Diet and Nutrition Therapy for Chronic Illness

This is the second of a two-part post that first appeared on GreenMedInfo.com. Information about the author follows the references. If you missed the first post, read it at http://aswellasicanbe.com/chronic-illness/fight-autoimmune-diseases/

 

A Low Lectin Diet As a Therapeutic Intervention for Autoimmune Disease

In effect, researchers propose that minimizing intake of lectin-rich food substrates can lessen the persistent antigenic stimulation that results in defective immunological tolerance and causes the immune system to target the body itself (Source). Immunological tolerance is essentially the ability of the immune system to discriminate self from non-self, which is lost with autoimmune disorders (Source). This is also the rationale behind therapeutic regimens such as the paleo diet and autoimmune paleo protocol.

Whereas acute lectin toxicity in humans is insidious, manifesting with symptoms such as nausea, abdominal distention, vomiting, and diarrhea, “In experimental animals fed on diets containing plant lectins the evident symptoms are a loss of appetite, decreased body weight and eventually death” (Source). Therefore, a disease resulting from the effects of lectins can be long-latency, incubating in a sense for many years or decades before culminating in a life-threatening disorder. Thus, it is difficult to correlate symptoms with lectins, and many people may not make a connection between their health issues and the foods they are eating.

A Healthy Dose of Skepticism: More Research is Required

A well-warranted criticism of lectin science and the paleo community is that the foundations of their anti-nutrient arguments are based on animal and in vitro (cell culture) studies, which may not be fairly extrapolated to human physiology. On a ladder representing evidentiary quality, where meta-analyses and systemic reviews are positioned at the top, these study designs occupy lower rungs, are oftentimes found to be methodologically inadequate, and may not predict human reactions (Source).

Many of the studies upon which paleo advocates hang their hats are rodent models, where laboratory animals are fed disproportionately large levels of lectins or lectins from raw legumes, which may not be applicable to human health (Source). The lectin soybean agglutinin (SBA) is commonly cited as inducing intestinal permeability in paleo circles, yet piglet models have shown that disturbed barrier function only occurs when SBA is included at high levels in their diets (Source). Thus, a dose-response relationship may occur and a threshold may be reached beyond which lectin consumption is not tolerated. In addition, some of these same animal models, in fact, reveal that lectin toxicity is reduced by inclusion of oligosaccharides and simple sugars such as sucrose, which naturally occurs in the diet, given the specificity of lectins for carbohydrate moieties (Source).

Also commonly demonized is the peanut lectin, which has been shown in cell culture studies to disrupt the cytoskeletal (filaments and tubules) organization of intestinal tight junctions and lead to intestinal permeability, a phenomenon which may account for the increased allergenicity of peanuts. Paleo champions recommend avoidance of peanuts due to their atherogenic effects in animal models, yet human trials demonstrate that peanuts may improve cardiovascular risk, illustrating that animal studies may not be generalizable to human physiology (Source).

Another point with merit is that many foods included on the paleo diet, such as avocado, banana, beetroot, blackberries, broccoli, Brussels sprouts, cabbage, cantaloupe, carrots, cauliflower, cherries, cucumber, garlic, grapes, leek, mushrooms, mustard, oregano, parsley, peach, pomegranate, potato, pumpkin, taro, tea, tomato as well as various spices and nuts have all been demonstrated to exhibit lectin activity (Source)(Source). This underscores the need to distinguish between lectins and potentially toxic lectins, as the latter may predict poor physiological responses, with the immunostimulatory and gut barrier compromising effects of prolamins and agglutinins being implicated as some of the worst.

Moreover, lectin content varies, and some lectins are relatively innocuous since they are denatured by cooking (Source). Other studies, however, suggest that some lectins are not neutralized with cooking, so researchers have not yet arrived at firm conclusions in this respect. Historically, many ancestral practices, such as soaking and sprouting grains, treating corn with lye, eliminating the hull and bran of brown rice to consume the lower lectin white rice, or peeling and de-seeding vegetables, became intuitive cultural rituals in order to minimize lectin consumption. However, most of us in the industrial age have abandoned these practices and adopt mono-diets where so-called anti-nutrient rich foods are ingested in excess. Soaking, sprouting, and cooking nuts and beans, as well as fermenting vegetables, have been similarly elucidated to decrease the content of phytates, another much-maligned anti-nutrient (Source).

However, whether these approaches have scientific merit is still hotly contested. A recent randomized, cross-over trial challenges the validity of these preparation techniques and concluded not only that soaking did not improve gastrointestinal tolerance, but flatulence ratings were higher for all points for soaked nuts compared to unsoaked. Moreover, the researchers state, “Recommendations to soak nuts prior to consumption to reduce phytate concentrations and improve gastrointestinal tolerance have received much attention in the popular press. This is despite no supporting scientific evidence for the practice” (Source).

Bioindividuality May Dictate Vulnerability to Anti-Nutrients

One reason lectins may pose a problem for some individuals but not others is due to genetic variability in the cell surface glycoconjugates (carbohydrates covalently linked with other chemical species) to which lectins attach, and due to the fact that the glycoprotein tips to which lectins bind are hidden behind sialic acid molecules (Source). However, this protective screen of sialic acid molecules can be removed by the enzyme neuraminidase that accompanies pathogens such as influenza and streptococci, which cause the flu virus and Strep throat, respectively (Source). In fact, this explains the ability of infections to induce or exacerbate autoimmune disease: “This facilitation of lectins by micro-organisms throws a new light on postinfectious diseases and makes the folklore cure of fasting during a fever seem sensible” (Source).

The prevailing gut ecology may also influence susceptibility to the adverse effects of lectins. For instance, the red kidney bean lectin PHA is lethal for rats when administered in high doses, but non-toxic in germ-free animals devoid of a microbiome (Source). These findings suggest that the toxic effects of PHA could be mediated by its ability to enhance navigation of gut bacteria into systemic circulation (Source).

The centrality of the microbiota to food reactions is also applicable to another anti-nutrient frequently cited in the paleo community, phytic acid. Also known as phytate, the storage form of phosphorus in plants analogous to phosphorus in animals, phytic acid is often cited as another reason why grains and beans are excluded from a paleo diet. Phytates have been observed to bind to and inhibit absorption of minerals such as calciumzinc, and magnesium (Source). However, phytates have also been demonstrated to elicit paradoxical hormetic effects, having antioxidant, anticancer, anti-inflammatory, and anti-osteoporotic activity (Source).

Also neglected is the fact that the commensal microbes that inhabit the gut synthesize phytase, an enzyme that degrades phytate, in a dose-dependent manner (Source). In someone with dysbiosis, however, a condition applicable to almost anyone with chronic illness, this ability may be compromised. Much of the reaction to anti-nutrients may, therefore, be contingent upon the functional medicine pillar of biochemical individuality, which is a confluence of genetic proclivities, microbial terrain, environmental stressors, and the prevailing landscape of the body.

When to Implement a Low-Lectin Diet

While some lectins such as WGA and gluten are unequivocally inflammatory in most cases of chronic illness, the science on lectins is far from settled. For example, lectins may exhibit beneficial hormetic effects, as some studies reveal that lectins induce apoptosis and autophagy (self-devouring) of cancer cells, modulate endocrine and immune function, and serve as metabolic signals for the gut.

However, because of the detriment to quality of life incurred by autoimmune disorders, a therapeutic trial of a low-lectin dietary regimen like the paleo or autoimmune paleo diet is deserving of consideration. While there is a paucity of high-quality peer-reviewed human studies, the clinical experience of countless physicians supports the efficacy of these interventions. In addition, data is accruing in favor of these dietary interventions for cardiometabolic conditions and autoimmune diseases, which is further described in my article “Landmark Study Suggests Efficacy of Autoimmune Paleo Protocol”.

The success of these dietary protocols may not only be attributed to their eschewal of immunogenic foods, but also to their inclusion of bioavailable nutrients. According to the hierarchy of healing practiced by naturopathic doctors, less invasive, low-risk modalities should be attempted first when possible according to the therapeutic order, a philosophy with which dietary strategies such as these are compatible.

Researchers echo the aforementioned sentiments, with: “Although it is common knowledge that some dietary lectins can adversely affect the growth and health of young animals…it has not been rigorously established that findings with animals are also directly applicable to humans. However, because the glycosylation state of the human gut is basically similar to that of higher animals, it may be confidently predicted that the effects of dietary lectins will have similarities in both humans and animals” (Source). Self-experimentation through an elimination diet is the gold standard for identifying reactions to food constituents, and lectins are no exception.


References

1. Vasconcelos, I.M., & Oliveira, J. T.A. (2004). Antinutritional properties of plant lectins. Toxicon, 44(4), 385-403.

2. Vojdani, A. (2015). Lectins, agglutinins, and their roles in autoimmune reactivities. Alternative Therapies, 21(1), 46-51.

3. Ramadass, B., & Dokladny, K. (2010). Sucrose co-administration reduces the toxic effect of lectin on gut permeability and intestinal bacterial colonization. Digestive Disease Science, 55, 2778-2784.

4. Liener, I.E. (2009). Implications of antinutritional components in soybean foods. Implications of antinutritional components in soybean foods, 34(1), 31-67.

5. Otte, J.M. et al. (2001). Mechanisms of lectin (phytohemagglutinin)-induced growth in small intestinal epithelial cells. Digestion, 64, 169-178.

6. Kordás, K. et al. (2000). Diverse effects of phytohaemagglutinin on gastrointestinal secretions in rats. Journal of Physiology, 94, 31-36.

7. Thompson, L.U., Tenebaum, A.V., & Hui, H. (1986). Effect of lectins and the mixing of proteins on rate of protein digestibility. Journal of Food Science, 51, 150-152.

8. Cordain, L. et al. (2000). Modulation of immune function by dietary lectins in rheumatoid arthritis. British Journal of Nutrition, 83(3), 207-217.

9. Pusztai, A. (1993). Dietary lectins are metabolic signals for the gut and modulate immune and hormone functions. European Journal of Clinical Nutrition, 47, 691-699.

10. Bardocz, S. et al. (1996). The effect of phytohaemagglutinin on the growth, body composition, and plasma insulin of the rat at different dietary concentrations. British Journal of Nutrition, 76, 613-626

11. Banwell, J.G. et al. (1988). Bacterial overgrowth by indigenous microflora in the phytohemagglutinin-fed rat. Canadian Journal of Microbiology, 34, 1009-1013.

12. Oliveira, J.T.A. et al. (1994). Canavalia brasiliensis seeds. Protein quality and nutritional implications of dietary lectin. Journal of Science, Food, & Agriculture, 64, 417-424.

13. Hornig, M. (2013). The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Current Opinions in Rheumatology, 25, 488-795.

14. Lucky, D. et al. (2013). The role of the gut in autoimmunity. Indian Journal of Medical Research,138, 732–743.

15. Russell, S.L., & Finlay, B.B. (2012). The impact of gut microbes in allergic diseases. Current Opinions in Gastroenterology, 28, 563–569.

16. Tilg, H., & Kaser, A. (2011). Gut microbiome, obesity, and metabolic dysfunction. Journal of Clinical Investigations, 121, 2126-2132.

17. Zhao, L. (2013). The gut microbiota and obesity: from correlation to causality. Nature Reviews Microbiology, 11, 639–647.

18. Freed, D.J. (1999). Do dietary lectins cause disease? The evidence is suggestive—and raises interesting possibilities for treatment. British Journal of Medicine, 318(7190) ,1023–1024.

19. Haas, H. et al. (1999). Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils. European Journal of Immunology, 29, 918-927.

20. Berger, A. (2000). Th1 and Th2 responses: what are they? The British Medical Journal, 321, 424.

21. Vojdani, A., Kharrazian, D., & Mukherjee, P.S. (2013).  The prevalence of antibodies against wheat and milk proteins in blood donors and their contribution to neuroautoimmune reactivities. Nutrients, 6(1), 15-36.

22. Vojdani, A., & Tarash, I. (2013). Cross-reaction between gliadin and different food and tissue antigens. Food and Nutrition Science, 4(1), 20-32.

23. Brady, P.G., Vannier, A.M., & Banwell, J.G. (1978). Identification of the dietary lectin, wheat germ agglutinin, in human intestinal contents. Gastroenterology, 75, 236-239.

24. Pusztai, A. et al. (1993a). Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins. British Journal of Nutrition, 70, 313-321.

25. Doherty, M., & Barry, R.E. (1981). Gluten-induced mucosal changes in subjects without overt small-bowel disease. Lancet, I, 517-520.

26. de Punder, K., & Pruimboom, L. (2013). The Dietary Intake of Wheat and other Cereal Grains and Their Role in Inflammation. Nutrients, 5(3), 771-797. doi:  10.3390/nu5030771

27. Balakireva, A., & Zamyatnin Jr., A.A. (2016). Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities. Nutrients, 8(10), 644.  doi:  10.3390/nu8100644

28. Hardy M.Y. et al. (2015). Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides. Journal of Autoimmunity, 56, 56–65. doi: 10.1016/j.jaut.2014.10.003.

29. Fasano, A. (2012). Leaky gut and autoimmune disease. Clinical Reviews in Allergy and Immunology, 42(1), 71-78.

30. Hollon et al. (2015). Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity. Nutrients, 7(3), 1565-1576.

31. Fasano, A., & Shea-Donohue, T. (2005). Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. National Clinical Practice in Gastroenterology and Hepatology, 2(9).

32. Nilsen E.M. et al. (1998). Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology, 115, 551–563. doi: 10.1016/S0016-5085(98)70134-9.

33. Aziz, I., Hadjivassiliou, M., & Sanders, D.S. (2015). The spectrum of noncoeliac gluten sensitivity. National Reviews in Gastroenterology & Hepatology, 12, 516–526. doi: 10.1038/nrgastro.2015.107.

34. Jackson, J. et al. (2014). Gluten sensitivity and relationship to psychiatric symptoms in people with schizophrenia. Schizophrenia Research, 59, 539–542. doi: 10.1016/j.schres.2014.09.023.

35. Lionetti, E. et al. (2015). Gluten Psychosis: Confirmation of a New Clinical Entity. Nutrients, 7, 5532–5539. doi: 10.3390/nu7075235.

36. Bracken, M.B. et al. (2009). Why animal studies are often poor predictors of human reactions to exposure. Journal of the Royal Society of Medicine, 102(3), 120–122. doi: 10.1258/jrsm.2008.08k033

37. Zhao, Y. et al. (2011). Effects of Soybean Agglutinin on Intestinal Barrier Permeability and Tight Junction Protein Expression in Weaned Piglets. International Journal of Molecular Sciences, 12(12), 8502-8512.

38. Price, D.B. et al. (2014). Peanut allergens alter intestinal barrier permeability and tight junction localisation in Caco-2 cell cultures. Cell Physiology and Biochemistry, 33(6), 1758-1777. doi: 10.1159/000362956.

39. Kritchevsky, D., Tepper, S.A., & Klurfeld, D.M. (1998). Lectin may contribute to the atherogenicity of peanut oil. Lipids, 33(8), 821-823.

40. Nouran, G. et al. (2010). Peanut consumption and cardiovascular risk. Public Health Nutrition, 13(10), 1581-1586.  doi: 10.1017/S1368980009992837.

41. Nachbar, M.S., & Oppenheim, J.D. (1980). Lectins in the United States diet: a survey of lectins in commonly consumed foods and a review of the literature. American Journal of Clinical Nutrition, 33(11), 2338-2345.

42. Vidal-Valverde, C. et al. (1994). Effect of processing on some antinutritional factors of lentils. Journal of Agriculture and Food Chemistry, 42(10), 2291-2295. doi: 10.1021/jf00046a039

43. Uchigata, Y. et al. (1987). Pancreatic islet cell surface glycoproteins containing Gal β(1-4)GNAc-R identified by cytotoxic monoclonal antibodies. Journal of Experimental Medicine, 165, 124–139.

43. Rattray, E.A.S., Palmer, R., & Pusztai, A. (1974). Toxicity of kidney beans (Phaseolus vulgaris L.) to conventional and gnotobiotic rats. Journal of the Science of Food and Agriculture, 25, 1035-1040.

44. Reinhold, J.G. et al. (1973). Effects of purified phytate and phytate-rich breach upon metabolism of zinc, calcium, phosphorus, and nitrogen in man. The Lancet, 301(7798), 283-288.

45. Bohn, T. et al. (2004). Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans. American Journal of Clinical Nutrition, 79(3), 418-423.

46. Lopez-Gonzalez, A.A. et al. (2013). Protective effect of myo-inositol hexaphosphate (phytate) on bone mass loss in postmenopausal women. European Journal of Nutrition, 52(2), 717-726.

47. Markiewicz, L.H. et al. (2013). Diet shapes the ability of human intestinal microbiota to degrade phytate—in vitro studies. Journal of Applied Microbiology, 115(1), 247-259.

48. Yau, T. et al. (2015). Lectins with potential for anti-cancer therapy. Molecules, 20(3), 3791-3810. doi: 10.3390/molecules20033791.

49. Pusztai, A. (1993). Dietary lectins are metabolic signals for the gut and modulate immune and hormone functions. European Journal of Clinical Nutrition, 47(10), 691-699.

50. Taylor, H. et al. (2017). The effects of ‘activating’ almonds on consumer acceptance and gastrointestinal tolerance. European Journal of Nutrition.

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