Problems with Wheat

Discoveries in the last 15 years have implicated wheat in a range of autoimmune diseases.  Celiac disease affects a small (but increasing) segment of the population.  This disease is triggered by an allergy to gluten, a specific protein in wheat.  But there are at least two other important antinutrients in wheat that affect everyone, whether or not they are gluten-intollerant. 

The first, and possibly more benign, is WGA (Wheat Germ Agglutenin), a toxic component of wheat that is usually destroyed by cooking.  Importantly, it is much more sensitive to wet heat than dry heat(i.e. baking), which may not be 100% effective in denaturing WGA. This agluttinin, (a type of lectin) can bind to receptors in the small intestine, effectively "gumming them up" and preventing complete absorption of nutrients.  In addition to limiting the nutritional value of meals containing WGA, lectins can also cause gastrointestinal distress or dysbiosis by passing more undigested food to the large intestine, where it is fermented by the microbiota.

The second, and more worrisome component of wheat, is gliadin.  Sometimes referred to as a type of or component of gluten, in 2000 gliadin was found to mimic the ability of cholera toxin to open the tight junctions between intestinal epithelial cells.  By activating the "zonulin" receptor, gliadin (and cholera toxin) make the gut permeable to large particles of food, which enter the body undigested.  Until the early 1980's it was believed that the human digestive system was impermeable to larger particles of food and that only food that was completely broken down into its amino acid, sugar, and lipid components could be absorbed by the body.  This is mostly true, but gliadin can short-circuit the natural process.

Source: Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. 2011

The outcome of increased intestinal permeability is immune exposure to the entire gamut of ingested substances.  The resulting inflammatory response binds and removes the transgressive food particles, but not before 1) increasing systemic inflammation, and 2) teaching the immune system to recognize and react to a very large array of compounds ... some of which may look like compounds in the human body. 

Therefore, ingestion of wheat sets up the necessary and sufficient conditions for the generation of autoimmunity.

Sources:

Pusztai A, Ewen SWB, Grant G, Brown DS, Stewart JC, Peumans WJ, Van Damme EJM, Bardocz S. Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins. British Journal of Nutrition. 1993 July;70(01):313–321.

Fasano A. Leaky Gut and Autoimmune Diseases. Clinical Reviews in Allergy & Immunology. 2012 February 1;42(1):71–78.

Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. 2011 January 1;91(1):151–175.

Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D’Agate C, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scandinavian Journal of Gastroenterology. 2006 April;41(4):408–419.

Further Reading:

Gluten Freedom: The Nation's Leading Expert Offers the Essential Guide to a Healthy, Gluten-Free Lifestyle Hardcover – April 29, 2014
by Alessio Fasano and Susie Flaherty

Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health Paperback – June 3, 2014
by William Davis

The Wahls Protocol: How I Beat Progressive MS Using Paleo Principles and Functional Medicine Hardcover – March 13, 2014
by Terry Wahls M.D. and Eve Adamson 

Antinutrients in Wheat

Grains don't want to be eaten.  As Dr. George Diggs makes clear in his youtube video, plants protect their leaves from herbivores and their seeds from seed-eaters with a whole range of chemical defenses.  In the case of seeds like wheat, there are multiple lines of defense, any one of which should give a thoughtful eater pause.  In combination, these defenses indicate that wheat should not be eaten by humans.

This is a much stronger argument than saying that some humans are gluten-intolerant or gluten-sensitive.  While gluten can be hard to digest for some people and has been identified as the causative agent in Celiac Disease, it is only one of an array of antinutrient compounds found in wheat.

Source: Scientific American, Surprises from Celiac Disease

• Wheat Germ Agglutinin (WGA) binds to cells in the intestine and can cause the gut to leak and create inflammation in the immune system.1,2,3,5
• Wheat Amylase Trypsin Inhibitors may fuel inflammation and immune reactions. 4
• Gliadin, a compound that specifically increases intestinal permeability, an idea first popularized as "leaky gut syndrome".6,7,8

Caveats: not all of these compounds are harmful to everyone, preparation (e.g. cooking) can destroy some toxins like WGA, and 'the dose makes the poison', so low doses of these antinutrients should have less effect than large doses.  But the fact remains that wheat is not a perfect food.  It increases inflammation, and in susceptible individuals provides the necessary and sufficient conditions for developoing autoimmunity, arthritis, diabetes, etc.

Gliadin is particularly worrisome because of its ability to 'tear holes in the gut'.  Gliadin (a component of gluten) mimics cholera toxins that can unlock the tight junctions sealing intestinal cells to one another.  Without intact junctions between the cells, open holes in the gut lining open are large enough to allow undigested food into the body.  These chunks of food have been detected using genetic testing and observed in animal studies (cite paper found WGA bound to everything).

Source: Scientific American, Surprises from Celiac Disease

This is not just a problem for people with Celiac's disease or gluten sensitivity. Wheat's gliadens have the same effect in everyone; they increase inflammation load (your body has to clean up everything that spilled into your blood after you ate wheat), and they provide the exposure of your immune system to foreign compounds which may trigger autoimmune conditions such as M.S., arthritis, diabetes, etc.  This topic is discussed in depth in this interview with Dr. Alessio Fasano, the researcher who discovered how wheat mimics cholera toxins to break down intestinal epithelium.

Sources
1.van Buul, V. J. & Brouns, F. J. P. H. Health effects of wheat lectins: A review. Journal of Cereal Science 59, 112–117 (2014).
2.Catassi, C. et al. Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders. Nutrients 5, 3839–3853 (2013).
3.Sollid, L. M. & Jabri, B. Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat Rev Immunol 13, 294–302 (2013).
4.de Punder, K. & Pruimboom, L. The Dietary Intake of Wheat and other Cereal Grains and Their Role in Inflammation. Nutrients 5, 771–787 (2013).
5.Junker, Y. et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med 209, 2395–2408 (2012).
6.Pellegrina, C. D. et al. Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction. Toxicology and Applied Pharmacology 237, 146–153 (2009).
7.Pusztai, A. et al. Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins. British Journal of Nutrition 70, 313–321 (1993).
8. Fasano, Alessio, et al. "Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease." The Lancet 355.9214 (2000): 1518-1519.