The British Naturopathic Association's annual Study Day on June 23rd 2012 will have the theme of Naturopathic Approaches to Endocrinology. MIfHI graduates, Drs. Tom and Jacqueline Greenfield, are presenting a lecture entitled: A Nutrigenomic Approach to Endocrinology. A summary of their lecture follows:

Medical endocrinologists typically deal with major hormonal imbalances pharmacologically. A reductionistic approach to the body perceives the organ which is producing increased or decreased levels of hormones as the source of the organic dysfunction; the "cure" is either hormone replacement therapy, suppression of excess hormone production or blocking receptor sites. In the same way, nutritional supplementation can be used to make up for deficiencies or excess to directly enhance or suppress the function of specific hormonal pathways. However this is not necessarily treating the patient as a whole: it could be seen as linear thinking, not looking for the reason behind the disturbance in homoeostasis, or whether the cause of the imbalance is still there. As naturopaths how can we support health in the patient with endocrine-related disorders using natural methods and a more holistic approach?

Nutrigenomics has brought a growing awareness of the potential for modification of food intake to promote health and reduce the risk of diet-related diseases. It is a way of altering the expression of genes through nutrition: a nutrigenomic perspective views nutrients as cell-signalling mechanisms which are detected by sensors in the cell: a variation in nutrient levels triggers a cellular mechanism which changes gene expression, protein and metabolite production. This can restore balance in many body systems where the individual's genes have been programmed during gestation to survive in an environment in which they no longer find themselves.

In our presentation we discuss ways of influencing hormonal pathways through diet and nutritional supplementation at the level of the gene using the example of types of thyroid dysfunction and diabetes. We also look at a commonly-supplemented hormone in detail: vitamin D, it's role in many disease processes; we review a hypothesis for the role of vitamin D3 and it's metabolite in dysregulation of androgen and glucocorticoid receptors in autoimmune disease.

Knowing what diseases to prevent and how to address existing illness is the key to individualised medicine. As naturopaths we can target prevention to the specific disease tendencies of the individual rather than assume everyone will get the same illnesses. We present a system devised by Dr. Peter D'Adamo ND which looks at three overriding responses to the environment: reactive, thrifty and tolerant, further refined by gene clusters, or haplotypes, in proximity to the blood group gene on 9q34. We discuss simple in-clinic biomarkers that can be used to assess the patient's epigenetics: how to determine their disease susceptibilities and which preventive measures may be the most appropriate for them; in the presence of an existing disorder, how to know which pathways to upregulate or downregulate through dietary intervention. We also discuss an educational opportunity for practitioners and the informed public to become certified in human individuality.

Other speakers at the event are Dr. Marilyn Glenville Ph.D., nutritionist specialising in women’s health, Alison Cullen, education manager at Bioforce UK, and Marian Baartz MSc., Iridologist. The event is open to non-members of the British Naturopathic Association.

A study by Karlic et. al. [1] found that a vegetarian diet has a significant impact on a gene regulating carnitine metabolism. Carnitine is an amino acid (protein constituent) and a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. A “conditionally essential” nutrient is one that can be manufactured in the body, but the requirements of individuals might exceed dietary intake during specific disease states. Carnitine not obtained from food is synthesized in the body from two essential amino acids, lysine and methionine. Carnitine is found in higher levels in meat products as it is present in high levels in muscle tissue.

Vegetarian diets therefore contain less carnitine, and also often contain more carbodydrate than omnivorous diets as sources of concentrated vegetable proteins are not so readily available as animal proteins.

The study found increased expression of a gene [2] called Organic Cation Transporter 2 (OCTN2) in vegetarians which caused elevated levels of OCTN2 in cell membranes, compensating for lower carnitine levels obtained from the diet. Thus a vegetarian lifestyle has an impact on fat metabolism causing a remarkable stimulation of carnitine uptake.

The bioavailability of L-carnitine varies due to dietary composition. Bioavailability of L-carnitine in vegetarians who are adapted to low-carnitine diets is higher (66% to 86% of available carnitine) than regular red-meat eaters adapted to high-carnitine diets (54% to 72% of available carnitine). Carnitine influences carbohydrate metabolism. Abnormal carnitine regulation is implicated in complications of diabetes mellitus, cardiomyopathy, obesity, endocrine imbalances and other disorders. [3]

According to The Blood Type Diet and The GenoType Diet, individuals with a particular genetic characteristic and the associated metabolic consequences may be recommended to reduce the amount of red meat in their diets. This may be due to specific disease susceptibility and/or reduced ability to digest and metabolise red meats. Some of the consequences of increased carbohydrate intake in these individuals may be compensated for by the natural epigenetic effect of lowered carnitine intake on the gene that enhances the concentration of this nutrient and resultant increased bioavailability.

References:
1. Karlic H, Schuster D, Varga F, Klindert G, Lapin A, Haslberger A, Handschur M: "Vegetarian Diet Affects Genes of Oxidative Metabolism and Collagen Synthesis." Ann Nutr Metab 2008;53:29-32. Pubmed 18772587

2. OMIM OCTN2

3. Flanagan JL, Simmons PA, Vehige J, Willcox MDP, Garrett Q: "Role of carnitine in disease." Nutrition & Metabolism 2010, 7:30 doi:10.1186/1743-7075-7-30

Here's a preview of a guest editorial I was asked to write for the British Naturopathic Journal about where Naturopathy is heading over the next decade:

With the dramatic rise in access to information over the last decade our patients are becoming experts in their own conditions and ways to heal themselves. The increase in patient knowledge means the days where a patient will accept uncritically the word of the physician are coming to an end, particularly where the advice given does not correspond with what they have read or expect to hear.

How does this change our role - how can we keep up with the new expectation of our patients: That we have a knowledge of their disease as detailed as they do and the skills to offer specific treatment? Traditional naturopaths might say stick to the basics: Fresh air; clean water; hydrotherapy; pure diet; exercise; right thinking; fasting when appropriate. This approach will always give the healing power of nature a chance to restore and maintain health in most situations with which we are presented. In reality many people nowadays have the pressure of work, family or other financial and time constraints, and the option to resort to orthodox treatment: They demand something more, a quicker, easier solution to their problems, or advice that they can't get for themselves. Unless we specialise in the naturopathic approach to treating patients with one particular type of condition, how can the polymath respond to this challenge while staying true to the core principles of naturopathy?

The essence of naturopathic philosophy maintains that every patient is unique, and every treatment must be tailored to that individual. As experts in assessing types of patients and with the ability to compare the person in our office with those we have treated before, we are in a good position to judge their differences and similarities to others and recognise the therapeutic significance. Naturopaths have access to tests, experience in taking body measurements, and the ability to interpret the results and offer advice. With genetic testing, orthodox medicine is moving towards a scientific understanding of the patient's individuality, and naturopathic medicine must follow this example. Genetic tests are available for use with functional medicine, but are still relatively expensive and the results often too complex for the average patient to easily relate. Another way to determine patient individuality is to use traditional observations and simple tests that can be done in the clinic - the body has many external signs that can indicate specific tendencies, patterns and needs: Iridology is one system, reflexology another. Despite their regular and efficient use by many practitioners these systems often lack clinical validation as primary assessment tools, a factor which is is frequently being questioned.

One system using scientific measurements of individuality that can be carried out in the clinic while remaining true to core naturopathic concepts is 'The GenoType Diet', a therapeutic system devised by naturopathic physician Dr. Peter D'Adamo. Having evolved from 'The Blood Group Diet', naturopaths using this system will initially classify the patient into one of six major categories based on their blood group; further refinements are then made according to genetic and epigenetic factors determined by simple biometric measurements taken in the consulting room, along with the clinical judgements of the practitioner. An example of this would be D2:D4 ratio: The difference between the second and fourth digit on each hand. Many published papers show how this characteristic can be influenced by hormone levels in-utero; the epigenetic effects last throughout life; measurement simply requires a ruler, and that the patient still has these four fingers. The practitioner can also assess the likelihood of these prenatal influences being due to maternal hormone exposure or hormone-mimicking xenobiotics.

D'Adamo offers this system to practitioners who know and understand his work. Any level of personalisation can be added to the secure online data collection tool according to the patient's requirements or clinical need; a complete dietary and lifestyle report is accessed via a complex database that makes millions of calculations based on how a particular food influences this patient. In addition to calorific value, factors such as enhancement of methylation, histone activation, acetylation requirements or contribution to glycation of a particular dietary component may be factored in according to the genetic tendencies of the patient. If any factors change, for example: The patient's weight; exercise regime; family history; conventional medication prescription; adjustment to the patient's data may result in changes to their recommendations, so the advice can be updated with each clinic visit.

Systems such as this are the future of naturopathic medicine: Patients feel satisfied that they are getting personalised healthcare they can't get elsewhere, while the practitioner can integrate their own favourite therapeutic approach according to individual need. By 2020 this approach may well be standard procedure in naturopathic healthcare.

A recent study in the British Journal of Nutrition [1] has found that dark chocolate contains antioxidants that are protective to DNA, but this effect only lasts for a day. Researchers in Milan, Italy, measured plasma epicatechin levels, DNA damage in mononuclear blood cells, and plasma total antioxidant activity in 20 volunteers on a balanced diet with standardised levels of antioxidants. After a washout period the subjects were given 45g of either dark chocolate (DC, containing 860 mg polyphenols, of which 58 mg epicatechin) or white chocolate (WC, no epicatechin).

The results found that increased levels of epicatechin in the blood of those who had eaten the dark chocolate lasted for nearly a day; between 2 hours and 22 hours after DC intake. This corresponded with lower levels of DNA damage to the blood cells, but eating the dark chocolate did not affect total antioxidant activity. Eating WC did not make any difference to the factors measured. The researchers conclude: "DC may transiently improve DNA resistance to oxidative stress." They add: “the present results are clinically encouraging especially in the field of the diet therapy of obesity, pathology related to greater incidence of cardiovascular disease and cancer”. Unfortunately regular consumption of dark chocolate does not increase long-term epicatechin levels, so according to this study, dark chocolate must be consumed daily to get these benefits.

Chocolate has long been known to be an important part of a healthy diet According to Donatella Lippi of the Department of Anatomy, Histology and Legal Medicine, University of Florence, Italy [2]:

The Aztecs believed that cocoa pods symbolized life and fertility, and that eating the fruit of the cocoa tree allowed them to acquire wisdom and power. Cocoa was said to have nourishing, fortifying, and aphrodisiac qualities.

One well-researched benefit of chocolate is improving the health of the heart. In a Data from The Stockholm Heart Epidemiology Study showed how of 1169 non-diabetic patients having their first heart attack, those who were regular consumers of chocolate were more likely to survive. [3] A study on dark chocolate published in the International Journal of Cardiology [4] measured the effect of 45g of dark chocolate on blood circulation in the coronary arteries as measured by doppler ultrasound. After two weeks of daily intake the researchers conclude:

Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects.

Epicatechins are a type of polyphenol antioxidant in the catechin family. Catechins are found in tea, wine, fruits and vegetables as well as dark chocolate. However it is the bitter principles in the chocolate that contain the beneficial antioxidants: An editorial in The Lancet [5] points out that some chocolate manufacturers may darken the natural cocoa solids and remove the bitter flavanols, "so even a dark-looking chocolate can have no flavanol". In addition, cacao colouring can contain more than the maximum EU permitted level of mercury (1 mcg/g). [6] Manufacturers rarely label their products with this information. In addition, 45g of dark chocolate contains about 200 calories, so calorific intake must be taken into account as part of the risk/benefit calculation. One way round that might be to use raw cacao nibs which contain no sugar and are also unheated, thereby likely to have a higher catechin content, although the consumer may not see the benefit of this over drinking red wine, for example.

Therefore the amount of chocolate consumed is not necessarily proportionate to it's health benefits: Another paper from the British Journal of Nutrition [7] demonstrated that even doubling the the polyphenol content in the same size dose of chocolate had no significant dose-related benefits:

It was observed that the 500 mg polyphenol dose was equally effective in reducing fasting blood glucose levels, systolic BP and diastolic BP as the 1000 mg polyphenol dose suggesting that a saturation effect might occur with increasing dose of polyphenols.

Dark chocolate is suitable for individuals of all blood groups. [8] However, a recent paper in the Journal of Cardiovascular Pharmacology [9] suggests that in addition to the well-known antioxidant effects, one way chocolate may directly help cardiovascular system is by improving nitric oxide function. Nitric oxide recycling is an important function that can sometimes be inadequate in those with the B antigen (blood groups B and AB), probably due to genetic linkage of the argininosuccinate synthase enzyme. [10]

When giving the gift of chocolate to loved ones it may be prudent to ensure adequate polyphenol content, absence of colouring, and to draw attention to the health benefits of both moderation and regular consumption.

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References:

1. Spadafranca A, Martinez Conesa C, Sirini S, Testolin G. "Effect of dark chocolate on plasma epicatechin levels, DNA resistance to oxidative stress and total antioxidant activity in healthy subjects." Br J Nutr. 2009 Nov 5:1-7. PMID: 19889244
doi: 10.1017/S0007114509992698

2. Lippi D. "Chocolate and medicine: dangerous liaisons?" Nutrition. 2009 Nov-Dec;25(11-12):1100-3.
PMID: 19818277

3. Janszky I, Mukamal KJ, Ljung R, Ahnve S, Ahlbom A, Hallqvist J. "Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program." J Intern Med. 2009 Sep;266(3):248-57. PMID: 19711504

4. Shiina Y, Funabashi N, Lee K, et. al. "Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic Doppler echocardiography in healthy adults." Int J Cardiol. 2009 Jan 24;131(3):424-9. PubMed PMID: 18045712.

5. Lancet. 2007 Dec 22;370(9605):2070. "The devil in the dark chocolate." [No authors listed] PMID: 18156011
doi:10.1016/S0140-6736(07)61873-X

6. Ogimoto M, Uematsu Y, Suzuki K, Kabashima J, Nakazato M. ["Survey of toxic heavy metals and arsenic in existing food additives (natural colors)"]. Shokuhin Eiseigaku Zasshi (Journal of the Food Hygienic Society of Japan). 2009 Oct;50(5):256-60. PMID: 19897953

7. Almoosawi S, Fyfe L, Ho C, Al-Dujaili E. "The effect of polyphenol-rich dark chocolate on fasting capillary whole blood glucose, total cholesterol, blood pressure and glucocorticoids in healthy overweight and obese subjects." Br J Nutr. 2009 Oct 13:1-9. PMID: 19825207

8. Blood Type Diet/ Nutrient Value Encyclopedia: TypeBase 4 - Chocolate

9. Galleano M, Oteiza PI, Fraga CG. "Cocoa, chocolate, and cardiovascular disease." J Cardiovasc Pharmacol. 2009 Dec;54(6):483-90. PMID: 19701098

10. Website - The Individualist: Nitric Oxide

A marker on the fingertips present at birth may predict adult-onset diabetes, according to a study published in the International Journal of Epidemiology [1].

Dermatoglyphics, the study of skin markings made by ridges on hands and feet, is used as a way of measuring gene expression determined by the early pre-birth environment. On each fingertip, the number of dermal ridges (the ridge count) provides a measure of fingertip growth activity during the early foetal period. These dermal ridges are formed during gestational weeks 12–19, and the resulting fingertip ridge appearance (i.e., the fingerprint) is fixed permanently.

Changes in the uterine environment can influence the activity of genes which either stimulate or inhibit growth of specific areas of the body. According to the study by Kahn and colleagues, those with specific dermatoglyphic patterns were more likely to develop type 2 diabetes after the age of 50, even when other influencing factors were taken into account. The ratio of the difference between the number of ridges on the thumb and 5th finger is one way of predicting the probability of an individual developing diabetes in later life:

Fingerprints may provide a useful tool to investigate prenatal developmental plasticity.

Epigenetics, or the influence of environment on gene expression, has become recognised as an influencing factor in type 2 diabetes [2]. Other body measurements predicting similar disease risk, such as the waist-to-thigh ratio, are also correlated with fingertip ridge counts [3]. Evidence for the significance of epigenetic influences during early prenatal life is compelling, and should be used as the basis for a preventive strategy starting before conception. Dermatoglyphics is used in The GenoType Diet, along with other markers of gene expression, not only to predict future disease risks, but to target specific prevention strategies.

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References:

1. Kahn HS, Graff M, Stein AD, Lumey LH. "A fingerprint marker from early gestation associated with diabetes in middle age: the Dutch Hunger Winter Families Study." Int J Epidemiol. 2009 Feb;38(1):101-9.
PMID: 18684786

2. Ling C, Groop L. "Epigenetics: a molecular link between environmental factors and type 2 diabetes." Diabetes. 2009 Dec;58(12):2718-25.
PMID: 19940235

3. Kahn HS, Graff M, Stein AD, Zybert PA, McKeague IW, Lumey LH. "A fingerprint characteristic associated with the early prenatal environment." Am J Hum Biol. 2008 Jan-Feb;20(1):59-65.
PMID: 17929242