/day for 30 days.</p>
<p>Follow-up:</p>
<ul>
<li>25(OH)D = 118 ng/mL</li>
<li>No hypercalcemia</li>
<li>Clinical improvements noted</li>
</ul>
<p>This is within the <strong>low-risk / high-benefit</strong> zone repeatedly documented in large cohorts.</p>
<h3>Case 3: Severe Hypercalcemia and Renal Impairment Induced by Prolonged High-Dose Vitamin D3 Supplementation</h3>
<p>A 23-year-old previously healthy male had been taking high-dose vitamin D3 (50,000 IU daily) for several consecutive months, along with a multivitamin supplement containing calcium. He subsequently developed biochemical evidence of severe vitamin D intoxication. He was then referred to me.</p>
<ul>
<li>Serum 25(OH)D3 &gt; 200 ng/mL (markedly elevated)</li>
<li>Serum calcium 4.0 mmol/L (severe hypercalcemia)</li>
<li>Parathyroid hormone suppressed to 8.63 pg/mL (PTH suppression consistent with vitamin D toxicity)</li>
<li>Serum creatinine increased to 202 µmol/L</li>
<li>eGFR decreased to 39 mL/min/1.73 m² (acute kidney injury)</li>
</ul>
<p>This case illustrates the <strong>potential dangers of unsupervised high-dose vitamin D supplementation</strong>, especially when <strong>combined with exogenous calcium</strong>, leading to life-threatening hypercalcemia and renal impairment.</p>
<hr>
<h2>6. Lifestyle &amp; Endocrine Factors Are Integral</h2>
<p>Vitamin D status is influenced by:</p>
<ul>
<li>Sunlight &amp; circadian rhythm</li>
<li>Physical activity</li>
<li>Cortisol &amp; stress</li>
<li>Liver &amp; kidney function</li>
<li>Microbiome health</li>
<li>Toxic load</li>
<li>Other micronutrients sufficiency</li>
</ul>
<p>These factors align with the Orthomolecular view that <strong> nutrients do not work alone - they function within the body's entire biochemical network. </strong></p>
<hr>
<h2>7. Practical Orthomolecular Recommendations</h2>
<ol style="font-weight: 600;">
<li>Test Beyond 25(OH)D
<ul style="font-weight: normal;">
<li>Include PTH, calcium, phosphorus, magnesium, CRP, liver markers.</li>
</ul>
</li>
<li>Individualize the dose
<ul style="font-weight: normal;">
<li>Typical effective ranges:
<ul>
<li>5,000 IU/day</li>
<li>10,000 IU/day</li>
<li>Short-term high-dose therapy for resistant cases</li>
</ul>
</li>
</ul>
</li>
<li>Always include cofactors
<ul style="font-weight: normal;">
<li>Magnesium, K<sub>2</sub>, C, zinc, selenium.</li>
</ul>
</li>
<li>Improve lifestyle factors
<ul style="font-weight: normal;">
<li>Sunlight, gut repair, detoxification, stress reduction.</li>
</ul>
</li>
<li>Recheck levels every 3-6 months</li>
</ol>
<hr>
<h2>Conclusion</h2>
<p>Vitamin D is not simply "take a pill and your level rises."</p>
<p>It reflects a complex integration of:<br>Genes × Sunlight × Micronutrients × Metabolism × Inflammation × Endocrine Health = Necessity of a Personalized Dose</p>
<p>Orthomolecular Medicine restores the entire biochemical terrain - enabling Vitamin D to function as intended.</p>
<h2>8. This Is One More Example of the Root-Cause Model of Chronic Disease</h2>
<p>Vitamin D resistance is not an isolated phenomenon.</p>
<p>It exemplifies a deeper truth: Chronic diseases arise from disruptions across multiple root drivers - genetic, metabolic, inflammatory, toxic, nutritional, and endocrine.</p>
<p>As I detailed in:<br><strong>Cheng, R. Z. From Mutation to Metabolism: Root Cause Analysis of Cancer's Initiating Drivers [13],</strong> <br>health and disease are determined not by a single molecule (like vitamin C or D) or a single mechanism (like mitochondrial dysfunction or gut dysbiosis), but by the <em>interconnected matrix</em> of:</p>
<ul>
<li>Environmental toxin exposures</li>
<li>Chronic infections</li>
<li>Micronutrients</li>
<li>Cellular metabolism</li>
<li>Oxidative stress</li>
<li>Mitochondrial function</li>
<li>Hormonal regulation</li>
<li>Immune resilience</li>
</ul>
<p>Vitamin D resistance is simply one more illustration of this unifying principle:</p>
<p>To restore health, we must identify and correct as many root drivers as possible - not chase downstream symptoms or the mechanism between root drivers and clinical diseases.</p>
<p>Orthomolecular Medicine is the framework that recognizes and addresses these root drivers systematically.</p>
<div style="padding: 0.25rem; border-top: #3c7680 solid; border-bottom: #3c7680 solid; border-bottom-width: 1px;">
<h2>About the Author</h2>
<p>Richard Z. Cheng, M.D., Ph.D. is Editor-in-Chief of the <em>Orthomolecular Medicine News Service</em>. He is a U.S.-based, NIH-trained, board-certified physician specializing in integrative oncology, orthomolecular medicine, and metabolic/functional medicine, with clinical practices in both the United States and China.</p>
<p>Dr. Cheng is a Hall of Fame inductee of the International Society for Orthomolecular Medicine and a Fellow of the American Academy of Anti-Aging and Regenerative Medicine (A4M). He has been active in advancing nutrition-based, root-cause approaches to chronic disease, co-founding the China Low Carb Medicine Alliance and serving as an expert reviewer for the South Carolina Board of Medical Examiners.</p>
<p>He is the author of the forthcoming book <em>21st Century Medicine: Integrative Orthomolecular Medicine for Chronic Disease Reversal and Longevity</em>, which summarizes insights from five decades of clinical practice and research.</p>
<p><em>More of Dr. Cheng's writings are available at:</em> <a href="https://substack.com/@rzchengmd">https://substack.com/@rzchengmd</a></p>
</div>
<h2>References</h2>
<ol>
<li>Shraim, R.; Timofeeva, M.; Wyse, C.; Geffen, J. van; Weele, M. van; Romero-Ortuno, R.; Lopez, L.M.; Kleber, M.E.; Pilz, S.; März, W.; Fletcher, B.S.; Wilson, J.F.; Theodoratou, E.; Dunlop, M.G.; McManus, R.; Zgaga, L. Genome-Wide Gene-Environment Interaction Study Uncovers 162 Vitamin D Status Variants Using a Precise Ambient UVB Measure. <em>Nat Commun</em> 2025, 16, (1), 10774. DOI: 10.1038/s41467-025-65820-x.</li>
<li>Cheng, R.Z. Understanding and Addressing Vitamin D Resistance: A Comprehensive Approach Integrating Genetic, Environmental, and Nutritional Factors. <em>Orthomolecular Medicine News Service</em> 2024, 20, (13).; Available online: <a href="https://orthomolecular.org/resources/omns/v20n13.shtml">https://orthomolecular.org/resources/omns/v20n13.shtml</a>.</li>
<li>Manson, J.E.; Cook, N.R.; Lee, I.-M.; Christen, W.; Bassuk, S.S.; Mora, S.; Gibson, H.; Gordon, D.; Copeland, T.; D'Agostino, D.; Friedenberg, G.; Ridge, C.; Bubes, V.; Giovannucci, E.L.; Willett, W.C.; Buring, J.E.; VITAL Research Group Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. <em>N Engl J Med</em> 2019, 380, (1), 33-44. DOI: 10.1056/NEJMoa1809944.</li>
<li>Garland, C.F.; Kim, J.J.; Mohr, S.B.; Gorham, E.D.; Grant, W.B.; Giovannucci, E.L.; Baggerly, L.; Hofflich, H.; Ramsdell, J.W.; Zeng, K.; Heaney, R.P. Meta-Analysis of All-Cause Mortality According to Serum 25-Hydroxyvitamin D. <em>Am J Public Health</em> 2014, 104, (8), e43-50. DOI: 10.2105/AJPH.2014.302034.</li>
<li>McDonnell, S.L.; Baggerly, C.; French, C.B.; Baggerly, L.L.; Garland, C.F.; Gorham, E.D.; Lappe, J.M.; Heaney, R.P. Serum 25-Hydroxyvitamin D Concentrations ≥40 Ng/Ml Are Associated with &gt;65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. <em>PLoS One</em> 2016, 11, (4), e0152441. DOI: 10.1371/journal.pone.0152441.</li>
<li>Vieth, R. Vitamin D Toxicity, Policy, and Science. <em>J Bone Miner Res</em> 2007, 22 Suppl 2, V64-68. DOI: 10.1359/jbmr.07s221.</li>
<li>Vieth, R. Vitamin D Supplementation, 25-Hydroxyvitamin D Concentrations, and Safety. <em>Am J Clin Nutr</em> 1999, 69, (5), 842-856. DOI: 10.1093/ajcn/69.5.842.</li>
<li>Demay, M.B.; Pittas, A.G.; Bikle, D.D.; Diab, D.L.; Kiely, M.E.; Lazaretti-Castro, M.; Lips, P.; Mitchell, D.M.; Murad, M.H.; Powers, S.; Rao, S.D.; Scragg, R.; Tayek, J.A.; Valent, A.M.; Walsh, J.M.E.; McCartney, C.R. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. <em>J Clin Endocrinol Metab </em> 2024, 109, (8), 1907-1947. DOI: 10.1210/clinem/dgae290.</li>
<li>Are You Vitamin D Deficient? Available online: <a href="https://www.grassrootshealth.net/project/daction/">https://www.grassrootshealth.net/project/daction/</a> (accessed 3 December 2025).</li>
<li>McDonnell, S.L.; Baggerly, C.; French, C.B.; Baggerly, L.L.; Garland, C.F.; Gorham, E.D.; Lappe, J.M.; Heaney, R.P. Serum 25-Hydroxyvitamin D Concentrations ≥40 Ng/Ml Are Associated with &gt;65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. <em>PLoS One</em> 2016, 11, (4), e0152441. DOI: 10.1371/journal.pone.0152441.</li>
<li>Chowdhury, R.; Kunutsor, S.; Vitezova, A.; Oliver-Williams, C.; Chowdhury, S.; Kiefte-de-Jong, J.C.; Khan, H.; Baena, C.P.; Prabhakaran, D.; Hoshen, M.B.; Feldman, B.S.; Pan, A.; Johnson, L.; Crowe, F.; Hu, F.B.; Franco, O.H. Vitamin D and Risk of Cause Specific Death: Systematic Review and Meta-Analysis of Observational Cohort and Randomised Intervention Studies. <em>BMJ</em> 2014, 348, g1903. DOI: 10.1136/bmj.g1903.</li>
<li>Holick, M.F.; Binkley, N.C.; Bischoff-Ferrari, H.A.; Gordon, C.M.; Hanley, D.A.; Heaney, R.P.; Murad, M.H.; Weaver, C.M.; Endocrine Society Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline. <em>J Clin Endocrinol Metab</em> 2011, 96, (7), 1911-1930. DOI: 10.1210/jc.2011-0385.</li>
<li>Cheng, R.Z. From Mutation to Metabolism: Root Cause Analysis of Cancer's Initiating Drivers. 2025. DOI: 10.20944/preprints202509.0903.v1; Available online: <a href="https://www.preprints.org/manuscript/202509.0903/v1">https://www.preprints.org/manuscript/202509.0903/v1</a>.</li>
</ol>
<p style="font-size: small; text-align: center;">OMNS free subscription <a href="http://orthomolecular.org/subscribe.html">http://orthomolecular.org/subscribe.html</a><br>OMNS archive link: <a href="http://orthomolecular.org/resources/omns/index.shtml">http://orthomolecular.org/resources/omns/index.shtml</a></p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/all-about-cholesterol-1</id>
    <published>2025-11-17T06:00:05-08:00</published>
    <updated>2025-11-17T06:00:05-08:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/all-about-cholesterol-1"/>
    <title>All About Cholesterol</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p class="article-info" style="font-size: large; font-style:italic;">
    Explained</p>
<p class="article-subhead">The latest science on how blood levels of HDL, LDL and more relate to cardiovascular health
</p>
<p class="article-byline" style="margin: 1rem auto 1rem 1rem;">
    <span class="author-byline" style="padding:0.25rem; border-top:#3c7680 solid; border-bottom:#3c7680 solid; border-bottom-width: 1px;">By
        Amber Dance</span>
    <br><br>
    <span class="pub-date">02.14.2024<span>
</span></span></p>
<div class="article-content">
    <div class="article-text -drop-cap">
        <p><span style="float: left; font-family: Georgia, serif; font-size: 3rem; line-height:1; margin-right: 0.1em; font-weight: bold;">W</span>hen
            C. Michael Gibson of Boston saw his doctor in the spring of 2023, the blood test results were confusing.
            His cholesterol levels were decent — he was already taking statins to keep the “bad” cholesterol low — but
            the arteries delivering blood to his heart were nonetheless crammed with dangerous plaque. “It didn’t make
            sense,” says Gibson, himself a cardiologist at Beth Israel Deaconess Medical Center.</p>
        <p>So Gibson asked his physician to check his blood for a specific kind of cholesterol called lipoprotein(a).
            And there was the explanation: He had more than double the normal amount of that cholesterol. Gibson turned
            out to be one of the unlucky people who has inherited a predisposition toward high lipoprotein(a) levels; he
            suspects that his grandfather, who died of a heart attack at age 45, had it too.</p>
        <p>About one in five people have this unfortunate heritage, and there’s nothing they can do to combat it — but
            soon that might change. Scientists are researching medications that can lower lipoprotein(a), as well as
            other approaches that could slash the risk of <a href="https://knowablemagazine.org/content/article/health-disease/2024/polygenic-risk-score-genes-heart-disease-cancer-coming-to-clinic">cardiovascular
                disease</a> more than drugs like statins can.</p>
        <p>Statins, approved in the late 1980s to lower levels of low-density lipoprotein (LDL) cholesterol, have been a
            lifesaving tool: They cut risk of heart attack and stroke by up to 50 percent for the more than 200 million
            people globally who take the medications. Yet even statin takers still get heart disease, and some still
            die. Cardiovascular disease remains the leading cause of death in the United States and <a href="https://knowablemagazine.org/content/article/health-disease/2018/finlands-bold-push-change-heart-health-nation">across
                the world</a>. Clearly, something’s been missing from the cholesterol picture.</p>
        <p>The picture coming into focus today incorporates not just bad, LDL cholesterol and good, high-density
            lipoprotein (HDL) cholesterol, but also lipoprotein(a) and a poorly understood substance called “remnant
            cholesterol.” Medical researchers aim to minimize all of these except HDL. And HDL cholesterol itself,
            though it’s still understood to be beneficial, has turned out to be more complex than anticipated. Various
            attempts to raise HDL levels haven’t improved people’s health beyond what statins already achieve.</p>
        <p>Yet despite this and other disappointments in which medicines haven’t panned out as expected, many
            researchers feel optimistic about treatments currently in clinical trials. “It’s really an exciting time,”
            says Stephen Nicholls, a cardiologist at Monash Health in Melbourne, Australia.</p>
        <div class="article-image -caption-full"></div>
        <h2>LDL cholesterol</h2>
        <p>Though it gets a bad rap among the health-conscious, cholesterol plays important roles in our body: It helps
            to control the stability and fluidity of cell membranes and is an important starting ingredient for making
            hormones such as testosterone and estrogen. What matters for our health is the company that the cholesterol
            molecule keeps when it travels.</p>
        <p>Its waxy nature means it can’t mix well with water, so it can’t pass through the bloodstream on its own: Lone
            cholesterol molecules would separate out, like oil does in water. Cholesterol’s solution is to join up with
            complexes of proteins and fats, called lipoproteins, that carry it around. These lipoprotein carriers
            include LDL, HDL and other types. Cholesterol, in addition to being cargo, is a structural part of these
            carriers, too.</p>
        <p>Lipoproteins are made in the gut and <a href="https://knowablemagazine.org/content/article/health-disease/2018/invisible-liver-disease-balloons-view">liver</a>,
            and they deliver cholesterol and fat to body tissues. Fat goes to muscles, to be used for energy, or to fat
            tissue for storage. Cholesterol is dropped off in tissues to be incorporated into cell membranes or made
            into hormones. Cholesterol can also be returned to the liver where it can be stored, incorporated into new
            lipoproteins, turned into bile acids used by the digestive system to break down fats, or sent to be
            excreted.</p>
        <p>When the delivery particles from the liver have dropped off most of their fats, they become LDL particles,
            which are still jam-packed with cholesterol. The problem happens when these LDL particles, instead of
            returning to the liver to be recycled, squeeze into blood vessel walls and get chemically modified. There,
            they incite or exacerbate an immune reaction called inflammation. In response, immune cells come in to eat
            LDL particles — but if they eat too much, they can get stuck in the blood vessel wall. This forms the
            beginnings of an atherosclerotic plaque.</p>
        <p>Over time, that plaque accumulates more cholesterol, more fat and more immune cells, reducing the space
            through which blood can flow and deliver oxygen to tissues. If a plaque limits blood supply to the heart, it
            might cause chest pain called angina. A plaque might also lead to formation of a blood clot, which may break
            off and clog vessels elsewhere. The clot might cause a stroke in the <a href="https://knowablemagazine.org/content/article/mind/2022/mapping-brain-understand-mind">brain</a>,
            for example, or a heart attack.</p>
        <p>Today, it’s clear that the less LDL cholesterol in the bloodstream, the better. Statins are good at achieving
            this, cutting LDL cholesterol levels by up to about half. And for those who need a bigger effect, or who
            can’t tolerate statins (muscle pain or weakness is an occasional side effect), there are newer medicines.
            “We now have the ability to get almost anyone’s LDL cholesterol down into the range that we would consider
            appropriate,” says Steven Nissen, a cardiologist at the Cleveland Clinic in Ohio.</p>
        <div class="article-image -caption-full"></div>
        <h2>Lipoprotein(a)</h2>
        <p>But these LDL-cholesterol treatments generally don’t do much against levels of lipoprotein(a), pronounced
            “lipoprotein-little-a.” This substance, composed of LDL cholesterol particles plus an extra protein,
            apolipoprotein(a), is mysterious: Scientists don’t know what its natural job is, though since
            apolipoprotein(a) has some similarity to a protein involved in blood clotting, it <a href="https://www.jlr.org/article/S0022-2275(20)34568-5/fulltext">might have a role in wound
                healing</a>. But it can’t be all that important to animal survival: Weirdly, the gene that carries
            instructions for making apolipoprotein(a) is found <a href="https://www.pnas.org/doi/abs/10.1073/pnas.94.22.11992">only in certain primates</a>. (A similar
            gene evolved in hedgehogs.)</p>
        <p>It’s also unclear why lipoprotein(a) is such a bad version of cholesterol, but it’s clearly up to no good
            much of the time. It delivers cholesterol to the blood vessel walls like LDL does, promotes blood clotting
            that blocks arteries and can cause inflammation and increase the risk of clots. And if your lipoprotein(a)
            is high — too bad. “Statins won’t get it down,” laments Gibson. “Exercise doesn’t get it down. Diet doesn’t
            get it down.”</p>
        <p>Some of the newer LDL cholesterol-lowering drugs <a href="https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037184">can reduce lipoprotein(a)</a>
            cholesterol a bit, but probably not enough to significantly reduce cardiovascular risk, says Anand Rohatgi,
            a cardiologist at the University of Texas Southwestern Medical Center in Dallas. The only thing physicians
            can do, in extreme cases, is to regularly administer a blood-cleaning procedure called apheresis to remove
            lipoprotein(a).</p>
        <div class="article-image -caption-center"></div>
        <p>For a long time, doctors ignored lipoprotein(a). “Nobody measured it, because you could not do anything about
            it,” says Prakriti Gaba, a cardiologist at Brigham and Women’s Hospital in Boston. That may be about to
            change now that several groups are testing medicines that target the substance. (Gaba got her own levels
            checked at a cardiology conference, where booths offering free tests have sprung up recently.)</p>
        <p>Many of these experimental medications use genetic technology to silence the apolipoprotein(a) gene. In a
            handful of small studies, involving dozens to a few hundred subjects each, different
            apolipoprotein(a)-silencing therapies cut lipoprotein(a) levels <a href="https://www.sciencedirect.com/science/article/pii/S073510972100259X">by varying levels, from no
                change up to 92 percent</a>. But it isn’t yet known whether cutting lipoprotein(a) will actually reduce
            cardiovascular problems. “We won’t know for a while,” says Leslie Cho, a cardiologist at the Cleveland
            Clinic who’s coleading one of the trials.</p>
        <p>Cho’s HORIZON study, the farthest along, is testing a lipoprotein(a)-gene-silencing treatment compared to a
            <a href="https://knowablemagazine.org/content/article/mind/2023/how-placebo-effect-went-mainstream">placebo</a>
            in more than 8,300 people with high lipoprotein(a) and a history of heart problems such as heart attack or
            stroke. The hope is that reducing lipoprotein(a) will decrease the rate of heart attacks, strokes, need for
            a medical procedure to improve blood flow, and death, but HORIZON isn’t expected to have results <a href="https://classic.clinicaltrials.gov/ct2/show/NCT04023552">until 2025</a>. Another trial that Gaba
            is involved in, called OCEAN(a)-Outcomes, is <a href="https://clinicaltrials.gov/study/NCT05581303">testing
                a similar approach</a> in about 6,000 people, but is not expected to be completed until the end of 2026.
        </p>
        <h2>HDL cholesterol</h2>
        <p>Just as lipoprotein(a) and LDL cholesterol are known as the baddies, HDL cholesterol has long been considered
            a good guy. HDL particles are thought to help by sucking cholesterol out of plaques. The HDL then takes this
            cholesterol to the liver for recycling or disposal. It’s the cardiovascular system’s cholesterol “garbage
            truck,” says Bob Eckel, a retired cardiometabolic physician and professor emeritus at the University of
            Colorado Anschutz Medical Campus.</p>
        <p>If high levels of HDL cholesterol are good, scientists reasoned, then more of this cleanup crew should be
            even better. Exercising and weight loss can both raise HDL cholesterol. Scientists have tried to do the same
            with medications — but with <a href="https://academic.oup.com/eurjpc/article/26/5/533/5925680">disappointing
                results</a>. The drugs did raise HDL cholesterol levels, yes, but they didn’t save lives in people
            already on statins, and they were weaker than statins at stopping heart attacks and strokes.
            <strong>“</strong>To sum it up very simplistically, approaches to raise HDL failed. Nothing really worked,”
            says Anatol Kontush, a lipid biochemist at the Sorbonne University in Paris.
        </p>
        <div class="article-image -caption-full"></div>
        <p>It’s not entirely clear why raising HDL cholesterol in statin-takers bombed. It might be that the idea of
            boosting HDL cholesterol was simply wrong. High HDL cholesterol might be a marker for good cardiovascular
            health, rather than a direct cause of it, says Rohatgi. If so, artificially amplifying its levels wouldn’t
            help.</p>
        <p>But the problem also might have been an overly simplistic understanding of HDL cholesterol. Scientists now
            know that HDL comes in many types and can do many jobs. In addition to hoovering up cholesterol from
            plaques, it can fight inflammation — that’s good. But sometimes, HDL can turn bad and promote inflammation
            instead, Cho says, though it’s not clear how. And, she adds, people who are genetically wired to make too
            much HDL cholesterol can have an enhanced risk for heart disease.</p>
        <p>The problem, then, may be that various drugs meant to amplify HDL cholesterol focused on quantity over
            quality, and increased the wrong kind of HDL. For example, one promising category of drugs raised HDL levels
            by inhibiting an enzyme that transfers cholesterol away from HDL particles, giving it to LDL particles.
            Several studies found these inhibitors <a href="https://www.ahajournals.org/doi/10.1161/circresaha.117.311978">failed to improve heart health</a>.
            It might be that stopping the transfer of cholesterol away from HDL particles means the particles had less
            capacity to pick up new cholesterol from plaques, leaving the cholesterol to languish there. In other words,
            these garbage trucks were already full.</p>
        <p>So the new plan, a last-ditch effort to save lives with HDL, is to help HDL do its cholesterol-removal job
            better, rather than to just make more of it. Gibson, for example, is chairing a clinical trial of a medicine
            called CSL112. It’s made of the key protein component of HDL particles — that is, it’s the starting material
            for HDL particles but still empty of cholesterol. These CSL112 molecules seem to work by creating new HDL
            molecules <a href="https://academic.oup.com/ehjcvp/article/9/4/387/7036762">primed to pack in as much
                cholesterol as they can possibly hold</a>. In a preliminary study of more than 1,200 people, two-thirds
            of whom received CSL112 infusions, the treatment was safe. And when the scientists took blood samples for
            lab tests, they found that the higher the dose of CSL112 participants received, the more their blood <a href="https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.116.025687">was able to suck up
                cholesterol</a>.</p>
        <div class="article-image -caption-center"></div>
        <p>In another study called AEGIS-II, the researchers tested CSL112 infusions in a larger group of people who had
            just suffered a heart attack and could be most likely to benefit from treatment. Following <a href="https://classic.clinicaltrials.gov/ct2/show/NCT03473223">18,200 people for a year</a>, it asked
            whether CSL112 prevents second heart attacks, strokes and death in this population. “That’s a really big,
            definitive study, and if that doesn’t work, then I suspect the field will completely abandon HDL,” said
            Nicholls some months back.</p>
        <p>In mid-February, CSL of King of Prussia, Pennsylvania — CSL112’s makers — announced that the study <a href="https://www.prnewswire.com/news-releases/csl-announces-top-line-results-from-the-phase-3-aegis-ii-trial-evaluating-the-efficacy-and-safety-of-csl112-apolipoprotein-a-i-human-302059156.html">did
                not achieve its main goal of reducing major cardiac events</a> such as stroke, heart attack or death.
            The researchers are still analyzing the data and will present results in more depth at the American College
            of Cardiology conference in April.</p>
        <h2>Triglycerides</h2>
        <p>If the HDL waters seem murky, the situation with triglycerides, the fatty component of blood that’s carried
            around in lipoprotein particles, is muddier still. The amount a person has depends on lifestyle: <a href="https://knowablemagazine.org/content/article/health-disease/2017/balance-not-carbs-or-fat-key-healthy-eating">diet</a>,
            <a href="https://knowablemagazine.org/content/article/health-disease/2019/exercise-as-medicine">exercise</a>
            and so on. High triglycerides are <a href="https://www.sciencedirect.com/science/article/abs/pii/S0140673614611776">linked to a greater
                risk</a> for cardiovascular disease, and very high levels can lead to inflammation of the pancreas,
            known as pancreatitis. Thus, it made sense to posit that getting rid of triglycerides would be a healthy
            thing to do, and many studies <a href="https://academic.oup.com/edrv/article/40/2/537/5126386">have
                attempted just that</a> — with boggling results.
        </p>
        <div class="article-image -caption-center"></div>
        <p>One top candidate to reduce triglycerides is based on fish oil, which is high in the <a href="https://knowablemagazine.org/content/article/society/2025/uncovering-the-impact-of-artisanal-fisheries">omega-3
                fatty acids</a> eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Diets rich in fatty fish or
            omega-3s have long been linked to lower rates of cardiovascular problems. The fish or fish oil supplements
            are thought to work by cutting down on fat production by the liver.</p>
        <p>So, in a study called REDUCE-IT, researchers tested a highly purified derivative of EPA in more than 4,000
            people with cardiovascular disease or diabetes. They compared these patients to a similar number of people
            who received inert mineral oil as a placebo.</p>
        <p>At first glance, the results reported in 2019 looked “really spectacular,” says Nicholls, who wasn’t involved
            in the trial. In the group that had taken the EPA for about five years, risk of major cardiovascular
            problems or death <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1812792">dropped by 25 percent or
                more</a> compared to those getting a placebo. But oddly, this benefit came without a big reduction in
            the triglycerides themselves.</p>
        <p>In other words, “if EPA is working, it’s doing something other than lowering triglycerides,” says Kenneth
            Feingold, an endocrinologist and emeritus professor of medicine at the University of California, San
            Francisco. EPA might counter inflammation, for example, or stabilize the membranes of heart cells.</p>
        <p>Based on the REDUCE-IT results, the US Food and Drug Administration approved the purified EPA derivative in
            2019 as a medicine for people with high triglycerides and other <a href="https://knowablemagazine.org/content/article/health-disease/2024/why-isnt-dental-health-considered-primary-medical-care">cardiovascular
                risk factors</a>. But things got more confusing in 2020, when Nicholls, Nissen and colleagues published
            another trial, called STRENGTH. This study also aimed to lower triglycerides in high-risk patients, about
            6,500 of them, using EPA plus DHA. The researchers compared these patients to people who received a corn oil
            placebo. But the team halted their study early because, although triglyceride levels did fall, EPA plus DHA
            <a href="https://jamanetwork.com/journals/jama/article-abstract/2773120">didn’t seem to have any beneficial
                effect</a> on the rate of heart attack, stroke, hospitalization for heart problems, or death.
        </p>
        <p>Researchers are still debating why REDUCE-IT hit paydirt but STRENGTH faltered. Looking back at REDUCE-IT,
            some experts <a href="https://jamanetwork.com/journals/jamacardiology/article-abstract/2797283">see a
                problem with the mineral oil placebo</a> that was used. LDL cholesterol levels and signs of inflammation
            went up in that group — and if the control participants were worse off than if they’d received nothing at
            all, then their data would make the experimental treatment look better than it really is.</p>
        <p>But Gibson, who was part of the REDUCE-IT team, argues for a different explanation: that pure EPA is better
            than the EPA/DHA combo. And supporting REDUCE-IT’s conclusions, he points to an older, 1990s study that
            compared people taking EPA plus statins with people taking statins alone and also found <a href="https://www.thelancet.com/article/S0140-6736(07)60527-3/fulltext">fewer major coronary events</a>
            in the EPA group.</p>
        <p>Then, in 2022, came the latest blow to the once-promising idea of lowering triglycerides: the PROMINENT
            trial, in which Eckel and colleagues tested a drug called pemafibrate that reduces blood triglycerides. The
            10,000-plus study participants had type 2 diabetes, high triglycerides and low HDL, and were at risk for
            cardiovascular events. But even though triglyceride levels fell by about 26 percent, on average, in the
            group receiving the drug, this <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2210645">made no
                difference</a> to the rate of cardiovascular events.</p>
        <p>Taken together, the results suggest that triglycerides indicate poor cardiovascular health without being the
            reason behind the problem. “Triglycerides were just innocent bystanders,” concludes Eckel. The exception, he
            adds, might be people with very high triglycerides who are at risk of pancreatitis and might still benefit
            from triglyceride-lowering treatment.</p>
        <div id="newsletter-promo-item">
            <div class="newsletter-promo" style="background-color:#fff;border-top:4px solid #3c7680;border-bottom:1px solid #3c7680;">
                <div class="newsletter-promo-img" style="display: grid;"></div>
                <div class="newsletter-promo-content">
                    <p><strong>Stay in the Know</strong><br><a href="https://knowablemagazine.org/newsletter-signup" style="border-bottom:none;"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em>
                        newsletter today</p>
                </div>
            </div>
        </div>
        <h2>Remnant cholesterol</h2>
        <p>This is a loosely used term, with science still to be settled. In the doctor’s office, physicians assume that
            any cholesterol that isn’t HDL or LDL is a leftover or “remnant” fraction. From a molecular point of view,
            remnant cholesterol is a fat-delivering lipoprotein in an intermediate state: It left the liver, loaded with
            fat and cholesterol, and has dropped off some of its triglycerides in the body’s tissues, but not so much of
            its cargo that it’s become an LDL lipoprotein. Chylomicrons from the gut, once depleted of fats, also become
            remnant particles.</p>
        <p>In people with healthy metabolisms, the body quickly disposes of remnant particles. But if a person has a
            problem such as diabetes or obesity, these fatty remnants might stick around. Remnant cholesterol may <a href="https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.115.306249">accumulate in atherosclerotic
                plaques</a>, potentially making it <a href="https://journals.lww.com/co-lipidology/Abstract/2020/06000/Remnant_lipoproteins__are_they_equal_to_or_more.5.aspx">as
                dangerous as the classic bad LDL cholesterol</a>. Indeed, high levels of remnant cholesterol have been
            <a href="https://academic.oup.com/eurheartj/article/42/42/4324/6323611">linked to cardiovascular disease</a>
            in some studies, <a href="https://www.jacc.org/doi/abs/10.1016/j.jacc.2020.10.008">quite independently of
                patients’ LDL cholesterol measurements</a>. That suggests that getting rid of those remnants could be
            beneficial.
        </p>
        <p>The substances remain a bit of a black box, though. “We still don’t know precisely how to define them, we
            don’t know precisely how to measure them, so it’s kind of difficult to be precise about remnants,” says
            Feingold. Nonetheless, some researchers are interested in treatments that might target remnants in addition
            to, or instead of, triglycerides. For example, Nicholas Marston, a cardiologist at Brigham and Women’s, and
            colleagues are testing a medication called olezarsen that, he says, appears to promote clearance of the
            cholesterol-carrying particles. But it will take more study to learn if that translates into fewer
            cardiovascular problems.</p>
        <p>Remnant cholesterol is “probably important,” says Nissen — so even though the science is still nascent, he
            says he feels hopeful about the potential of treatments targeting it.</p>
        <p>In sum, the emerging picture is one in which certain forms of HDL cholesterol are good and all the other
            lipoproteins are bad. The best approach, experts suggest, may be to reduce all the non-HDL cholesterol —
            whether by diet and exercise or some of these new medicines, should they prove effective.</p>
        <p>“If it’s not HDL, we should minimize it,” says Feingold. “The lower, the better.”</p>
        <p><em>Editor’s note: This article was amended February 15, 2024, to add the preliminary results of the AEGIS-II
                trial aimed at raising levels of HDL and to remove a speculative quote about the ramifications of a
                positive result from the trial.</em></p>
    </div>
</div>
<link rel="canonical" href="https://knowablemagazine.org/content/article/health-disease/2024/cholesterol-and-heart-disease-explained">
<meta name="syndication-source" content="https://knowablemagazine.org/content/article/health-disease/2024/cholesterol-and-heart-disease-explained" doi="10.1146/knowable-021424-1">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/did-em-cell-em-mislead-the-world-about-low-carb-diets-and-cancer</id>
    <published>2025-10-20T13:45:33-07:00</published>
    <updated>2025-10-20T13:45:51-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/did-em-cell-em-mislead-the-world-about-low-carb-diets-and-cancer"/>
    <title>Did &lt;em&gt;Cell&lt;/em&gt; Mislead the World About Low-Carb Diets and Cancer</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p><strong>FOR IMMEDIATE RELEASE</strong> <br><strong>Orthomolecular Medicine News Service, October 19, 2025</strong></p>
<h2>A Dangerous Misunderstanding - And the Silence That Followed</h2>
<p style="padding-top: 10px;"><b>By Richard Z. Cheng, M.D., Ph.D., Lance Long, Thomas Seyfried, Ph.D., and Tomas Duraj, M.D.</b></p>
<hr>
<h2>🧠 A Confusing Claim: Can Low-Carb Diets Promote Cancer Spread?</h2>
<p>A recent article published in <i>Cell</i> - one of the most prestigious journals in science - made a troubling claim: that "glucose restriction" might actually help cancer spread to the lungs.</p>
<p>The study, by Wu et al., caught global attention, especially in China where some of the authors practice. But it also created <b>widespread confusion and fear</b> among doctors, researchers, and cancer patients - not because it presented surprising new data, but because the <b>entire design and interpretation of the study was fundamentally flawed</b>.</p>
<hr>
<h2>⚠️ Not a Low-Carb Study - Just Two High-Glucose Diets</h2>
<p>Here's what the researchers actually did:</p>
<p>They fed mice two different experimental diets:</p>
<ul>
<li style="padding-left: 10px;">One diet had <b>40% carbohydrates</b>
</li>
<li style="padding-left: 10px;">The other had <b>60% carbohydrates</b>
</li>
</ul>
<p>Then, they referred to the 40% carb diet as "low-carb" or "glucose-restricted."</p>
<p>But that is <b>scientifically incorrect and highly misleading</b>.</p>
<p>In clinical nutrition and cancer therapy, a <b>true low-carb or ketogenic diet</b> typically contains less <b>than 10% carbohydrates</b> - not 40%.</p>
<p><b>Both diets used in this study were high-glucose diets</b>, and neither induced the metabolic state of <b>ketosis</b>, which is the hallmark of real low-carb therapy.</p>
<p>Even worse, the authors did <b>not measure blood ketones or blood sugar</b>, so there's no evidence that the mice were in any kind of glucose-restricted or fat-burning state.</p>
<p>Yet the authors went on to claim that "glucose restriction" increased the risk of lung metastasis - when in reality, <b>they never tested glucose restriction at all</b>.</p>
<p>This is not just a minor technical oversight. It is a <b>critical mischaracterization</b> that risks misleading doctors, researchers, and especially patients - many of whom are exploring safe, non-toxic dietary strategies like the ketogenic diet to support cancer treatment.</p>
<hr>
<h2>❗ We Pointed This Out to <i>Cell</i> - They Refused to Publish Our Rebuttal</h2>
<p>Recognizing the public health risks of this misinformation, we submitted a detailed rebuttal to <i>Cell</i>.</p>
<p>We carefully explained:</p>
<ul>
<li style="padding-left: 10px;">The diet used in the study was <b>not low-carb</b>
</li>
<li style="padding-left: 10px;">The authors failed to measure glucose or ketones</li>
<li style="padding-left: 10px;">No evidence of actual glucose restriction was presented</li>
<li style="padding-left: 10px;">Their conclusions about metastasis and diet were therefore invalid</li>
</ul>
<p>We respectfully requested that <i>Cell</i> publish our rebuttal as a commentary or technical note - not to attack, but to promote scientific clarity and protect public understanding.</p>
<p>The response from <i>Cell's</i> Editor-in-Chief, Dr. John W. Pham?</p>
<p><i>"We appreciate the points that you raise, but we do not have a format for the kind of commentary that you propose."</i></p>
<p>In other words: <b>the journal that published this potentially harmful claim refused to publish a correction or allow informed dissent</b>.</p>
<p>This is even more concerning than the original article. In a healthy scientific system, there must be room for respectful debate - especially when public health is at stake.</p>
<hr>
<h2>🔍 What the Study Claimed - and Why It's Misleading</h2>
<p>The <i>Cell</i> study claimed that "glucose restriction" increased the release of a molecule called TRAIL from tumor cells, which may influence immune cells in the lungs and increase metastasis.</p>
<p>But again:</p>
<ul>
<li style="padding-left: 10px;">No true glucose restriction occurred</li>
<li style="padding-left: 10px;">No metabolic data (like ketones, insulin, or glucose levels) was reported</li>
<li style="padding-left: 10px;">Food intake and body weight were not tracked</li>
<li style="padding-left: 10px;">Both diets were high in carbohydrates - neither represents a real-world low-carb or ketogenic intervention</li>
</ul>
<p>It's entirely possible that the mice were metabolically stressed, overfed, or had immune changes <b>unrelated to carbohydrate levels</b>. But without proper metabolic tracking, we cannot know.</p>
<p>Despite this, the paper drew public conclusions about low-carb diets that may <b>deter patients from using safe, science-based dietary tools</b> to support their health.</p>
<hr>
<h2>✅ What Real Low-Carb or Ketogenic Therapy Looks Like</h2>
<p>True ketogenic metabolic therapy for cancer has been studied extensively and includes:</p>
<ul>
<li style="padding-left: 10px;"><b>Less than 10% carbohydrate intake</b></li>
<li style="padding-left: 10px;">Moderate protein to avoid excess glucose production</li>
<li style="padding-left: 10px;">High healthy fat intake (70-80% of calories)</li>
<li style="padding-left: 10px;">Tracking of glucose, ketones, insulin, and other biomarkers</li>
<li style="padding-left: 10px;">Optional fasting to deepen metabolic shifts</li>
<li style="padding-left: 10px;">Measurable therapeutic ketosis (via ketone levels or glucose-ketone index)</li>
</ul>
<p>Over 100 studies, both in animals and humans, suggest that ketogenic diets may:</p>
<ul>
<li style="padding-left: 10px;">Slow tumor growth</li>
<li style="padding-left: 10px;">Reduce inflammation</li>
<li style="padding-left: 10px;">Improve immune function</li>
<li style="padding-left: 10px;">Lower insulin and glucose - two key fuels for cancer cells</li>
<li style="padding-left: 10px;">In some cases, delay or reduce metastasis</li>
</ul>
<hr>
<h2>🧭 Final Word: When Science Goes Wrong, We Must Speak Up</h2>
<p>This case reveals two serious problems:</p>
<ol>
<li style="padding-left: 10px;">A world-renowned journal published a paper <b>that misrepresents what a low-carb diet is</b>, and draws misleading conclusions that may harm patients.</li>
<li style="padding-left: 10px;">When independent researchers respectfully pointed out the error, the journal <b>refused to publish their rebuttal</b>.</li>
</ol>
<p>That's not science. That's narrative control.</p>
<p>As scientists and physicians, we must speak up when flawed research risks misleading the public - especially when the media and patients trust high-profile journals to guide life-and-death decisions.</p>
<p>That's why we're sharing our rebuttal here, through the <b>Orthomolecular Medicine News Service</b> - a platform that honors open scientific dialogue and puts human optimal wellness first.</p>
<hr>
<h2>References</h2>
<p><a name="Ref1" target="_blank"></a></p>
<p>1. Wu CY, Huang CX, Lao XM, Zhou ZW, Jian JH, Li ZX, Wu YY, Liu ZY, Chen L, Liu L, Zheng L, Wei Y, Kuang DM. Glucose restriction shapes pre-metastatic innate immune landscapes in the lung through exosomal TRAIL. Cell. 2025 Oct 2;188(20):5701-5716.e19. doi: 10.1016/j.cell.2025.06.027. Epub 2025 Jul 15. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/40669460" target="_blank">40669460</a>.</p>
<p><a name="Ref2" target="_blank"></a></p>
<p>2. Seyfried TN. Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. Wiley; 2012. <a href="https://onlinelibrary.wiley.com/doi/book/10.1002/9781118310311" target="_blank">https://onlinelibrary.wiley.com/doi/book/10.1002/9781118310311</a></p>
<p><a name="Ref3" target="_blank"></a></p>
<p>3. Duraj T, Kalamian M, Zuccoli G, Maroon JC, D'Agostino DP, Scheck AC, Poff A, Winter SF, Hu J, Klement RJ, Hickson A, Lee DC, Cooper I, Kofler B, Schwartz KA, Phillips MCL, Champ CE, Zupec-Kania B, Tan-Shalaby J, Serfaty FM, Omene E, Arismendi-Morillo G, Kiebish M, Cheng R, El-Sakka AM, Pflueger A, Mathews EH, Worden D, Shi H, Cincione RI, Spinosa JP, Slocum AK, Iyikesici MS, Yanagisawa A, Pilkington GJ, Chaffee A, Abdel-Hadi W, Elsamman AK, Klein P, Hagihara K, Clemens Z, Yu GW, Evangeliou AE, Nathan JK, Smith K, Fortin D, Dietrich J, Mukherjee P, Seyfried TN. Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma. BMC Med. 2024 Dec 5;22(1):578. doi: 10.1186/s12916-024-03775-4. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/39639257" target="_blank">39639257</a>; PMCID: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622503" target="_blank">PMC11622503</a>.</p>
<p><a name="Ref4" target="_blank"></a></p>
<p>4. Klement RJ. Anti-tumor effects of ketogenic diets and their synergism with other treatments in mice: Bayesian evidence synthesis of 1755 individual mouse survival data. Biomed J. 2024 Feb;47(1):100609. doi: 10.1016/j.bj.2023.100609. Epub 2023 May 26. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/37245566" target="_blank">37245566</a>; PMCID: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900256" target="_blank">PMC10900256</a>.</p>
<p><a name="Ref5" target="_blank"></a></p>
<p>5. Mukherjee P, Augur ZM, Li M, Hill C, Greenwood B, Domin MA, Kondakci G, Narain NR, Kiebish MA, Bronson RT, Arismendi-Morillo G, Chinopoulos C, Seyfried TN. Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma. Commun Biol. 2019 May 29;2:200. doi: 10.1038/s42003-019-0455-x. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/31149644" target="_blank">31149644</a>; PMCID: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541653" target="_blank">PMC6541653</a>.</p>
<hr>
<h2>👥 About the Authors</h2>
<p><b>Richard Z. Cheng, M.D., Ph.D.</b> <br>Editor-in-Chief of OMNS. A U.S.-trained, board-certified physician specializing in orthomolecular and integrative cancer therapies. Based in the USA and China.</p>
<p><b>Lance Long</b> <br>Science writer and editor focused on metabolic health and evidence-based nutrition.</p>
<p><b>Thomas Seyfried, Ph.D.</b> <br>Professor of Biology at Boston College. Author of <i>Cancer as a Metabolic Disease</i> and a leading voice in the mitochondrial theory of cancer.</p>
<p><b>Tomas Duraj, M.D.</b> <br>Researcher and clinician developing frameworks for ketogenic cancer therapy.</p>
<p><span style="font-size: 8.0pt; font-family: 'Georgia',serif; mso-fareast-font-family: Calibri; mso-fareast-theme-font: minor-latin; mso-bidi-font-family: Aptos; mso-ansi-language: EN-CA; mso-fareast-language: EN-CA; mso-bidi-language: AR-SA;">OMNS free subscription link <a href="https://orthomolecular.acemlna.com/lt.php?x=4lZy~GE7IaXPEp.r-tu7gOhw~3UojwMjw~gyYXg4IaSe5pN6-Uy.zuR02I2kiNc~jvYwYnLHI-HNU537ztPKwSbc1k" target="_blank">http://orthomolecular.org/subscribe.html</a><br>OMNS archive link <a href="https://orthomolecular.acemlna.com/lt.php?x=4lZy~GE7IaXPEp.r-tu7gOhw~3UojwMjw~gyYXg4IaSe5pN6-Uy.zuR02I2kiNc~jvYwYnLHIMHNU537ztPKwSbc1k" target="_blank">http://orthomolecular.org/resources/omns/index.shtml</a> </span></p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/mitochondria-the-core-of-exercise-longevity-heart-health-and-cancer-prevention</id>
    <published>2025-10-13T06:00:01-07:00</published>
    <updated>2025-10-13T06:00:01-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/mitochondria-the-core-of-exercise-longevity-heart-health-and-cancer-prevention"/>
    <title>Mitochondria: The Core of Exercise, Longevity, Heart Health, and Cancer Prevention</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p><strong>FOR IMMEDIATE RELEASE</strong><br><strong>Orthomolecular Medicine News Service, October 11, 2025<br><span style="font-size: 8.0pt; font-family: 'Georgia',serif; mso-fareast-font-family: Calibri; mso-fareast-theme-font: minor-latin; mso-bidi-font-family: Aptos; color: black; mso-ansi-language: EN-CA; mso-fareast-language: EN-CA; mso-bidi-language: AR-SA;">OMNS free subscription link <a href="https://orthomolecular.acemlna.com/lt.php?x=4lZy~GE6J6aZ5X.q0Qy4hBGf~qIgv_Hyv~gzZKU5IIOe6p4vy0y7xOFt23Uj-RVfjDZo2nTMIYGd55KKyOxGVuFw1E" target="_blank">http://orthomolecular.org/subscribe.html</a><br></span><span style="font-size: 8.0pt; font-family: 'Georgia',serif; mso-fareast-font-family: Calibri; mso-fareast-theme-font: minor-latin; mso-bidi-font-family: Aptos; color: black; mso-ansi-language: EN-CA; mso-fareast-language: EN-CA; mso-bidi-language: AR-SA;">OMNS archive link <a href="https://orthomolecular.acemlna.com/lt.php?x=4lZy~GE6J6aZ5X.q0Qy4hBGf~qIgv_Hyv~gzZKU5IIOe6p4vy0y7xOFt23Uj-RVfjDZo2nTMIYGd55KKyOxGVuFw1U" target="_blank">http://orthomolecular.org/resources/omns/index.shtml</a></span><br></strong></p>
<p><b>Richard Z. Cheng, M.D., Ph.D.</b></p>
<hr>
<h2>Introduction: From Gyms to Longevity Hubs</h2>
<p>CrossFit and other forms of high-intensity training<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref1" target="_blank">[1-3]</a><span> </span>have transformed fitness worldwide. Athletes in their 20s and 30s push limits, but often encounter plateaus: recovery slows, fatigue sets in, injuries take longer to heal.</p>
<p>At the same time, another demographic is surging - adults over 50 who seek not just fitness, but vitality, resilience, and independence<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref4" target="_blank">[4,5]</a>. They want energy for family, travel, and life.</p>
<p><b>The bridge between these two worlds is mitochondrial health.</b></p>
<hr>
<h2>Mitochondria: The Master Switch for Performance, Aging, and Disease</h2>
<p>Mitochondria are not simply "power plants." They determine how effectively we move, recover, and resist disease.</p>
<h3>For younger adults</h3>
<ul>
<li>
<b>Endurance and performance:</b><span> </span>More mitochondria mean higher VO₂max, greater ATP production, and delayed fatigue. Even short-term interval training can rapidly increase mitochondrial density and oxidative enzyme activity<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref6" target="_blank">[6-9]</a>.</li>
<li>
<b>Recovery:</b><span> </span>Efficient mitochondria accelerate cellular repair, reduce soreness, and restore energy stores after exertion<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref9" target="_blank">[9]</a>.</li>
<li>
<b>Metabolic flexibility:</b><span> </span>Athletes with robust mitochondria switch smoothly between fat and carbohydrate fuels, burn less lactate, and sustain higher intensities<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref10" target="_blank">[10-14]</a>.</li>
</ul>
<table width="650">
<tbody>
<tr>
<th height="40" width="200">Benefit</th>
<th width="350">Mitochondria's Role</th>
<th width="100">Evidence</th>
</tr>
<tr>
<td height="40">Endurance</td>
<td>ATP production, fatigue resistance, higher VO2max</td>
<td><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref6" target="_blank">[6,8]</a></td>
</tr>
<tr>
<td height="40">Faster Recovery</td>
<td>Cellular repair, reduced soreness, rapid energy replenishment</td>
<td><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref7" target="_blank">[7,9]</a></td>
</tr>
<tr>
<td height="40">Metabolic Flexibility</td>
<td>Efficient substrate switching, fat oxidation, lactate control</td>
<td><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref10" target="_blank">[10-12]</a></td>
</tr>
</tbody>
</table>
<h3>For older adults</h3>
<ul>
<li>
<b>Slowing aging:</b><span> </span>Declining mitochondrial function accelerates oxidative stress, inflammation, and tissue damage. Exercise and caloric restriction preserve mitochondrial biogenesis and delay these processes<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref15" target="_blank">[15-18]</a>.</li>
<li>
<b>Muscle preservation:</b><span> </span>Impaired mitochondria contribute to sarcopenia. High-intensity or resistance exercise helps maintain muscle quality by improving mitochondrial turnover and reducing oxidative damage<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref19" target="_blank">[19-23]</a>.</li>
<li>
<b>Cardiovascular protection:</b><span> </span>Strong mitochondrial capacity reduces the risk of heart disease and preserves cardiac output with age<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref24" target="_blank">[24-26]</a>.</li>
<li>
<b>Cancer and dementia prevention:</b><span> </span>Dysfunctional mitochondria drive genomic instability, oxidative injury, and impaired cell regulation - mechanisms linked with both cancer and neurodegeneration. Restoring mitochondrial health reduces risk<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref25" target="_blank">[25-29]</a>.</li>
</ul>
<table width="650">
<tbody>
<tr>
<th height="40" width="200">Effect</th>
<th width="350">Mitochondria's Role</th>
<th width="100">Evidence</th>
</tr>
<tr>
<td height="40">Slow Aging</td>
<td>Maintain cellular energy, curb oxidative stress</td>
<td><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref15" target="_blank">[15,17,18]</a></td>
</tr>
<tr>
<td height="40">Preserve Muscle</td>
<td>Support muscle mass/function; mitigate sarcopenia</td>
<td><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref19" target="_blank">[19-22]</a></td>
</tr>
<tr>
<td height="40">Protect the Heart</td>
<td>Prevent cardiac aging; improve myocardial energetics</td>
<td><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref24" target="_blank">[24,25]</a></td>
</tr>
<tr>
<td height="40">Reduce Cancer/Dementia</td>
<td>Limit oxidative damage, neurodegeneration, mutations</td>
<td><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref19" target="_blank">[19,20,25]</a></td>
</tr>
</tbody>
</table>
<h3>In short:</h3>
<ul>
<li>For the young: mitochondria = peak performance.</li>
<li>For the old: mitochondria = resilience and independence.</li>
</ul>
<hr>
<h2>Why Mitochondria Fail: Upstream Root Causes</h2>
<p>In my<span> </span><i>From Mutation to Metabolism</i><span> </span>series, I outlined ten upstream categories of root causes that converge on mitochondrial dysfunction - not only in cancer, but also in atherosclerotic cardiovascular disease (ASCVD), diabetes, and aging<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref28" target="_blank">[28,29]</a>. Across chronic diseases, recurring upstream drivers consistently damage mitochondria:</p>
<ol>
<li>
<b>Environmental and dietary toxins</b><span> </span>- pesticides, plastics, heavy metals, processed foods.</li>
<li>
<b>Nutrient deficiencies</b><span> </span>- inadequate vitamins, minerals, and antioxidants.</li>
<li>
<b>Chronic inflammation and infections</b><span> </span>- driving oxidative stress and immune imbalance.</li>
<li>
<b>Hormonal and metabolic disruption</b><span> </span>- insulin resistance, circadian rhythm disturbances.</li>
<li>
<b>Lifestyle and psychosocial stressors</b><span> </span>- poor sleep, overtraining, emotional stress.</li>
</ol>
<h3>👉 Additional note:</h3>
<p>Bright environmental light-especially intense blue-spectrum light-can oxidize mitochondrial cytochromes in the retina because of their chromophore sensitivity, damaging mitochondrial DNA and metabolism. Prolonged exposure to bright sunlight, snow glare, or beach reflections can therefore accelerate oxidative injury to retinal mitochondria. Wearing dark or protective glasses in such conditions helps preserve mitochondrial health in the eyes and nervous system<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref30" target="_blank">[30-33]</a>.</p>
<h3>The Central Role of Toxins</h3>
<p>As outlined in Part 2 of my series<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref29" target="_blank">[29]</a>, many modern toxins are directly<span> </span><b>mitochondriotoxic:</b></p>
<ul>
<li>Plastics and pesticides disrupt mitochondrial respiratory chain enzymes.</li>
<li>Heavy metals (e.g., mercury, lead) generate ROS and collapse redox balance.</li>
<li>Ultra-processed foods introduce emulsifiers and additives that damage gut barriers, triggering systemic inflammation that impairs mitochondria.</li>
<li>Air pollutants and endocrine disruptors accelerate cardiovascular aging, diabetes, and neurodegeneration via mitochondrial injury.</li>
</ul>
<p>These burdens help explain why a<span> </span><b>30-year-old athlete hits a plateau</b><span> </span>and why a<span> </span><b>60-year-old loses vitality</b><span> </span>more rapidly.</p>
<hr>
<h2>Critique of the "Hallmarks of Aging"</h2>
<p>The<span> </span><i>Hallmarks of Aging</i><span> </span>framework<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref34" target="_blank">[34,35]</a><span> </span>has shaped much of modern geroscience for over a decade. First proposed in 2013<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref34" target="_blank">[34]</a><span> </span>with nine categories - genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication - it was expanded in 2023<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref35" target="_blank">[35]</a><span> </span>to twelve by adding disabled macroautophagy, chronic inflammation ("inflammaging"), and microbiome disturbance.</p>
<p>This framework has been valuable for organizing observations. Yet the "hallmarks" are<span> </span><b>downstream expressions</b>, not true root causes. Many hallmarks-genomic instability, telomere attrition, epigenetic alterations, deregulated nutrient sensing, senescence, stem cell exhaustion, inflammaging-are<span> </span><b>driven by earlier mitochondrial stress</b><span> </span>(e.g., ROS, redox collapse, NAD⁺/ATP imbalance) and upstream toxins, infections, and deficiencies.</p>
<ul>
<li>
<b>Genomic instability</b><span> </span>is largely fueled by mitochondrial ROS, toxins, and micronutrient deficiencies.</li>
<li>
<b>Telomere attrition</b><span> </span>reflects oxidative stress, inflammation, and metabolic overload - all downstream effects of mitochondrial stress.</li>
<li>
<b>Epigenetic alterations</b><span> </span>mirror environmental and nutritional inputs mediated through mitochondrial metabolism.</li>
<li>
<b>Nutrient sensing pathways</b><span> </span>(AMPK, mTOR, sirtuins) are set by mitochondrial NAD⁺/ATP balance.</li>
<li>
<b>Senescence and stem cell exhaustion</b><span> </span>accelerate when mitochondrial energy reserves collapse.</li>
<li>
<b>Inflammaging</b><span> </span>(chronic low-grade inflammation) is often initiated by mitochondrial danger signals (mtDNA fragments, ROS leakage) and perpetuated by toxin exposure.</li>
</ul>
<p>In other words, what López-Otín and colleagues cataloged as "hallmarks" are<span> </span><b>symptoms</b>, not origins.</p>
<p>From the<span> </span><b>Integrative Orthomolecular Medicine (IOM)<span> </span></b>perspective, the true root drivers of aging are the same ten categories I have outlined in my<span> </span><i>From Mutation to Metabolism</i><span> </span>series: dietary imbalance, environmental toxins, chronic infections, gut dysbiosis, oxidative stress, chronic inflammation, hormonal and metabolic dysregulation, immune dysfunction, stem cell exhaustion, and psychological stress/lifestyle imbalance.</p>
<p>All of these upstream drivers converge on<span> </span><b>mitochondrial dysfunction</b>, making mitochondria the<span> </span><b>master hallmark</b><span> </span>and central integrator of aging.</p>
<h3>Therefore:</h3>
<ul>
<li>The "hallmarks" are<span> </span><b>descriptive signs</b><span> </span>- useful markers of damage and dysfunction.</li>
<li>But they are<span> </span><b>not initiating drivers</b>. They do not explain why mitochondria fail in the first place.</li>
<li>True intervention requires moving<span> </span><i>upstream</i>, addressing toxins, nutrient deficiencies, infections, and metabolic stress - the real starting points of aging.</li>
</ul>
<p>This reorientation is critical for both science and practice. Focusing on superficial hallmarks risks expensive "miracle anti-aging drugs" that tweak pathways but never address root causes. By contrast, targeting upstream drivers - through diet, detoxification, orthomolecular nutrition, exercise, and lifestyle - restores mitochondria and improves multiple hallmarks simultaneously.</p>
<hr>
<h2>IOM Mitochondria Optimization: What Works</h2>
<p>Low-Carb, Ketogenic Diet and Intermittent Fasting: Fuel for Mitochondria</p>
<p>One of the most powerful ways to restore mitochondrial health is through dietary strategy.</p>
<ul>
<li>
<b>Low-Carb and Ketogenic Diets:</b><span> </span>Restricting carbohydrates lowers blood sugar and insulin, reducing mitochondrial overload and oxidative stress. Ketones (β-hydroxybutyrate) serve as a clean fuel, generating fewer reactive oxygen species compared to glucose. Studies show ketogenic metabolism enhances mitochondrial biogenesis, improves redox balance, and increases resilience against oxidative injury<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref36" target="_blank">[36,37,37,38]</a>.</li>
<li>
<b>Intermittent Fasting:</b><span> </span>Periods of fasting activate AMPK and sirtuin pathways, stimulating autophagy and mitochondrial renewal. Fasting also lowers inflammation, improves insulin sensitivity, and promotes metabolic flexibility<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref39" target="_blank">[39-41]</a>.</li>
<li>
<b>Exercise Endurance Benefits:<span> </span></b>Both ketogenic metabolism and intermittent fasting increase reliance on fat oxidation, sparing glycogen and reducing lactate buildup. Endurance athletes often experience improved "second wind" capacity, greater stamina, and faster recovery when adapted to fat and ketones as fuel. Older adults also gain - fasting and low-carb diets preserve muscle, maintain mitochondrial biogenesis, and prevent fatigue from rapid glucose swings<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref41" target="_blank">[42,43]</a>.</li>
<li>
<b>Clinical Impact:<span> </span></b>Together, low-carb and fasting strategies have demonstrated benefits for diabetes, obesity, neurodegenerative conditions, cancer management, and longevity. For athletes, they improve fat oxidation and endurance. For older adults, they preserve function and delay age-related decline<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref44" target="_blank">[44-47]</a>.</li>
</ul>
<p>In practical terms: alternating between fasting periods and fat-based fuel sources mimics evolutionary energy cycles - giving mitochondria both rest and renewal.</p>
<hr>
<h2>Key Nutrients and Lifestyle Interventions</h2>
<p><b>Exercise is the ignition. Nutrition is the fuel. Together, they upgrade mitochondria.</b></p>
<ul>
<li>
<b>Vitamin C</b><span> </span>- 3,000-10,000 mg/day in divided doses. Supports recovery, collagen formation, antioxidant defense, and vascular health<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref48" target="_blank">[48]</a>.</li>
<li>
<b>Vitamin D3</b><span> </span>- 5,000-10,000 IU/day, adjusted to maintain blood levels of 50-100 ng/ml. Strengthens immunity, bones, and muscles<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref49" target="_blank">[49,50]</a>.</li>
<li>
<b>Niacin (B3)</b><span> </span>- 500-2,000 mg/day of instant-release niacin (titrated upward to minimize flushing). Boosts NAD⁺ and supports mitochondrial repair<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref51" target="_blank">[51-53]</a>.</li>
<li>
<b>Magnesium</b><span> </span>- 500-1,000 mg/day (glycinate or threonate forms preferred). Critical for ATP production, muscle relaxation, and energy metabolism<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=c410003ef13d451727aeff9082c29a5c.416&amp;s=e6f033a9aadadbf0d34bc49dd3c541f3#Ref54" target="_blank">[54,55]</a>.</li>
<li>
<b>CoQ10</b><span> </span>- 200-400 mg/day. Enhances cardiac function, endurance, and mitochondrial electron transport.</li>
<li>
<b>Omega-3</b><span> </span>- 2,000 mg/day or more of combined EPA+DHA from marine sources. Provides anti-inflammatory and neuroprotective benefits.</li>
<li>
<b>L-carnitine</b><span> </span>- 1,000-3,000 mg/day. Facilitates fatty acid transport into mitochondria, improving fat burning and exercise endurance.</li>
<li>
<b>Sleep, stress control, circadian rhythm</b><span> </span>- Protect mitochondrial repair cycles.</li>
<li>
<b>Other supportive tools:</b><span> </span>Red-Blue therapy (NIR/PBMT + methylene blue), and additional orthomolecular nutrients.</li>
</ul>
<p>For younger athletes:<span> </span><b>better performance and fewer injuries.</b></p>
<p>For seniors:<span> </span><b>slowing aging, preventing ASCVD and cancer, preserving independence.</b></p>
<hr>
<h2>Conclusion: The Mitochondrial Advantage</h2>
<ul>
<li>For the young: mitochondria mean performance and endurance.</li>
<li>For the old: mitochondria mean resilience and youthfulness.</li>
<li>For all: mitochondria are the master hallmark - the central key to energy, health, and longevity.</li>
</ul>
<h3>One mitochondrion, one solution: energy for life.</h3>
<p>I am living proof myself. For nearly two decades, I have practiced intermittent fasting, usually eating only two meals a day-the first after noon and the last before 7 p.m. In the mornings, I often play competitive badminton on an empty stomach, usually for two hours. I can still vigorously compete with players who are 10, 20, or even 30 years younger than me. I hardly experience significant low blood sugar symptoms, even if I fast for more than a day. This is because I have effectively trained my body to release, burn, and convert stored fat into energy-whereas many people cannot.</p>
<p>What I often see is that many younger players run out of energy and show signs of fatigue, while I'm still going strong-almost like the<span> </span><b>Energizer Bunny</b>. People often ask me what my secret is. Half-jokingly, I reply:<span> </span><i>I'm a meat eater, while you are grass eaters (carbs)</i>. 🤣</p>
<ul>
<li>
<b>For young athletes:</b><span> </span>mitochondria = peak performance.</li>
<li>
<b>For seniors:</b><span> </span>mitochondria = youthfulness and resilience.</li>
</ul>
<hr>
<h2>About the Author</h2>
<p><b>Richard Z. Cheng, M.D., Ph.D.</b><span> </span>-<span> </span><i>Editor-in-Chief, Orthomolecular Medicine News Service</i></p>
<p>Dr. Cheng is a U.S.-based, NIH-trained, board-certified physician specializing in integrative cancer therapy, orthomolecular medicine, functional &amp; anti-aging medicine. He maintains active practices in both the United States and China.</p>
<p>A Fellow of the American Academy of Anti-Aging Medicine and a Hall of Fame inductee of the International Society for Orthomolecular Medicine, Dr. Cheng is a leading advocate for nutrition-based, root-cause health strategies. He also serves as an expert reviewer for the South Carolina Board of Medical Examiners, and co-founded both the China Low Carb Medicine Alliance and the Society of International Metabolic Oncology.</p>
<p>Dr. Cheng offers online Integrative Orthomolecular Medicine consultation services.<br>📰 Follow his latest insights on Substack:<span> </span><a href="https://substack.com/@rzchengmd" target="_blank">https://substack.com/@rzchengmd</a></p>
<hr>
<h2>References:</h2>
<p><a name="Ref1" target="_blank"></a><span></span></p>
<p>1. Gibala, M.J.; McGee, S.L. Metabolic Adaptations to Short-Term High-Intensity Interval Training: A Little Pain for a Lot of Gain? Exerc Sport Sci Rev 2008, 36, 58-63, doi:<a href="https://doi.org/10.1097/JES.0b013e318168ec1f" target="_blank">10.1097/JES.0b013e318168ec1f</a>.</p>
<p><a name="Ref2" target="_blank"></a><span></span></p>
<p>2. Batacan, R.B.; Duncan, M.J.; Dalbo, V.J.; Tucker, P.S.; Fenning, A.S. Effects of High-Intensity Interval Training on Cardiometabolic Health: A Systematic Review and Meta-Analysis of Intervention Studies. Br J Sports Med 2017, 51, 494-503, doi:<span> </span><a href="https://doi.org/10.1136/bjsports-2015-095841" target="_blank">10.1136/bjsports-2015-095841</a>.</p>
<p><a name="Ref3" target="_blank"></a><span></span></p>
<p>3. Nicolò, A.; Girardi, M. The Physiology of Interval Training: A New Target to HIIT. J Physiol 2016, 594, 7169-7170, doi:<span> </span><a href="https://doi.org/10.1113/JP273466" target="_blank">10.1113/JP273466</a>.</p>
<p><a name="Ref4" target="_blank"></a><span></span></p>
<p>4. Pak, C.; Kambil, A. Over 50 and Ready to Shop: Serving the Aging Consumer. Journal of Business Strategy 2006, 27, 18-28, doi:<span> </span><a href="https://doi.org/10.1108/02756660610710319" target="_blank">10.1108/02756660610710319</a>.</p>
<p><a name="Ref5" target="_blank"></a><span></span></p>
<p>5. Barbaccia, V.; Bravi, L.; Murmura, F.; Savelli, E.; Viganò, E. Mature and Older Adults' Perception of Active Ageing and the Need for Supporting Services: Insights from a Qualitative Study. Int J Environ Res Public Health 2022, 19, 7660, doi:<span> </span><a href="https://doi.org/10.3390/ijerph19137660" target="_blank">10.3390/ijerph19137660</a>.</p>
<p><a name="Ref6" target="_blank"></a><span></span></p>
<p>6. Zoladz, J.A.; Majerczak, J.; Galganski, L.; Grandys, M.; Zapart-Bukowska, J.; Kuczek, P.; Kołodziejski, L.; Walkowicz, L.; Szymoniak-Chochół, D.; Kilarski, W.; et al. Endurance Training Increases the Running Performance of Untrained Men without Changing the Mitochondrial Volume Density in the Gastrocnemius Muscle. Int J Mol Sci 2022, 23, 10843, doi:<span> </span><a href="https://doi.org/10.3390/ijms231810843" target="_blank">10.3390/ijms231810843</a>.</p>
<p><a name="Ref7" target="_blank"></a><span></span></p>
<p>7. Mesquita, P.H.C.; Vann, C.G.; Phillips, S.M.; McKendry, J.; Young, K.C.; Kavazis, A.N.; Roberts, M.D. Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities. Front Physiol 2021, 12, 725866, doi:<span> </span><a href="https://doi.org/" target="_blank">10.3389/fphys.2021.725866</a>.</p>
<p><a name="Ref8" target="_blank"></a><span></span></p>
<p>8. Feng, Y.; Rao, Z.; Tian, X.; Hu, Y.; Yue, L.; Meng, Y.; Zhong, Q.; Chen, W.; Xu, W.; Li, H.; et al. Endurance Training Enhances Skeletal Muscle Mitochondrial Respiration by Promoting MOTS-c Secretion. Free Radic Biol Med 2025, 227, 619-628, doi:<span> </span><a href="https://doi.org/10.1016/j.freeradbiomed.2024.12.038" target="_blank">10.1016/j.freeradbiomed.2024.12.038</a>.</p>
<p><a name="Ref9" target="_blank"></a><span></span></p>
<p>9. MacInnis, M.J.; Zacharewicz, E.; Martin, B.J.; Haikalis, M.E.; Skelly, L.E.; Tarnopolsky, M.A.; Murphy, R.M.; Gibala, M.J. Superior Mitochondrial Adaptations in Human Skeletal Muscle after Interval Compared to Continuous Single-Leg Cycling Matched for Total Work. J Physiol 2017, 595, 2955-2968, doi:<span> </span><a href="https://doi.org/10.1113/JP272570" target="_blank">10.1113/JP272570</a>.</p>
<p><a name="Ref10" target="_blank"></a><span></span></p>
<p>10. San-Millán, I.; Brooks, G.A. Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals. Sports Med 2018, 48, 467-479, doi:<span> </span><a href="https://doi.org/10.1007/s40279-017-0751-x" target="_blank">10.1007/s40279-017-0751-x</a>.</p>
<p><a name="Ref11" target="_blank"></a><span></span></p>
<p>11. Lovell, D.I.; Stuelcken, M.; Eagles, A. Exercise Testing for Metabolic Flexibility: Time for Protocol Standardization. Sports Med Open 2025, 11, 31, doi:<span> </span><a href="https://doi.org/10.1186/s40798-025-00825-w" target="_blank">10.1186/s40798-025-00825-w</a>.</p>
<p><a name="Ref12" target="_blank"></a><span></span></p>
<p>12. Palmer, B.F.; Clegg, D.J. Metabolic Flexibility and Its Impact on Health Outcomes. Mayo Clin Proc 2022, 97, 761-776, doi:<span> </span><a href="https://doi.org/10.1016/j.mayocp.2022.01.012" target="_blank">10.1016/j.mayocp.2022.01.012</a>.</p>
<p><a name="Ref13" target="_blank"></a><span></span></p>
<p>13. Smith, R.L.; Soeters, M.R.; Wüst, R.C.I.; Houtkooper, R.H. Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocr Rev 2018, 39, 489-517, doi:<span> </span><a href="https://doi.org/10.1210/er.2017-00211" target="_blank">10.1210/er.2017-00211</a>.</p>
<p><a name="Ref14" target="_blank"></a><span></span></p>
<p>14. Flockhart, M.; Nilsson, L.C.; Tais, S.; Ekblom, B.; Apró, W.; Larsen, F.J. Excessive Exercise Training Causes Mitochondrial Functional Impairment and Decreases Glucose Tolerance in Healthy Volunteers. Cell Metab 2021, 33, 957-970.e6, doi:<span> </span><a href="https://doi.org/10.1016/j.cmet.2021.02.017" target="_blank">10.1016/j.cmet.2021.02.017</a>.</p>
<p><a name="Ref15" target="_blank"></a><span></span></p>
<p>15. Chistiakov, D.A.; Sobenin, I.A.; Revin, V.V.; Orekhov, A.N.; Bobryshev, Y.V. Mitochondrial Aging and Age-Related Dysfunction of Mitochondria. Biomed Res Int 2014, 2014, 238463, doi:<span> </span><a href="https://doi.org/10.1155/2014/238463" target="_blank">10.1155/2014/238463</a>.</p>
<p><a name="Ref16" target="_blank"></a><span></span></p>
<p>16. Srivastava, S. The Mitochondrial Basis of Aging and Age-Related Disorders. Genes (Basel) 2017, 8, 398, doi:<span> </span><a href="https://doi.org/10.3390/genes8120398" target="_blank">10.3390/genes8120398</a>.</p>
<p><a name="Ref17" target="_blank"></a><span></span></p>
<p>17. Somasundaram, I.; Jain, S.M.; Blot-Chabaud, M.; Pathak, S.; Banerjee, A.; Rawat, S.; Sharma, N.R.; Duttaroy, A.K. Mitochondrial Dysfunction and Its Association with Age-Related Disorders. Front Physiol 2024, 15, 1384966, doi:<span> </span><a href="https://doi.org/10.3389/fphys.2024.1384966" target="_blank">10.3389/fphys.2024.1384966</a>.</p>
<p><a name="Ref18" target="_blank"></a><span></span></p>
<p>18. Jia, L.; Wei, Z.; Luoqian, J.; Wang, X.; Huang, C. Mitochondrial Dysfunction in Aging: Future Therapies and Precision Medicine Approaches. MedComm - Future Medicine 2025, 4, e70026, doi:<span> </span><a href="https://doi.org/10.1002/mef2.70026" target="_blank">10.1002/mef2.70026</a>.</p>
<p><a name="Ref19" target="_blank"></a><span></span></p>
<p>19. Coen, P.M.; Musci, R.V.; Hinkley, J.M.; Miller, B.F. Mitochondria as a Target for Mitigating Sarcopenia. Front Physiol 2018, 9, 1883, doi:<span> </span><a href="https://doi.org/10.3389/fphys.2018.01883" target="_blank">10.3389/fphys.2018.01883</a>.</p>
<p><a name="Ref20" target="_blank"></a><span></span></p>
<p>20. Short, K.R.; Bigelow, M.L.; Kahl, J.; Singh, R.; Coenen-Schimke, J.; Raghavakaimal, S.; Nair, K.S. Decline in Skeletal Muscle Mitochondrial Function with Aging in Humans. Proc Natl Acad Sci U S A 2005, 102, 5618-5623, doi:<span> </span><a href="https://doi.org/10.1073/pnas.0501559102" target="_blank">10.1073/pnas.0501559102</a>.</p>
<p><a name="Ref21" target="_blank"></a><span></span></p>
<p>21. Wyckelsma, V.L.; Levinger, I.; McKenna, M.J.; Formosa, L.E.; Ryan, M.T.; Petersen, A.C.; Anderson, M.J.; Murphy, R.M. Preservation of Skeletal Muscle Mitochondrial Content in Older Adults: Relationship between Mitochondria, Fibre Type and High-Intensity Exercise Training. J Physiol 2017, 595, 3345-3359, doi:<span> </span><a href="https://doi.org/10.1113/JP273950" target="_blank">10.1113/JP273950</a>.</p>
<p><a name="Ref22" target="_blank"></a><span></span></p>
<p>22. Crupi, A.N.; Nunnelee, J.S.; Taylor, D.J.; Thomas, A.; Vit, J.-P.; Riera, C.E.; Gottlieb, R.A.; Goodridge, H.S. Oxidative Muscles Have Better Mitochondrial Homeostasis than Glycolytic Muscles throughout Life and Maintain Mitochondrial Function during Aging. Aging (Albany NY) 2018, 10, 3327-3352, doi:<span> </span><a href="https://doi.org/10.18632/aging.101643" target="_blank">10.18632/aging.101643</a>.</p>
<p><a name="Ref23" target="_blank"></a><span></span></p>
<p>23. Burtscher, J.; Strasser, B.; Burtscher, M. A Mito-Centric View on Muscle Aging and Function. Front Public Health 2023, 11, 1330131, doi:<span> </span><a href="https://doi.org/10.3389/fpubh.2023.1330131" target="_blank">10.3389/fpubh.2023.1330131</a>.</p>
<p><a name="Ref24" target="_blank"></a><span></span></p>
<p>24. Dai, D.-F.; Rabinovitch, P.S.; Ungvari, Z. Mitochondria and Cardiovascular Aging. Circ Res 2012, 110, 1109-1124, doi:<span> </span><a href="https://doi.org/10.1161/CIRCRESAHA.111.246140" target="_blank">10.1161/CIRCRESAHA.111.246140</a>.</p>
<p><a name="Ref25" target="_blank"></a><span></span></p>
<p>25. Sinha, A.; Jaiswal, N.; Jadiya, P.; Tomar, D. Mitochondrial Connection to Alzheimer's Disease and Heart Failure. Current Opinion in Physiology 2025, 44, 100830, doi:<span> </span><a href="https://doi.org/10.1016/j.cophys.2025.100830" target="_blank">10.1016/j.cophys.2025.100830</a>.</p>
<p><a name="Ref26" target="_blank"></a><span></span></p>
<p>26. Mi, Y.; Qi, G.; Brinton, R.D.; Yin, F. Mitochondria-Targeted Therapeutics for Alzheimer's Disease: The Good, the Bad, the Potential. Antioxid Redox Signal 2021, 34, 611-630, doi:<span> </span><a href="https://doi.org/10.1089/ars.2020.8070" target="_blank">10.1089/ars.2020.8070</a>.</p>
<p><a name="Ref27" target="_blank"></a><span></span></p>
<p>27. Broadfoot, M. Mitochondrial Dysfunction Linked to Alzheimer's Onset and Treatment Response. Mayo Clinic News Network 2025.</p>
<p><a name="Ref28" target="_blank"></a><span></span></p>
<p>28. Cheng, R.Z. From Mutation to Metabolism: Root Cause Analysis of Cancer's Initiating Drivers 2025.</p>
<p><a name="Ref29" target="_blank"></a><span></span></p>
<p>29. Cheng, R.Z. From Mutation to Metabolism: Environmental and Dietary Toxins as Upstream Drivers of Mitochondrial Dysfunction and Chronic Disease 2025.</p>
<p><a name="Ref30" target="_blank"></a><span></span></p>
<p>30. Tao, J.-X.; Zhou, W.-C.; Zhu, X.-G. Mitochondria as Potential Targets and Initiators of the Blue Light Hazard to the Retina. Oxidative medicine and cellular longevity 2019, 2019, doi:<span> </span><a href="https://doi.org/10.1155/2019/6435364" target="_blank">10.1155/2019/6435364</a>.</p>
<p><a name="Ref31" target="_blank"></a><span></span></p>
<p>31. Osborne, N.N.; Kamalden, T.A.; Majid, A.S.A.; del Olmo-Aguado, S.; Manso, A.G.; Ji, D. Light Effects on Mitochondrial Photosensitizers in Relation to Retinal Degeneration. Neurochem Res 2010, 35, 2027-2034, doi:<span> </span><a href="https://doi.org/10.1007/s11064-010-0273-5" target="_blank">10.1007/s11064-010-0273-5</a>.</p>
<p><a name="Ref32" target="_blank"></a><span></span></p>
<p>32. Godley, B.F.; Shamsi, F.A.; Liang, F.-Q.; Jarrett, S.G.; Davies, S.; Boulton, M. Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells. J Biol Chem 2005, 280, 21061-21066, doi:<span> </span><a href="https://doi.org/10.1074/jbc.M502194200" target="_blank">10.1074/jbc.M502194200</a>.</p>
<p><a name="Ref33" target="_blank"></a><span></span></p>
<p>33. Osborne, N.N.; Núñez-Álvarez, C.; Del Olmo-Aguado, S. The Effect of Visual Blue Light on Mitochondrial Function Associated with Retinal Ganglions Cells. Exp Eye Res 2014, 128, 8-14, doi:<span> </span><a href="https://doi.org/10.1016/j.exer.2014.08.012" target="_blank">10.1016/j.exer.2014.08.012</a>.</p>
<p><a name="Ref34" target="_blank"></a><span></span></p>
<p>34. López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The Hallmarks of Aging. Cell 2013, 153, 1194-1217, doi:<span> </span><a href="https://doi.org/10.1016/j.cell.2013.05.039" target="_blank">10.1016/j.cell.2013.05.039</a>.</p>
<p><a name="Ref35" target="_blank"></a><span></span></p>
<p>35. López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. Hallmarks of Aging: An Expanding Universe. Cell 2023, 186, 243-278, doi:<span> </span><a href="https://doi.org/10.1016/j.cell.2022.11.001" target="_blank">10.1016/j.cell.2022.11.001</a>.</p>
<p><a name="Ref36" target="_blank"></a><span></span></p>
<p>36. Hasan-Olive, M.M.; Lauritzen, K.H.; Ali, M.; Rasmussen, L.J.; Storm-Mathisen, J.; Bergersen, L.H. A Ketogenic Diet Improves Mitochondrial Biogenesis and Bioenergetics via the PGC1α-SIRT3-UCP2 Axis. Neurochem Res 2019, 44, 22-37, doi:<span> </span><a href="https://doi.org/10.1007/s11064-018-2588-6" target="_blank">10.1007/s11064-018-2588-6</a>.</p>
<p><a name="Ref37" target="_blank"></a><span></span></p>
<p>37. Rojas-Morales, P.; Pedraza-Chaverri, J.; Tapia, E. Ketone Bodies, Stress Response, and Redox Homeostasis. Redox Biol 2020, 29, 101395, doi:<span> </span><a href="https://doi.org/10.1016/j.redox.2019.101395" target="_blank">10.1016/j.redox.2019.101395</a>.</p>
<p><a name="Ref38" target="_blank"></a><span></span></p>
<p>38. Chu, Y.; Zhang, C.; Xie, M. Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts. Front Aging 2021, 2, 681513, doi:<span> </span><a href="https://doi.org/10.3389/fragi.2021.681513" target="_blank">10.3389/fragi.2021.681513</a>.</p>
<p><a name="Ref39" target="_blank"></a><span></span></p>
<p>39. Conn, M.O.; Marko, D.M.; Schertzer, J.D. Intermittent Fasting Increases Fat Oxidation and Promotes Metabolic Flexibility in Lean Mice but Not Obese Type 2 Diabetic Mice. Am J Physiol Endocrinol Metab 2024, 327, E470-E477, doi:<span> </span><a href="https://doi.org/10.1152/ajpendo.00255.2024" target="_blank">10.1152/ajpendo.00255.2024</a>.</p>
<p><a name="Ref40" target="_blank"></a><span></span></p>
<p>40. Zhang, A.; Wang, J.; Zhao, Y.; He, Y.; Sun, N. Intermittent Fasting, Fatty Acid Metabolism Reprogramming, and Neuroimmuno Microenvironment: Mechanisms and Application Prospects. Front Nutr 2024, 11, 1485632, doi:<span> </span><a href="https://doi.org/10.3389/fnut.2024.1485632" target="_blank">10.3389/fnut.2024.1485632</a>.</p>
<p><a name="Ref41" target="_blank"></a><span></span></p>
<p>41. Anton, S.D.; Moehl, K.; Donahoo, W.T.; Marosi, K.; Lee, S.A.; Mainous, A.G.; Leeuwenburgh, C.; Mattson, M.P. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring) 2018, 26, 254-268, doi:<span> </span><a href="https://doi.org/10.1002/oby.22065" target="_blank">10.1002/oby.22065</a>.</p>
<p><a name="Ref42" target="_blank"></a><span></span></p>
<p>42. Holcomb, L.E.; O'Neill, C.C.; DeWitt, E.A.; Kolwicz, S.C. The Effects of Fasting or Ketogenic Diet on Endurance Exercise Performance and Metabolism in Female Mice. Metabolites 2021, 11, 397, doi:<span> </span><a href="https://doi.org/10.3390/metabo11060397" target="_blank">10.3390/metabo11060397</a>.</p>
<p><a name="Ref43" target="_blank"></a><span></span></p>
<p>43. McSwiney, F.T.; Wardrop, B.; Hyde, P.N.; Lafountain, R.A.; Volek, J.S.; Doyle, L. Keto-Adaptation Enhances Exercise Performance and Body Composition Responses to Training in Endurance Athletes. Metabolism 2018, 81, 25-34, doi:<span> </span><a href="https://doi.org/10.1016/j.metabol.2017.10.010" target="_blank">10.1016/j.metabol.2017.10.010</a>.</p>
<p><a name="Ref44" target="_blank"></a><span></span></p>
<p>44. Hansen, B.; Roomp, K.; Ebid, H.; Schneider, J.G. Perspective: The Impact of Fasting and Caloric Restriction on Neurodegenerative Diseases in Humans. Adv Nutr 2024, 15, 100197, doi:<span> </span><a href="https://doi.org/10.1016/j.advnut.2024.100197" target="_blank">10.1016/j.advnut.2024.100197</a>.</p>
<p><a name="Ref45" target="_blank"></a><span></span></p>
<p>45. Arora, S.K.; McFarlane, S.I. The Case for Low Carbohydrate Diets in Diabetes Management. Nutr Metab (Lond) 2005, 2, 16, doi:<span> </span><a href="https://doi.org/10.1186/1743-7075-2-16" target="_blank">10.1186/1743-7075-2-16</a>.</p>
<p><a name="Ref46" target="_blank"></a><span></span></p>
<p>46. Choi, J.H.; Cho, Y.J.; Kim, H.-J.; Ko, S.-H.; Chon, S.; Kang, J.-H.; Kim, K.-K.; Kim, E.M.; Kim, H.J.; Song, K.-H.; et al. Effect of Carbohydrate-Restricted Diets and Intermittent Fasting on Obesity, Type 2 Diabetes Mellitus, and Hypertension Management: Consensus Statement of the Korean Society for the Study of Obesity, Korean Diabetes Association, and Korean Society of Hypertension. J Obes Metab Syndr 2022, 31, 100-122, doi:<span> </span><a href="https://doi.org/10.7570/jomes22009" target="_blank">10.7570/jomes22009</a>.</p>
<p><a name="Ref47" target="_blank"></a><span></span></p>
<p>47. Gavidia, K.; Kalayjian, T. Treating Diabetes Utilizing a Low Carbohydrate Ketogenic Diet and Intermittent Fasting Without Significant Weight Loss: A Case Report. Front Nutr 2021, 8, 687081, doi:<span> </span><a href="https://doi.org/10.3389/fnut.2021.687081" target="_blank">10.3389/fnut.2021.687081</a>.</p>
<p><a name="Ref48" target="_blank"></a><span></span></p>
<p>48. Levy, T.E.; Gordon, G. Primal Panacea; 2012 Second Printing edition.; Medfox Publishing: Henderson, NV, 2011; ISBN 978-0-9837728-0-4.</p>
<p><a name="Ref49" target="_blank"></a><span></span></p>
<p>49. Grant, W.B.; Wimalawansa, S.J.; Pludowski, P.; Cheng, R.Z. Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines. Nutrients 2025, 17, 277, doi:<span> </span><a href="https://doi.org/10.3390/nu17020277" target="_blank">10.3390/nu17020277</a>.</p>
<p><a name="Ref50" target="_blank"></a><span></span></p>
<p>50. Grant, W.B.; Boucher, B.J.; Cheng, R.Z.; Pludowski, P.; Wimalawansa, S.J. Vitamin D and Cardiovascular Health: A Narrative Review of Risk Reduction Evidence. Nutrients 2025, 17, 2102, doi:<span> </span><a href="https://doi.org/10.3390/nu17132102" target="_blank">10.3390/nu17132102</a>.</p>
<p><a name="Ref51" target="_blank"></a><span></span></p>
<p>51. Pirinen, E.; Auranen, M.; Khan, N.A.; Brilhante, V.; Urho, N.; Pessia, A.; Hakkarainen, A.; Kuula, J.; Heinonen, U.; Schmidt, M.S.; et al. Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab 2020, 31, 1078-1090.e5, doi:<span> </span><a href="https://doi.org/10.1016/j.cmet.2020.04.008" target="_blank">10.1016/j.cmet.2020.04.008</a>.</p>
<p><a name="Ref52" target="_blank"></a><span></span></p>
<p>52. Cantó, C.; Menzies, K.J.; Auwerx, J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab 2015, 22, 31-53, doi:<span> </span><a href="https://doi.org/10.1016/j.cmet.2015.05.023" target="_blank">10.1016/j.cmet.2015.05.023</a>.</p>
<p><a name="Ref53" target="_blank"></a><span></span></p>
<p>53. Beltrà, M.; Pöllänen, N.; Fornelli, C.; Tonttila, K.; Hsu, M.Y.; Zampieri, S.; Moletta, L.; Corrà, S.; Porporato, P.E.; Kivelä, R.; et al. NAD+ Repletion with Niacin Counteracts Cancer Cachexia. Nat Commun 2023, 14, 1849, doi:<span> </span><a href="https://doi.org/10.1038/s41467-023-37595-6" target="_blank">10.1038/s41467-023-37595-6</a>.</p>
<p><a name="Ref54" target="_blank"></a><span></span></p>
<p>54. Levy, T. Magnesium: Reversing Disease: Levy MD, Jd: 9780998312408: Amazon.Com: Books Available online:<span> </span><a href="https://www.amazon.com/Magnesium-Reversing-MD-Jd-Levy/dp/0998312401/ref=pd_lpo_2?pd_rd_i=0998312401&amp;psc=1" target="_blank">https://www.amazon.com/Magnesium-Reversing-MD-Jd-Levy/dp/0998312401/ref=pd_lpo_2?pd_rd_i=0998312401&amp;psc=1</a><span> </span>(accessed on 12 February 2022).</p>
<p><a name="Ref55" target="_blank"></a><span></span></p>
<p>55. Dean, C. The Magnesium Miracle (Second Edition): Dean M.D. N.D., Carolyn: 9780399594441: Amazon.Com: Books Available online:<span> </span><a href="https://www.amazon.com/Magnesium-Miracle-Second-Carolyn-Dean/dp/0399594442" target="_blank">https://www.amazon.com/Magnesium-Miracle-Second-Carolyn-Dean/dp/0399594442</a><span> </span>(accessed on 12 February 2022).</p>
<hr>
<p> </p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/why-early-life-micronutrient-deficiency-leaves-lasting-damage-even-when-corrected-later</id>
    <published>2025-10-06T06:00:09-07:00</published>
    <updated>2025-10-06T06:00:09-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/why-early-life-micronutrient-deficiency-leaves-lasting-damage-even-when-corrected-later"/>
    <title>Why Early-Life Micronutrient Deficiency Leaves Lasting Damage - Even When Corrected Later</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p><b>By Richard Z. Cheng, M.D., Ph.D. Editor-in-Chief</b></p>
<p> </p>
<h2>Introduction</h2>
<p>Orthomolecular medicine emphasizes providing the body with the<span> </span><i>optimal</i><span> </span>concentrations of essential nutrients. Yet much of clinical nutrition focuses on correcting deficiencies only after they are discovered later in life. A crucial question is often overlooked:<span> </span><b>what happens if the deficiency occurred during early life-infancy, childhood, or even prenatally?</b><span> </span>Can later supplementation fully repair the damage?</p>
<p>While preparing for a cancer debate hosted by the Children's Health Defense, we identified ten categories of root drivers for cancer and other chronic diseases (Cheng, 2025, in preparation). One of these root drivers is<span> </span><i>Developmental &amp; Early-Life Programming</i>. This article takes a deeper look into that driver-focusing specifically on how micronutrient insufficiency during pregnancy, infancy, and childhood can leave permanent impacts that last a lifetime.</p>
<p>The emerging answer from animal and human studies is sobering:<span> </span><b>deficiencies in vitamins C and D during early life can cause changes in brain, immune, lung, and skeletal development that may never be fully reversed, even with later supplementation.</b></p>
<hr>
<h2>Vitamin C: Irreversible Impacts on Brain Development</h2>
<p>Humans, like guinea pigs, cannot make their own vitamin C. Animal studies clearly show that when vitamin C is lacking during pregnancy or early childhood, the brain-especially the hippocampus, which controls learning and memory-suffers damage that cannot be fully repaired later.</p>
<p><b>Lasting hippocampal damage:</b><span> </span>Guinea pigs born to vitamin-C deficient mothers had smaller hippocampal volume and fewer new brain cells. Even after vitamin C was given later, the brain never fully caught up<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref1" target="_blank">(1)</a>.</p>
<ul>
<li>
<i><b>Memory and neuron loss:</b><span> </span>In another study, young guinea pigs that lacked vitamin C early in life had fewer hippocampal neurons and poorer memory performance, confirming that early deficiency programs the brain for lasting problems</i><span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref2" target="_blank">(2)</a>.</li>
<li>
<b>Synapse and neurotransmitter disruption:</b><span> </span>A follow-up study found that vitamin C deficiency also weakens the brain's communication system. The deficient animals had fewer connections between brain cells (fewer synapses) and disturbances in the balance of brain chemicals like serotonin. These changes help explain why the animals developed memory deficits that did not disappear, even after vitamin C was reintroduced<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref3" target="_blank">(3)</a>.</li>
<li>Vitamin C is not only an antioxidant but also a cofactor for enzymes regulating collagen synthesis and DNA demethylation (TET enzymes). These<span> </span><b>epigenetic roles</b><span> </span>suggest that deficiency during critical developmental windows can "program"long-lasting structural and functional changes<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref4" target="_blank">(4)</a>.</li>
</ul>
<hr>
<h2>Vitamin D: Programming Lungs, Immunity, and Bones for Life</h2>
<p>Vitamin D is now recognized as a key hormone regulating development well beyond bones. A wealth of animal and human studies confirm that prenatal or early-life deficiency leaves<span> </span><b>long-term marks that supplementation later cannot fully erase</b>.</p>
<ul>
<li>
<b>Lung Development:</b><span> </span>In mice, antenatal vitamin-D deficiency caused narrowed airways and simplified alveoli. Even after postnatal vitamin-D supplementation,<span> </span><b>tracheal narrowing persisted</b>, and lung function remained impaired<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref5" target="_blank">(5,6)</a>.</li>
<li>
<b>Immune Programming:</b><span> </span>Prenatal vitamin-D deficiency left lasting "memory"in hematopoietic stem cells, skewing immune cell development long into adulthood<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref7" target="_blank">(7,8)</a>.</li>
<li>This cohort study showed that<span> </span><b>maternal vitamin D insufficiency was associated with lower whole-body and lumbar spine bone-mineral content in children at age 9</b>, indicating persistent skeletal effects<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref9" target="_blank">(9)</a>.</li>
<li>This follow-up indicated that maternal vitamin D deficiency during pregnancy predicted<span> </span><b>lower peak bone mass in their children at age ~20</b>, suggesting long-lasting skeletal programming<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref10" target="_blank">(10)</a>.</li>
</ul>
<p>Mechanistically, vitamin D deficiency during development influences epigenetic marks, gene expression, and hormone-sensitive signaling pathways, consistent with the<span> </span><b>Developmental Origins of Health and Disease (DOHaD)</b><span> </span>model<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref8" target="_blank">(8,</a><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref11" target="_blank">11-13)</a>.</p>
<hr>
<p>While vitamins C and D are central examples, research shows that other essential micronutrients also have time-sensitive roles in shaping lifelong health. A brief overview illustrates just how broad this principle is.</p>
<h3>Beyond C &amp; D: Other Early-Life Micronutrients with Lasting Effects (and Excellent Safety When Used Appropriately)</h3>
<h3>Iodine - Brain Wiring Depends on It</h3>
<p>Even mild iodine insufficiency in early pregnancy has been linked to lower verbal IQ and reading scores in school-age children. Timing matters: benefits are greatest when adequacy is ensured<span> </span><b>before or early in pregnancy</b><span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref14" target="_blank">(14-17)</a>.</p>
<h3>Iron - Learning Circuits Need Iron on Time</h3>
<p>Infancy is a high-risk window for iron deficiency. Follow-up studies into adolescence show persistent deficits in cognition, motor skills, and behavior after early-life iron deficiency, even when anemia is later corrected<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref18" target="_blank">(18)</a>.</p>
<h3>Folate (with B12) - Neural Tube Closure is a One-Time Event</h3>
<p>Peri-conceptional folic acid<span> </span><b>prevents neural tube defects (NTDs)</b>; this is now standard of care worldwide because catch-up later is impossible. Low maternal B12 independently raises NTD risk and is associated with poorer early neurodevelopment; folate and B12 adequacy together are safest<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref19" target="_blank">(19-23)</a>.</p>
<h3>Choline - Attention and Information-Processing Speed</h3>
<p>Randomized feeding trials show that maternal choline intake at ~2× current recommendations in the third trimester improved<span> </span><b>infant information-processing speed</b>, consistent with choline's role in methylation and cell-membrane formation during brain development<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref24" target="_blank">(24)</a>.</p>
<h3>Omega-3 DHA - Vision and Early Cognition</h3>
<p>DHA is a structural fat in the developing retina and brain. Randomized trials report<span> </span><b>better visual acuity</b><span> </span>and, in some studies, higher cognitive scores in infants receiving adequate DHA in milk/formula during early life<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref25" target="_blank">(25-27)</a>.</p>
<h3>Zinc - Growth, Immunity, and Neurodevelopmental Programming</h3>
<p>Zinc participates in DNA/RNA synthesis and synaptic plasticity. Deficiency during gestation can alter neuronal development in animal models; in humans, maternal zinc supplementation reduces<span> </span><b>preterm birth</b><span> </span>in low-zinc settings (a risk factor for later problems). Neurodevelopmental benefits appear context-dependent; ensuring adequacy is prudent and safe<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref28" target="_blank">(28-32)</a>.</p>
<h3>Vitamin A (retinoids) - Lung Structure and Function</h3>
<p>Retinoids guide airway and alveolar development. Maternal vitamin-A repletion at recommended levels improved<span> </span><b>offspring lung function</b><span> </span>years later in a randomized trial, underscoring a true developmental "window"<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref33" target="_blank">(33-36)</a>.</p>
<h3>Selenium - Thyroid and Redox Systems that Steer Development</h3>
<p>Selenoproteins support thyroid-hormone activation and redox balance in the developing brain. Emerging human data link low maternal selenium to adverse pregnancy and child outcomes; adequacy is essential, though unlike C and D, selenium has a narrower margin of safety, meaning supplementation should stay within recommended ranges<span> </span><a href="https://orthomolecular.activehosted.com/index.php?action=social&amp;chash=7d04bbbe5494ae9d2f5a76aa1c00fa2f.414&amp;s=f0efd3bc0da85c987defc367c0d5071a#Ref41" target="_blank">(37-41)</a>.</p>
<hr>
<h2>The Takeaway: Prevention, Not Catch-Up</h2>
<p>These findings reinforce a central principle of orthomolecular medicine:<span> </span><b>timing matters</b>. The body's critical growth periods demand optimal nutrition. Once developmental windows close, no amount of supplementation later may fully restore what was lost.</p>
<p>For clinicians, policymakers, and families, the implications are clear:</p>
<ul>
<li>Vitamin sufficiency must be ensured<span> </span><b>before conception, during pregnancy, and in early childhood</b>.</li>
<li>Routine screening of vitamin D and C status in pregnant women and young children should be a public health priority.</li>
<li>Orthomolecular medicine provides a science-based framework for early, safe, and effective prevention.</li>
</ul>
<p>Optimal nutrition during pregnancy and early childhood is one of the most cost-effective public health measures we have. Unlike pharmaceuticals, micronutrient sufficiency is safe, affordable, and universally accessible.</p>
<hr>
<h2>About the Author</h2>
<p><b>Richard Z. Cheng, M.D., Ph.D.</b><span> </span>-<span> </span><i>Editor-in-Chief, Orthomolecular Medicine News Service</i></p>
<p>Dr. Cheng is a U.S.-based, NIH-trained, board-certified physician specializing in integrative cancer therapy, orthomolecular medicine, functional &amp; anti-aging medicine. He maintains active practices in both the United States and China.</p>
<p>A Fellow of the American Academy of Anti-Aging Medicine and a Hall of Fame inductee of the International Society for Orthomolecular Medicine, Dr. Cheng is a leading advocate for nutrition-based, root-cause health strategies. He also serves as an expert reviewer for the South Carolina Board of Medical Examiners, and co-founded both the China Low Carb Medicine Alliance and the Society of International Metabolic Oncology.</p>
<p>Dr. Cheng offers<span> </span><b>online Integrative Orthomolecular Medicine consultation services</b>.<br>📰 Follow his latest insights on Substack:<span> </span><a href="https://substack.com/@rzchengmd" target="_blank">https://substack.com/@rzchengmd</a></p>
<hr>
<h2>References</h2>
<p> </p>
<p><a name="Ref1" target="_blank"></a><span></span></p>
<p>1. Tveden-Nyborg P, Vogt L, Schjoldager JG, Jeannet N, Hasselholt S, Paidi MD, et al. Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs. PLoS One. 2012;7(10):e48488.</p>
<p><a name="Ref2" target="_blank"></a><span></span></p>
<p>2. Tveden-Nyborg P, Johansen LK, Raida Z, Villumsen CK, Larsen JO, Lykkesfeldt J. Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs. Am J Clin Nutr. 2009 Sept;90(3):540-6.</p>
<p><a name="Ref3" target="_blank"></a><span></span></p>
<p>3. Hansen SN, Schou-Pedersen AMV, Lykkesfeldt J, Tveden-Nyborg P. Spatial Memory Dysfunction Induced by Vitamin C Deficiency Is Associated with Changes in Monoaminergic Neurotransmitters and Aberrant Synapse Formation. Antioxidants (Basel). 2018 June 29;7(7):82.</p>
<p><a name="Ref4" target="_blank"></a><span></span></p>
<p>4. Camarena V, Wang G. The epigenetic role of vitamin C in health and disease. Cell Mol Life Sci. 2016 Apr;73(8):1645-58.</p>
<p><a name="Ref5" target="_blank"></a><span></span></p>
<p>5. Saadoon A, Ambalavanan N, Zinn K, Ashraf AP, MacEwen M, Nicola T, et al. Effect of Prenatal versus Postnatal Vitamin D Deficiency on Pulmonary Structure and Function in Mice. Am J Respir Cell Mol Biol. 2017 Mar;56(3):383-92.</p>
<p><a name="Ref6" target="_blank"></a><span></span></p>
<p>6. Waiden J, Heydarian M, Oak P, Koschlig M, Kamgari N, Hagemann M, et al. Prenatal vitamin D supplementation mitigates inflammation-related alveolar remodeling in neonatal mice. Am J Physiol Lung Cell Mol Physiol. 2023 Aug 1;325(2):L95-103.</p>
<p><a name="Ref7" target="_blank"></a><span></span></p>
<p>7. Ueda K, Chin SS, Sato N, Nishikawa M, Yasuda K, Miyasaka N, et al. Prenatal vitamin D deficiency exposure leads to long-term changes in immune cell proportions. Sci Rep. 2024 Aug 27;14(1):19899.</p>
<p><a name="Ref8" target="_blank"></a><span></span></p>
<p>8. Oh J, Riek AE, Bauerle KT, Dusso A, McNerney KP, Barve RA, et al. Embryonic vitamin D deficiency programs hematopoietic stem cells to induce type 2 diabetes. Nat Commun. 2023 June 13;14(1):3278.</p>
<p><a name="Ref9" target="_blank"></a><span></span></p>
<p>9. Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, et al. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet. 2006 Jan 7;367(9504):36-43.</p>
<p><a name="Ref10" target="_blank"></a><span></span></p>
<p>10. Zhu K, Whitehouse AJO, Hart PH, Kusel M, Mountain J, Lye S, et al. Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: a prospective cohort study. J Bone Miner Res. 2014;29(5):1088-95.</p>
<p><a name="Ref11" target="_blank"></a><span></span></p>
<p>11. Ideraabdullah FY, Belenchia AM, Rosenfeld CS, Kullman SW, Knuth M, Mahapatra D, et al. Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD). J Endocrinol. 2019 May;241(2):R65-80.</p>
<p><a name="Ref12" target="_blank"></a><span></span></p>
<p>12. Bianco-Miotto T, Craig JM, Gasser YP, Dijk SJ van, Ozanne SE. Epigenetics and DOHaD: from basics to birth and beyond. Journal of Developmental Origins of Health and Disease. 2017 Oct;8(5):513-9.</p>
<p><a name="Ref13" target="_blank"></a><span></span></p>
<p>13. Fetahu IS, Höbaus J, Kállay E. Vitamin D and the epigenome. Front Physiol. 2014;5:164.</p>
<p><a name="Ref14" target="_blank"></a><span></span></p>
<p>14. Bath SC, Steer CD, Golding J, Emmett P, Rayman MP. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet. 2013 July 27;382(9889):331-7.</p>
<p><a name="Ref15" target="_blank"></a><span></span></p>
<p>15. Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr. 2009 Feb;89(2):668S-72S.</p>
<p><a name="Ref16" target="_blank"></a><span></span></p>
<p>16. Skeaff SA. Iodine deficiency in pregnancy: the effect on neurodevelopment in the child. Nutrients. 2011 Feb;3(2):265-73.</p>
<p><a name="Ref17" target="_blank"></a><span></span></p>
<p>17. Gowachirapant S, Jaiswal N, Melse-Boonstra A, Galetti V, Stinca S, Mackenzie I, et al. Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Nov;5(11):853-63.</p>
<p><a name="Ref18" target="_blank"></a><span></span></p>
<p>18. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006 May;64(5 Pt 2):S34-43; discussion S72-91.</p>
<p><a name="Ref19" target="_blank"></a><span></span></p>
<p>19. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991 July 20;338(8760):131-7.</p>
<p><a name="Ref20" target="_blank"></a><span></span></p>
<p>20. Molloy AM, Kirke PN, Troendle JF, Burke H, Sutton M, Brody LC, et al. Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification. Pediatrics. 2009 Mar;123(3):917-23.</p>
<p><a name="Ref21" target="_blank"></a><span></span></p>
<p>21. Behere RV, Deshmukh AS, Otiv S, Gupte MD, Yajnik CS. Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India. Front Endocrinol (Lausanne). 2021;12:619176.</p>
<p><a name="Ref22" target="_blank"></a><span></span></p>
<p>22. D'souza N, Behere RV, Patni B, Deshpande M, Bhat D, Bhalerao A, et al. Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial. Front Pediatr. 2021;9:755977.</p>
<p><a name="Ref23" target="_blank"></a><span></span></p>
<p>23. Cruz-Rodríguez J, Díaz-López A, Canals-Sans J, Arija V. Maternal Vitamin B12 Status during Pregnancy and Early Infant Neurodevelopment: The ECLIPSES Study. Nutrients. 2023 Jan;15(6):1529.</p>
<p><a name="Ref24" target="_blank"></a><span></span></p>
<p>24. Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. FASEB J. 2018 Apr;32(4):2172-80.</p>
<p><a name="Ref25" target="_blank"></a><span></span></p>
<p>25. Birch EE, Garfield S, Hoffman DR, Uauy R, Birch DG. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol. 2000 Mar;42(3):174-81.</p>
<p><a name="Ref26" target="_blank"></a><span></span></p>
<p>26. Birch EE, Carlson SE, Hoffman DR, Fitzgerald-Gustafson KM, Fu VLN, Drover JR, et al. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr. 2010 Apr;91(4):848-59.</p>
<p><a name="Ref27" target="_blank"></a><span></span></p>
<p>27. Uauy R, Hoffman DR, Mena P, Llanos A, Birch EE. Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials. J Pediatr. 2003 Oct;143(4 Suppl):S17-25.</p>
<p><a name="Ref28" target="_blank"></a><span></span></p>
<p>28. Adamo AM, Oteiza PI. Zinc deficiency and neurodevelopment: the case of neurons. Biofactors. 2010;36(2):117-24.</p>
<p><a name="Ref29" target="_blank"></a><span></span></p>
<p>29. Zinc supplementation for improving pregnancy and infant outcome [Internet]. [cited 2025 Aug 24]. Available from:<span> </span><a href="https://www.who.int/tools/elena/review-summaries/zinc-pregnancy--zinc-supplementation-for-improving-pregnancy-and-infant-outcome" target="_blank">https://www.who.int/tools/elena/review-summaries/zinc-pregnancy--zinc-supplementation-for-improving-pregnancy-and-infant-outcome</a></p>
<p><a name="Ref30" target="_blank"></a><span></span></p>
<p>30. Mendes Garrido Abregú F, Caniffi C, Arranz CT, Tomat AL. Impact of Zinc Deficiency During Prenatal and/or Postnatal Life on Cardiovascular and Metabolic Diseases: Experimental and Clinical Evidence. Adv Nutr. 2022 June 1;13(3):833-45.</p>
<p><a name="Ref31" target="_blank"></a><span></span></p>
<p>31. Tamura T, Goldenberg RL, Ramey SL, Nelson KG, Chapman VR. Effect of zinc supplementation of pregnant women on the mental and psychomotor development of their children at 5 y of age. Am J Clin Nutr. 2003 June;77(6):1512-6.</p>
<p><a name="Ref32" target="_blank"></a><span></span></p>
<p>32. Caulfield LE, Putnick DL, Zavaleta N, Lazarte F, Albornoz C, Chen P, et al. Maternal gestational zinc supplementation does not influence multiple aspects of child development at 54 mo of age in Peru123. The American Journal of Clinical Nutrition. 2010 July 1;92(1):130-6.</p>
<p><a name="Ref33" target="_blank"></a><span></span></p>
<p>33. Checkley W, West KP, Wise RA, Baldwin MR, Wu L, LeClerq SC, et al. Maternal vitamin A supplementation and lung function in offspring. N Engl J Med. 2010 May 13;362(19):1784-94.</p>
<p><a name="Ref34" target="_blank"></a><span></span></p>
<p>34. James ML, Ross AC, Bulger A, Philips JB, Ambalavanan N. Vitamin A and retinoic acid act synergistically to increase lung retinyl esters during normoxia and reduce hyperoxic lung injury in newborn mice. Pediatr Res. 2010 June;67(6):591-7.</p>
<p><a name="Ref35" target="_blank"></a><span></span></p>
<p>35. Ross AC, Ambalavanan N. Retinoic acid combined with vitamin A synergizes to increase retinyl ester storage in the lungs of newborn and dexamethasone-treated neonatal rats. Neonatology. 2007;92(1):26-32.</p>
<p><a name="Ref36" target="_blank"></a><span></span></p>
<p>36. Timoneda J, Rodríguez-Fernández L, Zaragozá R, Marín MP, Cabezuelo MT, Torres L, et al. Vitamin A Deficiency and the Lung. Nutrients. 2018 Aug 21;10(9):1132.</p>
<p><a name="Ref37" target="_blank"></a><span></span></p>
<p>37. Polanska K, Krol A, Sobala W, Gromadzinska J, Brodzka R, Calamandrei G, et al. Selenium status during pregnancy and child psychomotor development-Polish Mother and Child Cohort study. Pediatr Res. 2016 June;79(6):863-9.</p>
<p><a name="Ref38" target="_blank"></a><span></span></p>
<p>38. Hubalewska-Dydejczyk A, Duntas L, Gilis-Januszewska A. Pregnancy, thyroid, and the potential use of selenium. Hormones (Athens). 2020 Mar;19(1):47-53.</p>
<p><a name="Ref39" target="_blank"></a><span></span></p>
<p>39. Demircan K, Chillon TS, Jensen RC, Jensen TK, Sun Q, Bonnema SJ, et al. Maternal selenium deficiency during pregnancy in association with autism and ADHD traits in children: The Odense Child Cohort. Free Radic Biol Med. 2024 Aug 1;220:324-32.</p>
<p><a name="Ref40" target="_blank"></a><span></span></p>
<p>40. Calcaterra V, Cena H, Scavone IAM, Zambon I, Taranto S, Ricciardi Rizzo C, et al. Thyroid Health and Selenium: The Critical Role of Adequate Intake from Fetal Development to Adolescence. Nutrients. 2025 July 18;17(14):2362.</p>
<p><a name="Ref41" target="_blank"></a><span></span></p>
<p>41. Batyrova G, Taskozhina G, Umarova G, Umarov Y, Morenko M, Iriskulov B, et al. Unveiling the Role of Selenium in Child Development: Impacts on Growth, Neurodevelopment and Immunity. J Clin Med. 2025 Feb 14;14(4):1274.</p>
<p><span>OMNS free subscription</span><a href="http://orthomolecular.org/subscribe.html" target="_blank"> http://orthomolecular.org/subscribe.html</a><br><span>OMNS archive </span><a href="http://orthomolecular.org/resources/omns/index.shtml" target="_blank">http://orthomolecular.org/resources/omns/index.shtml</a></p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/the-clock-is-ticking-how-epigenetics-could-help-save-wildlife-from-collapse</id>
    <published>2025-09-29T06:00:01-07:00</published>
    <updated>2025-09-29T06:00:01-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/the-clock-is-ticking-how-epigenetics-could-help-save-wildlife-from-collapse"/>
    <title>The clock is ticking: How epigenetics could help save wildlife from collapse</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p class="article-info"> </p>
<p style="font-size: large; font-weight: 600;" class="article-subhead">In polar bears, dolphins, baboons and more, molecular signatures of aging are changing how conservationists assess population health, resilience and risk</p>
<p class="article-byline"><span style="border-top: 2px solid; border-bottom: 2px solid;" class="author-byline">By Elie Dolgin</span><br><span class="pub-date">09.22.2025<span> </span></span></p>
<div class="article-content">
<div class="article-text -drop-cap">
<p>Wildlife conservation is a race against time — too often, a losing one. Typically, by the time scientists detect signs of species decline, populations have already collapsed. Genetic diversity is already depleted. Birth rates have plunged. And by the time these biological red flags are seen, the window for effective intervention has nearly closed.</p>
<p>That’s what happened with the passenger pigeon: Once the most abundant bird in North America, it vanished in the blink of an ecological eye — wiped out by unchecked hunting and habitat destruction before anyone realized how fast the population was unraveling.</p>
<p>The same story played out with the Chinese river dolphin, the Pyrenean ibex and the Caribbean monk seal. Silent declines went unnoticed for years until the tipping point had passed, leaving conservationists to document extinctions instead of preventing them.</p>
<p><a href="https://knowablemagazine.org/content/article/living-world/2019/san-diegos-frozen-zoo-chance-animal-immortality">And the northern white rhino</a>? By the time the world finally paid attention, the damage was irreversible. Poachers had reduced the species to two surviving individuals — both female.</p>
<p>Determined to avoid more preventable losses, scientists have begun hunting for molecular warning signs that appear before populations spiral. But early leads, such as stress hormones and the length of the specialized tips of chromosomes — telomeres — have proved fickle, too easily swayed by the daily chaos of life in the wild. That’s why many scientists are now pinning their hopes on a novel tool called an epigenetic clock.</p>
<p>This molecular timekeeper doesn’t keep time like a wristwatch, though. Instead, it measures “biological age,” a hidden ledger that can echo the calendar’s count but also offers a more nuanced reflection of how fast an organism is wearing down from stress, disease and environmental hardship.</p>
<p>Epigenetic clocks work by analyzing patterns of chemical tags called methyl groups that get added to or subtracted from DNA at predictable sites across the <a href="https://knowablemagazine.org/content/article/living-world/2020/the-blueprint-life-neatly-folded">genome</a> as animals grow older. Some of these methylation signatures are remarkably stable and tightly linked to aging across many species. And, crucially for conservationists, they can be read from a simple tissue or blood sample.</p>
<div class="article-image -caption-center"><br></div>
<p>That makes epigenetic clocks especially valuable for elusive or <a href="https://knowablemagazine.org/content/article/health-disease/2021/genetic-tricks-longest-lived-animals">long-lived species</a>, where accurate age data are often missing. <a href="https://onlinelibrary.wiley.com/doi/10.1111/1755-0998.14120">Wildlife biologists are already using these clocks</a> to understand the age structures of animal populations, offering insights into their reproduction, survival and longevity. But the clocks hold deeper promise. When an animal’s biological age runs higher than its chronological one, it can signal physiological strain — a kind of molecular distress flare that may go off before any other visible signs of problems.</p>
<p>The potential for detecting accelerated aging before a population begins to visibly collapse is what excites Colin Garroway, an evolutionary ecologist at the University of Manitoba in Winnipeg, Canada. “Almost everything else we have is a lagging indicator of species decline,” he says. “This is at least potentially forward-looking.”</p>
<p>Garroway’s confidence in the power of epigenetic clocks took shape through a study of polar bears from the Canadian Arctic. In work now <a href="https://www.biorxiv.org/content/10.1101/2024.01.05.574416v2.full">posted on the preprint server bioRxiv</a>, he and his colleagues found that bears born in recent decades are aging markedly faster than those from earlier generations — their biological ages outpacing their chronological ones. The likely cause, the researchers conclude: Longer ice-free periods are stranding bears on land, cutting off access to the seals that form the core of their diet, ultimately sapping the fat reserves they need to survive.</p>
<p>“The change is too fast and too significant for them,” says coauthor Evan Richardson, a polar bear ecologist with Environment and Climate Change Canada, the government agency that partially funded the study. That burden is then evident in the telltale molecular marks on the animals’ DNA.</p>
<p>Richardson hopes the findings will force the “harder discussions” around polar bear management. But beyond sounding the alarm for this one imperiled species, he and his colleagues are hopeful that the wider conservation community will embrace epigenetic clocks as a proactive tool to safeguard biodiversity — before the point of no return.</p>
<p>As Meaghan Jones, a University of Manitoba medical geneticist involved in the research, puts it: “This is a way to monitor populations in real time and see how stress is impacting them while recovery is still possible.”</p>
<h2>Clocking in</h2>
<p>The idea of tracking biological age through molecular changes first gained traction in studies of human DNA. Beginning in the early 2010s, biogerontologist Steve Horvath — then at UCLA and now with the anti-aging biotech company Altos Labs — identified <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014821">dozens</a> and later <a href="https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-10-r115">hundreds</a> of sites in the genome where DNA methylation tags were predictably gained or lost as people grew older. He used methylation patterns to construct a statistical model that could estimate a person’s age, launching the first epigenetic clocks.</p>
<p>Horvath’s clocks emerged as powerful health indicators, with individuals whose biological age exceeded their chronological one showing a higher risk of chronic illness or early death — and <a href="https://www.annualreviews.org/content/journals/10.1146/annurev-publhealth-060222-015657">that same logic</a>, outlined in the 2025 issue of the <em>Annual Review of Public Health</em>, soon found a foothold in wildlife biology, too.</p>
<div class="article-image -caption-center"><br></div>
<p>In 2021, for example, a team led by Jenny Tung, an evolutionary anthropologist now at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, developed a baboon-specific version of the epigenetic clock and applied it to a wild population in Kenya’s Amboseli basin. The researchers found that males with a <a href="https://elifesciences.org/articles/66128">high dominance rank tended to be biologically older</a> than their lower-status peers, even when their chronological ages were the same.</p>
<p>It was a compelling demonstration that the clock could connect ecologically relevant pressures to accelerated aging in a wild animal. And contrary to what might be expected — that social success would track with better health — it revealed the biological toll of dominance. “Attaining and maintaining high rank is costly,” Tung says.</p>
<p>Other studies linking life stressors to accelerated aging would eventually follow — Garroway’s polar bear work among the most prominent — but most early adopters of epigenetic clocks for wildlife biology focused on a more basic goal: filling gaps in demographic data.</p>
<p>Traditionally, estimating the age of wildlife involves methods such as tooth extraction to count growth rings, which is labor-intensive and intrusive. Epigenetic clocks, in contrast, require a small tissue or blood sample, often obtainable through remote methods like dart biopsies. From there, researchers extract DNA and use lab methods to read the methylation patterns known to change with age. Then they apply statistical models to compare the patterns with animals of known ages.</p>
<p>Inspired by the work of Horvath and others, wildlife biologists began adapting epigenetic clocks for the animals they study: humpback whales, lampreys, sea turtles, salmon. Then, in 2017, Horvath secured a $1.5 million grant to build clocks for a menagerie of species.</p>
<h2>Lions and tigers and bears</h2>
<p>Horvath began cold-emailing field biologists, zoo veterinarians and wildlife researchers, inviting anyone with blood, DNA or other archived tissues in their freezers to join the project. “Whoever had samples became a partner,” he says.</p>
<p>Specimens poured in — for <a href="https://www.science.org/doi/10.1126/science.abq5693">nearly 350 animal species in total</a>, representing 25 of the 26 known taxonomic orders of mammal. Horvath generated clocks for elephants, bats, zebras, monkeys, marmots, mole rats and more. From this, he and his global network of collaborators built a <a href="https://www.nature.com/articles/s43587-023-00462-6">universal mammalian epigenetic clock</a>, one that factored in each species’ maximum lifespan alongside observable shifts in DNA methylation over time. The result was a clock that could accurately gauge an individual’s age, both chronological and biological, from a DNA sample — not just in humans or lab mice, but in otters, opossums and Tasmanian devils, too.</p>
<p>Horvath’s main aim was to explore how aging unfolds across the animal kingdom and what accelerates the process — potentially uncovering antiaging mechanisms that might be replicated pharmaceutically. But there were clear applications for conservation, starting with the infilling of missing details about survival and reproduction in the wild.</p>
<p>In Alaska, for example, wildlife biologist Susannah Woodruff, then with the US Fish and Wildlife Service and now with the state’s Department of Fish and Game, turned to the pan-mammalian clock to estimate the ages of the state’s polar bears. Working independently of the Canadian team pursuing similar questions, she and her colleagues first ran samples through this “universal” clock and found it performed reasonably well, producing estimates within a year or two of the bears’ true ages. “That’s pretty good,” Woodruff says.</p>
<p>Building a clock tailored specifically to polar bears was better still. Doing that required getting blood samples from known-age individuals — something not feasible for every species — but in Woodruff’s case, she had access to nearly 200 such bears. And as a <a href="https://onlinelibrary.wiley.com/doi/10.1002/ece3.71870">head-to-head comparison</a> published in July showed, the bear-specific clock yielded more precise and reliable results, pinpointing age to within plus-or-minus nine months.</p>
<div class="article-image -caption-full"><br></div>
<p>Short of developing a bespoke species clock, the next best thing can be to adapt one from closely related kin. That’s the approach taken to study the Lahille’s dolphin by conservation medicine veterinarian Ashley Barratclough of the nonprofit National Marine Mammal Foundation in San Diego. This vulnerable subspecies of bottlenose dolphin is found off the coast of South America, with fewer than 600 individuals left in the wild. Few have reliable age records.</p>
<p>Barratclough and her colleagues first <a href="https://www.mdpi.com/2673-5636/2/3/30">created a clock</a> for the common bottlenose dolphin, using blood and skin samples collected from known-age animals maintained by the US Navy. In collaboration with Brazilian marine biologist Pedro Fruet, Barratclough then applied the tool to the genetically distinct Lahille’s dolphin, filling in demographic black holes that, among other things, identified reproductive-age females, thus providing a focal point for conservationists to target in their efforts to rebuild the population.</p>
<p>“For an endangered cetacean species like the Lahille’s bottlenose dolphin, every piece of demographic information is extremely important to understand the future of the population,” says Fruet, founder of the conservation group Kaosa.<strong> </strong>“And the epigenetic clock tool is helping us to refine and get estimates that we couldn’t otherwise.”</p>
<p>Notably, in Brazil’s Patos Lagoon, where the true ages of some Lahille’s dolphins are known, the tool also revealed signs of accelerated aging, notes Fruet — a finding he fears may reflect the impact of pollutants from industry and agriculture, among other stresses. Barratclough has documented similar effects in the Gulf Coast of Louisiana, where dolphins exposed to oil pollution from the 2010 Deepwater Horizon disaster appear to <a href="https://www.sciencedirect.com/science/article/pii/S0006320724001320">have aged faster</a> than their counterparts living in cleaner waters elsewhere.</p>
<div class="article-image -caption-center"><br></div>
<h2>Worse for wear</h2>
<p>As evidence grows that epigenetic clocks can not only reveal true age but also flag premature aging, researchers are beginning to probe how environmental hardships shape the tempo of aging in the wild. At the University of Edinburgh in Scotland, for example, evolutionary biologist Tom Little and disease ecologist Amy Pedersen are now experimentally manipulating factors such as food availability and parasite load in wild wood mouse populations and then tracking the epigenetic fallout over time.</p>
<p>“If you look at the human literature, we’ve got all these things — diet, stress, infections — that we know influence biological age,” Little says. “But in wildlife, we just don’t know what environmental features drive animals to be gray before their time.”</p>
<p>Such research, however, requires running large numbers of samples through expensive molecular tests, and a major barrier to wider-scale adoption of wildlife clocks remains cost. The most commonly used testing platform — the Horvath Mammalian Array manufactured by the genomics giant Illumina and sold by the nonprofit <a href="https://clockfoundation.org/about-the-clock-foundation/">Epigenetic Clock Development Foundation</a> — runs about $200 per sample, which adds up quickly when trying to analyze dozens or hundreds of wild animals.</p>
<p>“It becomes very cost-prohibitive, especially in my budgetary world,” says Aaron Shafer, a population geneticist at Trent University in Peterborough, Canada, who is studying whether epigenetic clocks can reveal premature signs of aging linked to <a href="https://knowablemagazine.org/content/article/living-world/2024/chronic-wasting-disease-how-to-control-it">chronic wasting disease</a>, a deadly neurodegenerative illness affecting deer populations across North America. At the same time, Shafer is spearheading the development of lower-cost, custom-built tests to make the technology more accessible for conservation use.</p>
<p>In parallel, Garroway and Jones, together with Levi Newediuk, a wildlife ecologist at Mount Royal University in Calgary, Alberta, have been working on ways to <a href="https://onlinelibrary.wiley.com/doi/10.1111/1755-0998.14120">streamline the use of epigenetic clocks in wildlife research</a> so it can be applied in more species and settings. They also want to drive home the relevance of epigenetic clock data to policy decisions, by connecting biological aging directly to habitat degradation.</p>
<p>In their polar bear study, for instance, the researchers didn’t just document faster aging. They tied those biological shifts to tangible environmental change. Bears born in recent decades, as <a href="https://knowablemagazine.org/content/article/living-world/2022/as-arctic-warms-beavers-move-in">Arctic temperatures have risen</a>, showed clear signs of accelerated biological aging, the scientists found. And unpublished follow-up analyses indicate that the effect plays out unevenly across regions, shaped by the distinct ecological pressures faced by each population of bears.</p>
<div id="newsletter-promo-item">
<div class="newsletter-promo" style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;">
<div class="newsletter-promo-img" style="display: grid;"><br></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a href="https://knowablemagazine.org/newsletter-signup" style="border-bottom: none;"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<p>According to Newediuk, the trend was most pronounced around Hudson Bay, where <a href="https://knowablemagazine.org/content/article/food-environment/2018/arctic-warms-its-losing-more-just-ice">seasonal sea ice</a> breaks up earlier and forms later than it once did, curtailing hunting opportunities and limiting access to seals. In contrast, bears from regions with more stable ice, such as those living near the Beaufort Sea and around other parts of the high Arctic, are aging more slowly.</p>
<p>The findings, in other words, lend weight to long-standing concerns that vanishing sea ice isn’t just threatening the bears’ hunting grounds — it’s quietly eroding their biological resilience. “They’re in trouble, for sure,” Newediuk says.</p>
<p>Fortunately for the threatened wildlife, accelerated aging isn’t necessarily a one-way street. As Tung’s investigation of baboons has shown, it can be slowed — potentially reversed. Tung found that when male baboons lost dominance rank, their epigenetic clocks seemed to slow down. In a couple instances, biological age even ticked backward as males fell in social status, despite the passage of time.</p>
<p>That means the rate of aging is “not necessarily a fixed trait,” says Tung. And if it can be delayed in baboons, perhaps it can be rolled back in other species as well. “It opens the door to that possibility,” she says.</p>
</div>
</div>
<p><link rel="canonical" href="https://knowablemagazine.org/content/article/living-world/2025/epigenetic-clock-can-help-save-wildlife"> <meta name="syndication-source" content="https://knowablemagazine.org/content/article/living-world/2025/epigenetic-clock-can-help-save-wildlife" doi="10.1146/knowable-092225-1"></p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/dash-style-diet-helps-control-blood-glucose</id>
    <published>2025-08-19T14:33:06-07:00</published>
    <updated>2025-08-19T14:33:10-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/dash-style-diet-helps-control-blood-glucose"/>
    <title>DASH-style diet helps control blood glucose</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<div style- solid border-top:="" border-bottom:="">
  <p style="font-size: large;">—by Vicki Contie for NIH</p>
</div>
<div style="border: 0; border-left: 0.5rem solid #2c648e; background-color: #dbeefb; margin-top: 1rem; margin-bottom: 1rem; padding:0.5rem;">
<h2>At a Glance</h2>
  <ul style="font-size: large; font-weight: 600;">
    <li>Compared to a typical American diet, a DASH-style eating plan for people with diabetes led to more time with blood glucose in the recommended range.</li>
    <li>The results suggest that a modified DASH diet could help control blood sugar levels in adults with type 2 diabetes.</li>
  </ul>
</div>
<p>The Dietary Approaches to Stop Hypertension (DASH) diet was developed more than 30 years ago by NIH-supported research teams. It was designed to reduce high blood pressure. Studies have since shown that the DASH diet can have positive effects on cardiovascular health and may have other health benefits.</p>
<p>The DASH diet encourages eating fruits, vegetables, whole grains, and low-fat dairy products. It favors lean sources of protein, like beans and lean meats, and suggests limiting saturated fats and sugar-sweetened food and drinks. Because it emphasizes foods and nutrients that can also help control blood sugar, the diet is often recommended for people who have diabetes. But details of its impact on blood glucose control and variability are not fully understood.</p>
<p>A research team led in part by Dr. Elizabeth Selvin at Johns Hopkins Bloomberg School of Public Health aimed to take a closer look. They tweaked the DASH diet in ways designed to help people with type 2 diabetes. The modified diet, called DASH for Diabetes (DASH4D), suggests that carbohydrates be only about 45% of total calorie intake, compared to 55% in the original DASH diet. DASH4D also encourages less dietary potassium, to protect kidney health, and more unsaturated fats compared to the original DASH diet.</p>
<p>The clinical trial included 89 people with type 2 diabetes. Their mean age was 67 years, and 67% were female. The study used a crossover design, in which participants were fed one of four different diets, in random order, for five weeks. With at least one-week breaks in between, they were fed all four diets. Two of the diets were DASH4D, with either higher or lower salt intake (to evaluate blood pressure). The other two diets were typical of what’s eaten by many American adults, with either higher or lower salt. All meals were carefully measured and prepared in a clinical research kitchen. The diets were designed to maintain a stable weight, and participants ate no other foods during the study.</p>
<p>The researchers used a continuous glucose monitor to measure each participant’s blood glucose levels during each diet period. The monitor, attached to the upper arm, measured blood glucose levels every 15 minutes for up to two weeks. Study results were reported in <em>Nature Medicine</em> on August 5, 2025.</p>
<p>Overall, the DASH4D eating plans led to more time with blood glucose in the recommended range (between 70 and 180 mg/dl) and less time with glucose above 180 mg/dl compared to the typical American diets. DASH4D also led to significantly reduced mean glucose levels. On average, mean glucose was 11 mg/dl lower than when the people ate the typical American diets.</p>
<p>For participants with the highest blood glucose levels at the start, DASH4D led to more time in the optimal blood glucose range—about two or three more hours per day compared to the typical diet. </p>
<p>Because the study compared participants with themselves under different diet conditions, it eliminated variability between people, enhancing the statistical power of the study. This allowed the team to detect meaningful treatment effects despite the relatively small study size.</p>
<p>“The original DASH diet has long been recommended for people with diabetes and other health conditions due to its effectiveness in lowering blood pressure, but this is the first time a controlled study has shown a significant improvement in glucose control as well,” Selvin says.</p>
<h3>References</h3>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/40764427/">DASH4D diet for glycemic control and glucose variability in type 2 diabetes: a randomized crossover trial.</a> Fang M, Wang D, Rebholz CM, Echouffo-Tcheugui JB, Tang O, Wang NY, Mitchell CM, Pilla SJ, Appel LJ, Selvin E. <em>Nat Med.</em> 2025 Aug 5. doi: 10.1038/s41591-025-03823-3. Online ahead of print. PMID: 40764427.</p>
<h3>Funding</h3>
<p>NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Advancing Translational Sciences (NCATS), and National Heart, Lung, and Blood Institute (NHLBI); Sheikh Khalifa Stroke Institute at Johns Hopkins University School of Medicine; Johns Hopkins O’Brien Center to Advance Kidney Health Equity.</p>
]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/mighty-mitochondria-cell-powerhouses-harnessed-for-healing</id>
    <published>2025-07-14T06:00:01-07:00</published>
    <updated>2025-07-14T06:00:01-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/mighty-mitochondria-cell-powerhouses-harnessed-for-healing"/>
    <title>Mighty mitochondria: Cell powerhouses harnessed for healing</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p class="article-info" style="margin-left: 15%; margin-right: 15%;"><strong>Editor's Note:</strong> While this article does not directly mention micronutrients, mitochondria continue to be a focus of supplement research, as these tiny power plants are the source of much oxidative stress in our cells. Learning more about their abilities is crucial to developing supplement strategies for optimal health.</p>
<p class="article-subhead">Infusion of the tiny, sausage-shaped structures helps to rejuvenate tissues deprived of blood. Researchers hope the technique can treat a variety of damaged organs.</p>
<p class="article-byline" style="font-variant: small-caps; border-style: solid; border-width: 2px 0px 2px 0px; border-colour: darkcyan;"><span class="author-byline">By Jackie Rocheleau</span> <span class="pub-date">07.08.2025<span> </span></span></p>
<div class="article-content">
<div class="article-text -drop-cap">
<p><span style="float: left; font-size: 58px; font-weight: bold; line-height: .62; padding: 6px 7px 0 3px; text-transform: capitalize;">J</span>ames McCully was in the lab extracting tiny structures called mitochondria from cells when researchers on his team rushed in. They’d been operating on a pig heart and couldn’t get it pumping normally again.</p>
<p>McCully studies heart damage prevention at Boston Children’s Hospital and Harvard Medical School and was keenly interested in <a href="https://knowablemagazine.org/content/article/living-world/2022/mitochondria-origin-eukaryotes">mitochondria</a>. These power-producing organelles are particularly important for organs like the heart that have high energy needs. McCully had been wondering whether transplanting healthy mitochondria into injured hearts might help restore their function.</p>
<p>The pig’s heart was graying rapidly, so McCully decided to try it. He loaded a syringe with the extracted mitochondria and injected them directly into the heart. Before his eyes, it began beating normally, returning to its rosy hue.</p>
<p>Since that day almost 20 years ago, McCully and other researchers have replicated that success in pigs and other animals. Human transplantations followed, in babies who suffered complications from heart surgery — sparking a new field of research using <a href="https://www.nature.com/articles/s42255-024-01200-x">mitochondria transplantation</a> to treat damaged organs and disease. In the last five years, a widening array of scientists have begun exploring mitochondria transplantation for <a href="https://elifesciences.org/articles/98554#content">heart damage after cardiac arrest</a>, <a href="https://link.springer.com/article/10.1186/s12967-021-02878-3">brain damage following stroke</a> and damage to organs destined for transplantation.</p>
<div class="article-image -caption-center"><br></div>
<p>Mitochondria are best known for producing usable energy for cells. But they also send molecular signals that help to keep the body in equilibrium and manage its immune and stress responses. Some types of cells may naturally donate healthy mitochondria to other cells in need, such as <a href="https://knowablemagazine.org/content/article/mind/2022/mapping-brain-understand-mind">brain cells</a> after a stroke, in a process called mitochondria transfer. So the idea that clinicians could boost this process by transplanting mitochondria to reinvigorate injured tissue made sense to some scientists.</p>
<p>From studies in <a href="https://journals.physiology.org/doi/full/10.1152/ajpheart.00883.2012?rfr_dat=cr_pub++0pubmed&amp;url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org"> rabbits and rat heart cells</a>, McCully’s group has reported that <a href="https://journals.biologists.com/bio/article/4/5/622/1395/Actin-dependent-mitochondrial-internalization-in">the plasma membranes of cells engulf the mitochondria</a> and shuttle them inside, where they fuse with the cell’s internal mitochondria. There, they seem to cause <a href="https://www.nature.com/articles/s41598-024-82578-2">molecular changes that help recover heart function</a>: When comparing blood- and oxygen-deprived pig hearts treated with mitochondria to ones receiving placebos, McCully’s group saw differences in gene activity and proteins that indicated less <a href="https://knowablemagazine.org/content/article/living-world/2024/apoptosis-necrosis-and-other-ways-cells-can-die">cell death</a> and less inflammation.</p>
<p>About 10 years ago, Sitaram Emani, a cardiac surgeon at Boston Children's Hospital, reached out to McCully about his work with animal hearts. Emani had seen how some babies with heart defects couldn’t fully recover after heart surgery complications and wondered whether McCully’s mitochondria transplantation method could help them.</p>
<p>During surgery to repair heart defects, surgeons use a drug to stop the heart so they can operate. But if the heart is deprived of blood and oxygen for too long, mitochondria start to fail and cells start to die, in a condition called ischemia. When blood begins flowing again, instead of returning the heart to its normal state, it can damage and kill more cells, resulting in ischemia-reperfusion injury.</p>
<p>Since McCully’s eight years of studies in <a href="https://journals.physiology.org/doi/full/10.1152/ajpheart.00567.2008">rabbits</a> and <a href="https://www.sciencedirect.com/science/article/pii/S2452302X19302608?via%3Dihub">pigs</a> hadn’t revealed safety concerns with mitochondria transplantation, McCully and Emani thought it would be worth trying the procedure in babies unlikely to regain enough heart function to come off heart-lung support.</p>
<div class="article-image -caption-full"><br></div>
<p>Parents of 10 patients agreed to the experimental procedure, which was approved by the institute’s review board. In a pilot that ran from 2015 to 2018, McCully extracted pencil-eraser-sized muscle samples from the incisions made for the heart surgery, used a filtration technique to isolate mitochondria and checked that they were functional. Then the team injected the organelles into the baby’s heart.</p>
<p><a href="https://www.jtcvs.org/article/S0022-5223(20)33142-1/fulltext">Eight of those 10 babies regained enough heart function</a> to come off life support, compared to just four out of 14 similar cases from 2002 to 2018 that were used for historical comparison, the team reported in 2021. The treatment also shortened recovery time, which averaged two days in the mitochondrial transplant group compared with nine days in the historical control group. Two patients did not survive — in one case, the intervention came after the rest of the baby’s organs began failing, and in another, a lung issue developed four months later. The group has now performed this procedure on 17 babies.</p>
<p>The transplant procedure remains experimental and is not yet practical for wider clinical use, but McCully hopes that it can one day be used to treat <a href="https://app.jove.com/t/62230/a-large-animal-model-for-acute-kidney-injury-temporary-bilateral">kidney</a>, <a href="https://journals.physiology.org/doi/full/10.1152/ajplung.00221.2019?rfr_dat=cr_pub++0pubmed&amp;url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org">lung</a>, <a href="https://journals.lww.com/annalsofsurgery/abstract/2025/06000/mitochondrial_transplantation__a_novel_therapy_for.20.aspx">liver</a> and <a href="https://linkinghub.elsevier.com/retrieve/pii/S0741-5214(19)31188-7">limb</a> injuries from interrupted blood flow.</p>
<p>The results have inspired other clinicians whose patients suffer from similar ischemia-reperfusion injuries. One is ischemic stroke, in which clots prevent blood from reaching the brain. Doctors can dissolve or physically remove the clots, but they lack a way to protect the brain from reperfusion damage. “You see patients that lose their ability to walk or talk,” says Melanie Walker, an endovascular neurosurgeon at the University of Washington School of Medicine in Seattle. “You just want to do better and there’s just nothing out there.”</p>
<p>Walker came across McCully’s mitochondrial transplant studies 12 years ago and, in reading further, was especially struck by a report on mice from researchers at Massachusetts General Hospital and Harvard Medical School that showed the brain’s support and protection cells — the astrocytes — may <a href="https://www.nature.com/articles/nature18928">transfer some of their mitochondria to stroke-damaged neurons</a> to help them recover. Perhaps, she thought, mitochondria transplantation could help in human stroke cases too.</p>
<p>She spent years working with animal researchers to figure out how to safely deliver mitochondria to the brain. She tested the procedure’s safety in a clinical trial with just four people with ischemic stroke, using a catheter fed through an artery in the neck to manually remove the blockage causing the stroke, then pushing the catheter further along and releasing the mitochondria, which would travel up blood vessels to the brain.</p>
<div class="article-image -caption-full"><br></div>
<p>The findings, published in 2024 in the <em>Journal of Cerebral Blood Flow &amp; Metabolism</em>, show that <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11615905/">the infused patients suffered no harm</a>; the trial was not designed to test effectiveness. Walker’s group is now recruiting participants to further assess the intervention’s safety. The next step will be to determine whether the mitochondria are getting where they need to be, and functioning. “Until we can show that, I do not believe that we will be able to say that there’s a therapeutic benefit,” Walker says.</p>
<p>Researchers hope that organ donation might also gain from mitochondria transplants. Donor organs like kidneys suffer damage when they lack blood supply for too long, and transplant surgeons may reject kidneys with a higher risk of these injuries.</p>
<p>To test whether mitochondrial transplants can reinvigorate them, transplant surgeon-scientist Giuseppe Orlando of Wake Forest University School of Medicine in Winston-Salem and his colleagues injected mitochondria into four pig kidneys, and a control substance into three pig kidneys. In 2023 in the <em>Annals of Surgery</em>, they reported <a href="https://journals.lww.com/annalsofsurgery/fulltext/2023/12000/mitochondria_transplantation_mitigates_damage_in.55.aspx">fewer dying cells in the mitochondria-treated kidneys</a>, and far less damage. Molecular analyses also showed a boost in energy production.</p>
<p>It’s still early days, Orlando says, but he’s confident that mitochondria transplantation could become a valuable tool in rescuing suboptimal organs for donation.</p>
<p>The studies have garnered both excitement and skepticism. “It’s certainly a very interesting area,” says Koning Shen, a postdoctoral mitochondrial biologist at the University of California, Berkeley, and coauthor of an overview of the <a href="http://arjournals.annualreviews.org/eprint/XVYMRWXYBRY2VHNCXGCE/full/10.1146/annurev-cellbio-120420-015303">signaling roles of mitochondria</a> in the 2022 <em>Annual Review of Cell and Developmental Biology</em>. She adds that scaling up extraction of mitochondria and learning how to store and preserve the isolated organelles are major technical hurdles to making such treatments a larger reality. “That would be amazing if people are getting to that stage,” she says.</p>
<p>“I think there are a lot of thoughtful people looking at this carefully, but I think the big question is, what’s the mechanism?” says Navdeep Chandel, a mitochondria researcher at Northwestern University in Chicago. He doubts that donor mitochondria fix or replace dysfunctional native organelles, but says it’s possible that mitochondria donation triggers stress and <a href="https://www.nature.com/articles/s41586-024-07340-0">immune signals</a> that indirectly benefit damaged tissue.</p>
<div id="newsletter-promo-item">
<div style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;" class="newsletter-promo">
<div style="display: grid;" class="newsletter-promo-img"><br></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a style="border-bottom: none;" href="https://knowablemagazine.org/newsletter-signup"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<p>Whatever the mechanism, some animal studies do suggest that the mitochondria must be functional to impart their benefits. Lance Becker, chair of emergency medicine at Northwell Health in New York who studies the role of mitochondria in cardiac arrest, conducted a study comparing fresh mitochondria, mitochondria that had been frozen then thawed, and a placebo to treat rats following cardiac arrest. The 11 rats receiving fresh, functioning mitochondria had <a href="https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02759-0#Sec19">better brain function and a higher rate of survival three days later</a> than the 11 rats receiving a placebo; the non-functional frozen-thawed mitochondria did not impart these benefits.</p>
<p>It will take more research into the mechanisms of mitochondrial therapy, improved mitochondria delivery techniques, larger trials and a body of reported successes before mitochondrial transplants can be FDA-approved and broadly used to treat ischemia-reperfusion injuries, researchers say. The ultimate goal would be to create a universal supply of stored mitochondria — a mitochondria bank, of sorts — that can be tapped for transplantation by a wide variety of health care providers.</p>
<p>“We’re so much at the beginning — we don’t know how it works,” says Becker. “But we know it’s doing something that is mighty darn interesting.”</p>
</div>
</div>
<p><link href="https://knowablemagazine.org/content/article/technology/2025/mitochondrial-therapy-to-treat-damaged-organs" rel="canonical"> <meta doi="10.1146/knowable-070825-1" content="https://knowablemagazine.org/content/article/technology/2025/mitochondrial-therapy-to-treat-damaged-organs" name="syndication-source"></p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/research-in-context-can-we-slow-aging</id>
    <published>2025-05-12T06:00:02-07:00</published>
    <updated>2025-05-12T06:00:02-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/research-in-context-can-we-slow-aging"/>
    <title>Research in Context: Can we slow aging?</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[	<header>
		<div style="border-style: solid; border-color: #2c648e; border-width: 1px 1px 1px 15px; padding: 1rem; margin-bottom: 2rem;">
		<h2 style="font-style: italic;">What happens in our bodies as we age, and what can be done about it</h2>
		<p>Aging is a leading cause of disease and disability. This special <em>Research in Context</em> feature explores research into the biology of aging, including how to measure its speed and progression and ways it might be slowed down or even reversed.</p>
		<p style="font-weight: bold;">—by Brian Doctrow, Ph.D.</p>
		<p><span style="font-size: large; font-variant: small-caps;">Reposted from the National Institutes of Health</span><br>
		<a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging" target="new">https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging</a></p>
		</div>
	</header>
<main>
		<section class="intro" style="margin-bottom: 2rem;">
			<p>With advancing age comes an increased risk of disease and disability. As people live longer, they are more likely to develop at least one age-related disease. And as the global population gets older, the global burden of these diseases is expected to grow. Instead of treating each individual disease as it arises, a more effective way to reduce this burden would be to attack them at their common root: the aging process itself.</p>
			<p>Scientists today understand aging as the tendency that all things have to degrade over time. Dr. Tony Wyss-Coray, who studies brain aging and neurodegeneration at Stanford University, likens it to what happens to a car. “You get it off the lot and it's all shiny, and everything works perfectly. As you keep driving it over the years, all the parts look older. It may still run fine, but the exposure to the elements and usage leads to a growing level of wear and tear and then ultimately dysfunction.”</p>
			<p>Similarly, aging in people results from the gradual accumulation of defects and damage to the molecules and cells that make up our bodies. Unlike a car, our bodies have built-in mechanisms for repairing this damage. But even these repair mechanisms wear out over time. Eventually, enough damage accumulates to affect the function of whole organs and systems.</p>
			<p>NIH-funded researchers have been working to better understand aging at the molecular level. They’re studying ways to measure differences in how people age before health problems appear. They’re also exploring possible ways to slow, or even reverse, aging at the molecular level. This could lead to better approaches to prevent or treat age-related disease and disability.</p>
		</section>
		<section class="aging" style="margin-bottom: 2rem;">
			<h3>Measuring Aging</h3>
			<p>Before you can tell if a treatment could slow or even reverse aging, you need to know how fast someone is aging in the first place. It’s no secret that people age at different rates. Some people remain healthy and disease-free well into their ninth or even tenth decade of life. Others develop age-related diseases, such as cancer, heart disease, and dementia, much earlier. The concept of “biological age” is often used to describe these differences. Biological age reflects the molecular damage that accumulates over the years and eventually leads to disease and disability.</p>
			<p>Differences in biological age can develop years before age-related diseases appear. So a treatment to slow aging would also need to start well before such diseases appear. Then, to find out if a treatment worked or not, you’d have to track people for the rest of their lives. That’s why researchers have been working to develop “aging clocks” to measure a person’s biological age.</p>
			<p>One approach is to measure various biomarkers and compare them to what’s typical for a given chronological age. Dr. Daniel Belsky, who studies aging at the Columbia Mailman School of Public Health, explains, “We use the general population as a reference, and we say, ‘the average 50-year-old looks like this, the average 60-year-old looks like this, the average 70-year-old looks like this.’ We take your biomarker levels and line them up against that population average, and we say, ‘Aha, you look about like a 55-year-old, so we’re going to call you biologically 55.’ If you happen to be 65 years old, that's great news. If you happen to be 45, it’s not great news.”</p>
			<p>Belsky has taken this a step further. Instead of just an aging clock, which shows how much someone has aged, Belsky’s team, in collaboration with Dr. Terrie Moffitt’s team at Duke University and the Dunedin Longitudinal Study, developed an aging “speedometer.” It shows how fast or slow someone is aging.</p>
			<p>The researchers focused on chemical modifications to DNA, called DNA methylation, that change with age. To develop the measure, they used data from the Dunedin Study, a long-term health study of more than 1,000 people born in New Zealand in 1972-73. As part of the study, participants received comprehensive health evaluations at four time points from ages 26 to 45. These gathered DNA methylation data from blood samples and 19 biomarkers that track the function of various organ systems. Using machine-learning tools, the team developed an algorithm to identify DNA methylation patterns at age 45 that correlate with changes in the 19 biomarkers over a 20-year period. They named this algorithm DunedinPACE (Dunedin Pace of Aging Calculated from the Epigenome).</p>
			<p>Belsky and his colleagues then applied DunedinPACE to data from other long-term studies. People in these studies with a faster rate of aging, as measured by DunedinPACE, had a greater risk of poor health, developing chronic disease, or dying earlier.</p>
			<p>Belsky hopes that DunedinPACE could be used to test age-slowing interventions. It could also help to identify people who are aging faster than normal, and so at greater risk of age-related disease. “Say I’m 45 this year and I’m going to age into eligibility for certain cancer screenings,” he explains. “If I was aging biologically more rapidly, my doctor might think, ‘Oh, you know what, we should start some of these screenings a year or two earlier.’ Or if I’m aging slowly, they might say, ‘you know, you could decide to wait a year or two.’”</p>
			<p>It turns out that different organs can age at different rates, too, even in the same person. So, for example, someone might have a heart that’s aged more than the rest of their body. Wyss-Coray has shown that it’s possible to measure the aging of individual organs based on levels of certain proteins in the blood. Accelerated aging in a specific organ increases the risk of diseases affecting that organ. So, knowing the aging rates of individual organs could help to further focus care on those organs most likely to cause problems in the future.</p>
		</section>
		<section class="rejuvenating" style="margin-bottom: 2rem;">
			<h3>Rejuvenating old brains</h3>
			<p>Among the most serious health effects of aging are in the brain. As we age, the ability of neurons to strengthen connections, called synaptic plasticity, decreases. Synaptic plasticity, particularly in a region of the brain called the hippocampus, is required for learning and memory. Thus, the loss of plasticity with age can lead to cognitive impairment and increased susceptibility to neurodegenerative diseases. Preserving or restoring this ability might keep people cognitively healthy and able to live independently for longer.</p>
			<p>In 2014, Wyss-Coray and his colleagues showed that blood from young mice could have beneficial effects on the brains of aged mice. When the blood of a young mouse was introduced into an old mouse, it altered how genes related to synaptic plasticity were activated, or expressed, in the aged mouse. It also increased measures of plasticity in the hippocampus of the aged mouse. When the researchers injected aged mice with blood plasma from young mice, it improved learning and memory. These results suggested that something in the young mice’s blood could reverse the age-related loss of plasticity.</p>
			<p>About the youngest blood you can get is from the umbilical cord at birth. Injecting aged mice with plasma from human umbilical cord blood had similar effects on gene expression, plasticity, and cognitive function as plasma from young mice. So, whatever anti-aging factor was in young mouse plasma could also be found in human cord plasma.</p>
			<p>To find out what this factor might be, the team compared proteins in cord plasma and plasma from young and aged mice and humans. They zeroed in on a protein called tissue inhibitor of metalloproteinases 2 (TIMP2). TIMP2 could also be found in the mouse hippocampus, where its levels declined with age. Injecting aged mice with TIMP2 increased its level in the brain, promoted plasticity in the hippocampus, and improved learning and memory. When cord blood was depleted of TIMP2, it had no effect on learning and memory in aged mice. This showed that TIMP2 was responsible for these effects.</p>
			<p>The findings suggest that plasma from young donors, or components of their plasma, might be used to treat neurodegeneration. Wyss-Coray founded a company, Alkahest Inc., to perform clinical trials of this approach. But it may be some time before plasma-based treatments are ready for widespread use. More generally, Wyss-Coray’s findings support the notion that at least some of the consequences of aging are reversible.</p>
		</section>
		<section class="restricting" style="margin-bottom: 2rem;">
			<h3>Restricting calories</h3>
			<p>Age-reversing therapies like these are still some way in the future. Are there measures people can take now to at least slow the aging process?</p>
			<p>“Absolutely,” Belsky says, “and none of them are very exciting.” The things people already do to stay healthy in general are also the best ways to stave off the effects of aging. “Physical activity is the closest thing to a fountain of youth that we know of,” he explains. Healthy eating can also play a major role in staving off the effects of aging.</p>
			<p>Still, there are hints of lifestyle interventions that may have potential to lengthen life and delay aging. One that’s been particularly well-studied is calorie restriction (CR). This is where you reduce the total number of calories you consume, but still get enough of the essential nutrients. From yeast to rodents, studies have found that CR can increase longevity and delay age-related diseases.</p>
			<p>To find out whether CR might have benefits in humans, too, NIH funded the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study. More than 200 healthy, middle-aged volunteers were randomly assigned to two groups. Participants in one group were challenged to reduce their daily caloric intake by 25% for two years and given dietary and behavioral strategies for doing so. Those in the other group continued to eat their normal diets.</p>
			<p>Participants in the CR group managed to achieve an average 12.5% calorie reduction. For a 2,000 calorie-per-day diet, that amounts to 250 fewer calories per day, about the number of calories in a bagel. Participants lost an average of 10% of their body weight, mostly from fat.</p>
			<p>Researchers led by Belsky examined the pace of biological aging in CALERIE participants. Those in the CR group had a much slower pace of aging as measured by clinical blood biomarkers. They also had a small but significant decrease in DunedinPACE, while participants in the other group did not.</p>
			<p>One interesting result was that CR led to a small but significant decline in muscle tissue. But there was no significant decline in muscle strength. This suggests that CR may have improved the quality of muscle in the body.</p>
			<p>Researchers wanted to explore this result further and find out how CR improved muscle health. The team was led by Luigi Ferrucci, the scientific director of NIH’s National Institute on Aging (NIA), and also included Belsky. They analyzed thigh muscle biopsies taken from a subset of CALERIE participants at the start of the study and at one-year intervals.</p>
			<p>The team identified more than 1,000 genes whose expression differed between the CR and control groups. Many of the affected genes had already been found to be affected by CR in animal models. Gene expression increased in biological pathways related to muscle formation and repair, circadian clock regulation, and mechanisms tied to aging. Meanwhile, expression decreased in pathways related to inflammation. Several of these pathway changes appeared to mediate the effect of CR on muscle strength.</p>
			<p>Notably, CR also had an effect on RNA splicing. Genes must be transcribed into messenger RNA (mRNA) before they can be translated into protein. This mRNA undergoes splicing to reach its final form. A single gene can thus produce more than one protein if its mRNA gets spliced in different ways. CR led to changes in the splicing variants produced from many genes, including those involved in muscle physiology and aging.</p>
			<p>Over the long term, CR might be able to prevent age-related declines in muscle function. Ferrucci is optimistic that even a small amount of CR could go a long way toward preserving people’s health as they age, although further study is needed.</p>
			<p>But Ferrucci echoes Belsky’s view that there are many practical measures that we already know can slow aging. “Being physically active is the best gift that you can give to yourself,” he says.</p>
			<p>Other measures he recommends include not smoking, maintaining a healthy weight, getting good sleep, getting all recommended vaccines, getting preventive cancer screenings, and treating hypertension and high cholesterol. “People have demonstrated that if you do these things, which are all feasible, you can increase your life expectancy by 10 years. We don’t need a magic pill,” he adds. “The magic pill is already here.”</p>
		</section>
	</main>
		<section class="references" style="margin-bottom: 2rem; font-size: small;">
			<h3>References</h3>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/32367804/">Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm.</a> Belsky DW, Caspi A, Arseneault L, Baccarelli A, Corcoran DL, Gao X, Hannon E, Harrington HL, Rasmussen LJ, Houts R, Huffman K, Kraus WE, Kwon D, Mill J, Pieper CF, Prinz JA, Poulton R, Schwartz J, Sugden K, Vokonas P, Williams BS, Moffitt TE. <em>Elife</em>. 2020 May 5;9:e54870. doi: 10.7554/eLife.54870. PMID: 32367804.</p>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/35029144/">DunedinPACE, a DNA methylation biomarker of the pace of aging.</a> Belsky DW, Caspi A, Corcoran DL, Sugden K, Poulton R, Arseneault L, Baccarelli A, Chamarti K, Gao X, Hannon E, Harrington HL, Houts R, Kothari M, Kwon D, Mill J, Schwartz J, Vokonas P, Wang C, Williams BS, Moffitt TE. <em>Elife</em>. 2022 Jan 14;11:e73420. doi: 10.7554/eLife.73420. PMID: 35029144.</p>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/38057571/">Organ aging signatures in the plasma proteome track health and disease.</a> Oh HS, Rutledge J, Nachun D, Pálovics R, Abiose O, Moran-Losada P, Channappa D, Urey DY, Kim K, Sung YJ, Wang L, Timsina J, Western D, Liu M, Kohlfeld P, Budde J, Wilson EN, Guen Y, Maurer TM, Haney M, Yang AC, He Z, Greicius MD, Andreasson KI, Sathyan S, Weiss EF, Milman S, Barzilai N, Cruchaga C, Wagner AD, Mormino E, Lehallier B, Henderson VW, Longo FM, Montgomery SB, Wyss-Coray T. <em>Nature</em>. 2023 Dec;624(7990):164-172. doi: 10.1038/s41586-023-06802-1. Epub 2023 Dec 6. PMID: 38057571.</p>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/24793238/">Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.</a> Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. <em>Nat Med.</em> 2014 Jun;20(6):659-63. doi: 10.1038/nm.3569. Epub 2014 May 4. PMID: 24793238.</p>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/28424512/">Human umbilical cord plasma proteins revitalize hippocampal function in aged mice.</a> Castellano JM, Mosher KI, Abbey RJ, McBride AA, James ML, Berdnik D, Shen JC, Zou B, Xie XS, Tingle M, Hinkson IV, Angst MS, Wyss-Coray T. <em>Nature.</em> 2017 Apr 27;544(7651):488-492. doi: 10.1038/nature22067. Epub 2017 Apr 19. PMID: 28424512.</p>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/28531269/">Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis.</a> Belsky DW, Huffman KM, Pieper CF, Shalev I, Kraus WE. <em>J Gerontol A Biol Sci Med Sci</em>. 2017 Dec 12;73(1):4-10. doi: 10.1093/gerona/glx096. PMID: 28531269.</p>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/37118425/">Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.</a> Waziry R, Ryan CP, Corcoran DL, Huffman KM, Kobor MS, Kothari M, Graf GH, Kraus VB, Kraus WE, Lin DTS, Pieper CF, Ramaker ME, Bhapkar M, Das SK, Ferrucci L, Hastings WJ, Kebbe M, Parker DC, Racette SB, Shalev I, Schilling B, Belsky DW. <em>Nat Aging</em>. 2023 Mar;3(3):248-257. doi: 10.1038/s43587-022-00357-y. Epub 2023 Feb 9. PMID: 37118425.</p>
				<p><a href="https://pubmed.ncbi.nlm.nih.gov/37823711/">Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.</a> Das JK, Banskota N, Candia J, Griswold ME, Orenduff M, de Cabo R, Corcoran DL, Das SK, De S, Huffman KM, Kraus VB, Kraus WE, Martin CK, Racette SB, Redman LM, Schilling B, Belsky DW, Ferrucci L. <em>Aging Cell</em>. 2023 Dec;22(12):e13963. doi: 10.1111/acel.13963. Epub 2023 Oct 12. PMID: 37823711.</p>
		</section>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/celebrating-the-101st-birthday-of-dr-ken-walker-dr-j-gifford-jones-a-legacy-of-medical-wisdom-and-longevity</id>
    <published>2025-04-07T10:41:19-07:00</published>
    <updated>2025-04-07T10:42:59-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/celebrating-the-101st-birthday-of-dr-ken-walker-dr-j-gifford-jones-a-legacy-of-medical-wisdom-and-longevity"/>
    <title>Celebrating the 101st Birthday of Dr. Ken Walker (Dr. J. Gifford-Jones): A Legacy of Medical Wisdom and Longevity</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p><strong><span style="font-size: 10.5pt; font-family: 'Georgia',serif; mso-bidi-font-family: Aptos; color: black;">FOR IMMEDIATE RELEASE</span></strong><span style="font-size: 10.5pt; font-family: 'Georgia',serif; color: black;"> <br><strong><span style="font-family: 'Georgia',serif; mso-bidi-font-family: Aptos;"><a href="https://orthomolecular.org/resources/omns/index.shtml">Orthomolecular Medicine News Service</a>, March 26, 2025</span></strong> </span></p>
<h3>Richard Z. Cheng, M.D., Ph.D.</h3>
<h2>Highlights:</h2>
<ul>
<li><b>Interview of Dr. Ken Walker by Drs. Thomas E. Levy and Richard Z. Cheng</b></li>
<li><b>Introducing Dr. W. Gifford-Jones' Latest Book: Healthy Retirement Residence Living: What Does the Doctor Say?</b></li>
</ul>
<p style="margin-left: 10%; margin-right: 10%;"><i>Dr. Walker had a massive heart attack 28 years ago at the age of 73. Against his cardiologist's advice, he declined statins and instead followed the recommendations of Dr. Linus Pauling—two-time Nobel laureate and founder of Orthomolecular Medicine—by taking high-dose vitamin C (10 grams or more daily). Today, he is alive and well, while the cardiologists who urged him to take statins have all passed away.</i></p>
<p style="border-top: 0.5px solid black; border-bottom: 0.5px solid black; padding: 10px; text-align: center;">Link to the interview videos:<br><a href="https://orthomolecular.acemlna.com/lt.php?x=3TxtmrUFUqPUT55qA3P3heCgAqAjugHuwhY3YKPMKXfNE8KsytDMguCf2XyniQBfx1OzX5IWIFea954KyNDIU.l" target="_blank">https://rzchengmd.substack.com/p/the-longevity-code-a-101-year-old?r=lbr5k</a></p>
<p>February 2025 marks a remarkable milestone-<b>the 101st birthday of Dr. Ken Walker</b>, known to millions as<span> </span><b>Dr. J. Gifford-Jones</b>, the beloved Canadian doctor, medical columnist, and prolific author. His legacy as a tireless advocate for<span> </span><b>medical freedom, high-dose vitamin C, and longevity</b><span> </span>continues to inspire generations of physicians and health-conscious individuals worldwide.</p>
<p>I had the honor, alongside<span> </span><b>Dr. Thomas Levy</b>, of interviewing Dr. Walker about his secrets to longevity, and his insights remain as profound today as they were then. A firm believer in the<span> </span><b>power of orthomolecular medicine, preventive health, and personal responsibility</b>, he often challenged conventional medical dogma in pursuit of science-backed, patient-centered care.</p>
<p>Dr. Walker's<span> </span><b>decades-long advocacy for vitamin C</b>, inspired by the pioneering work of<span> </span><b>Dr. Linus Pauling</b>, was ahead of its time. Long before mainstream medicine recognized the importance of<span> </span><b>nutritional and metabolic health</b>, he was urging readers to take charge of their well-being with<span> </span><b>natural, evidence-based solutions</b>.</p>
<p>His advocacy for<span> </span><b>high-dose vitamin C and orthomolecular medicine</b><span> </span>deeply resonates with me on a personal level. I have been following and promoting an<span> </span><b>integrative orthomolecular approach to health</b><span> </span>that includes a<span> </span><b>healthy diet (low-carb ketogenic diet, low in ultra-processed foods, low in omega-6 seed oils, intermittent fasting), high doses of orthomolecular nutrient supplements, regular exercise (I play moderate-intensity badminton 3-4 times a week, ~2 hours each time), and daily exposure to near-infrared light (photobiomodulation therapy, PBMT at 660 and 850 nm wavelength)</b>. My parents, ~90 years old, and I have been adhering to these principles for many years. Recently, we underwent a<span> </span><b>comprehensive physical exam, including a carotid ultrasound</b>, and to our delight (although I am not surprised), our arteries were found to be<span> </span><b>completely free of plaques or stenosis-squeaky clean</b>. This personal experience is a testament to the power of the<span> </span><b>very principles Dr. Walker championed</b>-nutritional medicine and proactive health management.</p>
<p>Beyond his medical writings, Dr. Walker's<span> </span><b>unwavering spirit, intellectual curiosity, and sharp wit</b><span> </span>made him a beloved figure in the health community. His columns, spanning decades, were a beacon of<span> </span><b>truth in medicine</b>, encouraging countless readers to rethink<span> </span><b>heart disease, cancer prevention, and optimal aging</b>.</p>
<p>As we celebrate his<span> </span><b>101st birthday</b>, we honor not only his contributions to medicine but also his<span> </span><b>personal example of healthy living and resilience</b>. His legacy reminds us that the<span> </span><b>pursuit of truth, good health, and longevity</b><span> </span>is a lifelong journey-one that he championed with passion and dedication.</p>
<p>Happy<span> </span><b>101st birthday, Dr. Walker!</b><span> </span>Your wisdom continues to guide and inspire us all.</p>
<p><b>Dr. Walker's impact on health and longevity extends beyond his personal journey. Even at the age of 101, his commitment to empowering people with knowledge continues through his latest book.</b></p>
<h3>Introducing Dr. W. Gifford-Jones' Latest Book: Healthy Retirement Residence Living: What Does the Doctor Say?</h3>
<p>Upon more than 50 years of writing a weekly medical column, Dr. W. Gifford-Jones, at the age of 100, brings us his 10th book:<span> </span><i>Healthy Retirement Residence Living: What Does the Doctor Say?</i><span> </span>Drawing on experience gained over decades of fighting for better health for Canadians, this must-read guide empowers seniors and their families with the information they won't hear from the marketing teams at retirement residences - and the book challenges the sector to step up.</p>
<p>Dr. Gifford-Jones addresses the realities of moving into a retirement home-a transition filled with uncertainty and change. With his straightforward approach, he provides advice to help readers navigate the challenges, adapt to their new environment, and enjoy a fulfilling lifestyle. The book emphasizes wellness, independence, and making informed decisions about retirement living. It is packed with health tips, candid humor, and decades of medical wisdom.</p>
<p>Each chapter looks at health risks and challenges in retirement residence living, offering a doctor's advice with the characteristic humour and common-sense style for which Dr. Gifford-Jones is well known. A chapter entitled, "Where is the bar?", chides the owners of retirement homes for depriving residences of a cozy pub-like environment for gathering at the day's end. In another chapter, Gifford-Jones cautions against the combination of ample food and little exercise. Several chapters offer the kind of medical advice that doctors deliver best on topics dealing with bathrooms and bowel health.</p>
<p>With Canada's aging population, this book is more relevant than ever. Dr. W. Gifford-Jones' insights will resonate with readers who are considering retirement residence living or who are supporting loved ones through the process.</p>
<p><i>To purchase a copy, visit<span> </span><a href="https://orthomolecular.acemlna.com/lt.php?x=3TxtmrUFUqPUT55qA3P3heCgAqAjugHuwhY3YKPMKXfNE8KsytDMguCf2XyniQBfx1OzX5IWIFea954KyNDIUOB" target="_blank">www.docgiff.com/books</a><span> </span>or call 613-222-2227.</i></p>
<p><i><span>OMNS free subscription link </span><a href="https://orthomolecular.acemlna.com/lt.php?x=3TxtmrUFUqPUT55qA3P3heCgAqAjugHuwhY3YKPMKXfNE8KsytDMguCf2XyniQBfx1OzX5IWIFea954KyNDHWON" target="_blank">http://orthomolecular.org/subscribe.html</a></i></p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/midlife-eating-patterns-tied-to-health-decades-later</id>
    <published>2025-04-01T15:22:55-07:00</published>
    <updated>2025-04-01T15:23:01-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/midlife-eating-patterns-tied-to-health-decades-later"/>
    <title>Midlife eating patterns tied to health decades later</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<p>Several studies have shown links between healthy eating and prevention of chronic diseases, like diabetes or heart disease. Others have found ties between a high-quality diet and longer life. But less common are studies that examine the links between various dietary patterns and healthy aging overall, including the long-term impact of midlife food choices.</p><p><a class="read-more" href="https://comparativeguide.com/blogs/news/midlife-eating-patterns-tied-to-health-decades-later">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<p>Photo by <a href="https://www.shopify.com/stock-photos/@lunchmoney?utm_campaign=photo_credit&amp;utm_content=Free+Greek+Dinner+In+Restaurant+Image%3A+Stunning+Photography&amp;utm_medium=referral&amp;utm_source=credit">Michele Krozser</a> from <a href="https://www.shopify.com/stock-photos/api-food-drink?utm_campaign=photo_credit&amp;utm_content=Free+Greek+Dinner+In+Restaurant+Image%3A+Stunning+Photography&amp;utm_medium=referral&amp;utm_source=credit">Burst</a></p>
<h3>At a Glance</h3>
<ul>
<li>People who ate healthier diets in midlife were more likely to live into their 70s without major chronic disease.</li>
<li>The results suggest that a variety of healthful eating patterns can promote healthy aging in later years.</li>
</ul>
<div style="border-top: 0.5px solid blue; border-bottom: 0.5px solid blue; padding: 10px 0 0 0; margin-bottom: 20px;">
<p><strong>— by Vicki Contie</strong></p>
</div>
<p>As the U.S. population ages, there’s growing interest in finding ways to protect physical, mental, and cognitive health in later years. Several studies have shown links between healthy eating and prevention of chronic diseases, like diabetes or heart disease. Others have found ties between a high-quality diet and longer life. But less common are studies that examine the links between various dietary patterns and healthy aging overall, including the long-term impact of midlife food choices.</p>
<p>A research team led by Drs. Frank Hu of the Harvard T.H. Chan School of Public Health, Anne-Julie Tessier of the University of Montreal, and Marta Guasch-Ferré of the University of Copenhagen decided to take a closer look. They examined data gathered in two long-term studies of health and lifestyle. The Nurses’ Health Study enrolled women ages 30 to 55 years, and the Health Professionals Follow-Up Study enrolled men ages 40 to 75 years.</p>
<p>The team assessed participant data every four years beginning in 1986 for up to 30 years. Participants were excluded if they had a serious chronic disease at the start. The final study population included about 70,000 women and 35,000 men, for a total of more than 105,000 participants. Results appeared in<span> </span><em>Nature Medicine</em><span> </span>on March 24, 2025.</p>
<p>The researchers first examined how closely each participant’s self-reported eating patterns adhered to eight different healthy diet patterns. Among these were the Alternative Healthy Eating Index, the NIH-supported DASH diet (Dietary Approaches to Stop Hypertension), the MIND diet, the Planetary Health Diet Index, and a Mediterranean diet. All the diets encourage eating plant-based foods, unsaturated fats, nuts, and legumes while reducing the amount of red or processed meats and added sugars. Some also include healthy animal-based foods like fish and low-fat dairy products.</p>
<p>The scientists also looked at consumption of ultra-processed foods. Such foods typically contain industrially manufactured ingredients like high-fructose corn syrup, flavoring agents, unhealthy fats, and emulsifiers.</p>
<p>The team then assessed the associations between adherence to each eating pattern and healthy aging at age 70 or older. They found that over 9% of participants, about 9,800 people, had achieved healthy aging. That is, they were free of major chronic disease and had positive measures of cognitive, physical, and mental health.</p>
<p>The participants who had most closely followed the Alternative Healthy Eating Index were most likely to have healthy aging by age 70. The same held true by age 75. Participants who mostly closely adhered to any of the other healthy eating patterns also boosted their odds of healthy aging.</p>
<p>Regardless of specific diet, people who ate more fruits, vegetables, whole grains, unsaturated fats, nuts, legumes and low-fat dairy were more likely to have healthy aging. Healthy aging was less likely in those who ate more trans fats, salt, sugary drinks, and red or processed meats. In addition, people who ate more ultra-processed foods had a 32% reduced chance of healthy aging.</p>
<p>“Studies have previously investigated dietary patterns in the context of specific diseases or how long people live,” Hu explains. “Ours takes a multifaceted view, asking, how does diet impact people’s ability to live independently and enjoy a good quality of life as they age?”</p>
<p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/40128348/">Optimal dietary patterns for healthy aging.</a><span> </span>Tessier AJ, Wang F, Korat AA, Eliassen AH, Chavarro J, Grodstein F, Li J, Liang L, Willett WC, Sun Q, Stampfer MJ, Hu FB, Guasch-Ferré M.<span> </span><em>Nat Med</em>. 2025 Mar 24. doi: 10.1038/s41591-025-03570-5. Online ahead of print. PMID:40128348.</p>
<p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Institute on Aging (NIA); U.S. Department of Agriculture; Canadian Institutes of Health Research; Novo Nordisk Foundation.</p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/new-survey-shows-u-s-veterans-use-of-natural-products-for-chronic-pain</id>
    <published>2025-03-24T06:00:01-07:00</published>
    <updated>2025-03-24T06:00:01-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/new-survey-shows-u-s-veterans-use-of-natural-products-for-chronic-pain"/>
    <title>New Survey Shows U.S. Veterans’ Use of Natural Products for Chronic Pain</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<div style="margin-bottom: 2rem;">
<p><a href="https://www.nccih.nih.gov/research/research-results/new-survey-shows-us-veterans-use-of-natural-products-for-chronic-pain?nav=govd" target="_blank"><strong><em>Original article</em></strong></a> from the National Center for Complementary and Integrative Health</p>
</div>
<div class="row">
<div class="col">
<div class="row">
<div class="col">
<div>
<div class="row">
<div class="col">
<div color="#212529" id="3-head231792" class="css-6x0yqj">
<div class="css-1w7tu5a">
<div class="css-1z0obd3">
<div class="css-pkp2i6">
<p>A new survey of United States military veterans with chronic pain shows prevalent use of multiple natural products with, or in some cases, as substitutes for, prescribed pain medications. Although natural products, including dietary supplements, are commonly used, there is little information about their use for chronic pain. While many of the survey participants expressed concerns about safety, a significant proportion had not discussed their natural product use with their health care providers. Many, however, expressed their desire to have more informed conversations about natural product use with their providers.</p>
<p>The survey, which was piloted with 52 participants in the U.S. Department of Veterans Affairs (VA) Whole Health Options and Pain Education (wHOPE) pragmatic trial, was developed by researchers from the<span> </span><a href="https://painmanagementcollaboratory.org/">Pain Management Collaboratory</a><a href="https://www.nccih.nih.gov/tools/privacy#nccih-linking-policy" aria-label="Link to External Link Policy" aria-describedby="linkOpenInNewTab"><span class="externalIcon"></span><span class="sr-only">Link to External Link Policy</span></a><span> </span>to gain information about natural product use for chronic pain. The survey was co-sponsored by the National Institutes of Health (led by the National Center for Complementary and Integrative Health), the Department of Defense, and the VA. Findings were published in the journal<span> </span><i>Global Advances in Integrative Medicine and Health</i>.</p>
<p>Among the findings from the survey: </p>
<ul>
<li>All of the respondents had chronic pain, with 80 percent reporting disabling pain every day. </li>
<li>Sixty-seven percent of respondents were prescribed non-opioid pain medication, 15 percent were prescribed opioids, and 17 percent reported not using any pain medication. </li>
<li>The most frequently used natural products were vitamins/minerals (94 percent), followed by herbals/botanicals (60 percent) and cannabis (40 percent). </li>
<li>One-third of respondents reported substituting natural products for pain medications.</li>
<li>Approximately half of the survey participants expressed concerns about interactions of natural products with either pain medications (55 percent) or other natural products (52 percent).</li>
<li>Nearly all participants (98 percent) believed providers should discuss natural product use with their patients to help prevent potential harm; however, only 52 percent said they had disclosed natural product use to their health care providers. </li>
</ul>
<p>According to 2010-2014 data from the National Health Interview Survey, U.S. military veterans experienced pain and severe pain more often than nonveterans did, with 65.5 percent of veterans reporting pain in the prior 3 months. Additionally, a disproportionate number of mental health problems in veterans with chronic pain has been associated with an increase in prescription opioid use and negative outcomes. </p>
<p>Many health care systems, including the VA, recommend nonpharmacologic therapies, such as cognitive behavioral therapy, exercise, and complementary and integrative health approaches, as first-line treatments for chronic pain. Natural products are the most frequently used complementary health approach in the United States and are often used alone or in combination with medications for chronic pain. </p>
<p>The study authors said the survey was shown to be acceptable and feasible in the small but diverse sample of veterans with chronic pain and that the study produced descriptive information about natural products for pain, helping fill a knowledge gap. They noted that although some natural products are generally considered safe, many may be mislabeled, contain adulterants, have side effects, or interact with other products or medications, especially in people with more than one health condition who are taking multiple medications. </p>
<p>The authors noted that although many clinicians lack knowledge and up-to-date information about natural products, there are several online evidence-based natural product databases that clinicians can access. This may encourage clinician communication with patients and informed shared decision making, possibly leading to improved safety and pain-related outcomes in patients.</p>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
<div>
<div class="row">
<div class="col">
<div color="#212529" id="1-heading-reference" class="css-g8r7kc">
<div class="css-1w7tu5a">
<div class="css-1z0obd3">
<h2 style="margin-top: 2rem;" id="reference" class="">Reference</h2>
</div>
</div>
<div class="css-1w7tu5a">
<div class="css-1vh85y5">
<ul>
<li>Seal KH, Feinberg T, Moore L, et al.<span> </span><a href="https://pubmed.ncbi.nlm.nih.gov/40026674/" target="_blank">Natural product use for chronic pain: a new survey of patterns of use, beliefs, concerns, and disclosure to providers</a>.<span> </span><i>Global Advances in Integrative Medicine and Health</i>. 2025;14:27536130251320101.</li>
</ul>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="shortP row">
<div class="col">
<div class="Additionalresources-module--additionalresources--c11f8">
<div class="row">
<div class="col">
<h5>Additional Resources</h5>
<p class="mb5"><a href="https://www.nccih.nih.gov/health/pain">Pain</a></p>
<p class="mb5"><a href="https://www.nccih.nih.gov/health/complementary-health-practices-for-us-military-veterans-and-families">Complementary Health Practices for U.S. Military, Veterans, and Families</a></p>
</div>
</div>
</div>
</div>
</div>
<div class="row">
<div class="col">
<p><b>Publication Date:<span> </span></b>February 26, 2025</p>
</div>
</div>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/health-consequences-of-early-exposure-to-sugar</id>
    <published>2025-03-17T07:00:07-07:00</published>
    <updated>2025-03-17T07:00:07-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/health-consequences-of-early-exposure-to-sugar"/>
    <title>Health Consequences of Early Exposure to Sugar</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<div class="header">
<p>From <strong><em><a href="https://newsinhealth.nih.gov">NIH News in Health, newsinhealth.nih.gov</a></em></strong></p>
</div>
<div role="main" class="l-content">
<div class="region region-content">
<div class="clearfix block block-system block-system-main-block" id="block-mainpagecontent">
<div class="nihnih-theme-colors-purple" role="article" data-history-node-id="5831">
<p>Experts recommend that kids eat no added sugars before age 2. Yet most kids are exposed to added sugars at a very early age, even before birth through their mother’s bloodstream.</p>
<p>Scientists studied the long-term health effects of sugar exposure in the womb and early childhood. To do this, they looked at the health of adults in the United Kingdom who were conceived or born around the end of sugar rationing. The rationing had begun during World War II. The amount of sugar allowed for each person was within today’s U.S. dietary guidelines. After rationing ended, sugar intake nearly doubled.</p>
<p>The researchers looked at data from more than 60,000 people born in the U.K. between October 1951 and March 1956. Those born before July 1954 likely had reduced exposure to sugar due to rationing. Those born in July 1954 and later didn’t experience sugar rationing. As a result, they were born into a more sugar-rich environment.</p>
<p>Kids exposed to less sugar early in life had a lower chance of getting diabetes or high blood pressure decades later. Health benefits increased with longer exposure to rationing. For those with reduced sugar exposure for at least 19 months after birth, the risk of getting diabetes dropped by about 35%. The risk of high blood pressure dropped by about 20%.</p>
<p>“It is hard to find situations where people are randomly exposed to different nutritional environments early in life, and follow them for 50 to 60 years,” says Dr. Tadeja Gracner of the University of Southern California, who led the study. “The end of rationing provided us with a novel natural experiment to overcome some of these challenges.” </p>
<h3>References</h3>
<div class="grid-col-fill">
<div class="clearfix text-formatted field field--name-field-sidebar-box-content field--type-text-long field--label-hidden field__item">
<p><a href="https://pubmed.ncbi.nlm.nih.gov/39480913/">Exposure to sugar rationing in the first 1000 days of life protected against chronic disease.</a> Gracner T, Boone C, Gertler PJ.<em>Science</em>. 2024 Oct 31:eadn5421. doi: 10.1126/science.adn5421. Online ahead of print. PMID:39480913.</p>
</div>
</div>
</div>
</div>
</div>
</div>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/nutritional-interventions-in-the-treatment-of-schizophrenia-a-case-report</id>
    <published>2025-03-10T06:00:04-07:00</published>
    <updated>2025-03-10T06:00:04-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/nutritional-interventions-in-the-treatment-of-schizophrenia-a-case-report"/>
    <title>Nutritional Interventions in the Treatment of Schizophrenia: A Case Report</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<div style="margin-bottom: 2rem; font-variant: small-caps;">Photo by <a href="https://www.shopify.com/stock-photos/@farah?utm_campaign=photo_credit&amp;utm_content=Browse+Free+HD+Images+of+Person+Holds+Their+Head+While+Sitting+On+A+Couch&amp;utm_medium=referral&amp;utm_source=credit">Farah</a> from <a href="https://www.shopify.com/stock-photos/furniture?utm_campaign=photo_credit&amp;utm_content=Browse+Free+HD+Images+of+Person+Holds+Their+Head+While+Sitting+On+A+Couch&amp;utm_medium=referral&amp;utm_source=credit">Burst</a>
</div>
    <header>
        <p class="lede" style="font-weight: 700; font-size: small;">FOR
            IMMEDIATE RELEASE<br>
            Orthomolecular Medicine News Service, February 20, 2025</p>
        <p class="author" style="font-weight: 700; font-size: medium;">by Aarti Midha, M.D.</p>
        <h2 style="margin-top: 2rem;">Abstract</h2>
        <p>Schizophrenia is a psychiatric disorder for which conventional medicine uses antipsychotic medications. This
            is a case report of a 28-year-old male who arrived at my clinic in 2018 with symptoms of muttering,
            fearfulness, and withdrawn behavior and was taking antipsychotics and benzodiazepines for many years. We
            investigated him for metabolic causes, and the investigations revealed raised serum aluminum and high HSCRP.
            We started with the nutrients N-acetylcysteine, alpha-lipoic acid, and antioxidants to reduce oxidative
            stress and enhance phase 2 detoxification support, along with other nutrients. He also started an
            antioxidant-rich, gluten-free diet with probiotics. He started improving after three months. We monitored
            serum aluminum levels in this process. We started reducing psychotropic medications thereafter and continued
            antioxidant support to reduce inflammation and oxidative stress. He has been symptom-free for the last four
            years. He is on a low-dose mood stabilizer along with antioxidant support. He has not taken any
            antipsychotics in the last four years. Based on the positive outcome, we propose the role of nutritional
            intervention in reducing inflammation in psychiatric disorders.</p>
        <p class="keywords" style="font-variant: small-caps;">Keywords: case report, schizophrenia,
            heavy metal toxins, aluminum</p>
    </header>
    <section>
        <h2 style="margin-top: 2rem;">Introduction</h2>
        <p>Schizophrenia is characterized by a variety of symptoms, such as hallucinations, delusions, disordered
            thinking, and poor social functioning. Research indicates that a variety of genetic, environmental, and
            neurological factors may play a role in the development of schizophrenia, even though its precise
            etiology is still unknown.</p>
        <p>The probable involvement of environmental toxins, in particular heavy metals, in the development of
            schizophrenia has attracted increasing attention in recent years. These days, the environment is heavily
            contaminated with heavy metals like lead, cadmium, mercury, aluminum and arsenic. Toxic levels of all of
            these heavy metals can be found in the air, water, soil, and food, often in locations near industrial
            and trash disposal sites.</p>
        <p>Chronic exposure to these heavy metals impairs numerous normal biological functions and results in a
            series of health problems<sup><a href="#Ref1">1</a></sup>, such as aberrant immunological responses and
            neuropathological conditions<sup><a href="#Ref2">2,3</a></sup>. Moreover, it has been reported that toxic
            heavy metals can cause oxidative stress and subsequently DNA damage, lipid peroxidation, and protein
            modification, all of which play a role in the pathogenesis of numerous diseases because of chronic
            inflammation, including cancer, diabetes, and neurological disorders<sup><a href="#Ref4">4</a></sup>. Toxic
            heavy metals are an important risk factor for psychiatric diseases since they cause neurobehavioral
            alterations and disrupt dopamine receptors<sup><a href="#Ref5">5</a></sup>.</p>
        <p>Numerous studies have studied the link between exposure to heavy metals and the likelihood of developing
            schizophrenia<sup><a href="#Ref6">6</a></sup>.</p>
        <p>A 28-year-old male who arrived at my clinic in 2018 with symptoms of muttering, fearfulness and withdrawn
            behavior, with a medication history of many antipsychotics and benzodiazepines over many years with no
            relief in symptoms.</p>
        <p>This longitudinal case study is of a medication-resistant schizophrenia patient who had a history of heavy
            metal exposure and got improved with nutritional interventions and is now asymptomatic for last 4 years.
            This case study seeks to further explore the potential connection between heavy metal toxicity, chronic
            inflammation and schizophrenia.</p>
        <p>This case study makes a significant contribution to the field by highlighting the significance of taking
            environmental factors into account when managing and treating this crippling disease and by shedding light
            on the involvement of heavy metal toxins in the etiology and development of schizophrenia.</p>
    </section>
    <section>
        <h2 style="margin-top: 2rem;">Timeline</h2>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2018-09-27</div>
            <div class="column" style="flex: left; padding: 0.5rem;">The patient was investigated for routine
                investigations along with blood and urine levels of heavy metal toxins. His serum aluminum level was
                63.59 μg/mL. His HSCRP was 4.78 mg/l.</div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2018-09-28</div>
            <div class="column" style="flex: left; padding: 0.5rem;">We started antioxidants and phase 2 detoxification
                nutrients support: N-acetylcysteine 1200 mg, alpha-lipoic acid 300 mg, taurine 1000 mg, and
                phosphatidylcholine 1 g along with Vitamin C, magnesium, and Vit D3, and started a gluten-free diet. We
                observed mild improvement in clinical symptoms.
            </div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2018-10-22</div>
            <div class="column" style="flex: left; padding: 0.5rem;">He was complaining of low-grade fever and body
                aches. He was referred to a physician for workup. There was nothing significant from the physician's
                side. We started minocycline 50 mg in the morning and evening.
            </div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2018-10-23</div>
            <div class="column" style="flex: left; padding: 0.5rem;">His symptoms started improving. We increased the
                minocycline dose to 100 mg BD for 2 weeks along with probiotics. He had improvement in psychotic
                symptoms also.
            </div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2018-12-28</div>
            <div class="column" style="flex: left; padding: 0.5rem;">We started observing clinical improvement.
            </div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2019-04-03</div>
            <div class="column" style="flex: left; padding: 0.5rem;">His serum aluminum test was repeated. It was 24.16
                ug/ml. There was clinical improvement His family started adding gluten to his diet. After starting
                gluten, his aggression has increased. So, family members stopped giving gluten. We presumed gluten
                intolerance and a hyperpermeable gut. He used to improve after a few weeks of stopping gluten.
            </div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2020-01-29</div>
            <div class="column" style="flex: left; padding: 0.5rem;">He was symptom-free. He was not taking any
                antipsychotics. He was on oxcarbamazepine 300 mg , pregablin 75 mg along with antioxidants.
            </div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2021-05-22</div>
            <div class="column" style="flex: left; padding: 0.5rem;">He was stable on oxcarbazepine 300 mg OD and
                antioxidants. His family is enjoying gluten in their diet on and off.
            </div>
        </div>
        <div class="row" style="display: flex;">
            <div class="column" style="flex: left; padding: 0.5rem; min-width: 8rem;">2024- 12-07</div>
            <div class="column" style="flex: left; padding: 0.5rem;">Not only asymptomatic, he is also planning to start
                a new business in Jaipur.
            </div>
        </div>
    </section>
    <section>
        <h2 style="margin-top: 2rem;">Discussion</h2>
        <p>This longitudinal case study of the patient leaves us concerned that people diagnosed with schizophrenia may
            be covert sufferers of undiagnosed environmental toxin exposure, inflammation, hyperpermeable gut, and
            oxidative stress.</p>
        <p>The patient has been in follow-up with the treating doctor for the last six years, and both the patient and
            their family are satisfied with the progress made. The patient continues to follow an anti-inflammatory
            diet, take antioxidants, and regularly use a low-dose mood stabilizer, oxcabamazeipine 300 mg, with
            antioxidants such as vitamin C and n-acetylcysteine, and vitamin D and magnesium. These interventions have
            contributed to the patient's improvement. During this 6 year follow-up period there has been no relapse in
            schizophrenic symptoms.</p>
        <p>Recent studies have suggested metabolic syndrome as a risk factor for schizophrenia, attributed to poor
            dietary habits, unhealthy lifestyles, and physical inactivity of the patient<sup><a href="#Ref7">7</a></sup>
            and side effects of second-generation antipsychotics<sup><a href="#Ref8">8</a></sup>. On the other hand,
            heavy metal toxins such as As<sup><a href="#Ref9">9</a></sup> and Pb<sup><a href="#Ref10">10</a></sup> were
            found to be associated with metabolic diseases, suggesting a role of abnormal metabolism in linking toxic
            heavy metal exposure and schizophrenia.</p>
        <p>The gluten intolerance hypothesis is based on mechanisms linking gluten intake, immune reactions and
            inflammation with the development of schizophrenia. In this model, it is proposed that within the subgroup
            of people with schizophrenia and related psychosis with inflammation, consumption of gluten can drive an
            immune response and is implicated in the pathophysiology of the illness. Elevated anti-gliadin antibodies
            (AGA) are more frequent in people with schizophrenia than in people without, and AGA has been positively
            associated with peripheral inflammatory markers<sup><a href="#Ref11">11</a></sup>.</p>
    </section>
    <section>
        <h2 style="margin-top: 2rem;">Family Perspective</h2>
        <p>We admitted our brother multiple times to a psychiatric hospital but did not get results with standard
            medications. We have always been keen to investigate any alternative therapies that could provide relief and
            enhance the quality of life for our brother as we watch him suffer from incapacitating symptoms.</p>
        <p>Initially we were unaware of nutritional interventions for treatment of schizophrenia. The idea of adding
            particular foods and supplements to our loved one's diet felt strange to us because we had mainly relied on
            conventional medical treatments.</p>
        <p>Patience, empathy, and a willingness to make big dietary modifications for our family were necessary to
            support our loved one during this journey. Together, we discovered the significance of including
            anti-inflammatory and antioxidant-rich foods in our diets, as well as the need to stay away from items that
            contain aluminum. This required alterations to our grocery shopping, meal preparation, and cooking
            techniques. Even if it wasn't always simple, seeing how these treatments might improve the mental health of
            our brother made it all worthwhile.</p>
        <p>We eventually began to see improvements in our brother's health. The symptoms lessened in intensity and
            frequency, enabling him to participate more actively in their everyday lives and interpersonal interactions.
            His mood, cognitive capacity, and behavior all improved. These developments offered us reason for optimism
            and strengthened our faith in the effectiveness of dietary therapies as an additional strategy for treating
            schizophrenia.</p>
        <p>In conclusion, we have seen firsthand as family members how nutritional therapies can significantly reduce
            inflammation brought on by aluminum in the treatment of schizophrenia. We urge other families to learn more
            about these therapies, educate themselves on the possible advantages, and work cooperatively with medical
            professionals to include them in the care of their loved ones.</p>
    </section>
    <section>
        <h2 style="margin-top: 2rem;">Conclusion</h2>
        <p>Treatment of schizophrenia with medication is limited and often comes with severe side effects. This case
            report explores potential mechanisms and nutritional interventions for improving the condition. Nutritional
            interventions that aim to reduce oxidative stress and inflammation can be a safe and effective addition to
            treatment.</p>
        <div>
<span style="font-variant: small-caps;">Author contact: Dr Aarti Midha,</span> <a href="mailto:gawriaarti@yahoo.com">gawriaarti@yahoo.com</a>
</div>
    </section>
    <footer>
        <h2 style="margin-top: 2rem;">Further Reading</h2>
        <p>Orthomolecular nutrition has been shown to help prevent and reverse schizophrenia. A low-carb ketogenic diet
            can contribute to recovery<sup><a href="#Ref12">12-14</a></sup>. High-dose supplementation with vitamins and
            micronudtrients, importantly niacin (vitamin B3), has been successful in reversing schizophrenia<sup><a href="#Ref14">14-16</a></sup>.</p>
        <h2 style="margin-top: 2rem;">References</h2>
        <ol style="line-height: 1.5em;">
            <li id="Ref1">Sun HJ, Xiang P, Luo J, et al. (2016) Mechanisms of arsenic disruption on gonadal, adrenal and
                thyroid
                endocrine systems in humans: A review. <em>Environ Int.</em> 95:61-68. <a href="https://pubmed.ncbi.nlm.nih.gov/27502899">https://pubmed.ncbi.nlm.nih.gov/27502899</a>
            </li>
            <li id="Ref2"> Schultz SK, Andreasen NC (1999) Schizophrenia. <em>Lancet</em>, 353:1425-1430.
                <a href="https://pubmed.ncbi.nlm.nih.gov/27502899">https://pubmed.ncbi.nlm.nih.gov/27502899</a>
            </li>
            <li id="Ref3">Suzuki Y, Inoue T, Ra C (2011) Autoimmunity-inducing metals (Hg, Au and Ag) modulate mast cell
                signaling, function and survival. <em>Curr Pharm Des.</em> 17:3805-3814. <a href="https://pubmed.ncbi.nlm.nih.gov/22103852">https://pubmed.ncbi.nlm.nih.gov/22103852</a>
            </li>
            <li id="Ref4">Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease.
                <em>Toxicology</em>,
                283:65-87. <a href="https://pubmed.ncbi.nlm.nih.gov/21414382">https://pubmed.ncbi.nlm.nih.gov/21414382</a>
            </li>
            <li id="Ref5">Finefrock AE, Bush AI, Doraiswamy PM (2003) Current status of metals as therapeutic targets in
                Alzheimer's disease. <em>J Am Geriatr Soc.</em> 51:1143-1148. <a href="https://pubmed.ncbi.nlm.nih.gov/12890080">https://pubmed.ncbi.nlm.nih.gov/12890080</a>
</li>
            <li id="Ref6">Ma J, Yan L, Guo T, et al. (2019) Association of Typical Toxic Heavy Metals with
                Schizophrenia. <em>
                    Int J
                    Environ Res Public Health.
                </em> 16:4200. <a href="https://pubmed.ncbi.nlm.nih.gov/31671526">https://pubmed.ncbi.nlm.nih.gov/31671526</a>
</li>
            <li id="Ref7">Saha S, Chant D, McGrath J (2007) A systematic review of mortality in schizophrenia: Is the
                differential
                mortality gap worsening over time? <em>Arch Gen Psychiatry,</em> 64:1123-1131.
                <a href="https://pubmed.ncbi.nlm.nih.gov/17909124">https://pubmed.ncbi.nlm.nih.gov/17909124</a>
            </li>
            <li id="Ref8">Henderson DC, Vincenzi B, Andrea NV, et al. (2015) Pathophysiological mechanisms of increased
                cardiometabolic risk in people with schizophrenia and other severe mental illnesses. <em>Lancet
                    Psychiatry,</em>
                2:452-464. <a href="https://pubmed.ncbi.nlm.nih.gov/26360288">https://pubmed.ncbi.nlm.nih.gov/26360288</a>
</li>
            <li id="Ref9">Spratlen MJ, Grau-Perez M, Best LG, et al. (2018) The Association of Arsenic Exposure and
                Arsenic
                Metabolism With the Metabolic Syndrome and Its Individual Components: Prospective Evidence from the
                Strong Heart Family Study. <em>Am J Epidemiol.</em> 187:1598-1612. <a href="https://pubmed.ncbi.nlm.nih.gov/29554222">https://pubmed.ncbi.nlm.nih.gov/29554222</a>
</li>
            <li id="Ref10">Xia J, Jin C, Pan Z, et al. (2018) Chronic exposure to low concentrations of lead induces
                metabolic
                disorder and dysbiosis of the gut microbiota in mice. <em>Sci. Total Environ.</em> 631-632:439-448.
                <a href="https://pubmed.ncbi.nlm.nih.gov/29529432">https://pubmed.ncbi.nlm.nih.gov/29529432</a>
            </li>
            <li id="Ref11">DL, Kelly HK, Demyanovich WW, et al. (2018) Anti-gliadin antibodies (AGA IgG) related to
                peripheral
                inflammation in schizophrenia, <em>Brain Behav Immun. </em>69:57-59. <a href="https://pubmed.ncbi.nlm.nih.gov/29074356">https://pubmed.ncbi.nlm.nih.gov/29074356</a>
            </li>
            <li id="Ref12">Sarnyai Z, Kraeuter AK, Palmer CM (2019) Ketogenic diet for schizophrenia: clinical
                implication. <em>
                    Curr
                    Opin Psychiatry.
                </em> 32:394-401. <a href="https://pubmed.ncbi.nlm.nih.gov/31192814">https://pubmed.ncbi.nlm.nih.gov/31192814</a>
</li>
            <li id="Ref13">Choi J, Kang J, Kim T, Nehs CJ (2024) Sleep, mood disorders, and the ketogenic diet:
                potential
                therapeutic targets for bipolar disorder and schizophrenia. <em>Front Psychiatry.</em> 15:1358578.
                <a href="https://pubmed.ncbi.nlm.nih.gov/38419903">https://pubmed.ncbi.nlm.nih.gov/38419903</a>
            </li>
            <li id="Ref14">ISOM (2006) Sister Theresa Feist. Orthomolecular Medicine Hall of Fame.
                <a href="https://isom.ca/profile/theresa-feist">https://isom.ca/profile/theresa-feist</a>
            </li>
            <li id="Ref15">Smith RG (2017) Niacin Treatment of Schizophrenia. <em>Orthomolecular Medicine News
                    Service.</em>
                <a href="https://orthomolecular.org/resources/omns/v13n23.shtml">https://orthomolecular.org/resources/omns/v13n23.shtml</a>
            </li>
            <li id="Ref16">Levy TE (2023) Schizophrenia is Chronic Encephalitis ... and Niacin Cures It. <em>
                    Orthomolecular
                    Medicine
                    News Service.
                </em> <a href="https://orthomolecular.org/resources/omns/v19n40.shtml">https://orthomolecular.org/resources/omns/v19n40.shtml</a>
            </li>
        </ol>
        <h3>Orthomolecular Medicine</h3>
        <p>Orthomolecular medicine uses safe, effective nutritional therapy to fight illness.<br>
            For more information:
            <a href="http://www.orthomolecular.org">http://www.orthomolecular.org<br>
                </a><a href="http://orthomolecular.org/subscribe.html">OMNS free subscription</a> |
                <a href="http://orthomolecular.org/resources/omns/index.shtml">OMNS archive</a>
        </p>
    </footer>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/bacteria-found-to-eat-forever-chemicals-and-even-some-of-their-toxic-byproducts</id>
    <published>2025-01-24T11:04:39-08:00</published>
    <updated>2025-01-24T11:04:44-08:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/bacteria-found-to-eat-forever-chemicals-and-even-some-of-their-toxic-byproducts"/>
    <title>Bacteria found to eat forever chemicals -- and even some of their toxic byproducts</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<p>A team has identified a strain of bacteria that can break down and transform at least three types of PFAS, and, perhaps even more crucially, some of the toxic byproducts of the bond-breaking process.</p><p><a class="read-more" href="https://comparativeguide.com/blogs/news/bacteria-found-to-eat-forever-chemicals-and-even-some-of-their-toxic-byproducts">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<div><a href="https://www.sciencedaily.com/releases/2025/01/250123163111.htm">https://www.sciencedaily.com/releases/2025/01/250123163111.htm</a></div>
<div class="share-summary">A team has identified a strain of bacteria that can break down and transform at least three types of PFAS, and, perhaps even more crucially, some of the toxic byproducts of the bond-breaking process.</div>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/understanding-the-sudden-rise-of-type-2-diabetes-in-children</id>
    <published>2024-08-05T06:00:02-07:00</published>
    <updated>2024-08-05T06:00:02-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/understanding-the-sudden-rise-of-type-2-diabetes-in-children"/>
    <title>Understanding the sudden rise of type 2 diabetes in children</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<span data-mce-fragment="1">In type 2 diabetes, the body struggles to use insulin effectively. This vital hormone, made by beta cells in the pancreas, helps glucose in the bloodstream enter cells in muscle, fat and the liver, where it’s used for energy. But sometimes those cells gradually lose their ability to respond to insulin, forcing the beta cells to pump out more and more of it. If the beta cells can’t keep up, blood glucose levels will begin to rise, leading to a diagnosis of </span><a href="https://knowablemagazine.org/content/article/health-disease/2021/what-does-mean-have-prediabetes" data-mce-fragment="1" data-mce-href="https://knowablemagazine.org/content/article/health-disease/2021/what-does-mean-have-prediabetes">prediabetes<span data-mce-fragment="1"> </span></a><span data-mce-fragment="1">and, eventually, diabetes.</span><p><a class="read-more" href="https://comparativeguide.com/blogs/news/understanding-the-sudden-rise-of-type-2-diabetes-in-children">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<p class="article-info"> </p>
<h2>The metabolic disorder was long known as a disease of adulthood. Now, it’s spiking in kids and teens, with worrisome consequences.</h2>
<p style="text-decoration: overline underline;" class="article-byline"><span class="author-byline">By Charlotte Huff&amp;nbsp</span> <span> </span> <span class="pub-date"> 2024.07.31</span></p>
<div class="article-content">
<div class="article-text -drop-cap">
<p>The appearance of type 2 diabetes in children and teens puzzled physicians from the start. <a href="https://www.texaschildrens.org/find-a-provider/fida-f-bacha-md">Fida Bacha </a>recalls working as a pediatric endocrinology fellow in Pittsburgh shortly after 2000 when young, overweight and obese patients began to arrive at the clinic, some describing increased thirst, more frequent trips to the bathroom and other symptoms of what was then called adult-onset diabetes.</p>
<p>“It was a new realization that we are dealing with a disease that used to be only an adult disease that is now becoming a disease of childhood,” says Bacha, who practices at Texas Children’s Hospital in Houston.</p>
<p>More than two decades later, physicians and researchers are still trying to unravel what’s driving the emergence and proliferation of youth-onset disease, particularly among marginalized communities including Hispanics/Latinos. The increasing prevalence of obesity among young people is clearly one contributor, but researchers are also scrutinizing the potential influence of other lifestyle and environmental factors — everything from exposure to chronic stress and air pollution to sugar-rich diets. Along with physiological factors, such as where they carry excess fat, youths from lower socioeconomic levels may be vulnerable due to aspects of daily life beyond their control, such as more limited access to healthy food and opportunities to safely exercise in less-polluted neighborhoods.</p>
<p>As researchers try to sort out the interplay among genetics, metabolic factors and environmental influences in Hispanic and other populations, their goal is to answer this key question: Why do some seemingly at-risk adolescents progress to diabetes while others do not?</p>
<p>Long-term, the challenges and health stakes are significant. When type 2 diabetes first emerged in youths, clinicians initially thought its progression would mirror that in adults and thus could be treated accordingly. That hasn’t panned out, says <a href="https://www.niddk.nih.gov/about-niddk/staff-directory/biography/linder-barbara">Barbara Linder</a>, a pediatric endocrinologist and senior advisor for childhood diabetes research at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). For instance, researchers have determined that metformin, a commonly prescribed oral antidiabetic medication in adults, doesn’t work as well in young people.</p>
<p>“We know that the disease is very aggressive in youth and very difficult to treat,” Linder says. “So it’s really imperative that we develop effective approaches to prevention. And to do this we obviously need to be able to effectively identify which youth are at the highest risk.”</p>
<p>Even with treatment, young people develop other medical problems related to diabetes faster than adults, according to a study that followed 500 youths, more than one-third of them Hispanic. Sixty percent <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2100165">developed at least one complication within about 15 years</a> after diagnosis, when just in their 20s.</p>
<p>“It’s really alarming,” says <a href="https://directory.uthscsa.edu/academics/profile/rodriguezl30">Luisa Rodriguez</a>, a pediatric endocrinologist who studies type 2 diabetes and obesity in children at the University of Texas Health Science Center at San Antonio. For every 10 adolescents with youth-onset diabetes, she points out, “six of them, within a decade span, are going to develop a significant comorbidity that will highly impact their lifespan and quality of life.”</p>
<div class="article-image -caption-center"></div>
<h2>Insulin resistance</h2>
<p>In type 2 diabetes, the body struggles to use insulin effectively. This vital hormone, made by beta cells in the pancreas, helps glucose in the bloodstream enter cells in muscle, fat and the liver, where it’s used for energy. But sometimes those cells gradually lose their ability to respond to insulin, forcing the beta cells to pump out more and more of it. If the beta cells can’t keep up, blood glucose levels will begin to rise, leading to a diagnosis of <a href="https://knowablemagazine.org/content/article/health-disease/2021/what-does-mean-have-prediabetes">prediabetes </a>and, eventually, diabetes.</p>
<p>In the past, type 2 diabetes typically didn’t arise until well into adulthood. But now, cases in US youths ages 10 to 19 are rising fast. Since 2002-2003, overall diagnoses have doubled from 9 per 100,000 youths to 17.9 per 100,000 in 2017-2018, <a href="https://www.cdc.gov/diabetes/php/data-research/?CDC_AAref_Val=https://www.cdc.gov/diabetes/data/statistics-report/index.html">particularly among Asians, Pacific Islanders, Blacks and Hispanics</a>. If those rising rates persist, the number of type 2 diabetes cases in young people is projected to skyrocket from 28,000 in 2017 to 220,000 by 2060.</p>
<p>Various factors have been linked to insulin resistance in childhood or adolescence, <a href="https://www.annualreviews.org/content/journals/10.1146/annurev-med-042120-012033">including obesity, inactivity and genetics</a>, according to a review of the causes of type 2 diabetes in youths published in the 2022 <em>Annual Review of Medicine</em>. The disease tends to run in families regardless of race or ethnicity, which suggests that genes matter. Among US Hispanics, adults of Mexican or Puerto Rican heritage are most likely to be diagnosed, followed by Central and South Americans and Cubans.</p>
<p>Obesity is also a contributing factor: Slightly more than <a href="https://www.cdc.gov/obesity/php/data-research/childhood-obesity-facts.html?CDC_AAref_Val=https://www.cdc.gov/obesity/data/childhood.html">one-fourth of Hispanic youths are obese</a>, a higher percentage than for any other major racial or ethnic group. Children also are more likely to develop type 2 diabetes if their mother has the disease or developed gestational diabetes during pregnancy. One theory is that fetal exposure to maternal diabetes while in the womb can spur metabolic changes following birth.</p>
<p>Puberty is also highly influential — most cases are diagnosed after its onset. During puberty, youths temporarily experience insulin resistance, due in large part to an increase in hormones, Linder says. Most youths offset that transient resistance by secreting more insulin, she says. But for reasons that are still unclear, a subpopulation of adolescents does not. “When they’re faced with this stress test of puberty, they can’t increase their insulin secretion enough to compensate,” Linder says. “And that’s probably why they develop type 2 diabetes.”</p>
<p>One analysis, which looked at type 2 diabetes trends from 2002 to 2018, identified the peak <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091237/pdf/nihms-1881252.pdf">age for diagnosis as 16 years</a> in boys and girls. The sole exception involved Black youths, in whom diagnoses peaked at 13 years, and possibly earlier among Black girls, which may be linked to an earlier start of menstruation.</p>
<p>American Diabetes Association guidelines recommend that clinicians screen overweight or obese youths for the disease starting at age 10 or once puberty starts, whichever is earlier, if they have one or more risk factors. These include a family history of the disease, signs of insulin resistance or affiliation with certain racial/ethnic groups, including Hispanic/Latino.</p>
<p>During checkups, clinicians can look for a visible sign of insulin resistance, an associated skin condition called acanthosis nigricans, says <a href="https://physicians.wustl.edu/people/paulina-cruz-bravo-md/">Paulina Cruz Bravo</a>, a physician and diabetes researcher at Washington University School of Medicine in St. Louis. The skin changes tend to appear in the neck area or along folds in the skin, including in the armpits and on the elbows and knees, she says. “The top layer of the skin gets thickened. It’s described as a velvety appearance of the skin — it’s darker compared to the skin in other places.”</p>
<div class="article-image -caption-center"></div>
<p>Where an adolescent carries any excess pounds also matters, as insulin resistance has been associated with a type of fat called visceral fat, says <a href="https://www.chla.org/profile/alaina-vidmar-md">Alaina Vidmar</a>, a pediatric endocrinologist at Children’s Hospital Los Angeles. Unlike the more common type of fat, called subcutaneous and felt by pinching around the waistline, visceral fat surrounds the liver and other vital organs, increasing the risk for type 2 diabetes, fatty liver disease and other conditions.</p>
<p>“You really need the liver to process glucose to be able to utilize your insulin well,” Vidmar says. “And if it is full of fat, you are unable to do that.” <a href="https://knowablemagazine.org/content/article/health-disease/2018/invisible-liver-disease-balloons-view">Fatty liver disease</a>, which has been associated both with obesity and type 2 diabetes, is most common in Hispanic adults, followed by white adults and Black adults, according to a meta-analysis looking at 34 studies.</p>
<p>Imaging scans would be the ideal way to identify the extent and location of visceral fat in adolescents, Vidmar says. But given that routine scanning would be costly, clinicians can instead measure an adolescent’s waist circumference, “a great surrogate marker,” she says.</p>
<div class="article-image -caption-center"></div>
<p>Still, obesity accounts for only a portion of the type 2 risk profile, reflecting the complexities involved in understanding the pathophysiology of youth-onset disease. Roughly <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799572">one-fourth of youths with type 2 diabetes are not obese</a>, according to a meta-analysis published in 2022 in <em>JAMA Network Open</em>. Asian youths are least likely to be obese; roughly one-third don’t meet the criteria for obesity.</p>
<p>Moreover, while obesity and insulin resistance boost the risk of developing diabetes, those factors alone don’t predict whether an adolescent is eventually diagnosed with the disease, according to the authors of the <em>Annual Review of Medicine </em>overview. Instead, they point to the role of impaired beta cell function.</p>
<p>In one study involving 699 youths with type 2 diabetes, the standard antidiabetic drug metformin <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1109333">controlled blood glucose levels in only about half the participants</a>. (The medication was least effective among Black youths, for reasons that are unclear, according to the researchers.) Another analysis of the same study population identified a 20 percent to 35 percent <a href="https://diabetesjournals.org/care/article/36/6/1749/33280/Effects-of-Metformin-Metformin-Plus-Rosiglitazone">decline in beta function each year in diabetic youths, </a>compared with prior studies showing about a 7 percent to 11 percent annual decline in diabetic adults.</p>
<p>“What we see in the youth is that beta cell function fails very rapidly,” Linder says, adding that the beta cell decline tends to correlate with the lack of response to metformin.</p>
<p>It’s unknown whether specific racial or ethnic groups are more vulnerable to loss of beta cell function, says Linder, who hopes that a new large-scale NIDDK study launching this summer will identify any such physiological and other differences among populations. The study, called Discovery of Risk Factors for Type 2 Diabetes in Youth Consortium, aims to enroll 3,600 overweight or obese adolescent boys and girls, 36 percent of them Hispanic. Bacha and other investigators on the project plan to follow the youths through puberty, looking at genetic and physiological markers such as insulin resistance and beta cell function. Their goal is to track who develops type 2 diabetes and what factors precipitate the disease.</p>
<p>In addition, researchers will learn about the participants’ mental health, lifestyles and social determinants of health, Linder says. To that end, families will be asked to share details about nutrition, physical activity and sleep, as well as food insecurity, exposure to racism and other stressors.</p>
<p>“Stress induces certain hormones that antagonize insulin, so they create more insulin resistance,” Linder says. “Stress also is associated with chronic inflammation in the body, which affects the ability of the body to respond normally.”</p>
<div class="article-image -caption-center"></div>
<h2>Zooming in on risk factors in Hispanic kids</h2>
<p>Already, researchers who have studied at-risk Hispanic youths and their families have begun to flesh out environmental and other influences rooted in daily life that can boost the likelihood of obesity or diabetes. <a href="https://www.chla.org/profile/michael-i-goran-phd">Michael Goran</a>, a child obesity researcher at Children’s Hospital Los Angeles, has led a research project called the Study of Latino Adolescents at Risk (SOLAR), which tracked 328 Hispanic/Latino youths considered at highest risk of youth-onset diabetes based on their body mass index and family history of the disease. The participants, recruited in two waves between 2000 and 2015, completed health questionnaires and underwent annual exams, including imaging scans and other measurements.</p>
<p>One analysis found that Hispanic youths <a href="https://diabetesjournals.org/diabetes/article/66/7/1789/40024/Longitudinal-Associations-Between-Ambient-Air">who lived in neighborhoods with higher levels of air pollution</a> were more likely to experience a breakdown in beta cell function. “Which we weren’t necessarily expecting — we don’t know the mechanism of that,” says Goran, <a href="https://www.annualreviews.org/doi/abs/10.1146/annurev.nutr.25.050304.092625">who coauthored a close look at pediatric insulin resistance</a> in the 2005 <em>Annual Review of Nutrition</em>.</p>
<p>In more recent years, he’s turned his attention to studying nutrition shortly after birth, with a focus on infant formulas that contain corn syrup. Those formulas are more likely to spike blood sugar than are lactose-based formulas, he says. “If you’re spiking blood glucose with corn syrup in babies,” he says, “you can see how that would be problematic for long-term control of blood sugars.”</p>
<p>In one study, Goran and colleagues looked at obesity trends in 15,246 children who received formula through the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Babies who consumed any formula with corn syrup <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157812/">were 10 percent more likely to be obese by age 2</a> than babies who didn’t. Nearly 90 percent of the study’s participants were Hispanic.</p>
<div id="newsletter-promo-item">
<div class="newsletter-promo" style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;" data-mce-style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;">
<div class="newsletter-promo-img" style="display: grid;" data-mce-style="display: grid;"></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a href="https://knowablemagazine.org/newsletter-signup" style="border-bottom: none;" data-mce-style="border-bottom: none;"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<p>In other research, epidemiologist <a href="https://einsteinmed.edu/faculty/9078/carmen-isasi/">Carmen Isasi </a>of the Albert Einstein College of Medicine in New York helped lead the Study of Latinos (SOL) Youth study, which delved into the extent to which a child’s family circumstances contribute to obesity and metabolic changes that may boost risk of youth-onset diabetes. Isasi and colleagues found chronic stress to be pervasive. Three-quarters of parents and caregivers reported stress and 29 percent detailed three or more stressors related to health, work or relationships. The higher <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549811/pdf/chi.2016.0205.pdf">the number of parental stressors, the more likely the child was to be obese</a>.</p>
<p>Isasi also has looked at the relationship between food insecurity and metabolic health. Hispanic youths raised in households with the highest levels of food insecurity <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9595113/">had significantly worse metabolic results</a>, including elevated blood glucose and triglycerides, a type of cholesterol.<strong> </strong>Families dealing with food insecurity, Isasi says, probably have a lower-quality diet and skimp on costlier protein and fresh produce.</p>
<p>Preventing diabetes has proved challenging. A review paper looking at diet-related and other lifestyle initiatives targeting Hispanic youths found few studies to date that have shown improvements in body mass index or blood glucose levels.</p>
<p>Adolescents of lower socioeconomic status may also shoulder responsibilities that can undercut efforts to stay healthy, says <a href="https://www.bcm.edu/people-search/erica-soltero-37031">Erica Soltero</a>, a behavioral scientist at Houston’s Baylor College of Medicine, who works with Hispanic youths. For instance, older teens may struggle to attend an exercise class if they have an after-school job or must pick up younger siblings or start dinner. Technology, Soltero says, may be a better way to reach busy Hispanic teens; she’s piloting a study that will provide <a href="https://pubmed.ncbi.nlm.nih.gov/36775009/">text-based lifestyle guidance to Hispanic teens with obesity</a>.</p>
<p>Approved medication options remain limited for children and teens. If metformin doesn’t work, the alternative is insulin, and parents may resist giving injections because of the difficulties involved, Rodriguez says. She’s involved with an ongoing study in youths with type 2 diabetes to <a href="https://clinicaltrials.gov/study/NCT04596631">study the effectiveness of oral semaglutide</a>, one of the newer diabetes drugs that also has achieved notable weight loss. Rodriguez estimates the results will be available by 2026.</p>
<p>The new NIDDK study won’t assess medication treatments, as it’s an observational study. But researchers involved are bullish that study-related insights could lead to better prevention and treatment approaches. “If someone is predisposed to beta cell dysfunction, should we be much more aggressive in treating their overweight/obesity,” Bacha says, “so that this beta cell function is preserved for a longer period of time?” Doctors could, for example, decide to start treatment earlier, she says.</p>
<p>Neither are researchers like Soltero deterred by the long-standing difficulties involved with revamping lifestyle habits. Soltero, who has worked with overweight and obese Hispanic adolescents to improve exercise and make dietary changes, describes them as often highly motivated given the damage they’ve seen the disease inflict on their own families.</p>
<p>“A lot of times they’ll have a touch point with a relative who’s on dialysis and maybe had a digit amputated,” Soltero says. Or “they’ll say, ‘I don’t want to prick myself every day like my Uncle So-and-So.’ Or ‘I don’t want to be on medicine for the rest of my life like my grandma.’ ”</p>
<p><em>This story is part of </em> Knowable Magazine’s<em> Spanish-language series on science that affects or is conducted by Latinos in the United States, supported by </em><a href="https://nam02.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.hhmi.org%2F&amp;data=05%7C02%7Ceemerson%40annualreviews.org%7C9680594d883342983af308dcb19041c6%7C3197fc830bae43caa05eb95b89394b0f%7C0%7C0%7C638580480393977730%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&amp;sdata=w9LSMKrckaaWV9xPR79WXsShulzC2Mszz1Q3x8HeXR4%3D&amp;reserved=0"><em>HHMI</em></a><em>’s Science and Educational Media Group.</em></p>
</div>
</div>
<link href="https://knowablemagazine.org/content/article/health-disease/2024/type-2-diabetes-children" rel="canonical"> <meta doi="10.1146/knowable-073124-1" content="https://knowablemagazine.org/content/article/health-disease/2024/type-2-diabetes-children" name="syndication-source">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/what-can-we-do-about-ultraprocessed-foods</id>
    <published>2024-06-03T06:00:02-07:00</published>
    <updated>2024-06-03T06:00:02-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/what-can-we-do-about-ultraprocessed-foods"/>
    <title>What can we do about ultraprocessed foods?</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<span data-mce-fragment="1">From breakfast cereals and protein bars to flavored yogurt and frozen pizzas, ultraprocessed foods are everywhere, filling aisle upon aisle at the supermarket. Fully </span><a href="https://www.sciencedirect.com/science/article/pii/S0022316622110011?via%3Dihub" data-mce-fragment="1" data-mce-href="https://www.sciencedirect.com/science/article/pii/S0022316622110011?via%3Dihub">58 percent</a><span data-mce-fragment="1"> of the calories consumed by adults and </span><a href="https://jamanetwork.com/journals/jama/fullarticle/2782866" data-mce-fragment="1" data-mce-href="https://jamanetwork.com/journals/jama/fullarticle/2782866">67 percent</a><span data-mce-fragment="1"> of those consumed by children in the United States are made up of these highly palatable foodstuffs with their highly manipulated ingredients.</span><p><a class="read-more" href="https://comparativeguide.com/blogs/news/what-can-we-do-about-ultraprocessed-foods">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<p class="article-info"> Researchers are figuring out the features of these foods that harm our health — and proposing ways ahead</p>
<p class="article-byline"><span class="author-byline">By Alice Callahan</span> <span class="pub-date">09.20.2023<span> </span></span></p>
<div class="article-content">
<div class="article-text -drop-cap">
<p>From breakfast cereals and protein bars to flavored yogurt and frozen pizzas, ultraprocessed foods are everywhere, filling aisle upon aisle at the supermarket. Fully <a href="https://www.sciencedirect.com/science/article/pii/S0022316622110011?via%3Dihub">58 percent</a> of the calories consumed by adults and <a href="https://jamanetwork.com/journals/jama/fullarticle/2782866">67 percent</a> of those consumed by children in the United States are made up of these highly palatable foodstuffs with their highly manipulated ingredients.</p>
<p>And ultraprocessed foods are not just filling our plates; they’re also taking up more and more space in global conversations about public health and nutrition. In the last decade or so, researchers have ramped up efforts to define ultraprocessed foods and to probe how their consumption correlates to health: A wave of recent studies have linked the foods to heightened risk for conditions ranging from cardiovascular disease and cancer to obesity and depression.</p>
<p>Still, some researchers — and perhaps unsurprisingly, industry representatives — question the strength of the evidence against ultraprocessed foods. The category is too poorly defined and the studies too circumstantial, they say. Plus, labeling such a large portion of our grocery carts as unhealthy ignores the benefits of industrial food processing in making food affordable, safe from foodborne pathogens, easy to prepare and in some cases more sustainable — such as through the development of <a href="https://pubmed.ncbi.nlm.nih.gov/35325028/">plant-derived products</a> designed to replace meat and milk.</p>
<p>“You cannot throw the baby out with the bathwater and decide that you’re going to just dump everything” that’s ultraprocessed, says Ciarán Forde, a sensory science and eating behavior researcher at Wageningen University in the Netherlands and coauthor of a <a href="https://www.annualreviews.org/doi/10.1146/annurev-nutr-062220-030123">2022 look at food processing and diets in the <em>Annual Review of Nutrition</em></a>.</p>
<p>As the debate about ultraprocessed foods roils on, one path forward is to invest in understanding the mechanisms by which ultraprocessed foods affect health. If the foods are indeed harmful, what about them — what features? — makes them so, and why? Through feeding volunteers carefully formulated diets and watching their consumption behavior, researchers can identify the qualities that make these foods both so appealing and so unhealthful, they say. Such studies could help to pinpoint the most harmful types of ultraprocessed foods — ones that might be targeted with warning labels and other policies — and guide companies in tweaking their recipes to produce more healthful options.</p>
<p>“I think the biological mechanisms are really important both to strengthen the evidence, but also to find solutions,” says Filippa Juul, a nutritional epidemiologist at New York University. That said, Juul adds, she thinks there’s already enough evidence about the harms of ultraprocessed foods to recommend that people eat less of them.</p>
<h2>Sifting the evidence on ultraprocessed foods</h2>
<p>To study ultraprocessed foods, researchers must be able to define them, and even this is contentious. Food preparation involves processes like grinding, cooking, <a href="https://knowablemagazine.org/content/article/food-environment/2024/evolution-of-koji-mold-soy-sauce-sake">fermenting</a> and pasteurizing — methods that have long been used to make foods safer and more digestible, palatable and storable. But according to the most widely used classification system, called NOVA, ultraprocessed foods are distinguished by additional industrial techniques, like hydrolysis, hydrogenation and extrusion, and with ingredients like emulsifiers, thickeners, flavors and other additives that are rarely found in home kitchens.</p>
<div class="article-image -caption-full"></div>
<p>Most of the evidence that ultraprocessed foods are harmful comes from observational studies in which participants are asked about the foods they eat and have their health tracked over time. These studies have consistently found that people who ate more ultraprocessed foods were more likely to develop <a href="https://www.bmj.com/content/365/bmj.l1451">cardiovascular disease</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/35750049/">high blood pressure</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/36854188/">type 2 diabetes</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/37360305/">some types of cancer</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/34455267/">obesity</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/36537321/">depression</a> and <a href="https://www.annualreviews.org/doi/abs/10.1146/annurev-food-062520-090235">inflammatory</a> diseases of the gastrointestinal tract such as <a href="https://pubmed.ncbi.nlm.nih.gov/36731590/">Crohn’s disease</a>, as well as to <a href="https://academic.oup.com/aje/article/191/7/1323/6539986">die</a> during the course of the studies.</p>
<p>Such observational studies can’t prove that ultraprocessed foods caused these health problems, in part because other factors in people’s lives could account for their greater risk of illness and death, Juul says. In the United States, for example, people who eat more ultraprocessed foods also tend to have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855172/">lower incomes and education levels</a> and to live in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340456/">poorer neighborhoods</a>; and unmeasured factors such as stress, sleep and exposure to racism and weight bias could confound the correlation between food processing and health.</p>
<p>However, Juul adds, the association between ultraprocessed foods and poor health is remarkably consistent in research from around the world. And though ultraprocessed foods often have poor nutritional profiles — containing more sugar, sodium and saturated fat than their minimally processed counterparts — that’s not the whole story: Studies that have adjusted for differences in nutritional quality have found <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747015/">an association of similar magnitude remains</a>. “There seems to be something else about these foods; it’s not just about the nutrients,” Juul says.</p>
<p>Unlike observational studies, randomized controlled trials can provide direct evidence that a particular diet causes health issues, but so far, only one <a href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30248-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413119302487%3Fshowall%3Dtrue">short-term trial</a> of this type has been published. In the tightly controlled study, led by National Institutes of Health nutrition and metabolism scientist Kevin Hall and published in 2019, 20 participants lived at a clinical center for one month and were offered either minimally processed foods or ultraprocessed foods for two weeks, then the other for two weeks. The meals were matched for overall calories, carbohydrates, sugar, fiber, fat, protein and salt, and participants were told they could eat as much or as little as they liked.</p>
<p>During two weeks on the ultraprocessed diet, participants ate an average of 508 more calories per day and gained about two pounds, the study found; during two weeks on the minimally processed diet, they lost about the same amount.</p>
<div class="article-image -caption-center"></div>
<p>That result was surprising to Hall, who had predicted that the level of processing wouldn’t matter since the two diets had similar nutrient levels. It also raised new questions: What is it about ultraprocessed foods that makes us eat more? And do all ultraprocessed foods have similar effects on us? The answer to the second question is probably not, Hall says. For example, in a <a href="https://diabetesjournals.org/care/article/46/7/1335/148548/Ultra-Processed-Food-Consumption-and-Risk-of-Type">2023 study</a>, overall intake of ultraprocessed food correlated with a greater risk of type 2 diabetes, but some food types — including cereals, whole grain breads, yogurt and dairy-based desserts like ice cream — were linked with a lower risk.</p>
<p>Hall says it will take a lot more research to figure out which subcategories of ultraprocessed foods are unhealthy and why; different mechanisms may underlie different maladies. A long list of mechanisms could contribute, adds Juul — such as food additives that affect the microbiome; the foods’ rapid and easy digestibility; chemicals absorbed from packaging; or the displacement of healthy foods from the diet. “It's likely a combination of all of these things,” she says.</p>
<h2>Why do we eat more ultraprocessed foods?</h2>
<p>If people outside of lab settings eat about 500 extra calories per day on an ultraprocessed diet, as they did in Hall’s 2019 study, it could help to explain why obesity rates have grown in recent decades, he believes. Hall is now focused on understanding why ultraprocessed foods would drive us to do this.</p>
<p>One possible explanation is energy density, or the number of calories per gram of food. In Hall’s 2019 NIH trial, for example, energy density was higher for the ultraprocessed foods, primarily because they contained less water, than for the minimally processed foods. <a href="https://pubmed.ncbi.nlm.nih.gov/36460778/">Previous research</a> has shown that people tend to consume more calories when they eat energy-dense foods, perhaps because the foods are less physically filling to the gastrointestinal tract and allow for more calories to be consumed in a shorter amount of time, interfering with normal satiety signaling. When Hall and colleagues <a href="https://pubmed.ncbi.nlm.nih.gov/37117850/">looked back</a> at 2,733 meals served in two NIH trials comparing different types of diets, they found that energy density was one of the most important determinants of calorie intake within a given meal.</p>
<div class="article-image -caption-full"></div>
<p>Hall and colleagues also saw in the study that participants ate more when they were offered foods containing greater amounts of certain pairs of nutrients — fat and sugar, fat and <a href="/article/food-environment/2023/salt-taste-surprisingly-mysterious">sodium</a>, or carbohydrates and sodium — than are found in nature, or in whole foods. Such foods are “hyperpalatable,” explains Tera Fazzino, a behavioral psychologist at the University of Kansas who <a href="https://pubmed.ncbi.nlm.nih.gov/31689013/">defined</a> the term. Hyperpalatable foods have been shown in animal and human studies to excessively activate reward-sensing circuits in the brain, and it’s more difficult to stop eating them, she says.</p>
<p>That’s different from the way we enjoy other foods, Fazzino adds. An apple, for example, contains naturally occurring sugars that make it pleasant to eat, but it’s not hyperpalatable because it doesn’t also contain lots of fat. In a similar manner, many of the foods that Fazzino enjoys when she visits family in Italy, such as fish lightly seasoned with olive oil and salt, and biscotti made with butter and a touch of sugar, leave her feeling perfectly satisfied, she says.</p>
<p>In contrast, it can feel like an act of resistance to stop eating hyperpalatable foods, such as the many packaged snack foods formulated with tasty combinations of carbohydrate, fat and salt, Fazzino says. And that’s a worry, because Fazzino’s research indicates that <a href="https://pubmed.ncbi.nlm.nih.gov/35581172/">the prevalence of hyperpalatable foods in the US increased</a> from 49 percent in 1988 to 69 percent in 2018.</p>
<p>At the NIH, Hall is currently running another clinical trial to try to tease apart the contributions of energy density and hyperpalatability to how much food people eat. In this study, participants will try four different diets, all matched for nutrient levels, for one week each. One is minimally processed. The other three are ultraprocessed, and either dense in calories or hyperpalatable, or both.</p>
<div class="article-image -caption-full"></div>
<p>In the Netherlands, meanwhile, eating behavior researcher Forde is focused on yet another food characteristic to explain greater calorie intake of ultraprocessed foods: texture. Many ultraprocessed foods are “effectively prechewed when they arrive on your plate because they’re softly textured,” Forde says — and that makes them easier to eat more quickly.</p>
<p>Research by Forde and others has found that people eat meals with harder textures more slowly. And in a recent trial, participants consumed <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257473/">26 percent fewer calories from hard-textured lunches than they did from softly textured ones</a>. Calorie intake was lowest of all when people ate a meal that was both hard-textured and also minimally processed.</p>
<p>Forde’s group is now planning a randomized controlled trial, funded in part by food companies, that will test participants’ intake of two different ultraprocessed diets for two weeks. Forde predicts that people will eat more of the “fast diet” that is soft in texture than the “slow diet,” which has been designed to have harder textures.</p>
<p>Other researchers are looking at ultraprocessed foods from the perspective of <a href="/article/mind/2021/foods-abuse-nutritionists-consider-food-addiction">addiction biology</a>. Because we can eat these foods quickly, and they often lack much structure or fiber to slow their digestion, they deliver a quick dose of calories and a rewarding spike in the neurotransmitter dopamine to the brain, says Alexandra DiFeliceantonio, a neuroscientist who studies eating behavior at the Fralin Biomedical Research Institute at Virginia Tech Carilion.</p>
<p>In an ongoing study, she and colleagues are giving people calorie-matched, rapidly digested sugar (“fast calories”) or slowly digested sugars with added fiber (“slow calories”) along with previously unfamiliar flavors. DiFeliceantonio hypothesizes that people will develop a stronger preference for the flavors paired with the fast calories. And this, she adds, could help explain why we might struggle to stop eating certain ultraprocessed foods that were “literally engineered to be delicious,” she says.</p>
<h2>Regulate? Or reformulate?</h2>
<p>DiFeliceantonio hopes that studies like hers will help disentangle what it is about ultraprocessed foods that cause overeating, and support new regulations that lead to more healthful choices. “Then,” she says, “you have a really strong scientific foundation for making changes in the environment, and not just asking people to make changes on an individual level.” Regulations might include limiting how the foods are advertised (for example, not during television shows for children) or requiring neighborhood markets to carry fresh foods in addition to packaged ones.</p>
<div id="newsletter-promo-item">
<div style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;" class="newsletter-promo">
<div style="display: grid;" class="newsletter-promo-img"></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a style="border-bottom: none;" href="https://knowablemagazine.org/newsletter-signup"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<p>Some public health experts say that regardless of the mechanisms, we know enough that we should be taking steps to reduce the consumption of ultraprocessed foods right now. “Whether they’re hyperpalatable, whether they’re energy-dense, whatever the cause is, the effect has been huge,” says Barry Popkin, an economist and nutrition epidemiologist at the University of North Carolina at Chapel Hill.</p>
<p>Popkin points to countries that have already imposed <a href="https://pubmed.ncbi.nlm.nih.gov/33865500/">regulations and restrictions</a> on certain ultraprocessed foods. Chile, for example, has added warning labels on the front of food packages and taxed sugary drinks; the country has also banned certain foods in schools and restricted their marketing to children — policies associated with a <a href="https://pubmed.ncbi.nlm.nih.gov/32045424/">drop in sugary beverage purchases</a> and <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003220">improved nutritional quality of packaged foods</a>. More than <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2802843">50 countries</a>, covering about 20 percent of the world’s population, now <a href="/article/health-disease/2019/do-soda-taxes-work">tax sugary drinks</a> because of their effects on health, and many other countries, including Israel, Canada, Brazil and Mexico, are adding warning labels to unhealthy foods, Popkin says.</p>
<p>Forde worries that such policies will only make food more expensive and slow progress in developing more sustainable foods. It would be more productive, he says, to encourage food companies to leverage their processing technologies to make healthier products. (Forde sits on an advisory council of Kerry Group, a food and ingredient company.) They could use food-processing techniques to reduce the caloric density of foods or incorporate more texture so that people eat a bit slower, he says. “If processing is the problem, processing is also by far the best solution we currently have,” he adds.</p>
<p>Hall would also like to see food scientists work with nutrition scientists to take on this challenge. Take a chicken nugget, for example. By adding a bit of fiber and tweaking the salt and fat content, skilled food scientists might be able to make it less energy-dense and remove its hyperpalatable qualities, he says. Whether people will still want to eat such a nugget remains to be seen.</p>
</div>
</div>
<link rel="canonical" href="https://knowablemagazine.org/content/article/food-environment/2023/what-can-we-do-about-ultraprocessed-foods"> <meta name="syndication-source" content="https://knowablemagazine.org/content/article/food-environment/2023/what-can-we-do-about-ultraprocessed-foods" doi="10.1146/knowable-092023-2">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/21st-century-diets-stone-age-bodies</id>
    <published>2024-05-27T09:00:03-07:00</published>
    <updated>2024-05-29T09:39:20-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/21st-century-diets-stone-age-bodies"/>
    <title>21st Century Diets ~ Stone Age Bodies</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p style="font-weight: bold;"><span style="font-size: 1.25rem;"> by Lyle MacWilliam</span><br>Co-founder, NutriSearch<br>and author of the <br><em>NutriSearch Comparative Guide to Nutritional Supplements™</em> series</p>
<h1>Introduction</h1>
<p>Prevailing nutritional patterns of the late Palaeolithic Period, occurring 100,000 to 50,000 years ago, established epigenetic (genetically expressed) regulatory mechanisms for the human species that continue to be expressed today. These ancient dietary patterns prescribe a reference standard for the optimal health of modern-day humankind; deviation from this ancestral norm is believed to be a principal cause of the rising prevalence of degenerative disease in our modern world. <sup>1</sup></p>
<p>During the intervening millennia, genetic evolution selectively created many observable changes to the human genome (such as hair, eye and skin pigmentation, and immune defences against microorganisms); however, core biochemical and physiological processes have remained resolutely inviolate.<sup>2</sup> Anthropological data from Africa, humanity's mother continent, reveal a pre-historic dietary plant-to-animal ratio of close to 1:1, with fish and shellfish comprising much of the animal component.<sup>3</sup> These diets, high in unprocessed plant fibre and indigenous fruits, would have been slightly alkaline, which remains the prevailing norm for modern human biology and physiology.</p>
<p>Archaeological evidence further reveals that, as a growing wave of humanity pressed outward from the East African plains, cultural and nutritional patterns began to diverge from this central norm. A growing discord between humankind's ancient genetic tapestry and the rapidly devolving cultural and nutritional patterns of early hunter-gatherer societies is evident in a recent worldwide study of 229 tribal societies. The findings reveal net acid loads of hunter-gatherer diets that reflect their particular geographic locations and that become progressively more positive as plant-to-animal dietary ratios decline.<sup>4</sup></p>
<p>These profound changes in humankind's cultural and biological environments, enhanced by the introduction of agriculture and animal husbandry about 10,000 years ago, were further magnified with the arrival of the industrial revolution. According to Cordain and co-workers, such paradigm shifts occurred too recently and too swiftly on an evolutionary scale for the human genome to adapt.<sup>5</sup> They contend that, in conjunction with this growing discord between our ancient biology and the prevailing nutritional and cultural patterns of contemporary populations, many of the so-called diseases of civilization have emerged <sup>6</sup> ― consequences of 21st Century diets and Stone-Age bodies.</p>
<h1>Dietary Acid/Alkaline Balance</h1>
<p>The Neolithic (9500 BCE) and industrial periods altered seven functional characteristics in our ancestral diets that have proved detrimental to the wellbeing of modern humankind. These include: glycemic load; fatty acid composition; macronutrient composition; micronutrient density; sodium-potassium ratio; fiber content; and acid-alkaline balance.<sup>5</sup> This position paper will focus on a principal factor, the increased net acid load of modern diets and its health implications; within this context, the relevance of other dietary factors will be discussed. We will also review two disease processes, osteoporosis and cancer, and the role played by chronic acidosis in their etiology.</p>
<h2>What is Net Acid Load?</h2>
<p>The acidity or alkalinity of any solution is determined by the relative concentrations of hydrogen (H<sup>+</sup>) and hydroxide (OH<sup>-</sup>) ions within the solvent and is expressed as pH, meaning "<b>p</b>ower of <b>H</b>ydrogen." The pH of a solution is a mathematical calculation based on a logarithmic scale from 0-14, where 7 is neutral (pH = -log [H<sup>+</sup>]). This is the pH of distilled water, where the relative concentrations of H<sup>+</sup> and OH<sup>-</sup> are equal, as represented by the following chemical equation.</p>
<p style="margin-left: 10%; text-indent: 10%;"><b><span style="font-size: large; font-weight: 800; line-height: 125%;">H<sub>2</sub>0 ↔ H<sub>(aq)</sub><sup>+</sup> + OH<sub>(aq)</sub><sup>-</sup></span></b></p>
<p>For every unit <i>below</i> pH 7.0, the concentration of H<sup>+ </sup>increases by a factor of 10. Such solutions are said to be acidic. For every unit <i>above</i> 7.0, the concentration of OH<sup>-</sup> is increased similarly. Such solutions are said to be alkaline. For example, a can of cola has a pH of about 2.5, over 10,000 times the acidity of the human cell. All living cells <i>must</i> operate within strict confines of a physiological pH that is slightly alkaline. Human blood, for example, has a pH of 7.365. If it drops below 7.0 (acidemia) or rises above 7.8 (alkalemia), coma and death can quickly follow. Consequently, the human body does <i>everything</i> in its power to ensure that the pH of its tissues remains within stringent confines.</p>
<div style="margin:2rem;">
<p style="font-size: 0.6rem; text-align: center;"><img data-sanitized-https:="" data-sanitized-data-mce-src="https://cdn.shopify.com/s/files/1/1793/9087/files/pHScale_480x480.jpg?v=1714845582" data-mce-src="https://cdn.shopify.com/s/files/1/1793/9087/files/pHScale_480x480.jpg?v=1714845582" src="https://cdn.shopify.com/s/files/1/1793/9087/files/pHScale_480x480.jpg?v=1714845582" alt="" data-sanitized-data-mce-fragment="1" data-mce-fragment="1"><br><a href="https://www.vecteezy.com/free-vector/ph">pH Vectors by Vecteezy</a></p>
</div>
<p><i>Net acid load</i> is an expression that refers to the contribution of acid (H<sup>+</sup>) to the cells of the body from foods that are consumed. As such, it represents the total <i>body burden</i> of dietary acid. A net acid load of zero would imply that the foods eaten were exactly balanced in their relative acidity and alkalinity. While our ancestral diets were slightly alkaline, today's modern Western diet has a high net acid load. This has severe implications for long-term health.</p>
<h2>What is meant by acid-foods?</h2>
<p><img width="288" height="252" alt="graph showing steady decrease in urine pH with net acid load" style="float: left; margin: 0.5rem 1rem 0.5rem 0;" src="https://cdn.shopify.com/s/files/1/1793/9087/files/changeinpH_480x480.gif?v=1715541071">People frequently confuse the <i>acidity</i> of a food source with its <i>acid load. </i>It appears paradoxical, but a lemon (which is quite acidic) will actually <i>reduce </i>the body's acid load, once its mineral contents (generally found in the pulp) are absorbed into the body fluids. This is because the predominant minerals within the lemon (i.e. the electrically positive cations of calcium, potassium, sodium and magnesium) have an alkalizing (acid-reducing) effect on the body. They do this by forming mineral hydroxides and carbonates in our cells, which act like molecular sponges to "suck up" excess acidity. Most fresh fruits and vegetables are replete with health promoting alkali minerals, which is in part why countless epidemiological studies have substantiated their health promoting effects.<sup>7</sup> Other minerals, including some found in the amino acids and proteins consumed in our diet, are <i>acid promoting</i>. These negatively charged anions (chloride, sulfate, phosphate, nitrate and some sulfur-containing amino acids) draw hydrogen into solution to form hydrochloric, sulfuric and phosphoric acids, and assorted weak organic acids in our cells. Foods that are predominant in these elements are commonly called acid-foods because they <i>contribute </i>to the body's net acid load. To determine if a particular food is acid absorbing or acid yielding, the food is completely oxidized to collect its mineral ash, then mixed with water to measure the resultant pH. The ash consists of the combined mineral contents of the food.</p>
<p>When organic matter is consumed, digestive enzymes cleave the constituent proteins, carbohydrates, fats and nucleic acids into their basic building blocks for absorption from the gut into the blood. All materials absorbed into the blood pass through the liver for detoxification inspection, ultimately reporting to the kidneys; it is here where the blood's pH is continually monitored and adjusted.<sup>8</sup> At the cellular level, dietary constituents are further oxidized by complex respiratory pathways, or are used to manufacture other structural components for the cell. During these metabolic exchanges, compounds containing sodium, potassium, magnesium, calcium, nitrogen, sulfur, chlorine and phosphorus are formed that can also contribute to the net acid load of the cell.<sup>9</sup></p>
<p>A more accurate means of calculating the net acid load of a diet consists of directly measuring the acid and ammonium in the urine, then subtracting the measured level of bicarbonate (HCO<sub>3</sub><sup>-</sup>) to yield a NEA (net excreted acid) score.<sup>10</sup> The NEA provides a measure of the <i>total</i> acid load of a <i>mixed</i> diet that is contributed to the body.</p>
<p>The NEA correlates closely with the pH of the urine as measured by narrow-range pH paper, something that can easily be done at home.</p>
<div style="float: left;">
<table style="width: 176.75pt; margin-right: 6.75pt;">
<tbody>
<tr>
<td style="width: 122.4pt; border-top: solid windowtext 1.0pt; border-left: solid windowtext 1.0pt; border-bottom: none; border-right: none; background: silver; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p><b><span lang="EN-US" style="font-size: 10.0pt; font-family: 'Arial',sans-serif; color: black;">Table 1-2:' </span></b></p>
</td>
<td style="width: 54.35pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: none; border-right: solid windowtext 1.0pt; background: silver; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: center;"><b><span lang="EN-US" style="font-size: 10.0pt; font-family: 'Arial',sans-serif; color: black;">PRAL </span></b></p>
</td>
</tr>
<tr style="height: 13.5pt;">
<td style="width: 122.4pt; border-top: none; border-left: solid windowtext 1.0pt; border-bottom: double windowtext 2.25pt; border-right: none; background: silver; padding: 0cm 5.4pt 0cm 5.4pt; height: 13.5pt;">
<p style="text-align: center;"><b><span lang="EN-US" style="font-size: 10.0pt; font-family: 'Arial',sans-serif; color: black;">Food group/100g</span></b></p>
</td>
<td style="width: 54.35pt; border-top: none; border-left: none; border-bottom: double windowtext 2.25pt; border-right: solid windowtext 1.0pt; background: silver; padding: 0cm 5.4pt 0cm 5.4pt; height: 13.5pt;">
<p style="text-align: center;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif; color: black;">(mEq/day)</span></b></p>
</td>
</tr>
<tr style="height: 13.5pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 13.5pt;">
<p>Processed Cheeses</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 13.5pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">31.5</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Hard Cheeses</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">21.4</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Soft Cheeses</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">10.0</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Meats &amp; Meat Products</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">9.5</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Cottage Cheese</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">8.7</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Eggs (whole)</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">8.2</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Low Protein Cheeses</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">8.0</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Fish</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">7.9</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Pasta</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">7.2</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Grain products (n/i pasta)</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">5.2</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Nuts and Fruits</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">4.5</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Yogurt</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">1.4</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Sugars/sweets</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">0.8</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Milk</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">0.7</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Legumes</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">0.5</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>Fats and Oils</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">0.0</span></b></p>
</td>
</tr>
<tr style="height: 13.5pt;">
<td style="width: 122.4pt; border-top: none; border-left: solid windowtext 1.0pt; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0cm 5.4pt 0cm 5.4pt; height: 13.5pt;">
<p>Vegetables</p>
</td>
<td style="width: 54.35pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0cm 5.4pt 0cm 5.4pt; height: 13.5pt;">
<p style="text-align: right;"><b><span lang="EN-US" style="font-size: 9.0pt; font-family: 'Arial',sans-serif;">-3.2</span></b></p>
</td>
</tr>
<tr style="height: 12.75pt;">
<td style="width: 122.4pt; border: none; border-left: solid windowtext 1.0pt; background: silver; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p>As adapted from:</p>
</td>
<td style="width: 54.35pt; border: none; border-right: solid windowtext 1.0pt; background: silver; padding: 0cm 5.4pt 0cm 5.4pt; height: 12.75pt;">
<p style="text-align: center;"><b> </b></p>
</td>
</tr>
<tr style="height: 13.5pt;">
<td colspan="2" style="width: 176.75pt; border-top: none; border-left: solid windowtext 1.0pt; border-bottom: solid windowtext 1.0pt; border-right: solid black 1.0pt; background: silver; padding: 0cm 5.4pt 0cm 5.4pt; height: 13.5pt;">
<p><i>Remer and Mantz,</i> 1995 July;95(7):791-7.</p>
</td>
</tr>
</tbody>
</table>
</div>
<p>Figure 1-1, adapted from Remer and Mantz (1995),<sup>11</sup> shows how one can estimate the body's NEA by simply measuring the pH of the urine with narrow-range pH paper. Low protein diets or those high in vegetables and fruits will provide a low acid load, whereas high protein diets or those with a paucity of fruits and vegetables will have a high acid load. This is reflected in the milli-equivalents (mEq) of total acids excreted per day.</p>
<p>Another index, called PRAL (potential renal acid load), provides an estimate of the net acid excretion for an <i>individual</i> food source.<sup>12</sup> Using detailed charts, it is easy to identify the contribution of an individual food source to the total body burden of acid contributed from the diet. Table 1-2 provides a summary of PRAL values by food group, as reported by Remer and Manz.<sup>11</sup> Using the PRAL values, it is possible to estimate the acid load per 100 grams of an individual food or food group.</p>
<h2>Chronic metabolic acidosis</h2>
<p>The role of nutrition in pH homeostasis (balance) has been a subject of controversy for almost a century. Physiological research demonstrates that the prodigious capacity of the kidneys to excrete excess acid precludes any direct measure of changes to acid-base balance due to diet. In healthy individuals fed diets that create a 10-fold increase in their acid load, changes in blood pH are barely detectible, confirming the textbook knowledge of full compensatory balance.<sup>13</sup>' However, this tenacity of the blood not to deviate from its physiological norm does not' preclude the possibility of a net retention of acid somewhere within the body, or the ability of the body to draw down its mineral stores in order to replace alkalizing minerals lost in the excretion of excess acid.</p>
<p>The pH of the blood and extracellular fluids bathing our cells is one of the most tightly regulated processes in human physiology.<sup>14</sup> Even minute changes to the pH of these fluids invoke powerful regulatory responses necessary for our survival. In the blood, these responses involve the release of excess carbon dioxide (a volatile acid) from our lungs, the utilization of bicarbonate buffer (HCO<sub>3</sub><sup>-</sup>)<sup> </sup>to mop up excess acid, and the formation and removal of ammonia through our kidneys (urine) and skin (perspiration). Within the cells themselves, the buffering role falls principally to the phosphate (PO<sub>4</sub><sup>-3</sup>) buffering system. About 85% of the phosphate ions used in intracellular pH buffering comes from potassium phosphate deposits on our bones and teeth.<sup>15</sup></p>
<p>Normally, these homeostatic responses are more than sufficient to deal with the day-to-day production of acids from cellular metabolism and return our cellular fluids to a slightly alkaline pH. Even in situations of extreme metabolic stress, where the body is forced to generate large quantities of lactic acid (such as in running a marathon), these regulatory mechanisms will soon return the pH to normal. However, if excess acid is continually introduced ― either through pathological conditions or through the diet ― a state of low-grade, chronic metabolic acidosis will occur.</p>
<p>To preserve pH balance under conditions of chronic acid load, the body must continually draw on its alkaline reserves by releasing calcium, potassium and magnesium from the bone matrix to neutralize excess acid. In addition, the body begins to break down muscle protein in order to release the amino acid glutamine. In turn, glutamine is converted to glutamic acid (glutamate) by the liver and, in doing so, binds with excess hydrogen ions to generate ammonia (NH<sub>4</sub><sup>+</sup>). The ammonia is then excreted in the urine, along with chloride (Cl<sup>-</sup>) ions that are needed to balance the electrochemical charge.<sup>16, 17</sup></p>
<p style="margin-left: 72.0pt; text-indent: 36.0pt;"><b><span style="font-size: 14.0pt; line-height: 125%;">Glutamine + H<sup>+</sup> ↔ Glutamate + NH<sub>4</sub><sup>+</sup></span></b></p>
<p>These two catabolic processes, if unchecked, result in the gradual loss of protein, calcium and related alkali minerals from the bone (osteopenia), and progressive muscle wasting (sarcopenia), both of which are age-related degenerative processes.</p>
<p>The fact is, low-grade (sub-clinical) chronic metabolic acidosis does exist normally in humans eating ordinary diets that yield normal net rates of endogenous acid production. Furthermore, this phenomenon has also been observed in other animal species.<sup>18</sup><sup><span style="font-family: 'Arial',sans-serif;">, </span>19</sup> The degree of acidosis increases with age, which explains the gradual decline in skeletal and muscle mass that occurs with aging.<sup>20</sup> If you have ever noticed the pungent aroma in a seniors' center, it is likely from the high levels of ammonia excreted in the urine of the acidotic residents.</p>
<p>Mainstream medicine has yet to recognize chronic metabolic acidosis, except as can occur through serious illness, such as diabetes and cancer. The heated debate amongst medical practitioners (who claim it is impossible to acidify the blood, except in the case of life-threatening disease) and the scientific research community (who finds otherwise) overlooks a simple misunderstanding. Acidosis is a <i>process,</i> not an end-game; like the voltage potential of a charged battery, acidosis is the electrochemical force that attempts to <i>drive</i> the pH of the blood <i>toward</i> acidity. Only if not countered by the prevailing regulatory mechanisms of the body, will the end-game ― <i>acidemia</i> (acid blood) ― inevitably result.</p>
<p>As previously mentioned, compared to our ancestral diets, which were alkaline preserving, the modern Western diet is acid producing. Research by Sebastian and coworkers shows that the NEA of the ancestral diet was approximately -88 mEg/day, as compared to +48 mEq/d for the Western diet.<sup>21</sup> While many proponents of alkaline (vegetarian) diets cite the high protein intake of the contemporary diets as the main contributor to acid load, the role of proteins in pH balance is exceedingly complex and dependent on the specific amino acid content of the protein(s) in question (plant protein vs. animal protein). A high protein intake <i>can</i> be acid forming, due to the phosphate and sulfur groups found in the amino-acid building blocks of animal proteins; however, protein degradation can also counteract some of its own acid load by increasing the renal capacity to excrete excess acid (as mentioned previously with glutamine). Thus, it appears that the shift from alkaline to acid load may come largely through displacing the bicarbonate-yielding fruits and vegetables with acid-yielding grains and dairy products.<sup>8</sup> In other words, it may not be so much an <i>excess</i> of acid-producing foods, but a <i>paucity</i> of alkaline-yielding vegetables that tips the scale from a healthy alkaline diet toward one of chronic metabolic acidosis.<sup>22</sup></p>
<h3>Chloride Balance</h3>
<p>This paper reports another important regulatory mechanism that appears to have been largely overlooked in the ongoing debate about chronic acidosis: the significant contribution by sodium chloride ― more specifically, the role of the chloride ion (Cl<sup>-1</sup>), itself ― to the net acid load of the body. Evidence of such participation has been very recently reported by Frassetto and coworkers, of the University of California, who found that the concentration of NaCl in the blood can <i>independently </i>predict the acid-alkaline status of the body.<sup>23</sup> The authors contend that, depending on the level of dietary intake, the concentration of chloride in the blood can predict a startling <b>50-100% </b>of the acidosis-producing effect of the diet. This finding is supported by the earlier work of Kellum and others, whose investigations into the determinants of blood pH concluded that it was the relative concentration of chloride to other strong ions (known as the strong ion difference) ― and <i>not</i> the level of bicarbonate (HCO<sub>3</sub><sup>-</sup>) buffer ― that determines the level of acidosis.<sup>24</sup><sup><span style="font-family: 'Arial',sans-serif;">, </span>25</sup> According to Kellum, the chloride ion can <i>singularly</i> act as a strong base, drawing hydrogen into solution. Consequently, as the level of chloride increases, so too does the level of acidity (pH decreases).</p>
<p>A typical American diet contains amounts of sodium chloride <i>far above</i> evolutionary norms and potassium <i>far below</i> those norms. It is estimated that our ancestral diet had a potassium/sodium ratio of 10:1, which has now been inverted to 1:3, reflecting a 30-fold change.<sup>26</sup> This inverted ratio of potassium to sodium in our contemporary diet, compared to our ancestral diet, is known to adversely affect cardiovascular function and contribute to hypertension and stroke. The very recent finding that diets containing substantial sodium chloride and diets that are acid producing can act <i>independently</i> to induce and sustain increased tissue acidity suggests a potent 'tag-team' combination, enhanced by increasing age and the kidney's impaired ability to excrete excess acidity.<sup>27</sup><sup><span style="font-family: 'Arial',sans-serif;">, </span>28</sup></p>
<p><b>These findings have huge implications, considering the amount of salt in the human diet, and suggest that sodium intake may play a role <i>equal </i>to or <i>greater </i>than net acid load of <i>all</i> other nutrients in the process of acidosis</b>.</p>
<h2>Acidosis and Disease</h2>
<p>The great French scientist, Louis Pasteur once said, 'The germ is nothing, the inner terrain is everything.' Within this context, chronic metabolic acidosis represents a profound disruption of our inner biological terrain, and one that is consistently observed in most physical and mental degenerative diseases. According to some clinicians, chronic acidosis is a clinical barometer by which we can measure the degenerative process.<sup>29</sup></p>
<p>In animal and human studies, metabolic acidosis has been shown to:</p>
<ul>
<li>increase Reactive Oxygen Species (ROS), impair oxidative phosphorylation (energy transfer), and invoke oxidative damage;<sup>30-32</sup>
</li>
<li>create aberrations in intestinal absorption of minerals and other nutrients;<sup>33, 34</sup>
</li>
<li>elevate insulin and cortisol levels;<sup>35, 36</sup>
</li>
<li>cause derangements in endocrine hormone balance;<sup>37, 38</sup>
</li>
<li>impair immunity and increase systemic inflammation;<sup>32, 36, 39-41</sup>
</li>
<li>reduce skeletal mineral and protein content and impair the function of bone-building cells;<sup>42-49</sup>
</li>
<li>retard skeletal growth;<sup>50-52</sup>
</li>
<li>promote proteolysis of protein and age-related muscle wasting;<sup>42, 44-47, 53-55</sup>
</li>
<li>induce hypertension and cardiovascular dysfunction;<sup>56, 57</sup>
</li>
<li>decrease insulin sensitivity and promote obesity, and;<sup>22, 50, 51, 58</sup>
</li>
<li>activate critical cellular signalling molecules linked to inflammation and carcinogenesis.<sup>59, 60</sup>
</li>
</ul>
<p>The <i>real</i> problem with chronic acidosis may not be so much one of excessive protein intake as it is one of chronic alkaline deficiency. It is well known that the standard North American diet falls woefully short of the daily intake of the fresh fruits and vegetables needed to supply the alkalizing minerals to effect pH balance. Several studies confirm that returning to an alkaline diet closer to our physiological norm will ameliorate the negative effects of excess acid load.<sup>61-63</sup></p>
<p>Too much acid, too much salt, chasing too few minerals. It is clear that today's dietary patterns are in serious discord with our genetically prescribed needs. As a society, we have neglected and abused our 'biological terrain' and degenerative disease is the consequence of our folly.</p>
<h3>Osteoporosis</h3>
<p>To protect at all costs the pH balance of the blood, the body sacrifices bone tissue through direct chemical dissolution of the bone surface, conscripting the minerals as buffers against the corrosive effects of excess acidity. As little as one week on a mildly acidic diet is sufficient to show a detectible drop in bone minerals from the bone surface.<sup>64</sup></p>
<img src="https://cdn.shopify.com/s/files/1/1793/9087/files/MetabolicAcidosis_480x480.gif?v=1715541071" width="363" height="243" alt="schematic diagram of the mechanisms by which excess H+ leads to release of bone calcium" style="float: left; margin: 0.5rem 1rem 0.5rem 0;">
<p>Consequently, acid-producing diets can dramatically alter both bone structure and function. A high dietary acid load has been shown to both <i>increase </i>bone resorption (a process by which the bone structure is remodeled) and <i>decrease</i> bone formation.<sup>65</sup></p>
<p>In the process, calcium (Ca<sup>+2</sup>) and carbonate (CO<sub>3</sub><sup>-2</sup>) are released from the bone mineral matrix.<sup>65, 66</sup> This release of calcium into the blood and its excretion in the urine is <i>not </i>compensated by equivalent calcium uptake in the gut. Sodium (Na<sup>+</sup>), potassium (K<sup>+</sup>), and assorted phosphate (PO<sub>4</sub><sup>-3 </sup>and HPO<sub>3</sub><sup>-</sup>)<sup> </sup>ions are also released from the bone surface to combine with the excess hydrogen (H<sup>+</sup>) in the blood.<sup>67-69</sup> Unchecked, this degradative process leads to thinner, weaker bones (osteopenia) and, if not corrected, osteoporosis (hollowed out bones).</p>
<p>It begins with the release of the alkaline minerals sodium and potassium from the bone surface, which the blood uses as its first line of defense against excess acid. Failure to restore pH balance then stimulates osteoclast (bone-destroying cells) activity and shuts down osteoblast (bone-forming cells) activity, precipitating the release of calcium and the carbonate/phosphate buffers from the bone mineral matrix and the increase of calcium (hypercalciuria) in the blood.<sup>65</sup> Arnett and coworkers have shown that bone resorption by osteoclasts is absolutely dependent on extracellular acidification; these cells are inactive at alkaline pH levels (above 7.3) and show maximum stimulation at a pH of about 6.9. Resorption is most sensitive to changes in acidity at a pH of about 7.1 (close to the interstitial pH in bone).<sup>70</sup> This cell-mediated response is likely affected through the release of the stress-related hormone cortisol, high levels of which are known to concurrently deplete muscle protein and accelerate mineral loss (a likely reason why prolonged stress, which raises blood cortisol levels, will accelerate bone loss).<sup>35</sup></p>
<p>Researchers with the massive Framingham Osteoporosis Study, published in 2001, contend that the consumption of fresh fruits and vegetables is a prudent means of interrupting this bone destroying process.<sup>71</sup> Because fruits and vegetables metabolize to bicarbonate, investigation has recently turned toward supplementation of the diet with alkaline salts, such as potassium bicarbonate and potassium citrate.<sup>72, 73</sup></p>
<p>Maurer and coworkers (2003) were the first to demonstrate that even very mild diet-induced acidosis will lead to the destruction of precious bone mineral, an effect that could be immediately and significantly reversed with the administration of bicarbonate mineral salts.<sup>35</sup> The treatments are generally well tolerated and help replenish the body's alkaline reserves while also serving to reverse the dysfunctional potassium/sodium ratio characteristic of modern diets. In one study, neutralization of dietary acid load using potassium bicarbonate (KHCO<sub>3</sub>) supplements improved calcium and phosphorus balances, reduced bone resorption, improved nitrogen balance (through reduced muscle wasting) and helped mitigate the normal age-related decline in growth hormone levels.<sup>19</sup> Other investigations demonstrate the remarkable bone preserving effect of this simple mineral salt. Dietary intervention with potassium-rich and bicarbonate rich foods and KHCO<sub>3 </sub>supplements confer striking protection against the bone-wasting effects of today's high-acid Western diet.<sup>74-77</sup> 'KHCO<sub>3 </sub>supplementation can also reduce hypertension and risk of stroke, prevent kidney stones by reducing calcium excretion, and protect against osteopenia and osteoporosis by increasing the retention of calcium and phosphorus, reducing bone resorption, and enhancing bone formation.<sup>78</sup> The dose of bicarbonate required to provide skeletal protection was found to be 60-120 mg/d, or about 1-2 teaspoons of potassium bicarbonate each day.<sup>79</sup></p>
<h3>Cancer</h3>
<p>In his elegantly written documentary, <i>Anticancer ~ A new Way of Life, </i>physician, researcher and cancer survivor, David Servan-Schreiber, paints a startling expos' of mainstream medicine's abject failure to address the true causes of cancer.<sup>80</sup> He contends that it is our modern Western diet and lifestyle that acts as a 'fertilizer' for cancer, helping to prepare our biological terrain for the incursion of this deadly process. According to Servan-Schreiber, the disease can best be understood as a breakdown in the balance between pre-cancerous cells that lie dormant in our bodies and our own natural defenses, which normally keep them at bay. By preparing the 'soil' with diets that are highly glycemic and highly acidic, these cancerous seeds germinate and morph into fast-growing clusters of mutated cells that soon become immortal and divide without end, spreading a growing tsunami of hyper-acidity that kills normal cells to make room for the new kids on the block. He argues that our best defense is a good offense, through simple and practical dietary and lifestyle changes.</p>
<p>Servan-Schreiber's arguments are well supported by a wealth of epidemiological and clinical studies, which confirm that more than 60% of cancer deaths can be avoided by simply adopting healthier lifestyles.<sup>80-82</sup> A very recent study demonstrated that women with breast cancer that had already spread to the lymph glands (metastasized), and whose treatment focused on diet, lifestyle change and stress reduction, saw their risk of dying from cancer drop a remarkable 66% compared to those women who chose the conventional treatments of 'cut, burn and poison.' <sup>83-86</sup> As well, researchers at the Universit' de Montr'al confirm that high fruit and vegetable intake diminishes the risk of breast cancer in genetically-prone, high-risk individuals by a stunning 73%. It seems that an alkaline diet confers the ability to down-regulate the cancer-causing genes that can lead to the development of this type of cancer.<sup>87</sup></p>
<p>In a study of 93 men with prostate cancer who refused conventional treatment and chose instead to modify their diet, exercise habits and stress levels, researchers found a marked reduction of their levels of prostate specific antigen (PSA), a blood marker for prostate cancer. Moreover, their blood was <i>7-fold</i> more capable of inhibiting cancer growth than those seeking conventional treatment.<sup>88</sup> In a very recent study, the same researchers found that such lifestyle changes modified the expression of more than 500 genes within the prostate, stimulating the cancer-protective genes and inhibiting cancer-promoting genes.<sup>89</sup></p>
<p>Such strong evidence begs the question:' What is it about our Western diet that seems to kick-start the cancer process? While a growing volume of observational, clinical and epidemiological evidence points to the role of chronic tissue acidosis in the genesis and maintenance of cancer,<sup>90</sup> a review of the literature on acid-forming diets and cancer reveals a paucity of research. The vast majority of cancer studies are looking through the <i>wrong</i> end of the microscope ― focusing on treatment/cure rather than prevention and risk mitigation. Nobel Laureate James Watson (co-discoverer of the molecular structure of DNA), describes today's cancer industry as, 'intellectually bankrupt, fiscally wasteful and therapeutically useless.' However, recent studies <i>have </i>emerged that provide an intriguing insight into the relationship between diet and cancer.</p>
<p>As previously mentioned, an acid-promoting diet initiates a broad cascade of biochemical and physiological changes to our inner terrain that appear to set us up for cancer. These include: chronic oxidative stress, enhanced catabolism (muscle wasting and destruction of skeletal reserves), elevation of insulin and cortisol, systemic inflammation, obesity, and impaired immunity. Each of these aberrations is known <i>singularly </i>to be involved with the genesis of the cancer process. Just imagine the implications when they are <i>all </i>pulling on the same rope.</p>
<p>Cancerous cells are formed continuously in the human body, with an estimated 10,000 cells active at any given time, their growth normally kept in check by an active, healthy immune system.<sup>91</sup> Abnormalities in our acid/alkaline balance seem to play a major role in the genesis of cancer by knee-capping our immune response to allow cancerous growths to start.<sup>32</sup> The glucocorticoid hormone, cortisol (responsible for the muscle wasting and bone depleting effects of chronic acidosis) is well known for its inhibitory effects on our immune system and is over-expressed in highly acidic tissues.<sup>36</sup> High levels of inflammation also block the body's natural defenses by disarming its natural killer (NK) cells (specialized white blood cells) and enhancing the production of chemical signalling molecules, such as prostaglandin E2 (PGE2), to further inhibit immunity and encourage unchecked growth.<sup>92, 93</sup> Measuring the level of systemic inflammation can, in fact, predict a patient's survival time for several cancers.<sup>94-96</sup></p>
<p>It was the father of modern pathology, Rudolph Virchow, who first observed that people often develop cancer at the exact spot where they had sustained an injury. Virchow advanced the hypothesis that cancer was a wound repair that had gone awry. The finding that cancer is most often directly related to a chronic inflammatory state adds support to Virchow's position, as inflammation is intricately related to the healing process.<sup>97</sup> Cancer, in fact, requires inflammation to both initiate and sustain its growth. For this reason, cancer cells secrete inflammatory proteins and other signaling molecules seen in natural wound repair, to fuel their growth.</p>
<p>Yet the unchallenged growth of cancer appears to rely principally on a single pro-inflammatory agent present in all cells but highly expressed in cancer cells ― Nuclear factor kappa-β (NFkβ) ― the 'master switch' that regulates inflammation throughout the body. Once activated, this cellular protein migrates to the nucleus of the cell, where it can switch on over 400 genes that control the body's inflammatory cascade.<sup>98</sup> According to Albert Baldwin, of the University of North Carolina, almost every cancer agent known to pharmacology is an inhibitor of NFkβ. In fact, the entire industry focus appears intent on finding an appropriate drug that will expressly inhibit this critical biochemical trigger.</p>
<p>Simply put, you could not find a better way to set us up for systemic inflammation and cancer than our acid-forming Western diet. Systemic tissue acidity (pH ~ 7.0 or less) has been shown to switch on NFkβ and other inflammation-signaling chemicals, such as C-reactive protein.(CRP) and cyclooxygenase-2 (COX-2), an enzyme central to the manufacture of other important inflammation-signaling molecules.<sup>32, 99</sup> At the same time, hyper-acidity within the tumor site (assisted by an already acidic condition) further cripples the immune system by knocking out of action the specialized white blood cells responsible for culling aberrant cells.<sup>100-102</sup> Acidification of tissues through imprudent dietary and lifestyle choices appears to tip the scales in favor of harm, <i>enslaving</i> our innate immune responses, which would normally swing into action to search out and destroy these invasive growths.<sup>36</sup></p>
<p>While the pH of cancer cells is neutral to slightly alkaline, the pH of the fluid surrounding these cells (extracellular fluid) is highly acidic due to acids secreted by cancerous cells, conferring upon them the ability to invade. Recent studies show that the administration of potassium and sodium bicarbonate salts can markedly enhance cancer kill rates and arrest cancer growths.<sup>103-105</sup> Other investigations have shown that interfering with the over-expression of carbonic anhydrase, an enzyme responsible for acidification of the tumor through conversion of bicarbonate to carbon dioxide (thereby removing the buffering effect of HCO<sub>3</sub><sup>-</sup>), can attenuate the invasiveness of cancer.<sup>106-110</sup> Some practitioners are now beginning to use bicarbonate therapy in their clinics, with remarkable results,<sup>110</sup> supporting the argument that it is a lack of bicarbonate and other alkalizing nutrients in the diet that predisposes us toward cancer and other degenerative processes.</p>
<h1>Conclusions</h1>
<p>Oxidative stress, insulin resistance, cortisol-induced catabolism, systemic inflammation ― <i>all</i> are consequences of a diet and lifestyle out of sync with our genetically prescribed patterns. They work synergistically to alter the body's ancestral biological terrain, defeat its natural defenses and dramatically increase our lifetime risk of cancer, osteoporosis, and other serious chronic diseases. The good news is that we can control these risk factors <i>ourselves</i>, with appropriate diet and lifestyle changes, so that the threat of these and other degenerative processes need not loom so large.</p>
<p>The following are some suggestions for kicking the 'acid' habit, returning your body to a healthy alkaline balance, and reducing your lifetime risk of degenerative disease, which unnecessarily cuts short so many lives today:</p>
<ul>
<li>bring pH balance back to the dinner table by serving meals that consist of 60-80% alkalizing fruits and vegetables;</li>
<li>stir-fry or steam your vegetables to preserve mineral and vitamin content, which is usually lost from overcooking and boiling;</li>
<li>Reduce your reliance on acid-producing dairy products, particularly hard cheeses, which should be used as condiments only;</li>
<li>Seriously reduce your use of acid-promoting white flour and substitute with multi-grain flour;</li>
<li>Start each day with an alkalizing glass of lemon water by squeezing a fresh lemon (NO SUGAR) into pure water ― and make sure you include the pulp;</li>
<li>Drink 6-8 glasses of water each day to help flush acidic wastes out of the body;</li>
<li>Choose fresh fish and organically grown chicken over red meats and limit your protein intake from meat to about 4 ounces a day (about the size of a deck of playing cards);</li>
<li>Throw out your sugar bowl ― really;</li>
<li>Trade in your table salt (sodium chloride contains traces of over 6o chemicals from the refining process) and choose natural sea salt, which contains a mixture of alkaline mineral complexes;</li>
<li>Don't drink sugary sodas (a single can of cola contains over 9 teaspoons of sugar and requires 32 glasses of water to neutralize its acidity);</li>
<li>Increase your intake of inflammation-reducing omega-3 fats, found in fish and flax seeds, and reduce your intake of inflammation-promoting omega-6 fats found in vegetable oils, fatty meats and dairy products;</li>
<li>Get some exercise every day, preferably aerobic exercise, to blow out excess acid-producing CO<sub>2 </sub>from your tissues and help maintain muscle tone; and,</li>
</ul>
<p>Lastly, learn to chill out, laugh and love a little more. Stress relief is now understood as a vital component of reducing tissue acidity and inflammation and protecting your long-term health.</p>
<h2 style="font-family: Arial, Helvetica, sans-serif; font-weight: 600; text-decoration: underline;">Reference List</h2>
<p>(1) Eaton SB, Konner M. Paleolithic nutrition. A consideration of its nature and current implications. <i>N Engl J Med</i> 1985 January 31;312(5):283-9.</p>
<p>(2) Smith E, Morowitz HJ. Universality in intermediary metabolism. <i>Proc Natl Acad Sci U S A</i> 2004 September 7;101(36):13168-73.</p>
<p>(3) Eaton SB, Konner MJ, Cordain L. Diet-dependent acid load, Paleolithic nutrition, and evolutionary health promotion. <i>Am J Clin Nutr</i> 2010 February;91(2):295-7.</p>
<p>(4) Strohle A, Hahn A, Sebastian A. Estimation of the diet-dependent net acid load in 229 worldwide historically studied hunter-gatherer societies. <i>Am J Clin Nutr</i> 2010 February;91(2):406-12.</p>
<p>(5) Cordain L, Eaton SB, Sebastian A et al. Origins and evolution of the Western diet: health implications for the 21st century. <i>Am J Clin Nutr</i> 2005 February;81(2):341-54.</p>
<p>(6) O'Keefe JH, Jr., Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. <i>Mayo Clin Proc</i> 2004 January;79(1):101-8.</p>
<p>(7) New SA. Intake of fruit and vegetables: implications for bone health. <i>Proc Nutr Soc</i> 2003 November;62(4):889-99.</p>
<p>(8) Berardi J. Covering Nutritional Bases. <i>ScienceLink</i> 2003;Available at: URL: <u><a href="http://www.johnberardi.com/articles/nutrition/bases.htm">http://www.johnberardi.com/articles/nutrition/bases.htm</a></u>. Accessed February 2, 2010.</p>
<p>(9) Acid and Alkaline in the Diet. <i>RawFoodExplained com</i> 2010;Available at: URL: <u><a href="http://www.rawfoodexplained.com/acid-and-alkaline-substances/acid-and-alkaline-in-the-diet.html">http://www.rawfoodexplained.com/acid-and-alkaline-substances/acid-and-alkaline-in-the-diet.html</a></u>. Accessed February 8, 2010.</p>
<p>(10) Remer T, Manz F. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. <i>Am J Clin Nutr</i> 1994 June;59(6):1356-61.</p>
<p>(11) Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. <i>J Am Diet Assoc</i> 1995 July;95(7):791-7.</p>
<p>(12) Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. <i>J Am Diet Assoc</i> 1995 July;95(7):791-7.</p>
<p>(13) Vormann J, Daniel H. The role of nutrition in human acid-base homeostasis. <i>Eur J Nutr</i> 2001 October;40(5):187-8.</p>
<p>(14) Kellum JA. Determinants of blood pH in health and disease. <i>Crit Care</i> 2000;4(1):6-14.</p>
<p>(15) Kim B. Essential Details on Acid and Alkaline-Forming Effects of Food and How Your Body Maintains a Healthy pH. <i>Dr Ben Kim</i> 2010;Available at: URL: <u><a href="http://drbenkim.com/ph-body-blood-foods-acid-alkaline.htm">http://drbenkim.com/ph-body-blood-foods-acid-alkaline.htm</a></u>. Accessed December 2, 2010.</p>
<p>(16) Frassetto L, Morris RC, Jr., Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. <i>J Clin Endocrinol Metab</i> 1997 January;82(1):254-9.</p>
<p>(17) Welbourne TC, Joshi S. Enteral glutamine spares endogenous glutamine in chronic acidosis. <i>JPEN J Parenter Enteral Nutr</i> 1994 May;18(3):243-7.</p>
<p>(18) Riond JL. Animal nutrition and acid-base balance. <i>Eur J Nutr</i> 2001 October;40(5):245-54.</p>
<p>(19) Frassetto L, Morris RC, Jr., Sellmeyer DE, Todd K, Sebastian A. Diet, evolution and aging--the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. <i>Eur J Nutr</i> 2001 October;40(5):200-13.</p>
<p>(20) Frassetto L, Morris RC, Jr., Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. <i>J Clin Endocrinol Metab</i> 1997 January;82(1):254-9.</p>
<p>(21) Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris RC, Jr. Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors. <i>Am J Clin Nutr</i> 2002 December;76(6):1308-16.</p>
<p>(22) Berkemeyer S. Acid-base balance and weight gain: are there crucial links via protein and organic acids in understanding obesity? <i>Med Hypotheses</i> 2009 September;73(3):347-56.</p>
<p>(23) Frassetto LA, Morris RC, Jr., Sebastian A. Dietary sodium chloride intake independently predicts the degree of hyperchloremic metabolic acidosis in healthy humans consuming a net acid-producing diet. <i>Am J Physiol Renal Physiol</i> 2007 August;293(2):F521-F525.</p>
<p>(24) Kellum JA, Song M, Almasri E. Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. <i>Chest</i> 2006 October;130(4):962-7.</p>
<p>(25) Story DA, Morimatsu H, Bellomo R. Hyperchloremic acidosis in the critically ill: one of the strong-ion acidoses? <i>Anesth Analg</i> 2006 July;103(1):144-8, table.</p>
<p>(26) Challem J. The pH Nutrition Guide to Acid / Alkaline Balance. <i>Natural News</i> 2010;Available at: URL: <u><a href="http://www.naturalnews.com/Report_acid_alkaline_pH_1.html">http://www.naturalnews.com/Report_acid_alkaline_pH_1.html</a></u>. Accessed February 10, 2010.</p>
<p>(27) Frassetto LA, Morris RC, Jr., Sellmeyer DE, Sebastian A. Adverse effects of sodium chloride on bone in the aging human population resulting from habitual consumption of typical American diets. <i>J Nutr</i> 2008 February;138(2):419S-22S.</p>
<p>(28) Frings-Meuthen P, Baecker N, Heer M. Low-grade metabolic acidosis may be the cause of sodium chloride-induced exaggerated bone resorption. <i>J Bone Miner Res</i> 2008 April;23(4):517-24.</p>
<p>(29) Philpott WH. Metabolic Acidosis and Degenerrative Disease. <i>J Orthomol Nutr</i> 1987;2(4):211-2.</p>
<p>(30) Bento LM, Fagian MM, Vercesi AE, Gontijo JA. Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial coupling and calcium transport in rats. <i>Nephrol Dial Transplant</i> 2007 October;22(10):2817-23.</p>
<p>(31) Rustom R, Wang B, McArdle F et al. Oxidative stress in a novel model of chronic acidosis in LLC-PK1 cells. <i>Nephron Exp Nephrol</i> 2003;95(1):e13-e23.</p>
<p>(32) Kellum JA, Song M, Li J. Science review: extracellular acidosis and the immune response: clinical and physiologic implications. <i>Crit Care</i> 2004 October;8(5):331-6.</p>
<p>(33) Charoenphandhu N, Wongdee K, Tudpor K, Pandaranandaka J, Krishnamra N. Chronic metabolic acidosis upregulated claudin mRNA expression in the duodenal enterocytes of female rats. <i>Life Sci</i> 2007 April 17;80(19):1729-37.</p>
<p>(34) Wongdee K, Teerapornpuntakit J, Riengrojpitak S, Krishnamra N, Charoenphandhu N. Gene expression profile of duodenal epithelial cells in response to chronic metabolic acidosis. <i>Mol Cell Biochem</i> 2009 January;321(1-2):173-88.</p>
<p>(35) Maurer M, Riesen W, Muser J, Hulter HN, Krapf R. Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. <i>Am J Physiol Renal Physiol</i> 2003 January;284(1):F32-F40.</p>
<p>(36) Lardner A. The effects of extracellular pH on immune function. <i>J Leukoc Biol</i> 2001 April;69(4):522-30.</p>
<p>(37) Brungger M, Hulter HN, Krapf R. Effect of chronic metabolic acidosis on thyroid hormone homeostasis in humans. <i>Am J Physiol</i> 1997 May;272(5 Pt 2):F648-F653.</p>
<p>(38) Wiederkehr MR, Kalogiros J, Krapf R. Correction of metabolic acidosis improves thyroid and growth hormone axes in haemodialysis patients. <i>Nephrol Dial Transplant</i> 2004 May;19(5):1190-7.</p>
<p>(39) Krieger NS, Frick KK, LaPlante SK, Michalenka A, Bushinsky DA. Regulation of COX-2 mediates acid-induced bone calcium efflux in vitro. <i>J Bone Miner Res</i> 2007 June;22(6):907-17.</p>
<p>(40) Yorio T, Page RD, Frazier LW. Prostaglandin regulation of H+ secretion in amphibian epithelia. <i>Am J Physiol</i> 1991 May;260(5 Pt 2):R866-R872.</p>
<p>(41) Bushinsky DA, Parker WR, Alexander KM, Krieger NS. Metabolic, but not respiratory, acidosis increases bone PGE(2) levels and calcium release. <i>Am J Physiol Renal Physiol</i> 2001 December;281(6):F1058-F1066.</p>
<p>(42) Ballmer PE, McNurlan MA, Hulter HN, Anderson SE, Garlick PJ, Krapf R. Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans. <i>J Clin Invest</i> 1995 January;95(1):39-45.</p>
<p>(43) Disthabanchong S, Radinahamed P, Stitchantrakul W, Hongeng S, Rajatanavin R. Chronic metabolic acidosis alters osteoblast differentiation from human mesenchymal stem cells. <i>Kidney Int</i> 2007 February;71(3):201-9.</p>
<p>(44) Kleger GR, Turgay M, Imoberdorf R, McNurlan MA, Garlick PJ, Ballmer PE. Acute metabolic acidosis decreases muscle protein synthesis but not albumin synthesis in humans. <i>Am J Kidney Dis</i> 2001 December;38(6):1199-207.</p>
<p>(45) May RC, Masud T, Logue B, Bailey J, England B. Chronic metabolic acidosis accelerates whole body proteolysis and oxidation in awake rats. <i>Kidney Int</i> 1992 June;41(6):1535-42.</p>
<p>(46) May RC, Bailey JL, Mitch WE, Masud T, England BK. Glucocorticoids and acidosis stimulate protein and amino acid catabolism in vivo. <i>Kidney Int</i> 1996 March;49(3):679-83.</p>
<p>(47) Williams B, Layward E, Walls J. Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis. <i>Clin Sci (Lond)</i> 1991 May;80(5):457-62.</p>
<p>(48) Wongdee K, Riengrojpitak S, Krishnamra N, Charoenphandhu N. Claudin expression in the bone-lining cells of female rats exposed to long-standing acidemia. <i>Exp Mol Pathol</i> 2009 December 24.</p>
<p>(49) Frick KK, LaPlante K, Bushinsky DA. RANK ligand and TNF-alpha mediate acid-induced bone calcium efflux in vitro. <i>Am J Physiol Renal Physiol</i> 2005 November;289(5):F1005-F1011.</p>
<p>(50) Goldberg R, Reshef-Bankai E, Coleman R, Green J, Maor G. Chronic acidosis-induced growth retardation is mediated by proton-induced expression of Gs protein. <i>J Bone Miner Res</i> 2006 May;21(5):703-13.</p>
<p>(51) Green J. The physicochemical structure of bone: cellular and noncellular elements. <i>Miner Electrolyte Metab</i> 1994;20(1-2):7-15.</p>
<p>(52) Green J, Goldberg R, Maor G. PTH ameliorates acidosis-induced adverse effects in skeletal growth centers: the PTH-IGF-I axis. <i>Kidney Int</i> 2003 February;63(2):487-500.</p>
<p>(53) Ruggieri F, Caso G, Wegmann M et al. Does increasing blood pH stimulate protein synthesis in dialysis patients? <i>Nephron Clin Pract</i> 2009;112(4):c276-c283.</p>
<p>(54) Garibotto G, Sofia A, Robaudo C et al. Kidney protein dynamics and ammoniagenesis in humans with chronic metabolic acidosis. <i>J Am Soc Nephrol</i> 2004 June;15(6):1606-15.</p>
<p>(55) Baldwin DN, Spencer JL, Jeffries-Stokes CA. Carbohydrate intolerance and kidney stones in children in the Goldfields. <i>J Paediatr Child Health</i> 2003 July;39(5):381-5.</p>
<p>(56) Zhang L, Curhan GC, Forman JP. Diet-dependent net acid load and risk of incident hypertension in United States women. <i>Hypertension</i> 2009 October;54(4):751-5.</p>
<p>(57) Murakami K, Sasaki S, Takahashi Y, Uenishi K. Association between dietary acid-base load and cardiometabolic risk factors in young Japanese women. <i>Br J Nutr</i> 2008 September;100(3):642-51.</p>
<p>(58) Kopple JD, Kalantar-Zadeh K, Mehrotra R. Risks of chronic metabolic acidosis in patients with chronic kidney disease. <i>Kidney Int Suppl</i> 2005 June;(95):S21-S27.</p>
<p>(59) Krieger NS, Bushinsky DA, Frick KK. Cellular mechanisms of bone resorption induced by metabolic acidosis. <i>Semin Dial</i> 2003 November;16(6):463-6.</p>
<p>(60) Krieger NS, Frick KK, Bushinsky DA. Mechanism of acid-induced bone resorption. <i>Curr Opin Nephrol Hypertens</i> 2004 July;13(4):423-36.</p>
<p>(61) Bell JA, Whiting SJ. Effect of fruit on net acid and urinary calcium excretion in an acute feeding trial of women. <i>Nutrition</i> 2004 May;20(5):492-3.</p>
<p>(62) Frassetto LA, Todd KM, Morris RC, Jr., Sebastian A. Worldwide incidence of hip fracture in elderly women: relation to consumption of animal and vegetable foods. <i>J Gerontol A Biol Sci Med Sci</i> 2000 October;55(10):M585-M592.</p>
<p>(63) New SA. Intake of fruit and vegetables: implications for bone health. <i>Proc Nutr Soc</i> 2003 November;62(4):889-99.</p>
<p>(64) Bushinsky DA, Chabala JM, Gavrilov KL, Levi-Setti R. Effects of in vivo metabolic acidosis on midcortical bone ion composition. <i>Am J Physiol</i> 1999 November;277(5 Pt 2):F813-F819.</p>
<p>(65) Bushinsky DA. Acid-base imbalance and the skeleton. <i>Eur J Nutr</i> 2001 October;40(5):238-44.</p>
<p>(66) Bushinsky DA, Sessler NE, Glena RE, Featherstone JD. Proton-induced physicochemical calcium release from ceramic apatite disks. <i>J Bone Miner Res</i> 1994 February;9(2):213-20.</p>
<p>(67) Bushinsky DA, Levi-Setti R, Coe FL. Ion microprobe determination of bone surface elements: effects of reduced medium pH. <i>Am J Physiol</i> 1986 June;250(6 Pt 2):F1090-F1097.</p>
<p>(68) Bushinsky DA, Wolbach W, Sessler NE, Mogilevsky R, Levi-Setti R. Physicochemical effects of acidosis on bone calcium flux and surface ion composition. <i>J Bone Miner Res</i> 1993 January;8(1):93-102.</p>
<p>(69) Chabala JM, Levi-Setti R, Bushinsky DA. Alteration in surface ion composition of cultured bone during metabolic, but not respiratory, acidosis. <i>Am J Physiol</i> 1991 July;261(1 Pt 2):F76-F84.</p>
<p>(70) Arnett T. Regulation of bone cell function by acid-base balance. <i>Proc Nutr Soc</i> 2003 May;62(2):511-20.</p>
<p>(71) Tucker KL, Hannan MT, Kiel DP. The acid-base hypothesis: diet and bone in the Framingham Osteoporosis Study. <i>Eur J Nutr</i> 2001 October;40(5):231-7.</p>
<p>(72) Phend C. Counteracting Acidic Diet Reduces Markers of Bone Loss in Older Adults. <i>Medpage Today</i> 2008 December 3;Available at: URL: <u><a href="http://www.medpagetoday.com/PrimaryCare/DietNutrition/12006">http://www.medpagetoday.com/PrimaryCare/DietNutrition/12006</a></u>. Accessed February 13, 2010.</p>
<p>(73) Marangella M, Di SM, Casalis S, Berutti S, D'Amelio P, Isaia GC. Effects of potassium citrate supplementation on bone metabolism. <i>Calcif Tissue Int</i> 2004 April;74(4):330-5.</p>
<p>(74) Frassetto L, Morris RC, Jr., Sebastian A. Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women. <i>J Clin Endocrinol Metab</i> 2005 February;90(2):831-4.</p>
<p>(75) Lanham-New SA. The balance of bone health: tipping the scales in favor of potassium-rich, bicarbonate-rich foods. <i>J Nutr</i> 2008 January;138(1):172S-7S.</p>
<p>(76) Lutz J. Calcium balance and acid-base status of women as affected by increased protein intake and by sodium bicarbonate ingestion. <i>Am J Clin Nutr</i> 1984 February;39(2):281-8.</p>
<p>(77) Mathur RP, Dash SC, Gupta N, Prakash S, Saxena S, Bhowmik D. Effects of correction of metabolic acidosis on blood urea and bone metabolism in patients with mild to moderate chronic kidney disease: a prospective randomized single blind controlled trial. <i>Ren Fail</i> 2006;28(1):1-5.</p>
<p>(78) Morris RC, Jr., Schmidlin O, Tanaka M, Forman A, Frassetto L, Sebastian A. Differing effects of supplemental KCl and KHCO3: pathophysiological and clinical implications. <i>Semin Nephrol</i> 1999 September;19(5):487-93.</p>
<p>(79) Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris RC, Jr. Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. <i>N Engl J Med</i> 1994 June 23;330(25):1776-81.</p>
<p>(80) Servan-Schreiber D. <i>Anticancer: A New Way of Life</i>. 3rd ed. Toronto: Harper-Collins Publishers; 2009.</p>
<p>(81) Stewart BW, Kleihues P. World Cancer Report. Lyon, France: World Health Organization (WHO); 2003.</p>
<p>(82) Yatani R, Shiraishi T, Nakakuki K et al. Trends in frequency of latent prostate carcinoma in Japan from 1965-1979 to 1982-1986. <i>J Natl Cancer Inst</i> 1988 July 6;80(9):683-7.</p>
<p>(83) Andersen BL, Farrar WB, Golden-Kreutz DM et al. Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial. <i>J Clin Oncol</i> 2004 September 1;22(17):3570-80.</p>
<p>(84) Andersen BL, Farrar WB, Golden-Kreutz D et al. Distress reduction from a psychological intervention contributes to improved health for cancer patients. <i>Brain Behav Immun</i> 2007 October;21(7):953-61.</p>
<p>(85) Andersen BL, Yang HC, Farrar WB et al. Psychologic intervention improves survival for breast cancer patients: a randomized clinical trial. <i>Cancer</i> 2008 December 15;113(12):3450-8.</p>
<p>(86) Thornton LM, Andersen BL, Crespin TR, Carson WE. Individual trajectories in stress covary with immunity during recovery from cancer diagnosis and treatments. <i>Brain Behav Immun</i> 2007 February;21(2):185-94.</p>
<p>(87) Ghadirian P, Narod S, Fafard E, Costa M, Robidoux A, Nkondjock A. Breast cancer risk in relation to the joint effect of BRCA mutations and diet diversity. <i>Breast Cancer Res Treat</i> 2009 September;117(2):417-22.</p>
<p>(88) Ornish D, Weidner G, Fair WR et al. Intensive lifestyle changes may affect the progression of prostate cancer. <i>J Urol</i> 2005 September;174(3):1065-9.</p>
<p>(89) Ornish D, Magbanua MJ, Weidner G et al. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. <i>Proc Natl Acad Sci U S A</i> 2008 June 17;105(24):8369-74.</p>
<p>(90) Orive G, Reshkin SJ, Harguindey S, Pedraz JL. Hydrogen ion dynamics and the Na+/H+ exchanger in cancer angiogenesis and antiangiogenesis. <i>Br J Cancer</i> 2003 October 20;89(8):1395-9.</p>
<p>(91) Roland-Mieszkowski M. <span style="font-family: 'Arial Narrow',sans-serif;">Cancer - A Biophysicist's Point of View</span>. <i>Digital Recordings com</i> 2004 July 21;Available at: URL: <u><a href="http://www.digital-recordings.com/publ/cancer.html">http://www.digital-recordings.com/publ/cancer.html</a></u>. Accessed February 12, 2010.</p>
<p>(92) Huang M, Stolina M, Sharma S et al. Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. <i>Cancer Res</i> 1998 March 15;58(6):1208-16.</p>
<p>(93) Baxevanis CN, Reclos GJ, Gritzapis AD, Dedousis GV, Missitzis I, Papamichail M. Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer. <i>Cancer</i> 1993 July 15;72(2):491-501.</p>
<p>(94) Wallace JM. Nutritional and botanical modulation of the inflammatory cascade--eicosanoids, cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy. <i>Integr Cancer Ther</i> 2002 March;1(1):7-37.</p>
<p>(95) Crumley AB, McMillan DC, McKernan M, McDonald AC, Stuart RC. Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer. <i>Br J Cancer</i> 2006 March 13;94(5):637-41.</p>
<p>(96) Al Murri AM, Bartlett JM, Canney PA, Doughty JC, Wilson C, McMillan DC. Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. <i>Br J Cancer</i> 2006 January 30;94(2):227-30.</p>
<p>(97) Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. <i>N Engl J Med</i> 1986 December 25;315(26):1650-9.</p>
<p>(98) Goepp JG. What is Nuclear Factor kappa Beta? Life Extension , 31-40. 2006. <br> Ref Type: Magazine Article</p>
<p>(99) Miyazawa K, Inoue K. Complement activation induced by human C-reactive protein in mildly acidic conditions. <i>J Immunol</i> 1990 July 15;145(2):650-4.</p>
<p>(100) Severin T, Muller B, Giese G et al. pH-dependent LAK cell cytotoxicity. <i>Tumour Biol</i> 1994;15(5):304-10.</p>
<p>(101) Loeffler DA, Juneau PL, Heppner GH. Natural killer-cell activity under conditions reflective of tumor micro-environment. <i>Int J Cancer</i> 1991 July 30;48(6):895-9.</p>
<p>(102) Redegeld F, Filippini A, Sitkovsky M. Comparative studies of the cytotoxic T lymphocyte-mediated cytotoxicity and of extracellular ATP-induced cell lysis. Different requirements in extracellular Mg2+ and pH. <i>J Immunol</i> 1991 November 15;147(10):3638-45.</p>
<p>(103) Robey IF, Baggett BK, Kirkpatrick ND et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. <i>Cancer Res</i> 2009 March 15;69(6):2260-8.</p>
<p>(104) Raghunand N, Gillies RJ. pH and chemotherapy. <i>Novartis Found Symp</i> 2001;240:199-211.</p>
<p>(105) Raghunand N, He X, van SR et al. Enhancement of chemotherapy by manipulation of tumour pH. <i>Br J Cancer</i> 1999 June;80(7):1005-11.</p>
<p>(106) Winum JY, Rami M, Scozzafava A, Montero JL, Supuran C. Carbonic anhydrase IX: a new druggable target for the design of antitumor agents. <i>Med Res Rev</i> 2008 May;28(3):445-63.</p>
<p>(107) Pastorekova S, Parkkila S, Zavada J. Tumor-associated carbonic anhydrases and their clinical significance. <i>Adv Clin Chem</i> 2006;42:167-216.</p>
<p>(108) Thiry A, Dogne JM, Masereel B, Supuran CT. Targeting tumor-associated carbonic anhydrase IX in cancer therapy. <i>Trends Pharmacol Sci</i> 2006 November;27(11):566-73.</p>
<p>(109) Rafajova M, Zatovicova M, Kettmann R, Pastorek J, Pastorekova S. Induction by hypoxia combined with low glucose or low bicarbonate and high posttranslational stability upon reoxygenation contribute to carbonic anhydrase IX expression in cancer cells. <i>Int J Oncol</i> 2004 April;24(4):995-1004.</p>
<p>(110) Mac Farlane AB. Sodium Bicarbonate Lessons in Cancer and General pH Management. <i>International Medical Veritas Association</i> 2007 July 4;Available at: URL: <u><a href="http://www.health-forums.com/alt-support-cancer/sodium-bicarbonate-lessons-cancer-long-read-but-worth-even-if-you-do-not-have-cancer-14887.html">http://www.health-forums.com/alt-support-cancer/sodium-bicarbonate-lessons-cancer-long-read-but-worth-even-if-you-do-not-have-cancer-14887.html</a></u>. Accessed February 15, 2010.</p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/what-s-next-in-the-ozempic-era</id>
    <published>2024-04-29T06:00:00-07:00</published>
    <updated>2024-04-29T06:00:00-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/what-s-next-in-the-ozempic-era"/>
    <title>What’s next in the Ozempic era?</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<h2 class="article-subhead">Diabetes, weight loss and now heart health: A new family of drugs is changing the way scientists are thinking about obesity — and more uses are on the horizon</h2>
<p class="article-byline"><span style="font-size: large; font-weight: bold;" class="author-byline">By Matías A. Loewy</span><span style="font-size: large; font-style: italic;" class="pub-date"> 2024-04-17 </span></p>
<p style="font-size: small;"><em>Article originally published in </em><a href="https://knowablemagazine.org/content/article/health-disease/2024/whats-next-in-the-ozempic-era" target="_blank">Knowable</a> <em>magazine.</em></p>
<div class="article-text -drop-cap">
<p>Few drugs have achieved the stardom that semaglutide, marketed in the United States as Ozempic or Wegovy, has today. A synthetic, injectable version of an intestinal hormone, it is the flagship of a new category of drugs initially developed for diabetes that rose to fame in the medical and public arena as an effective weapon against obesity. Semaglutide has proved so successful that its manufacturer, the Danish company Novo Nordisk, is unable to keep up with demand.</p>
<p>The US Food and Drug Administration approved semaglutide in 2017 to improve the control of blood sugar levels in adults with type 2 diabetes — and then, in June 2021, <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014">for chronic weight management in adults who are obese or overweight</a> and have related risk factors, such as high blood pressure or diabetes.</p>
<p><a href="https://mashable.com/article/wegovy-ozempic-kim-kardashian-weight-loss">Social networks boosted the drug’s fame</a>: In mid-2022, a viral TikTok clip claimed Kim Kardashian had used semaglutide to lose 15 pounds so that she could wear an iconic Marilyn Monroe dress to the Met Gala in New York. In the months that followed, everyone from former British Prime Minister Boris Johnson to billionaire entrepreneur Elon Musk acknowledged resorting to the medication to tamp down their appetites and slim down. Today, <a href="https://www.pewresearch.org/science/2024/02/26/how-americans-view-weight-loss-drugs-and-their-potential-impact-on-obesity-in-the-u-s/">three out of four Americans say they have heard of this type of drug</a> — and of those, more than half consider it a good option for weight loss, according to a Pew Research survey.</p>
<p>Last November, however, the ones with their eyes on the drug were cardiologists. At the opening of the 2023 annual meeting of the American Heart Association in Philadelphia, results of a clinical trial generated tremendous interest: Semaglutide, it appeared, was a new tool to treat heart disease.</p>
<p>The trial, <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2307563">called SELECT, was conducted in 41 countries with more than 17,000</a> people who were overweight or obese and at high cardiovascular risk but who didn’t have diabetes. It found that a weekly subcutaneous injection of 2.4 milligrams of semaglutide can, in addition to helping people lose an average of 15 percent of their original weight, reduce the risk of heart attack, stroke or death by 20 percent. It’s a magnitude of effect that puts it in the same category as other drugs that prevent cardiovascular events, such as low-dose aspirin, antihypertensives and statins to lower <a href="https://knowablemagazine.org/content/article/health-disease/2024/cholesterol-and-heart-disease-explained">cholesterol</a>.</p>
<p>From the study, scientists could calculate the total number of people who would need to be treated to produce the desired benefit in one of them. They found that treating 67 diabetes-free overweight or obese patients at high risk of a cardiovascular event for 40 months would prevent one major cardiovascular event, such as heart attack or stroke, or death due to heart disease. By way of comparison, this is the same number of patients with a cardiovascular history who must take <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838845/">aspirin</a> or <a href="https://thennt.com/nnt/anti-hypertensives-to-prevent-death-heart-attacks-and-strokes/">hypertension drugs</a> for 60 months to avoid one stroke.</p>
<div class="article-image -caption-right"></div>
<p>Based on the study results, in early March <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or">the FDA approved the use of injectable semaglutide to reduce the risk of cardiovascular death</a>, myocardial infarction and stroke in adults with cardiovascular disease who are obese or overweight.</p>
<p>“It’s a milestone. For the first time, we have a drug, semaglutide, that not only causes weight loss, but also reduces the formation of atherosclerotic plaque and prevents deaths and cardiovascular events,” says Paola Harwicz, a cardiologist and obesity specialist in Buenos Aires who headed the Cardiometabolism Council of the Argentine Society of Cardiology and participated in the meeting in Philadelphia.</p>
<p>Several studies suggest that the drug reduces the buildup of plaque in the arteries; in one of them, in patients with type 2 diabetes, <a href="https://www.mdpi.com/2227-9059/11/5/1362">four months of treatment with semaglutide</a> reduced carotid artery thickness, a clinical marker of atherosclerosis, by 13 percent.</p>
<p>A role for semaglutide and related drugs in staving off cardiovascular disease — the cause of one in three deaths worldwide — further boosts the drug’s prospects in the market by vastly expanding the universe of specialists who can prescribe it. It also repositions being overweight as one of the main truly modifiable risk factors for cardiovascular disease.</p>
<h2>Dealing with extra pounds</h2>
<p>According to the classic medical approach, to lose weight there must be an imbalance between calories taken in and calories burned: You either eat fewer or expend more. But in the last 30 years, new evidence has shown it is far more complicated than<strong> </strong>that, says Julio César Montero, a medical nutritionist and president of the Argentine Society of Obesity and Eating Disorders.</p>
<p>The emerging thinking among those working in this field, and reflected in a statement by the <a href="https://academic.oup.com/edrv/article/38/4/267/3892397">Endocrine Society</a>, is that obesity is due to two related but distinct processes: the already mentioned energy imbalance (eating more calories than the body expends) and the resetting of the body weight “set point” — the weight that the body determines as its goal — to a higher value.</p>
<p>People with obesity have a disorder of the energy homeostasis system, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Thus, the body responds to weight loss by tenaciously trying to regain the lost pounds and return to its (higher value) target weight.</p>
<div class="article-image -caption-center"></div>
<p>The mechanism behind the body’s quest to return to its body weight set point is not yet fully understood, but it explains why it is so difficult to achieve an effective treatment to manage obesity. It is estimated that only one in five people who lose between 5 and 10 percent of their initial weight through diet and exercise in six months manage to keep off the weight for more than a year. Losing and sustaining weight loss isn’t made easier by modernity’s <a href="https://www.annualreviews.org/content/journals/10.1146/annurev.anthro.35.081705.123301">sedentary way of life</a> and the wide range of readily available <a href="https://knowablemagazine.org/content/article/food-environment/2023/what-can-we-do-about-ultraprocessed-foods">ultraprocessed foods</a>. By 2035, it’s projected that <a href="https://www.worldobesity.org/news/economic-impact-of-overweight-and-obesity-to-surpass-4-trillion-by-2035">more than half of the world’s population</a> will be overweight or obese.</p>
<p>Until now, <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00059-7/fulltext">traditional anti-obesity drugs</a> have had limited effectiveness. Most act on brain-signaling chemicals — neurotransmitters — to reduce appetite, an approach pioneered in the 1960s with the use of amphetamines that has continued to today with safer derivatives and some other, nonamphetamine, drugs. Another often-used drug is orlistat (marketed as Alli or Xenical), which reduces fat absorption from food.</p>
<p>But for all of these, the effects over the short and medium term are relatively modest, achieving a reduction of 6 percent to 10 percent of a person’s starting weight. Moreover, adverse effects, ranging from insomnia, nervousness and increased blood pressure to diarrhea and fecal incontinence, limit their widespread use.</p>
<h2>The role of hormones</h2>
<p>In search of new ways to understand and treat obesity, in recent decades scientists have turned their gaze to the hormones secreted by the intestine.</p>
<p>Specifically, research has focused on <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1642697/">a group of 10 hormones</a> that have roles in optimizing the process of digestion and absorption of nutrients from the food we eat. They are also how the gastrointestinal tract sends signals to the brain about the body’s energy status, in many cases influencing metabolism and contributing to the regulation of our appetites.</p>
<p>The new strategy “has changed the therapeutic landscape of obesity to target underlying mechanisms” and spurred “<a href="https://www.annualreviews.org/doi/10.1146/annurev-med-043021-014919">an auspicious new era of highly effective drugs</a>,” write endocrinologist Ania Jastreboff of Yale School of Medicine and her colleague Robert Kushner of Northwestern University in a 2023 article in the <em>Annual Review of Medicine</em>.</p>
<div class="article-image -caption-center"></div>
<p>One such hormone is glucagon-like peptide type 1, or GLP-1, discovered in the 1980s. Semaglutide, the active molecule in Ozempic and Wegovy, is a lab-made lookalike that mimics the action of GLP-1. Like GLP-1 itself, and like an earlier drug, liraglutide, that was approved in 2010, it suppresses the release of glucagon — a hormone secreted by the pancreas to raise blood sugar levels. It also promotes the growth and function of pancreatic beta cells, which are responsible for producing insulin, the hormone that ensures that sugar from food enters the body’s cells to give them energy.</p>
<p>Both of these actions regulate blood sugar levels, which is why these drugs were initially intended to tackle diabetes. A series of <a href="https://pubmed.ncbi.nlm.nih.gov/30615985/">clinical trials called SUSTAIN</a>, which evaluated the drug in about 8,000 patients with type 2 diabetes, showed that semaglutide is more effective than other available drugs (sitagliptin, marketed as Januvia; exenatide, or Byetta; dulaglutide, or Trulicity; and insulin glargine, or Lantus) in reducing <a href="https://diabetes.org/about-diabetes/a1c">glycosylated hemoglobin</a> scores — a test that measures average blood glucose levels over the prior three months. Maintaining blood sugar levels within the target range is a goal in the treatment of diabetes to avoid complications.</p>
<p>But it was soon realized that these drugs came with a bonus, since GLP-1 doesn’t act only on the pancreas. It also acts on centers in the brain that control appetite. And it decreases stomach movements and emptying, so people feel full for longer. These two mechanisms contribute to reducing food intake, but, unlike older anti-obesity drugs, “they do so in a more physiological way, with few adverse effects,” says Montero. One of the best effects, he adds, is that they take away suffering, because they assuage food cravings. <a href="https://pubmed.ncbi.nlm.nih.gov/36655300/">Patients report</a> a reduced desire to eat highly seasoned and salty foods, or foods rich in carbohydrates, as well as a better ability to resist urges.</p>
<div class="article-image -caption-full"></div>
<p>For Harwicz, semaglutide can be a facilitator that helps people make better decisions. One of her patients, a man weighing more than 160 kilograms (over 350 pounds) with a history of diabetes who had failed multiple previous attempts to lose weight, was able to lose 35 kilos (77 pounds) — more than 20 percent of his body weight — with weekly injections of the drug, along with dietary education and a tailored physical activity plan. “He really feels like he’s succeeding because the medication is helping him,” she says. “It’s important to modify lifestyle; medication isn’t magic. But people can make better food choices and reduce the amount they eat with a lot more peace of mind.”</p>
<p>Of course, like any drug, semaglutide does not work in all patients, nor is it tolerated by all. In the SELECT study, for example, 16.6 percent of participants receiving semaglutide dropped out of the trial because of adverse effects, mainly digestive problems such as nausea, vomiting and diarrhea.</p>
<h2>More in the pipeline</h2>
<p>Everything indicates that the injections of semaglutide are just the beginning in this new era of weight loss drugs. In addition to a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01185-6/abstract">high-dose oral version of semaglutide</a> that showed promising effects in trials and is on the horizon for approval, a tsunami of clinical trial results is anticipated for new drugs that also operate on the gut-brain axis and re-create the action of other intestinal and pancreatic hormones.</p>
<p>One of these is glucose-dependent insulinotropic polypeptide (GIP), which promotes insulin release after meals and reduces appetite. Another hormone is glucagon, which counterbalances the action of insulin by raising blood sugar, helps eliminate fat from the liver and increases satiety. And a third is amylin, which delays stomach emptying, accelerates satiety and decreases the desire to eat.</p>
<p>Collectively, such therapies have been dubbed “nutrient-stimulated hormone-based treatments” because they mimic the action of hormones that are released or function when specialized sensor cells in the digestive tract detect food intake. And they promise to enhance slimming effects, alone or in combination, partly through a physiological reset that prevents the body from stubbornly returning to a weight range that seems predetermined. In other words, it reduces the body’s tendency to regain the lost pounds.</p>
<p>One of the newer drugs, tirzepatide from Eli Lilly (marketed as Mounjaro or Zepbound), acts both on GLP-1 and GIP receptors. It <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management#:~:text=Today%2C%20the%20U.S.%20Food%20and,weight%2Drelated%20condition%20(such%20as">obtained FDA approval November 2023</a> for the treatment of obesity. <a href="https://jamanetwork.com/journals/jama/fullarticle/2812936">One of the clinical studies</a> of this drug reported an average decrease of 25.3 percent of initial weight in those who received a weekly injection for 88 weeks.</p>
<p>Another experimental drug from Eli Lilly, retatrutide — dubbed “triple G” because it acts on GLP-1, GIP and glucagon receptors — could be next on the list. Last June, a study led by Jastreboff <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2301972">reported weight declines never before seen with a single drug</a>. Patients without diabetes averaged a 24 percent body weight loss in just 48 weeks (11 months). And in the group receiving the highest dose, one-fourth of the patients dropped more than 30 percent of their weight. That’s close to the results of highly effective, but more drastic, bariatric surgery.</p>
<p>“I never imagined that physicians would have to worry about our patients losing <em>too </em>much weight when taking an anti-obesity drug,” Kushner says. “This is really an interesting turning point in obesity science and practice, an important paradigm shift in how we think about and manage people living with obesity.”</p>
<p>Kushner and Jastreboff suggest in their article that combining various members of these hormone-based drugs could target the many intertwined mechanisms of obesity. Montero agrees: “There is a swarm of hormones that form a spider web. And touching more than one thread at a time may move the web better, potentiating the effect and making interventions more comfortable, with fewer adverse events,” he says.</p>
<div class="article-image -caption-full"></div>
<p>What is more, semaglutide and tirzepatide could also have benefits in other diseases, such as <a href="https://www.nature.com/articles/s41598-023-48267-2">alcohol abuse disorder</a> and other compulsive or addictive behaviors, such as smoking, excessive shopping and nail-biting. The drugs also <a href="https://www.kidney-international.org/article/S0085-2538(23)00756-1/fulltext">reduce inflammation</a>, which could help to limit damage to various organs and structures, such as the kidneys and joints. There are also preliminary studies of the effects of the drug in preventing <a href="https://onlinelibrary.wiley.com/doi/10.1002/oby.23772">cancer</a>, and for the treatment of <a href="https://pubmed.ncbi.nlm.nih.gov/30741689/">Parkinson’s</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/37730113/">Alzheimer’s</a>, although further studies are still needed to confirm their results. Writing in 2023, the editors of the journal <a href="https://www.aaas.org/news/sciences-2023-breakthrough-glp-1-agonists-show-promise-against-obesity-associated-disease"><em>Science</em></a> declared that no scientific breakthrough in that year had been so transformative in so many fields, affecting everything from financial markets to popular culture.</p>
<p>But, as with any medical innovation, unavoidable challenges also loom on the horizon. Although the visible adverse effects of GLP-1 receptor agonists — nausea, vomiting, constipation and diarrhea — are usually mild and limited to the gastrointestinal tract, other more unusual but serious complications have raised concerns, such as a possible increased risk of pancreatitis. In addition, animal studies (not yet demonstrated in humans) suggest that there is a link to thyroid cancer risk.</p>
<p>Another barrier is the cost of these drugs. In the United States, a monthly treatment with semaglutide costs almost $1,000; the price drops almost 10-fold in countries such as Japan, the United Kingdom and Australia. In Latin America, where obesity rates have grown faster than in other parts of the world, the drug remains unaffordable for the bulk of the population. In Argentina, for example, in March an Ozempic pen with four doses of 1 mg cost 409,000 pesos, which is equivalent to more than twice the monthly minimum wage. More than two pens per month would be required to reach the 2.4 mg per week dose used in the SELECT cardiovascular prevention study.</p>
<p>To make matters worse, studies show that the benefits on weight fade or diminish sharply when the treatment is stopped, so it would have to be continued long-term. Research published in 2022, for example, found that patients <a href="https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14725">regained two-thirds of their lost weight within a year of stopping medication.</a></p>
<p>“Our enthusiasm as clinicians with these drugs wanes if you think about it from a public health point of view,” says Patricio López Jaramillo, an endocrinologist, researcher and rector of the University of Santander in Bucaramanga, Colombia. He thinks that the use of the drugs should be placed within a broader societal package that extends beyond “the rational, linear and disciplinary vision” of medical specialists.</p>
<p>“New anti-obesity drugs should be considered as a useful tool, if financial access is improved,” he says. “And [use] must be framed within global actions and programs that allow populations to have real possibilities to practice healthy lifestyle habits, such as exercising, following a balanced diet and staying away from smoking.”</p>
<div id="newsletter-promo-item">
<div style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;" class="newsletter-promo">
<div style="display: grid;" class="newsletter-promo-img"></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a style="border-bottom: none;" href="https://knowablemagazine.org/newsletter-signup"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<p>Kushner says physicians need to reexamine the kind of lifestyle advice given to people receiving these new drugs, de-emphasizing calorie counting and daily weigh-ins. More focus should be placed on health impacts rather than weight loss, high-quality protein intake should be encouraged, and the importance of physical activity and resistance exercise to preserve muscle mass should be emphasized.</p>
<p>One option could be to use tests to predict which patients will have better results with the various medications and who, perhaps, should think about surgery or other approaches. “Not all patients respond to treatment,” says Andrés Acosta, an Ecuadorian physician and researcher who heads the <a href="https://www.mayo.edu/research/labs/precision-medicine-obesity/overview">Precision Obesity Medicine Laboratory</a> at the Mayo Clinic in Rochester, Minnesota. It is important to identify those who would benefit most, he adds.</p>
<p>Acosta cofounded a company that last year launched a test that identifies patients with a feature called “hungry gut” — those who move food quickly from their stomachs and, consequently, lose satiety faster. This could be a subgroup that particularly benefits from these new anti-obesity drugs, he hypothesizes. For a drug market that could be worth $100 billion by 2030, it wouldn’t hurt to ensure that resources are invested in the patients who will get the most from them.</p>
<p><em>Article translated by Debbie Ponchner</em></p>
<p><em>Editor’s note: This article was updated on April 17, 2024, to correct the location of the Mayo Clinic. It is in Rochester, Minnesota, not Rochester, New York, as originally stated.</em></p>
</div>
<link href="https://knowablemagazine.org/content/article/health-disease/2024/whats-next-in-the-ozempic-era" rel="canonical"> <meta doi="10.1146/knowable-041724-1" content="https://knowablemagazine.org/content/article/health-disease/2024/whats-next-in-the-ozempic-era" name="syndication-source">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/all-about-cholesterol</id>
    <published>2024-04-22T06:00:00-07:00</published>
    <updated>2024-04-22T06:00:00-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/all-about-cholesterol"/>
    <title>All about cholesterol</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<span data-mce-fragment="1">When C. Michael Gibson of Boston saw his doctor in the spring of 2023, the blood test results were confusing. His cholesterol levels were decent — he was already taking statins to keep the “bad” cholesterol low — but the arteries delivering blood to his heart were nonetheless crammed with dangerous plaque. “It didn’t make sense,” says Gibson, himself a cardiologist at Beth Israel Deaconess Medical Center.</span><p><a class="read-more" href="https://comparativeguide.com/blogs/news/all-about-cholesterol">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<h2 class="article-subhead">The latest science on how blood levels of HDL, LDL and more relate to cardiovascular health</h2>
<p class="article-byline" style="font-size: large;"><span class="author-byline">By Amber Dance</span><br><span class="pub-date">02.14.2024</span><br><em>Originally published in </em><a href="https://knowablemagazine.org/content/article/health-disease/2024/cholesterol-and-heart-disease-explained">Knowable Magazine</a></p>
<div class="article-content">
<div class="article-text -drop-cap">
<p>When C. Michael Gibson of Boston saw his doctor in the spring of 2023, the blood test results were confusing. His cholesterol levels were decent — he was already taking statins to keep the “bad” cholesterol low — but the arteries delivering blood to his heart were nonetheless crammed with dangerous plaque. “It didn’t make sense,” says Gibson, himself a cardiologist at Beth Israel Deaconess Medical Center.</p>
<p>So Gibson asked his physician to check his blood for a specific kind of cholesterol called lipoprotein(a). And there was the explanation: He had more than double the normal amount of that cholesterol. Gibson turned out to be one of the unlucky people who has inherited a predisposition toward high lipoprotein(a) levels; he suspects that his grandfather, who died of a heart attack at age 45, had it too.</p>
<p>About one in five people have this unfortunate heritage, and there’s nothing they can do to combat it — but soon that might change. Scientists are researching medications that can lower lipoprotein(a), as well as other approaches that could slash the risk of <a href="https://knowablemagazine.org/content/article/health-disease/2024/polygenic-risk-score-genes-heart-disease-cancer-coming-to-clinic">cardiovascular disease</a> more than drugs like statins can.</p>
<p>Statins, approved in the late 1980s to lower levels of low-density lipoprotein (LDL) cholesterol, have been a lifesaving tool: They cut risk of heart attack and stroke by up to 50 percent for the more than 200 million people globally who take the medications. Yet even statin takers still get heart disease, and some still die. Cardiovascular disease remains the leading cause of death in the United States and <a href="https://knowablemagazine.org/content/article/health-disease/2018/finlands-bold-push-change-heart-health-nation">across the world</a>. Clearly, something’s been missing from the cholesterol picture.</p>
<p>The picture coming into focus today incorporates not just bad, LDL cholesterol and good, high-density lipoprotein (HDL) cholesterol, but also lipoprotein(a) and a poorly understood substance called “remnant cholesterol.” Medical researchers aim to minimize all of these except HDL. And HDL cholesterol itself, though it’s still understood to be beneficial, has turned out to be more complex than anticipated. Various attempts to raise HDL levels haven’t improved people’s health beyond what statins already achieve.</p>
<p>Yet despite this and other disappointments in which medicines haven’t panned out as expected, many researchers feel optimistic about treatments currently in clinical trials. “It’s really an exciting time,” says Stephen Nicholls, a cardiologist at Monash Health in Melbourne, Australia.</p>
<div class="article-image -caption-full"></div>
<h2>LDL cholesterol</h2>
<p>Though it gets a bad rap among the health-conscious, cholesterol plays important roles in our body: It helps to control the stability and fluidity of cell membranes and is an important starting ingredient for making hormones such as testosterone and estrogen. What matters for our health is the company that the cholesterol molecule keeps when it travels.</p>
<p>Its waxy nature means it can’t mix well with water, so it can’t pass through the bloodstream on its own: Lone cholesterol molecules would separate out, like oil does in water. Cholesterol’s solution is to join up with complexes of proteins and fats, called lipoproteins, that carry it around. These lipoprotein carriers include LDL, HDL and other types. Cholesterol, in addition to being cargo, is a structural part of these carriers, too.</p>
<p>Lipoproteins are made in the gut and <a href="https://knowablemagazine.org/content/article/health-disease/2018/invisible-liver-disease-balloons-view">liver</a>, and they deliver cholesterol and fat to body tissues. Fat goes to muscles, to be used for energy, or to fat tissue for storage. Cholesterol is dropped off in tissues to be incorporated into cell membranes or made into hormones. Cholesterol can also be returned to the liver where it can be stored, incorporated into new lipoproteins, turned into bile acids used by the digestive system to break down fats, or sent to be excreted.</p>
<p>When the delivery particles from the liver have dropped off most of their fats, they become LDL particles, which are still jam-packed with cholesterol. The problem happens when these LDL particles, instead of returning to the liver to be recycled, squeeze into blood vessel walls and get chemically modified. There, they incite or exacerbate an immune reaction called inflammation. In response, immune cells come in to eat LDL particles — but if they eat too much, they can get stuck in the blood vessel wall. This forms the beginnings of an atherosclerotic plaque.</p>
<p>Over time, that plaque accumulates more cholesterol, more fat and more immune cells, reducing the space through which blood can flow and deliver oxygen to tissues. If a plaque limits blood supply to the heart, it might cause chest pain called angina. A plaque might also lead to formation of a blood clot, which may break off and clog vessels elsewhere. The clot might cause a stroke in the <a href="https://knowablemagazine.org/content/article/mind/2022/mapping-brain-understand-mind">brain</a>, for example, or a heart attack.</p>
<p>Today, it’s clear that the less LDL cholesterol in the bloodstream, the better. Statins are good at achieving this, cutting LDL cholesterol levels by up to about half. And for those who need a bigger effect, or who can’t tolerate statins (muscle pain or weakness is an occasional side effect), there are newer medicines. “We now have the ability to get almost anyone’s LDL cholesterol down into the range that we would consider appropriate,” says Steven Nissen, a cardiologist at the Cleveland Clinic in Ohio.</p>
<div class="article-image -caption-full"></div>
<h2>Lipoprotein(a)</h2>
<p>But these LDL-cholesterol treatments generally don’t do much against levels of lipoprotein(a), pronounced “lipoprotein-little-a.” This substance, composed of LDL cholesterol particles plus an extra protein, apolipoprotein(a), is mysterious: Scientists don’t know what its natural job is, though since apolipoprotein(a) has some similarity to a protein involved in blood clotting, it <a href="https://www.jlr.org/article/S0022-2275(20)34568-5/fulltext">might have a role in wound healing</a>. But it can’t be all that important to animal survival: Weirdly, the gene that carries instructions for making apolipoprotein(a) is found <a href="https://www.pnas.org/doi/abs/10.1073/pnas.94.22.11992">only in certain primates</a>. (A similar gene evolved in hedgehogs.)</p>
<p>It’s also unclear why lipoprotein(a) is such a bad version of cholesterol, but it’s clearly up to no good much of the time. It delivers cholesterol to the blood vessel walls like LDL does, promotes blood clotting that blocks arteries and can cause inflammation and increase the risk of clots. And if your lipoprotein(a) is high — too bad. “Statins won’t get it down,” laments Gibson. “Exercise doesn’t get it down. Diet doesn’t get it down.”</p>
<p>Some of the newer LDL cholesterol-lowering drugs <a href="https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037184">can reduce lipoprotein(a)</a> cholesterol a bit, but probably not enough to significantly reduce cardiovascular risk, says Anand Rohatgi, a cardiologist at the University of Texas Southwestern Medical Center in Dallas. The only thing physicians can do, in extreme cases, is to regularly administer a blood-cleaning procedure called apheresis to remove lipoprotein(a).</p>
<div class="article-image -caption-center"></div>
<p>For a long time, doctors ignored lipoprotein(a). “Nobody measured it, because you could not do anything about it,” says Prakriti Gaba, a cardiologist at Brigham and Women’s Hospital in Boston. That may be about to change now that several groups are testing medicines that target the substance. (Gaba got her own levels checked at a cardiology conference, where booths offering free tests have sprung up recently.)</p>
<p>Many of these experimental medications use genetic technology to silence the apolipoprotein(a) gene. In a handful of small studies, involving dozens to a few hundred subjects each, different apolipoprotein(a)-silencing therapies cut lipoprotein(a) levels <a href="https://www.sciencedirect.com/science/article/pii/S073510972100259X">by varying levels, from no change up to 92 percent</a>. But it isn’t yet known whether cutting lipoprotein(a) will actually reduce cardiovascular problems. “We won’t know for a while,” says Leslie Cho, a cardiologist at the Cleveland Clinic who’s coleading one of the trials.</p>
<p>Cho’s HORIZON study, the farthest along, is testing a lipoprotein(a)-gene-silencing treatment compared to a <a href="https://knowablemagazine.org/content/article/mind/2023/how-placebo-effect-went-mainstream">placebo</a> in more than 8,300 people with high lipoprotein(a) and a history of heart problems such as heart attack or stroke. The hope is that reducing lipoprotein(a) will decrease the rate of heart attacks, strokes, need for a medical procedure to improve blood flow, and death, but HORIZON isn’t expected to have results <a href="https://classic.clinicaltrials.gov/ct2/show/NCT04023552">until 2025</a>. Another trial that Gaba is involved in, called OCEAN(a)-Outcomes, is <a href="https://clinicaltrials.gov/study/NCT05581303">testing a similar approach</a> in about 6,000 people, but is not expected to be completed until the end of 2026.</p>
<h2>HDL cholesterol</h2>
<p>Just as lipoprotein(a) and LDL cholesterol are known as the baddies, HDL cholesterol has long been considered a good guy. HDL particles are thought to help by sucking cholesterol out of plaques. The HDL then takes this cholesterol to the liver for recycling or disposal. It’s the cardiovascular system’s cholesterol “garbage truck,” says Bob Eckel, a retired cardiometabolic physician and professor emeritus at the University of Colorado Anschutz Medical Campus.</p>
<p>If high levels of HDL cholesterol are good, scientists reasoned, then more of this cleanup crew should be even better. Exercising and weight loss can both raise HDL cholesterol. Scientists have tried to do the same with medications — but with <a href="https://academic.oup.com/eurjpc/article/26/5/533/5925680">disappointing results</a>. The drugs did raise HDL cholesterol levels, yes, but they didn’t save lives in people already on statins, and they were weaker than statins at stopping heart attacks and strokes. <strong>“</strong>To sum it up very simplistically, approaches to raise HDL failed. Nothing really worked,” says Anatol Kontush, a lipid biochemist at the Sorbonne University in Paris.</p>
<div class="article-image -caption-full"></div>
<p>It’s not entirely clear why raising HDL cholesterol in statin-takers bombed. It might be that the idea of boosting HDL cholesterol was simply wrong. High HDL cholesterol might be a marker for good cardiovascular health, rather than a direct cause of it, says Rohatgi. If so, artificially amplifying its levels wouldn’t help.</p>
<p>But the problem also might have been an overly simplistic understanding of HDL cholesterol. Scientists now know that HDL comes in many types and can do many jobs. In addition to hoovering up cholesterol from plaques, it can fight inflammation — that’s good. But sometimes, HDL can turn bad and promote inflammation instead, Cho says, though it’s not clear how. And, she adds, people who are genetically wired to make too much HDL cholesterol can have an enhanced risk for heart disease.</p>
<p>The problem, then, may be that various drugs meant to amplify HDL cholesterol focused on quantity over quality, and increased the wrong kind of HDL. For example, one promising category of drugs raised HDL levels by inhibiting an enzyme that transfers cholesterol away from HDL particles, giving it to LDL particles. Several studies found these inhibitors <a href="https://www.ahajournals.org/doi/10.1161/circresaha.117.311978">failed to improve heart health</a>. It might be that stopping the transfer of cholesterol away from HDL particles means the particles had less capacity to pick up new cholesterol from plaques, leaving the cholesterol to languish there. In other words, these garbage trucks were already full.</p>
<p>So the new plan, a last-ditch effort to save lives with HDL, is to help HDL do its cholesterol-removal job better, rather than to just make more of it. Gibson, for example, is chairing a clinical trial of a medicine called CSL112. It’s made of the key protein component of HDL particles — that is, it’s the starting material for HDL particles but still empty of cholesterol. These CSL112 molecules seem to work by creating new HDL molecules <a href="https://academic.oup.com/ehjcvp/article/9/4/387/7036762">primed to pack in as much cholesterol as they can possibly hold</a>. In a preliminary study of more than 1,200 people, two-thirds of whom received CSL112 infusions, the treatment was safe. And when the scientists took blood samples for lab tests, they found that the higher the dose of CSL112 participants received, the more their blood <a href="https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.116.025687">was able to suck up cholesterol</a>.</p>
<div class="article-image -caption-center"></div>
<p>In another study called AEGIS-II, the researchers tested CSL112 infusions in a larger group of people who had just suffered a heart attack and could be most likely to benefit from treatment. Following <a href="https://classic.clinicaltrials.gov/ct2/show/NCT03473223">18,200 people for a year</a>, it asked whether CSL112 prevents second heart attacks, strokes and death in this population. “That’s a really big, definitive study, and if that doesn’t work, then I suspect the field will completely abandon HDL,” said Nicholls some months back.</p>
<p>In mid-February, CSL of King of Prussia, Pennsylvania — CSL112’s makers — announced that the study <a href="https://www.prnewswire.com/news-releases/csl-announces-top-line-results-from-the-phase-3-aegis-ii-trial-evaluating-the-efficacy-and-safety-of-csl112-apolipoprotein-a-i-human-302059156.html">did not achieve its main goal of reducing major cardiac events</a> such as stroke, heart attack or death. The researchers are still analyzing the data and will present results in more depth at the American College of Cardiology conference in April.</p>
<h2>Triglycerides</h2>
<p>If the HDL waters seem murky, the situation with triglycerides, the fatty component of blood that’s carried around in lipoprotein particles, is muddier still. The amount a person has depends on lifestyle: <a href="https://knowablemagazine.org/content/article/health-disease/2017/balance-not-carbs-or-fat-key-healthy-eating">diet</a>, <a href="https://knowablemagazine.org/content/article/health-disease/2019/exercise-as-medicine">exercise</a> and so on. High triglycerides are <a href="https://www.sciencedirect.com/science/article/abs/pii/S0140673614611776">linked to a greater risk</a> for cardiovascular disease, and very high levels can lead to inflammation of the pancreas, known as pancreatitis. Thus, it made sense to posit that getting rid of triglycerides would be a healthy thing to do, and many studies <a href="https://academic.oup.com/edrv/article/40/2/537/5126386">have attempted just that</a> — with boggling results.</p>
<div class="article-image -caption-center"></div>
<p>One top candidate to reduce triglycerides is based on fish oil, which is high in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Diets rich in fatty fish or omega-3s have long been linked to lower rates of cardiovascular problems. The fish or fish oil supplements are thought to work by cutting down on fat production by the liver.</p>
<p>So, in a study called REDUCE-IT, researchers tested a highly purified derivative of EPA in more than 4,000 people with cardiovascular disease or diabetes. They compared these patients to a similar number of people who received inert mineral oil as a placebo.</p>
<p>At first glance, the results reported in 2019 looked “really spectacular,” says Nicholls, who wasn’t involved in the trial. In the group that had taken the EPA for about five years, risk of major cardiovascular problems or death <a href="https://www.nejm.org/doi/full/10.1056/nejmoa1812792">dropped by 25 percent or more</a> compared to those getting a placebo. But oddly, this benefit came without a big reduction in the triglycerides themselves.</p>
<p>In other words, “if EPA is working, it’s doing something other than lowering triglycerides,” says Kenneth Feingold, an endocrinologist and emeritus professor of medicine at the University of California, San Francisco. EPA might counter inflammation, for example, or stabilize the membranes of heart cells.</p>
<p>Based on the REDUCE-IT results, the US Food and Drug Administration approved the purified EPA derivative in 2019 as a medicine for people with high triglycerides and other <a href="https://knowablemagazine.org/content/article/health-disease/2024/why-isnt-dental-health-considered-primary-medical-care">cardiovascular risk factors</a>. But things got more confusing in 2020, when Nicholls, Nissen and colleagues published another trial, called STRENGTH. This study also aimed to lower triglycerides in high-risk patients, about 6,500 of them, using EPA plus DHA. The researchers compared these patients to people who received a corn oil placebo. But the team halted their study early because, although triglyceride levels did fall, EPA plus DHA <a href="https://jamanetwork.com/journals/jama/article-abstract/2773120">didn’t seem to have any beneficial effect</a> on the rate of heart attack, stroke, hospitalization for heart problems, or death.</p>
<p>Researchers are still debating why REDUCE-IT hit paydirt but STRENGTH faltered. Looking back at REDUCE-IT, some experts <a href="https://jamanetwork.com/journals/jamacardiology/article-abstract/2797283">see a problem with the mineral oil placebo</a> that was used. LDL cholesterol levels and signs of inflammation went up in that group — and if the control participants were worse off than if they’d received nothing at all, then their data would make the experimental treatment look better than it really is.</p>
<p>But Gibson, who was part of the REDUCE-IT team, argues for a different explanation: that pure EPA is better than the EPA/DHA combo. And supporting REDUCE-IT’s conclusions, he points to an older, 1990s study that compared people taking EPA plus statins with people taking statins alone and also found <a href="https://www.thelancet.com/article/S0140-6736(07)60527-3/fulltext">fewer major coronary events</a> in the EPA group.</p>
<p>Then, in 2022, came the latest blow to the once-promising idea of lowering triglycerides: the PROMINENT trial, in which Eckel and colleagues tested a drug called pemafibrate that reduces blood triglycerides. The 10,000-plus study participants had type 2 diabetes, high triglycerides and low HDL, and were at risk for cardiovascular events. But even though triglyceride levels fell by about 26 percent, on average, in the group receiving the drug, this <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2210645">made no difference</a> to the rate of cardiovascular events.</p>
<p>Taken together, the results suggest that triglycerides indicate poor cardiovascular health without being the reason behind the problem. “Triglycerides were just innocent bystanders,” concludes Eckel. The exception, he adds, might be people with very high triglycerides who are at risk of pancreatitis and might still benefit from triglyceride-lowering treatment.</p>
<div id="newsletter-promo-item">
<div class="newsletter-promo" style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;">
<div class="newsletter-promo-img" style="display: grid;"></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a href="https://knowablemagazine.org/newsletter-signup" style="border-bottom: none;"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<h2>Remnant cholesterol</h2>
<p>This is a loosely used term, with science still to be settled. In the doctor’s office, physicians assume that any cholesterol that isn’t HDL or LDL is a leftover or “remnant” fraction. From a molecular point of view, remnant cholesterol is a fat-delivering lipoprotein in an intermediate state: It left the liver, loaded with fat and cholesterol, and has dropped off some of its triglycerides in the body’s tissues, but not so much of its cargo that it’s become an LDL lipoprotein. Chylomicrons from the gut, once depleted of fats, also become remnant particles.</p>
<p>In people with healthy metabolisms, the body quickly disposes of remnant particles. But if a person has a problem such as diabetes or obesity, these fatty remnants might stick around. Remnant cholesterol may <a href="https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.115.306249">accumulate in atherosclerotic plaques</a>, potentially making it <a href="https://journals.lww.com/co-lipidology/Abstract/2020/06000/Remnant_lipoproteins__are_they_equal_to_or_more.5.aspx">as dangerous as the classic bad LDL cholesterol</a>. Indeed, high levels of remnant cholesterol have been <a href="https://academic.oup.com/eurheartj/article/42/42/4324/6323611">linked to cardiovascular disease</a> in some studies, <a href="https://www.jacc.org/doi/abs/10.1016/j.jacc.2020.10.008">quite independently of patients’ LDL cholesterol measurements</a>. That suggests that getting rid of those remnants could be beneficial.</p>
<p>The substances remain a bit of a black box, though. “We still don’t know precisely how to define them, we don’t know precisely how to measure them, so it’s kind of difficult to be precise about remnants,” says Feingold. Nonetheless, some researchers are interested in treatments that might target remnants in addition to, or instead of, triglycerides. For example, Nicholas Marston, a cardiologist at Brigham and Women’s, and colleagues are testing a medication called olezarsen that, he says, appears to promote clearance of the cholesterol-carrying particles. But it will take more study to learn if that translates into fewer cardiovascular problems.</p>
<p>Remnant cholesterol is “probably important,” says Nissen — so even though the science is still nascent, he says he feels hopeful about the potential of treatments targeting it.</p>
<p>In sum, the emerging picture is one in which certain forms of HDL cholesterol are good and all the other lipoproteins are bad. The best approach, experts suggest, may be to reduce all the non-HDL cholesterol — whether by diet and exercise or some of these new medicines, should they prove effective.</p>
<p>“If it’s not HDL, we should minimize it,” says Feingold. “The lower, the better.”</p>
<p><em>Editor’s note: This article was amended February 15, 2024, to add the preliminary results of the AEGIS-II trial aimed at raising levels of HDL and to remove a speculative quote about the ramifications of a positive result from the trial.</em></p>
</div>
</div>
<link rel="canonical" href="https://knowablemagazine.org/content/article/health-disease/2024/cholesterol-and-heart-disease-explained"> <meta name="syndication-source" content="https://knowablemagazine.org/content/article/health-disease/2024/cholesterol-and-heart-disease-explained" doi="10.1146/knowable-021424-1">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/a-clinicians-experience-of-15-years-of-intermittent-fasting</id>
    <published>2024-04-15T06:00:03-07:00</published>
    <updated>2024-04-15T06:00:04-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/a-clinicians-experience-of-15-years-of-intermittent-fasting"/>
    <title>A Clinician&apos;s Experience of 15 Years of Intermittent Fasting</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p><span style="font-weight: bold;">Orthomolecular Medicine News Service, April 9, 2024 </span>
<br><a href="http://orthomolecular.org/subscribe.html"><em>OMNS free subscription</em></a>
<br><a href="http://orthomolecular.org/resources/omns/index.shtml"><em>OMNS archive</em></a></p>
<p style="font-size: large; font-weight: bold;">by Richard Z. Cheng, M.D., Ph.D.</p>
<p>About 15 years ago, a group of my friends I used to hang out with started playing badminton. Didn't want to be left out, so I started learning and playing badminton with them. But these people were 20-30 years younger than I. I couldn't catch up physically, not surprisingly, I might add. It was an embarrassing experience. So, I started researching how to improve my physical endurance. Having a Ph.D. in biochemistry really helped. I quickly zeroed in on boosting energy metabolism and improving mitochondrial function to help improve my exercise endurance. Diet and nutrition are two of the areas that I really focused on. Intermittent fasting and low carbohydrate/ketogenic diet are 2 dietary patterns that I concluded to be most likely mitochondrial energy metabolism friendly which I started practicing right away. I also started taking relatively high (orthomolecular) doses of vitamins and micronutrients that I felt would help my mitochondrial energy metabolism.</p>
<p>This practice quickly helped me to improve my badminton court performance. One of my high moments that I still remember vividly even today was in late summer of 2016. I was playing badminton as usual that evening. About 40 minutes before the courts closure, I was playing with a young post doc (who had been playing badminton longer than I had) in his early 30s. After a while, he was tired and left the court. Another young man of similar age who claimed to be a Shaolin kongfu practitioner came onto the court to play with me. About fifteen minutes into the game, he was on the floor, exhausted. I jokingly shouted to my friends on the court: anyone else wants to challenge this old man? A third post doc came to play with me until the gym closure. I still didn't feel too exhausted.</p>
<p>A week later, on a lecturing tour in Beijing and Shanghai with Thomas Levy (we were invited by a top-notch infectious disease expert in China for a major research project using vitamin C against HIV), I proudly shared with the audience of this interesting experience, winning rounds of applause.</p>
<p>I have many other such instances. Back in 2017 or 2018, I and my daughter joined a group tour of high school students and their parents to the Great Wall in Beijing. I was the only one who went to the top in one breath, leaving a busload of high school students and their parents flabbergasted.</p>
<p>I continue to play badminton 2-3 hours each session, 2-3 times a week with people 10-30 years younger. I often surprise badminton friends when they find out my age. My endurance is better than many of these players, not to mention ordinary people without regular exercise.</p>
<p>In addition to improved exercise endurance, I have seen a significant improvement in my overall health, including much improved emotional status. My insulin resistance markers (HOMA-IR, TG/HDL, and TyG) were mildly elevated about 10 years ago and now they are all within ideal ranges. My bone mineral density is on top of the normal range, better than ~80% of people in their 20s-30s. My coronary calcium score is better than most men my age.</p>
<p>I have also been prescribing and recommending intermittent fasting (as part of my integrative orthomolecular medicine protocol) to my patients, clients, and audience. I have seen significant improvement even complete reversal of many chronic diseases including (but not limited to) coronary heart disease and carotid plaque (atherosclerotic cardiovascular diseases) <a data-sanitized-data-mce-href="#Ref9" data-mce-href="#Ref9" href="#Ref9">(Cheng 2022a</a>, <a data-sanitized-data-mce-href="#Ref10" data-mce-href="#Ref10" href="#Ref10">Cheng 2022b)</a>, type 2 diabetes and other metabolic diseases, autoimmune diseases <a data-sanitized-data-mce-href="#Ref11" data-mce-href="#Ref11" href="#Ref11">(Cheng 2022c)</a>, cancer <a data-sanitized-data-mce-href="#Ref10" data-mce-href="#Ref10" href="#Ref10">(Cheng 2022d)</a>, even osteoporosis.</p>
<p>The recent news release of a poster presentation of intermittent fasting associated with increased cardiovascular risks is irresponsible, misleading and may potentially cause harm to the public <a data-sanitized-data-mce-href="#Ref13" data-mce-href="#Ref13" href="#Ref13">(Cheng 2024)</a>. An umbrella review of 23 meta-analyses on intermittent fasting was just published on Lancet <a data-sanitized-data-mce-href="#Ref55" data-mce-href="#Ref55" href="#Ref55">(Sun 2024)</a>. The authors concluded that intermittent fasting may have beneficial effects on a range of health outcomes for adults with overweight or obesity. IF may decrease many metabolic health parameters such waist circumference, fat mass, LDL-C, Triglycerides, cholesterol, fasting insulin, and blood pressure, while increasing HDL-C and muscle (fat free mass). Below is a brief review of intermittent fasting studies:</p>
<h3>Studies showing benefits of intermittent fasting on cardiovascular health:</h3>
<p>Intermittent fasting (IF) has been shown to have a range of potential benefits for cardiovascular health. It can improve cardiac energetics and activate survival signaling pathways, leading to a longer lifespan <a data-sanitized-data-mce-href="#Ref1" data-mce-href="#Ref1" href="#Ref1">(Abdellatif 2020)</a>. This dietary pattern can also reduce blood pressure, insulin resistance, and oxidative stress, and improve appetite regulation and gut microbiome diversity <a data-sanitized-data-mce-href="#Ref59" data-mce-href="#Ref59" href="#Ref59">(Varady 2021)</a>. Furthermore, intermittent fasting may improve body composition, ectopic fat, and classic cardiometabolic risk factors, and increase protein and fat oxidation <a data-sanitized-data-mce-href="#Ref24" data-mce-href="#Ref24" href="#Ref24">(Dote-Montero 2022)</a>. It has been suggested that intermittent fasting could reduce the risk of cardiovascular disease by improving weight control, hypertension, dyslipidemia, and diabetes <a data-sanitized-data-mce-href="#Ref23" data-mce-href="#Ref23" href="#Ref23">(Dong 2020)</a>. However, further research is needed to fully understand the potential benefits of intermittent fasting for cardiovascular health <a data-sanitized-data-mce-href="#Ref33" data-mce-href="#Ref33" href="#Ref33">(Hamer 2023)</a>.</p>
<h3>Intermittent fasting for metabolic diseases</h3>
<p>Intermittent fasting has been shown to have a range of potential benefits for metabolic health. It can improve metabolic and inflammatory parameters, particularly when combined with regular physical exercise <a data-sanitized-data-mce-href="#Ref63" data-mce-href="#Ref63" href="#Ref63">(Zhang 2023)</a>. Different intermittent fasting approaches, such as alternate day fasting and time-restricted eating, have been found to be effective in weight loss and improving cardiometabolic risk factors <a data-sanitized-data-mce-href="#Ref64" data-mce-href="#Ref64" href="#Ref64">(Zhu 2020)</a>. Aligning food habits with the circadian clock through early time-restricted feeding can also improve metabolic health <a data-sanitized-data-mce-href="#Ref8" data-mce-href="#Ref8" href="#Ref8">(Charlot 2021)</a>. Intermittent fasting regimens, including time-restricted feeding, have been linked to improvements in dyslipidemia and blood pressure <a data-sanitized-data-mce-href="#Ref60" data-mce-href="#Ref60" href="#Ref60">(Vasim 2022)</a>. These regimens can also improve the lipid profile, decrease inflammatory responses, and change the expression of genes related to inflammatory response and other factors <a data-sanitized-data-mce-href="#Ref2" data-mce-href="#Ref2" href="#Ref2">(Azevedo 2013)</a>. Furthermore, intermittent fasting may optimize intestinal microbiota, adipocyte status, and metabolic health <a data-sanitized-data-mce-href="#Ref44" data-mce-href="#Ref44" href="#Ref44">(Matías-Pérez 2022)</a>.</p>
<h3>Intermittent fasting's impact on longevity</h3>
<p>Intermittent fasting has been linked to longevity and improved healthspan, with potential benefits for various diseases. <a data-sanitized-data-mce-href="#Ref41" data-mce-href="#Ref41" href="#Ref41">Longo (2021)</a> and <a data-sanitized-data-mce-href="#Ref37" data-mce-href="#Ref37" href="#Ref37">Hu (2020)</a> both highlight the role of IF in activating cellular repair and rejuvenation pathways, as well as its impact on gut microbiota and circadian rhythm. IF has been shown to have disease-modifying effects, particularly in metabolic disorders, cancer, and neurodegenerative diseases <a data-sanitized-data-mce-href="#Ref48" data-mce-href="#Ref48" href="#Ref48">(Mishra 2020</a>; <a data-sanitized-data-mce-href="#Ref40" data-mce-href="#Ref40" href="#Ref40">Longo 2014)</a>. It may also improve metabolic health and insulin sensitivity <a data-sanitized-data-mce-href="#Ref36" data-mce-href="#Ref36" href="#Ref36">(Hoddy 2020)</a>. The neurobiological mechanisms of IF, including its effects on brain-derived neurotrophic factor, have been explored <a data-sanitized-data-mce-href="#Ref45" data-mce-href="#Ref45" href="#Ref45">(Mattson 2005)</a>. Furthermore, a diet that mimics fasting has been found to promote multi-system regeneration and enhanced cognitive performance <a data-sanitized-data-mce-href="#Ref5" data-mce-href="#Ref5" href="#Ref5">(Brandhorst 2015)</a>.</p>
<h3>Intermittent fasting has also been shown to be beneficial for brain health.</h3>
<p>Intermittent fasting has been shown to have potential benefits for brain health, particularly in the context of aging and neurodegenerative diseases <a data-sanitized-data-mce-href="#Ref28" data-mce-href="#Ref28" href="#Ref28">(Francis 2020</a>, <a data-sanitized-data-mce-href="#Ref53" data-mce-href="#Ref53" href="#Ref53">Seidler 2022)</a>. It can upregulate brain-derived neurotrophic factor (BDNF), which is crucial for cognitive function <a data-sanitized-data-mce-href="#Ref54" data-mce-href="#Ref54" href="#Ref54">(Seidler 2022)</a>. However, the evidence for short-term cognitive benefits in healthy individuals is inconclusive <a data-sanitized-data-mce-href="#Ref32" data-mce-href="#Ref32" href="#Ref32">(Gudden 2021)</a>. IF may also have positive effects on mental health, including affective and cognitive disorders <a data-sanitized-data-mce-href="#Ref21" data-mce-href="#Ref21" href="#Ref21">(Currenti 2020)</a>. The metabolic switch induced by IF, which leads to the production of ketones, can enhance brain function and resilience <a data-sanitized-data-mce-href="#Ref47" data-mce-href="#Ref47" href="#Ref47">(Mattson 2018)</a>. However, the specific effects of IF on brain health and cognitive function may vary depending on factors such as age, obesity, and fasting patterns <a data-sanitized-data-mce-href="#Ref32" data-mce-href="#Ref32" href="#Ref32">(Gudden 2021)</a>.</p>
<h3>Intermittent fasting for cancer prevention and treatment:</h3>
<p>Intermittent fasting has shown potential in cancer prevention and treatment, with studies suggesting its ability to limit cancer cell adaptability, survival, and growth <a data-sanitized-data-mce-href="#Ref58" data-mce-href="#Ref58" href="#Ref58">(Tiwari 2022)</a>. However, the safety and feasibility of IF during chemotherapy are still being explored <a data-sanitized-data-mce-href="#Ref42" data-mce-href="#Ref42" href="#Ref42">(Lutes 2020)</a>. IF, particularly time-restricted eating, has been found to synchronize circadian rhythms and upregulate autophagy, potentially preventing tumorigenesis and slowing tumor progression <a data-sanitized-data-mce-href="#Ref26" data-mce-href="#Ref26" href="#Ref26">(Fang 2023)</a>. Despite these promising findings, the need for high-quality randomized clinical trials to further investigate the effects of IF on cancer incidence and prognosis is emphasized <a data-sanitized-data-mce-href="#Ref19" data-mce-href="#Ref19" href="#Ref19">(Clifton 2021)</a>. Furthermore, the potential anticancer effect of IF in animal experiments warrants further exploration in well-designed clinical trials <a data-sanitized-data-mce-href="#Ref31" data-mce-href="#Ref31" href="#Ref31">(Giannakou 2020)</a>.</p>
<h3>Intermittent fasting for weight loss and bone health</h3>
<p>Intermittent fasting has been shown to have potential benefits for weight loss and metabolic health <a data-sanitized-data-mce-href="#Ref18" data-mce-href="#Ref18" href="#Ref18">(Clayton 2023</a>, <a data-sanitized-data-mce-href="#Ref57" data-mce-href="#Ref57" href="#Ref57">Tinsley 2015a</a>, <a data-sanitized-data-mce-href="#Ref30" data-mce-href="#Ref30" href="#Ref30">Gerboğa 2023)</a>. However, its effects on bone health are less clear. Some studies suggest that IF may not have a significant impact on bone metabolism <a data-sanitized-data-mce-href="#Ref17" data-mce-href="#Ref17" href="#Ref17">(Clayton 2020)</a>, while others indicate that it could potentially compromise bone health, particularly when combined with other dietary restrictions <a data-sanitized-data-mce-href="#Ref18" data-mce-href="#Ref18" href="#Ref18">(Clayton 2023</a>, <a data-sanitized-data-mce-href="#Ref35" data-mce-href="#Ref35" href="#Ref35">Hisatomi 2019)</a>.</p>
<h3>The impact of intermittent fasting on muscular health and exercise endurance</h3>
<p>Intermittent fasting combined with resistance training can improve body composition and muscular performance <a data-sanitized-data-mce-href="#Ref57" data-mce-href="#Ref57" href="#Ref57">(Tinsley 2015b)</a>. It may also enhance endurance by engaging metabolic and cellular signaling pathways <a data-sanitized-data-mce-href="#Ref42" data-mce-href="#Ref42" href="#Ref42">(Marosi 2018)</a>.</p>
<h3>Intermittent fasting for mental and emotional health</h3>
<p>Intermittent fasting has been shown to have a positive impact on mental and emotional health. It can improve brain health, including signaling, neurogenesis, and synaptic plasticity <a data-sanitized-data-mce-href="#Ref21" data-mce-href="#Ref21" href="#Ref21">(Currenti 2020</a>, <a data-sanitized-data-mce-href="#Ref28" data-mce-href="#Ref28" href="#Ref28">Francis 2020)</a>. The practice has also been linked to enhanced cognitive performance, particularly in athletes <a data-sanitized-data-mce-href="#Ref14" data-mce-href="#Ref14" href="#Ref14">(Cherif 2015)</a>. Fasting can lead to increased vigilance, mood improvement, and a sense of well-being <a data-sanitized-data-mce-href="#Ref27" data-mce-href="#Ref27" href="#Ref27">(Fond 2013)</a>. It has been associated with a reduction in β-amyloid accumulation, a marker of Alzheimer's disease, and has been proposed as a potential preventive intervention for dementia <a data-sanitized-data-mce-href="#Ref25" data-mce-href="#Ref25" href="#Ref25">(Elias 2023)</a>. Furthermore, intermittent fasting has been found to be safe and well-tolerated, leading to improvements in emotional and physical well-being <a data-sanitized-data-mce-href="#Ref62" data-mce-href="#Ref62" href="#Ref62">(Wilhelmi de Toledo 2019)</a>.</p>
<h3>Intermittent fasting for autoimmune diseases</h3>
<p>Intermittent fasting has shown promising results in the treatment of autoimmune diseases. Studies have demonstrated its ability to ameliorate symptoms and promote recovery in mouse models of multiple sclerosis <a data-sanitized-data-mce-href="#Ref3" data-mce-href="#Ref3" href="#Ref3">(Bai 2020</a>, <a data-sanitized-data-mce-href="#Ref15" data-mce-href="#Ref15" href="#Ref15">Cignarella 2018</a>, <a data-sanitized-data-mce-href="#Ref51" data-mce-href="#Ref51" href="#Ref51">Razeghi 2016)</a>. Medically supervised water-only fasting has also been associated with remission of autoimmune diseases <a data-sanitized-data-mce-href="#Ref29" data-mce-href="#Ref29" href="#Ref29">(Fuhrman 2002)</a>. The immunomodulatory effects of intermittent fasting, including its ability to strengthen circadian rhythms, lower inflammatory factors, and enrich microbials, have been highlighted in a systematic review <a data-sanitized-data-mce-href="#Ref34" data-mce-href="#Ref34" href="#Ref34">(He 2023)</a>. Furthermore, a diet mimicking fasting has been shown to promote regeneration and reduce autoimmunity and multiple sclerosis symptoms in mouse models <a data-sanitized-data-mce-href="#Ref16" data-mce-href="#Ref16" href="#Ref16">(Choi 2016)</a>.</p>
<h3>Evolutionary perspective on intermittent fasting</h3>
<p>Human ancestors were hunters-gatherers and evolved in environments with sporadic food availability, leading to periods of fasting and feasting, relying mostly on fatty animal meats for millions of years until ~10,000 years ago when agriculture appeared <a data-sanitized-data-mce-href="#Ref51" data-mce-href="#Ref51" href="#Ref51">(Pattillo 2019</a>, <a data-sanitized-data-mce-href="#Ref46" data-mce-href="#Ref46" href="#Ref46">Mattson 2019</a>, <a data-sanitized-data-mce-href="#Ref4" data-mce-href="#Ref4" href="#Ref4">Ben-Dor 2021)</a>. This evolutionary pressure favored individuals with cognitive capabilities and metabolic adaptations that could thrive during food scarcity <a data-sanitized-data-mce-href="#Ref51" data-mce-href="#Ref51" href="#Ref51">(Pattillo 2019)</a>. The wide range of cognitive abilities like spatial navigation, decision-making, and creativity evolved to enable success in food acquisition <a data-sanitized-data-mce-href="#Ref51" data-mce-href="#Ref51" href="#Ref51">(Pattillo 2019)</a>. Metabolic switching between glucose and ketone body utilization was a key adaptation to intermittent food deprivation <a data-sanitized-data-mce-href="#Ref51" data-mce-href="#Ref51" href="#Ref51">(Pattillo 2019</a>, <a data-sanitized-data-mce-href="#Ref36" data-mce-href="#Ref36" href="#Ref36">Hoddy 2020)</a>. Intermittent fasting patterns that incorporate periods of fasting may enhance neuroplasticity and cognition by stimulating the same neural signaling pathways that evolved to cope with food scarcity <a data-sanitized-data-mce-href="#Ref51" data-mce-href="#Ref51" href="#Ref51">(Pattillo 2019</a>, <a data-sanitized-data-mce-href="#Ref36" data-mce-href="#Ref36" href="#Ref36">Hoddy 2020)</a>.</p>
<h3>Impact of intermittent fasting on energy and mitochondrial function</h3>
<p>Intermittent fasting has been shown to enhance energy metabolism and mitochondrial function in various studies. <a data-sanitized-data-mce-href="#Ref53" data-mce-href="#Ref53" href="#Ref53">Real-Hohn (2018)</a> found that a combination of IF and high-intensity intermittent exercise (HIIE) improved physical endurance and metabolic pathways, while <a data-sanitized-data-mce-href="#Ref50" data-mce-href="#Ref50" href="#Ref50">Pak (2022)</a> demonstrated that prolonged IF increased mitochondrial activity in neurons. IF has also been linked to improved health and disease resistance <a data-sanitized-data-mce-href="#Ref6" data-mce-href="#Ref6" href="#Ref6">(Cabo, 2020)</a>, and to changes in liver mitochondrial function <a data-sanitized-data-mce-href="#Ref48" data-mce-href="#Ref48" href="#Ref48">(Menezes-Filho, 2019)</a>. The metabolic switch induced by IF and exercise can enhance endurance capacity <a data-sanitized-data-mce-href="#Ref43" data-mce-href="#Ref43" href="#Ref43">(Marosi, 2018)</a>, and improve metabolic flexibility in short-term high-fat diet-fed mice <a data-sanitized-data-mce-href="#Ref22" data-mce-href="#Ref22" href="#Ref22">(Dedual, 2019)</a>. <a data-sanitized-data-mce-href="#Ref7" data-mce-href="#Ref7" href="#Ref7">Carlson (1994)</a> found that fasting increased fat oxidation and protein oxidation, contributing to energy homeostasis. These findings collectively suggest that IF can boost energy metabolism and mitochondrial function, potentially through a variety of mechanisms.</p>
<h3>Summary</h3>
<p>As part of an integrative approach, intermittent fasting, when practiced properly under the supervision of a qualified and experienced healthcare provider, can offer tremendous benefit to one's health and well-being.</p>
<p> </p>
<h3>References:</h3>
<ol>
<li>Abdellatif M, Sedej S. Cardiovascular benefits of intermittent fasting. Cardiovasc Res. 2020 Mar 1;116(3):e36-e38. doi: 10.1093/cvr/cvaa022. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyMDc3NDc2&amp;sig=GANxGyXeDqDD54dgpTKaQTKNRBWU2XfaNoTr1PCMsDv5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14957" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyMDc3NDc2&amp;sig=GANxGyXeDqDD54dgpTKaQTKNRBWU2XfaNoTr1PCMsDv5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14957" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyMDc3NDc2&amp;sig=GANxGyXeDqDD54dgpTKaQTKNRBWU2XfaNoTr1PCMsDv5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14957">32077476</a>.</li>
<li>Azevedo FR, Ikeoka D, Caramelli B. Effects of intermittent fasting on metabolism in men. Rev Assoc Med Bras (1992). 2013 Mar-Apr;59(2):167-73. doi: 10.1016/j.ramb.2012.09.003. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjIzNTgyNTU5&amp;sig=GghjsB7usECFUVe7LyEN2kbgFD9qqLWnrWLnUoVCLjr6&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14958" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjIzNTgyNTU5&amp;sig=GghjsB7usECFUVe7LyEN2kbgFD9qqLWnrWLnUoVCLjr6&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14958" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjIzNTgyNTU5&amp;sig=GghjsB7usECFUVe7LyEN2kbgFD9qqLWnrWLnUoVCLjr6&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14958">23582559</a>.</li>
<li>Bai M, Wang Y, Han R, Xu L, Huang M, Zhao J, Lin Y, Song S, Chen Y. Intermittent caloric restriction with a modified fasting-mimicking diet ameliorates autoimmunity and promotes recovery in a mouse model of multiple sclerosis. J Nutr Biochem. 2021 Jan;87:108493. doi: 10.1016/j.jnutbio.2020.108493. Epub 2020 Sep 11. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyOTIwMDkx&amp;sig=A6rjiPw9t9asNGhTnbbFizmoxFoFFuSS3Hf3Lifd8uY1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14959" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyOTIwMDkx&amp;sig=A6rjiPw9t9asNGhTnbbFizmoxFoFFuSS3Hf3Lifd8uY1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14959" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyOTIwMDkx&amp;sig=A6rjiPw9t9asNGhTnbbFizmoxFoFFuSS3Hf3Lifd8uY1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14959">32920091</a>.</li>
<li>Ben-Dor M, Sirtoli R, Barkai R. The evolution of the human trophic level during the Pleistocene. Am J Phys Anthropol. 2021 Aug;175 Suppl 72:27-56. doi: 10.1002/ajpa.24247. Epub 2021 Mar 5. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzNjc1MDgz&amp;sig=7mceEkTdForeCnGwLUWRPVrR8643iwKmigrdjhRZojWC&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14960" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzNjc1MDgz&amp;sig=7mceEkTdForeCnGwLUWRPVrR8643iwKmigrdjhRZojWC&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14960" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzNjc1MDgz&amp;sig=7mceEkTdForeCnGwLUWRPVrR8643iwKmigrdjhRZojWC&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14960">33675083</a>.</li>
<li>Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2MDk0ODg5&amp;sig=2GLvffVSvbmatYPXWJdpFLASamfbCsdnsmionZ2c37UW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14961" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2MDk0ODg5&amp;sig=2GLvffVSvbmatYPXWJdpFLASamfbCsdnsmionZ2c37UW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14961" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2MDk0ODg5&amp;sig=2GLvffVSvbmatYPXWJdpFLASamfbCsdnsmionZ2c37UW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14961">26094889</a> ; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNDUwOTczNA==&amp;sig=9VtUb7RevYTaahrvis6jjYRT3qEGbzD1P5AGEqr3YcaY&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14962" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNDUwOTczNA==&amp;sig=9VtUb7RevYTaahrvis6jjYRT3qEGbzD1P5AGEqr3YcaY&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14962" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNDUwOTczNA==&amp;sig=9VtUb7RevYTaahrvis6jjYRT3qEGbzD1P5AGEqr3YcaY&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14962">PMC4509734</a> .</li>
<li>Cabo, R., M. Matteson. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med. 2020 Jan 16;382(3):298. doi: 10.1056/NEJMx190038. Erratum for: N Engl J Med. 2019 Dec 26;381(26):2541-2551. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMxOTQwNzEx&amp;sig=HFSMJqyaaZYgBfVB94FDw785aczeacz2NqsV4Z6eKJ99&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14963" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMxOTQwNzEx&amp;sig=HFSMJqyaaZYgBfVB94FDw785aczeacz2NqsV4Z6eKJ99&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14963" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMxOTQwNzEx&amp;sig=HFSMJqyaaZYgBfVB94FDw785aczeacz2NqsV4Z6eKJ99&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14963">31940711</a>.</li>
<li>Carlson MG, Snead WL, Campbell PJ. Fuel and energy metabolism in fasting humans. Am J Clin Nutr. 1994 Jul;60(1):29-36. doi: 10.1093/ajcn/60.1.29. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjgwMTczMzQ=&amp;sig=4dcnCVpjcZEJ4Wcc7RwUsHai7BKeSJw4vvoRH9TA7Pnp&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14964" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjgwMTczMzQ=&amp;sig=4dcnCVpjcZEJ4Wcc7RwUsHai7BKeSJw4vvoRH9TA7Pnp&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14964" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjgwMTczMzQ=&amp;sig=4dcnCVpjcZEJ4Wcc7RwUsHai7BKeSJw4vvoRH9TA7Pnp&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14964">8017334</a>.</li>
<li>Charlot A, Hutt F, Sabatier E, Zoll J. Beneficial Effects of Early Time-Restricted Feeding on Metabolic Diseases: Importance of Aligning Food Habits with the Circadian Clock. Nutrients. 2021 Apr 22;13(5):1405. doi: 10.3390/nu13051405. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzOTIxOTc5&amp;sig=43jVvif75M7dyMtvz9axS3ytvSXvpnTMs3qaKpwQWmHQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14965" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzOTIxOTc5&amp;sig=43jVvif75M7dyMtvz9axS3ytvSXvpnTMs3qaKpwQWmHQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14965" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzOTIxOTc5&amp;sig=43jVvif75M7dyMtvz9axS3ytvSXvpnTMs3qaKpwQWmHQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14965">33921979</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODE0MzUyMg==&amp;sig=4RnzZ7YyJZwBZvW4uqkYJRvncdLpdxsUAk2XAH9gaRtA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14966" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODE0MzUyMg==&amp;sig=4RnzZ7YyJZwBZvW4uqkYJRvncdLpdxsUAk2XAH9gaRtA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14966" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODE0MzUyMg==&amp;sig=4RnzZ7YyJZwBZvW4uqkYJRvncdLpdxsUAk2XAH9gaRtA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14966">PMC8143522</a>.</li>
<li>Cheng, RZ. (2022a) Reversal of Cardiovascular Diseases with Orthomolecular Medicine. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MThuMTIuc2h0bWw=&amp;sig=AWqwv4DJH9A5tZarsgcHJ6VRWNfZf2s6odAxDduCZRXb&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14967" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MThuMTIuc2h0bWw=&amp;sig=AWqwv4DJH9A5tZarsgcHJ6VRWNfZf2s6odAxDduCZRXb&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14967" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MThuMTIuc2h0bWw=&amp;sig=AWqwv4DJH9A5tZarsgcHJ6VRWNfZf2s6odAxDduCZRXb&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14967">http://orthomolecular.org/resources/omns/v18n12.shtml</a>
</li>
<li>Cheng, RZ. (2022b) Reversing CVD with Orthomolecular Medicine. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ5b3V0dS5iZSUyRjBvZVplSlJwMFdZJTNGc2klM0R4NjI4VHVjS0sxX294aFN4&amp;sig=2eynvMQdZ1hGAhooz3UteJVhxFHL2pWGug8xS5Zft29A&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14968" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ5b3V0dS5iZSUyRjBvZVplSlJwMFdZJTNGc2klM0R4NjI4VHVjS0sxX294aFN4&amp;sig=2eynvMQdZ1hGAhooz3UteJVhxFHL2pWGug8xS5Zft29A&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14968" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ5b3V0dS5iZSUyRjBvZVplSlJwMFdZJTNGc2klM0R4NjI4VHVjS0sxX294aFN4&amp;sig=2eynvMQdZ1hGAhooz3UteJVhxFHL2pWGug8xS5Zft29A&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14968">https://youtu.be/0oeZeJRp0WY?si=x628TucKK1_oxhSx</a>
</li>
<li>Cheng, RZ. (2022c) Autoimmune diseases. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ5b3V0dS5iZSUyRm5vU2NLODBIVk1zJTNGc2klM0RNNXNLWFNDU1VYZzJQVmxl&amp;sig=HnXJMSpgJojvmNZ95NJ5jcbfbWoG7ZGSebt9ckrN37EX&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14969" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ5b3V0dS5iZSUyRm5vU2NLODBIVk1zJTNGc2klM0RNNXNLWFNDU1VYZzJQVmxl&amp;sig=HnXJMSpgJojvmNZ95NJ5jcbfbWoG7ZGSebt9ckrN37EX&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14969" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ5b3V0dS5iZSUyRm5vU2NLODBIVk1zJTNGc2klM0RNNXNLWFNDU1VYZzJQVmxl&amp;sig=HnXJMSpgJojvmNZ95NJ5jcbfbWoG7ZGSebt9ckrN37EX&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14969">https://youtu.be/noScK80HVMs?si=M5sKXSCSUXg2PVle</a>
</li>
<li>Cheng, RZ (2022d) Integrative Cancer Treatment. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuZHJ3bGMuY29tJTJGYmxvZyUyRjIwMjIlMkYxMSUyRjAxJTJGMjM1MSUyRg==&amp;sig=BR48yhoL9NsGvVH2kaZaLWRdgMTy7GW2uovXcAQtxLpw&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14970" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuZHJ3bGMuY29tJTJGYmxvZyUyRjIwMjIlMkYxMSUyRjAxJTJGMjM1MSUyRg==&amp;sig=BR48yhoL9NsGvVH2kaZaLWRdgMTy7GW2uovXcAQtxLpw&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14970" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuZHJ3bGMuY29tJTJGYmxvZyUyRjIwMjIlMkYxMSUyRjAxJTJGMjM1MSUyRg==&amp;sig=BR48yhoL9NsGvVH2kaZaLWRdgMTy7GW2uovXcAQtxLpw&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14970">https://www.drwlc.com/blog/2022/11/01/2351/</a>
</li>
<li>Cheng, RZ. (2024) American Heart Association's Irresponsible News Release of the Intermittent Fasting Study <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MjBuMDUuc2h0bWw=&amp;sig=4k48BvFWH1f4kYTGFV3v7o3EBidgFpFLwcqXGYGPXsr7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14971" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MjBuMDUuc2h0bWw=&amp;sig=4k48BvFWH1f4kYTGFV3v7o3EBidgFpFLwcqXGYGPXsr7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14971" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MjBuMDUuc2h0bWw=&amp;sig=4k48BvFWH1f4kYTGFV3v7o3EBidgFpFLwcqXGYGPXsr7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14971">http://orthomolecular.org/resources/omns/v20n05.shtml</a>
</li>
<li>Cherif A, Roelands B, Meeusen R, Chamari K. Effects of Intermittent Fasting, Caloric Restriction, and Ramadan Intermittent Fasting on Cognitive Performance at Rest and During Exercise in Adults. Sports Med. 2016 Jan;46(1):35-47. doi: 10.1007/s40279-015-0408-6. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2NDM4MTg0&amp;sig=BVKQH8C74TjdgE1bni9e37CJCFp8zxEq7dTH9qj5SPTN&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14972" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2NDM4MTg0&amp;sig=BVKQH8C74TjdgE1bni9e37CJCFp8zxEq7dTH9qj5SPTN&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14972" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2NDM4MTg0&amp;sig=BVKQH8C74TjdgE1bni9e37CJCFp8zxEq7dTH9qj5SPTN&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14972">26438184</a>.</li>
<li>Cignarella F, Cantoni C, Ghezzi L, Salter A, Dorsett Y, Chen L, Phillips D, Weinstock GM, Fontana L, Cross AH, Zhou Y, Piccio L. Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metab. 2018 Jun 5;27(6):1222-1235.e6. doi: 10.1016/j.cmet.2018.05.006. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5ODc0NTY3&amp;sig=BmJKAHHLyv9ZDtuinqkx2XN1xYr6SJCd1rHyiLWEWBTf&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14973" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5ODc0NTY3&amp;sig=BmJKAHHLyv9ZDtuinqkx2XN1xYr6SJCd1rHyiLWEWBTf&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14973" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5ODc0NTY3&amp;sig=BmJKAHHLyv9ZDtuinqkx2XN1xYr6SJCd1rHyiLWEWBTf&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14973">29874567</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjQ2MDI4OA==&amp;sig=9gkNNRdKCELCa87M59F3dZH2jgzWmHV4jVmvue1PbKTt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14974" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjQ2MDI4OA==&amp;sig=9gkNNRdKCELCa87M59F3dZH2jgzWmHV4jVmvue1PbKTt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14974" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjQ2MDI4OA==&amp;sig=9gkNNRdKCELCa87M59F3dZH2jgzWmHV4jVmvue1PbKTt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14974">PMC6460288</a>.</li>
<li>Choi IY, Piccio L, Childress P, Bollman B, Ghosh A, Brandhorst S, Suarez J, Michalsen A, Cross AH, Morgan TE, Wei M, Paul F, Bock M, Longo VD. A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep. 2016 Jun 7;15(10):2136-2146. doi: 10.1016/j.celrep.2016.05.009. Epub 2016 May 26. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI3MjM5MDM1&amp;sig=4Ca3EHuV92kpXXpfRzhwNGbzXMbuTRgCAiyEngTXsSoA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14975" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI3MjM5MDM1&amp;sig=4Ca3EHuV92kpXXpfRzhwNGbzXMbuTRgCAiyEngTXsSoA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14975" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI3MjM5MDM1&amp;sig=4Ca3EHuV92kpXXpfRzhwNGbzXMbuTRgCAiyEngTXsSoA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14975">27239035</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNDg5OTE0NQ==&amp;sig=12wtGVNfnwhnfFwhbsELUCqxdn57j8TjQdP6igdTqk4B&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14976" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNDg5OTE0NQ==&amp;sig=12wtGVNfnwhnfFwhbsELUCqxdn57j8TjQdP6igdTqk4B&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14976" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNDg5OTE0NQ==&amp;sig=12wtGVNfnwhnfFwhbsELUCqxdn57j8TjQdP6igdTqk4B&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14976">PMC4899145</a>.</li>
<li>Clayton, D.J., James, L.J., Sale, C., Templeman, I., Betts, J.A., &amp; Varley, I. (2020). Severely restricting energy intake for 24 h does not affect markers of bone metabolism at rest or in response to re-feeding. European Journal of Nutrition, 59, 3527 - 3535.</li>
<li>Clayton, D.J., Varley, I., &amp; Papageorgiou, M. (2023). Intermittent fasting and bone health: a bone of contention? The British Journal of Nutrition, 130, 1487 - 1499.</li>
<li>Clifton KK, Ma CX, Fontana L, Peterson LL. Intermittent fasting in the prevention and treatment of cancer. CA Cancer J Clin. 2021 Nov;71(6):527-546. doi: 10.3322/caac.21694. Epub 2021 Aug 12. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0MzgzMzAw&amp;sig=E5PFjzTzcxw41HmLVVx3HoKLrf2A1mj8N1Tn1VngZh16&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14977" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0MzgzMzAw&amp;sig=E5PFjzTzcxw41HmLVVx3HoKLrf2A1mj8N1Tn1VngZh16&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14977" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0MzgzMzAw&amp;sig=E5PFjzTzcxw41HmLVVx3HoKLrf2A1mj8N1Tn1VngZh16&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14977">34383300</a>.</li>
<li>Correia JM, Santos I, Pezarat-Correia P, Minderico C, Mendonca GV. Effects of Intermittent Fasting on Specific Exercise Performance Outcomes: A Systematic Review Including Meta-Analysis. Nutrients. 2020 May 12;12(5):1390. doi: 10.3390/nu12051390. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyNDA4NzE4&amp;sig=7pZvQPzFu6n1e4cptuodx67vcS23nvZHGt91VcNhuF2F&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14978" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyNDA4NzE4&amp;sig=7pZvQPzFu6n1e4cptuodx67vcS23nvZHGt91VcNhuF2F&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14978" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyNDA4NzE4&amp;sig=7pZvQPzFu6n1e4cptuodx67vcS23nvZHGt91VcNhuF2F&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14978">32408718</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzI4NDk5NA==&amp;sig=99pudGySBrPXAN8EAhwV6kVjFCHWJy6NWcfx7FEHcuX7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14979" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzI4NDk5NA==&amp;sig=99pudGySBrPXAN8EAhwV6kVjFCHWJy6NWcfx7FEHcuX7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14979" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzI4NDk5NA==&amp;sig=99pudGySBrPXAN8EAhwV6kVjFCHWJy6NWcfx7FEHcuX7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14979">PMC7284994</a>.</li>
<li>Currenti W, Godos J, Castellano S, Mogavero MP, Ferri R, Caraci F, Grosso G, Galvano F. Time restricted feeding and mental health: a review of possible mechanisms on affective and cognitive disorders. Int J Food Sci Nutr. 2021 Sep;72(6):723-733. doi: 10.1080/09637486.2020.1866504. Epub 2020 Dec 25. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzMzU2Njg4&amp;sig=DrADXNox95gozrsRQSFiMyWpopPyzNVbbiF34Fku314b&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14980" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzMzU2Njg4&amp;sig=DrADXNox95gozrsRQSFiMyWpopPyzNVbbiF34Fku314b&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14980" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzMzU2Njg4&amp;sig=DrADXNox95gozrsRQSFiMyWpopPyzNVbbiF34Fku314b&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14980">33356688</a>.</li>
<li>Dedual MA, Wueest S, Borsigova M, Konrad D. Intermittent fasting improves metabolic flexibility in short-term high-fat diet-fed mice. Am J Physiol Endocrinol Metab. 2019 Nov 1;317(5):E773-E782. doi: 10.1152/ajpendo.00187.2019. Epub 2019 Sep 10. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMxNTAzNTEz&amp;sig=5C3XdsSKEk8YErVznDmK4xr8VzdD6sEsvc6QhFoYcGND&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14981" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMxNTAzNTEz&amp;sig=5C3XdsSKEk8YErVznDmK4xr8VzdD6sEsvc6QhFoYcGND&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14981" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMxNTAzNTEz&amp;sig=5C3XdsSKEk8YErVznDmK4xr8VzdD6sEsvc6QhFoYcGND&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14981">31503513</a>.</li>
<li>Dong TA, Sandesara PB, Dhindsa DS, Mehta A, Arneson LC, Dollar AL, Taub PR, Sperling LS. Intermittent Fasting: A Heart Healthy Dietary Pattern? Am J Med. 2020 Aug;133(8):901-907. doi: 10.1016/j.amjmed.2020.03.030. Epub 2020 Apr 21. PMID: 32330491; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzQxNTYzMQ==&amp;sig=F9R72zwMMcfC7YPdewWAxgCxJ4HxY3yZnt5ycfnzZ3s5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14983" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzQxNTYzMQ==&amp;sig=F9R72zwMMcfC7YPdewWAxgCxJ4HxY3yZnt5ycfnzZ3s5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14983" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzQxNTYzMQ==&amp;sig=F9R72zwMMcfC7YPdewWAxgCxJ4HxY3yZnt5ycfnzZ3s5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14983">PMC7415631</a>.</li>
<li>Dote-Montero M, Sanchez-Delgado G, Ravussin E. Effects of Intermittent Fasting on Cardiometabolic Health: An Energy Metabolism Perspective. Nutrients. 2022 Jan 23;14(3):489. doi: 10.3390/nu14030489. PMID: 35276847; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODgzOTE2MA==&amp;sig=8q1qwvXw3jBE9FnW3KXabfheNazzu5QMUEko22nVhaJw&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14984" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODgzOTE2MA==&amp;sig=8q1qwvXw3jBE9FnW3KXabfheNazzu5QMUEko22nVhaJw&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14984" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODgzOTE2MA==&amp;sig=8q1qwvXw3jBE9FnW3KXabfheNazzu5QMUEko22nVhaJw&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14984">PMC8839160</a>.</li>
<li>Elias A, Padinjakara N, Lautenschlager NT. Effects of intermittent fasting on cognitive health and Alzheimer's disease. Nutr Rev. 2023 Aug 10;81(9):1225-1233. doi: 10.1093/nutrit/nuad021. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MDQzNzY0&amp;sig=2QKU6M3UzVurz1WPQCxgA5t7b45FCDwkgjB18H8yaQBE&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14985" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MDQzNzY0&amp;sig=2QKU6M3UzVurz1WPQCxgA5t7b45FCDwkgjB18H8yaQBE&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14985" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MDQzNzY0&amp;sig=2QKU6M3UzVurz1WPQCxgA5t7b45FCDwkgjB18H8yaQBE&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14985">37043764</a> ; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA0MTM0MjY=&amp;sig=8oFHse5Lz9nCSt1FcDtAdaEsHVyxeekhcZVwZn79uQjW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14986" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA0MTM0MjY=&amp;sig=8oFHse5Lz9nCSt1FcDtAdaEsHVyxeekhcZVwZn79uQjW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14986" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA0MTM0MjY=&amp;sig=8oFHse5Lz9nCSt1FcDtAdaEsHVyxeekhcZVwZn79uQjW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14986">PMC10413426</a> .</li>
<li>Fang R, Yan L, Liao Z. Abnormal lipid metabolism in cancer-associated cachexia and potential therapy strategy. Front Oncol. 2023 May 2;13:1123567. doi: 10.3389/fonc.2023.1123567. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MjA1MTk1&amp;sig=2H4b9PHGFVfZAEAkssWK1mhyJTpFcc3sMRZjwvRJf9J5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14987" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MjA1MTk1&amp;sig=2H4b9PHGFVfZAEAkssWK1mhyJTpFcc3sMRZjwvRJf9J5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14987" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MjA1MTk1&amp;sig=2H4b9PHGFVfZAEAkssWK1mhyJTpFcc3sMRZjwvRJf9J5&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14987">37205195</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAxODU4NDU=&amp;sig=CLYRFuF1MYUGqRHHLvLocnPgEjfxkrCATQ5dUQGwtD9r&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14988" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAxODU4NDU=&amp;sig=CLYRFuF1MYUGqRHHLvLocnPgEjfxkrCATQ5dUQGwtD9r&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14988" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAxODU4NDU=&amp;sig=CLYRFuF1MYUGqRHHLvLocnPgEjfxkrCATQ5dUQGwtD9r&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14988">PMC10185845</a>.</li>
<li>Fond G, Macgregor A, Leboyer M, Michalsen A. Fasting in mood disorders: neurobiology and effectiveness. A review of the literature. Psychiatry Res. 2013 Oct 30;209(3):253-8. doi: 10.1016/j.psychres.2012.12.018. Epub 2013 Jan 15. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjIzMzMyNTQx&amp;sig=2EsgQvUdn9CVN1QHqeSHBAq8uvTeNphS32QQUWfAmqU2&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14989" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjIzMzMyNTQx&amp;sig=2EsgQvUdn9CVN1QHqeSHBAq8uvTeNphS32QQUWfAmqU2&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14989" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjIzMzMyNTQx&amp;sig=2EsgQvUdn9CVN1QHqeSHBAq8uvTeNphS32QQUWfAmqU2&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14989">23332541</a>.</li>
<li>Francis, N. (2020). The role of intermittent fasting in brain health. Alzheimer's &amp; Dementia, 16. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZkb2kub3JnJTJGMTAuMTAwMiUyRmFsei4wNDM5MzA=&amp;sig=FxvVrndA1epGeF8sdKniNqASRgRoswC4BTBrceoHQNGn&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14990" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZkb2kub3JnJTJGMTAuMTAwMiUyRmFsei4wNDM5MzA=&amp;sig=FxvVrndA1epGeF8sdKniNqASRgRoswC4BTBrceoHQNGn&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14990" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZkb2kub3JnJTJGMTAuMTAwMiUyRmFsei4wNDM5MzA=&amp;sig=FxvVrndA1epGeF8sdKniNqASRgRoswC4BTBrceoHQNGn&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14990">https://doi.org/10.1002/alz.043930</a>
</li>
<li>Fuhrman J, Sarter B, Calabro DJ. Brief case reports of medically supervised, water-only fasting associated with remission of autoimmune disease. Altern Ther Health Med. 2002 Jul-Aug;8(4):112, 110-1. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjEyMTI2MTYy&amp;sig=HJotGE7cFkRhvQbLuRC8P4URukaXt8k83zn5XhKeYWck&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14991" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjEyMTI2MTYy&amp;sig=HJotGE7cFkRhvQbLuRC8P4URukaXt8k83zn5XhKeYWck&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14991" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjEyMTI2MTYy&amp;sig=HJotGE7cFkRhvQbLuRC8P4URukaXt8k83zn5XhKeYWck&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14991">12126162</a>.</li>
<li>Gerboğa, R., &amp; Bekar, C. (2023). Effects of Intermittent Fasting on Weight Loss and Cardiometabolic Health. Current Perspectives on Health Sciences. Effects of Intermittent Fasting on Weight Loss and Cardiometabolic Health | Semantic Scholar</li>
<li>Giannakou, K., Papakonstantinou, C., Chrysostomou, S., &amp; Lamnisos, D. (2020). The effect of intermittent fasting on cancer prevention: a systematic review. European Journal of Public Health, 30.</li>
<li>Gudden J, Arias Vasquez A, Bloemendaal M. The Effects of Intermittent Fasting on Brain and Cognitive Function. Nutrients. 2021 Sep 10;13(9):3166. doi: 10.3390/nu13093166. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0NTc5MDQy&amp;sig=3wzTTUfnCDXZh1q2moowBYpAsSMe3wxGc4Ld8oHkQonF&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14992" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0NTc5MDQy&amp;sig=3wzTTUfnCDXZh1q2moowBYpAsSMe3wxGc4Ld8oHkQonF&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14992" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0NTc5MDQy&amp;sig=3wzTTUfnCDXZh1q2moowBYpAsSMe3wxGc4Ld8oHkQonF&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14992">34579042</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODQ3MDk2MA==&amp;sig=EuaPr7rSKKwrSt3pcQZEqFsyfwbMbDBbCLvM3Trddv5F&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14993" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODQ3MDk2MA==&amp;sig=EuaPr7rSKKwrSt3pcQZEqFsyfwbMbDBbCLvM3Trddv5F&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14993" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODQ3MDk2MA==&amp;sig=EuaPr7rSKKwrSt3pcQZEqFsyfwbMbDBbCLvM3Trddv5F&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14993">PMC8470960</a>.</li>
<li>Hamer, O., Abouzaid, A., &amp; Hill, J.E. (2023). Intermittent fasting for the prevention of cardiovascular disease: implications for clinical practice. British Journal of Cardiac Nursing. [PDF] Intermittent fasting for the prevention of cardiovascular disease: implications for clinical practice | Semantic Scholar</li>
<li>He Z, Xu H, Li C, Yang H, Mao Y. Intermittent fasting and immunomodulatory effects: A systematic review. Front Nutr. 2023 Feb 28;10:1048230. doi: 10.3389/fnut.2023.1048230. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM2OTI1OTU2&amp;sig=2PQ8tguQV8EHdBzQLP4puPUeYi5MUh8zoZhY32Kun1gz&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14994" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM2OTI1OTU2&amp;sig=2PQ8tguQV8EHdBzQLP4puPUeYi5MUh8zoZhY32Kun1gz&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14994" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM2OTI1OTU2&amp;sig=2PQ8tguQV8EHdBzQLP4puPUeYi5MUh8zoZhY32Kun1gz&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14994">36925956</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAwMTEwOTQ=&amp;sig=3QjWs7Pb18aXqxxRbioKXhLNZobE1eJW67evbkGwXoxH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14995" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAwMTEwOTQ=&amp;sig=3QjWs7Pb18aXqxxRbioKXhLNZobE1eJW67evbkGwXoxH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14995" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAwMTEwOTQ=&amp;sig=3QjWs7Pb18aXqxxRbioKXhLNZobE1eJW67evbkGwXoxH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14995">PMC10011094</a>.</li>
<li>Hisatomi Y, Kugino K. Changes in bone density and bone quality caused by single fasting for 96 hours in rats. PeerJ. 2019 Jan 9;6:e6161. doi: 10.7717/peerj.6161. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjQzNjc3&amp;sig=7nFLeEH2fnNiyUEwkBWboQMMnTVUNxkLPTe1AM8umxE1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14996" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjQzNjc3&amp;sig=7nFLeEH2fnNiyUEwkBWboQMMnTVUNxkLPTe1AM8umxE1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14996" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjQzNjc3&amp;sig=7nFLeEH2fnNiyUEwkBWboQMMnTVUNxkLPTe1AM8umxE1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14996">30643677</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMzMDAzNg==&amp;sig=6X4zYT1q8Gu48ERjUQjGayKhj8HB8twjZK85TzAuMHnn&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14997" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMzMDAzNg==&amp;sig=6X4zYT1q8Gu48ERjUQjGayKhj8HB8twjZK85TzAuMHnn&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14997" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMzMDAzNg==&amp;sig=6X4zYT1q8Gu48ERjUQjGayKhj8HB8twjZK85TzAuMHnn&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14997">PMC6330036</a>.</li>
<li>Hoddy KK, Marlatt KL, Çetinkaya H, Ravussin E. Intermittent Fasting and Metabolic Health: From Religious Fast to Time-Restricted Feeding. Obesity (Silver Spring). 2020 Jul;28 Suppl 1(Suppl 1):S29-S37. doi: 10.1002/oby.22829. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyNzAwODI3&amp;sig=HASMsJv9oDWBbX8eo8z61x5oFvpigZVWm4iuiU4Kww8K&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14998" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyNzAwODI3&amp;sig=HASMsJv9oDWBbX8eo8z61x5oFvpigZVWm4iuiU4Kww8K&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14998" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyNzAwODI3&amp;sig=HASMsJv9oDWBbX8eo8z61x5oFvpigZVWm4iuiU4Kww8K&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14998">32700827</a> ; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzQxOTE1OQ==&amp;sig=E9TgufoFW67HsX3Y9WH6RJ8DiuQQHkKA6BLSceFF6dxQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14999" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzQxOTE1OQ==&amp;sig=E9TgufoFW67HsX3Y9WH6RJ8DiuQQHkKA6BLSceFF6dxQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14999" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNzQxOTE1OQ==&amp;sig=E9TgufoFW67HsX3Y9WH6RJ8DiuQQHkKA6BLSceFF6dxQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A14999">PMC7419159</a> .</li>
<li>Hu D, Xie Z, Ye Y, Bahijri S, Chen M. The beneficial effects of intermittent fasting: an update on mechanism, and the role of circadian rhythm and gut microbiota. Hepatobiliary Surg Nutr. 2020 Oct;9(5):597-602. doi: 10.21037/hbsn-20-317. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzMTYzNTEw&amp;sig=ArcjmjhnvDDJ5KmbijYfZeqWVw7WxmuQ9zhH722xb8kQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15000" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzMTYzNTEw&amp;sig=ArcjmjhnvDDJ5KmbijYfZeqWVw7WxmuQ9zhH722xb8kQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15000" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMzMTYzNTEw&amp;sig=ArcjmjhnvDDJ5KmbijYfZeqWVw7WxmuQ9zhH722xb8kQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15000">33163510</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRlBNQzc2MDM5MzI=&amp;sig=CDafTXs2qPpJWu52jAxFr1hForgkofrgP6Q6ei1BYhgc&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15001" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRlBNQzc2MDM5MzI=&amp;sig=CDafTXs2qPpJWu52jAxFr1hForgkofrgP6Q6ei1BYhgc&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15001" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRlBNQzc2MDM5MzI=&amp;sig=CDafTXs2qPpJWu52jAxFr1hForgkofrgP6Q6ei1BYhgc&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15001">PMC7603932</a>.</li>
<li>King B. 2023. The Theory Behind Intermittent Fasting: Returning to Natural Eating | Shortform Books. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuc2hvcnRmb3JtLmNvbSUyRmJsb2clMkZ0aGVvcnktYmVoaW5kLWludGVybWl0dGVudC1mYXN0aW5nJTJGJTJG&amp;sig=4CHNsEV8ciKMi8WHBpWkwZhgDUojtVXofsTxSBzbnuk3&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15002" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuc2hvcnRmb3JtLmNvbSUyRmJsb2clMkZ0aGVvcnktYmVoaW5kLWludGVybWl0dGVudC1mYXN0aW5nJTJGJTJG&amp;sig=4CHNsEV8ciKMi8WHBpWkwZhgDUojtVXofsTxSBzbnuk3&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15002" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuc2hvcnRmb3JtLmNvbSUyRmJsb2clMkZ0aGVvcnktYmVoaW5kLWludGVybWl0dGVudC1mYXN0aW5nJTJGJTJG&amp;sig=4CHNsEV8ciKMi8WHBpWkwZhgDUojtVXofsTxSBzbnuk3&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15002">https://www.shortform.com/blog/theory-behind-intermittent-fasting/</a>
</li>
<li>Li Y, Liang J, Tian X, Chen Q, Zhu L, Wang H, Liu Z, Dai X, Bian C, Sun C. Intermittent fasting promotes adipocyte mitochondrial fusion through Sirt3-mediated deacetylation of Mdh2. Br J Nutr. 2023 Nov 14;130(9):1473-1486. doi: 10.1017/S000711452300048X. Epub 2023 Feb 23. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM2ODE1MzAy&amp;sig=14EgaPrz3rAv7VpBAETfkme6AjPU9eJMzkkyYAib4ytg&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15003" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM2ODE1MzAy&amp;sig=14EgaPrz3rAv7VpBAETfkme6AjPU9eJMzkkyYAib4ytg&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15003" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM2ODE1MzAy&amp;sig=14EgaPrz3rAv7VpBAETfkme6AjPU9eJMzkkyYAib4ytg&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15003">36815302</a>.</li>
<li>Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014 Feb 4;19(2):181-92. doi: 10.1016/j.cmet.2013.12.008. Epub 2014 Jan 16. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI0NDQwMDM4&amp;sig=7UNv1FddHdr267cCRgVAzfBxsMrk1HkmJxT1YNVHfUBK&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15004" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI0NDQwMDM4&amp;sig=7UNv1FddHdr267cCRgVAzfBxsMrk1HkmJxT1YNVHfUBK&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15004" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI0NDQwMDM4&amp;sig=7UNv1FddHdr267cCRgVAzfBxsMrk1HkmJxT1YNVHfUBK&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15004">24440038</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRlBNQzM5NDYxNjA=&amp;sig=DvNfV5eFALfHjeMzWw5QtdBKTz59a9yLW9wLNHLAekk&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15005" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRlBNQzM5NDYxNjA=&amp;sig=DvNfV5eFALfHjeMzWw5QtdBKTz59a9yLW9wLNHLAekk&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15005" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRlBNQzM5NDYxNjA=&amp;sig=DvNfV5eFALfHjeMzWw5QtdBKTz59a9yLW9wLNHLAekk&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15005">PMC3946160</a>.</li>
<li>Longo VD, Di Tano M, Mattson MP, Guidi N. Intermittent and periodic fasting, longevity and disease. Nat Aging. 2021 Jan;1(1):47-59. doi: 10.1038/s43587-020-00013-3. Epub 2021 Jan 14. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1MzEwNDU1&amp;sig=JAhG2CjT3xfdjNhxVK59veEgUDZhhKK75tSAa7rbgCzS&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15006" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1MzEwNDU1&amp;sig=JAhG2CjT3xfdjNhxVK59veEgUDZhhKK75tSAa7rbgCzS&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15006" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1MzEwNDU1&amp;sig=JAhG2CjT3xfdjNhxVK59veEgUDZhhKK75tSAa7rbgCzS&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15006">35310455</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODkzMjk1Nw==&amp;sig=3yyWHVkN2a5B8VHsyZpxXFfxh9otjdUuFRAJU7PTnyDM&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15007" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODkzMjk1Nw==&amp;sig=3yyWHVkN2a5B8VHsyZpxXFfxh9otjdUuFRAJU7PTnyDM&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15007" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODkzMjk1Nw==&amp;sig=3yyWHVkN2a5B8VHsyZpxXFfxh9otjdUuFRAJU7PTnyDM&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15007">PMC8932957</a>.</li>
<li>Lutes, C., Zelig, R.S., &amp; Rigassio Radler, D.L. (2020). Safety and Feasibility of Intermittent Fasting During Chemotherapy for Breast Cancer. Topics in Clinical Nutrition, 35, 168 - 177.</li>
<li>Marosi K, Moehl K, Navas-Enamorado I, Mitchell SJ, Zhang Y, Lehrmann E, Aon MA, Cortassa S, Becker KG, Mattson MP. Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation. FASEB J. 2018 Jul;32(7):3844-3858. doi: 10.1096/fj.201701378RR. Epub 2018 Feb 27. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5NDg1OTAz&amp;sig=3CowdzaoGdRVuziR7jfAf6YGKkZYAWTCALJDvnuRmieT&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15008" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5NDg1OTAz&amp;sig=3CowdzaoGdRVuziR7jfAf6YGKkZYAWTCALJDvnuRmieT&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15008" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5NDg1OTAz&amp;sig=3CowdzaoGdRVuziR7jfAf6YGKkZYAWTCALJDvnuRmieT&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15008">29485903</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNTk5ODk3Nw==&amp;sig=5XjtmuEfePmWQCiLBKYaotcNag1BvQfdXyc67zgfqRnQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15009" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNTk5ODk3Nw==&amp;sig=5XjtmuEfePmWQCiLBKYaotcNag1BvQfdXyc67zgfqRnQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15009" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNTk5ODk3Nw==&amp;sig=5XjtmuEfePmWQCiLBKYaotcNag1BvQfdXyc67zgfqRnQ&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15009">PMC5998977</a>.</li>
<li>Matías-Pérez D, Hernández-Bautista E, García-Montalvo IA. Intermittent fasting may optimize intestinal microbiota, adipocyte status and metabolic health. Asia Pac J Clin Nutr. 2022 Mar;31(1):16-23. doi: 10.6133/apjcn.202203_31(1).0002. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1MzU3MDk5&amp;sig=5uEWbbeC7VcQ9KNNM2tsfzfAV1ef2GCGSDE1Wek4bjJt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15010" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1MzU3MDk5&amp;sig=5uEWbbeC7VcQ9KNNM2tsfzfAV1ef2GCGSDE1Wek4bjJt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15010" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1MzU3MDk5&amp;sig=5uEWbbeC7VcQ9KNNM2tsfzfAV1ef2GCGSDE1Wek4bjJt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15010">35357099</a>.</li>
<li>Mattson MP. Energy intake, meal frequency, and health: a neurobiological perspective. Annu Rev Nutr. 2005;25:237-60. doi: 10.1146/annurev.nutr.25.050304.092526. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjE2MDExNDY3&amp;sig=9AgnAFDekkHYEs5YWrHbH6UgHHLChQsREUA2SRgn36iH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15011" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjE2MDExNDY3&amp;sig=9AgnAFDekkHYEs5YWrHbH6UgHHLChQsREUA2SRgn36iH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15011" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjE2MDExNDY3&amp;sig=9AgnAFDekkHYEs5YWrHbH6UgHHLChQsREUA2SRgn36iH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15011">16011467</a>.</li>
<li>Mattson MP. An Evolutionary Perspective on Why Food Overconsumption Impairs Cognition. Trends Cogn Sci. 2019 Mar;23(3):200-212. doi: 10.1016/j.tics.2019.01.003. Epub 2019 Jan 19. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjcwMzI1&amp;sig=HRiFN5LHsTKmho1VBULbASHk2ZAR6TQMWghpYciiU7WN&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15012" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjcwMzI1&amp;sig=HRiFN5LHsTKmho1VBULbASHk2ZAR6TQMWghpYciiU7WN&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15012" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjcwMzI1&amp;sig=HRiFN5LHsTKmho1VBULbASHk2ZAR6TQMWghpYciiU7WN&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15012">30670325</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjQxMjEzNg==&amp;sig=Gqs4nzrhHNWrKmTc8TkMPp6SkVpgFcwLmzJTNMT1hnN1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15013" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjQxMjEzNg==&amp;sig=Gqs4nzrhHNWrKmTc8TkMPp6SkVpgFcwLmzJTNMT1hnN1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15013" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjQxMjEzNg==&amp;sig=Gqs4nzrhHNWrKmTc8TkMPp6SkVpgFcwLmzJTNMT1hnN1&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15013">PMC6412136</a>.</li>
<li>Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci. 2018 Feb;19(2):63-80. doi: 10.1038/nrn.2017.156. Epub 2018 Jan 11. Erratum in: Nat Rev Neurosci. 2020 Aug;21(8):445. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5MzIxNjgy&amp;sig=D5VnRSSJ3qQUbnwe39HK4BwawZEMJzNaJ72hcTpccEEG&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15014" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5MzIxNjgy&amp;sig=D5VnRSSJ3qQUbnwe39HK4BwawZEMJzNaJ72hcTpccEEG&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15014" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI5MzIxNjgy&amp;sig=D5VnRSSJ3qQUbnwe39HK4BwawZEMJzNaJ72hcTpccEEG&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15014">29321682</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNTkxMzczOA==&amp;sig=H69LGjhuCCfAFqKCDGD3t8NT1srRj416xtXeTyTbZDy8&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15015" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNTkxMzczOA==&amp;sig=H69LGjhuCCfAFqKCDGD3t8NT1srRj416xtXeTyTbZDy8&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15015" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNTkxMzczOA==&amp;sig=H69LGjhuCCfAFqKCDGD3t8NT1srRj416xtXeTyTbZDy8&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15015">PMC5913738</a>.</li>
<li>Menezes-Filho SL, Amigo I, Luévano-Martínez LA, Kowaltowski AJ. Fasting promotes functional changes in liver mitochondria. Biochim Biophys Acta Bioenerg. 2019 Feb 1;1860(2):129-135. doi: 10.1016/j.bbabio.2018.11.017. Epub 2018 Nov 20. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNDY1NzQ5&amp;sig=HBHhwHxsNqyWC6d5J2So8MyXqk3fKhsrBsabmjMtbEZE&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15016" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNDY1NzQ5&amp;sig=HBHhwHxsNqyWC6d5J2So8MyXqk3fKhsrBsabmjMtbEZE&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15016" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNDY1NzQ5&amp;sig=HBHhwHxsNqyWC6d5J2So8MyXqk3fKhsrBsabmjMtbEZE&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15016">30465749</a>.</li>
<li>Mishra, S., &amp; Singh, B. (2020). Intermittent Fasting and Metabolic Switching: A Brief Overview. Biomedical and Pharmacology Journal, 13, 1555-1562.</li>
<li>Pak M, Bozkurt S, Pınarbaşı A, Öz Arslan D, Aksungar FB. Effects of Prolonged Intermittent Fasting Model on Energy Metabolism and Mitochondrial Functions in Neurons. Ann Neurosci. 2022 Jan;29(1):21-31. doi: 10.1177/09727531211072303. Epub 2022 Feb 2. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1ODc1NDI2&amp;sig=Gw4YV4d7ukXTTYN1h7QKjYmy4o1foRGG4sjTogwk29e7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15017" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1ODc1NDI2&amp;sig=Gw4YV4d7ukXTTYN1h7QKjYmy4o1foRGG4sjTogwk29e7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15017" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1ODc1NDI2&amp;sig=Gw4YV4d7ukXTTYN1h7QKjYmy4o1foRGG4sjTogwk29e7&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15017">35875426</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTMwNTkxMw==&amp;sig=2qJP2BKfkXdyZ5yx1MwEXMhyGZPD21fbNrg8GcPYd2aj&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15018" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTMwNTkxMw==&amp;sig=2qJP2BKfkXdyZ5yx1MwEXMhyGZPD21fbNrg8GcPYd2aj&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15018" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTMwNTkxMw==&amp;sig=2qJP2BKfkXdyZ5yx1MwEXMhyGZPD21fbNrg8GcPYd2aj&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15018">PMC9305913</a>.</li>
<li>Pattillo, A. 2019. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuaW52ZXJzZS5jb20lMkZhcnRpY2xlJTJGNTc4MzUtaW50ZXJtaXR0ZW50LWZhc3RpbmctZXZvbHV0aW9u&amp;sig=D5YQ5pTj2bjV2AVen6Lmwmng3CE5d5EjPb5ZkcVqvTKa&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15019" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuaW52ZXJzZS5jb20lMkZhcnRpY2xlJTJGNTc4MzUtaW50ZXJtaXR0ZW50LWZhc3RpbmctZXZvbHV0aW9u&amp;sig=D5YQ5pTj2bjV2AVen6Lmwmng3CE5d5EjPb5ZkcVqvTKa&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15019" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuaW52ZXJzZS5jb20lMkZhcnRpY2xlJTJGNTc4MzUtaW50ZXJtaXR0ZW50LWZhc3RpbmctZXZvbHV0aW9u&amp;sig=D5YQ5pTj2bjV2AVen6Lmwmng3CE5d5EjPb5ZkcVqvTKa&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15019">https://www.inverse.com/article/57835-intermittent-fasting-evolution</a>
</li>
<li>Razeghi Jahromi S, Ghaemi A, Alizadeh A, Sabetghadam F, Moradi Tabriz H, Togha M. Effects of Intermittent Fasting on Experimental Autoimune Encephalomyelitis in C57BL/6 Mice. Iran J Allergy Asthma Immunol. 2016 Jun;15(3):212-9. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI3NDI0MTM2&amp;sig=BWZeSG3NYEtMRiTXonWFhZDiJXeB8NtwA55c2LsPNcon&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15020" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI3NDI0MTM2&amp;sig=BWZeSG3NYEtMRiTXonWFhZDiJXeB8NtwA55c2LsPNcon&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15020" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI3NDI0MTM2&amp;sig=BWZeSG3NYEtMRiTXonWFhZDiJXeB8NtwA55c2LsPNcon&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15020">27424136</a>.</li>
<li>Real-Hohn A, Navegantes C, Ramos K, Ramos-Filho D, Cahuê F, Galina A, Salerno VP. The synergism of high-intensity intermittent exercise and every-other-day intermittent fasting regimen on energy metabolism adaptations includes hexokinase activity and mitochondrial efficiency. PLoS One. 2018 Dec 21;13(12):e0202784. doi: 10.1371/journal.pone.0202784. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNTc2MzI1&amp;sig=J2KzecoPn2ELSjnjwhihRpYgGPKwvXA55WM3BwD6wJEp&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15021" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNTc2MzI1&amp;sig=J2KzecoPn2ELSjnjwhihRpYgGPKwvXA55WM3BwD6wJEp&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15021" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNTc2MzI1&amp;sig=J2KzecoPn2ELSjnjwhihRpYgGPKwvXA55WM3BwD6wJEp&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15021">30576325</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMwMzA3MQ==&amp;sig=BojwthN5YRxhEnb2FLzgVbzTaYXBTqYLrPUfT5bJaRiS&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15022" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMwMzA3MQ==&amp;sig=BojwthN5YRxhEnb2FLzgVbzTaYXBTqYLrPUfT5bJaRiS&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15022" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMwMzA3MQ==&amp;sig=BojwthN5YRxhEnb2FLzgVbzTaYXBTqYLrPUfT5bJaRiS&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15022">PMC6303071</a>.</li>
<li>Seidler K, Barrow M. Intermittent fasting and cognitive performance - Targeting BDNF as potential strategy to optimise brain health. Front Neuroendocrinol. 2022 Apr;65:100971. doi: 10.1016/j.yfrne.2021.100971. Epub 2021 Dec 18. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0OTI5MjU5&amp;sig=HGxZBjvdcvj6kuuuqNku4gvkYqXc2gRf2wPM3UQVZQPB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15023" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0OTI5MjU5&amp;sig=HGxZBjvdcvj6kuuuqNku4gvkYqXc2gRf2wPM3UQVZQPB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15023" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0OTI5MjU5&amp;sig=HGxZBjvdcvj6kuuuqNku4gvkYqXc2gRf2wPM3UQVZQPB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15023">34929259</a>.</li>
<li>Sun ML, Yao W, Wang XY, Gao S, Varady KA, Forslund SK, Zhang M, Shi ZY, Cao F, Zou BJ, Sun MH, Liu KX, Bao Q, Xu J, Qin X, Xiao Q, Wu L, Zhao YH, Zhang DY, Wu QJ, Gong TT. Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials. EClinicalMedicine. 2024 Mar 11;70:102519. doi: 10.1016/j.eclinm.2024.102519. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM4NTAwODQw&amp;sig=3rTSSWjy2D4FzCfrVJUKap7duQ7eVjRNek4qZ7b3gDhB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15024" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM4NTAwODQw&amp;sig=3rTSSWjy2D4FzCfrVJUKap7duQ7eVjRNek4qZ7b3gDhB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15024" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM4NTAwODQw&amp;sig=3rTSSWjy2D4FzCfrVJUKap7duQ7eVjRNek4qZ7b3gDhB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15024">38500840</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA5NDUxNjg=&amp;sig=DLpBY54W9ipkx6eWjYuFsVL6rLypjFB44W8mJGEE4AXA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15025" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA5NDUxNjg=&amp;sig=DLpBY54W9ipkx6eWjYuFsVL6rLypjFB44W8mJGEE4AXA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15025" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA5NDUxNjg=&amp;sig=DLpBY54W9ipkx6eWjYuFsVL6rLypjFB44W8mJGEE4AXA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15025">PMC10945168</a>.</li>
<li>Tinsley GM, La Bounty PM. (2015a) Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev. 2015 Oct;73(10):661-74. doi: 10.1093/nutrit/nuv041. Epub 2015 Sep 15. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2Mzc0NzY0&amp;sig=RfHXeR45kNX1LhqfdngJUvVRnaFSyx1twga2C1dPF2f&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15026" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2Mzc0NzY0&amp;sig=RfHXeR45kNX1LhqfdngJUvVRnaFSyx1twga2C1dPF2f&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15026" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjI2Mzc0NzY0&amp;sig=RfHXeR45kNX1LhqfdngJUvVRnaFSyx1twga2C1dPF2f&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15026">26374764</a>.</li>
<li>Tinsley, G.M., Butler, N.K., Forsse, J.S., Bane, A.A., Morgan, G.B., Hwang, P.S., Grandjean, P.W., &amp; La Bounty, P.M. (2015b). Intermittent fasting combined with resistance training: effects on body composition, muscular performance, and dietary intake. Journal of the International Society of Sports Nutrition, 12, P38 - P38.</li>
<li>Tiwari S, Sapkota N, Han Z. Effect of fasting on cancer: A narrative review of scientific evidence. Cancer Sci. 2022 Oct;113(10):3291-3302. doi: 10.1111/cas.15492. Epub 2022 Aug 10. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1ODQ4ODc0&amp;sig=BQrQ9mLDpipyRWpbF1DgyFX9rWC8AZff2Qf58BtE2VYG&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15027" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1ODQ4ODc0&amp;sig=BQrQ9mLDpipyRWpbF1DgyFX9rWC8AZff2Qf58BtE2VYG&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15027" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1ODQ4ODc0&amp;sig=BQrQ9mLDpipyRWpbF1DgyFX9rWC8AZff2Qf58BtE2VYG&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15027">35848874</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTUzMDg2Mg==&amp;sig=2ddyDgRaudtyQ2De48JyEk2TYN6NaVZ53W7p7sjHoHvA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15028" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTUzMDg2Mg==&amp;sig=2ddyDgRaudtyQ2De48JyEk2TYN6NaVZ53W7p7sjHoHvA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15028" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTUzMDg2Mg==&amp;sig=2ddyDgRaudtyQ2De48JyEk2TYN6NaVZ53W7p7sjHoHvA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15028">PMC9530862</a>.</li>
<li>Varady KA, Cienfuegos S, Ezpeleta M, Gabel K. Cardiometabolic Benefits of Intermittent Fasting. Annu Rev Nutr. 2021 Oct 11;41:333-361. doi: 10.1146/annurev-nutr-052020-041327. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0NjMzODYw&amp;sig=D9NmtKYuEofWno7oiU5qVo8yAfzLYpFJWhpWLypkHjJH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15029" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0NjMzODYw&amp;sig=D9NmtKYuEofWno7oiU5qVo8yAfzLYpFJWhpWLypkHjJH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15029" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM0NjMzODYw&amp;sig=D9NmtKYuEofWno7oiU5qVo8yAfzLYpFJWhpWLypkHjJH&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15029">34633860</a>.</li>
<li>Vasim I, Majeed CN, DeBoer MD. Intermittent Fasting and Metabolic Health. Nutrients. 2022 Jan 31;14(3):631. doi: 10.3390/nu14030631. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1Mjc2OTg5&amp;sig=BFkUxRzSJK31cmMr8mJWhVd2xFwgAgBwBiPozu4enxcd&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15030" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1Mjc2OTg5&amp;sig=BFkUxRzSJK31cmMr8mJWhVd2xFwgAgBwBiPozu4enxcd&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15030" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM1Mjc2OTg5&amp;sig=BFkUxRzSJK31cmMr8mJWhVd2xFwgAgBwBiPozu4enxcd&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15030">35276989</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODgzOTMyNQ==&amp;sig=BNGrmKa3casfjYJwz1qxj1Dg7c96HWu7NjzhzZ1QLf6w&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15031" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODgzOTMyNQ==&amp;sig=BNGrmKa3casfjYJwz1qxj1Dg7c96HWu7NjzhzZ1QLf6w&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15031" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODgzOTMyNQ==&amp;sig=BNGrmKa3casfjYJwz1qxj1Dg7c96HWu7NjzhzZ1QLf6w&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15031">PMC8839325</a>.</li>
<li>Wei E. 2021. <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZibG9nLmluc2lkZXRyYWNrZXIuY29tJTJGdGFwcGluZy1pbnRvLWFuY2VzdHJhbC1odW5nZXIteW91ci1wZXJzb25hbC1yb2FkbWFwLXRvLWZhdC1sb3NzLXN1Y2Nlc3M=&amp;sig=CcqqdKhYaLJ8JGHFzkz4LgE3w7waKLxmDmtpB6JJyd2e&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15032" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZibG9nLmluc2lkZXRyYWNrZXIuY29tJTJGdGFwcGluZy1pbnRvLWFuY2VzdHJhbC1odW5nZXIteW91ci1wZXJzb25hbC1yb2FkbWFwLXRvLWZhdC1sb3NzLXN1Y2Nlc3M=&amp;sig=CcqqdKhYaLJ8JGHFzkz4LgE3w7waKLxmDmtpB6JJyd2e&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15032" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZibG9nLmluc2lkZXRyYWNrZXIuY29tJTJGdGFwcGluZy1pbnRvLWFuY2VzdHJhbC1odW5nZXIteW91ci1wZXJzb25hbC1yb2FkbWFwLXRvLWZhdC1sb3NzLXN1Y2Nlc3M=&amp;sig=CcqqdKhYaLJ8JGHFzkz4LgE3w7waKLxmDmtpB6JJyd2e&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15032">https://blog.insidetracker.com/tapping-into-ancestral-hunger-your-personal-roadmap-to-fat-loss-success</a>
</li>
<li>Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A. Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS One. 2019 Jan 2;14(1):e0209353. doi: 10.1371/journal.pone.0209353. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjAxODY0&amp;sig=AuCBAhByJrucTh3X5BqscMB3rUmsK1CDjSqCmQxa5kLA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15033" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjAxODY0&amp;sig=AuCBAhByJrucTh3X5BqscMB3rUmsK1CDjSqCmQxa5kLA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15033" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMwNjAxODY0&amp;sig=AuCBAhByJrucTh3X5BqscMB3rUmsK1CDjSqCmQxa5kLA&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15033">30601864</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMxNDYxOA==&amp;sig=G1W6c9CyS4bj3if6UqqZ9GVgfz9QyS1qb3wJ5PcFyphW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15034" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMxNDYxOA==&amp;sig=G1W6c9CyS4bj3if6UqqZ9GVgfz9QyS1qb3wJ5PcFyphW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15034" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjMxNDYxOA==&amp;sig=G1W6c9CyS4bj3if6UqqZ9GVgfz9QyS1qb3wJ5PcFyphW&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15034">PMC6314618</a>.</li>
<li>mialonZhang L, Wang Y, Sun Y, Zhang X. Intermittent Fasting and Physical Exercise for Preventing Metabolic Disorders through Interaction with Gut Microbiota: A Review. Nutrients. 2023 May 11;15(10):2277. doi: 10.3390/nu15102277. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MjQyMTYw&amp;sig=715Ae7ptuZGGE4k6PEtxVAtNoQMjRcjHHriwPeEbGvjx&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15035" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MjQyMTYw&amp;sig=715Ae7ptuZGGE4k6PEtxVAtNoQMjRcjHHriwPeEbGvjx&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15035" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjM3MjQyMTYw&amp;sig=715Ae7ptuZGGE4k6PEtxVAtNoQMjRcjHHriwPeEbGvjx&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15035">37242160</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAyMjQ1NTY=&amp;sig=4zrJvYLMaqdP4VgHH29ULvKUCJKV8SBXnNGzwNafRmdB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15036" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAyMjQ1NTY=&amp;sig=4zrJvYLMaqdP4VgHH29ULvKUCJKV8SBXnNGzwNafRmdB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15036" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAyMjQ1NTY=&amp;sig=4zrJvYLMaqdP4VgHH29ULvKUCJKV8SBXnNGzwNafRmdB&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15036">PMC10224556</a>.</li>
<li>Zhu S, Surampudi P, Rosharavan B, Chondronikola M. Intermittent fasting as a nutrition approach against obesity and metabolic disease. Curr Opin Clin Nutr Metab Care. 2020 Nov;23(6):387-394. doi: 10.1097/MCO.0000000000000694. PMID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyODY4Njg2&amp;sig=4EHaFkk7hnuqG4FZ9HpCjiA8Vw2Pr5SzqZzjBHEk1UHt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15037" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyODY4Njg2&amp;sig=4EHaFkk7hnuqG4FZ9HpCjiA8Vw2Pr5SzqZzjBHEk1UHt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15037" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZwdWJtZWQubmNiaS5ubG0ubmloLmdvdiUyRjMyODY4Njg2&amp;sig=4EHaFkk7hnuqG4FZ9HpCjiA8Vw2Pr5SzqZzjBHEk1UHt&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15037">32868686</a>; PMCID: <a data-sanitized-data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODcyNjY0Mg==&amp;sig=2UDsHJ5XvApV1JXygWwYDaQBbVU4Hs8m7czxZPqtVc1C&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15038" data-mce-href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODcyNjY0Mg==&amp;sig=2UDsHJ5XvApV1JXygWwYDaQBbVU4Hs8m7czxZPqtVc1C&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15038" href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DODcyNjY0Mg==&amp;sig=2UDsHJ5XvApV1JXygWwYDaQBbVU4Hs8m7czxZPqtVc1C&amp;iat=1712675007&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=hKgsSPhnFJcYt%2FIAsYpgvpams7I3inWZJky50niuQbHRB9C7%3AGST3jCnDKH8B4MuEk4zSzfaCKfqhwdcM&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=312A322A1A15038">PMC8726642</a> .</li>
</ol>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/nutrient-depletion-of-our-foods</id>
    <published>2024-04-08T06:00:03-07:00</published>
    <updated>2024-04-08T06:00:03-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/nutrient-depletion-of-our-foods"/>
    <title>Nutrient Depletion of our Foods</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p><span style="font-size: large;"><strong>by Lyle MacWilliam</strong></span><br>NutriSearch co-founder and author of the <em>NutriSearch Comparative Guide to Nutritional Supplements</em>™</p>
<p style="text-align: center; font-family: cursive, serif;"><em>“Nations endure only as long as their topsoil.”</em> <br><strong>~Henry Cantwell Wallace</strong></p>
<p>The calculus is simple: plants cant make minerals, and without minerals vitamins dont work.</p>
<p>We are made of the stuff of the earth. Consequently, if the minerals are not in the soil, they are not in the plants grown in the soil; and if they are not in the plants grown in the soil, they are <em>not</em> in our bodies. As such, it is not surprising that any depletion in the mineral and nutrient content of our soils reflects an increase in nutritionally related diseases in both animal and human populations.</p>
<p style="text-align: center; max-width: 640px; margin: 0px 10% 20px 10%;"><em><q>The alarming fact is that foods―fruits, vegetables and grains―now being raised on millions of acres of land that no longer contain enough of certain needed nutrients, are starving us―no matter how much we eat of them.</q></em> <br>~ U.S. Senate Document 264</p>
<p>The remarkable thing about the preceding declaration is that it was issued in 1936―over 73 years ago. Since that time, the United States and other industrialized nations have been losing arable land at an unprecedented rate. Today in the U.S., topsoil is eroding at a rate ten times faster than the rate of replenishment, not bad considering that countries such as Africa, India and China are experiencing erosion rates 30 to 40 times the replenishment rate. Today, estimates place the chronological reserves of our global topsoil at less than 50 years ―and as the topsoil goes, so go the nutrients.<a href="#Ref1"><sup>1</sup></a></p>
<p>Findings released at the 1992 RIO Earth Summit confirm that mineral depletion of our global topsoil reserve is rampant. At the time, U.S. and Canadian agricultural soils had lost 85% of their mineral content. Asian and South American soils were down 76% while throughout Africa, Europe and Australia, soils were depleted by 74%, 72% and 55% respectively.<a href="#Ref1"><sup>1</sup></a> Tragically, there has been precious little done to forestall the inevitable exhaustion of these precious mineral stores.</p>
<p>In March, 2006, the United Nations recognized a new kind of malnutrition―<em>multiple micronutrient depletion</em>. According to Catherine Bertini, Chair of the UN Standing Committee on Nutrition, the overweight are <em>just</em> as malnourished as the starving. In essence, it is not the <em>quantity</em> of food that is at issue―it is the <em>quality</em>.<a href="#Ref2"><sup>2</sup></a></p>
<h2>Modern Agriculture Impoverishes our Soils</h2>
<p>The earths arable soils are a wafer-thin envelope of mineral-containing carbonaceous materials. They are about 95% mineral content, once you remove the water and airspaces. Soils buffer and filter water and airborne pollutants, store critical moisture and important minerals and micronutrients, and are essential reservoirs for carbon dioxide and methane. Soil degradation is one of the largest threats to the long-term environmental sustainability of our planet.</p>
<p>Soil depletion was well understood in primitive societies, which would migrate every few years to new lands or would replenish the soils with organic wastes. In our recent history, the western migration of Europeans to the New World witnessed families moving every few years as their dry land farming practices repeatedly played out the soil. The first sign of nutrient exhaustion did not come from crop failure, but appeared as increased sickness and disease among both the animals and humans who relied upon the land.<a href="#Ref3"><sup>3</sup></a> Those who did not leave their farms observed inevitable declines in crop production, followed by outright collapse of the land, as was witnessed in the great dust bowl formations of the 1930s.</p>
<p>Today, we have nowhere else to go. With the landmasses of the great continents now overtaken by a crush of humanity, we can no longer simply pick up and leave for greener pastures. We must make do with what we havesoil erosion, contamination with industrial pollutants, and depletion of our limited mineral resources is global.<a href="#Ref4"><sup>4-11</sup></a> Nevertheless, modern agricultural practices continue to consume water, fuel and topsoil at unsustainable rates, seemingly oblivious to natures inviolate dictate to give back to the earth what we have taken. Instead of replenishing, modern agriculture truncates natures nutrient and hydrologic cycles. Both crops and livestock deplete our soils by removal of the minerals and nutrients contained in the produce sold. Once shipped to outside markets, the resulting deficiencies are seldom reconciled. There is little recognition of the need to rebuild the essential elements removed from this natural cycle.</p>
<h3>Impoverished soils, impoverished crops</h3>
<p>The depletion of the nutrient content of our soils, through unsustainable agricultural practices, results in the inevitable loss of nutrient value in our crops. Historical data shows the average mineral content of vegetables grown in U.S. soils has dropped precipitously over the last century.<a href="#Ref1"><sup>1</sup></a> Research published in the <em>Journal of the American College of Nutrition</em> in 2004 found significant declines in the mineral and vitamin content of 43 garden crops grown in U.S. markets.<a href="#Ref12"><sup>12</sup></a> As well, an investigative report published by Life Extension Foundation demonstrated that the vitamin and mineral content of several foods dropped dramatically between 1963 and 2000. Collard greens showed a 62% loss of vitamin C, a 41% loss of vitamin A and a 29% loss of calcium. Potassium and magnesium were down 52% and 84% respectively. Cauliflower had lost almost one-half of its vitamin C, thiamine and riboflavin, and most of the calcium in commercial pineapples had disappeared. According to the report, when asked to explain the precipitous drop in the calcium content observed in commercial corn, the U.S. Department of Agriculture replied that the 78% loss was not significant because no one eats corn for calcium, adding that the nutritional content of produce is not as important as appearance and yield.<a href="#Ref13"><sup>13</sup></a></p>
<p>The U.S. data corroborate findings for vegetable crops grown between 1940 and 2002 in Great Britain, which show mineral losses ranging from 15% to 62% for common minerals and trace elements.<a href="#Ref2"><sup>2</sup></a> Moreover, in an earlier study, the same authors also found detrimental changes in the natural ratio of minerals, such as calcium and magnesium, in the foods tested.<a href="#Ref14"><sup>14</sup></a> Similarly, a Canadian study found dramatic declines in the nutrient content of produce grown over a 50 year interval to 1999. During that time, the average Canadian spud lost 57% of its vitamin C and iron, 28% of its calcium, 50% of its riboflavin and 18% of its niacin. The story was the same for all 25 fruits and vegetables analyzed. The Canadian data showed that nearly 80% of the foods tested showed large drops in their calcium and iron content, three-quarters showed significant decreases in vitamin A, one-half lost vitamin C and riboflavin and one-third lost thiamine.<a href="#Ref15"><sup>15</sup></a></p>
<p>Selective breeding of new crop varieties that place a premium on yield, appearance and other commercially desirable characteristics has also been attributed to the depletion of the nutritional value of our foods.<a href="#Ref16"><sup>16</sup></a> Dr. Phil Warman of Nova Scotias Agricultural College argues that the emphasis on appearance, storability, and yieldwith little or no emphasis on nutritional contenthas added considerably to the overall nutrient depletion of our food supply. The U.S. Department of Agriculture standards for fruits and vegetables are limited to size, shape and colorthey do not even consider nutritional value.<a href="#Ref1"><sup>1</sup></a> With standards like these, it is not surprising that you have to eat eight oranges today to get the same amount of vitamin A your grandparents got from a single orange.<a href="#Ref15"><sup>15</sup></a></p>
<h3>How nutrients are removed from soils</h3>
<p>Erosion of topsoil by wind and water is accelerated by overcultivating, overgrazing and destruction of natural ground cover. The loss of organic matter results in a concurrent loss of nitrogen, minerals, and trace elements and reduces the ability of soil to hold moisture and support the growth of healthy plants. The nutrient demands from high-yield crops place a further burden on the limited nutritional capacity of our soils. For example, in 1930 an acre of land would yield about 50 bushels of corn. By 1960, yields had reached 200 bushels per acre―far beyond the capacity of the soil to sustain itself.<a href="#Ref17"><sup>17</sup></a></p>
<p>Erosion, in combination with high-yield nutrient extraction, also depletes the soil of its alkalizing minerals (calcium, potassium and magnesium). This loss of natural buffering capacity results in the release of acids from natural clay deposits and the soil becomes increasingly acidic. Conversely, over-irrigation with hard (alkaline) water causes some soils to leach important minerals while accumulating others (such as calcium). As a result, the soil becomes too alkaline to sustain crop growth.</p>
<p>It is true that nitrate, phosphate and potassium (NPK) fertilizers, first introduced in the early 1900s, significantly increase crop yield, but they do so at great expense. Over-use of these chemical fertilizers has been found to <em>accelerate</em> the depletion of these vital micronutrients and trace elements and reduce their bioavailability to plants.<a href="#Ref18"><sup>18</sup></a> NPK fertilizers will gradually reduce soil pH, rendering the soils too acidic to support beneficial bacteria and fungi. These symbiotic organisms assist the plant in absorbing nutrients from the soil. Once gone, uptake of micronutrients by plants is significantly impaired.<a href="#Ref19"><sup>19</sup></a> Moreover, in acidic soils, NPK application has been found to bind soil-based selenium, making it unavailable for root absorption.<a href="#Ref20"><sup>20</sup></a></p>
<p>Application of NPK fertilizers to replenish the major growth-promoting nutrients fails to address the concurrent losses of micronutrients and trace elements (such as copper, zinc and molybdenum) that occur in intensively cultivated soils. According to Dr. William Albrecht of the University of Missouri, the use of NPK fertilizers means malnutrition, attack by insects, bacteria and fungi, weed takeover, and crop loss in dry weather.<a href="#Ref21"><sup>21</sup></a> Albrecht contends that the use of chemical fertilizers to chase yield actually weakens the crop, making it <em>more </em>susceptible to pests and disease. Consequently, the commercial farmer has no choice but to rely on harmful chemical pesticides to protect his crop and his investment.</p>
<h3>Nutrient depletion forces pesticide abuse</h3>
<p>The weakening of both our soils and crops through the indiscriminate practices of commercial agriculture creates an overwhelming dependence on the use of pesticides and herbicides in order to maintain crop yield. These extremely toxic organochlorine (OC) and organophopshorus (OP) derivatives kill our soils by slaughtering the symbiotic bacteria and fungi that promote nutrient uptake in plants. They also inactivate critical enzyme systems within the plant roots that are involved in mineral absorption,<a href="#Ref19"><sup>19</sup></a> and they destroy the soil micro-organisms needed to create the organic-mineral complexes that naturally replenish the soil.<a href="#Ref18"><sup>18</sup></a></p>
<p>To make matters worse, these environmental poisons end up on our dinner table.</p>
<p>Dr. Jerome Weisner, Science Advisor for President John F. Kennedy, said in 1963: The use of pesticides is far more dangerous than radioactive fallout. Unfortunately, he underestimated their potential. While potentially lethal, most radioactive fallout eventually decays to background levels. Pesticides, on the other hand, are <em>persistent</em> environmental toxins that accumulate and concentrate along the food chain, building up in the fatty tissues of the body. All of us carry a lifetime body burden of these environmental poisons and suffer their cumulative effects.</p>
<p>The evidence is unassailable: human exposure to pesticides is ubiquitous and occurs most commonly through the food we eat.<a href="#Ref22"><sup>22-46</sup></a> What is at dispute is whether low levels of exposures can cause harm. Some studies refute the claim that environmental exposure to pesticide residues is harmful.<a href="#Ref47"><sup>47-49</sup></a> Other studies provide startling evidence that pesticides can elicit harmful biological effectssometimes at exquisitely low levels<a href="#Ref24"><sup>24</sup></a> <a href="#Ref25"><sup>, 25</sup></a><a href="#Ref43"><sup>, 43</sup></a><a href="#Ref50"><sup>, 50</sup></a>as a result of chronic environmental exposures.<a href="#Ref26"><sup>26</sup></a><a href="#Ref37"> <sup>, 37</sup></a><a href="#Ref51"><sup>, 51</sup></a><a href="#Ref52"><sup>, 52</sup></a></p>
<p>Harmful synergistic effects from combinations of pesticides and chemical agents can occur at levels of environmental exposure.<a href="#Ref37"><sup>37</sup></a><a href="#Ref53"><sup>, 53</sup></a> In some cases, pesticide cocktails have been found to elicit toxic effects at levels significantly <em>below</em> those expressed by the individual chemicals.<a href="#Ref54"><sup>54-57</sup></a> In one study, a cocktail of aldicarb, atrazine and nitrate, in the same order of magnitude to that found in groundwater across the United States, induced endocrine, immune and behavioral changes at doses that could not be observed for the single compounds at the same concentrations.<a href="#Ref56"><sup>56</sup></a></p>
<p>While the industry continues to claim that pesticides and herbicides are safe and effective, a recent study suggests that women with breast cancer are five to nine times more likely to have significant levels of pesticide residues in their blood.<a href="#Ref58"><sup>58</sup></a> As well, pesticides and herbicides have been linked to a wide range of human health effects, including immune suppression, hormone disruption, diminished intelligence, reproductive abnormalities, neurological and behavioral disorders, and cancer.<a href="#Ref51"><sup>51</sup></a><a href="#Ref52"><sup>, 52</sup></a> They are also potent endocrine hormone disruptors and can be passed easily through the placenta to the unborn infant, which is extremely vulnerable to toxins that disrupt the developmental process.<a href="#Ref59"><sup>59-62</sup></a> Children are particularly susceptible to pesticides because of a higher level of food intake for their body weight and a still-maturing immune system.</p>
<p>No matter how conscientious we may be, we are constantly exposedthrough the foods we eat, the water we drink, and the air we breatheto environmental levels of these toxins that may manifest in subtle or profound ways. That is why it is exceedingly important to protect yourself and your children, as much as you can, by choosing sensible dietary alternatives to commercially processed foodsthe principal source of pesticide exposure.</p>
<h2>Organic Agriculture Improves Nutrient Content</h2>
<p>For the vast majority of human history, agriculture used organic growing practices. It was only during the last 100 years that the use of synthetic chemicals was introduced to the food supply. Organic foods grown today are subject to stringent production standards. Under organic production, the use of conventional non-organic chemicals is greatly restricted. If livestock are involved, they must be reared without the use of antibiotics or growth hormones, and animals must be fed a healthy diet. In most countries, organic crops must not be genetically modified. Since the early 1990s, organic food production has grown about 20% a year, far ahead of the rest of the food industry. In both developed and developing nations organic agriculture now accounts for 12% of global food production.<a href="#Ref63"><sup>63</sup></a></p>
<p>The natural mulching and cultivation techniques employed through organic gardening feed the soil rather than the plant by returning many of the nutrients lost through plant growth and by encouraging the growth of beneficial fungi, nitrogen-fixing bacteria, and other beneficial micro-organisms. Healthy <em>living</em> soil, in turn, promotes the symbiosis of plants with these soil microbes, thereby enhancing the transfer of essential nutrients into the plants. In contrast to conventional agriculture, organic agriculture <em>embraces</em> the natural replenishing cycles of nature.</p>
<p>Consumers who wish to minimize their pesticide exposure from conventional foods can do so confidently by purchasing organically grown produce and meats, or by adopting organic agricultural practices for their own food supply. An organic diet is beneficial in a number of ways:</p>
<ul>
<li>It significantly reduces the number of harmful synthetic chemicals ingested;</li>
<li>It avoids the use of genetically modified plants that are bred for yield rather than nutrition;</li>
<li>It reduces exposure to harmful food additives and colorings;</li>
<li>It increases the intake of beneficial nutrients.</li>
</ul>
<p>In a 2003 exposure study in the Seattle area, children two-to-four years of age who consumed organically grown fruits and vegetables had urine levels of pesticides six times lower than children who consumed conventionally grown foods. According to the authors of the study, the consumption of organic fruits, vegetables, and juices can reduce children's exposure levels from <em>above</em> to <em>below </em>the U.S. Environmental Protection Agency's current guidelines, thereby shifting exposures from a range of <em>uncertain</em> risk to a range of <em>negligible </em>risk.<a href="#Ref64"><sup>64</sup></a></p>
<p>While no systematic or clinical studies on the safety of genetically modified (GMO) foods currently exist, adverse microscopic and molecular effects in different organs and tissues have been reported.<sup><a href="#Ref65">65</a></sup> Some investigations reveal evidence of harm from the consumption of such foods, although the mechanism remains to be explained.<sup><a href="#Ref66">66</a></sup> The results of most studies indicate that GMO foods may cause hepatic, pancreatic, renal, or reproductive effects and may alter haematological, biochemical, and immunologic parameters.<sup><a href="#Ref67">67</a></sup> Because genetic-modification techniques alter specific proteins expressed by a plant, focus has now turned to evidence that certain GMO foods may elicit harmful allergic responses in sensitive individuals.<sup><a href="#Ref68">68-70</a></sup></p>
<p>Over 300 food additives, including aspartame, phosphoric acid, monosodium glutamate and trans-hydrogenated fats, and various preservatives, stabilizers, artificial sweeteners and colorings, are allowed in conventional foods. Conversely, artificial sweeteners, colorings and most chemical additives are banned in certified organically grown foods. Food colorings have been shown to have a wide range of harmful effects. Tartrazine (Yellow E102), for example, has been linked to severe allergic response, headaches, asthma, growth retardation and hyperactivity disorder in children.<sup><a href="#Ref71">71</a></sup><sup><a href="#Ref72">, 72</a></sup></p>
<p>There is a growing body of evidence confirming the health promoting effects of organically grown foods. Some studies reveal that organic crops are higher in vitamin C, iron, natural sugars, magnesium and phosphorus, and lower in harmful nitrates than conventional crops.<sup>73</sup><sup>, 74</sup> An independent review, published in the <em>Journal of Complimentary Medicine</em>, found that organic crops had markedly higher levels of nutrients for all 21 nutrients evaluated than did conventionally grown produce. Organically grown spinach, lettuce, cabbage and potatoes expressed particularly high levels of minerals.<sup>74</sup></p>
<p>Research conducted by the University of California, Davis, shows that organically grown tomatoes and peppers have higher levels of flavonoids and vitamin C than conventionally grown tomatoes.<sup><a href="#Ref75">75</a></sup> The health promoting effects of these secondary plant metabolites, manufactured by the plant to protect it from the oxidative damage of solar radiation, are well established. High intensity conventional agricultural practices appear to disrupt the natural production of these plant metabolites, leading to a loss of flavonoid content in conventional crops. Conversely, organic practices are shown to stimulate the plants oxidative defense mechanisms, leading to enhanced production of these important phytonutrients.<sup><a href="#Ref76">76</a></sup> It is precisely because organic crops are not protected by pesticides that their fruits contain higher levels of flavonoids and polyphenols than conventional fruits including up to 50% more antioxidants.<sup><a href="#Ref76">76-78</a></sup></p>
<p>One caution regarding the consumption of organic foods, particularly lettuce, is the evidence of contamination with <em>E coli </em>bacteria and other pathogens from unwashed fruits and vegetables. Under-washed organic produce is more apt to harbour these unwanted guests than conventionally grown foods.<sup><a href="#Ref79">79</a></sup><sup><a href="#Ref80">, 80</a></sup></p>
<h2>Nutrient Depletion through Food Preparation</h2>
<p>Nutrient depletion of foods also occurs through the harvesting, storing and transport to markets that may be half a world away. To reduce damage and facilitate transport, produce (particularly fruits) are often picked green, interrupting the natural maturation cycle; they are then ripened artificially upon reaching destination, thus further reducing the nutritional value of the food. Despite the dwindling nutrient content of foodstuffs by the time they reach the pantry, it is in the final preparation for the dinner table where considerably greater nutrient diminution occurs. The amount of this loss depends upon the way foods are prepared and the method of cooking, if any.</p>
<p>In food preparation, the greater the surface area to volume ratio, the greater will be the nutrient depletion. For example, thin slicing of carrots, (particularly if done on the diagonal) maximizes this ratio, exposing a large area of the carrot to the depleting effects of oxygen and to the leaching effects of the cooking medium. Foods prepared in this manner may look appealing, but they have sacrificed much of their antioxidant and mineral content through the preparation process. Cubing the fruit or vegetable, or simply serving it whole, will minimize surface exposure and preserve greater nutrient content.</p>
<p>Thiamine is the nutrient most susceptible to thermal degradation in meats, and vitamin C is the most heat labile nutrient in produce. Consequently, they are generally used as an indicator of overall nutrient depletion. Nutrients are lost from foods because of their unavoidable exposure to light, heat, oxygen, and changes in acidity (pH). Cooking methods that minimize these effects will provide the greatest nutritional value at the dinner table.</p>
<h3>Storage of Foods</h3>
<p>Freezing appears to be the most desirable method of long-term storage, as opposed to nutrient depleting practices of canning, dehydration and salting. The ideal temperature for freezing is -18C. At this temperature, nutrient loss, as measured by thiamine (meats) and vitamin C (produce), degrades slowly over time. It is important to use moisture-proof bags or containers as foods will dehydrate even though frozen, leading to considerable antioxidant depletion. Packaging foods in airproof containers will also limit antioxidant loss caused by contact with oxygen. When preparing foods for freezing, use the largest cuts possible, or freeze the food whole to reduce nutrient degradation due to surface area exposure.<sup><a href="#Ref81">81</a></sup></p>
<p>Refrigeration of fruits and vegetables is necessary to preserve nutritional value once the produce has ripened. Placing these foods in a crisper and using moisture-proof bags will help preserve moisture content. Avoid dehydration of your produce, whether refrigerating or freezing; the process of dehydration can lead to extensive losses of certain phytonutrients.<sup><a href="#Ref82">82</a></sup> Even with these precautions, fresh fruits will deteriorate rapidly and should be frozen to preserve nutritional value if not used within a few days.</p>
<h3>Cooking Methodologies</h3>
<p>Preserving nutritional content appears to vary with cooking methodology, food type, and nutrient.<sup><a href="#Ref83">83</a></sup><sup><a href="#Ref84">, 84</a></sup> Although there is no hard-and-fast rule, the consensus of the research indicates that microwave cooking, baking, and steaming are the <em>least</em> destructive processes and preserve the <em>greatest</em> nutritional content of foods. On the other hand, boiling (while preserving the antioxidant content of certain phytonutrients)<sup><a href="#Ref84">84</a></sup> is generally the <em>worst</em> method for preserving water-soluble vitamins and minerals, which are quickly leached out of the food.<sup><a href="#Ref85">85</a></sup><sup><a href="#Ref86">, 86</a></sup> This section briefly outlines four cooking methodologiesboiling, steaming, frying and microwave cookingand provides a relative comparison of each.</p>
<h3>Boiling</h3>
<p>Those cooking methods that make use of water, such as boiling, scalding and blanching (with the exception of steaming), are generally associated with the greatest nutrient losses in both meats and vegetables.<sup><a href="#Ref87">87</a></sup> Boiling has been shown to reduce folic acid content by over 50% in spinach and 56% in broccoli, in contrast to steaming, which showed no significant decrease in folate levels.<sup><a href="#Ref88">88</a></sup> In another study, vitamin C losses from broccoli due to boiling exceeded 30% as opposed to about 20% for steaming and less than 10% for microwaving.<sup><a href="#Ref89">89</a></sup> One study investigating the retention of several B-complex vitamins showed that boiling and deep-frying were the most aggressive of all cooking methods in depleting vitamin content. Boiling, more so than deep frying, also dramatically reduces overall mineral content.<sup><a href="#Ref90">90</a></sup></p>
<p>The combination of boiling and stir-frying, a popular method of food preparation in Asian cultures, leads to dramatic losses of chlorohpyll, soluble proteins and sugars, vitamin C and glucosinolates in vegetables.<sup><a href="#Ref91">91</a></sup> These losses occur mainly from the leaching of the nutrients into the water, rather than their wholesale destruction.<sup><a href="#Ref92">92</a></sup> The addition of a small amount of salt as well as reducing the volume of cooking water have been shown to reduce the degree of leaching.<sup><a href="#Ref93">93</a></sup> Rather than total immersion in water, it is better to boil foods in a shallow layer of water in order to reduce leaching. Also, rather than discarding the cooking juices, reclaim the nutrients by using the liquid for the preparation of broths or gravies.</p>
<h3>Steaming</h3>
<p>While there is conflicting evidence regarding the stability of vitamin C during steaming,<sup><a href="#Ref84">84</a></sup><sup><a href="#Ref94">, 94</a></sup> most studies report that steaming provides good retention of both vitamins and minerals in various food types. Recent studies confirm that steaming, microwaving and stir-frying for short durations are best at preserving the health promoting factors (glucosinolates and isothiocyanates) found in vegetables of the Brassica family (broccoli, Brussels sprouts, cauliflower and cabbage).<sup><a href="#Ref95">95-97</a></sup> In a study using twelve types of vegetables, steaming and roasting bested several other cooking methods in preserving B-complex vitamins.<sup><a href="#Ref98">98</a></sup></p>
<p>Of all cooking methods, steaming appears to be one of the best for nutrient retention in vegetables. Both nutrient content and presentation are optimized when the vegetable is not immersed in the water and when exposure time is minimized.</p>
<h3>Frying</h3>
<p>In a study of nutrient loss in 20 vegetables using different cooking methods, microwave cooking and baking best preserved antioxidant status, whereas pressure cooking and boiling showed the greatest losses. Frying of vegetables occupied an intermediate position with respect to preserving antioxidant content.<sup><a href="#Ref99">99</a></sup><sup><a href="#Ref100">, 100</a></sup> Frying appears to have little effect on mineral content, nor does it appear to cause significant loss of phytonutrients.<sup><a href="#Ref101">101</a></sup><sup><a href="#Ref102">, 102</a></sup> Some studies show fried foods to be a good source of vitamin E;<sup><a href="#Ref71">103</a></sup> other studies show that frying does not affect the flavonoid content of certain vegetables.<sup><a href="#Re104">104</a></sup> However, frying does appear to be destructive of overall antioxidant activity, more so than either sauting (quickly frying with little fat) or baking.<sup><a href="#Ref105">105</a></sup> Similar to boiling, frying can cause significant nutrient loss of the health promoting glucosinolates and B-complex vitamins found in Brassica and other vegetables.<sup><a href="#Ref96">96</a></sup><sup><a href="#Ref98">, 98</a></sup>As well, deep frying has been found to incur severe denaturation of proteins in some vegetables.<sup><a href="#Ref106">106</a></sup></p>
<p>Frying has little apparent impact on the protein or mineral content of meats,<sup><a href="#Ref107">107</a></sup> and similar to roasting, is credited with removing over 50% of carcinogenic polychlorinated biphenyls from fish during the cooking process.<sup><a href="#Ref108">108</a></sup> One recent study showed that frying, baking, broiling and microwaving, reduced the level of organochlorines (DDT derivatives and PCBs) found in fish by as much as 68%.<sup><a href="#Ref109">109</a></sup> Another study showed that roasting meat in its own fat is preferable to deep-frying as it reduces the formation of harmful trans-fats.<sup><a href="#Ref110">110</a></sup></p>
<p>Heterocyclic amines (HAs) are genotoxic compounds formed when meats are cooked at high temperatures, particularly when pan frying and barbecuing. These compounds pose a significant carcinogenic risk; it is not known if there is, in fact, any level of exposure that can be considered safe. Interestingly, a very recent analysis of HAs from six commercial burger outlets in California revealed high levels of these compounds in all samples, which reached over 1,000 nannograms per entre.<sup><a href="#Ref111">111</a></sup> It has been found that the use of red wine marinades while frying fish and poultry can significantly reduce the formation of these genotoxic amines, formed during cooking process.<sup><a href="#Ref112">112</a></sup><sup><a href="#Ref113">, 113</a></sup> As well, the addition of a small amount of carbohydrate (potato starch or potato flour) to hamburger meat has been found to reduce formation of damaging HAs created during the barbeque process.<sup><a href="#Ref110">110</a> </sup>Caution should be used if frying with margarine as opposed to better cooking oils, such as canola, soy and olive oil. Steaks fried in margarine were shown to create high levels of mutagenic aldehydes.<sup><a href="#Ref114">114</a></sup></p>
<h3>Microwaving</h3>
<p>While there has been controversy about the effects of microwaves on food quality and safety, overall, there are only slight differences between microwave and conventional cooking with respect to vitamin and mineral retention.<sup><a href="#Ref115">115</a></sup> There is evidence that microwaving can reduce carotenoids in some foods;<sup><a href="#Ref116">116</a></sup> other studies confirm that microwaving preserves bioflavonoid content and appears to be the most effective method for cooking legumes.<sup><a href="#Ref117">117</a></sup><sup><a href="#Ref118">,118</a></sup> Some studies suggest that vitamin C is not stable under microwave conditions;<sup><a href="#Ref119">119</a></sup> other research confirms that the preservation of the B-complex vitamins, vitamin C, and flavonoids may reflect the amount of water and power used in the cooking process.<sup><a href="#Ref104">104</a></sup><sup><a href="#Ref120">, 120</a></sup> In one particular study, broccoli cooked by microwave was shown to preserve over 90% of its vitamin C and <em>all </em>of its health promoting sulforaphane content.<sup><a href="#Ref94">94</a></sup> Other investigations confirm that reducing both water use and cooking time optimize the nutritional content of foods cooked by microwave.<sup><a href="#Ref97">97</a></sup><sup><a href="#Ref121">, 121</a></sup> An analysis of the preservation of antioxidant activity for 20 different vegetables concluded that microwave cooking, along with grilling and baking, was the preferred method to optimize nutritional value.<sup><a href="#Ref99">99</a></sup></p>
<p>Concern has been expressed about the potential generation of mutagenic compounds from microwave cooking; however, a review of the literature finds little support for this argument.<sup><a href="#Ref122">122-126</a></sup> In fact, the evidence suggests that microwaves <em>do not</em> change the nutritional content of foods or create carcinogens, as can occur in conventional cooking, presumably because the foods are not heated beyond the boiling point of water.<sup><a href="#Ref127">127</a></sup> Several studies report that cooking with microwaves allows foods to maintain more of the nutrient content because the vitamins and minerals are not leached out as with conventional cooking.<sup><a href="#Ref128">128-130</a></sup> In fact, cooking of meats in a microwave (in particular, smoked and preserved meats, such as bacon) avoids the creation of carcinogenic heterocyclic amines (HCAs) and N-nitrosamines (NNAs) that is known to occur in conventional cooking.<sup><a href="#Ref131">131-136</a></sup></p>
<h2>Conclusions</h2>
<p>The conveniences of modern living incur many trade-offs when it comes to eating a healthy diet. Most of us are simply unaware of our level of exposure to persistent environmental toxins through the foods we place daily on our table. Nor do we fully appreciate the degree to which the nutritional value of our food supply has been bludgeoned by our over-reliance on commercial, chemically based agriculture. The fact is, without fortified cereals, most of us would not even come close to meeting our daily nutritional requirements for vitamins, minerals and trace elements. Less than one-third of North Americans eat the minimum recommended five servings of fruits and vegetables every day. Now we find that even if a person accidentally <em>does</em> eat a vegetable, it doesnt have nearly the nutrition that nature intended.</p>
<p>Whats a mother to do?</p>
<p>To start with, we can begin to identify those foods most highly exposed to chemical fertilizers and choose, instead, to supplement our diets with organically grown alternatives. We can learn how to grow our own produce on family owned or community garden plots and use organic growing techniques, such as composting and feeding the soil, to replenish the nutrients. If we cant grow our own gardens, we can choose to support local farmers and agriculturalists, encouraging the growth of a local organic farming culture, and we can support organic growers the world over with the purchase power of our consumer dollar. In the home, we can learn to adapt culinary and cooking techniques that <em>optimize</em>, rather than <em>compromise</em>, the nutritional value of the foods we purchase.</p>
<p>Finally, we can learn to stop treating vegetables as a side dish and understand that optimal nutritional intake is our best defense against illness and disease.</p>
<h2>Reference List</h2>
<p id="Ref1">(1) Marler JB, Wallin JR. Human Health, the Nutritional Quality of Harvested Food and Sustainable Farming Systems. Nutrition Security Institute 2006; Available at: URL: <u><a href="http://www.nutritionsecurity.org/PDF/NSI_White%20Paper_Web.pdf">http://www.nutritionsecurity.org/PDF/NSI_White%20Paper_Web.pdf</a></u>. Accessed November 4, 2009.</p>
<p id="Ref2">(2) Thomas D. The mineral depletion of foods available to us as a nation (1940-2002)--a review of the 6th Edition of McCance and Widdowson. Nutr Health 2007;19(1-2):21-55.</p>
<p id="Ref3">(3) Farm Land Mineral Depletion. Medical Missionary Press 2009; Available at: URL: <u><a href="http://www.mmpress.info/id58.htm">http://www.mmpress.info/id58.htm</a></u>. Accessed November 4, 2009.</p>
<p id="Ref4">(4) Horrigan L, Lawrence RS, Walker P. How sustainable agriculture can address the environmental and human health harms of industrial agriculture. Environ Health Perspect 2002 May;110(5):445-56.</p>
<p id="Ref5">(5) Lilburne LR, Hewitt AE, Sparling GP, Selvarajah N. Soil quality in New Zealand: policy and the science response. J Environ Qual 2002 November;31(6):1768-73.</p>
<p id="Ref6">(6) McMichael AJ. Global environmental change and human health: new challenges to scientist and policy-maker. J Public Health Policy 1994;15(4):407-19.</p>
<p id="Ref7">(7) Boardman J, Shepheard ML, Walker E, Foster ID. Soil erosion and risk-assessment for on- and off-farm impacts: a test case using the Midhurst area, West Sussex, UK. J Environ Manage 2009 June;90(8):2578-88.</p>
<p id="Ref8">(8) Griffin TS, Honeycutt CW. Effectiveness and efficacy of conservation options after potato harvest. J Environ Qual 2009 July;38(4):1627-35.</p>
<p id="Ref9">(9) Gunderson PD. Biofuels and North American agriculture--implications for the health and safety of North American producers. J Agromedicine 2008;13(4):219-24.</p>
<p id="Ref10">(10) Liu YY, Ukita M, Imai T, Higuchi T. Recycling mineral nutrients to farmland via compost application. Water Sci Technol 2006;53(2):111-8.</p>
<p id="Ref11">(11) Robert M. [Degradation of soil quality: health and environmental risks]. Bull Acad Natl Med 1997 January;181(1):21-40.</p>
<p id="Ref12">(12) Davis DR, Epp MD, Riordan HD. Changes in USDA food composition data for 43 garden crops, 1950 to 1999. J Am Coll Nutr 2004 December;23(6):669-82.</p>
<p id="Ref13">(13) Vegetables without Vitamins. Life Extension Foundation [March]. 2001. <br> Ref Type: Magazine Article</p>
<p id="Ref14">(14) Thomas D. A study on the mineral depletion of the foods available to us as a nation over the period 1940 to 1991. Nutr Health 2003;17(2):85-115.</p>
<p id="Ref15">(15) Picard A. Today's fruits and vegetables lack yesterday's nutrition. Globe and Mail 2002 July 6;Available at: URL: globeandmail.com. AccessedNovember 4, 9 A.D.</p>
<p id="Ref16">(16) Fan MS, Zhao FJ, Fairweather-Tait SJ, Poulton PR, Dunham SJ, McGrath SP. Evidence of decreasing mineral density in wheat grain over the last 160 years. J Trace Elem Med Biol 2008;22(4):315-24.</p>
<p id="Ref17">(17) Karr M. Mineral Depletion in Soils. longevitylibrary com 2009; Available at: URL: <u><a href="http://longevitylibrary.com/article/99.htm">http://longevitylibrary.com/article/99.htm</a></u>. Accessed November 4, 2009.</p>
<p id="Ref18">(18) Drucker R. Depleted Soil and Compromised Food Sources: What You Can Do about It. Nutrition Wellness 2006 July 7; Available at: URL: <u><a href="http://www.nutritionalwellness.com/archives/2006/jul/07_depleted_soil.php">http://www.nutritionalwellness.com/archives/2006/jul/07_depleted_soil.php</a></u>. Accessed May 11, 2009.</p>
<p id="Ref19">(19) Soil Mineral Depletion: Can a Healthy diet be sufficient in today's world? Physical Nutrition 2009; Available at: URL: <u><a href="http://www.physicalnutrition.net/soil-mineral-depletion.htm">http://www.physicalnutrition.net/soil-mineral-depletion.htm</a></u>. Accessed May 11, 2009.</p>
<p id="Ref20">(20) Stockdale T. A speculative discussion of some problems arising from the use of ammonium nitrate fertiliser on acid soil. Nutr Health 1992;8(4):207-22.</p>
<p id="Ref21">(21) Soil Depletion. TJ Clark com 2006; Available at: URL: <u><a href="http://www.tjclark.com.au/colloidal-minerals-library/soil-depletion.htm">http://www.tjclark.com.au/colloidal-minerals-library/soil-depletion.htm</a></u>. Accessed November 4, 2009.</p>
<p id="Ref22">(22) Ackerman LB. Overview of human exposure to dieldrin residues in the environment and current trends of residue levels in tissue. Pestic Monit J 1980 September;14(2):64-9.</p>
<p id="Ref23">(23) Albers JM, Kreis IA, Liem AK, van ZP. Factors that influence the level of contamination of human milk with poly-chlorinated organic compounds. Arch Environ Contam Toxicol 1996 February;30(2):285-91.</p>
<p id="Ref24">(24) Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 2002 April;8(2):185-92.</p>
<p id="Ref25">(25) Bharadwaj L, Dhami K, Schneberger D, Stevens M, Renaud C, Ali A. Altered gene expression in human hepatoma HepG2 cells exposed to low-level 2,4-dichlorophenoxyacetic acid and potassium nitrate. Toxicol In Vitro 2005 August;19(5):603-19.</p>
<p id="Ref26">(26) Biscardi D, De FR, Feretti D et al. [Genotoxic effects of pesticide-treated vegetable extracts using the Allium cepa chromosome aberration and micronucleus tests]. Ann Ig 2003 November;15(6):1077-84.</p>
<p id="Ref27">(27) Carpy SA, Kobel W, Doe J. Health risk of low-dose pesticides mixtures: a review of the 1985-1998 literature on combination toxicology and health risk assessment. J Toxicol Environ Health B Crit Rev 2000 January;3(1):1-25.</p>
<p id="Ref28">(28) Dougherty CP, Henricks HS, Reinert JC, Panyacosit L, Axelrad DA, Woodruff TJ. Dietary exposures to food contaminants across the United States. Environ Res 2000 October;84(2):170-85.</p>
<p id="Ref29">(29) Grote K, Andrade AJ, Grande SW et al. Effects of peripubertal exposure to triphenyltin on female sexual development of the rat. Toxicology 2006 May 1;222(1-2):17-24.</p>
<p id="Ref30">(30) Gupta PK. Pesticide exposure--Indian scene. Toxicology 2004 May 20;198(1-3):83-90.</p>
<p id="Ref31">(31) Jiang QT, Lee TK, Chen K et al. Human health risk assessment of organochlorines associated with fish consumption in a coastal city in China. Environ Pollut 2005 July;136(1):155-65.</p>
<p id="Ref32">(32) Katz JM, Winter CK. Comparison of pesticide exposure from consumption of domestic and imported fruits and vegetables. Food Chem Toxicol 2009 February;47(2):335-8.</p>
<p id="Ref33">(33) Kawahara J, Yoshinaga J, Yanagisawa Y. Dietary exposure to organophosphorus pesticides for young children in Tokyo and neighboring area. Sci Total Environ 2007 June 1;378(3):263-8.</p>
<p id="Ref34">(34) Luo Y, Zhang M. Multimedia transport and risk assessment of organophosphate pesticides and a case study in the northern San Joaquin Valley of California. Chemosphere 2009 May;75(7):969-78.</p>
<p id="Ref35">(35) Moser VC, Simmons JE, Gennings C. Neurotoxicological interactions of a five-pesticide mixture in preweanling rats. Toxicol Sci 2006 July;92(1):235-45.</p>
<p id="Ref36">(36) Nakata H, Kawazoe M, Arizono K et al. Organochlorine pesticides and polychlorinated biphenyl residues in foodstuffs and human tissues from china: status of contamination, historical trend, and human dietary exposure. Arch Environ Contam Toxicol 2002 November;43(4):473-80.</p>
<p id="Ref37">(37) Peng J, Peng L, Stevenson FF, Doctrow SR, Andersen JK. Iron and paraquat as synergistic environmental risk factors in sporadic Parkinson's disease accelerate age-related neurodegeneration. J Neurosci 2007 June 27;27(26):6914-22.</p>
<p id="Ref38">(38) Reed L, Buchner V, Tchounwou PB. Environmental toxicology and health effects associated with hexachlorobenzene exposure. Rev Environ Health 2007 July;22(3):213-43.</p>
<p id="Ref39">(39) Rivas A, Cerrillo I, Granada A, Mariscal-Arcas M, Olea-Serrano F. Pesticide exposure of two age groups of women and its relationship with their diet. Sci Total Environ 2007 August 15;382(1):14-21.</p>
<p id="Ref40">(40) Tryphonas H. The impact of PCBs and dioxins on children's health: immunological considerations. Can J Public Health 1998 May;89 Suppl 1:S49-7.</p>
<p id="Ref41">(41) Tsydenova OV, Sudaryanto A, Kajiwara N, Kunisue T, Batoev VB, Tanabe S. Organohalogen compounds in human breast milk from Republic of Buryatia, Russia. Environ Pollut 2007 March;146(1):225-32.</p>
<p id="Ref42">(42) Viquez OM, Valentine HL, Friedman DB, Olson SJ, Valentine WM. Peripheral nerve protein expression and carbonyl content in N,N-diethlydithiocarbamate myelinopathy. Chem Res Toxicol 2007 March;20(3):370-9.</p>
<p id="Ref43">(43) Wade MG, Parent S, Finnson KW et al. Thyroid toxicity due to subchronic exposure to a complex mixture of 16 organochlorines, lead, and cadmium. Toxicol Sci 2002 June;67(2):207-18.</p>
<p id="Ref44">(44) Waliszewski SM, Pardio VT, Waliszewski KN et al. Organochlorine pesticide residues in cow's milk and butter in Mexico. Sci Total Environ 1997 December 3;208(1-2):127-32.</p>
<p id="Ref45">(45) Weiss J, Papke O, Bergman A. A worldwide survey of polychlorinated dibenzo-p-dioxins, dibenzofurans, and related contaminants in butter. Ambio 2005 December;34(8):589-97.</p>
<p id="Ref46">(46) Bloom MS, Vena JE, Swanson MK, Moysich KB, Olson JR. Profiles of ortho-polychlorinated biphenyl congeners, dichlorodiphenyldichloroethylene, hexachlorobenzene, and Mirex among male Lake Ontario sportfish consumers: the New York State Angler cohort study. Environ Res 2005 February;97(2):178-94.</p>
<p id="Ref47">(47) Carpy SA, Kobel W, Doe J. Health risk of low-dose pesticides mixtures: a review of the 1985-1998 literature on combination toxicology and health risk assessment. J Toxicol Environ Health B Crit Rev 2000 January;3(1):1-25.</p>
<p id="Ref48">(48) Swirsky GL, Stern BR, Slone TH, Brown JP, Manley NB, Ames BN. Pesticide residues in food: investigation of disparities in cancer risk estimates. Cancer Lett 1997 August 19;117(2):195-207.</p>
<p id="Ref49">(49) Gammon DW, Aldous CN, Carr WC, Jr., Sanborn JR, Pfeifer KF. A risk assessment of atrazine use in California: human health and ecological aspects. Pest Manag Sci 2005 April;61(4):331-55.</p>
<p id="Ref50">(50) Mao H, Fang X, Floyd KM, Polcz JE, Zhang P, Liu B. Induction of microglial reactive oxygen species production by the organochlorinated pesticide dieldrin. Brain Res 2007 December;1186:267-74.</p>
<p id="Ref51">(51) Abhilash PC, Singh N. Pesticide use and application: an Indian scenario. J Hazard Mater 2009 June 15;165(1-3):1-12.</p>
<p id="Ref52">(52) Gupta PK. Pesticide exposure--Indian scene. Toxicology 2004 May 20;198(1-3):83-90.</p>
<p id="Ref53">(53) Moser VC, Simmons JE, Gennings C. Neurotoxicological interactions of a five-pesticide mixture in preweanling rats. Toxicol Sci 2006 July;92(1):235-45.</p>
<p id="Ref54">(54) Boyd CA, Weiler MH, Porter WP. Behavioral and neurochemical changes associated with chronic exposure to low-level concentration of pesticide mixtures. J Toxicol Environ Health 1990 July;30(3):209-21.</p>
<p id="Ref55">(55) Porter WP, Green SM, Debbink NL, Carlson I. Groundwater pesticides: interactive effects of low concentrations of carbamates aldicarb and methomyl and the triazine metribuzin on thyroxine and somatotropin levels in white rats. J Toxicol Environ Health 1993 September;40(1):15-34.</p>
<p id="Ref56">(56) Porter WP, Jaeger JW, Carlson IH. Endocrine, immune, and behavioral effects of aldicarb (carbamate), atrazine (triazine) and nitrate (fertilizer) mixtures at groundwater concentrations. Toxicol Ind Health 1999 January;15(1-2):133-50.</p>
<p id="Ref57">(57) Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-Slechta DA. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson's disease. J Neurosci 2000 December 15;20(24):9207-14.</p>
<p id="Ref58">(58) Charlier C, Albert A, Herman P et al. Breast cancer and serum organochlorine residues. Occup Environ Med 2003 May;60(5):348-51.</p>
<p id="Ref59">(59) Brucker-Davis F, Wagner-Mahler K, Delattre I et al. Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations. Hum Reprod 2008 August;23(8):1708-18.</p>
<p id="Ref60">(60) Noren K, Meironyte D. Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20-30 years. Chemosphere 2000 May;40(9-11):1111-23.</p>
<p id="Ref61">(61) Wigle DT, Arbuckle TE, Walker M, Wade MG, Liu S, Krewski D. Environmental hazards: evidence for effects on child health. J Toxicol Environ Health B Crit Rev 2007 January;10(1-2):3-39.</p>
<p id="Ref62">(62) Stefanidou M, Maravelias C, Spiliopoulou C. Human exposure to endocrine disruptors and breast milk. Endocr Metab Immune Disord Drug Targets 2009 September;9(3):269-76.</p>
<p id="Ref63">(63) Organic Food. Wikipedia Online Encyclopedia 2009; Available at: URL: <u><a href="http://en.wikipedia.org/wiki/Organic_food">http://en.wikipedia.org/wiki/Organic_food</a></u>. Accessed June 11, 2009.</p>
<p id="Ref64">(64) Curl CL, Fenske RA, Elgethun K. Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Environ Health Perspect 2003 March;111(3):377-82.</p>
<p id="Ref65">(65) Magana-Gomez JA, de la Barca AM. Risk assessment of genetically modified crops for nutrition and health. Nutr Rev 2009 January;67(1):1-16.</p>
<p id="Ref66">(66) Pryme IF, Lembcke R. In vivo studies on possible health consequences of genetically modified food and feed--with particular regard to ingredients consisting of genetically modified plant materials. Nutr Health 2003;17(1):1-8.</p>
<p id="Ref67">(67) Dona A, Arvanitoyannis IS. Health risks of genetically modified foods. Crit Rev Food Sci Nutr 2009 February;49(2):164-75.</p>
<p id="Ref68">(68) Cantani A. Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks? Eur Rev Med Pharmacol Sci 2009 January;13(1):41-50.</p>
<p id="Ref69">(69) Key S, Ma JK, Drake PM. Genetically modified plants and human health. J R Soc Med 2008 June;101(6):290-8.</p>
<p id="Ref70">(70) Moneret-Vautrin DA. [Allergic risk and role of the Allergy Vigilance Network]. Bull Acad Natl Med 2007 April;191(4-5):807-14.</p>
<p id="Ref71">(71) Hanssen M, Marsden J. E for Additives. 2nd ed. London: Harper Collins; 1987.</p>
<p id="Ref72">(72) Ward NI, Soulsbury KA, Zettel VH, Colquhoun ID, Bunday S, Barnes B. The Influence of the Chemical Additive Tartrazine on the Zinc Status of Hyperactive Children—a Double-blind Placebo-controlled Study. Journal of Nutritional &amp; Environmental Medicine 1990;1(1):51-7.</p>
<p id="Ref73">(73) Lester GE, Manthey JA, Buslig BS. Organic vs conventionally grown Rio Red whole grapefruit and juice: comparison of production inputs, market quality, consumer acceptance, and human health-bioactive compounds. J Agric Food Chem 2007 May 30;55(11):4474-80.</p>
<p id="Ref74">(74) Worthington V. Nutritional quality of organic versus conventional fruits, vegetables, and grains. J Altern Complement Med 2001 April;7(2):161-73.</p>
<p id="Ref75">(75) Mitchell A. A two-year comparison of several quality and nutritional characteristics in tomatoes and peppers. University of California (Davis Campus) website 2009; Available at: URL: <u><a href="http://mitchell.ucdavis.edu/documents/Comparisons%20of%20Organic%20and%20Conventional_%20EccoFarm_2005.pdf">http://mitchell.ucdavis.edu/documents/Comparisons%20of%20Organic%20and%20Conventional_%20EccoFarm_2005.pdf</a></u>. Accessed June 11, 2009.</p>
<p id="Ref76">(76) Carbonaro M, Mattera M, Nicoli S, Bergamo P, Cappelloni M. Modulation of antioxidant compounds in organic vs conventional fruit (peach, Prunus persica L., and pear, Pyrus communis L.). J Agric Food Chem 2002 September 11;50(19):5458-62.</p>
<p id="Ref77">(77) Asami DK, Hong YJ, Barrett DM, Mitchell AE. Comparison of the total phenolic and ascorbic acid content of freeze-dried and air-dried marionberry, strawberry, and corn grown using conventional, organic, and sustainable agricultural practices. J Agric Food Chem 2003 February 26;51(5):1237-41.</p>
<p id="Ref78">(78) Brandt K, Molgaard JP. Organic agriculture: does it enhance or reduce the nutritional value of plants foods? Journal of Science and Food Agriculture 2001;81(9):924-31.</p>
<p id="Ref79">(79) Mukherjee A, Speh D, Dyck E, ez-Gonzalez F. Preharvest evaluation of coliforms, Escherichia coli, Salmonella, and Escherichia coli O157:H7 in organic and conventional produce grown by Minnesota farmers. J Food Prot 2004 May;67(5):894-900.</p>
<p id="Ref80">(80) Mukherjee A, Speh D, ez-Gonzalez F. Association of farm management practices with risk of Escherichia coli contamination in pre-harvest produce grown in Minnesota and Wisconsin. Int J Food Microbiol 2007 December 15;120(3):296-302.</p>
<p id="Ref81">(81) Severi S, Bedogni G, Manzieri AM, Poli M, Battistini N. Effects of cooking and storage methods on the micronutrient content of foods. Eur J Cancer Prev 1997 March;6 Suppl 1:S21-S24.</p>
<p id="Ref82">(82) Lee SU, Lee JH, Choi SH et al. Flavonoid content in fresh, home-processed, and light-exposed onions and in dehydrated commercial onion products. J Agric Food Chem 2008 September 24;56(18):8541-8.</p>
<p id="Ref83">(83) McKillop DJ, Pentieva K, Daly D et al. The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet. Br J Nutr 2002 December;88(6):681-8.</p>
<p id="Ref84">(84) Miglio C, Chiavaro E, Visconti A, Fogliano V, Pellegrini N. Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetables. J Agric Food Chem 2008 January 9;56(1):139-47.</p>
<p id="Ref85">(85) Galgano F, Favati F, Caruso M, Pietrafesa A, Natella S. The influence of processing and preservation on the retention of health-promoting compounds in broccoli. J Food Sci 2007 March;72(2):S130-S135.</p>
<p id="Ref86">(86) Song L, Thornalley PJ. Effect of storage, processing and cooking on glucosinolate content of Brassica vegetables. Food Chem Toxicol 2007 February;45(2):216-24.</p>
<p id="Ref87">(87) Schroeder HA. Losses of vitamins and trace minerals resulting from processing and preservation of foods. Am J Clin Nutr 1971 May;24(5):562-73.</p>
<p id="Ref88">(88) McKillop DJ, Pentieva K, Daly D et al. The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet. Br J Nutr 2002 December;88(6):681-8.</p>
<p id="Ref89">(89) Galgano F, Favati F, Caruso M, Pietrafesa A, Natella S. The influence of processing and preservation on the retention of health-promoting compounds in broccoli. J Food Sci 2007 March;72(2):S130-S135.</p>
<p id="Ref90">(90) Pan X, Zhao H, Men J, Shen X. [Changes of vitamins and mineral retention factors in potato cooked by different methods]. Wei Sheng Yan Jiu 2007 July;36(4):485-7.</p>
<p id="Ref91">(91) Yuan GF, Sun B, Yuan J, Wang QM. Effects of different cooking methods on health-promoting compounds of broccoli. J Zhejiang Univ Sci B 2009 August;10(8):580-8.</p>
<p id="Ref92">(92) Song L, Thornalley PJ. Effect of storage, processing and cooking on glucosinolate content of Brassica vegetables. Food Chem Toxicol 2007 February;45(2):216-24.</p>
<p id="Ref93">(93) Kimura M, Itokawa Y. Cooking losses of minerals in foods and its nutritional significance. J Nutr Sci Vitaminol (Tokyo) 1990;36 Suppl 1:S25-S32.</p>
<p id="Ref94">(94) Galgano F, Favati F, Caruso M, Pietrafesa A, Natella S. The influence of processing and preservation on the retention of health-promoting compounds in broccoli. J Food Sci 2007 March;72(2):S130-S135.</p>
<p id="Ref95">(95) Song L, Thornalley PJ. Effect of storage, processing and cooking on glucosinolate content of Brassica vegetables. Food Chem Toxicol 2007 February;45(2):216-24.</p>
<p id="Ref96">(96) Yuan GF, Sun B, Yuan J, Wang QM. Effects of different cooking methods on health-promoting compounds of broccoli. J Zhejiang Univ Sci B 2009 August;10(8):580-8.</p>
<p id="Ref97">(97) Rungapamestry V, Duncan AJ, Fuller Z, Ratcliffe B. Changes in glucosinolate concentrations, myrosinase activity, and production of metabolites of glucosinolates in cabbage (Brassica oleracea Var. capitata) cooked for different durations. J Agric Food Chem 2006 October 4;54(20):7628-34.</p>
<p id="Ref98">(98) Zhao H, Yang X, Zhou R, Yang Y. [Study on vitamin B1, vitamin B2 retention factors in vegetables]. Wei Sheng Yan Jiu 2008 January;37(1):92-6.</p>
<p id="Ref99">(99) Jimenez-Monreal AM, Garcia-Diz L, Martinez-Tome M, Mariscal M, Murcia MA. Influence of cooking methods on antioxidant activity of vegetables. J Food Sci 2009 April;74(3):H97-H103.</p>
<p id="Ref100">(100) Kimura M, Itokawa Y, Fujiwara M. Cooking losses of thiamin in food and its nutritional significance. J Nutr Sci Vitaminol (Tokyo) 1990;36 Suppl 1:S17-S24.</p>
<p id="Ref101">(101) Gorinstein S, Leontowicz H, Leontowicz M et al. Comparison of the main bioactive compounds and antioxidant activities in garlic and white and red onions after treatment protocols. J Agric Food Chem 2008 June 25;56(12):4418-26.</p>
<p id="Ref102">(102) Ioku K, Aoyama Y, Tokuno A, Terao J, Nakatani N, Takei Y. Various cooking methods and the flavonoid content in onion. J Nutr Sci Vitaminol (Tokyo) 2001 February;47(1):78-83.</p>
<p id="Ref103">(103) Fillion L, Henry CJ. Nutrient losses and gains during frying: a review. Int J Food Sci Nutr 1998 March;49(2):157-68.</p>
<p id="Ref104">(104) Ioku K, Aoyama Y, Tokuno A, Terao J, Nakatani N, Takei Y. Various cooking methods and the flavonoid content in onion. J Nutr Sci Vitaminol (Tokyo) 2001 February;47(1):78-83.</p>
<p id="Ref105">(105) Murcia MA, Jimenez-Monreal AM, Garcia-Diz L, Carmona M, Maggi L, Martinez-Tome M. Antioxidant activity of minimally processed (in modified atmospheres), dehydrated and ready-to-eat vegetables. Food Chem Toxicol 2009 August;47(8):2103-10.</p>
<p id="Ref106">(106) Liu YM, Lin KW. Antioxidative ability, dioscorin stability, and the quality of yam chips from various yam species as affected by processing method. J Food Sci 2009 March;74(2):C118-C125.</p>
<p id="Ref107">(107) Fillion L, Henry CJ. Nutrient losses and gains during frying: a review. Int J Food Sci Nutr 1998 March;49(2):157-68.</p>
<p id="Ref108">(108) Sherer RA, Price PS. The effect of cooking processes on PCB levels in edible fish tissue. Qual Assur 1993 December;2(4):396-407.</p>
<p id="Ref109">(109) Wilson ND, Shear NM, Paustenbach DJ, Price PS. The effect of cooking practices on the concentration of DDT and PCB compounds in the edible tissue of fish. J Expo Anal Environ Epidemiol 1998 July;8(3):423-40.</p>
<p id="Ref110">(110) Kim JH, Park HG, Kim JH et al. The development of a novel cooking method (alternate roasting with its own fat) for chicken to improve nutritional value. J Food Sci 2008 May;73(4):S180-S184.</p>
<p id="Ref111">(111) Sullivan KM, Erickson MA, Sandusky CB, Barnard ND. Detection of PhIP in grilled chicken entrees at popular chain restaurants throughout California. Nutr Cancer 2008;60(5):592-602.</p>
<p id="Ref112">(112) Busquets R, Puignou L, Galceran MT, Skog K. Effect of red wine marinades on the formation of heterocyclic amines in fried chicken breast. J Agric Food Chem 2006 October 18;54(21):8376-84.</p>
<p id="Ref113">(113) Persson E, Sjoholm I, Nyman M, Skog K. Addition of various carbohydrates to beef burgers affects the formation of heterocyclic amines during frying. J Agric Food Chem 2004 December 15;52(25):7561-6.</p>
<p id="Ref114">(114) Sjaastad AK, Svendsen K. Exposure to mutagenic aldehydes and particulate matter during panfrying of beefsteak with margarine, rapeseed oil, olive oil or soybean oil. Ann Occup Hyg 2008 November;52(8):739-45.</p>
<p id="Ref115">(115) Cross GA, Fung DY. The effect of microwaves on nutrient value of foods. Crit Rev Food Sci Nutr 1982;16(4):355-81.</p>
<p id="Ref116">(116) Elizalde-Gonzalez MP, Hernandez-Ogarcia SG. Effect of cooking processes on the contents of two bioactive carotenoids in Solanum lycopersicum tomatoes and Physalis ixocarpa and Physalis philadelphica tomatillos. Molecules 2007;12(8):1829-35.</p>
<p id="Ref117">(117) el-Adawy TA. Nutritional composition and antinutritional factors of chickpeas (Cicer arietinum L.) undergoing different cooking methods and germination. Plant Foods Hum Nutr 2002;57(1):83-97.</p>
<p id="Ref118">(118) Gorinstein S, Leontowicz H, Leontowicz M et al. Comparison of the main bioactive compounds and antioxidant activities in garlic and white and red onions after treatment protocols. J Agric Food Chem 2008 June 25;56(12):4418-26.</p>
<p id="Ref119">(119) Yuan GF, Sun B, Yuan J, Wang QM. Effects of different cooking methods on health-promoting compounds of broccoli. J Zhejiang Univ Sci B 2009 August;10(8):580-8.</p>
<p id="Ref120">(120) Hoffman CJ, Zabik ME. Effects of microwave cooking/reheating on nutrients and food systems: a review of recent studies. J Am Diet Assoc 1985 August;85(8):922-6.</p>
<p id="Ref121">(121) Lopez-Berenguer C, Carvajal M, Moreno DA, Garcia-Viguera C. Effects of microwave cooking conditions on bioactive compounds present in broccoli inflorescences. J Agric Food Chem 2007 November 28;55(24):10001-7.</p>
<p id="Ref122">(122) Microwave Ovens and their Hazards. Canadian Centre for Occupational Health and Safety 2009; Available at: URL: <u><a href="http://www.ccohs.ca/oshanswers/phys_agents/microwave_ovens.html">http://www.ccohs.ca/oshanswers/phys_agents/microwave_ovens.html</a></u>.</p>
<p id="Ref123">(123) Radiation Emmissions from Microwave Ovens. Australian Radiation Protection and Nuclear Safety Agency 2009; Available at: URL: <u><a href="http://www.arpansa.gov.au/RadiationProtection/Factsheets/is_Microwave.cfm">http://www.arpansa.gov.au/RadiationProtection/Factsheets/is_Microwave.cfm</a></u>.</p>
<p id="Ref124">(124) Jonker D, Til HP. Human diets cooked by microwave or conventionally: comparative sub-chronic (13-wk) toxicity study in rats. Food Chem Toxicol 1995 April;33(4):245-56.</p>
<p id="Ref125">(125) Nader CJ, Spencer LK, Weller RA. Mutagen production during pan-broiling compared with microwave irradiation of beef. Cancer Lett 1981 July;13(2):147-52.</p>
<p id="Ref126">(126) Sirtori C, Paganuzzi M, Lombardo C et al. [Cooking meat in microwave ovens does not cause formation of mutagenic substances]. Minerva Med 1983 December 15;74(47-48):2803-6.</p>
<p id="Ref127">(127) Microwave Ovens and Food Safety. Health Canada 2009; Available at: URL: <u><a href="http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/prod/micro-f-a-eng.php">http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/prod/micro-f-a-eng.php</a></u>. Accessed October 1, 2009.</p>
<p id="Ref128">(128) Cross GA, Fung DY. The effect of microwaves on nutrient value of foods. Crit Rev Food Sci Nutr 1982;16(4):355-81.</p>
<p id="Ref129">(129) Jimenez-Monreal AM, Garcia-Diz L, Martinez-Tome M, Mariscal M, Murcia MA. Influence of cooking methods on antioxidant activity of vegetables. J Food Sci 2009 April;74(3):H97-H103.</p>
<p id="Ref130">(130) Galgano F, Favati F, Caruso M, Pietrafesa A, Natella S. The influence of processing and preservation on the retention of health-promoting compounds in broccoli. J Food Sci 2007 March;72(2):S130-S135.</p>
<p id="Ref131">(131) Felton JS, Fultz E, Dolbeare FA, Knize MG. Effect of microwave pretreatment on heterocyclic aromatic amine mutagens/carcinogens in fried beef patties. Food Chem Toxicol 1994 October;32(10):897-903.</p>
<p id="Ref132">(132) Hoffman CJ, Zabik ME. Effects of microwave cooking/reheating on nutrients and food systems: a review of recent studies. J Am Diet Assoc 1985 August;85(8):922-6.</p>
<p id="Ref133">(133) Miller BJ, Billedeau SM, Miller DW. Formation of N-nitrosamines in microwaved versus skillet-fried bacon containing nitrite. Food Chem Toxicol 1989 May;27(5):295-9.</p>
<p id="Ref134">(134) Nader CJ, Spencer LK, Weller RA. Mutagen production during pan-broiling compared with microwave irradiation of beef. Cancer Lett 1981 July;13(2):147-52.</p>
<p id="Ref135">(135) Sirtori C, Paganuzzi M, Lombardo C et al. [Cooking meat in microwave ovens does not cause formation of mutagenic substances]. Minerva Med 1983 December 15;74(47-48):2803-6.</p>
<p id="Ref136">(136) Sugimura T, Wakabayashi K, Nakagama H, Nagao M. Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. Cancer Sci 2004 April;95(4):290-9.</p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/side-benefits-not-side-effects</id>
    <published>2024-04-03T05:59:03-07:00</published>
    <updated>2024-04-03T05:59:04-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/side-benefits-not-side-effects"/>
    <title>Side Benefits, Not Side Effects</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<span data-mce-fragment="1">My 5-year-long self-experiment with lipoprotein(a) therapy -- to cure my heart disease -- has not been without side effects. </span><a href="https://online-store-web.shopifyapps.com/articles/new#Ref1" data-mce-fragment="1" data-mce-href="https://online-store-web.shopifyapps.com/articles/new#Ref1" target="_blank">[1]</a><span data-mce-fragment="1"> However, these side effects are not ones that I would ask my doctor or pharmacist about. </span>These side effects are also not the ones that most doctors over-caution about: for example, hypervitaminosis, toxicity, heart damage, inflammation of the stomach lining, and even carcinogenic effects.<p><a class="read-more" href="https://comparativeguide.com/blogs/news/side-benefits-not-side-effects">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[    <div>
        <p style="padding-bottom:10px;"><strong>FOR IMMEDIATE RELEASE</strong> 
            <br><strong>Orthomolecular Medicine News Service, February 22, 2024</strong>
            </p>
            <h2 style="padding-top:10px;padding-bottom:20px;"><b>A personal report by Hans W. Diel</b></h2>
            <p style="padding-bottom:10px;">OMNS (Feb 22, 2024) My 5-year-long self-experiment with lipoprotein(a) therapy -- to cure my heart disease -- has not been without side effects.
            <a href="#Ref1" target="_blank">[1]</a> However, these side effects are not ones that I would ask my doctor or pharmacist about. (The familiar statement "For risks and side effects, read the package leaflet and ask your doctor or pharmacist," which I am alluding to here, is obligatory for  advertising medicines in the media). These side effects are also not the ones that most doctors over-caution about: for example, hypervitaminosis, toxicity, heart damage, inflammation of the stomach lining, and even carcinogenic effects.
            </p>
            <p style="padding-bottom:10px;">No, to the contrary, during my self-experiment I experienced a whole series of miraculous healthy side effects that I only mentioned in passing in the documentation of my experiment with Linus Pauling's vitamin therapy. 
            <a href="#Ref1" target="_blank">[1,2]</a>
            </p>
            <p style="padding-bottom:10px;">Here, I refer to the successful treatment or prevention of sometimes serious illnesses as "side effects" because the threats and arrogance of pharma-fixated doctors towards the use of natural remedies is annoying and deceptive.  Often they say hardly a word about the sometimes very serious side effects of the drugs they prescribe as standard. Of course, the term "side effects" does not do justice to my personal experience in disease treatment and prevention. Each successful experience is a reason to provide more detail.
            </p>
            <p style="padding-bottom:5px;">The most gratifying "list of successes":
            </p>
            <ul>
<li style="padding-bottom:5px;padding-left:10px">Raynaud's syndrome cured
            </li>
<li style="padding-bottom:5px;padding-left:10px">High blood pressure (arterial hypertension) disappeared
            </li>
<li style="padding-bottom:5px;padding-left:10px">Cardiac arrhythmias no longer occur
            </li>
<li style="padding-bottom:5px;padding-left:10px">Heart rate significantly reduced
            </li>
<li style="padding-bottom:5px;padding-left:10px">Vitiligo stopped
            </li>
<li style="padding-bottom:10px;padding-left:10px">No coronavirus infection
            </li>
</ul>
            <p style="padding-bottom:10px;">How can the successes be explained? Here is a brief explanation:
            </p>
            <p style="padding-bottom:10px;">I am convinced that the decisive basis is the "therapy package" that I put together as part of my experiment with the Pauling therapy, supplemented by recommendations from the German physician Dr Ulrich Strunz.
            <a href="#Ref3" target="_blank">[3]</a> First, I got blood tests and identified a combination of micronutrients to compensate for nutrient deficiencies in my body. Then I took adequate doses of nutrient supplements every day, based on my body's needs. The blood testing has become routine for me. It helps me to maintain the right, optimum level. 
            </p>
            <p style="padding-bottom:10px;">I have not taken any medication, not a single one.
            </p>
            <p style="padding-bottom:10px;">OMNS readers will likely know which individual essential nutrients played a particular role in my success. They include adequate doses of vitamins C,D,E, and the B vitamins, along with minerals such as magnesium, zinc, and selenium, as well as omega-3 fatty acids. How and to what extent what actually worked cannot be traced in detail because my self-experiment had a different goal, namely to cure my heart disease, and was not specifically focused on these "side effects". However, according to my findings, the following assumptions are reasonable:
            </p>
            <p style="padding-bottom:10px;">With Raynaud's syndrome (a circulatory disorder of the fingers or toes caused by paroxysmal vasospasms, which are particularly noticeable when exposed to cold. Named after its discoverer, the French doctor Maurice Raynaud. Individual fingers become white and numb, as if they are dying. Painful and frightening), magnesium, as well as the amino acids arginine and citrulline are likely to have been the key factors. As already mentioned, the disease is cured.
            </p>
            <p style="padding-bottom:10px;">Blood pressure has been significantly and persistently reduced, especially after increased intake of arginine, citrulline, taurine, potassium and magnesium, and is now regularly in the range of 120 to 65 mmHg.
            </p>
            <p style="padding-bottom:10px;">The cardiac arrhythmia (ventricular arrhythmia), which was particularly evident under stress, has not occurred for five years now, as observed by regular cardiological examinations. Magnesium, potassium, taurine and probably also omega-3 have likely contributed significantly to this. I have raised my omega-3 index to 14%. (Dyerberg/Passwater have reported on the effect of omega-3 on arrhythmias in their book "The Missing Wellness Factors - EPA and DHA" 
            <a href="#Ref4" target="_blank">[4]</a> and William Sears/James Sears in "The Omega-3 Effect" 
            <a href="#Ref5" target="_blank">[5]</a>).
            </p>
            <p style="padding-bottom:10px;">I attribute the calming of the heart rate (now 55 - 60 bpm) primarily to magnesium, potassium, taurine and an adequate salt intake, which I have based on the recommendations of Brownstein "Salt Your Way to Health" 
            <a href="#Ref6" target="_blank">[6]</a> and Dinicolantonio "The Salt Fix" 
            <a href="#Ref7" target="_blank">[7]</a>, controlled by measuring the sodium level. My exercise and meditation sessions certainly also played a part. I did not take the beta blockers prescribed to relieve my heart "as part of heart failure therapy". For most individuals, eating plentiful servings of vegetables and fruits can provide adequate potassium.
            </p>
            <p style="padding-bottom:10px;">For the last 10 years, the spread of vitiligo (an autoimmune skin disease in which white patches form on the skin due to the loss of pigment cells in various parts of the body) has been halted. The complete therapy package certainly plays a fundamental role here too. However, I suspect that the high-dose vitamin D intake makes a decisive contribution. My vitamin D level has improved from 18 ng/ml - measured after my first heart attack - to 100 ng/ml. Jeff Bowles had similar experiences with vitamin D in his unconventional experiment (described in the book "The Miraculous Results of Extremely High Doses of the Sunshine Hormone Vitamin D3". 
            <a href="#Ref8" target="_blank">[8]</a>. Michael Holick also discusses autoimmune diseases and vitamin D in his book "The Vitamin D Solution" 
            <a href="#Ref9" target="_blank">[9]</a>.
            </p>
            <p style="padding-bottom:10px;">In the last 6 years I have not had a cold or flu. I attribute this in particular to the high-dose intake of vitamin C and vitamin D in particular, but also to the combined effect with magnesium and the other micronutrients that strengthen the immune system (e.g. zinc, selenium). I have also been spared coronavirus-related illnesses.
            </p>
            <p style="padding-bottom:20px;">All of this seems an unbelievable result for conventional medicine that mainly relies on drugs from pharmaceutical companies. I am tempted to illustrate the helplessness of this medicine with the advice of one of its representatives. To deal with Raynaud's syndrome, he advised me to place my hands under my armpits or buttocks to protect them when it is cold, e.g. in the car. He himself would always do this with his hands, which are also affected by this condition. Apart from wishing him a safe journey at all times, there is nothing more to add.
            </p>
            <h3>Disclaimer</h3>
            <p style="padding-bottom:10px;">I am not a doctor and therefore advise you to consult your doctor if you wish to use any of the experiences I have gained from my self-experiment. These are my personal experiences and do not constitute medical advice. Do not discontinue any medication without the consent of your doctor.
            </p>
            <p style="padding-bottom:10px;"><i>
            ( Hans W. Diel has been dealing specifically with the issue of lipoprotein(a) and the question of effective treatment options since his heart attack 12 years ago. After a second heart attack, he carried out a 5-year self-experiment on lipoprotein(a) therapy and the healing of his heart disease with natural remedies. He is the author of the book "Lipoprotein(a) - Der größte Risikofaktor für Herzinfarkt und Schlaganfall?" 
            </i>You can contact the author by email: <a href="mailto:hwdiel@icloud.com" target="_blank">hwdiel@icloud.com</a> )
            </p>
            <div style="font-family: Georgia,'Times New Roman',Times,serif; font-size: small; border-top: 1px solid #cccccc; padding: 0.25rem 0 0.25rem 0; border-bottom: 1px solid #cccccc; color: #333333;">
                <p>
                    <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnN1YnNjcmliZS5odG1sJTNGdXRtX3NvdXJjZSUzREFjdGl2ZUNhbXBhaWduJTI2dXRtX21lZGl1bSUzRGVtYWlsJTI2dXRtX2NvbnRlbnQlM0RTaWRlJTJCQmVuZWZpdHMlMjUyQyUyQk5vdCUyQlNpZGUlMkJFZmZlY3RzJTI2dXRtX2NhbXBhaWduJTNEU2lkZSUyQkJlbmVmaXRzJTI1MkMlMkJOb3QlMkJTaWRlJTJCRWZmZWN0cw==&amp;sig=Da4KVPF7zHhdfaTwv7FdQWFAzCJqWAHtfQykN6naPpZa&amp;iat=1708629183&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=XN8jRrkgqtzAN2sja9Md25L6Erjgs4lhzXqdFULbldIThGWv%3ADjuBKSkdW2L9THgTllkM96SCZhzsd66l&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=305A304A1A14562">OMNS free subscription</a>
                </p>
                <p>
                    <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZpbmRleC5zaHRtbCUzRnV0bV9zb3VyY2UlM0RBY3RpdmVDYW1wYWlnbiUyNnV0bV9tZWRpdW0lM0RlbWFpbCUyNnV0bV9jb250ZW50JTNEU2lkZSUyQkJlbmVmaXRzJTI1MkMlMkJOb3QlMkJTaWRlJTJCRWZmZWN0cyUyNnV0bV9jYW1wYWlnbiUzRFNpZGUlMkJCZW5lZml0cyUyNTJDJTJCTm90JTJCU2lkZSUyQkVmZmVjdHM=&amp;sig=7tpqihMND1qPa9WXquGtPQ2EWsXUCjJLFahyKMmVNx1b&amp;iat=1708629183&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=XN8jRrkgqtzAN2sja9Md25L6Erjgs4lhzXqdFULbldIThGWv%3ADjuBKSkdW2L9THgTllkM96SCZhzsd66l&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=305A304A1A14563">OMNS Archives</a>
                </p>
            </div>
            <h3>References</h3>
            <p id="Ref1" style="padding-bottom:10px;">1. Diel HW (2022) Lipoprotein(a): The biggest factor for heart attack and stroke? My self-experiment with the Pauling therapy and vitamin C. Orthomolecular Medicine News Service, 
            <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MThuMjcuc2h0bWwlM0Z1dG1fc291cmNlJTNEQWN0aXZlQ2FtcGFpZ24lMjZ1dG1fbWVkaXVtJTNEZW1haWwlMjZ1dG1fY29udGVudCUzRFNpZGUlMkJCZW5lZml0cyUyNTJDJTJCTm90JTJCU2lkZSUyQkVmZmVjdHMlMjZ1dG1fY2FtcGFpZ24lM0RTaWRlJTJCQmVuZWZpdHMlMjUyQyUyQk5vdCUyQlNpZGUlMkJFZmZlY3Rz&amp;sig=EAF9AM1fpUoCUhL1ip8Ugzp4cxXNXJdbHNdNsHvLqHnW&amp;iat=1708629183&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=XN8jRrkgqtzAN2sja9Md25L6Erjgs4lhzXqdFULbldIThGWv%3ADjuBKSkdW2L9THgTllkM96SCZhzsd66l&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=305A304A1A14572" target="_blank">http://orthomolecular.org/resources/omns/v18n27.shtml</a>
            </p>
            <p id="Ref2" style="padding-bottom:10px;">2. Pauling L (1986) How to Live Longer and Feel Better. (2006 Revised Ed) OSU Press, ISBN 9780870710964.
            </p>
            <p id="Ref3" style="padding-bottom:10px;">3. Diel H, Maki J (2022) Lipoprotein(a) - Der größte Risikofaktor für Herzinfarkt und Schlaganfall? (translated: Lipoprotein(a) - The biggest risk factor for heart attack and stroke?) Druckpunkt Ruhr, ISBN 9783982424507.
            </p>
            <p id="Ref4" style="padding-bottom:10px;">4. Dyerberg J, Passwater R. (2012) The Missing Wellness Factors - EPA and DHA. Basic Health Publications, ISBN 9781591203001.
            </p>
            <p id="Ref5" style="padding-bottom:10px;">5. Sears W, Sears J (2012) The Omega-3 Effect. Little Brown and Co., ISBN 9780316196840.
            </p>
            <p id="Ref6" style="padding-bottom:10px;">6. Brownstein D (2006) Salt Your Way to Health. Medical Alternative Press, ISBN 978-0966088243.
            </p>
            <p id="Ref7" style="padding-bottom:10px;">7. Dinicolantonio J (2017) The Salt Fix. Piatkus, ISBN 9780349417387.
            </p>
            <p id="Ref8" style="padding-bottom:10px;">8. Bowles J (2014) The Miraculous Results of Extremely High Doses of the Sunshine Hormone Vitamin D3. Jeff T Bowles Publishing LLC, ASIN B005FCKN25.
            </p>
            <p id="Ref9" style="padding-bottom:10px;">9. Holick M (2010) The Vitamin D Solution. Plume Books, ISBN 9780452296886.
            </p>
    </div>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/why-isn-t-dental-health-considered-primary-medical-care</id>
    <published>2024-03-25T11:50:30-07:00</published>
    <updated>2024-03-25T11:50:30-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/why-isn-t-dental-health-considered-primary-medical-care"/>
    <title>Why isn’t dental health considered primary medical care?</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<p>The patient’s teeth appeared to be well cared for, but dentist James Mancini did not like the look of his gums. By chance, Mancini knew the man’s physician, so he raised an alert about a potential problem — and a diagnosis soon emerged.</p>
<p>“Actually, Bob had leukemia,” says Mancini, clinical director of the Meadville Dental Center in Pennsylvania.</p><p><a class="read-more" href="https://comparativeguide.com/blogs/news/why-isn-t-dental-health-considered-primary-medical-care">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<p class="article-info"> </p>
<h2>Ailments of the mouth can put the body at risk for a slew of other ills. Some practitioners think dentistry should no longer be siloed.</h2>
<p class="article-byline"><span class="author-byline">By Lola Butcher</span> <span class="pub-date">03.21.2024<span> </span></span></p>
<div class="article-content">
<div class="article-text -drop-cap">
<p>The patient’s teeth appeared to be well cared for, but dentist James Mancini did not like the look of his gums. By chance, Mancini knew the man’s physician, so he raised an alert about a potential problem — and a diagnosis soon emerged.</p>
<p>“Actually, Bob had leukemia,” says Mancini, clinical director of the Meadville Dental Center in Pennsylvania. Though he wasn’t tired or having other symptoms, “his mouth was a disaster,” Mancini says. “Once his physician saw that, they were able to get him treated right away.”</p>
<p>Oral health is tightly connected to whole-body health, so Mancini’s hunch is not surprising. What is unusual is that the dentist and doctor communicated.</p>
<p>Historically, dentistry and medicine have operated as parallel fields: Dentists take care of the mouth, physicians the rest of the body. That is starting to change as many initiatives across the United States and other countries work to integrate oral and whole-body care to more effectively tackle <a href="https://knowablemagazine.org/content/article/health-disease/2021/what-does-mean-have-prediabetes">diabetes</a>, cardiovascular disease, joint replacements and many other conditions. The exact relationship between health of mouth and teeth and physical ailments elsewhere in the body is not well understood — and in some cases, is contentious — but experts agree there are links that should no longer be overlooked.</p>
<p>In recent years, dental hygienists have started working in medical clinics; physicians and dentists have started a professional association to promote working together; and a new kind of clinic — with dentists and doctors under one roof — is emerging.</p>
<p>“We are at a pivotal point — I call it the convergence era — where dentistry is not going to be separated from overall health for much longer,” says Stephen E. Thorne IV, founder and CEO of Pacific Dental Services, based in Irvine, California. “Dentistry will be brought into the primary care health-care team.”</p>
<h2>Sick mouth, sick body</h2>
<p>The list of connections between <a href="https://pubmed.ncbi.nlm.nih.gov/29099363/">oral health and systemic health</a> — conditions that affect the entire body — is remarkable. For starters, three common dental issues — cavities, tooth loss and periodontal disease — are all associated with heart disease, the leading cause of death in the United States. “To me, the number one hidden risk factor for the number one killer in our country is oral health,” says Ellie Campbell, a family physician in Cumming, Georgia, and board member of the <a href="https://www.aaosh.org/">American Academy for Oral Systemic Health</a>, founded in 2010 to increase awareness of how oral and whole-body health are related.</p>
<p>Periodontal disease, infection and inflammation of the gums and bone that support the teeth, is the main culprit. Nearly half of adults 30 and older have periodontal disease; by age 65, the rate climbs to about 70 percent. In the early stages, called gingivitis, gums are swollen and may bleed. Periodontitis, a more serious condition in which gums can pull away from the teeth, is the sixth most common human disease.</p>
<p>Periodontitis is associated with a slew of <a href="https://www.sciencedirect.com/science/article/pii/S0020653920317974">systemic ills</a>: heart attacks, strokes, heart failure, diabetes, endocarditis, chronic kidney disease, recurrent pneumonia, chronic obstructive pulmonary disease, gastritis, rheumatoid arthritis, cancer and cognitive impairment.</p>
<p>Bad habits, including tobacco use, alcohol consumption and high-sugar diets, are implicated too. They raise the risk for cavities and most oral diseases, and are also linked to ills such as cancer, chronic respiratory disease and diabetes.</p>
<div class="article-image -caption-center"></div>
<p>Such connections were apparently lost on officials at the University of Maryland in 1837, when the university rebuffed a proposal from two physicians to teach dentistry to the school’s medical students. At the time, <a href="https://historyofdentistryandmedicine.com/">medicine wanted nothing to do with dentistry</a>, which was practiced by unregulated and inadequately trained itinerants, says medical and dental historian Andrew I. Spielman, a dentist and oral surgeon at the New York University College of Dentistry. “There were a lot of charlatans,” he says. “They had a very bad reputation.”</p>
<p>The dismissal prompted the rejected physicians, Horace Hayden and Chapin Harris, to establish the world’s first dental school, the Baltimore College of Dental Surgery. Today, dentistry is a highly regulated profession, and the United States has 73 accredited dental schools.</p>
<p>Despite their disparate training, both doctors and dentists are aware that mouth health is important to whole-body health, Campbell says. “Ask a family practice doctor and they will say ‘Oh yeah, if the patient has diabetes, they’re going to have bad teeth and gums, and I can never get their diabetes better until the dentist fixes their gums,’” she says. “And the dentist is going to say, ‘Well, I’ll never get their gums better until the primary care doctor gets their sugar under control.’”</p>
<p>Mancini, the Pennsylvania dentist, says dentists often are asked to examine a patient’s mouth before physicians will proceed with certain treatments. “Physicians know any infection in a patient who’s being treated for cancer could be very much life-threatening,” he says. “The orthopedic guys are now sending all of their patients to the dentist for the same reason.”</p>
<h2>Hurdles to holistic care</h2>
<p>But working together to improve a patient’s health is not as simple as it might seem. A decade ago, the federal government hired the <a href="https://www.nnoha.org/">National Network for Oral Health Access</a> to run a pilot program merging oral and primary health-care centers. The network’s dental consultant, Irene Hilton, a dentist with the San Francisco Department of Public Health, said three barriers to integration became clear.</p>
<p>The fragmented <a href="https://www.annualreviews.org/content/journals/10.1146/annurev-publhealth-040119-094318">way that health care and dental care are paid for</a> is one of them. While more than 90 percent of Americans have health insurance, only 77 percent of US adults ages 19 to 64 have dental coverage, which typically is sold separately from health insurance. The nation’s largest insurer — the federal Medicare program — generally does <a href="https://www.kff.org/medicare/issue-brief/medicare-and-dental-coverage-a-closer-look/">not cover dental services</a>, and nearly half of Americans 65 and over have no dental coverage.</p>
<p>That causes problems for patients who need, say, a joint replacement that would be covered by insurance but who cannot afford the dental work that is needed in advance. Surgeons won’t replace a knee until patients first get their dental work done, Mancini says, “so we’re kind of the barrier to them improving their life.”</p>
<div class="article-image -caption-center"></div>
<p>Another barrier is that dentists and physicians are not routinely trained to work with each other, Hilton says.</p>
<p>Dental students study anatomy, physiology and other sciences related to the whole body, then home in on clinical care for mouth and teeth. But many physicians have almost no training in oral health. A 2009 survey found that 10 percent of medical schools that responded offered <a href="https://journals.lww.com/academicmedicine/fulltext/2011/02000/teaching_oral_health_in_u_s__medical_schools_.23.aspx">no oral health curriculum</a>, and 69 percent offered fewer than five hours on the subject.</p>
<p>A third issue is what Hilton calls infrastructure. In most cases, the electronic health records used by physicians are incompatible with those used by dentists, so sharing information electronically is impossible. Likewise, dental offices are typically not embedded in medical clinics, where doctor-dentist referrals might be easier.</p>
<p>If oral and systemic health are to be integrated broadly, “these are the things that have to be overcome or addressed,” Hilton says.</p>
<p>The situation is not much different in other parts of the world. In 2021 the World Health Organization — noting that oral diseases are a <a href="https://www.who.int/news-room/fact-sheets/detail/oral-health">global public health problem</a> affecting nearly 3.5 billion people — recommended that dentistry focus more on prevention and be more integrated with primary care services.</p>
<div id="newsletter-promo-item">
<div class="newsletter-promo" style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;">
<div class="newsletter-promo-img" style="display: grid;"></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a href="https://knowablemagazine.org/newsletter-signup" style="border-bottom: none;"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<h2>Demonstrated links</h2>
<p>In the past quarter-century, a great deal of research has demonstrated the links between oral and whole-body health. For example, when researchers followed 15,456 patients from 39 countries with stable coronary heart disease for nearly four years, they found that those who <a href="https://academic.oup.com/eurjpc/article/23/8/839/5927389">had lost the most teeth had the highest risk</a> of having a stroke, heart attack or cardiovascular death. Similarly, a study that tracked 7,466 US adults ages 44 to 66 for an average of 14.7 years revealed that those <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093423/">who had severe periodontitis had a greater risk of cancer</a> than those with no or mild periodontitis.</p>
<p>In 2015, the Harvard School of Dental Medicine launched <a href="https://oralhealth.hsdm.harvard.edu/">an initiative to support integration</a> of the two fields — in education, insurance and professional practice. (The initiative gets funding from dental product brands and health insurance companies, and Thorne, the Pacific Dental Services CEO, serves on its board.) “We’ve published papers identifying links between periodontal disease and diabetes, hypertension, dementia, adverse birth outcomes, low birth-weight babies, preterm birth, spontaneous abortion, kidney disease,” says Jane Barrow, the initiative’s executive director.</p>
<p>But correlation is not the same as cause and effect, and scientists have not nailed down the exact relationship between periodontitis, which affects <a href="https://www.nature.com/articles/6401037">more than 11 percent of the global population</a>, and various systemic diseases.</p>
<p>Periodontitis is associated with bacteria in the bloodstream and systemic inflammation, which can affect organs such as the liver and bone marrow. That, in turn, can trigger or aggravate other conditions. And the <a href="https://knowablemagazine.org/content/article/living-world/2019/oral-microbiome">periodontal bacteria</a> — that travel via the bloodstream, inhalation or ingestion — may also cause infections or exacerbate inflammation in other parts of the body.</p>
<p>When the major professional societies for periodontology in the United States and Europe convened a group of global experts in 2012 to review the science, they concluded that it was “biologically plausible” that the inflammation of periodontitis ups the risk of cardiovascular disease and influences type 2 diabetes and other maladies – but “plausible” was as far as they would go.</p>
<p>Seven years later, the European Federation of Periodontology and the World Heart Federation again gathered experts to review new studies on the link between periodontitis and cardiovascular problems. Again, though scientists had made some headway in identifying possible biological mechanisms to explain the link, experts have since concluded that the <a href="https://www.sciencedirect.com/science/article/pii/S0020653921001386">evidence does not yet prove</a> that periodontitis actually <em>causes</em> strokes, heart attacks or anything else.</p>
<p>Flipping the question on its head, does preventing or treating periodontal disease help to prevent heart problems? Several observational studies, in which researchers observe individuals and measure particular outcomes, but don’t intervene, suggest that oral health care, including toothbrushing and dental cleanings, make a difference. For example, a study that tracked the health habits of 11,869 adults 35 and older in Scotland found that within eight years, those who <a href="https://www.bmj.com/content/340/bmj.c2451">rarely brushed their teeth had more cardiovascular problems</a> compared with those who brushed twice a day.</p>
<div class="article-image -caption-center"></div>
<p>That still does not prove that preventing periodontitis will hold heart problems at bay: Some other habit or feature of the toothbrushing group could have been the important factor. The relationship is difficult to tease out, Barrow says, because people who are taking good care of their mouths tend to take good care of themselves in general. “Could you say that people who are taking care of their mouths are in better health overall? You would probably find that to be true,” she says. “Is it because they’re taking care of their mouth? I can’t say that.”</p>
<p>And nobody else should say that either, according to a 2018 editorial in the <em>Journal of the American Dental Association</em>. The coauthors, a group of dental and public health researchers, cautioned against <a href="https://jada.ada.org/article/S0002-8177(18)30240-X/fulltext">overstating the oral-systemic health connection</a>. “The main reason for maintaining good oral health is because it is important in and of itself,” they wrote.</p>
<p>One of the contributors, Bryan Michalowicz, a dental researcher at HealthPartners Institute in Minnesota, later led a team that reviewed the medical records and insurance claims of 9,503 patients to see if periodontitis treatment improved the health outcomes of those with coronary artery disease, cerebrovascular disease or type 2 diabetes.</p>
<p>Overall, cardiovascular patients who received <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290028">dental treatment and follow-up maintenance saw no difference</a> in the rate of heart attacks, strokes, bypass surgeries or angioplasty procedures compared to those who were not treated, the team reported in 2023. Likewise, periodontal treatment did not significantly lower the blood-sugar levels in patients with type 2 diabetes.</p>
<h2>Overdue integration</h2>
<p>But the data suggesting connections have been enough to spark many grassroots efforts at integration. In addition to the American Academy for Oral Systemic Health, the <a href="https://www.healthcarehygienists.org/">National Network of Healthcare Hygienists</a>, founded by hygienist Jamie Dooley in 2018, helps prepare hygienists who want to integrate oral health into health-care systems.</p>
<p>And in California, Thorne’s business is trying to make those interactions easy by putting dental and medical services under one roof. In December 2023, Pacific Dental Services opened a clinic, Culver Smiles Dentistry, in a space shared with a medical practice. It’s the first of 25 planned dental-medical practices that will operate through a partnership between <a href="http://www.memorialcare.org/">MemorialCare</a>, a big Southern California health system, and Pacific Dental.</p>
<p>Health-care leaders, Thorne says, are beginning to realize that they can improve their patients’ health by incorporating dental care into primary care.</p>
<p>It’s sort of crazy, he says, that our mouth and our jaw and our throat have been considered separate from the rest of our body for so long. “It is changing now, and health care is realizing that the mouth is the gateway to so much of our overall health.”</p>
</div>
</div>
<link rel="canonical" href="https://knowablemagazine.org/content/article/health-disease/2024/why-isnt-dental-health-considered-primary-medical-care"> <meta name="syndication-source" content="https://knowablemagazine.org/content/article/health-disease/2024/why-isnt-dental-health-considered-primary-medical-care" doi="10.1146/knowable-032124-1">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/how-gut-bacteria-connect-to-parkinson-s-disease</id>
    <published>2024-03-18T06:00:07-07:00</published>
    <updated>2024-03-18T06:00:07-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/how-gut-bacteria-connect-to-parkinson-s-disease"/>
    <title>How gut bacteria connect to Parkinson’s disease</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<span data-mce-fragment="1">Roughly a million people in the United States (and roughly 10 million people worldwide) live with Parkinson’s disease, a potent neurological disorder that progressively kills neurons in the brain. A growing number of studies are suggesting that it may be tied to an unlikely culprit: bacteria living inside our guts.</span><p><a class="read-more" href="https://comparativeguide.com/blogs/news/how-gut-bacteria-connect-to-parkinson-s-disease">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<p class="article-info"> </p>
<p class="article-subhead" style="font-size: large; font-style: italic;">Growing evidence suggests a link between the debilitating neurological illness and the microbes that live in our intestines. The vagus nerve may be a pathway.</p>
<p style="font-weight: bold; text-decoration: underline; text-underline-offset: 0.5rem;" class="article-byline"><span class="author-byline">By David Levin</span> <span class="pub-date">01.11.2024<span> </span></span></p>
<div class="article-content">
<div class="article-text -drop-cap">
<p>It can start small: a peculiar numbness; a subtle facial tic; an inexplicably stiff muscle. But then time goes by — and eventually, the tremors set in.</p>
<p>Roughly a million people in the United States (and roughly 10 million people worldwide) live with Parkinson’s disease, a potent neurological disorder that progressively kills neurons in the brain. As it does so, it can trigger a host of crippling symptoms, from violent tremors to excruciating muscle cramps, terrifying nightmares and constant brain fog. While medical treatments can alleviate some of these effects, researchers still don’t know exactly what causes the disease to occur in the first place.</p>
<p>A growing number of studies, however, are suggesting that it may be tied to an unlikely culprit: bacteria living inside our guts.</p>
<p>Every one of us has hundreds or thousands of microbial species in our stomach, small intestine and colon. These bacteria, collectively called our gut microbiome, are usually considerate guests: Although they survive largely on food that passes through our insides, they also give back, cranking out essential nutrients like niacin (which helps our body convert food into energy) and breaking down otherwise indigestible plant fiber into substances our bodies can use.</p>
<p>As Parkinson’s advances in the brain, researchers have reported that the species of bacteria present in the gut also shift dramatically, hinting at a possible cause for the disease. A 2022 paper published in the journal <em>Nature Communications </em><a href="https://www.nature.com/articles/s41467-022-34667-x">recorded those differences in detail</a>. After sequencing the mixed-together genomes of fecal bacteria from 724 people — a group with Parkinson’s and another without — the authors saw a number of distinct changes in the guts of people who suffered from the disease.</p>
<p>The Parkinson’s group had dramatically lower amounts of certain species of <em>Prevotella</em>, a type of bacterium that helps the body break down plant-based fiber (changes like this in gut flora could explain why people with Parkinson’s disease often experience constipation).<sup> </sup>At the same time, the study found, two harmful species of Enterobacteriaceae, a family of microbes that includes <em>Salmonella</em>, <em>E. coli</em> and other bugs, proliferated. Those bacteria may be involved in a chain of biochemical events that eventually kill brain cells in Parkinson’s patients, says Tim Sampson, a biologist at Emory University School of Medicine and coauthor of the study.</p>
<p>At first glance, the relationship between bacteria and brain disease isn’t exactly obvious. How can a change in gut microbes kick off a devastating neurodegenerative disorder? The relationship between the two may seem counterintuitive — but Sampson says it comes down to the subtle <a href="https://knowablemagazine.org/content/article/mind/2024/gut-brain-axis-mental-health-microbiome">ways that the brain and the gut are connected</a>.</p>
<div class="article-image -caption-right"></div>
<p>In the walls of the intestines, a network of neurons called the enteric nervous system lets the body sense what’s going on in the gut and respond accordingly. This circuitry controls muscle movement, local blood flow, secretion of mucus and other essential digestive functions.</p>
<p>Since the cells of the enteric nervous system are embedded in the gut wall, many of them come into close contact with the lumen — the cavity of the gut that contains the <a href="https://knowablemagazine.org/content/article/living-world/2017/getting-know-gut-microbiome">microbiome</a> ­— where they can interact directly with biochemicals created by bacteria. Some of these are sticky proteins called curli (pronounced CURL-eye) that may be implicated in Parkinson’s.</p>
<p>Under normal circumstances, curli proteins let Enterobacteria build biofilms, the gooey mats that protect the microbes and help them stay put in the gut. Yet if a curli molecule touches a common protein created by nerve cells — called alpha-synuclein — that protein begins to misfold and form a dangerous mass called an aggregate. Once created, these aggregates can spread widely though the nervous system, leapfrog from cell to cell and eventually enter the brain through the vagus nerve, the main pathway that carries signals between the brain and the gut. It’s thought that in some cases of Parkinson’s in humans, changes in the gut microbiome may activate that process, says Emeran Mayer, a gastroenterologist and neuroscientist at UCLA and coauthor of a recent <a href="https://www.annualreviews.org/doi/10.1146/annurev-med-042320-014032">overview of the gut-brain connection</a> in the <em>Annual Review of Medicine</em>.</p>
<div class="article-video -full-width">
<div class="video-container">
<p><span draggable="true" class="fr-video fr-fvc fr-dvb fr-draggable" contenteditable="false"><iframe class="fr-draggable" src="https://www.youtube.com/embed/DYwhqZuxSp8?wmode=opaque" height="360" width="640" allowfullscreen="" frameborder="0"></iframe></span></p>
</div>
<div class="article-video-caption">
<div class="caption">
<p>This video shows the structure of fibrils of alpha-synuclein, toxic particles that are implicated in Parkinson’s disease, as determined by scientists through cryo-electron microscopy.</p>
</div>
<p class="source">CREDIT: R. GUERRERO-FERREIRA <em>ET AL / eLIFE</em> 2018</p>
</div>
</div>
<p>Suspicion that the vagus plays a key role in neurodegenerative disease has been growing in recent years. A <a href="https://pubmed.ncbi.nlm.nih.gov/28446653">2017 study in the journal <em>Neurology</em></a><em>, </em>Mayer notes, showed that “If you cut the vagus nerve, it decreases the risk for Parkinson’s disease. That’s a pretty strong indication that … this degenerative material is transported, apparently, through the vagus nerve.”</p>
<p>Over the past few decades, a number of animal studies have shown that the vagus provides a physical conduit that molecules can use to move between the gut and brain — but although this neurological superhighway could play an important role in Parkinson’s, it’s still not clear if the nerve is a lynchpin in causing the disease itself.</p>
<div class="article-image -caption-center"></div>
<p>In addition to aggregates moving through the vagus, different triggers — like the lipids, vitamins and other organic compounds that gut bacteria produce — could travel through blood vessels to the brain, where they may cause inflammation and damage tissue. Likewise, says David Hafler, a neuroimmunologist at Yale University, immune cells that are activated in the gut may contribute to the neurological damage and dysfunction that occurs in Parkinson’s.</p>
<p>These immune cells, called T cells, can migrate out of the gut, enter the bloodstream and cross the blood-brain barrier, where they ultimately may kill off neurons. This sort of autoimmune response is the driver for other neurological diseases like multiple sclerosis, Hafler reasons, so it’s feasible that it plays a role in Parkinson’s as well. In both diseases, changes in the gut microbiome could be the potential trigger.</p>
<p>There’s already strong evidence for this idea. In 2016, Sampson found a direct connection between gut microbes and Parkinson’s disease: Using fecal samples from Parkinson’s patients, Sampson inoculated the guts of germ-free mice (animals with no naturally occurring microbiome), and the animals quickly <a href="https://www.cell.com/fulltext/S0092-8674(16)31590-2">developed Parkinson’s symptoms</a>. Today, using the new genetic survey of gut microbes he and his colleagues published in <em>Nature Communications</em>, he’s narrowing in on a few microbe families and using similar methods to reveal which precise species are the culprits.</p>
<p>Sampson’s approach comes with some caveats: Parkinson’s disease, after all, might be linked to multiple bacteria interacting in complex ways — so there likely won’t be a single smoking gun. It’s also not totally clear if changes in the microbiome are the root cause or if they just accelerate damage already taking place in the brain. The complexity of the microbiome is mind-boggling: There are hundreds of different types of bacteria involved, and each creates myriad molecules that affect digestion, the immune system and other important bodily functions.<sup> </sup>Sorting through all those components and identifying how they change in the face of disease will be an important next step.</p>
<div id="newsletter-promo-item">
<div style="background-color: #fff; border-top: 4px solid #3c7680; border-bottom: 1px solid #3c7680;" class="newsletter-promo">
<div style="display: grid;" class="newsletter-promo-img"></div>
<div class="newsletter-promo-content">
<p><strong>Stay in the Know</strong><br><a style="border-bottom: none;" href="https://knowablemagazine.org/newsletter-signup"><strong>Sign up</strong></a> for the <em>Knowable Magazine</em> newsletter today</p>
</div>
</div>
</div>
<p>And so, as tantalizing as the links between the microbiome and Parkinson’s may be, it could be decades before people who suffer from the disorder can reap any tangible benefits. Many of the researchers examining those links, like Mayer, also warn patients to be of wary of sweeping claims about drugs, supplements or even <a href="https://knowablemagazine.org/content/article/health-disease/2019/fecal-transplant-c-diff">fecal transplants</a> — seeding the gut with microbes from another, healthy person — that “treat” Parkinson’s by altering the microbiome.</p>
<p>“A lot of people make a lot of money selling individuals supplements, telling you that they’re going to slow your cognitive decline or prevent Parkinson’s disease,” says Mayer. But, he adds, “we don’t know the causal roles of the microbiome for sure. We know it from animal studies, so we have indirect evidence for it — but it’s been difficult to show in humans without a doubt that the microbes, and some of their signal molecules, play the main causal role.”<sup> </sup></p>
<p>Until definitive answers are found, researchers like Mayer will continue to chip away at the problem, microbe by microbe.</p>
</div>
</div>
<link href="https://knowablemagazine.org/content/article/health-disease/2024/gut-brain-axis-parkinsons-disease-microbiome" rel="canonical"> <meta doi="10.1146/knowable-011124-1" content="https://knowablemagazine.org/content/article/health-disease/2024/gut-brain-axis-parkinsons-disease-microbiome" name="syndication-source">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/annual-collection-of-top-vitamin-d-publications</id>
    <published>2024-03-11T06:00:02-07:00</published>
    <updated>2024-03-11T06:00:02-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/annual-collection-of-top-vitamin-d-publications"/>
    <title>Annual Collection of Top Vitamin D Publications</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[    <p style="padding-bottom:10px;"><strong>FOR IMMEDIATE RELEASE</strong> 
        <br><strong>Orthomolecular Medicine News Service, March 2, 2024</strong>
    </p>
        <h2 style="padding-top:10px;padding-bottom:20px;"><b>William B. Grant, PhD</b></h2> 
        <p style="padding-bottom:10px;">OMNS (March 2, 2024) The year 2023 marks 100 years after Elmer McCollum discovered vitamin D 
        <a href="#Ref1" target="_blank">[1]</a>. For the first 80 years after the discovery, vitamin D was mostly known for its role in regulating the absorption and metabolism of calcium. Beginning in the last decade of the twentieth century and accelerating in the early twenty-first century, it became apparent that vitamin D's health benefits extended far beyond bones. Many of the benefits occur through the hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D (calcitrol) entering the vitamin D receptor which nearly every cell in the body has, and affecting gene expression 
        <a href="#Ref2" target="_blank">[2]</a>. By 2013, it was apparent that "Adequate vitamin D status seems to be protective against musculoskeletal disorders (muscle weakness, falls, fractures), infectious diseases, autoimmune diseases, cardiovascular disease, type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive dysfunction and mental illness, and other diseases, as well as infertility and adverse pregnancy and birth outcomes." 
        <a href="#Ref3" target="_blank">[3]</a>. Early evidence supporting vitamin D's health benefits came from ecological studies related to sun exposure and season. Later, observational studies based on serum 25-hydroxyvitamin D [25(OH)D] and vitamin D supplementation as well as studies of mechanisms provided additional information. Since the medical system bases approval of pharmaceutical drugs on results from randomized controlled trials (RCTs), they were conducted for vitamin D. Unfortunately, nearly all vitamin D RCTs followed the guidelines for drugs, not nutrients. In drug trials, the only source of the drug is in the trial, the control arm participants receive a placebo, and it is assumed that there is a linear dose-response relationship. Results are evaluated on the basis of intention to treat, comparing results for those in the treatment arm with those in the control arm. Robert Heaney outlined the guidelines for nutrient trials in 2014 
        <a href="#Ref4" target="_blank">[4]</a>. The key guidelines as applied to vitamin D include measuring serum 25(OH)D concentration of prospective participants and enroll those with low concentrations, supplement with enough vitamin D to raise serum 25(OH)D concentrations to the optimal value for the outcome of interest, measure achieved 25(OH)D concentration and analyze the results based on 25(OH)D concentrations. Very few vitamin D RCTs have followed these guidelines. As a result, few have reported results that convince physicians to recommend vitamin D 
        <a href="#Ref5" target="_blank">[5]</a>. 
        </p>
        <p style="padding-bottom:10px;">Big Pharma became concerned that vitamin D supplementation could impact the income and profit of the drug industry around 2009, and, in response, convened a select committee of physicians and researchers to set guidelines for vitamin D supplementation (5057 Google Scholar citations) 
        <a href="#Ref6" target="_blank">[6]</a>. The recommendation was that people aged 1 to 70 years should take 600 IU/d (15 mcg/d) vitamin D while those 71 and older should take 800 IU/d (20 mcg/d) to achieve &gt; 20 ng/mL (50 nmol/L). This recommendation was based on an incorrect analysis of the vitamin D requirement for bone health 
        <a href="#Ref7" target="_blank">[7]</a>. About the same time, the Endocrine Society recommended higher vitamin D doses for people with vitamin D deficiency in order to achieve &gt; 30 ng/mL, which has over 12,000 Google Scholar citations 
        <a href="#Ref8" target="_blank">[8]</a>. Big Pharma used the Disinformation Playbook to discredit vitamin D (Grant, 2018), and again in 2024 (Aschwanden, 2024).
         </p>
        <p style="padding-bottom:10px;">Grant WB. Vitamin D acceptance delayed by Big Pharma following the Disinformation Playbook. 2018. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cCUzQSUyRiUyRm9ydGhvbW9sZWN1bGFyLm9yZyUyRnJlc291cmNlcyUyRm9tbnMlMkZ2MTRuMjIuc2h0bWw=&amp;sig=4g4biJ8tyiJZJQQaaGwyKeqZeEQ5qQhkCeaT5jfcbQk5&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14587" target="_blank">http://orthomolecular.org/resources/omns/v14n22.shtml</a>
        </p>
        <p style="padding-bottom:10px;">Aschwanden C. How Much Vitamin D Do You Need to Stay Healthy. Sci Am. 2024. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuc2NpZW50aWZpY2FtZXJpY2FuLmNvbSUyRmFydGljbGUlMkZob3ctbXVjaC12aXRhbWluLWQtZG8teW91LW5lZWQtdG8tc3RheS1oZWFsdGh5JTJG&amp;sig=HcEATeE9KHQT5Q6zQhah23oEcYmh5DaL48coj7dr3zVt&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14588" target="_blank">https://www.scientificamerican.com/article/how-much-vitamin-d-do-you-need-to-stay-healthy/</a> 
        </p>
        <p style="padding-bottom:10px;">For this year's top vitamin D publications, I searched the databases Google Scholar and SCOPUS, both of which show how many citations each publication has. Google Scholar is open access and generally indicates the URL for an open-access version of the publication. SCOPUS is not open access. I tried to find good representative publications in a variety of topics likely of interest to physicians, especially those interested in health maintenance and disease prevention rather than treatment. For each publication, I extracted about 100 words from the abstract.
        </p>
        <p style="padding-bottom:10px;">Conversions: 50 nmol/L = 20 ng/mL; 1 mcg vitamin D = 40 IU (125 mcg = 5,000 IU); 1 mmol calcium = 40 mg; 1 mmol phosphorus = 30 mg
        </p>
        <h3>Autoimmune diseases</h3>
        <p style="padding-bottom:20px;">Vitamin D deficiency has been observed in patients with rheumatoid arthritis (RA) and has been shown to be inversely related to disease activity, and vitamin D deficiency (VDD) may be implicated in the pathogenesis of the disease. VDD has also been observed in patients with systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, and idiopathic inflammatory myopathies. VDD has also been observed in systemic sclerosis. VDD may be implicated in the pathogenesis of autoimmunity, and it may be administered to prevent autoimmune disease and reduce pain in the context of autoimmune rheumatic disorders. 
        <a href="#Ref9" target="_blank">[9]</a>
        </p>
        <h3>Cancer</h3>
        <p style="padding-bottom:10px;">A post hoc subgroup of a vitamin D placebo-controlled trial found that 2000 IU/d vitamin D greatly reduced the risk of death for digestive cancer patients with p53 immunoreactive, defined by positivity for anti-p53 antibodies in serum and nuclear accumulation of p53 oncosuppressor protein in more than 99% of cancer cells, In the p53-immunoreactive subgroup (80 patients), 5-year relapse-free survival was significantly higher in the vitamin D group (13 patients [80.9%]) than the placebo group (1 patient [30.6%]; hazard ratio (HR), 0.27; 95% CI, 0.11-0.61; P = 0.002). 
        <a href="#Ref10" target="_blank">[10]</a>
        </p>
        <p style="padding-bottom:20px;">See this accompanying editorial 
        <a href="#Ref11" target="_blank">[11]</a>
        </p>
        <h3>Cardiovascular disease</h3>
        <p style="padding-bottom:10px;">"<b>Results:</b> Of the 1,321 records identified using the search strategy, a total of 19 cohort studies were included in the final meta-analysis. The pooled estimate of HR (95% CI) for low vs. high circulating 25(OH)D level was 1.75 (1.49-2.06) with I² value of 30.4%. In subgroup analysis, strong effects of circulating vitamin D were observed in healthy general population (pooled HR, 1.84; 95% CI, 1.43-2.38) and the clinical endpoint of sudden cardiac death (pooled HRs, 2.68; 95% CI, 1.48-4.83). The dose-response analysis at the reference level of &lt;50 nmol/L showed a significant negative association between circulating 25(OH)D and risk of sudden cardiac death and cardiovascular disease mortality." <a href="#Ref12" target="_blank">[12]</a>
        </p>
        <h3>Cerebrovascular disorder</h3>
        <p style="padding-bottom:10px;">"Vitamin D modulates the various molecular pathways, i.e., Nitric Oxide, PI3K-Akt Pathway, cAMP pathway, NF-kB Pathway, Sirtuin 1, Nrf2, FOXO, in cerebrovascular disorder. The current review shows evidence for vitamin D's mitigating or slowing the progression of these cerebrovascular disorders, which are significant causes of disability and death worldwide." 
        <a href="#Ref13" target="_blank">[13]</a>
        </p>
        <h3>Circulatory system</h3>
        <p style="padding-bottom:20px;">"This brief overview focuses on the cardiovascular and cerebrovascular effects of VitD and the cellular, molecular, and functional changes that occur in the circulatory system in VitD deficiency (VDD). It explores the links among VDD and adverse vascular remodeling, endothelial dysfunction, vascular inflammation, and increased risk for cardiovascular and cerebrovascular diseases. Improved understanding of the complex role of VDD in the pathogenesis of atherosclerotic cardiovascular diseases, stroke, and vascular cognitive impairment is crucial for all cardiologists, dietitians, and geriatricians, as VDD presents an easy target for intervention." 
        <a href="#Ref14" target="_blank">[14]</a>
        </p>
        <h3>Dementia</h3>
        <p style="padding-bottom:10px;">"We prospectively explored associations between vitamin D supplementation and incident dementia in 12,388 dementia-free persons from the National Alzheimer's Coordinating Center.
        </p>
        <p style="padding-bottom:20px;"><b>Highlights:</b> In a prospective cohort study, we assessed effects of Vitamin D on dementia incidence in 12,388 participants from the National Alzheimer's Coordinating Center dataset. Vitamin D exposure was associated with 40% lower dementia incidence versus no exposure. Vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment. Vitamin D effects were significantly greater in apolipoprotein E ε4 non-carriers versus carriers. Vitamin D has potential for dementia prevention, especially in the high-risk strata." 
        <a href="#Ref15" target="_blank">[15]</a>
        </p>
        <h3>Depression and anxiety</h3>
        <p style="padding-bottom:10px;">"<b>Results:</b> We identified 20 RCTs that matched all eligibility criteria, totaling 2,256 subjects, diagnosed with MDD, GAD, and depressive or anxiety symptoms. Supplementation with folic acid or L-methylfolate, B1, B12 or methylcobalamin, and vitamin D (in different doses and study duration) significantly decreased depression score scales by increasing response to standard pharmacological treatment or as monotherapy, including partial or complete remission. As for anxiety symptoms, the availability of results is limited to adjuvant vitamin D therapy." 
        <a href="#Ref16" target="_blank">[16]</a>
        </p>
        <p style="padding-bottom:20px;">"Ten meta-analyses of randomised controlled trials (RCTs) revealed significant reduction in depression symptoms comparing participants on vitamin D supplements to those on placebo (Pooled standardised mean difference: - 0.40; 95 % CI: - 0.60, - 0.21, p &lt;0.01: I2=89.1 %, p &lt; 0.01). Four meta-analyses of cohort studies (with one having two subgroups) revealed that participants with lower levels of serum 25(OH)D were at increased odds of depression than those with higher levels of serum 25(OH)D (Pooled odds ratio: 1.60; 95 % CI: 1.08, 2.36, p &lt; 0.01; I2=91.3 %, p &lt; 0.01."
        <a href="#Ref17" target="_blank">[17]</a>
        </p>
        <h3>Diabetes mellitus type 2</h3>
        <p style="padding-bottom:20px;">"Three randomized trials regarding vitamin D supplementation in prediabetic patients were included. Vitamin D reduced risk for diabetes by 15% (HR, 0.85 [95% CI, 0.75 to 0.96. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25(OH)D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (HR, 0.24 [CI, 0.16 to 0.36]). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46])." 
        <a href="#Ref18" target="_blank">[18]</a>
        </p>
        <h3>Foot ulcers</h3>
        <p style="padding-bottom:20px;">"<i>Materials and methods.</i> We included people with diabetes with one or more foot ulcers lasting for more than 6 weeks. Patients were randomly allocated to either a daily oral intake of high-dose (6800 IU/d or 170 μg/d) or low-dose (800 IU/ or 20 μg/d) vitamin D3. Findings/results. The intention-to-treat analysis showed a significantly higher rate of ulcer healing in the high-dose group with 21 of 30 (70%) healed ulcers compared to 12 of 34 (35%) in the low-dose group (P = 0.01). Median ulcer reduction at final follow-up was 100% in the high-dose group and 57% in the low-dose group." 
        <a href="#Ref19" target="_blank">[19]</a>
        </p>
        <h3>Microvascular complications</h3>
        <p style="padding-bottom:10px;">"<b>Research design and methods:</b> This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. 
        </p>
        <p style="padding-bottom:10px;"><b>Results:</b>  Compared with participants with 25(OH)D &lt;25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. </p>
        <p style="padding-bottom:20px;"><b>Conclusions:</b>  Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications." 
        <a href="#Ref20" target="_blank">[20]</a>
        </p>
        <h3>Respiratory tract infections</h3>
        <p style="padding-bottom:10px;">"<b><b>Results:</b> </b>This study included 31,466 United States adults ≥20 y of age (47.1 y, 55.5% women) with a mean serum 25(OH)D concentration of 66.2 nmol/L. After adjustments, compared with participants with a serum 25(OH)D concentration ≥75.0 nmol/L, those with a serum 25(OH)D concentration &lt;30 nmol/L had higher risk of head or chest cold (OR: 1.17; 95% CI: 1.01, 1.36) and other respiratory diseases, including influenza, pneumonia, and ear infections (OR: 1.84; 95% CI: 1.35, 2.51). In the stratification analyses, lower serum 25(OH)D concentrations were associated with a higher risk of head or chest cold in obese adults but not in nonobese adults." <a href="#Ref21" target="_blank">[21]</a>
        </p>
        <h3>Wound healing</h3>
        <p style="padding-bottom:20px;">"<b>Conclusion:</b> Vitamin D and calcium signaling are critical for the ability of epidermal and hair follicle stem cells to respond to wounding. VDD with the accompanying decrease in calcium signaling can result in delayed and/or chronic wounds, a major cause of morbidity, loss of productivity, and medical expense." 
        <a href="#Ref22" target="_blank">[22]</a>
        </p>
        <h3>Vitamin D recommendations</h3>
        <p style="padding-bottom:10px;">"The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. 
        </p>
        <p style="padding-bottom:10px;"><b>Results:</b> Based on networking discussions, the ranges of total serum 25(OH)D concentration indicating VDD [&lt;20 ng/mL (&lt;50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of VDD were developed." <a href="#Ref23" target="_blank">[23]</a>
        </p>
        <p style="padding-bottom:20px;">"Maintaining the population's vitamin D sufficiency (above 40 ng/mL) with vitamin D3 supplements and/or daily sun exposure is the most cost-effective way to reduce chronic diseases and sepsis, overcome viral epidemics and pandemics, and reduce healthcare costs. Furthermore, vitamin D sufficiency improves overall health (hence reducing absenteeism), reduces the severity of chronic diseases such as metabolic and cardiovascular diseases and cancer, decreases all-cause mortality, and minimizes infection-related complications such as sepsis and COVID-19-related hospitalizations and deaths. Properly using vitamin D is the most cost-effective way to reduce chronic illnesses and healthcare costs: thus, it should be a part of routine clinical care." 
        <a href="#Ref24" target="_blank">[24]</a>
        </p>
        <h3>FELDMAN AND PIKE'S VITAMIN D</h3>
        <p style="padding-bottom:20px;">This two-volume tome has 50 chapters in Vol.1 and 56 chapters in Vol. 2. The chapters were written by leading authorities in the field of vitamin D research.  The contents of the book are copyright protected. However, it should be possible to obtain the pre-publication content of various chapters by contacting the authors of the chapters. The URLs include the chapter titles. The authors of each chapter can be found by searching Google Scholar with "Hewison, vitamin D" and restricting the search to 2024.
        </p>
        <h3>FELDMAN AND PIKE'S VITAMIN D</h3>
        <p style="padding-bottom:10px;">Volume One: Biochemistry, Physiology and Diagnostics<br>
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZzaG9wLmVsc2V2aWVyLmNvbSUyRmJvb2tzJTJGZmVsZG1hbi1hbmQtcGlrZS1zLXZpdGFtaW4tZCUyRmhld2lzb24lMkY5NzgtMC0zMjMtOTEzODYtNw==&amp;sig=JNaGmTcbK6iaMFhUkbvyXRR3YTfYWE1JWGSFX1Ce5HB&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14589" target="_blank">https://shop.elsevier.com/books/feldman-and-pike-s-vitamin-d/hewison/978-0-323-91386-7</a>
        </p>
        <p style="padding-bottom:20px;">Volume Two: Health, Disease and Therapeutics<br>
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZzaG9wLmVsc2V2aWVyLmNvbSUyRmJvb2tzJTJGZmVsZG1hbi1hbmQtcGlrZS1zLXZpdGFtaW4tZCUyRmhld2lzb24lMkY5NzgtMC0zMjMtOTEzMzgtNg==&amp;sig=3jmwavDceFvRexT1Fxq5ivdREnv49qipTanBwd9QfgwD&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14590" target="_blank">https://shop.elsevier.com/books/feldman-and-pike-s-vitamin-d/hewison/978-0-323-91338-6</a>
        </p>
        <h3>FIFTH EDITION</h3>
        <p style="padding-bottom:10px;">Edited by Hewison M, Bouillon R, Giovannucci E, Goltzman D, Meyer M, Welsh J. <br>
        Academic Press, Elsevier, 2024
        </p>
        <p>
            <strong><a href="http://orthomolecular.org/subscribe.html">OMNS free subscription</a></strong>
            <br><strong><a href="http://orthomolecular.org/resources/omns/index.shtml">OMNS Archives</a></strong>
        </p>        
        <h3>References</h3>
        <p id="Ref1" style="padding-bottom:10px;">1.    Holick, M.F., The One-Hundred-Year Anniversary of the Discovery of the Sunshine Vitamin D(3): Historical, Personal Experience and Evidence-Based Perspectives. Nutrients, 2023. 15(3). 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubWRwaS5jb20lMkYyMDcyLTY2NDMlMkYxNSUyRjMlMkY1OTM=&amp;sig=H1kCxByLunLvMyNGBmbH4FTY6nQeCmJp2ivi8zPfasXa&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14591" target="_blank">https://www.mdpi.com/2072-6643/15/3/593</a>
        </p>
        <p id="Ref2" style="padding-bottom:10px;">2.	Shirvani, A., et al., Disassociation of Vitamin D's Calcemic Activity and Non-calcemic Genomic Activity and Individual Responsiveness: A Randomized Controlled Double-Blind Clinical Trial. Sci Rep, 2019. 9(1): p. 17685. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DNjg4MTQ0OCUyRg==&amp;sig=J5aAPabUSZ6yPevqjGmh6bwdaxzTAEreRGFVhx5irGyq&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14592" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881448/</a>
        </p>
        <p id="Ref3" style="padding-bottom:10px;">3.	Pludowski, P., et al., Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev, 2013. 12(10): p. 976-89.
        </p>
        <p id="Ref4" style="padding-bottom:10px;">4.	Heaney, R.P., Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev, 2014. 72(1): p. 48-54. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZhY2FkZW1pYy5vdXAuY29tJTJGbnV0cml0aW9ucmV2aWV3cyUyRmFydGljbGUlMkY3MiUyRjElMkY0OCUyRjE5MzM1NTQ=&amp;sig=AiYSEscABEuQopxLE7a3dmfAadUEi2J59GHUoT3JFWHr&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14593" target="_blank">https://academic.oup.com/nutritionreviews/article/72/1/48/1933554</a>
        </p>
        <p id="Ref5" style="padding-bottom:10px;">5.	Gallagher, J.C. and C.J. Rosen, Vitamin D: 100 years of discoveries, yet controversy continues. Lancet Diabetes Endocrinol, 2023. 11(5): p. 362-374.
        </p>
        <p id="Ref6" style="padding-bottom:10px;">6.	Ross, A.C., et al., The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab, 2011. 96(1): p. 53-8. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMzA0NjYxMSUyRg==&amp;sig=2xtBLZkVH9fHrALtwPGNLf3LwWBYB3VugtDDS734NiDV&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14594" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046611/</a>
        </p>
        <p id="Ref7" style="padding-bottom:10px;">7.	Holick, M.F., Evidence-based D-bate on health benefits of vitamin D revisited. Dermatoendocrinol, 2012. 4(2): p. 183-90. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMzQyNzE5OCUyRg==&amp;sig=CKTTB9GRriwEYxt3P3nZaULTXrJCMFxz57gjHJBYWajb&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14595" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427198/</a>
        </p>
        <p id="Ref8" style="padding-bottom:10px;">8.	Holick, M.F., et al., Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2011. 96(7): p. 1911-30. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZhY2FkZW1pYy5vdXAuY29tJTJGamNlbSUyRmFydGljbGUtcGRmJTJGOTYlMkY3JTJGMTkxMSUyRjIwMjg4MTc3JTJGamNlbTE5MTEucGRm&amp;sig=7w3VimFNzfUPD86cnoo28A4xefUT8GFNVzyocX8MSR22&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14596" target="_blank">https://academic.oup.com/jcem/article-pdf/96/7/1911/20288177/jcem1911.pdf</a>
        </p>
        <p id="Ref9" style="padding-bottom:10px;">9.	Athanassiou, L., et al., Vitamin D and Autoimmune Rheumatic Diseases. Biomolecules, 2023. 13(4). 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAxMzU4ODklMkY=&amp;sig=H7N6vbb7fenrejVRPZ2ksouddy3Qx2Zd7Y4zes2XoDuE&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14597" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135889/</a>
        </p>
        <p id="Ref10" style="padding-bottom:10px;">10.	Kanno, K., et al., Effect of Vitamin D Supplements on Relapse or Death in a p53-Immunoreactive Subgroup With Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial. JAMA Netw Open, 2023. 6(8): p. e2328886. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA0NDUyMDElMkY=&amp;sig=6AbcjoZwaBAYq77898LViFHXLJZz7uvMCjwpbGmVPP4e&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14598" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445201/</a>
        </p>
        <p id="Ref11" style="padding-bottom:10px;">11.	Holick, M.F., The Death D-Fying Vitamin D3 for Digestive Tract Cancers-The p53 Antibody Connection. JAMA Netw Open, 2023. 6(8): p. e2328883. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZqYW1hbmV0d29yay5jb20lMkZqb3VybmFscyUyRmphbWFuZXR3b3Jrb3BlbiUyRmZ1bGxhcnRpY2xlJTJGMjgwODU3NA==&amp;sig=7jy6bYm5TszqvTXTSJGWCUGzbUJnD6aSqtvwgW3fLAjo&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14599" target="_blank">https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808574</a>
        </p>
        <p id="Ref12" style="padding-bottom:10px;">12.	Kong, S.Y., et al., Circulating Vitamin D Level and Risk of Sudden Cardiac Death and Cardiovascular Mortality: A Dose-Response Meta-Analysis of Prospective Studies. J Korean Med Sci, 2023. 38(33): p. e260. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTA0NDI0OTclMkY=&amp;sig=81vmtTrYrJnuqLLXadfXjNW76paFkV8C5Ympt9hq5wt9&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14600" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442497/</a>
        </p>
        <p id="Ref13" style="padding-bottom:10px;">13.	Rihal, V., et al., Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives. Crit Rev Food Sci Nutr, 2023. 63(25): p. 7772-7794. 
        </p>
        <p id="Ref14" style="padding-bottom:10px;">14.	Pal, E., et al., Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases. Nutrients, 2023. 15(2). 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTg2NDgzMiUyRg==&amp;sig=Gb3CkysviCvsqzaQpbeCD41sGH1mLm5eASwgBn554Et6&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14601" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864832/</a>
        </p>
        <p id="Ref15" style="padding-bottom:10px;">15.	Ghahremani, M., et al., Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimers Dement (Amst), 2023. 15(1): p. e12404. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTk3NjI5NyUyRg==&amp;sig=Fn8HDpZYbVKd5hWZz85kUp2Z29d5pdjpZ6n2Z2Mxc4df&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14602" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976297/</a>
        </p>
        <p id="Ref16" style="padding-bottom:10px;">16.	Borges-Vieira, J.G. and C.K.S. Cardoso, Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials. Nutr Neurosci, 2023. 26(3): p. 187-207. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cudGFuZGZvbmxpbmUuY29tJTJGZG9pJTJGZnVsbCUyRjEwLjEwODAlMkYxMDI4NDE1WC4yMDIyLjIwMzE0OTQ=&amp;sig=VqF9X7AKDtbGPhoTqCwfFmu6MMkPGpqzn5199j2rrAw&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14603" target="_blank">https://www.tandfonline.com/doi/full/10.1080/1028415X.2022.2031494</a>
        </p>
        <p id="Ref17" style="padding-bottom:10px;">17.	Musazadeh, V., et al., Vitamin D protects against depression: Evidence from an umbrella meta-analysis on interventional and observational meta-analyses. Pharmacol Res, 2023. 187: p. 106605. 
        </p>
        <p id="Ref18" style="padding-bottom:10px;">18.	Pittas, A.G., et al., Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med, 2023. 176(3): p. 355-363. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuYWNwam91cm5hbHMub3JnJTJGZG9pJTJGZXBkZiUyRjEwLjczMjYlMkZNMjItMzAxOA==&amp;sig=EvDvfpX7oFZrdwMCcfMdg3Y6KWW9LLw8Nqg6FycjiUkH&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14604" target="_blank">https://www.acpjournals.org/doi/epdf/10.7326/M22-3018</a>
        </p>
        <p id="Ref19" style="padding-bottom:10px;">19.	Halschou-Jensen, P.M., et al., Improved Healing of Diabetic Foot Ulcers After High-dose Vitamin D: A Randomized Double-blinded Clinical Trial. Int J Low Extrem Wounds, 2023. 22(3): p. 466-474. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZqb3VybmFscy5zYWdlcHViLmNvbSUyRmRvaSUyRmFicyUyRjEwLjExNzclMkYxNTM0NzM0NjIxMTAyMDI2OA==&amp;sig=Cf6AoXeBcuVQseBuAnTE2zyh8WqvxGwhdKJinmoXt5wi&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14605" target="_blank">https://journals.sagepub.com/doi/abs/10.1177/15347346211020268</a>
        </p>
        <p id="Ref20" style="padding-bottom:10px;">20.	Chen, X., et al., Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study. Diabetes Care, 2023. 46(2): p. 270-277. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZkaWFiZXRlc2pvdXJuYWxzLm9yZyUyRmNhcmUlMkZhcnRpY2xlJTJGNDYlMkYyJTJGMjcwJTJGMTQ3NTIwJTJGVml0YW1pbi1ELVN0YXR1cy1WaXRhbWluLUQtUmVjZXB0b3ItUG9seW1vcnBoaXNtcw==&amp;sig=oz9ZkxHciMtTHijmLR1AxkeGXPRiQ48pgVX46LaZX8i&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14606" target="_blank">https://diabetesjournals.org/care/article/46/2/270/147520/Vitamin-D-Status-Vitamin-D-Receptor-Polymorphisms</a>
        </p>
        <p id="Ref21" style="padding-bottom:10px;">21.	Li, B., et al., Association between Serum 25-Hydroxyvitamin D Concentrations and Respiratory Infection among United States Adults. J Nutr, 2023. 153(1): p. 260-267. 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cuc2NpZW5jZWRpcmVjdC5jb20lMkZzY2llbmNlJTJGYXJ0aWNsZSUyRnBpaSUyRlMwMDIyMzE2NjIyMTMxMDgxJTNGdmlhJTI1M0RpaHVi&amp;sig=3Ey3WBcJQVMnvg5EwMwqceHBAU7o1dxdAuTSri8upfn4&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14607" target="_blank">https://www.sciencedirect.com/science/article/pii/S0022316622131081?via%3Dihub</a>
        </p>
        <p id="Ref22" style="padding-bottom:10px;">22.	Bikle, D.D., Role of vitamin D and calcium signaling in epidermal wound healing. J Endocrinol Invest, 2023. 46(2): p. 205-212.  
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTg1OTc3MyUyRg==&amp;sig=5AVMzzmoKTqViJXySVbeQWJb4Tw3sJ9aB5NziMSUTwj8&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14608" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859773/</a>
        </p>
        <p id="Ref23" style="padding-bottom:10px;">23.	Pludowski, P., et al., Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland. Nutrients, 2023. 15(3). 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DOTkyMDQ4NyUyRg==&amp;sig=7wuXtqiiZEN4bnjQEZMWdvLwXNiGgxZBTumTRABT5L6&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14609" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9920487/</a>
        </p>
        <p id="Ref24" style="padding-bottom:10px;">24.	Wimalawansa, S.J., Physiological Basis for Using Vitamin D to Improve Health. Biomedicines, 2023. 11(6). 
        <a href="https://orthomolecular.lt.acemlna.com/Prod/link-tracker?notrack=1&amp;redirectUrl=aHR0cHMlM0ElMkYlMkZ3d3cubmNiaS5ubG0ubmloLmdvdiUyRnBtYyUyRmFydGljbGVzJTJGUE1DMTAyOTUyMjclMkYr&amp;sig=BDWt4UB9xAdLsSKivEFxhtS34Arv8q92hdgn7qu84heT&amp;iat=1710088737&amp;a=%7C%7C474997177%7C%7C&amp;account=orthomolecular%2Eactivehosted%2Ecom&amp;email=TeFm04%2B7TK57e6A5%2BJJ%2FGMWG%2F7SJHCK9Tfd9qntjYsXYPg5Y%3Az4p%2FjnaknmgXwbAx5v16RQA9Y7Ydl2%2B6&amp;s=f0efd3bc0da85c987defc367c0d5071a&amp;i=306A315A1A14610" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295227/</a>
        </p>
]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/science-daily-old-brains-can-learn-new-tricks</id>
    <published>2023-05-29T06:30:01-07:00</published>
    <updated>2023-05-29T06:30:01-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/science-daily-old-brains-can-learn-new-tricks"/>
    <title>Science Daily: Old Brains Can Learn New Tricks</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p><span style="font-size: large; font-weight: bold;">Study Shows Older People Use Different Areas Of The Brain To Perform Same "Thinking Task" As Young</span></p>
<hr style="margin: 2em auto 2em auto; width: 60%; height: 2px; border-width: 0; color: gray; background-color: gray;">
<p>ORIGINAL ARTICLE:<br> <a href="http://www.sciencedaily.com/releases/1999/10/991021094811.htm">http://www.sciencedaily.com/releases/1999/10/991021094811.htm</a><br>Source: Science Daily / University of Toronto</p>
<hr style="margin: 2em auto 2em auto; width: 60%; height: 2px; border-width: 0; color: gray; background-color: gray;">
<p><span style="font-size: large;">Older adults who take a novel antioxidant that specifically targets cellular powerhouses, or mitochondria, see age-related vascular changes reverse by the equivalent of 15 to 20 years within six weeks, according to new University of Colorado Boulder research.</span></p>
<p>The study, published this week in the American Heart Association journal<span> <em><a href="https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.117.10787">Hypertension</a></em></span>, adds to a growing body of evidence suggesting pharmaceutical-grade nutritional supplements, or nutraceuticals, could play an important role in preventing heart disease-the nation's No. 1 killer. It also resurrects the notion that oral antioxidants, which have been broadly dismissed as ineffective in recent years, could reap measurable health benefits if properly targeted, the authors say.</p>
<p>"This is the first clinical trial to assess the impact of a mitochondrial-specific antioxidant on vascular function in humans," said lead author Matthew Rossman, a postdoctoral researcher in the department of integrative physiology. "It suggests that therapies like this may hold real promise for reducing the risk of age-related cardiovascular disease."</p>
<p>For the study, Rossman and senior author Doug Seals, director of the Integrative Physiology of Aging Laboratory, recruited 20 healthy men and women age 60 to 79 from the Boulder area.</p>
<p>Half took 20 milligrams per day of a supplement called MitoQ, made by chemically altering the naturally-occurring antioxidant Coenzyme Q10 to make it cling to mitochondria inside cells.</p>
<p>The other half took a placebo.</p>
<p>After six weeks, researchers assessed how well the lining of blood vessels, or the endothelium, functioned, by measuring how much subjects' arteries dilated with increased blood flow.</p>
<p>Then, after a two-week "wash out" period of taking nothing, the two groups switched, with the placebo group taking the supplement, and vice versa. The tests were repeated.</p>
<p>The researchers found that when taking the supplement, dilation of subjects' arteries improved by 42 percent, making their blood vessels, at least by that measure, look like those of someone 15 to 20 years younger. An improvement of that magnitude, if sustained, is associated with about a 13 percent reduction in heart disease, Rossman said. The study also showed that the improvement in dilation was due to a reduction in oxidative stress.</p>
<p>In participants who, under placebo conditions, had stiffer arteries, supplementation was associated with reduced stiffness.</p>
<p>Blood vessels grow stiff with age largely as a result of oxidative stress, the excess production of metabolic byproducts called free radicals which can damage the endothelium and impair its function. During youth, bodies produce enough antioxidants to quench those free radicals. But with age, the balance tips, as mitochondria and other cellular processes produce excess free radicals and the body's antioxidant defenses can't keep up, Rossman said.</p>
<p>Oral antioxidant supplements like vitamin C and vitamin E fell out of favor after studies showed them to be ineffective.</p>
<p>"This study breathes new life into the discredited theory that supplementing the diet with antioxidants can improve health," said Seals. "It suggests that targeting a specific source-mitochondria-may be a better way to reduce oxidative stress and improve cardiovascular health with aging."</p>
<p>The study was funded by the National Institutes of Health. MitoQ Limited provided supplements and some financial support.</p>
<p>This summer, Rossman and Seals plan to launch a three-month follow-up study to confirm the findings in a larger number of subjects and look more closely at the impact the compound has on mitochondria.</p>
<p>The same lab published another study recently, showing that a compound called nicotinamide riboside may also be able to reverse vascular aging in healthy subjects.</p>
<p>"Exercise and eating a healthy diet are the most well-established approaches for maintaining cardiovascular health," said Seals. "But at the public health level, not enough people are willing to do that. We're looking for complementary, evidence-based options to prevent age-related changes that drive disease. These supplements may be among them."</p>
<hr style="margin: 2em auto 2em auto; width: 60%; height: 2px; border-width: 0; color: gray; background-color: gray;">
<p>ORIGINAL ARTICLE AND SOURCES AT SCIENCE DAILY:<br><a href="http://www.sciencedaily.com/releases/1999/10/991021094811.htm">http://www.sciencedaily.com/releases/1999/10/991021094811.htm</a></p>]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/like-hungry-locusts-humans-can-easily-be-tricked-into-overeating</id>
    <published>2023-05-08T06:30:00-07:00</published>
    <updated>2023-05-08T06:30:00-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/like-hungry-locusts-humans-can-easily-be-tricked-into-overeating"/>
    <title>Like hungry locusts, humans can easily be tricked into overeating</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <summary type="html">
      <![CDATA[<span>Our bodies crave more food if we haven’t had enough protein, and this can lead to a vicious cycle — especially if we’re reaching for ultraprocessed instead of high-fiber whole foods</span><p><a class="read-more" href="https://comparativeguide.com/blogs/news/like-hungry-locusts-humans-can-easily-be-tricked-into-overeating">More</a></p>]]>
    </summary>
    <content type="html">
      <![CDATA[<p style="font-style: italic;">Q&amp;A — Entomologist and nutrition researcher Stephen Simpson</p>
<p class="article-subhead" style="font-size: large;">Our bodies crave more food if we haven’t had enough protein, and this can lead to a vicious cycle — especially if we’re reaching for ultraprocessed instead of high-fiber whole foods</p>
<p class="article-byline" style="text-decoration: underline;">By Tim Vernimmen</p>
<p class="pub-date">5.1.2023</p>
<div class="article-content">
<p>This story starts in an unusual place for an article about human nutrition: a cramped, humid and hot room somewhere in the Zoology building of the University of Oxford in England, filled with a couple hundred migratory <a href="https://knowablemagazine.org/article/living-world/2020/locusts-and-grasshoppers-things-know" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">locusts</a>, each in its own plastic box.</p>
<p>It was there, in the late 1980s, that entomologists Stephen Simpson and David Raubenheimer began working together on a curious job: rearing these notoriously voracious insects, to try and find out whether they were picky eaters.</p>
<p>Every day, Simpson and Raubenheimer would weigh each locust and feed it precise amounts of powdered foods containing varying proportions of proteins and carbohydrates. To their surprise, the young scientists found that whatever food the insects were fed, they ended up eating almost exactly the same amount of protein.</p>
<p>In fact, locusts feeding on food that was low in protein ate so much extra in order to reach their protein target that they ended up overweight — not chubby on the outside, since their exoskeleton doesn’t allow for bulges, but chock-full of fat on the inside.</p>
<p>Inevitably, this made Simpson and Raubenheimer wonder whether something similar might be causing the documented rise in obesity among humans. Many studies had reported that even as our consumption of fats and carbohydrates increased, our consumption of protein did not.</p>
<p>Might it be that, like locusts, we are tricked into overeating, in our case by the irresistible, low-protein, <a href="https://knowablemagazine.org/article/mind/2021/foods-abuse-nutritionists-consider-food-addiction" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">ultraprocessed foods</a> on the shelves of the stores where we do most of our foraging? That’s what Raubenheimer and Simpson, both now at the University of Sydney, argue in their recent book “ <a href="https://www.eatliketheanimals.com/" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">Eat Like the Animals</a>” and in <a href="https://www.annualreviews.org/doi/10.1146/annurev-nutr-071715-051118" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">an overview</a> in the <em>Annual Review of Nutrition</em>.</p>
<p>Simpson took us through the reasoning and the data in an interview with <em>Knowable Magazine</em>. This conversation has been edited for length and clarity.</p>
<p><strong>How does an entomologist end up studying nutrition in humans?</strong></p>
<p>My interest in feeding behavior goes all the way back to my undergraduate years in Australia, where I was studying the food choices of sheep blowfly maggots, which are laid in the wool of sheep and eat the sheep alive. For my PhD, I took an opportunity at the University of London, England, to study appetite and food intake control in migratory locusts, which exist in two extreme forms — one solitary and one aggregating in swarms that create devastating plagues.</p>
<p>Since they had this reputation for being absolutely voracious, we surely did not expect them to have a lot of nuance in the way they control what they eat. But I started to explore whether they could sense the requirement for different nutrients and use it to regulate their intake. That led to experiments with artificial diets of different nutrient compositions, which showed that <a href="https://doi.org/10.1016/0195-6663(91)90069-5" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">locusts have nutrient-specific appetites for protein and carbohydrate</a>: Their food tastes differently to them depending on what they need, and that enables them to balance their diets.</p>
<p>In 1987, I started working with David Raubenheimer at Oxford to find out what happens if you put locusts on a diet that forces different appetites to compete, by feeding the animals mixtures of proteins and carbohydrates in relative amounts that do not match their intake target. We made 25 different diets, measured how much the locusts ate, how quickly they developed, and how big they grew, and found that <a href="https://doi.org/10.1006/anbe.1993.1114" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">when protein and carbohydrate appetites compete, protein wins</a>.</p>
<p>What that means is that if you put animals on a low-protein, high-carb diet, they’ll eat more calories to get that limiting protein, and they’ll end up obese. Likewise, if you put them on a high-protein, low-carb diet, they don’t need to eat as much to get to their protein target, and they end up losing weight. It was at that point that we knew we had discovered a powerful new way of looking at nutrition.</p>
<p>We started looking at lots of different species of insects, and found that they, too, had the capacity to regulate their intake of protein and carbohydrate, and that protein was often, but not always, the prioritized nutrient.</p>
<p>By now, we have studied species from cats, dogs and free-ranging primates to fish in aquaculture to slime molds to humans, in a variety of contexts — from understanding health and disease to optimizing animal feed to conservation biology.</p>
<p><strong>You’ve found that the nutrient levels that animals aim for are the ones at which they grow, survive or reproduce best. Just by following their appetite, they eat exactly what they need. Why don’t we?</strong></p>
<p>There are two possibilities. Either our biology is broken, or it still works but we’re in the wrong environment. What we’ve shown in our studies is the latter. What has happened is our appetites, which evolved in natural environments, have now been subjected to highly engineered food environments which have been designed, in many ways, to hack our biology, to subvert our appetites.</p>
<p>One of our favorite examples came from a study we did in Sydney. We <a href="https://doi.org/10.1371/journal.pone.0025929" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">confined people in a sleep center</a> for three four-day periods and provided them with foods and menus which were varied and matched in palatability, but were all of the same nutrient composition for a given week.</p>
<p>We had a 25 percent protein week, a 15 percent protein week, and a 10 percent protein week, and the subjects didn’t know that was going on. As far as they were concerned, they were allowed to eat what they wanted, everything tasted equally well and there were lots of choices. But it turned out that during the low-protein week, people ate more, because their protein appetite would drive them to eat more calories, to try and get enough protein. They largely did this by increasing snacking between meals, and selectively on savory-flavored snacks.</p>
<p>We’ve subsequently discovered that when you’re low in protein, as is the case on a 10 percent protein diet, you have elevated levels of a hormone called FGF21, which is mainly released from the liver. What we’ve shown in <a href="https://doi.org/10.1016/j.celrep.2019.05.022" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">mouse experiments</a> and <a href="https://doi.org/10.1371/journal.pone.0161003" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">confirmed in humans</a> is that FGF21 switches on savory-seeking behavior, which is a proxy for eating protein.</p>
<p>Now, if you have that response and the nearest savory thing is a bag of barbecue-flavored potato crisps, that’s a protein decoy. You’ll be misdirected to eat that, but you’ll not get any substantial amount of protein. You’ll remain protein-hungry, and you’ll have to eat more to satisfy that protein appetite. That means you’re accumulating excess calories, and that is precisely what happens to us in our modern food environment.</p>
<p><strong>You argue that ultraprocessed foods are especially likely to make us consume too many calories. Why would that be so?</strong></p>
<p>Over the last couple of years, population survey data have shown that the average person in the US, Australia or the UK <a href="https://doi.org/10.1017/S1368980017001574" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">gets more than half their calories from highly processed foods</a> — in some cases it’s 90 percent or more. As the proportion of ultraprocessed food in the diet increases, protein intake remains largely the same, but energy intake goes up steeply because of the dilution of protein by the fats and carbs in these foods. So this protein appetite we discovered initially in locusts operates in us too. In our modern food environment, it drives us to overconsume energy, and that sets up a vicious cycle.</p>
<p>What we find is that as people become overweight, their metabolism becomes dysregulated. Their tissues become less responsive to insulin, which normally regulates protein metabolism. This makes protein metabolism less efficient, causing the body to break down lean tissues like muscle and bone and burn protein to produce energy.</p>
<p>That increases people’s protein target, so they’ll eat even more, put on more weight, become even more metabolically dysregulated, start craving more protein, and so on.</p>
<p>We’ve since taken that basic idea and used it in a paper at the end of last year to propose a new understanding of <a href="https://doi.org/10.1111/1471-0528.17290" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">why women are prone to put on weight during menopause</a>. That’s a period when protein breakdown rates go steeply upwards in bone and muscle because of the decline in reproductive hormones. And it is driving the same sort of outcome that I just described.</p>
<p>You also see it in aging, you see it in people who smoke, you see it with excess alcohol intake — these are all circumstances in which FGF21 goes up, protein appetite goes up, protein breakdown goes up, and you’ll end up in this sort of vicious cycle.</p>
<p><strong>As an entomologist, how did you manage to convince colleagues in nutrition science this matters?</strong></p>
<p>It’s just the accumulation of evidence. Last fall, we spoke at the Royal Society in London at a big obesity conference, and the response to our talk indicated to me that protein leverage is now accepted as one of the main, credible underlying explanations for obesity. Our evidence comes from pre-clinical studies, it comes from clinical studies, it comes from cohort studies, it comes from population-level analyses, it comes from deep mechanistic biology — it’s now unanswerably there. The remaining question is: Of the various influences that drive obesity, is protein appetite a main one? We think it probably is.</p>
<p><strong>Why would protein be the strongest driver of our appetites? What would be the biological logic?</strong></p>
<p>All three macronutrients — fat, carbs and protein — contain calories, so we can burn any of them to yield energy, and we can use any of them to make glucose, which is the preferred fuel for our cells and brain.</p>
<p>But only protein has nitrogen, which we need for many other purposes, from maintaining our cells to producing offspring. You don’t want to eat too little protein.</p>
<p>That leaves the question of why we don’t overeat it. Why do we eat fewer calories than we need on a high-protein diet, rather than eat excess protein? To us, that implied there is a cost to eating too much protein, and we set out to discover that cost in fruit flies. We designed <a href="https://doi.org/10.1073/pnas.0710787105" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">a large experiment</a> where we confined a thousand flies to one of 28 diets varying in the ratio of protein and carbohydrate, the two major macronutrients for flies. What we found was that flies lived longest on a lower-protein, high-carbohydrate diet, but laid most eggs on a higher-protein, lower-carbohydrate diet. A really-high-protein diet, finally, wasn’t better for either outcome.</p>
<p>That overturned a hundred years of thinking around restricting calories and aging: The dominant view was that reduced calories were what prolonged life, but our data showed that the type of calories matter, notably the ratio of protein to carbs. And it created quite a stir at the time — the paper came out in 2008.</p>
<p>We set out to do <a href="https://doi.org/10.1073/pnas.1422041112" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">the same experiment in mice</a>. To do that, we had to add fat as a third nutrient dimension to the dietary design. That involved an enormous study. We took more than 700 mice and put them on one of 25 different diets varying in the concentration and ratio of protein, carbohydrate and fat. It took 6 metric tons of experimental diet to run that study across the 3 or 4 years it took before the oldest mice died.</p>
<p>That was the first of a whole series of huge mouse experiments where we looked at different types of carbohydrate, different ratios of amino acids, and so on. The long and the short of it was that the mice lived longer on low-protein, high-carbohydrate diets, but reproduced better on high-protein, low-carbohydrate diets — very similar to the flies.</p>
<p>Importantly, the benefit of low protein was only realized <a href="https://doi.org/10.1038/s42255-021-00393-9" target="_blank" xmlns:xlink="http://www.w3.org/1999/xlink" rel="noopener noreferrer">when the carbohydrates were harder-to-digest complex carbohydrates</a> like fiber and starch, not simple sugars. If you translate that into human populations and look across the world for human populations that live the longest, lo and behold they’re the ones on diets low in protein and high in healthy carbohydrates and fats, such as Mediterranean-style diets and the traditional Okinawan diet.</p>
<p><strong>I’m sure they’re all very healthy, but how do people on these diets manage their appetites?</strong></p>
<p>That’s a really interesting question. The Okinawans certainly are hungry for protein. In traditional Japanese cuisine, there is an almost religious prominence given to umami flavors, which are the signature of protein, the savory characteristic in foods. So that’s like a societal protein appetite.</p>
<p>The other question is: On a 10 percent protein diet like the Okinawan diet, why aren’t they all suffering obesity because they have to eat far more to get their protein? The answer is that the traditional diet is low in energy, and high in fiber. By eating more to try and attain their protein target, they get more fiber instead of more calories, until their stomach is full. That’s a crucial distinction with the modern industrialized food environment, which isn’t just low in protein, but also low in fiber — and high in fats and carbs.</p>
<p><strong>If low protein and low fiber content are the main problem, would it help to just increase them in ultraprocessed foods? Or would that not be sufficient?</strong></p>
<p>Science has already nudged the industry in that direction in a couple of ways that are not altogether helpful. The high-protein snack industry is a phenomenon which reflects this science. Their response was: We’ve got a new market now for high-protein bars. Whether or not that’s ultimately going to help the world’s waistline is less clear at the moment, as the food environment as a whole remains replete with low-protein, low-fiber, ultrapalatable processed foods.</p>
<p>The principal driver for reducing protein content in ultraprocessed foods was that protein is more expensive than fats and carbohydrates. It was cheaper to take some of the protein out and add a little more fat and carbs, particularly when you can make things taste fantastic by mixing sugar and fat and a bit of salt together.</p>
<p>Some of the big providers of lifestyle interventions have shifted towards increasing the percent protein in the diet. And of course, all of the commercially successful fad diets of recent decades have been high-protein diets. But none of them takes account of the fact that there’s potentially a cost to a higher-protein diet.</p>
<p>As we’ve shown originally in flies and mice, a higher protein-to-carbohydrate ratio than we need speeds up aging in our tissues. That being said, if you’re suffering obesity and diabetes, the benefits of a high-protein diet in terms of weight loss may outweigh the costs. It’s a matter of understanding the relative costs and benefits associated with different diet compositions, relating them to personal goals and breaking away from some of the crazy diet zealotry that goes on online and is promoted by many of the fad diet industries.</p>
<p><strong>So you’d recommend eating more fiber and fewer carbs and fats rather than eating more protein? How does that affect your own choice of snacks outside of mealtimes?</strong></p>
<p>I have a deep love of food, cooking, and even hunting and gathering — I’m a fisherman. But I’m as susceptible to the siren call of ultraprocessed foods and beverages as everyone else. These products have been designed to be irresistible, so I avoid them, except on occasions. They are not in the house or my shopping trolley.</p>
<p>As a family, we eat whole foods, plenty of fruits and vegetables, pulses, nuts and grains, as well as dairy and high-quality meat, fish and poultry. There are many ways to mix a nutritionally balanced and delicious diet without the use of apps or computer programs. After all, no species in the history of life on Earth ever needed those.</p>
<p>The trick is to take advantage of our evolved biology of appetite by creating an environment in which our appetites can guide us to a healthy and balanced diet. We need to help our appetites work for ourselves and our health, not the profits of the food and beverage industries.</p>
</div>
<aside class="article-sidebar -right">
<div class="article-sidebar-text"></div>
</aside>
<div class="article-info">
<div class="article-doi">
<p>10.1146/knowable-050123-1</p>
</div>
<div style="padding: 1 rem 0 1rem 0;"><hr style="width: 75%&gt;&lt;/div&gt;&lt;div&gt;&lt;p class=;" article-author=""></div>
<div style="padding-bottom: 0.5rem;">
<b>Tim Vernimmen</b>, a freelance science journalist based near Antwerp, Belgium, has always had a healthy appetite, but now wonders how fitting that term really is. He does like to cook, which helps him steer clear of highly processed foods most of the time.</div>
</div>
<p>This article originally appeared in <a href="https://www.knowablemagazine.org/"><em>Knowable Magazine</em></a>, an independent journalistic endeavor from Annual Reviews. Sign up for the <a href="https://www.knowablemagazine.org/page/newsletter-signup">newsletter</a>.</p>
<img src="https://www.knowablemagazine.org/assets/images/logo-k.svg" alt="Knowable Magazine | Annual Reviews" style="height: 40px;"> <meta name="syndication-source" content="https://knowablemagazine.org/article/food-environment/2023/do-low-protein-diets-cause-overeating?utm_source=Knowable+Magazine&amp;utm_campaign=72f6d1c7ab-KM_NEWSLETTER_2023_05_07&amp;utm_medium=email&amp;utm_term=0_-72f6d1c7ab-%5BLIST_EMAIL_ID%5D" doi="10.1146/knowable-050123-1">]]>
    </content>
  </entry>
  <entry>
    <id>https://comparativeguide.com/blogs/news/eating-lots-of-fruits-and-vegetables-could-lower-miscarriage-risk</id>
    <published>2023-04-24T12:55:39-07:00</published>
    <updated>2023-04-24T12:55:40-07:00</updated>
    <link rel="alternate" type="text/html" href="https://comparativeguide.com/blogs/news/eating-lots-of-fruits-and-vegetables-could-lower-miscarriage-risk"/>
    <title>Eating Lots of Fruits and Vegetables Could Lower Miscarriage Risk</title>
    <author>
      <name>Gregory Gies</name>
    </author>
    <content type="html">
      <![CDATA[<p>Science writer Ryan Vingum at Labroots reports on a study from the University of Birmingham published in <i><a href="https://linkinghub.elsevier.com/retrieve/pii/S0015028223002960">Fertility and Sterility</a></i> that indicates a healthy diet full of fruits and vegetables prior to getting pregnant may significantly lower the risk of miscarriage.</p>
<p>Original article: <a href="https://www.labroots.com/trending/plants-and-animals/25149/eating-lots-fruits-vegetables-lower-miscarriage-risk">Eating Lots of Fruits and Vegetables Could Lower Miscarriage Risk | Plants And Animals (labroots.com)</a></p>]]>
    </content>
  </entry>
</feed>
