I am not a proponent of many supplements; the fact is that human trials with adequate subject numbers is lacking in most cases.  Too often supplements are justified with in vitro, animal, and observational evidence which then fail when they enter interventional trials.  It is difficult to explain this to lay people effectively, who prefer generalized, simple advice.

So I am excited to see that the latest data visualization from InformationIsBeautiful is on the scientific evidence on a number of supplements from only randomized, placebo-controlled human studies.  An interactive chart is available here, or a static image is below:

According to the website, the researchers looked at over 1500 abstracts on pubmed.org and cochrane.org for their data, then put all of the information into a Google Spreadsheet here, where all of the sources are available.  The bubbles are created from data on the spreadsheet, so changes are easy to make.  Several have been already based on comments on the site.

Clearly many of these are very debatable, and just examining abstracts isn’t very reliable.  Dose, context, and other study design features are also difficult to consider in a visual form like this without over-cluttering.  But I think it is a great start, and it gives people a quick and simple guide, better the majority of supplement sources on the web.

Here are some of the interesting things I read last week.

Nutrition Related

A new study finds that nursing home residents with advanced dementia are much more likely to have a feeding tube inserted if the hospital is for-profit, larger, and has a greater ICU use.  Quoted in the NYTimes, one of the authors suggests that more needs to be in place to respect patient choice.

We know that certain bacteria influence obesity in rodent studies, now we are finally moving to human investigation.

Ditch your bread maker and make Artisan bread, as suggested by Yoni Freedhoff.  I will be getting this book and experimenting!

“Beer may be good for your bones” describing a highly publicized study last week, which only measured silicon content in many beers (which is one component to bone health).  Relevant studies are only observational at this point; be wary of dramatic headlines.

Many people argue against meat consumption because animals supposedly use too much land and don’t supply much energy relative to that usage.   But switching to certain vegetarian foods may be even worse for the environment.

Another prospective study finds that coffee reduces diabetes risk, but also looked at timing of consumption.  They found that the association was apparent with black (caffeinated or decaffeinated) coffee at lunch only, where no association was found with tea or chicory.  Coffee with milk did not decrease risk, however.  See the paper for possible mechanisms and limitations.

Other

Sweatscience covers a study that found that stretching before running slowed them down.  This is the first evidence that stretching before an event negatively effects endurance exercise, and complements the ample evidence for nixing it prior to power, jumping, and sprinting events.

Sweatscience also on a study that found cooling of palms between weight lifting sets allowed a greater lifting of weight.  This adds to the central governor hypothesis.

It turns out that serotonin released from the gut is involved in bone homeostasis, and blocking it increases bone mass in a mouse model of osteoporosis.  A cool video about the study here.

Our universe may be a holographic projection of 2D processes elsewhere, suggest some astrophysicists.  Mind-blowing to say the least.

An excellent post about how electromagnetic radiation (from cell phones) doesn’t seem to increase cancer risk, and may actually prevent Alzheimer’s disease in a rodent model.  It may be useful for brain injury as well, or possibly even as a nootropic as noted by an author.

Two new social platforms launched: Google Buzz, which is integrated into gmail, and Sciencefeed.com, which is as of now very identical to friendfeed but targeted at scientists.

http://www.ted.com/talks/jamie_oliver.html

Comment: though he needs to check his facts on the life expectancy of the latest generation, he is an emotionally passionate speaker and hopefully his message reaches more who haven’t considered the ideas he discusses.  The way we have things setup now for children is truly atrocious.  Let me know what you think in the comments.

It is quite clear that for athletes, consuming protein and carbohydrate after a workout is crucial to recovery for subsequent sessions (replenish glycogen) and performance improvement.  The doses of each macronutrient, as well as the inclusion of fat (which according to preliminary evidence, certain types of fat may further increase protein synthesis, and fat for endurance athletes may increase total energy intake and increase performance) is debatable for endurance exercise versus resistance training, of which will be explored in future posts.

But, should similar post-workout recommendations for athletes be adopted by casual exercisers, where the goal is health instead of maximizing performance?  More importantly, should people with metabolic problems be chugging gatorade and the like after their workouts to replenish their glycogen?

A recent study by Newsom et al. (1) suggests that one marker of metabolic health, insulin sensitivity, is influenced by carbohydrate content that is consumed after exercise, and not total energy intake, and perhaps carbohydrate consumption should be kept low to maintain insulin sensitivity into the next day.

The study consisted of the following:

• 9 normal weight (BMI </= 25) sedentary men, average age 29+/-1 year with no history of metabolic or cardiovascular disease.
• 3 exercise trials (each 2 days) 7 or more days apart, exercising at a moderate intensity (60-65% VO2peak) for ~90 minutes (~45 minutes of treadmill exercise and ~45 minutes of cycle ergometer exercise) on the first day (roughly 800 kcal expended), and a number of metabolic tests were done on day two (VO2, VCO2, insulin sensitivity, intramuscular triglycerides).  The exercise intensities and durations intended to reduce glycogen by ~55%.
• For the 4th trial, subjects were sedentary.

The post exercise meals were the following:

• -adequate carbohydrate and total energy to replace what was expended (BAL)
• -deficient in carbohydrate but total energy replaced what was expended (LOW-CHO)
• -adequate carbohydrate but deficient in total energy that didn’t replace what was expended (LOW-EN)

The meals were consumed a half hour, 3 hours, and 8 hours after exercise was completed (and a snack 11 hours after).  The exercise was performed at 9:30am after an overnight fast and completed at 11:00am.

The total macronutrient breakdowns and energy over all meals are as follows (subjects were fasting going into the exercise):

Results

Resting energy expenditure, exercise energy expenditure, and respiratory exchange ratio during exercise were similar among the 3 trials, as intended.

Insulin sensitivity was measured on the day after the exercise, and while elevated in all trials compared to the sedentary group, statistical significance was only achieved in the LOW-CHO compared to the control group.  The LOW-EN and BAL groups (the same carbohydrate intakes, but different energy intakes) were similar, suggesting that carbohydrate is the important factor for insulin sensitivity.

In the LOW-CHO group, muscle glycogen was ~25% lower on the day after the exercise compared with CON, and in the BAL and LOW-EN groups, glycogen was similar to CON, suggesting that carbohydrate and not total calories is the important factor for glycogen replenishment.

Intramuscular triglycerides were similar in all groups on the day after exercise.

Palmitate rate of appearance and disappearance and oxidation were elevated in the LOW-EN trial compared to the CON.

Fasted plasma glucose, fatty acid, and insulin were similar the morning after exercise.  Plasma triacylglycerol concentrations in the morning after were not effected by exercise in the BAL group, but they were significantly lower in the LOW-CHO trial compared to the other trials.  Unexpectedly, triacylglycerol concentration in the LOW-EN group was significantly higher than the BAL group (with less fat and the same amount of carbohydrate).

Summary

The important findings for the study include the following:

• an energy deficit after 1 exercise session does not enhance the increase in insulin sensitivity to exercise
• a low carbohydrate consumption results in a lower muscle glycogen the next morning
• a low carbohydrate consumption results in an increased insulin sensitivity the next day
• insulin sensitivity improved even with an energy balance

The results confirm previous studies that suggest that when muscle glycogen is kept low, insulin sensitivity is maintained.  A recent study by Holtz et al. found that the the greater the carbohydrate deficit, the greater the insulin action, except they did not find an effect when subjects were in an energy balance.  However, as noted by the authors in this study, the carbohydrate intake was only 25% of total energy, compared to Holtz’s 50%.  It is possible that there is some threshold of carbohydrate restriction necessary to maintain insulin sensitivity the next day when in an energy balance.

Additionally, this study found that with differing energy or carbohydrate contents, fasting plasma triacylglycerol concentration is affected the next morning (but not by exercise itself), which adds to our limited understanding of how nutrition alters this.  As noted previously, the LOW-CHO trial suppressed triacylglycerol concentration, corroborating research showing that high carbohydrate diets elevate plasma triacylglycerol concentration.

Lastly, this may be support for low carbohydrate diets/ketogenic diets in combination with exercise for optimal improvement in metabolic markers of health, but further research is necessary.

Limitations

Because fat had to be reduced in the LOW-EN trial and increased in the LOW-CHO trial, it may have influence on the results.  However, fat is known not to have a great effect compared to carbohydrate on insulin.  Also, because of the low subject number, statistical significance of some of the measurements may not be appropriately represented.  Finally, hepatic glucose metabolism should be measured in subsequent studies along with the skeletal muscle to represent whole-body insulin sensitivity, and be conducted in other populations.

Studies will also have to elucidate whether any lack or difference in a change in insulin sensitivity is clearly associated with health risks or benefits, and if subsequent exercise sessions abolish any differences.  Until then, with much research showing superiority of high fat, low carbohydrate diets for people with metabolic problems/diabetes on metabolic markers, it is my opinion that this research further supports a low carbohydrate diet in concert with exercise for optimizing metabolic health.

Reference

1. Newsom SA, Schenk S, Thomas KM, Harber MP, Knuth ND, Goldenberg N, & Horowitz JF (2009). Energy deficit after exercise augments lipid mobilization but does not contribute to the exercise-induced increase in insulin sensitivity. Journal of applied physiology (Bethesda, Md. : 1985) PMID: 20044472

Here are some of the interesting things I read this week.

Nutrition Related

The ISSN published a huge 93 page, 511 reference review on sports nutrition (PDF).

A new study suggests that food form and portion size affect satiety.

Commentary on the recent saturated fat meta-analysis, raising a number of questions and questioning some of the interpretations by the authors.

A New York Times article about paleo-nutrition enthusiast John Durant.

The Warburg effect (that a low carbohydrate diet may starve cancer cells) is finally being tested on humans.

Eric Schlosser, author of Fast Food Nation, is apparently done writing about food issues.

A trial is recruiting older participants for a large study on Vitamin D and omega-3 fatty acids, as pointed out by sweatscience.

Other

Active resting may strengthen memory of newly learned information.

Some people in vegatative states may have some level of awareness and be able to communicate via fMRI.

The Primordial Soup theory of how life started seems to be increasingly rejected by new findings, one theory being from chemiosmosis.

Mechanical forces, along with biochemical regulation, alters gene expressions.

Here are some of the interesting things that I came across in the past week.

Nutrition Related

The ISSN published a review on caffeine and athletic performance (PDF).  It is a long one, and eventually I will get to reviewing it here.

There is a U curve for mortality for HbA1C in diabetic subjects, and further research will need to confirm and possibly influence guideline revision on treatment.

Does homocysteine really cause heart disease?  A review on the evidence. Though B vitamins like folic acid help with homocysteine lowering, it may not reduce disease risk.

A well written article by Alan Aragon on fructose.  Is it really the demon that most people think it is?  A recent journal review also came out this month on the topic.

Seems like a leptin mimic that likely better penetrates the blood brain barrier is in development, and undergoing study soon.  I am sure there are others in development, this was proposed nearly a decade ago as an obesity treatment (for selective leptin resistance).

Other

If you’ve been following the blog, last week I posted a link to a study that found Leukocyte Telomere Length loss was slowed in a prospective fish oil study, which may be a biomarker of ageing and explain why fish oil improves survival in CHD patients.  Now an observational study finds runners have longer LTL.  Paper here.

A description of how Bjorn Brembs and Bruno van Swinderen discovered a unique fly model for ADHD.  Very cool study and insight by Bjorn.

Here are some of the interesting things I read this week.

Nutrition Related

A new rapamycin study in Drosophilia suggests that the (m)TORC1 inhibition may have longevity promoting effects independent of those related to calorie restriction, since it was able to further increase lifespan in calorie restricted specimens.

In rats, a calorie restricted diet during lactation resulted in offspring that consumed less energy and were more resistance to weight gain on a high fat diet than those fed ad libitum, related possibly to leptin and likely other mechanisms.

Shift work (ie night work) creates health problems because of circadian desynchrony (internal clocks not in sync with schedule).  A new and important rat experiment suggests that food intake during the time they normally sleep was the cause of health problems; shifting food intake to the normal eating period even when they were kept awake when they normally sleep prevented desynchrony and metabolic disturbances.  Peripheral clocks entrained by food intake are scheduled to be covered in depth later this year.

Leptin and endocannabinoids oppose one another in their effects on food taste.

Fish oil may improve survival rate in patients with coronary artery disease, and leukocyte telomere length (LTL) was slowed in those who took it in this observational study, a biomarker of ageing and cardiovascular disease risk.

Many people are quick to point a finger at fructose (e.g. high fructose corn syrup) as a principal cause of modern health problems.  However, this review points out that the current human evidence fails to show unequivocally that moderate intakes is harmful.

Another study on the antioxidant/endurance performance issue; accumulating evidence suggests that vitamin-anxioxidants may prevent exercise induced adaptations (mainly mitochondrial biogenesis).  This one found no effect, however, with C and E.  A detailed review of this research is planned for this year.

A meta-analysis on the relationship between saturated fat and cardiovascular disease suggests there is none.  Ronald Krauss is an important name on this study, who has helped to elucidate the different subtypes of LDL (as well as many other important finds).

More evidence that resveratrol does not activate SIRT1 directly, but only does so when attached to a fluorophore.  A great summary of current issues here.

Green tea doesn’t really help you lose weight.  Sorry supplement manufacturers.

A rebuttal to a recent study/media frenzy on the relationship between butt fat and health risks by Peter at ObesityPanacea.com.

Other

A well written piece based on anecdotal and empirical evidence on cannabis’ potential ergogenicity in certain contexts.  I had not yet looked at research on cannabis in sport so this is a welcome summary.

Who says you need nucleic acids for evolution?  Prions don’t care.

Death to metabolic syndrome, suggest recent papers.  The term needs to be strictly defined or perhaps dropped from use completely.

A manuscript with Isaac Newton’s true apple/gravity story is digitized; the apple really didn’t hit his head.

A few of the blogs I follow aggregate interesting links each week with short summaries.  So, idea credit and shout-outs go to Weighty Matters, Obesity Panacea, and Summer Tomato.  I highly recommend subscribing to these blogs.

I realize that not all readers here will follow me on twitter, where I share and pass on interesting new research and articles that I encounter.  I also realize that not everyone wants to read in as much detail as I tend to summarize studies in (based on the short amount of time visitors tend to spend here so far, thanks Google Analytics). Additionally, I tend to focus on reviewing more than one paper when posting, so with shorter weekly summaries I can pass along research more quickly and it will likely be reviewed in detail down the road.  Finally, there are great nutrition related articles about issues not necessarily about research that should be shared to develop an encompassing perspective on the different angles of nutrition.  And of course, many people are able to cover certain topics much better than I, and should be highlighted.

Please feel free to add in the comments interesting studies or articles that you have encountered recently.

So here is the first iteration of the Weekly Summaries segment.

Nutrition Related

Two new methionine restriction studies were published recently, the first finding a decrease in mitochondrial oxidative stress.  The authors speculate that methionine is the main factor that improves health in calorie restriction studies and part of the reason it promotes longevity, though other research suggests they may differ mechanistically.  The second found that it increases mitchondrial biogenesis, which is expected.

Marion Nestle reviews recent studies about food labels and calorie estimations that result in fat gain.  I want to highlight a passage from one of the papers (PDF):

These calculations suggest that small changes in lifestyle

would have a minor effect on obesity prevention. Walking

an extra mile a day expends, roughly, an additional 60 kcal

compared with resting—equal to the energy in a small cookie.

Physiological considerations suggest that the apparent energy

imbalance for much of the US population is 5- to 10-

fold greater, far beyond the ability of most individuals to

address on a personal level. Rather, an effective public health

approach to obesity prevention will require fundamental

changes in the food supply and the social infrastructure.

Changes of this nature depend on more stringent regulation

of the food industry, agricultural policy informed by

public health, and investments by government in the social

environment to promote physical activity.

“These calculations suggest that small changes in lifestyle would have a minor effect on obesity prevention. Walking an extra mile a day expends, roughly, an additional 60 kcal compared with resting—equal to the energy in a small cookie. Physiological considerations suggest that the apparent energy imbalance for much of the US population is 5- to 10-fold greater, far beyond the ability of most individuals to address on a personal level. Rather, an effective public health approach to obesity prevention will require fundamental changes in the food supply and the social infrastructure. Changes of this nature depend on more stringent regulation of the food industry, agricultural policy informed by public health, and investments by government in the social environment to promote physical activity.”

Anyone who studies obesity realizes that the solution isn’t as elegantly simple as telling people to exercise more (which by itself does not promote weight loss) or giving them diet instructions.  There are many factors influencing weight, a lot which are not under our conscious control (which is why we need changes in infrastructure).  The next time you see a “fitness expert” who relies on faulty, simplistic practices, call them out on it.

Did we improve our nation’s health in the last decade? Analysis of over 1,000 objectives is in progress for the past decade set under Healthy People 2010, showing so far improvements in some areas but a worsening in many others.  The next version will apparently aim to involve the public more intimately in the goals.

Vitamin E shortens “quality-adjusted life years,” in a new data analysis using a Markov-model, further damning the vitamin-antioxidant as a supplement.  Many questions still remain (there are 7 other E vitamers in nature, and only 1 is usually supplemented), but whole food sources are always the best bet.

The Granola Health Myth by Fooducate.  While the article is short and rather vague, it brings up a good point: granola should be called out as a health food.  Not only do many granola products contain ingredients that contribute nothing to a healthy diet, never before in human history have we consumed it until recently.

The popular supplement Ginkgo biloba has been found in a large study to be ineffective at reducing dementia, Alzheimer’s, or cognitive decline.  A good review of this in context of previous research here.

Gretchen Reynolds from the New York Times writes about recent research challenging the paradigm that being overweight with a healthy metabolic profile is ok; risk of certain diseases still may be elevated.

Non Nutrition Related

Running shoes increase stress on lower extremity joints (knees, hips, ankles) compared to barefoot (free full text here).  The evidence continues to mount that our natural foot mechanics should be considered when designing shoes. Some companies get it, most don’t.

The efficacy of many treatments that physical therapists use is questioned in a recent New York Times article.  I would love to see rebuttals.

How does a cell pack away all of our DNA?  A new technique expands our understanding of how genetic material is organized and read.

As 2009 comes to an end, it is time to reflect on some of this year’s scientific advancements.

Please comment here, by email, or twitter on how I am doing with the blog so far.  Though I only started it a few months ago in September, I hope it has been a benefit to at least a few people.  I am very detail oriented, so posts will roll out slowly, and with over 40 topics already in draft, 2010 will be a busy year!

Happy new year!

Here are short comments on some of my favorite studies of this year.

Nutrition Related

Colman RJ, Anderson RM, Johnson SC, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys.; 2009:201-4. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19590001.

An update to the Rhesus monkey calorie restriction longitudinal study, now at 20 years, shows an 80% survival (and reduction of various diseases) in the calorie restricted group compared to 50% left in the control.

Ishikura Y, Ikeda G, Akimoto K, et al. Arachidonic Acid Supplementation Decreases P300 Latency and Increases P300 Amplitude of Event-Related Potentials in Healthy Elderly Men. Neuropsychobiology. 2009;60(2):73-79. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19752581.

Arachidonic acid is a nutrient despised by many nutritionists, but essential for nervous system development.  New research suggests is may be important to maintain some aspects of cognitive function in adults as well.  Reviewed on this blog here.

Bailey SJ, Winyard P, Vanhatalo A, et al. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. Journal of Applied Physiology. 2009. Available at: http://jap.physiology.org/cgi/doi/10.1152/japplphysiol.00722.2009.

Building on a study from 2 years ago, a recent study found that high nitrate vegetable juice (beet root) reduces the oxygen cost of exercise and improves time to exhaustion.  Reviewed on this blog here.

Barrès R, Osler ME, Yan J, et al. Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell metabolism. 2009;10(3):189-98. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19723495.

A gene that regulates mitochondrial biogenesis, central to insulin resistance, is found to be hypermethylated in diabetics.  In vitro experiments showed under what conditions this can happen and even which DNA methyltransferase isoform is involved, furthering our understanding of how epigenetics contributes to insulin resistance and suggesting possible treatment targets.  Reviewed on this blog here.

Cannell JJ, Hollis BW, Sorenson MB, Taft TN, Anderson JJ. Athletic performance and vitamin D. Medicine and science in sports and exercise. 2009;41(5):1102-10. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19346976.

A great review on some esoteric research dating back decades on how vitamin D concentration seems to influence athletic performance.  I am assisting in a current study on this subject, which will be published next year.  Expect to see posts about it soon.

Carrano AC, Liu Z, Dillin A, Hunter T. A conserved ubiquitination pathway determines longevity in response to diet restriction. Nature. 2009;1:1-5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19553937.

Further elucidation of mechanisms through which calorie restriction works.

Cheng Y, Meng Q, Wang C, et al. Leucine deprivation decreases fat mass by stimulation of lipolysis in WAT and upregulation of UCP1 in BAT. Diabetes. 2009;(June). Available at: http://www.ncbi.nlm.nih.gov/pubmed/19833890.

Deprivation of essential amino acids regulate fat mass.  Detailed blog post coming soon.

Dangour AD, Dodhia SK, Hayter A, et al. Nutritional quality of organic foods: a systematic review. The American journal of clinical nutrition. 2009;(C):4-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19640946.

A large review concludes that organic foods aren’t superior to non in a number of nutrients, though the issue is more complex.

Dean JT, Tran L, Beaven S, et al. Resistance to diet-induced obesity in mice with synthetic glyoxylate shunt. Cell metabolism. 2009;9(6):525-36. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19490907.

The first study that adds a synthetic (non native) metabolic pathway from different species into mice, showing benefit to health.

Ebbing M, Bonaa KH, Nygard O, et al. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA: The Journal of the American Medical Association. 2009;302(19):2119-2126. Available at: http://jama.ama-assn.org/cgi/doi/10.1001/jama.2009.1622.

The evidence continues to mount that too much folic acid and B12 has harmful consequences.

Felton aM, Felton a, Raubenheimer D, et al. Protein content of diets dictates the daily energy intake of a free-ranging primate. Behavioral Ecology. 2009;20(4):685-690. Available at: http://www.beheco.oxfordjournals.org/cgi/doi/10.1093/beheco/arp021.

Adding to protein leverage theory, spider monkeys consume energy to satisfy protein requirements, while total energy intake varies.

Frassetto La, Schloetter M, Mietus-Synder M, Morris RC, Sebastian a. Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet. European journal of clinical nutrition. 2009;63(8):947-55. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19209185.

A “paleo” diet improves health, though many people would disagree on how to define this type of diet.  More on paleo type diets in 2010.

Goodson JM, Groppo D, Halem S, Carpino E. Is Obesity an Oral Bacterial Disease? Journal of Dental Research. 2009.

Adding to the body of research showing certain bacterial populations change with obesity and perhaps that they may have a causal role in some cases.  ”Infectobesity” has been studied by measuring bacteria in the gut, but this one yields interesting oral data.

Hall KD, Guo J, Dore M, Chow CC. The Progressive Increase of Food Waste in America and Its Environmental Impact. Energy. 2009;4(11):9-14.

Americans waste about 40% of our food, which is an increase from previous data.

Kokkinos A, le Roux CW, Alexiadou K, et al. Eating Slowly Increases the Postprandial Response of the Anorexigenic Gut Hormones, Peptide YY and Glucagon-Like Peptide-1. The Journal of clinical endocrinology and metabolism. 2009;95(January):1-5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19875483.

A recent study showed differences in 2 gut hormones that influence appetite, are differed depending on eating speed.  But a close look at the study and previous literature suggest that is probably isn’t much to worry about.  Reviewed on this blog here.

Kroese FM, Evers C, De Ridder DT. How chocolate keeps you slim: The effect of food temptations on weight watching goal importance, intentions, and eating behavior. Appetite. 2009. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19666065.

Human behavior is important to understand when considering eating habits.   Contrary to what might be assumed, 2 experiments suggest that food temptations actually may improve compliance to healthy eating.

LeSauter J, Hoque N, Weintraub M, Pfaff DW, Silver R. Stomach ghrelin-secreting cells as food-entrainable circadian clocks. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(32):13582-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19633195.

Food influences peripheral circadian clocks, including stomach cells.  A close examination of these clocks coming in 2010.

Place N. Go rinse your mouth: a novel way to improve endurance performance? The Journal of physiology. 2009;587(Pt 11):2425-6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19332497.

Carbohydrate enhances performance during exercise of ~1 hour not by being used as a fuel source, but by modulating a yet unknown pathway in the mouth to the brain to reduce fatigue.

Tardy A, Lambert-Porcheron S, Malpuech-Brugère C, et al. Dairy and industrial sources of trans fat do not impair peripheral insulin sensitivity in overweight women. The American journal of clinical nutrition. 2009;90(1):88-94. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19474135.

Observational studies have demonized trans fat and led to their banning in some cities.  This study suggests that some of our conclusions may have been premature.

Stumvoll M, Kahn CR, Blu M. Antioxidants prevent health-promoting effects of physical exercise in humans ¨. Clinical Chemistry. 2009;2(12):2-7.

Another study suggesting that classic vitamin-antioxidants perhaps shouldn’t be included as supplements in diets, at least around exercise.  Mitohormesis/antioxidant/exercise research review coming in 2010.

Sumien N, Heinrich KR, Shetty RA, Sohal RS, Forster MJ. Prolonged Intake of Coenzyme Q10 Impairs Cognitive Functions in Mice. The Journal of nutrition. 2009;(C):3-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19710165.

Health benefits of dietary nutrients are dose dependent.  CoQ10 is no different, and actually worsens cognitive function with too high a dose.

Beher D, Wu J, Cumine S, et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chemical biology & drug design. 2009;74(6):619-24. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19843076.

Resveratrol does not activate SIRT1 directly as previously hyped, rather the target seems to be AMPK.  Seems to be an experimental artifact.

Other Fields

Bondesen Ba, Mills ST, Pavlath GK. The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms. American journal of physiology. Cell physiology. 2009;290(6):C1651-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16467402.

COX, classically regulating production of eicosanoids, also have a role in the control of muscle mass.  The research on NSAID use and resulting implications will be reviewed in a post sometime in the next year.

Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009:1-5. Available at: http://www.nature.com/doifinder/10.1038/nature08221.

The NIA recently started testing a number of substances, each at 3 separate centers for better data.  Rapamycin (mTOR inhibitor) is the first drug that can be qualified as having life extension properties in mice, even when started late in life.  More studies are in progress on rapamycin and other compounds.  It will still be a stretch for human application.

Gottlieb B, Chalifour LE, Mitmaker B, et al. BAK1 gene variation and abdominal aortic aneurysms. Human mutation. 2009;30(7):1043-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19514060.

Genome-wide analysis generally use saliva or blood samples to analyze gene variants.  This intriguing study found that between blood cells and tissue cells, BAK1 SNPs differed, in both diseased and normal subjects.  It may mean that instead of genetics having a significant effect on disease, intra and extracellular milieu may select for minority SNPs as a consequence.  This also adds further evidence that pathologies may not fit the traditional somatic mutation theories.

Pérez VI, Bokov A, Remmen HV, et al. Is the oxidative stress theory of aging dead? Biochimica et biophysica acta. 2009. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19524016.

Decades ago, free radicals were implicated in the ageing process.  While specific radicals in mitochondrial may have a role, in general the theory has been debunked with numerous antioxidant administrations and endogenous antioxidant gene manipulations showing no effect on lifespan in rodents.

Alvergne A, Lummaa V. Does the contraceptive pill alter mate choice in humans? Trends in ecology & evolution (Personal edition). 2009:1-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19818527.

A great review on the evidence that contraceptive pills are altering mate selection for both genders.  Perhaps it is time to be more proactive on this issue?

Blaauw B, Canato M, Agatea L, et al. Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2009;23(11):3896-905. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19661286.

This study adds clarity to the issue of when satellite cells are required for hypertrophy.  Overload and testosterone appear to require their activation, while the Akt pathway does not.

Heisenberg M. Is free will an illusion? Nature. 2009;459(May).

Free will is a heated topic in neuroscience, and this short article summarizes the issue well.

Miller GE, Chen E, Fok AK, et al. Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Current. 2009:1-6.

Poverty is one of the biggest factors influencing disease risk later in life, and we are starting to find mechanistic reasons why.

Milner CE, Cote KA. Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience with napping. Journal of sleep research. 2009;18(2):272-81. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19645971.

Many cultures take naps, and its effects on health and performance are intriguing.

Sharot T, Shiner T, Brown AC, Fan J, Dolan RJ. Dopamine Enhances Expectation of Pleasure in Humans. Current biology : CB. 2009:1-4. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19913423.

L-DOPA (dopamine) alters prediction of future pleasure (but not as a reward chemical itself as often wrongly suggested).

Barrick JE, Yu DS, Yoon SH, et al. Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature. 2009;461(7268):1243-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19838166.

An update to a 20 year experiment (40,000 generations) tracking evolution of E. coli.

Kapogiannis D, Barbey AK, Su M, et al. Cognitive and neural foundations of religious belief. PNAS. 2009;(3):1-6.

Evidence that religious belief seems to have hijacked evolutionary neural networks involved in emotion, abstract semantics, imagery, and more.  The fact that it was funded by the NIH is even better!

Campbell A, Hausenblas Ha. Effects of exercise interventions on body image: a meta-analysis. Journal of health psychology. 2009;14(6):780-93. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19687115.

Exercise improves many aspects of health independent of weight loss, including body image.  This meta-analysis on the issue was recently published.

Oxidative stress has been implicated implicated in insulin resistance, and a new study by Hoehn et al. (1) adds some convincing evidence that one specific radical, superoxide generated in the mitochondria, may be a unifying cause.  But the findings suggest that we may need to reconsider how we treat it.

The authors begin by suggesting that the failure of the recent ACCORD trial that found an increase in mortality when trying to lower glycated hemoglobin with drugs and/or insulin in diabetics may be explained by an increase in “intracellular stress by increasing nutrient delivery to an already stressed cell.”   Note: to be objective, there are other theories on polypharmacy and the sort.

Here is a summary of their experiments:

In vitro

Because an increase in mitochondrial oxidative stress has been found in differing models of inducing insulin resistance: inflammation, corticosteroids, chronic hyperinsulemia, or hyperlipidemia, it may be a common unifying mechanism governing it.  In these 4 models, mitochondrial superoxide was found to be increased.  Superoxide is formed mainly when electrons escape from complex I and/or III in the electron transport chain and react with oxygen.

Then, they induced insulin resistance in myocytes via incubation in the fatty acid palmitate and treated them with a mitochondrial uncoupler and an electron transport chain complex I inhibitor which reduce superoxide formation.  Both resulted in a reversal of insulin resistance, suggesting superoxide as a causal mechanism for induction of insulin resistance.

Superoxide scavengers were tested next, with 3 mitochondrial superoxide dismutase mimetics which also reversed palmitate induced insulin resistance.  A cytoplasmic superoxide dismutase mimetic had no effect, suggesting the mitochondrial derived superoxide is indeed the likely causal candidate.

Further evidence comes from the next experiment which involved genetic overexpression of the superoxide dismutase in the mitochondria (MnSOD); a 2.5 fold overexpression did not effect GLUT4 translocation in control myocytes but prevented insulin resistance induced by the 4 models described above, but seemed to potentiate insulin induced GLUT4 translocation, possibly because of an enhanced conversion of superoxide to hydrogen peroxide by superoxide dismutase.

Finally, using a compound to induce superoxide at complex III of the electron transport chain reduced insulin stimulated GLUT4 translocation in myocytes.  To make sure it was the superoxide and not the inhibition of complex III which caused insulin resistance, the investigators used another compound that blocks the electron transfer to where the previous compound binds on complex III, which prevented insulin resistance.  Two superoxide dismutase mimetics also prevented the complex III inhibition induced insulin resistance.  Interestingly, the inhibition did not influence insulin signaling through Akt as its phosphorylation was normal at varying insulin concentrations.

In vivo

The researchers then performed several in vivo studies in mice.  Acute dosing of a mitochondrial superoxide dismutase mimetic with a high fat diet improved glucose tolerance by an increase in muscle and fat insulin sensitivity.  Then, transgenic overexpression of mitochondrial superoxide dismutase showed a resistance to a insulin resistance induced by a high fat diet compared to controls after 1 week, 12 weeks, and 24 weeks.  In the latter 2 periods, the transgenic mice gained the same amount of weight as the controls but were more resistant to insulin resistance.  Then, in heterozygous mutant mice for mitochondrial superoxide dismutase, it was found that the resulting 70% reduction of the enzyme in muscle and fat impaired glucose tolerance on a low fat diet even with similar insulin concentrations to controls.

What does it mean?

Shuttling more nutrients through oxidative phosphorylation with insulin without increasing ATP consumption could increase mitochondrial superoxide because of ADP depletion and a reduction in electron carrier availability.  In this manner, superoxide induced insulin resistance is an antioxidant in that it reduces further superoxide production, because it prevents too much glucose from entering the cell and undergoing oxidative phosphorylation.  Superoxide also increases mitochondrial uncoupling and endogenous antioxidant genes in other studies, so insulin resistance seems to be another layer of protection that it adds to minimize cellular damage from overnutrition.

Fewer mitochondrial also may increase stress and result in an increased superoxide production.  Lifestyle interventions such as intermittent fasting/fasting, calorie restriction, and endurance exercise promote mitochondrial biogenesis and are beneficial to diabetics in other research (especially exercise).

Interestingly, previous studies have implicated hydrogen peroxide as the cause of insulin resistance.  Additionally, alpha lipoic acid, a compound available as a nutritional supplement, ameliorates insulin resistance and one of the proposed mechanisms is through its scavenging of hydrogen peroxide (and superoxide).  Human studies also exist for the use of lipoic acid for diabetes treatment (example).  I also recall that it stimulates mitochondrial biogenesis, likely via AMPK activation.   This study paradoxically suggests that an increase in hydrogen peroxide may actually increase insulin sensitivity, which will require further contextual study.  Though lipoic acid reduces glycation in other studies, the authors suggest (without comment on LA) that mitochondrial antioxidant therapy may theoretically impair protective mechanisms induced by superoxide without solving the underlying pathology, resulting in other problems such as AGE formation (glycation).  Clearly this deserves further study, especially with needed alternative treatments with the ACCORD failure.

Reference

1.  Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ, Stocker R, Van Remmen H, Kraegen EW, Cooney GJ, Richardson AR, & James DE (2009). Insulin resistance is a cellular antioxidant defense mechanism. Proceedings of the National Academy of Sciences of the United States of America, 106 (42), 17787-92 PMID: 19805130