Food Sensitivities and Epigenetics
Ginger Nash, ND
Determining dietary advice for our patients is notoriously complicated. As NDs, we must wrestle with this on a daily basis. Naturopathic physicians have the best training in nutritional science, and most of us have experience with a plethora of dietary systems. In addition, we are bombarded with information about the pros and cons of certain foods or ways of eating. A lesson I learned early on in my career is that there is no ideal diet that exists in a vacuum. A “paleo” diet works for some folks, and a vegan diet works for others.
Our profession acknowledges that a healthy diet is an essential aspect of good health, but what is the best method of determining this on an individualized basis? Of course, strides can be made for many people just by recommending that they avoid processed foods and choose whole foods instead. But barring that simple advice, how do we figure out what will make one patient well and another patient not so well? This article will discuss the basics of my approach to nutrition, with consideration of genetics, epigenetics, and food sensitivity testing through blood tests.
Allergies, Intolerances, or Sensitivities?
Considering how common food intolerances are, it would be wonderful if a relatively simple blood test looked for sensitivities. Initially, I used a number of these tests in practice, or patients brought in test results that other physicians had ordered. Generally, there are 3 types of food allergy and sensitivity testing, each looking for elevated levels of different immunoglobulins: IgE, IgG, and IgA. A true allergy is almost always mediated through IgE, with some studies1,2 suggesting a supporting role for IgG and IgA. IgE produces the severe, systemic, usually immediate reactions that one gets when ingesting even minute quantities of the offending food. Symptoms almost always occur shortly after eating and produce mild to severe anaphylaxis. We usually do not have to worry about diagnosing those types of true food allergies. A trip to the hospital with a child who cannot breathe is often the harsh way these diagnoses are found.
Food intolerances are much more pervasive and cause milder symptoms, but they are often the kinds of chronic complaints we see in practice. For example, eczema, digestive disturbances, headaches, and rhinitis or sinusitis have all been associated with food intolerance.3,4 Blood tests for IgG or IgA food intolerances are much more common in our profession and, in my opinion, more confusing. Why? I often found that many of the foods patients were eating frequently (because they enjoyed them and they seemed to make them feel good) were products that IgG testing identified as problematic. On the contrary, there were things that should seem problematic that showed no immune reaction at all. In other words, I found what I believe to be many false positives and a few false negatives. That is confusing. Exception is made for gliadin allergy, which is primarily mediated through IgA immunoglobulins. A major exception to this is the popular use of IgA testing for sensitivity to gliadin.
What are tests for IgG and IgA actually measuring? Most tests use a sample of the patient’s blood to look for basophil and mast cell degranulation and the activation of complement cascade when the blood is exposed to potential food triggers and antigens. Indeed, these mechanisms are part of the allergic response, but what they actually correlate to is up for debate.5 Some studies6-8 have shown that exposure to foods, not the presence of disease, will result in higher amounts of IgG antibodies in healthy individuals.
In addition, the samples that laboratories are using for antigen presentation may be problematic.5 Many of the foods used as antigen samples were not organic, and even if they were, there could easily be other microorganisms in the foods if they were not purified properly. This prompts the question whether a person is reacting to foods, or has the patient been exposed to certain pesticides, fungi, bacteria, or viruses that are causing reactions?
Evaluating food sensitivities or intolerances using these tests proved very difficult for me. In fact, testing is the most controversial aspect of diagnosis within the allopathic allergy community as well. For some studies,9,10 the results are not reproducible when evaluating the IgG reactions. As a clinician, I have found that there are just too many times when the test results do not match up with a patient’s symptoms.
Now this can cut both ways. If a patient has problems with the patency of the gut lining, he or she can react to almost any food that is breeching the intestinal barrier. Have you ever had a patient report a reaction to everything, even the most seemingly benign foods? That signals to me that the patient needs to heal the intestinal lining before any type of meaningful evaluation of proper diet can be made.
The Genetic Component
So how can we move forward? Do we just take a careful family history? Can food allergies be passed down through the genes? Certainly, but the mechanisms are poorly understood. The dysregulation of certain genes, resulting in a profusion of proinflammatory cytokines, is probably the culprit. For years, studies on identical twins have shown some genetic component. But the differences in appearance, severity, and manifestation of allergies in twins suggest that there is more at work than a single gene or mechanism.
Part of the answer to that riddle may be found in the science of epigenetics, studying how genes are activated or silenced without changing the underlying patterns of DNA. Research in this field has exploded in the past decade. The main mechanisms of epigenetics that have been elucidated are DNA methylation and histone acetylation. These 2 mechanisms work in concert with one another to reinforce the underlying activity of the genes. Some have said that they act as volume controls on gene expression.11
Methylation patterns are established in utero and in early infancy, and these settings can be passed down from one generation to another. Hence, what may seem locked in the genes may actually be somewhat changeable. Epigenetics looks at the way genes interact with our environment, part of which is diet. That is the truly exciting thing for NDs: we can influence and potentially change these patterns through diet and nutrition.
There is an interesting relationship between inflammation and methylation as well. Aberrant patterns of methylation distort cell function, changing the cell’s ability to control inflammation and make accurate copies of itself. If we address methylation through nutrition, we can help control the immune reactions that have a role in developing food sensitivities and intolerances. Epigenetic patterns can also give us insight into the type of metabolism and immune function in individuals. The emerging field of maternal and fetal medicine has described a certain amount of “anticipation” a person comes into the world with. If you are programmed for scarcity in utero, meaning you did not receive adequate nutrition, and then met with an abundance of calories, you are much more likely to develop diabetes, obesity, and heart disease. Conversely, if you are exposed to toxins like cigarette smoke, certain microbes, or even normal foods at too early a time, it may alter the patterns of gene expression, making you more likely to develop reactions to foods.12,13 An interesting question that is yet to be answered is whether environmental factors are more likely to affect those at risk on a genetic basis for food allergy.
After years of recommending that patients avoid the standard American diet and eat whole foods instead, I began to look into the science of blood type with regard to diet. Since blood type is genetically determined, this is another way my dietary advice is based in one’s genetics. After my initial interest, I went to work alongside Dr Peter D’Adamo, who has pioneered this approach, at his clinic in Wilton, Connecticut, and I owe a great deal of my understanding of this approach to his tutelage.
Although a comprehensive review of blood type physiology is beyond the scope of this article, there are a few key aspects that determine my initial understanding of individualized dietary advice. The first is that your blood type has a role in shaping the entire landscape of your gut. “Blood type” is actually a carbohydrate antigen that acts as food source for gut bacteria. Certain strains of bacteria have a greater affinity for the different carbohydrates, meaning that your gut bacteria eat certain foods based on your blood type. Recent evidence suggests that your diet has a role in the composition of your gut flora, which should come as no surprise to NDs. If you eat a diet that your beneficial gut bacteria want to consume, then you are likely to have far fewer problems with digestion. The recent discovery of enterotypes is somewhat old news to those of us who have been thinking about the fact that the differences in the composition of gut bacteria mean differences in one’s ability to digest, metabolize, and absorb various food groups.14 There is much more to understand about what gut types exist and how we can best support their healthy functioning.
Lectins Are in Charge
Another major aspect of diet and blood type is that blood type has a role in which foods your body likes and does not like. It does this through the activity of lectins. Lectins are molecules, sugar-binding proteins, that are found in abundance throughout the plant and legume world. They are highly specific to their sugar moieties. After all, the word lectin comes from the Latin word legere, or “I choose.” As I have said, your blood type is a sugar antigen, a carbohydrate structure found on the surface of many cells. It is not just found in your blood. Blood type is found extensively throughout the lining of your gut and all your digestive secretions. When you consume lectins that want to bind to your particular blood type, you damage the intestinal lining, diminish your ability to digest food, and lay the foundation for inflammation in the gut. Generalized, low-lectin diets continue to be recommended, but it is really Dr D’Adamo’s work that looked at the specificity of lectins for each person based on his or her blood type.
It is also worth mentioning that the gene that codes for your blood type also influences other aspects of physiology. With regard to your digestive system, your blood type is associated with the levels of intestinal alkaline phosphatase your body produces. Intestinal alkaline phosphatase helps you break down fats, cholesterol in particular, and helps absorb calcium from the gut.15-17 People with blood type O have 3 times the amount of intestinal alkaline phosphatase than individuals with blood type A. This suggests that individuals with blood type O are genetically predisposed to digest more animal proteins.
Epigenetics, an Emerging Science
If the body was a block of marble from which I am trying to carve a fine sculpture using diet as my tool, blood type might be considered the first major cuts into the block. The emerging science of epigenetics provides further direction in terms of applying tools to the marble. Evaluating the kind of experiences one had in the womb and looking at early environmental exposures help me determine the metabolic type of the individual in front of me. Most of this evaluation comes from simple biometric measurements that are low-tech and can be performed in my office in a matter of minutes. One does not need to perform expensive genetic testing.
If we continue with the analogy of creating a sculpture, the final details would come from the individual’s own experiences with food. I will always take a careful history and ask about reactions to any particular foods in the context of the patient’s reason for paying me a visit. If the patient has digestive disturbances, it is often easy for him or her to identify bothersome foods. If migraines or chronic sinus congestion is reported, those connections may be more difficult to ascertain. Just as importantly, to reiterate, the more imbalanced a patient is, the more reactions he or she may get. Over time, and with healing of the gut lining, patients may be able to tolerate foods that they previously felt were adversely affecting them. It would be interesting to see if a blood test would reveal elevated IgA levels at that time.
Following a diet that is based on one’s blood type, one’s epigenetic or metabolic type, and one’s ability to recognize foods that do not agree with them represents the basics of my approach. All these topics are large fields of study unto themselves, and I realize that I have not comprehensively addressed any of them. But I have found what I believe to be a sane approach to navigating through all the options that face us with regard to dietary advice. Hopefully, most of my patients would agree.
Ginger Nash, ND graduated from the National College of Naturopathic Medicine (Portland, Oregon) in 1998. After graduating, she worked in the field of women’s health and has had a general practice in New Haven, Connecticut, since 1999. Dr Nash teaches at the University of Bridgeport’s College of Naturopathic Medicine (Bridgeport, Connecticut) and has been teaching seminars for healthcare practitioners throughout the United States and Canada for over 10 years.
1. Berin MC. Mucosal antibodies in the regulation of tolerance and allergy to foods. Semin Immunopathol. 2012;34(5):633-642.
2. Guo H, Jiang T, Wang J, et al. The value of eliminating foods according to food-specific immunoglobulin G antibodies in irritable bowel syndrome with diarrhoea. J Intern Med Res. 2012;40(1):204-210.
3. Yawn BP, Fenton MJ. Summary of the NIAID-sponsored food allergy guidelines. Am Fam Physician. 2012;86(1):43-50.
4. Carroccio A, Mansueto P, Iacono G, et al. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012;107(12):1898-1907.
5. Miller SB. IgG food allergy testing by ELISA-EIA: what do they really tell us? http://www.tldp.com/issue/174/IgG%20Food%20Allergy.html. Accessed February 19, 2013.
6. Tomicić S, Norrman G, Fälth-Magnusson K, Jenmalm MC, Devenney I, Böttcher MF. High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life. Pediatr Allergy Immunol. 2009;20(1):35-41.
7. Savilahti EM, Rantanen V, Lin JS, et al. Early recovery from cow’s milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow’s milk epitopes. J Allergy Clin Immunol. 2010;125(6):1315-1321.e9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289532/. Accessed February 19, 2013.
8. Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124(2):292-300, 300.e1-97. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725434/. Accessed February 19, 2013.
9. Gerez IF, Shek LP, Chng HH, Lee BW. Diagnostic tests for food allergy. Singapore Med J. 2010;51(1):4-9.
10. Hamilton RG. Clinical laboratory assessment of immediate-type hypersensitivity. J Allergy Clin Immunol. 2010;125(2)(suppl 2):S284-S296.
11. D’Adamo P, Whitney C. Change Your Genetic Destiny. New York, NY: Broadway Books; 2007:4.
12. Hong X, Wang X. Early life precursors, epigenetics, and the development of food allergy. Semin Immunopathol. 2012;34(5):655-669.
13. Tan TH, Ellis JA, Saffery R, Allen KJ. The role of genetics and environment in the rise of childhood food allergy. Clin Exp Allergy. 2012;42(1):20-29.
14. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105-108.
15. Nakata N, Tozawa T. The ABO blood groups–dependent reference intervals for serum alkaline phosphatase isozymes and total activity in individuals 20-39 years of age [in Japanese]. Rinsho Byori. 1995;43(5):508-512.
16. Lallès JP. Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr Rev. 2010;68(6):323-332.
17. Malo MS, Alam SN, Mostafa G, et al. Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota. Gut. 2010;59(11):1476-1484.