Read More

Related to allergenic profile

EoE is an allergy-based disorder. It presents commonly in adults as long standing dysphagia, sometimes with food impaction.[3]

Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically; they are therefore regarded as first-line drug therapy. Elimination diets have similar efficacy as topical corticosteroids, but their long-term use is limited by compliance issues. Resolving the altered mucosal immune loss of tolerance offers a tantalising opportunity for natural resolution.

Findings

EoE, increasingly recognised in both adults and children, is characterised especially by oesophageal symptoms of dysphagia with impaction (a feeling of food being stuck at the lower end of the oesophagus) and biopsy evidence of significant eosinophil accumulation in the oesophageal epithelium.

Data collected so far suggest a multi-step allergy process starting with an atopic skin response that later primes the oesophagus on further allergen exposure – known as the ‘allergic march’, and which may be linked to thymic stromal lymphopoietin (TSLP).[4] Diagnosis of EoE is suggested by food impaction in a young adult with a personal and family history of allergy.

Nutritional Pearls

With respect to dietary counselling, the pearls that I would give you here are: when you talk to a patient with EoE, one thing that I use is the cardinal dysphasia diet. Explain the benefits of avoidance of anything that’s cut into anything other than a miniscule piece. The reduction of food mass especially food groups that are particularly notorious for catching in the oesophagus with a structural lesion such as EoE. Tough meat, doughy bread products, pasta — sometimes it will glom up and become very much of a bolus, rice, anything with a skin, like a potato skin, a fresh fruit or vegetable that’s raw and hard, those things are particularly likely to catch, so I just tell them, if you want a fresh fruit or vegetable, make sure it’s soft, cooked, and you cut it well. Those are dietary recommendations that I use routinely in all my EoE patients.

Next an exclusionary diet, or at least the exclusion of any recognised food allergens ahead of any clinical testing is worth undertaking as the benefits will be felt soon. Then, using digestive enzymes to aid in stomach and small intestinal degradation of antigens offers increased reduction in irritation.

TSLP inhibition through the inclusion of natural agent demonstrated in in-vitro studies to contribute to the suppression of the TSLP related allergic march are also worth exploring. These will include selenium, green tea, pineapple juice and berberine.[5],[6],[7],[8]

References

[2] Hruz P, Straumann A, Bussmann C, Heer P, Simon HU, Zwahlen M, et al. Escalating incidence of eosinophilic esophagitis: A 20 year prospective, population-based study in Olten County Switzerland. J Allergy Clin Immunol. 2011;128:1349–50. View Abstract

[3] Dellon ES. Eosinophilic esophagitis: diagnostic tests and criteria. Curr Opin Gastroenterol. 2012 Mar 22. [Epub ahead of print] View Abstract

[4] Sherrill JD, Gao PS, Stucke EM, Blanchard C, Collins MH, Putnam PE, Franciosi JP, Kushner JP, Abonia JP, Assa’ad AH, Kovacic MB, Biagini Myers JM, Bochner BS, He H, Hershey GK, Martin LJ, Rothenberg ME. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol. 2010 Jul;126(1):160-5.e3. View Abstract

[5] Moon PD, Kim HM. The suppression of thymic stromal lymphopoietin expression by selenium. Amino Acids. 2011 Nov 16. View Abstract

[6] Moon PD, Choi IH, Kim HM. Epigallocatechin-3-O-gallate inhibits the production of thymic stromal lymphopoietin by the blockade of caspase-1/NF-κB pathway in mast cells. Amino Acids. 2011 Aug 11. View Abstract

[7] Moon PD, Choi IH, Kim HM. Naringenin suppresses the production of thymic stromal lymphopoietin through the blockade of RIP2 and caspase-1 signal cascade in mast cells. Eur J Pharmacol. 2011 Dec 5;671(1-3):128-32. Epub 2011 Sep 24. View Abstract

[8] Moon PD, Choi IH, Kim HM. Berberine inhibits the production of thymic stromal lymphopoietin by the blockade of caspase-1/NF-κB pathway in mast cells. Int Immunopharmacol. 2011 Nov;11(11):1954-9. Epub 2011 Aug 19. View Abstract

Overview

Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly affecting the health and well-being of the host. Early microbial colonisation in infants is critically important for directing neonatal intestinal and immune development, and is especially attractive for studying the development of human-commensal interactions.

Study findings

The study, which confirms earlier findings that show breast-feeding boosts the developing immune system, elucidated the chatter between genes in the developing infant and the gut bacteria by analysing the relationship between bacterial communities found in the guts of 6 breast-fed 3-month-olds and 6 formula-fed 3-month-olds. The researchers compared the gut microbiome information to gene expression levels in the infant gut and identified genes involved in immunity and defense with altered expression levels in relation to the gut bacteria in breast-fed infants.

The authors concluded:

We demonstrate that differences in diet can affect, via gut colonisation, host expression of genes associated with the innate immune system.

“While we found that the microbiome of breastfed infants is significantly enriched in genes associated with ‘virulence,’ including resistance to antibiotics and toxic compounds. We also found a correlation between bacterial pathogenicity and the expression of host genes associated with immune and defence mechanisms,”

“Collectively, these data are consistent with previous findings that breast-feeding facilitates the adaptive, functional changes required for optimal transition from intrauterine to extrauterine life,” the authors write.

Comment

The implication is that in genetically susceptible neonates lack of breast milk ingestion may contribute to lack of interspecies variation and loss of complex immune priming and adaptability. This in turn may contribute to loss of flexibility in the young immune system and predispose people to amplifying genetic susceptibilities for allergies or other immune driven illnesses.

Reference

The WHO another data crunching megalith estimates that 6% of cancers in wealthy nations and 22% in low- and middle-income countries are caused by infectious agents: viruses such as HBV, HPV and hepatitis C virus (HCV), bacteria such as Helicobacter pylori and waterborne parasites.

However, the real impact on risk is: lifestyle as this affects cancer risk, too. In the past two decades as waistlines have expanded, so has the evidence linking obesity with the risk of breast, endometrial, colorectal and other cancers.

In the mid-1970s, epidemiological studies suggested that people who ate more fruits and vegetables were at lower risk of several cancers.[2] Last year, epidemiologist Tim Key based at Oxford University concluded somewhat controversially, from nearly three dozen large studies and meta-analyses from the last 20 years that “at least in relatively well-nourished Westernised populations, a general increase in total fruit and vegetable intake will not have a large impact on cancer rates”.[3]

It is possible that the intakes of fruits vegetables and their micronutrients just did not meet the biological needs of the cells to defeat abnormal cell development, as other researchers suggest a more paleothic diet that excludes processed foods as well as including fruits, vegetables and fibre offer a better solution.[4] Plus we know that certain vegetables and fruits have greater impact on prevention than others.

Is Cancer a disease of modern life?

Some scientists consider cancer to be a recent phenomenon, arguing that it was relatively rare in ancient times. Over the past century, population-based cancer incidence has increased dramatically. These higher rates are probably due to two factors: first, we are living longer; and second, our modern age has increased our exposure to cancer-causing chemicals in our environment and to radiation through X-rays, plane travel and other sources.[5]

Incidence of cancer is moving to the developed countries as weight, lifestyle and exposures increase

Can we stop cancer before it starts?

Dozens of studies suggest that preventing some cancers has become a real possibility. One way to prevent cancer is to limit exposure to acarcinogen. This approach worked for young chimney sweeps in nineteenth century England that had demonstrated a high incidence of testicular cancer. It is also clear that notsmoking cigarettes reduces lung cancer risk. Ten years after quitting, a former smoker has only about half the risk of lung cancer compared with someone who still smokes.

Changing addictive behaviours such as smoking is hard, but there may be other ways to prevent cancer. Researchers have recently developed a cancer-preventive vaccine, and others are testing nutrients that may protect against certain cancers.

Scientists are also re-examining ancient ideas about the benefit of a healthy diet by isolating beneficial nutrients and providing them in pill form. Many chemicals in foods have been shown to kill cancer cells in laboratory studies and to prevent cancer in animals. Some of the dietary components being studied are selenium, vitamin E, polyphenols (from green tea), lycopene (tomatoes), resveratrol (grapes and red wine) and omega-3 fatty acids (oily fish). These compounds work by many different mechanisms. For example, many nutrients — such as epigallocatechin gallate (EGCG) in green tea, resveratrol in red wine, and sulforaphane in broccoli — prevent cells from going through the cell cycle, which stops them dividing and giving rise to new cancer cells. In terms of individual cancers a recent research paper in the British Journal of Cancer concluded by stating: Vitamin B12 from diet may be protective against bladder cancer, whereas consuming processed meat may increase risk.[6]

How to optimise the benefits from a healthy diet

1. Remember – all vegetables are not created equal.

Phytonutrients are most often found in pungent vegetables (like onions and garlic), bitter ones (like mustard greens), or ones with acquired tastes (like mushrooms). There are also a number of fruit and vegetables that are not major sources of phytonutrients, – such as apples and potatoes, albeit that they support fibre and SCFA production. The most potent are cruciferous vegetables (those in the cabbage family), specifically broccoli and its payload of glucoraphanin — the precursor of sulforaphane.

2. Remember – all broccoli heads are not created equal.

“So, is broccoli a good way to deliver sulforaphane?” It seems the answer is absolutely no – Different heads of broccoli can vary as much as 20-fold in their content of glucoraphanin. The specific variety, growing conditions, time of year, distance of transport and other factors all affect the concentration of phytonutrients. In fact, the most consistent way to deliver glucoraphanin was to use three-day-old broccoli sprouts.[7] Adding a bit of daikon radish to the broccoli might help eliminate these differences. Daikon radish contains an enzyme, myrosinase, that catalyses the glucoraphanin conversion.

3. Remember – everyone has different genes.

Eating a known amount of phytonutrient doesn’t guarantee that a predictable amount of the cancer-fighting molecule will enter the bloodstream. Differences here can be traced to variations in the genes involved in the digestive processes. For example, the glutathione S-transferase M1 gene (GSTM1) influences the speed at which the body metabolises sulforaphane and expels it in the urine. The faster it happens, the less beneficial the broccoli.

GSTM1 is best understood in terms of the genes that influence phytonutrient metabolism, but it is only part of what is a rapidly growing list. An example of why this genetic variation makes so much difference is that, people who carry two copies of a particular variant of the UGT1A1 gene actually produce about 30% to 40% less than normal of a type of phase II liver enzyme. One study has shown that people with this genotype derive more cancer-protecting benefit from eating cabbage- and carrot-family vegetables — possibly because phytonutrients in these foods boost UGT1A1 activity closer to normal.[8]

4. Remember -human microbiomes vary.

Conversion of Soy Daidzein into Cancer Preventing Agents is affected by a variety of lifestyle modifiers.

This includes an impact from their genetic and digestive components. Our bacterial genes also determine the power of phytonutrients in our diet. Our digestive tract bacteria are significantly involved in the metabolism of the phytonutrients from soy, turning one type of isoflavones into another. So depending on your intestinal bacteria, two people who eat the same amount of soy each day might receive not only different quantities of isoflavones, but also different end-products.[9],[10]

The specific bacterium/bacteria responsible for equol which some scientists believe is one of the more beneficial forms of isoflavone; around 80% to 90% of people have bacteria that produce O-desmethylangolensin, a less active molecule. Equol and O-DMA are more biologically active than their precursor daidzein an isoflavone phytoestrogen found in soy. Interestingly, substantial interindividual differences in daidzein metabolism exist; approximately 30%-50% of the human population produce equol, and approximately 80%-90% produce O-DMA.[11]

5. Remember – your age at consumption impacts on benefits.

Studies, mostly conducted on animals and epidemiology analysis of human consumption of soy, miso and tofu suggests that benefits in terms of cancer reduction is linked to early age intake. It also seems unlikely that if the individual refuses to change from a typical western diet that the impact is minimal.[12] But eating it throughout formative years does seem to reduce risk against breast cancer despite a later shift in food selection.[13]

6. Remember – phytonutrients can be difficult to extract.

The essential ingredients found in berries and other phytonutrient foods tend to be available on a seasonal basis and may be too expensive to encourage year round consumption, this may lead to inadequate intakes of the foods to impact on cell differentiation and prevention, Supplementing the diet with concentrated food supplements is considered a supportive approach, but does not confer the same whole diet benefits and must not be seen as a replacement to overall food selection, but as a key nutrient amplifier.

7. Remember – The total diet is greater than its individual parts.

It is likely that these effects are not limited to experimental concoctions. Gut bacteria influence how phytonutrients are processed, but fibre intake and other aspects of the diet alter the gut ecosystem. Selecting food groups that favour a wide range of key nutrients as well as those that favour beneficial bacterial compositions will have a greater impact on risk reduction than isolated compounds. This may also include the use of specific strain bacteria and cooperative isolates to extract the best overall benefits.[14]

References

[2] Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer. 1975 Apr 15;15(4):617-31. View Abstract

[3] Key TJ. Fruit and vegetables and cancer risk. British Journal of Cancer (2011) 104, 6–11. doi:10.1038/sj.bjc.6606032 View Full Paper

[4] Lindeberg S. Paleolithic diets as a model for prevention and treatment of Western disease. Am J Hum Biol. 2012 Mar-Apr;24(2):110-5. doi: 10.1002/ajhb.22218. Epub 2012 Jan 19. View Abstract

[5] David AR, Zimmerman MR. Cancer: an old disease, a new disease or something in between? Nat Rev Cancer. 2010 Oct;10(10):728-33. Epub 2010 Sep 3. View Abstract

[6] J W Wu, A J Cross, D Baris, M H Ward, M R Karagas, A Johnson, M Schwenn, S Cherala, J S Colt, K P Cantor, N Rothman, D T Silverman and R Sinha Dietary intake of meat, fruits, vegetables, and selective micronutrients and risk of bladder cancer in the New England region of the United States British Journal of Cancer , (8 May 2012) | doi:10.1038/bjc.2012.187 View Abstract

[7] Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10367-72. View Full Paper

[8] Ambrosone CB, Tang L. Cruciferous vegetable intake and cancer prevention: role of nutrigenetics. Cancer Prev Res (Phila). 2009 Apr;2(4):298-300. Epub 2009 Mar 31. Review. View Full Paper

[9] Lampe JW. Is equol the key to the efficacy of soy foods? Am J Clin Nutr. 2009 May;89(5):1664S-1667S. Epub 2009 Apr 8. View Full Paper

[10] Atkinson C, Frankenfeld CL, Lampe JW. Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp Biol Med (Maywood). 2005 Mar;230(3):155-70. Review. View Full Paper

[11] Yuan JP, Wang JH, Liu X. Metabolism of dietary soy isoflavones to equol by human intestinal microflora–implications for health. Mol Nutr Food Res. 2007 Jul;51(7):765-81. Review. View Abstract

[12] Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008 Jan 15;98(1):9-14. Epub 2008 Jan 8. Review. View Full Paper

[13] Maskarinec G, Noh JJ. The effect of migration on cancer incidence among Japanese in Hawaii. Ethn Dis. 2004 Summer;14(3):431-9. View Abstract

[14] Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009 Oct 29;461(7268):1282-6 View Abstract

Whilst there are practical considerations – there has been one small study on home administration[1] and numerous anecdotal discussions regarding its use in a wide range of illnesses, for which a recovery has been confirmed.

A recent study ( March 2012)  published in the journal Gastroenterology is one of the largest exploring Clostridium difficile patients and their outcomes following faecal transplantation.[2]

Patients who suffer from protracted Clostridium difficile colitis despite receiving oral antibiotic therapy, often for months, have become a challenge for physicians all over the world.

The investigators reviewed data from 70 adults (mean age, 73; 86% outpatients) who had received up to 12 courses of antibiotics for CDI; most had received 3 to 6 courses. Most stool donors were close relatives of the patient. Transplantations were performed using a uniform protocol, which involved bowel preparation with an oral polyethylene glycol solution, followed by an infusion of stool into the caecum via colonoscope.

Three months after transplantation, 66 of the 70 patients reported complete resolution of symptoms. The four who did not respond all had the virulent 027 strain of C. difficile as well as other serious medical illnesses; all died within 3 months of transplantation. In the year following transplantation, four additional patients relapsed; two were treated successfully with antibiotics, and two received another faecal transplant. No complications of transplantation were reported.

No other C. difficile treatment achieves anything like the 94% eradication rate reported in this study, even in patients with relatively mild disease. Faecal transplantation would probably become the gold-standard treatment for CDI if the logistics of arranging it were not so daunting.

However, the discomfiture displayed by the physician is less of a problem for the ill patient – once the concept is fully understood and the application standardised – in as much as there is a preferred in hospital or at home methodology and pre transplant prep, then this therapy will be used more and more saving lives, money and families from unwanted misery and even death. Physician driven exclusion based on the ‘yuck’ factor is a poor and emotive based reason to avoid a compellingly safe and effective treatment.

References

[2] Mattila E, Uusitalo-Seppälä R, Wuorela M, Lehtola L, Nurmi H, Ristikankare M, Moilanen V, Salminen K, Seppälä M, Mattila PS, Anttila VJ, Arkkila P. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology. 2012 Mar;142(3):490-6. Epub 2011 Dec 7. View Abstract

Now as we know, to be politically correct we have to state that a ‘balanced diet’ – the unicorn of daily food choice can supply all that our bodies and brains need to feel tip top. We also know that according to the UK’s very own National Diet and Nutrition survey, that our balanced diet focused population suffers from vitamin deficiencies or inefficiencies across pretty much all vitamin groups.

Whilst in no way a suggestion that supplementation should replace the mythical source of all we need to thrive, there is a clear indication that isolated nutrients can have their benefits lost in the noise of analysis, and that multi-nutrients which operate in a synergistic manner may offer a level of functionality unable to be achieved through current UK eating habits in the general population.

Comment

The role of fatty acids and micro nutrients in terms of the health gains offered are well documented and poorly communicated. These latest papers help to add to the slow persuasion of our nutritionally minded ‘flat earthers’ that the investment in supplements may well be one of the best out of pocket spends they undertake.

References

[2] Kennedy DO, Veasey R, Watson A, Dodd F, Jones E, Maggini S, Haskell CF. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl). 2010 Jul;211(1):55-68. Epub 2010 May 8. View Abstract

[3] Jackson PA, Reay JL, Scholey AB, Kennedy DO. Docosahexaenoic acid-rich fish oil modulates the cerebral hemodynamic response to cognitive tasks in healthy young adults. Biol Psychol. 2012 Jan;89(1):183-90. Epub 2011 Oct 19. View Abstract

[4] Haskell CF, Robertson B, Jones E, Forster J, Jones R, Wilde A, Maggini S, Kennedy DO. Effects of a multi-vitamin/mineral supplement on cognitive function and fatigue during extended multi-tasking. Hum Psychopharmacol. 2010 Aug;25(6):448-61. View Abstract

Overview

At some point we all experience fatigue, but it usually resolves on its own and is easily explained. Sometimes it has a straight-forward organic explanation, sometimes not.  For many however, such organic explanations fail to present a validated route to satisfactory resolution. As research into persistent fatigue has progressed most clinicians comprehend that all explanatory models of the causes and mechanisms of fatigue and exhaustion proceed from the assumption that they are complex, multifactorial processes. For example, fatigue has been proposed to have biochemical, immunological, emotional, behavioural and cognitive components, to name a few that contribute to overall fatigue.

Fatigue is usually understood as a loss of overall energy and inability to perform even simple tasks without exertion. At the cellular level, fatigue is related to adversely altered cellular energy systems found primarily in the cellular mitochondria.

At the biochemical level fatigue is related to the metabolic energy available to tissues and cells, mainly through mitochondrial electron transport. Electron transport is directly linked to functional, intact inner mitochondrial membranes. Thus the integrity of mitochondrial membranes is critical to cell function and energy metabolism.[1]

Fatigue is the most common complaint of patients seeking general medical care; between 7% and 45% of primary care consultations involve fatigue as a major complaint.[2] It appears that some degree of fatigue may be identified in nearly all of the population,[3] indicating that fatigue is not simply an individual problem; it is also a public health problem. Fatigue can progress to the point that it causes disability comparable to that found in chronic medical patients.[4],[5]

The successful management or resolution of fatigue is also important in various physical activities of relatively healthy men and women, such as work and sports performance.

Many who experience fatigue do not initially seek primary care intervention but self-treat with stimulants such as central nervous system agonists that include caffeine, herbs and sugars. Although these provide short term increases in energy and perception of reduce fatigue, they have potential long term adverse health effects.[6],[7]

Fatigue: Successful Intervention

Recent clinical trials using patients with chronic fatigue[8] have shown the benefit of an oral non- central nervous system agonist; Lipid Replacement Therapy (LRT). Using naturally occurring glycophospholipids, cofactor nutrients and probiotics mitochondrial electron transport function can been restored and moderate to severe chronic fatigue can be significantly reduced in the process.[9],[10]

Additional studies have also identified significant improvements in energy, mood, affect and function in a healthy population following ingestion of the glycophospholipids and cofactor nutrients in a drink.[11],[12] These additional natural agents (principally antioxidants and bacterial mediators of immune tolerance) have also shown benefits from a molecular perspective in the inhibition of immune mediated inflammation and associated fatigue.[13],[14],[15],[16]

LRT is a dietary approach to replace damaged cellular lipids with undamaged (unoxidised) lipids to ensure proper function of cellular structures, such as cellular and organelle (mitochondrial) membranes. LRT can result in the cellular delivery of unoxidised, undamaged membrane glycophospholipids in order to replace damaged lipids and restore function to cellular membranes. LRT has proven to be an effective method to prevent ROS/RNS-associated changes in function and for use in the treatment of various clinical conditions.

In recent studies using LRT and co factor nutrients for 6 months or more has also reduced the blood levels of the amino acid homocysteine, which are related to increased risk for cardiovascular disease, stroke, cognitive loss, depression and immune dysfunction.[17]

The role of glycophospholipids and other food-derived agents are attractive as safe and effective interventions in the treatment of persistent and transient fatigue. Studies have been conducted on various populations from those with normal health and function to those undergoing complex treatments for cancer and those with persistent fatigue. These groups have shown between 30-40% improvement in fatigue perception and function utilising the internationally recognised Piper Fatigue Scale.[18],¹²

Mechanisms of Fatigue and its Resolution (click image to enlarge)

There are multiple explanations, for the development and maintenance of fatigue. Reduction in mitochondrial activity both activates and is activated by the innate immune system, and this can be resolved, in part, through the restoration of mitochondrial lipid membranes and the supply of absorbable energy relevant micronutrients. These favour the restoration and optimisation of ATP and NADH production, while prebiotics and probiotics favour immunological tolerance and the restitution of inflammasome induced dysbiosis and immune driven inflammation.

Mitochondria are responsible for many metabolic circuits and signaling pathways. Just a few examples of these include: oxidative phosphorylation, the mechanism our cells use to generate most intracellular ATP (cellular fuel); biosynthesis of key molecules including haeme and certain steroids as well as in many catabolic energy relevant pathways such as the β-oxidation of fatty acids; and regulation of calcium homeostasis. Importantly mitochondria are responsible for production of most of our cell’s reactive oxygen species (ROS) and some reactive nitrogen species (RNS). Significant oxidative damage to mitochondrial membranes also represents the point of no return of programmed cell death pathways that culminate in apoptosis or regulated necrosis.[19]

Immune Inflammation

Of clinical interest from an immunological perspective, recent studies suggest that mitochondria are significant players in the orchestration of innate immune responses via activation of a multiprotein complex called the inflammasome which results in the production and release of the pro-inflammatory cytokines IL-1β and IL-18.[20],[21]

These, in turn, contribute to defensive and coordinated management of the bacterial organisms that reside in our digestive tract. The digestive tract is home to trillions of bacteria and this represents the site of greatest density of innate immune receptors in the body. These receptors are key mediators in the management and maintenance of immune response and tolerance. Their inappropriate activation and expression by IL-1β and IL-18 leads to altered innate immune hyper-responsiveness and may contribute to immune mediated inflammatory diseases as well as fatigue through the subsequent development of persistent molecular inflammation.

Damage to mitochondrial components, especially the delicate inner mitochondrial membrane, leads to the cytosolic release of toxic proteins (caspases and non-caspases) that are normally confined in the mitochondria. These released proteins then bind to specialised innate immune inflammasome activating receptors called nucleotide-binding-and-oligomerisation domains (NOD’s).

These NOD receptors recognise not only intracellular pathogen-associated molecular patterns but also self-generated signals known as ‘damage-associated molecular patterns’ (DAMPs). Examples are extracellular ATP, uric acid and heat shock proteins that accumulate with stress and trigger inflammasome activity. New evidence has placed inflammasomes at the center stage of complex diseases (metabolic syndrome and carcinogenesis) and physiological processes (regulation of intestinal microbial ecology) and energy management.[22],[23],[24],[25],[26],[27],[28]

Increased toxic metabolites and trans-membrane ion leakage suppresses the core ability of the mitochondria to produce ATP and alter nutrient uptake resulting in overall reductions in energy and persistent fatigue.

Damage to mitochondrial membranes is typically due to ROS, RNS, environmental stressors, cellular aging and mitochondropathies. All of these factors also inhibit mitophagy – a natural process that normally limits ROS-related damage by safely removing damaged and inflammation-promoting mitochondria and mitochondrial components. This results in an inflammatory driven feed forward cycle, in which membrane damage continues to produce ROS and RNS and damage associated molecular patterns (DAMPs) contributing to numerous diseases and functional loss of cellular energy.

The innate immune receptors, known as pattern recognition receptors (PRRs) are stimulated by these DAMPs to induce the production of inflammatory cytokines, sustaining and promoting inflammation. These components, in turn, orchestrate the assembly of a supramolecular platform (the inflammasome), which then activates pro-inflammatory immune cytokines such as IL-1β, IL-18 and Nuclear Factor Kappa B (NFκβ). This process is the defining link between innate immune responses and mitochondrial functionality. Once activated additional innate immune effects include the induction of hyper-responsive actions that occur with with bacterial triggers from the gastrointestinal tract. The consequences include local inflammation, loss of mucosal barrier integrity and fatigue.[29],[30]

The molecular mechanisms utilised by bacteria in our gut to maintain immune homeostasis and tolerance through macrophage and dendritic cell activation can be manipulated to favour the promotion of anti-inflammatory cytokines such as IL-10 and TGFβ. The ingestion of probiotics and prebiotics can be used to mediate immune responsiveness via the promotion of regulatory Tcells, dendritic cells and low counter activation of either T helper-mediated: Th1 and Th2 driven inflammatory responses.[31],[32] The field of immune intervention via consumption of bacteria is over 100 years old, but has recently experienced a significant increase in interest, as the role of the bacteria in our gut is now understood to influence local and systemic illness.[33]

This sequence of events places mitochondria at the cross roads of bioenergetics metabolism, cell death signaling and the innate and adaptive immune system.

Healthy mitochondrial function (and death) determines appropriate management of energy production, fatigue control and innate immune driven inflammation responsiveness. Using LRT administered as a nutritional supplement with antioxidants assures that mitochondrial membrane permeability is maintained in the optimal range preventing oxidative membrane damage, and reducing the number of mitochondrial DNA deletions. Thus LRT can be used to restore mitochondrial and other cellular membrane functions via delivery of undamaged replacement lipids to cellular organelles.[34]

LRT is not just the dietary substitution of certain lipids with proposed health benefits; it is the actual replacement of damaged cellular lipids with undamaged lipids to ensure proper structure and function of cellular structures, mainly cellular and organelle membranes.¹²

Inflammation is an essential immune response that enables survival during infection or injury and maintains tissue homeostasis under a variety of noxious conditions. Inflammation comes at the cost of a transient decline in local tissue function, which can in turn contribute to the pathogenesis of diseases and loss of function related to altered homeostasis. Inflammation has been described as the ‘common soil’ of altered health and function.[35]

Inflammation driven fatigue is a recognised consequence of host defence, and raising immune responsiveness is an energy dependent process that is a component of post viral and bacterial infection as well as a more recently proposed response to altered microbial composition (dysbiosis) in the human gut due to environmental driven factors and mitochondrial damage.[36],[37]

This suggests that alterations to the microbial balance in the digestive tract may induce loss of tolerance and subsequent increase in receptor stimulation, which in turn is amplified via mitochondrial membrane permeability, DAMP production and inflammasome stimulation. This may then lead to ‘inflammasome-induced dysbiosis’, which whilst a relatively new area of research may provide some interesting pathophysiological connections.[38] (click image to enlarge)

Danger signals including those released as DAMPs can stimulate the overproduction of ROS. ROS then promote mitochondrial permeability transition (MPT) that favours membrane leakiness, additional ROS and feed forward uncoupling. The activation of the PRR/NOD receptors and inflammasome stimulates additional mitochondrial DNA to be released. This further stimulates the inflammasomes and activating the innate immune system to respond more vigorously, including the release of proinflammatory IL-1β and IL-18. Mitophagy normally assists in the management of this process by removing ROS producing mitochondria, but DAMPs, environmental stressors, dysbiosis, cytotoxic signals, nutrient deficiencies, mitochondropathies, and cellular aging have all been associated with the suppression of mitophagy and the subsequent accumulation of damaged mitochondria. This model reflects how the activation of mitochondrial damage with altered membrane permeability leads to the production of inflammation that increases fatigue and related conditions.

Resolution of Chronic Conditions

People with fatiguing conditions often exhibit “sickness” signs and symptoms for a variety of reasons.[39] One of these may be an increase in peripheral pro-inflammatory signaling. This notion is based on overwhelming evidence that pro-inflammatory cytokines are capable of inducing all the cardinal symptoms of CFS in humans.[40],[41]

The use of selected immune modulating probiotics along with LRT provides the cytokine milieu the opportunity to be beneficially altered through the management of mitochondrial membrane repair, DAMP reduction and PRR induced tolerance via changes in bacterial ratios in the gut towards ones that favour symbiosis. The activation of PRRs induces host-defense signaling pathways that culminate in the production of proinflammatory and antimicrobial molecules as well as anti-inflammatory molecules. Resolution of inflammasome-induced dysbiosis makes a considerable contribution towards improving mitochondrial fitness, just as mitochondrial fitness contributes to the healthy management of gut-mediated immune reactivity.

A central question in immunology is how the immune system discriminates between commensal and pathogenic bacteria. This problem is particularly important in the intestine, where trillions of commensal microorganisms continually challenge the immune system without eliciting a proinflammatory response, and where probiotics, when carefully selected by species and strain can amplify either desired outcome.[42]

The results – recovery from fatigue derived from LRT and associated pro and pre-biotics, along with antioxidants are likely due to reduced pro-inflammatory cytokines and reduced innate immune receptor hyper-sensitivity.

In addition to fatigue, mitochondrial dysfunction and the accumulation of damaged mitochondrial components have also been linked to a wide variety of chronic, metabolic and degenerative diseases, aging and cancer.[43]

LRT has been successfully used in clinical studies to reduce fatigue, increase mitochondrial function and protect cellular and mitochondrial membranes from oxidative damage.¹⁰ In multiple clinical studies fatigue was reduced 35-43% by oral administration of LRT and key nutrients. Even in severely fatigued patients with chronic fatigue syndrome or fibromyalgia syndrome, LRT reduced fatigue by 43.1%.

In the study by Agadjadyan et al.[44] LRT (supplied as NT Factor^®) reduced fatigue 35.5% in aging adults and significantly improved mitochondrial function to a level that was similar to that found in young, healthy adults.

This health altering intersection of immunity, oxidative stress and dysbiosis, can be found in the membranes of the mitochondria residing in our cells – not only of the gastrointestinal tract but all other tissues as well. The clinical use of LRT has the potential to decrease the effects of aging on mitochondria and improve mitochondrial function in chronic diseases, diminish fatigue and improve altered states of mucosal immunity through the participatory resolution of inflammasome mediated dysbiosis. The improvement in terms of restitution of mucosal and immunological tolerance has potential health benefits that extend systemically.[45]

References

[2] Lewis G, Wessely S: The epidemiology of fatigue: more questions than answers. J Epidemiol Community Health 1992, 46(2):92-97. View Full Paper

[3] Cloninger CR. A systematic method for clinical description and classification of personality variants.  A proposal. Arch Gen Psychiatry. 1987 Jun;44(6):573-88. View Abstract

[4] Nelson E, Kirk J, McHugo G, Douglass R, Ohler J, Wasson J, Zubkoff M. Chief complaint fatigue: a longitudinal study from the patient’s perspective. Fam Pract Res J. 1987 Summer;6(4):175-88.  View Abstract

[5] Nijrolder I, van der Windt DA, van der Horst HE. Prognosis of fatigue and functioning in primary care: a 1-year follow-up study. Ann Fam Med. 2008 Nov-Dec;6(6):519-27. View Abstract

[6] Gunja N, Brown JA. Energy drinks: health risks and toxicity. Med J Aust. 2012 Jan 16;196(1):46-9.  View Abstract

[7] Arria AM, Caldeira KM, Kasperski SJ, Vincent KB, Griffiths RR, O’Grady KE. Energy drink consumption and increased risk for alcohol dependence. Alcohol Clin Exp Res. 2011 Feb;35(2):365-75. doi: 10.1111/j.1530-0277.2010.01352.x. Epub 2010 Nov 12. View Abstract

[8] Avellaneda Fernández A, Pérez Martín A, Izquierdo Martínez M, Arruti Bustillo M, Barbado Hernández FJ, de la Cruz Labrado J, Díaz-Delgado Peñas R, Gutiérrez Rivas E, Palacín Delgado C, Rivera Redondo J, Ramón Giménez JR. Chronic fatigue syndrome: aetiology, diagnosis and treatment. BMC Psychiatry. 2009 Oct 23;9 Suppl 1:S1. Review. View Abstract

[9] Nicolson, G.L. and Ellithrope, R. Lipid replacement and antioxidant nutritional therapy for restoring mitochondrial function and reducing fatigue in chronic fatigue syndrome and other fatiguing illnesses.  J. Chronic Fatigue Syndr. 13(1): 57-68 (2006). View Full Paper

[10] Nicolson, G.L. and Settineri, R. Lipid Replacement Therapy: a functional food approach with new formulations for reducing cellular oxidative damage, cancer-associated fatigue and the adverse effects of cancer therapy. Funct. Food Health Dis. 4: 135-160 (2011). View Full Paper

[11] Ellithorpe, R.A., Settineri, R., Mitchell, C.A., Jacques, B., Ellithorpe, E. and Nicolson, G.L.  Lipid replacement therapy drink containing a glycophospholipid formulation rapidly and significantly reduces fatigue while improving energy and mental clarity. Funct. Food Health Dis. 8: 245-254 (2011). View Full Paper

[12] Nicolson GL, Ellithorpe RR, Ayson-Mitchell C, Jacques B, Settineri R. Lipid Replacement Therapy with a Glycophospholipid-Antioxidant-Vitamin Formulation Significantly Reduces Fatigue Within One Week. JANA Vol 13 No1 2010: 10-14 View Full Paper

[13] Ströhle A, Wolters M, Hahn A. Micronutrients at the interface between inflammation and infection–ascorbic acid and calciferol: part 1, general overview with a focus on ascorbic acid. Inflamm Allergy Drug Targets. 2011 Feb;10(1):54-63. Review. View Abstract

[14] Ströhle A, Wolters M, Hahn A.Micronutrients at the interface between inflammation and infection–ascorbic acid and calciferol. Part 2: calciferol and the significance of nutrient supplements. Inflamm Allergy Drug Targets. 2011 Feb;10(1):64-74. Review. View Abstract

[15] Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, Fleshner M, Green C, Pedersen BK, Hoffman-Goetz L, Rogers CJ, Northoff H, Abbasi A, Simon P. Position statement. Part one: Immune function and exercise. Exerc Immunol Rev. 2011;17:6-63. Review. View Abstract

[16] Walsh NP, Gleeson M, Pyne DB, Nieman DC, Dhabhar FS, Shephard RJ, Oliver SJ, Bermon S, Kajeniene A. Position statement. Part two: Maintaining immune health. Exerc Immunol Rev. 2011;17:64-103. Review.  View Abstract

[17] Nicolson GL, Ellithorpe R and Settineri R.  Blood homocysteine levels are significantly reduced with a glycophospholipid formulation (NTFactor® plus vitamin B-complex): a retrospective study in older subjects. Paper in Preparation.

[18] Piper BF, Dibble SL, Dodd MJ, Weiss MC, Slaughter RE, Paul SM. The revised Piper Fatigue Scale: psychometric evaluation in women with breast cancer. Oncol Nurs Forum. 1998 May;25(4):677-84.  View Abstract

[19] Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007 Jan;87(1):99-163. Review. View Abstract

[20] Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, Fitzgerald KA, Ryter SW, Choi AM. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011 Mar;12(3):222-30. Epub 2010 Dec 12. View Abstract

[21] Tschopp J. Mitochondria: Sovereign of inflammation? Eur J Immunol. 2011 May;41(5):1196-202. doi: 10.1002/eji.201141436. Review. View Abstract

[22] Franchi L, Muñoz-Planillo R, Núñez G. Sensing and reacting to microbes through the inflammasomes. Nat Immunol. 2012 Mar 19;13(4):325-32. doi: 10.1038/ni.2231. View Abstract

[23] Chen GY, Núñez G. Inflammasomes in intestinal inflammation and cancer. Gastroenterology. 2011 Dec;141(6):1986-99. Epub 2011 Oct 15. Review. View Abstract

[24] Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, Neale GA, Hooiveld GJ, Hijmans A, Vroegrijk I, van den Berg S, Romijn J, Rensen PC, Joosten LA, Netea MG, Kanneganti TD.Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15324-9. Epub 2011 Aug 29. View Abstract

[25] Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012 Jan;26(1):24-31. Epub 2011 Jul 2. Review. View Abstract

[26] Maes M, Twisk FN, Kubera M, Ringel K. Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. J Affect Disord. 2012 Feb;136(3):933-9. Epub 2011 Oct 4. View Abstract

[27] Franklin BS, Latz E. For gut’s sake: NLRC4 inflammasomes distinguish friend from foe. Nat Immunol. 2012 Apr 18;13(5):429-31. doi: 10.1038/ni.2289. View Abstract

[28] Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, Kau AL, Eisenbarth SC, Jurczak MJ, Camporez JP, Shulman GI, Gordon JI, Hoffman HM, Flavell RA. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012 Feb 1;482(7384):179-85. doi: 10.1038/nature10809. View Abstract

[29] Circu ML, Aw TY. Intestinal redox biology and oxidative stress. Semin Cell Dev Biol. 2012 Mar 30. [Epub ahead of print] View Abstract

[30] Maes M. Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Curr Opin Psychiatry. 2009 Jan;22(1):75-83. Review.  View Abstract

[31] Kelly D, Delday MI, Mulder I. Microbes and microbial effector molecules in treatment of inflammatory disorders. Immunol Rev. 2012 Jan;245(1):27-44. Review.  View Abstract

[32] Habil N, Al-Murrani W, Beal J, Foey AD. Probiotic bacterial strains differentially modulate macrophage cytokine production in a strain-dependent and cell subset-specific manner. Benef Microbes. 2011 Dec 1;2(4):283-93. View Abstract

[33] Gómez-Llorente C, Muñoz S, Gil A. Role of Toll-like receptors in the development of immunotolerance mediated by probiotics. Proc Nutr Soc. 2010 Aug;69(3):381-9. Epub 2010 Apr 23. Review. View Abstract

[34] Ellithorpe RR, Settineri R, Nicolson GL. Pilot study: reduction of fatigue by use of a dietary supplement containing glycophospholipids. J Am Nutraceut Assoc. 2003; 6(1): 23-28. View Full Paper

[35] Scrivo R, Vasile M, Bartosiewicz I, Valesini G. Inflammation as “common soil” of the multifactorial diseases. Autoimmun Rev. 2011 May;10(7):369-74. Epub 2010 Dec 30. Review. View Abstract

[36] Lakhan SE, Kirchgessner A. Gut inflammation in chronic fatigue syndrome. Nutr Metab (Lond). 2010 Oct 12;7:79. View Abstract

[37] Lamkanfi M, Kanneganti TD. The inflammasome: A remote control for metabolic syndrome. Cell Res. 2012 Apr 10. doi: 10.1038/cr.2012.55.  [Epub ahead of print] View Abstract

[38] Hirota SA, Ng J, Lueng A, Khajah M, Parhar K, Li Y, Lam V, Potentier MS, Ng K, Bawa M, McCafferty DM, Rioux KP, Ghosh S, Xavier RJ, Colgan SP, Tschopp J, Muruve D, MacDonald JA, Beck PL. NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflamm Bowel Dis. 2011 Jun;17(6):1359-72. doi: 10.1002/ibd.21478. Epub 2010 Sep 24. View Abstract

[39] Norheim KB, Jonsson G, Omdal R. Biological mechanisms of chronic fatigue. Rheumatology (Oxford). 2011 Jun;50(6):1009-18. Epub 2011 Feb 1. Review. View Abstract

[40] Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008, 9:46-56. View Abstract

[41] Raison CL, Lin JM, Reeves WC: Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun 2009, 23:327-337. View Abstract

[42] Lebeer, S., Vanderleyden, J. & De Keersmaecker, S.C. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat. Rev. Microbiol. 8, 171–184 (2010).  View Abstract

[43] Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359-407. Review. View Abstract

[44] Agadjanyan M, Vasilevko V, Ghochikyan A, Berns P, Kesslak P, Settineri R, Nicolson GL. Nutritional supplement (NTFactor) restores mitochondrial function and reduces moderately severe fatigue in aged subjects. J Chronic Fatigue Syndr 2003; 11(3): 23-26. View Full Paper

[45] Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012 Jan 1;3(1). [Epub ahead of print] View Abstract

The LEAP Project

Many Nutritional Therapists will consult people with a well-defined allergy or in some cases a range of symptoms that reflect an allergic response that do not meet the recognised IgE diagnosis. Some of these people will also be experiencing what is known as the ‘allergic march’ – the development of secondary allergenic profiles such as asthma after already having an established food allergy, such as peanut or shellfish.

The allergic march usually begins with eczema – a dry, red, scaly rash that causes considerable itching and discomfort. Eczema is most commonly diagnosed within the first few months of life. In 1/3 to 1/2 of children, eczema is associated with an underlying food allergy. Food allergies (peanut allergy, for instance) generally begin to appear within the first three years of a child’s life. Food allergy can cause gastrointestinal problems (such as colic, diarrhoea, etc.) and in some cases, it can be life threatening. As children age further, the allergic march may proceed to the development of asthma and/or rhino-conjunctivitis (sometimes called hayfever).

The pattern of development of allergic diseases – what types of disease occurs and the age at which they occur is highly reproducible (i.e. the pattern is the same in a large proportion of children and increasingly in adults as well).

Allergy is the result of a complex immune cascade leading to the dysregulated production of Th2 cytokines, the generation of allergen-specific IgE-producing B cells and the subsequent activation and degranulation of mast cells upon allergen challenge.

TSLP (Thymic Stromal Lymphopoietin)

One of the principle cells known to play very important roles in the development and resolution of allergy and other complications related to adverse immune responses in the mucosal and epithelial tissues are dendritic cells (DC’s). These cells when brought into contact with TSLP favour the allergenic profile – that is they convert naïve T cells into Th2 cells and amplify allergy risk and symptoms.[1] DCs are the professional antigen presenting cells that have the capability to sense invaded pathogens and tissue stress, then present antigen to T cells, thereby bridging the innate and adaptive immunity.

Click the image to enlarge

What this mechanism has helped to us to understand is that local tissues, in this case the epithelial tissues themselves, have the capacity to influence immune responses that in turn drive adaptive immune outcomes. This indicates that altered barrier quality and local inflammation may be a cause or at least an amplifier of allergenic inflammation via TSLP promotion.[2] Recent studies have revealed that various cell types other than epithelial cells and epidermal keratinocytes (such as mast cells, airway smooth muscle cells, fibroblasts, dendritic cells, trophoblasts, and cancer or cancer-associated cells) also express TSLP.[3]

Environmental factors such as Toll-like receptor ligands, a Nod2 ligand (innate immune signalling proteins), viruses, microbes (dysbiosis), allergen sources, helminths, diesel exhaust, cigarette smoke, and chemicals trigger TSLP production as well.

Compelling evidence implicates TSLP as playing a pivotal role in the pathobiology of allergic asthma and atopic dermatitis.[4] Other studies suggest it may have an amplifying effect in food allergy and inflammatory bowel disease.[5] These cross reactions suggest a critical role for TSLP as a driving factor in the emerging concept of tissue-specific control of immunity with TSLP secretion at the epithelial-DC interface acting as an initial and amplifying factor in the pro-allergic cascade also known as the allergic march.[6]

What can we do

Apart from the interesting relationships between tissue health and immune reactivity, postulated some time ago by Polly Matzinger and colleagues.[7] The clinical question is can we moderate inappropriate TSLP production and when and how should we do it? Is TSLP only problematic or can it confer benefit and does its role extend beyond the allergenic profile?

TSLP is capable of inducing tolerance, during maternal foetal tolerance requirements, especially during early pregnancy. TSLP promotes Th2 and Treg cells required for a successful pregnancy.[8] TSLP may induce thymically originating regulatory T cells, by being expressed by the epithelial cells present in the thymic tissue. Centrally produced Treg cells have similar roles to those produced in the periphery – most commonly in the gut, but are still important players in maintaining human tolerance.[9]

Certain cancer cells, however, seem to proliferate more easily when exposed to TSLP. The cancer-promoting activity of TSLP primarily required signalling through the TSLP receptor on CD4(+) T cells, promoting Th2-skewed immune responses and production of immunosuppressive factors such as IL-10 and IL-13 so permitting cancer cells to avoid destruction.[10],[11]

Our stomachs may also be the worse off post infection by H.Pylori through the induction of TSLP, as the altered T cell phenotype towards the Th2 cell presentation favours chronic and follicular gastritis.[12]

Natural Manipulation of TSLP

TSLP inhibition has been studied using three natural agents to determine their effectiveness in down regulating its output. The mineral selenium (Se) has various effects such as antioxidant, anti-tumour, anti-ulcer, and anti-inflammatory effects. One paper suggests it can impact in a significant manner on the mast cell promotion of TSLP indicating its potential use for inflammatory and allergenic illness.[13]

The same researchers have also identified the benefit can be repeated through the use of berberine and green tea extracts along with grapefruit juice.[14],[15],[16]

Other researchers have looked at the role of cis retinoic acid as a TSLP inhibitor via its action of the nuclear inflammation promoter NFkB and through the binding to the family of retinoic acid receptors (RAR) and the retinoid X receptors (RXR).[17]

The correction of any relevant dysbiosis, repair of barrier integrity and modification of diet selection to favour antioxidant rich foods will also be part of the programme to modify TSLP as it is driven in large part by the health of the local tissues.

The use of probiotics to increase IL-10 and TGF-Beta will also favour a T cell phenotype that regulates imbalances between Th2 and Th1 helper T cells.

Conclusion

TSLP is an interesting molecule that may represent a therapeutic target. We are unable to measure this cytokine for clinical purposes, but the strategy to apply for people with allergies, beyond the exclusionary principle of triggering foods or environmental exposure, permits us to approach the prevention or resolution with a key mechanism in mind.

Early days yet, but as more studies are done I expect a number of foods and food substrates will demonstrate benefit and may well reflect the genetic requirement for food selection.

References

[2] Wang YH, Liu YJ. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin Exp Allergy. 2009 Jun;39(6):798-806. Epub 2009 Apr 7. Review. View Full Paper

[3] Takai T. TSLP expression: cellular sources, triggers, and regulatory mechanisms. Allergol Int. 2012 Mar; 61(1):3-17. Epub 2012 Jan 25. View Full Paper

[4] Huston DP, Liu YJ. Thymic stromal lymphopoietin:a potential therapeutic target for allergy and asthma. Curr Allergy Asthma Rep. 2006 Sep;6(5):372-6. Review. View Abstract

[5] Blázquez AB, Mayer L, Berin MC. Thymic stromal lymphopoietin is required for gastrointestinal allergy but not oral tolerance. Gastroenterology. 2010 Oct;139(4):1301-9. Epub 2010 Jun 23. View Abstract

[6] Edwards MJ. Therapy directed against thymic stromal lymphopoietin. Drug News Perspect. 2008 Jul-Aug;21(6):312-6. Review. View Abstract

[7] Matzinger P, Kamala T. Tissue-based class control: the other side of tolerance. Nat Rev Immunol. 2011 Mar;11(3):221-30. View Abstract

[8] Li DJ, Guo PF. The regulatory role of thymic stromal lymphopoietin (TSLP) in maternal-fetal immune tolerance during early human pregnancy. J Reprod Immunol. 2009 Dec;83(1-2):106-8. Epub 2009 Oct 25. View Abstract

[9] Hanabuchi S, Ito T, Park WR, Watanabe N, Shaw JL, Roman E, Arima K, Wang YH, Voo KS, Cao W, Liu YJ. Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. J Immunol. 2010 Mar 15;184(6):2999-3007. Epub 2010 Feb 19. View Abstract

[10] Olkhanud PB, Rochman Y, Bodogai M, Malchinkhuu E, Wejksza K, Xu M, Gress RE, Hesdorffer C, Leonard WJ, Biragyn A. Thymic stromal lymphopoietin is a key mediator of breast cancer progression. J Immunol. 2011 May 15;186(10):5656-62. Epub 2011 Apr 13. View Abstract

[11] Pedroza-Gonzalez A, Xu K, Wu TC, Aspord C, Tindle S, Marches F, Gallegos M, Burton EC, Savino D, Hori T, Tanaka Y, Zurawski S, Zurawski G, Bover L, Liu YJ, Banchereau J, Palucka AK. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J Exp Med. 2011 Mar 14;208(3):479-90. Epub 2011 Feb 21. View Abstract

[12] Helicobacter pylori promotes the production of thymic stromal lymphopoietin by gastric epithelial cells and induces dendritic cell-mediated inflammatory Th2 responses. Kido M, Tanaka J, Aoki N, Iwamoto S, Nishiura H, Chiba T, Watanabe N. Infect Immun. 2010 Jan;78(1):108-14. Epub 2009 Oct 19. View Abstract

[13] Moon PD, Kim HM. The suppression of thymic stromal lymphopoietin expression by selenium. Amino Acids. 2011 Nov 16. View Abstract

[14] Moon PD, Choi IH, Kim HM. Berberine inhibits the production of thymic stromal lymphopoietin by the blockade of caspase-1/NF-κB pathway in mast cells. Int Immunopharmacol. 2011 Nov;11(11):1954-9. Epub 2011 Aug 19. View Abstract

[15] Moon PD, Choi IH, Kim HM. Epigallocatechin-3-O-gallate inhibits the production of thymic stromal lymphopoietin by the blockade of caspase-1/NF-κB pathway in mast cells. Amino Acids. 2011 Aug 11. View Abstract

[16] Moon PD, Choi IH, Kim HM. Naringenin suppresses the production of thymic stromal lymphopoietin through the blockade of RIP2 and caspase-1 signal cascade in mast cells. Eur J Pharmacol. 2011 Dec 5;671(1-3):128-32. Epub 2011 Sep 24. View Abstract

[17] Lee HC, Headley MB, Iseki M, Ikuta K, Ziegler SF. Cutting edge: Inhibition of NF-kappaB-mediated TSLP expression by retinoid X receptor. J Immunol. 2008 Oct 15;181(8):5189-93. View Abstract

• Limited Places: 30

• Cost: £185 (including VAT at 20%)

“Are You Ready To Close The Gap Between Where Your Nutrition Practice Is Right Now And Where You Want It To Be?”

What if you could attend just one seminar, and as a result, your practice income doubled, tripled or even quadrupled? Would you even consider missing it regardless of the cost or other commitments? Of course not. Yet if you’re like most Nutritional Therapists you are probably saying to yourself, “Yeah right, it sounds too good to be true. There is no silver bullet or one time fix. That’s just marketing hype. I doubt that it could really make that much of a difference.” And to some extent you would be right. Because whatever you learn from our seminar has to be put in place by YOU. Those that do, however, see significant increases in client satisfaction and better outcomes, time management, boundary control and increased income.

Our job is to help you achieve the Professionalism, Knowledge, Respect, Confidence and Profitability you deserve to run your clinic effectively and with personal satisfaction. This seminar provides you with the chance to enhance your clinical skills and strengthen your ability to communicate your expertise like never before and be rewarded accordingly.

Antony Haynes BA(Hons) DipION & Michael Ash BSc(Hons).DO.ND. FDipION. mIOD present a Proven Approach to Practice Success.

CPD Approval	Credits/hours
British Association for Applied Nutrition and Nutritional Therapy	Applied For

“Successful Seminar Repeated ”

For over a year, we have been asked by practitioners “when are you going to run the Profitable Practice seminar again?”

The next date has been set for May the 12th 2012 at the Burlington Hotel in Ireland

Our event explains and teaches proven strategies to make your Practice an unqualified success. With over 45 years experience in building profitable, successful practices Michael and Antony will lead and demonstrate how to achieve greater results and consistent success.

Places are limited to 30 so BOOK NOW!

“In just 1 day learn how to increase your earnings without seeing more patients, make your consultations more efficient and feel more confident. Learn how to have more fun with your work and discover how shared experiences of beneficial change and meaningful interactions impact on your clinical life with great effect.”

Learn How to Develop the Essential Components of a Successful Practice:

Money Management

• Produce more income from doing what you are already doing
• Understand money as a form of energy
• Understand your own financial value
• Increase and maintain for longer, income from nutritional recommendations
• Retain valued contact with patients for longer whilst increasing their appreciation and trust in you
• Learn how to manage your money to secure your future

Time Management

• Make effective use of your time with patients, and on each patient’s case
• Maximise efficiency of time with each patient
• Maximise fee-earning time, and minimise non-earning time
• Learn what systems to implement for an efficient operation

Well-Being

• Feel better about your work & improve your overall satisfaction
• Feel less stressed about your work
• Improve your ability to relate to patients
• Improve and control your boundaries with patients
• Achieve better rewards for your work

Vision

• Create a vision for your working life and your nutritional career
• Envisage the hours you want to work and the income you wish to earn
• Have more fun with what you do
• Increase success in your nutritional career

Patient Management

• Patient-centered and personalised nutritional therapy is the key to developing effective patient management and referrals.
• Learn how meaningful management produces better outcomes.
• Understand how to avoid exhaustion and increase cooperation.

Testimonials

Financial Results

In the 11 months after the first Profitable Practice Seminars the attending practitioners INCREASED their existing supplement turnover by over £100,000 without any significant increase in patient numbers.

Six practitioners increased their sales in the 11 months following the Profitable Practice seminar, compared to the previous 12 months, by these amounts:

Providing more profit, creating freedom from worry and investment in their future.

Attendees had this to say:

Thank you so much for such an inspiring and incredibly practical and useful day on Saturday. I really can’t tell you how much it has helped me already – I feel like a huge weight has lifted. I’m busy making lists and re-doing my consultation paperwork and generally being more proactive than I have been in MONTHS.

Amelia Freer Dip ION

Thank you for a most inspiring and encouraging day and for sharing your experience and insights from your own journeys. Your step by step guidance and advice was so helpful and enlightening and I have already taken action to improve my business model and the way I handle bookings, consultations, follow up and practitioner supplement discounts. I can highly recommend this seminar to anyone, who are looking to make the most of their practice – in every way.

I will let you know how I get on. Thanks again. Karina Athwal BSc Hons, Nutritional Therapy

Since attending the Profitable Practice Seminar I have substantially increased my turnover by implementing some very simple measures. I have found Nutri-Link to be outstanding as a company, my clients often comment on the efficiency of the service and the ease at which they can order products. I have found the technical support from Antony & Mike invaluable, it has allowed me to expand my practice and deliver excellent care to my clients.

Angela Beecroft BSc (Hons) Dip HV, Dip ION

“That was the best course I have ever been to, and I believe every practitioner should attend! It was so relevant to my clinical practice and since I have implemented some of the suggestions, I have earned hundreds more pounds, had some more time, and felt more confident in my boundaries with patients.”

Fiona Mealing Dip ION

“Saturday was fantastic, and a wonderful example of inspirational work”.

John McClinton Dip ION

“Thank you so much for the seminar on Saturday – it was insightful and inspirational and I’m feeling motivated and positive!”

Caroline Crawford Dip BCNH

Many thanks for the excellent seminar on Saturday. It was fabulously thorough and indeed more than fulfilled my expectations of what I hoped to receive from the day. I have long been making noises about needing to concentrate on building my practice and increasing my patient numbers but with the ultimate fear that this would take me above my capacity of hours available to invest in patients, alongside juggling family life, which ultimately acted as a huge disincentive. You have demonstrated so clearly that this may be far from true if I take action to change, and I need invest no additional time whatsoever, and could indeed reduce the hours that I have already committed to patients.

It was also hugely empowering to see the potential that can be achieved in turnover in a profession that I had long begun to think would not reap financial rewards (as I sure you are aware from my dreadfully under-ambitious target for turnover next year… you can stop laughing now!).

I will be in touch again soon for the shirt off your back. Many thanks, Mariam Donovan. BA (Hons) BCNH

Event Details

Location

Burlington Hotel, Upper Leeson Street, Dublin 4 Ireland

Timings

Start: 9.00 am – Finish: 5 pm

Limited Places

30

Cost

The cost is just £185 (including VAT)

This seminar will change the way you practice from the very next day and will help you to achieve your personal goals. We anticipate that you will recoup the seminar fee in the first month alone.

Book now to avoid disappointment. Call 08450 760 402.

IMPORTANT NOTE

This is NOT a marketing course for those establishing a practice. This seminar is designed for practitioners of at least 2 years’ clinical experience seeing at least 10 patients a month.

Attend this seminar and be prepared to be inspired & motivated.

Places are limited and likely to sell fast.

At present no chronic disease has a greater drag on global function than mental illness.

Core symptoms include depressed mood, anhedonia (reduced ability to experience pleasure from natural rewards), irritability, difficulties in concentrating, and abnormalities in appetite and sleep (‘neurovegetative symptoms’). In addition to mortality associated with suicide, depressed patients are more likely to develop coronary artery disease and type 2 diabetes. Depression also complicates the prognosis of a host of other chronic medical conditions. The chronic, festering nature of depression contributes substantially to the global burden of disease and disability.

Pharmaceutical manufacturers are currently withdrawing from this field of research, in part because of the complexity of the subject and lack of funding, and in part because of the relative lack of success in drug development for the effective and safe treatment of mental illness. There is evidence that anti-depressants work in severe depression but not mild depression.[2]

There is in the drug world, a degree of hope that the latest genetic technologies will help to identify effective treatment targets, and offer alternatives to the monoamines that have dominated psychiatric medications for half a century but as yet this has not translated into clinical use.

Nutritional therapy may not represent a stand-alone intervention for mental health, but to ignore its relevance in improving outcomes and overall health in the research drive to identify molecular ‘silver bullets’ will simply repeat the manifestly derisory clinical developments in the last few years.

There exists a well-established management of mental health through the judicious utilisation of ‘talking therapies’ including cognitive behavioural therapy (CBT) and many others.[3] In managing people with complex mental health issues, no single therapy has been able to establish completeness of outcomes. Integrating evidence based nutritional recommendations has a low risk to benefit ratio and will be an appealing proposal to those clinicians that recognise the need for integrative care.

People with severe mental health issue need to under the direct care of their medical doctor and support teams, communicating this to anyone seeking the use of food or supplements as their only strategy is very important and represents a genuine red flag for all practitioners.

Lifestyle Medicine for Mental Health Resolution and Prevention

Exercise and dietary selection, recognised as a valid medicine since man first began to record methods of improving health have an historical and developing role in prevention and treatment.[4]

Mediterranean diet

A healthy Mediterranean-style diet for example is thought to be protective as is regular exercise — so combining a regular dance class with a big Greek salad and a glass of red wine may make very attractive therapy.[5],[6]

Over the past decade, multiple epidemiological studies have shown that exercise, intellectual activity, social relationships and a healthy diet all lead to a lower risk of mental health problems including dementia and depression. Such findings are generally interpreted with caution by mainstream science, however, as many researchers remain sceptical about the benefits, and because withdrawing from social relationships and other activities can be an early symptom of dementia, not just a risk factor for it.

In terms of depression there are significant changes in researchers’ focus in the last 5-10 years as inflammation induced by lifestyle choices, in particular diet appear to be causally related to depressive behaviour.[7]

Mental Health and Genetics

Depression is so common that it seems the possibility of depression must be “hard-wired” into our brains. This has led biologists to propose several theories to account for how depression, or behaviours linked to it, can somehow offer an evolutionary advantage. For several years, researchers have seen links between depression and inflammation, or over-activation of the immune system. People with depression tend to present with higher levels of inflammation, even if they’re not fighting an infection.

Yet major depression is so detrimental to survival and reproduction that it is hard to understand why allelic variants that promote the disorder have not been culled from the human genome, why in fact, far from being culled, genes that promote depression are so common and numerous and appear to have actually increased in prevalence during recent human evolution.[8] This gene conferred relationship, and the connections between our immune system and mental health are discussed in a recent publication in Molecular Psychiatry.[9]

“The basic idea is that depression and the genes that promote it were very adaptive for helping people—especially young children—not die of infection in the ancestral environment, even if those same behaviours are not helpful in our relationships with other people,”

Psychosocial stress and its effect on mental health may be especially relevant in this regard. Stress is well recognised as a universal and powerful risk for the development of depression both during development and adulthood.[10]

Given this, it is not surprising that, to quote Firdaus Dhabhar,

“Stress perception by the brain may serve as an early warning signal to activate the immune system in preparation for a markedly increased likelihood of subsequent infection”.[11]

So many risks for depression, including obesity, sedentary lifestyle, dietary factors, diminished sleep and smoking, are at least partially non-social in nature but are all associated with increased inflammation suggesting that they may be depressogenic because they tap into pathways that initially evolved to fight infection and to encourage isolated behaviour, which diminished exposure risks and perhaps separated fighting members of the social group.[12],[13]

Dietary strategies clearly influence inflammation, as documented through both prospective observational studies as well as randomised controlled feeding trials in which participants agree to eat only the food provided to them.[14] Indeed, mechanistic studies have shown how various dietary components can modulate sympathetic activity, oxidative stress, transcription factor nuclear factor kappa B (NF-κB) activation, and proinflammatory cytokine production, thus modifying health risks and contributing to reduced risk of mental health problems.[15],[16]

So: Which Foods Are Best for the Brain?

Diet is inextricably and unquestionably linked to conditions such as heart disease, obesity, and diabetes as well as many other chronic illnesses. However, what we consume also seems to have significant implications for the brain: Unhealthy diets may increase risk for psychiatric and neurologic conditions, such as depression and dementia, whereas healthy diets may be protective.

This in turn opens up discussions around food selection, not as an adjunctive therapy to simply aid in recovery, but also as a preventative strategy. The ever increasing burden in terms of social dysfunction and medical cost driven by declining mental health should encourage a greater awareness of how foods, food groups and eating patterns may beneficially reduce this cost burden in our society.

Heading South, Or At Least Acting Greek May Actually Help.

Back in 2009 the journal Archives of General Psychiatry confirmed in a paper that people who followed a dietary lifestyle consistent with the Mediterranean diet benefitted from a number of disease risk reductions including mental health.

After studying more than 10,000 initially healthy Spaniards their results show that those who followed the Mediterranean dietary pattern (MDP) — rich in vegetables, fruits, nuts, whole grains, and fish — were 30% less likely to develop depression during the next 4 years than those who ate more meat, meat products, or whole-fat dairy.[17] In addition, a long favourite in salad dressing – olive oil, shows an intake related reduction in risk of ischaemic stroke.[18] Olive oil and exercise can now add reduction in risk for the development of cognitive decline and Alzheimer’s to their list of related benefits.

We already know that the much promoted ‘poly pill’ advocated as a pharmaceutical solution to lifestyle driven illness had its purported benefits knocked back by the ‘poly meal’, that recommended the Mediterranean diet as its mainstay.[19] This style of eating when accompanied by regular exercise extends its related benefits to mild cognitive impairment and the ever threatening degenerative illness called Alzheimers.[20],[21]

Fat: Which Type Helps?

Brain cells respond well to essential fatty acids

Our brains are made largely of fat and water, but not just any old fat; it requires special types of fat known as essential fatty acids. As you read this, fats are being incorporated into your brain.

The delicate fatty acid membranes that surround human cells and permit the proteins bound within them to function within the ‘fluid mosaic model’ described by Singer and Nicholson back in 1972 are vulnerable to damage.[22] Recent work suggests that a special fatty acid mix called a glycophospholipid may confer unique oxidative inhibition, repair existing membrane damage and increase ATP production leading to inhibition or prevention of mental ill health.[23],[24]

It has now been proven in human clinical trials that glycophospholipids will restore lost membrane vitality.  In an elderly population, individuals consuming six tablets (4000mg) of glycophospholipids per day restored their membrane health to levels normal for young healthy adults in just two months.[25] The implication being that in mental ill health in which ATP production is a feature, restoration by additional glycophospholipid supplementation may produce a clinical benefit greater than that achieved by dietary inclusion of EFA’s alone.

Other Mediterranean studies, these ones from Spain[26],[27] reported that consumption of both polyunsaturated fatty acids (found in nuts, seeds, fish, and leafy green vegetables) and monounsaturated fatty acids (found in olive oil, avocados, and nuts) decreases the risk for depression over time.

By contrast, there were clear dose-response relationships between dietary intake of trans fats, fast foods and depression risk. Trans fats are found extensively in processed foods, including some confectionary. Whilst childhood depression is rising, the incidence of attention deficit disorder is already well recognised and not surprisingly a link between polyunsaturated fatty acid deficiencies is linked to hyperactivity and attention deficit disorders in children.[28]

Oily Fish May Prevent Psychosis!

Our early ancestors experienced relatively rapid brain development and intellectual superiority thanks to their abundant source of omega three rich foods harvested from the oceans around the southern coast of Africa.[29] Thanks to their high levels of polyunsaturated fatty acids, namely omega-3 fatty acids, fish it seems can help fend off numerous diseases of the brain.

In 2010, a study using 33,000 women as its reference base found a correlation between fatty acids and vitamin D and a reduced incidence of psychotic like symptoms.[30] A follow up study also found that at risk individuals had a greater chance of avoiding a psychotic episode when consuming fish oils.[31]

It is the nature of long term nutritional studies that data often appears conflicting. Nutrients act through multiple mechanisms, and low intakes might be expected to lead to disorders quite distinct from the disease originally connected with the nutrient.

“The success of the RCT [randomised controlled trial] in evaluating medical treatments has, perhaps, blinded nutritionists, regulators, and editors to the fact that it is a method ill-suited for the evaluation of nutrient effects.” [32]

The long history of food related benefits extends beyond the one pathway one outcome strategy favoured by the pharmaceutical model. Triage theory related to long term modest nutrient deficiencies as proposed by Prof Ames and colleagues proposes a strategic sacrifice of nutrients to ATP promotion that creates deficiency diseases of nutrient latency such as mental ill health.[33]

Newer research pretty consistently shows that the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial in both depression and postpartum depression, respectively, and other studies suggest that omega-3 deficiency may be a compounding risk factor for suicide.[34]

In terms of food selection; oily, cold-water fish, such as salmon, herring, and mackerel, have the highest omega-3 levels.

Nutrient Packed Berries Carry An Oxidative Punch.

Blueberries may reverse damage in the brain

Berries are generally small nutrient dense fruits that use complex chemical combinations to protect their inner tissues from oxidative stress. These protective agents include polyphenols, namely anthocyanins. Not only are they tasty and nourishing they also hold some remarkable recuperative potential.

Back in 2010 a study using rats – admittedly not humans – found that these tightly bundled chemicals found in berries and other darkly pigmented fruits and vegetables may slow cognitive decline through antioxidant and anti-inflammatory properties. Natural polyphenols in berries and other fruits, vegetables, and nuts are now known to enhance brain health via their antioxidant and anti-inflammatory properties. Many publications using animal models report beneficial effects of berries and walnuts on memory, motor skills, and other behaviour.[35],[36]

An exciting in vitro study demonstrated age-related amyloid plaque deposition reversal and additional neuroprotection in the animals studied, and whilst the doses used are high, this outcome suggests an ancient conserved protective mechanism favoured by food selection.[37] This can be exploited in humans through suitable inclusion of these fruits, especially blueberries, in our daily diet.[38],[39] The researchers also detected a statistical trend towards fewer signs of depression, and lower blood sugar (glucose) levels, among the test group. Berries are attracting increasing interest as their transfer to human application is easy and surprisingly promising.[40]

Wholly Cow! What’s Good For Your Brain Is Good For The Planet, Too!

Already confirmed back in 2010, is that a diet rich in fruits, vegetables, whole grains, high quality meat and fish results in a remarkable 30% reduction in depressive behaviours and anxiety disorders compared to a typical western diet. Typical western diets are high in processed meats, fats and sugars.[41] Yet, very few professionals working with mental illness regard food selection as little more than to provide fuel.

A more recent paper in the journal Archives of Internal Medicine has reawakened the medical and wider community to the risks linked to consumption of processed meats and mortality. This is the first large-scale prospective longitudinal study showing that consumption of both processed and unprocessed red meat is associated with an increased risk of premature mortality from all causes as well as from cardiovascular disease and cancer, all linked to aberrant inflammation and associated inflammation driven depression.[42]

Current farming practices are in part to blame for this increase in red meat related mortality, they have and are changing, driven by the global growth in the human population. Food producers are facing increasing demands on food production and quality suffers. Intensive farming practices increase saturated fat and decrease very important good fatty acids in the meat…pasture-raised animals have a much healthier fatty acid profile.[43]

Booze – If I Must, But Just A Little…

To imbibe or abstain – a long discussed balance that does not always hinge on mental health outcomes! Much to the joy of those that enjoy a glass or two, low to moderate* alcohol consumption has been associated with numerous potential physiologic benefits, including improved cholesterol profiles, beneficial effects on platelet and clotting function, and improved insulin sensitivity.[44]

There is evidence from meta-analysis that moderate intake is linked to a reduction of Alzheimer’s risk[45] and wine has been demonstrated via its polyphenolic compounds to increase cerebro vascular blood flow potentially aiding cognition and mood.[46]

However, the health costs of alcohol consumption beyond low to moderate intake can quickly outweigh benefits to the brain, as heavy and long-term alcohol use can lead to alcohol abuse and dependence, impair memory function, contribute to neurodegenerative disease, and hinder psychosocial functioning.

* In the UK, the recommendation is no more than two to three units of alcohol a day for women and three to four units for men, with at least two or three alcohol-free days each week.

What’s a unit?

One unit of alcohol is 10 ml (1 cl) by volume, or 8 g by weight, of pure alcohol. For example:

• One unit of alcohol is about equal to:
• half a pint of ordinary strength beer, lager, or cider (3-4% alcohol by volume), or
• a small pub measure (25 ml) of spirits (40% alcohol by volume), or
• a standard pub measure (50 ml) of fortified wine such as sherry or port (20% alcohol by volume)

Caffeine and CNS Impact

Balck coffe may reduce mental health risks - in moderation

No other psychoactive drug is consumed more enthusiastically than caffeine infused beverages, and whilst there are many contradictory reports on its potential risks and benefits there is a steady trend of support for certain mental health risks being reduced.

Another meta-analysis (not my favourite type of research) suggested that consumption of between 1 and six(!) cups reduce the risk for stroke by 17%. This outcome suggests a conflicting or at least a negating role between the antioxidant benefits in coffee that diminishes oxidative damage of LDL cholesterol whilst also increasing a primary risk factor for stroke – blood pressure.[47] Further support for the daily infusion may be found in a paper that suggests insulin sensitivity is increased and inflammatory markers reduced by ingesting caffeine.[48]

So does this have any effect on depressive behaviour?  There does appear to be a related dose dependent benefit, with women who drink 2-3 cups per day demonstrating a 15% decreased risk for depression compared to their peers who drank just 1 cup daily. Increasing the intake to 4 cups per day saw the risks decrease by 20%.

So what are the mechanisms that may account for this? Serotonin and dopamine responses are improved in the short term response and antioxidant and anti-inflammatory benefits may diminish the cytokine burden linked to depressive illness already discussed.[49]

Habitual caffeine consumers who abstain from caffeine experience withdrawal symptoms such as headache, fatigue, difficulty concentrating, mood disturbances, and flu-like symptoms.[50] The caffeine withdrawal syndrome has been documented across many experimental studies suggesting its ingestion is not without risks of dependency and increased tolerance resulting in increased ingestion. The withdrawal syndrome has an onset at 12-24 h, peak at 20-48 h, and duration of about 1 week.

Although more research is clearly needed, coffee, when consumed without added cream or sugar, is a calorie-free beverage that may confer some mental health benefits, especially when used in individuals who do not have adverse subjective effects due to its stimulating effects, and when coffee is substituted for less healthy, unnatural, and/or high-calorie beverages, such as colas and other sugary and artificially sweetened sodas and soft drinks.[51]

Cacao And Its Sweet Benefits

Dark chocolate (>70%) has been described as mood food, and whilst a great deal of anecdotal evidence exists that chocolate affects mood, there is still some debate as to whether it reduces depressive behaviour or is consumed as part of depressive behaviour.[52],[53]

Chocolate’s mood state effects are purported to be due to its many psychoactive ingredients, including several biogenic stimulant amines, two analogues of anandamine (producing effects akin to cannabinoid-inducing euphoria) and interactions with several neurotransmitter systems (e.g. dopamine, serotonin and endorphins) as well as antioxidants including resveratrol, and other flavonoids; catechin, epicatechin, and procyanidins.[54],[55] However the authors suggest that the benefits are not sustained, with emotional “comfort” eating actually contributing to depressed mood.

Dark chocolate at doses between 6 – 40gms or so per day also confer cardiovascular benefits – via its polyphenolic compounds, immune benefits and stroke reduction – so keep it dark and in small daily doses.[56],[57],[58]

What To Avoid?

This list will seem depressingly familiar to all Nutritional Therapists as the nature of so many chronic illnesses involves activated and inappropriate immune promotion of inflammatory chemicals. The simple food suggestions listed here are to represent a starting point for supporting someone with a presenting complaint of mood or affect disorders.

I have contributed chapters to two books that along with the editor Martina Watts and colleagues explore the potential role of foods, food supplements and lifestyle change in the support of people with mental health issues.[59],[60] They provide far greater suggestions than can be delivered here.

A diet that contains saturated fats and refined simple carbohydrates and that lacks nutrient dense foods, vegetables and berries adversely impacts on our immune status, increasing inflammation, increasing oxidative stress and neurotrophins.[61] These are all understood to  contribute to risk of depression.

First strike research published in 2011 confirmed that adolescent’s diet is linked to their mental health.[62] This also has implication in utero as compounded dietary related issues begin very early in life and, unless mitigated by advantageous food selection as affected individual’s age, the risk for mental health issues increases.

The perinatal environment plays an important role in programming many aspects of physiology and behaviour including metabolism, body weight set point, energy balance regulation and predisposition to mental health-related disorders such as anxiety, depression and attention deficit hyperactivity disorder, learning and behavioural disorders/autistic spectrum. Maternal health and nutritional status heavily influence the early environment and have a long-term impact on critical central pathways, including the serotonergic system and dopaminergic systems.[63] In other words we are never too young or old to benefit from lifestyle interventions as described in this article.

Conclusion

Healthier diets are associated with reduced mental health symptoms and unhealthy diets with increased mental health symptoms over time.[64]

Future Perspectives

Looking ahead the gut will almost certainly be a key area of focus for future studies. Not only is the gut the site of nutrient absorption, but also the resident microbial ecosystem of the gut may fine tune the threshold of inflammation and its impact on a wide range of chronic health conditions including those referred to as mental health.[65]

References

[2] Fournier, J. C., et al. (2010). Antidepressant drug effects and depression severity. JAMA, 303, 47-53. View Abstract

[3] Thomas LJ, Abel A, Ridgway N, Peters T, Kessler D, Hollinghurst S, Turner K, Garland A, Jerrom B, Morrison J, Williams C, Campbell J, Kuyken W, Lewis G, Wiles N. Cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment resistant depression in primary care: the CoBalT randomised controlled trial protocol. Contemp Clin Trials. 2012 Mar;33(2):312-9. Epub 2011 Nov 11. View Abstract

[4] Herring MP, Puetz TW, O’Connor PJ, Dishman RK. Effect of exercise training on depressive symptoms among patients with a chronic illness: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012 Jan 23;172(2):101-11. View Abstract

[5] Scarmeas N, Luchsinger JA, Schupf N, Brickman AM, Cosentino S, Tang MX, Stern Y. Physical activity, diet, and risk of Alzheimer disease. JAMA. 2009 Aug 12;302(6):627-37. View Abstract

[6] Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, Morris MC. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J Clin Nutr. 2011 Mar;93(3):601-7. Epub 2010 Dec 22. View Full Paper

[7] Ekmekcioglu C. Are proinflammatory cytokines involved in an increased risk for depression by unhealthy diets? Med Hypotheses. 2012 Feb;78(2):337-40. Epub 2011 Dec 6. View Abstract

[8] Crespi B, Summers K, Dorus S. Adaptive evolution of genes underlying schizophrenia. Proc Biol Sci. 2007 Nov 22;274(1627):2801-10. View Full Paper

[9] Raison CL, Miller AH. The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D). Mol Psychiatry. 2012 Jan 31. doi: 10.1038/mp.2012.2. View Full Paper

[10] Handwerker WP. Cultural diversity, stress, and depression: working women in the Americas. J Women Health Gend Based Med 1999; 8: 1303–1311. View Abstract

[11] Dhabhar FS. Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation 2009; 16: 300–317. View Full Paper

[12] O’Connor MF, Bower JE, Cho HJ, Creswell JD, Dimitrov S, Hamby ME et al. To assess, to control, to exclude: effects of biobehavioral factors on circulating inflammatory markers. Brain Behav Immun 2009; 23: 887–897. View Full Paper

[13] Kiecolt-Glaser JK. Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge. Psychosom Med 2010; 72: 365–369.  View Full Paper

[14] Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol. 2006 Aug 15;48(4):677-85. Epub 2006 Jul 24. Review. View Abstract

[15] Calder PC, Albers R, Antoine JM, Blum S, Bourdet-Sicard R, Ferns GA, Folkerts G, Friedmann PS, Frost GS, Guarner F, Løvik M, Macfarlane S, Meyer PD, M’Rabet L, Serafini M, van Eden W, van Loo J, Vas Dias W, Vidry S, Winklhofer-Roob BM, Zhao J. Inflammatory disease processes and interactions with nutrition. Br J Nutr. 2009 May;101 Suppl 1:S1-45. Review. View Abstract

[16] Romier B, Schneider YJ, Larondelle Y, During A. Dietary polyphenols can modulate the intestinal inflammatory response. Nutr Rev. 2009 Jul;67(7):363-78. Review. View Abstract

[17] Sánchez-Villegas A, Delgado-Rodríguez M, Alonso A, Schlatter J, Lahortiga F, Serra Majem L, Martínez-González MA. Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra follow-up (SUN) cohort. Arch Gen Psychiatry. 2009 Oct;66(10):1090-8. View Abstract

[18] Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB. Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women. Circulation. 2009;119:1093-1100. View Full Paper

[19] Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec 18;329(7480):1447-50. Review. View Full Paper

[20] Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. Mediterranean diet and mild cognitive impairment. Arch Neurol. 2009;66:216-225. View Full Paper

[21] Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA. 2009;302:627-637. View Full Paper

[22] Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science. 1972 Feb 18;175(23):720-31. View Abstract

[23] Nicolson GL, Conklin KA. Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy. Clin Exp Metastasis. 2008;25(2):161-9. Epub 2007 Dec 5. Review. View Abstract

[24] Marazziti D, Baroni S, Picchetti M, Landi P, Silvestri S, Vatteroni E, Catena Dell’Osso M. Curr Med Chem. 2011;18(30):4715-21. Review. Mitochondrial alterations and neuropsychiatric disorders. View Abstract

[25] Agadjanyan M, Vasilevko V, Ghochikyan A, Berns P, Kesslak P, Settineri R, Nicolson G. Nutritional Supplement (NT Factor™) Restores Mitochondrial Function and Reduces Moderately Severe Fatigue in Aged Subjects. J Chronic Fatigue Syndr 2003; 11(3): 23-36 View Full Paper

[26] Sánchez-Villegas A, Verberne L, De Irala J, et al. Dietary fat intake and the risk of depression: the SUN project. PLoS One. 2011;6:e16268. View Full Paper

[27] Sánchez-Villegas A, Toledo E, de Irala J, Ruiz-Canela M, Pla-Vidal J, Martínez-González MA. Fast-food and commercial baked goods consumption and the risk of depression. Public Health Nutr. 2012;15:424-432. View Abstract

[28] Millichap JG, Yee MM. The diet factor in attention-deficit/hyperactivity disorder. Pediatrics. 2012 Feb;129(2):330-7. Epub 2012 Jan 9. View Abstract

[29] Cortés-Sánchez M, Morales-Muñiz A, Simón-Vallejo MD, Lozano-Francisco MC, Vera-Peláez JL, Finlayson C, Rodríguez-Vidal J, Delgado-Huertas A, Jiménez-Espejo FJ, Martínez-Ruiz F, Martínez-Aguirre MA, Pascual-Granged AJ, Bergadà-Zapata MM, Gibaja-Bao JF, Riquelme-Cantal JA, López-Sáez JA, Rodrigo-Gámiz M, Sakai S, Sugisaki S, Finlayson G, Fa DA, Bicho NF. Earliest known use of marine resources by Neanderthals. PLoS One. 2011;6(9):e24026. Epub 2011 Sep 14. View Full Paper

[30] Hedelin M, Löf M, Olsson M, Lewander T, Nilsson B, Hultman CM, Weiderpass E. Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33,000 women from the general population. BMC Psychiatry. 2010 May 26;10:38. View Full Paper

[31] Amminger GP, Schäfer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, Mackinnon A, McGorry PD, Berger GE. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54. View Full Paper

[32] R.P. Heaney, “Nutrients, endpoints, and the problem of proof,” J Nutr, 138:1591-95, 2008. View Full Paper

[33] Ames BN. Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake. J Nucleic Acids. 2010 Sep 22;2010. pii: 725071. View Full Paper

[34] Judge MP, Beck CT, Durham H, et al. Maternal docosahexaenoic acid (DHA, 22:6n-3) consumption during pregnancy decreases postpartum depression (PPD) symptomatology. FASEB J. 2011;25:349.7. View Abstract

[35] Berry extracts and brain aging: clearance of toxic protein accumulation in brain via induction of autophagy. Program and abstracts of the 240th National Meeting of the American Chemical Society; August 22-26, 2012; Boston, Massachusetts.

[36] Joseph JA, Shukitt-Hale B, Willis LM. Grape juice, berries, and walnuts affect brain aging and behavior. J Nutr. 2009 Sep;139(9):1813S-7S. Epub 2009 Jul 29. Review. View Full Paper

[37] Brewer GJ, Torricelli JR, Lindsey AL, Kunz EZ, Neuman A, Fisher DR, Joseph JA. Age-related toxicity of amyloid-beta associated with increased pERK and pCREB in primary hippocampal neurons: reversal by blueberry extract. J Nutr Biochem. 2010 Oct;21(10):991-8. Epub 2009 Dec 1. View Full Paper

[38] Goyarzu P, Malin DH, Lau FC, Taglialatela G, Moon WD, Jennings R, Moy E, Moy D, Lippold S, Shukitt-Hale B, Joseph JA. Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci. 2004 Apr;7(2):75-83 View Abstract

[39] Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA. Blueberry Supplementation Improves Memory in Older Adults (dagger). J Agric Food Chem. 2010 Jan 4. View Full Paper

[40] Miller MG, Shukitt-Hale B. Berry Fruit Enhances Beneficial Signaling in the Brain. J Agric Food Chem. 2012 Feb 3. View Abstract

[41] Jacka F, Pasco JA, Mykletun A, et al. Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry. 2010;167:305-311. View Full Paper

[42] Pan A, Sun Q, Bernstein AM; et al. Red meat consumption and mortality: results from 2 prospective cohort studies [published online March 12, 2012]. Arch Intern Med. doi:10.1001/archinternmed.2011.2287. View Full Paper

[43] Wood JD, Enser M.Factors influencing fatty acids in meat and the role of antioxidants in improving meat quality. Br J Nutr. 1997 Jul;78 Suppl 1:S49-60. Review. View full Paper

[44] Wayerer S, Schäufele M, Wiese B, et al; German AgeCoDe Study group (German Study on Ageing, Cognition and Dementia in Primary Care Patients). Current alcohol consumption and its relationship to incident dementia: results from a 3-year follow-up study among primary care attenders aged 75 years and older. Age Ageing. 2011;40:456-463. View Abstract

[45] Peters R, Peters J, Warner J, Beckett N, Bulpitt C. Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing. 2008;37:505-512. View Full Paper

[46] de Gaetano G, Di Castelnuovo A, Rotondo S, Iacoviello L, Donati MB. A meta-analysis of studies on wine and beer and cardiovascular disease. Pathophysiol Haemost Thromb. 2002;32:353-355. View Abstract

[47] Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies. Am J Epidemiol. 2011;174:993-1001. View Abstract

[48] Pasco JA, Nicholson GC, Williams LJ, et al. Association of high-sensitivity C-reactive protein with de novo major depression. Br J Psychiatry. 2010;197:372-377. View Full Paper

[49] Lucas M, Mirzaei F, Pan A, et al. Coffee, caffeine, and risk of depression among women. Arch Intern Med. 2011;171:1571-1578. View Abstract

[50] Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl). 2004 Oct;176(1):1-29. Epub 2004 Sep 21. Review. View Abstract

[51] Patil H, Lavie CJ, O’Keefe JH. Cuppa joe: friend or foe? Effects of chronic coffee consumption on cardiovascular and brain health. Mo Med. 2011 Nov-Dec;108(6):431-8. View Abstract

[52] Rose N, Koperski S, Golomb BA. Mood food: chocolate and depressive symptoms in a cross-sectional analysis. Arch Intern Med. 2010 Apr 26;170(8):699-703. View Full Paper

[53] Parker G, Crawford J. Chocolate craving when depressed: a personality marker. Br J Psychiatry. 2007;191:351-352. View Full Paper

[54] Katz DL, Doughty K, Ali A. Cocoa and chocolate in human health and disease. Antioxid Redox Signal. 2011 Nov 15;15(10):2779-811. doi: 10.1089/ars.2010.3697. Epub 2011 Jun 13. Review. View Abstract

[55] Parker, G., Parker, I. & Brotchie, H. (2006a) Mood state effects of chocolate. Journal of Affective Disorders,92, 149– 159. View Abstract

[56] Buijsse B, Weikert C, Drogan, Bergmann M, Boeing H. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J. 2010;31:1616-1623. View Abstract

[57] Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke in women. J Am Coll Cardiol. 2011;58:1828-1829. No Abstract Available

[58] Martin FP, Rezzi S, Peré-Trepat E, Kamlage B, Collino S, Leibold E, Kastler J, Rein D, Fay LB, Kochhar S. Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects. J Proteome Res. 2009 Dec;8(12):5568-79. View Abstract

[59] Nutrition and Mental Health – a handbook. Edited by Martina Watts, published by  Pavilion Publishing, 2008. Available Here

[60] Nutrition and Addiction: a handbook. Edited by Martina Watts, published by  Pavilion Publishing, 2011. Available Here

[61] Jevtović S, Karlović D, Mihaljević-Peleš A, Šerić V, Vrkić N, Jakšić N. Serum Brain-derived neurotrophic factor (BDNF): the severity and symptomatic dimensions of depression. Psychiatr Danub. 2011 Dec;23(4):363-9. View Abstract

[62] Jacka FN, Kremer P, Berk M, et al. A prospective study of diet quality and mental health in adolescents. PLoS One. 2011;6:e24805. View Full Paper

[63] Sullivan EL, Smith MS, Grove KL. Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology. 2011;93(1):1-8. Epub 2010 Nov 13. View Full Paper

[64] Parrott MD, Greenwood CE. Dietary influences on cognitive function with aging: from high-fat diets to healthful eating. Ann N Y Acad Sci. 2007;1114:389-397. View Abstract

[65] Lawrence BP, Sherr DH. You AhR what you eat? Nat Immunol. 2012 Jan 19;13(2):117-9. doi: 10.1038/ni.2213. No abstract available.