Sayer Ji

The Dark Side of Wheat: New Perspectives on Celiac Disease & Wheat Intolerance Part 3 of 3

by Sayer Ji on May 3rd, 2010


Editor’s Note:
Click here to see Part 1.
Click here to see Part 2.

WHEAT: AN EXCEPTIONALLY UNWHOLESOME GRAIN.

Wheat presents a special case insofar as wild and selective breeding has produced variations which include up to 6 sets of chromosomes (3 genomes worth!) capable of generating a massive number of proteins each with a distinct potentiality for antigenicity. Common bread wheat (Triticum aestivum), for instance, has over 23,788 proteins cataloged thus far. In fact, the genome for common bread wheat is actually 6.5 times larger than that of the human genome!

With up to a 50% increase in gluten content of some varieties of wheat, it is amazing that we continue to consider “glue-eating” a normal behavior, whereas wheat-avoidance is left to the “celiac” who is still perceived by the majority of health care practitioners as mounting a “freak” reaction to the consumption of something intrinsically wholesome.

Thankfully we don’t need to rely on our intuition, or even (not so) common sense to draw conclusions about the inherently unhealthy nature of wheat. A wide range of investigation has occurred over the past decade revealing the problem with the alcohol soluble protein component of wheat known as gliadin, the glycoprotein known as lectin (Wheat Germ Agglutinin), the exorphin known as gliadomorphin, and the excitotoxic potentials of high levels of aspartic and glutamic acid found in wheat. Add to these the anti-nutrients found in grains such as phytates, enzyme inhibitors, etc. and you have a substance which we may more appropriately consider the farthest thing from wholesome.

The remainder of this article will demonstrate the following adverse effects of wheat on both celiac and non-celiac populations:

    1) wheat causes damage to the intestines
    2) wheat causes intestinal permeability
    3) wheat has pharmacologically active properties
    4) wheat causes damage that is “out of the intestine” affecting distant organs
    5) wheat induces molecular mimicry
    6) wheat contains high concentrations of excitoxins.

1) WHEAT GLIADIN CREATES IMMUNE MEDIATED DAMAGE TO THE INTESTINES

Gliadin is classified as a prolamin, which is a wheat storage protein high in the amino acids proline and glutamine and soluble in strong alcohol solutions. Gliadin, once deamidated by the enzyme Tissue Transglutaminase, is considered the primary epitope for T-cell activation and subsequent autoimmune destruction of intestinal villi. Yet gliadin does not need to activate an autoimmune response, e.g. Celiac disease, in order to have a deleterious effect on intestinal tissue.
In a study published in GUT in 2007 a group of researchers asked the question: “Is gliadin really safe for non-coeliac individuals?” In order to test the hypothesis that an innate immune response to gliadin is common in patients with celiac disease and without celiac disease, intestinal biopsy cultures were taken from both groups and challenged with crude gliadin, the gliadin synthetic 19-mer (19 amino acid long gliadin peptide) and 33-mer deamidated peptides. Results showed that all patients with or without Celiac disease when challenged with the various forms of gliadin produced an interleukin-15-mediated response. The researchers concluded:

“The data obtained in this pilot study supports the hypothesis that gluten elicits its harmful effect, throughout an IL15 innate immune response, on all individuals [my italics].”

The primary difference between the two groups is that the celiac disease patients experienced both an innate and an adaptive immune response to the gliadin, whereas the non-celiacs experienced only the innate response. The researchers hypothesized that the difference between the two groups may be attributable to greater genetic susceptibility at the HLA-DQ locus for triggering an adaptive immune response, higher levels of immune mediators or receptors, or perhaps greater permeability in the celiac intestine. It is possible that over and above the possibility of greater genetic susceptibility, most of the differences are from epigenetic factors that are influenced by the presence or absence of certain nutrients in the diet. Other factors such as exposure to NSAIDs like naproxen or aspirin can profoundly increase intestinal permeability in the non-celiac, rendering them susceptible to gliadin’s potential for activating secondary adaptive immune responses. This may explain why in up to 5% of all cases of classically defined celiac disease the typical HLA-DQ haplotypes are not found. However, determining the factors associated greater or lesser degrees of susceptibility to gliadin’s intrinsically toxic effect should be a secondary to the fact that it is has been demonstrated to be toxic to both non-celiacs and celiacs.

2) WHEAT GLIADIN CREATES INTESTINAL PERMEABILITY

Gliadin upregulates the production of a protein known as zonulin, which modulates intestinal permeability. Over-expression of zonulin is involved in a number of autoimmune disorders, including celiac disease and Type 1 diabetes. Researchers have studied the effect of gliadin on increased zonulin production and subsequent gut permeability in both celiac and non-celiac intestines, and have found that “gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.”10 These results indicate, once again, that a pathological response to wheat gluten is a normal or human, species specific response, and is not based entirely on genetic susceptibilities. Because intestinal permeability is associated with wide range of disease states, including cardiovascular illness, liver disease and many autoimmune disorders, I believe this research indicates that gliadin (and therefore wheat) should be avoided as a matter of principle.

3) WHEAT GLIADIN HAS PHARMACOLOGICAL PROPERTIES

Gliadin can be broken down into various amino acid lengths or peptides. Gliadorphin is a 7 amino acid long peptide: Tyr-Pro-Gln-Pro-Gln-Pro-Phe which forms when the gastrointestinal system is compromised. When digestive enzymes are insufficient to break gliadorphin down into 2-3 amino acid lengths and a compromised intestinal wall allows for the leakage of the entire 7 amino acid long fragment into the blood, glaidorphin can pass through to the brain through circumventricular organs and activate opioid receptors resulting in disrupted brain function.

There have been a number of gluten exorphins identified: gluten exorphin A4, A5, B4, B5 and C, and many of them have been hypothesized to play a role in autism, schizophrenia, ADHD and related neurological conditions. In the same way that the celiac iceberg illustrated the illusion that intolerance to wheat is rare, it is possible, even probable, that wheat exerts pharmacological influences on everyone. What distinguishes the schizophrenic or autistic individual from the functional wheat consumer is the degree to which they are affected.

Below the tip of the “Gluten Iceberg,” we might find these opiate-like peptides to be responsible for bread’s general popularity as a “comfort food”, and our use of phrases like “I love bread,” or “this bread is to die for” to be indicative of wheat’s narcotic properties. I believe a strong argument can be made that the agricultural revolution that occurred approximately 10-12,000 years ago as we shifted from the Paleolithic into the Neolithic era was precipitated as much by environmental necessities and human ingenuity, as it was by the addictive qualities of psychoactive peptides in the grains themselves.
The world-historical reorganization of society, culture and consciousness accomplished through the symbiotic relationship with cereal grasses, may have had as much to do with our ability to master agriculture, as to be mastered by it. The presence of pharmacologically active peptides would have further sweetened the deal, making it hard to distance ourselves from what became a global fascination with wheat.

An interesting example of wheat’s addictive potential pertains to the Roman army. The Roman Empire was once known as the “Wheat Empire,” with soldiers being paid in wheat rations. Rome’s entire war machine, and its vast expansion, was predicated on the availability of wheat. Forts were actually granaries, holding up to a year’s worth of grain in order to endure sieges from their enemies. Historians describe soldiers’ punishment included being deprived of wheat rations and being given barley instead. The Roman Empire went on to facilitate the global dissemination of wheat cultivation which fostered a form of imperialism with biological as well as cultural roots.

The Roman appreciation for wheat, like our own, may have had less to do with its nutritional value as “health food” than its ability to generate a unique narcotic reaction. It may fulfill our hunger while generating a repetitive, ceaseless cycle of craving more of the same, and by doing so, enabling the surreptitious control of human behavior. Other researchers have come to similar conclusions. According to the biologists Greg Wadley & Angus Martin:

“Cereals have important qualities that differentiate them from most other drugs. They are a food source as well as a drug, and can be stored and transported easily. They are ingested in frequent small doses (not occasional large ones), and do not impede work performance in most people. A desire for the drug, even cravings or withdrawal, can be confused with hunger. These features make cereals the ideal facilitator of civilisation (and may also have contributed to the long delay in recognising their pharmacological properties).”

4) WHEAT LECTIN (WGA) DAMAGES OUR TISSUE.

Wheat contains a lectin known as Wheat Germ Agglutinin which is responsible for causing direct, non-immune mediated damage to our intestines, and subsequent to entry into the bloodstream, damage to distant organs in our body.

Lectins are sugar-binding proteins which are highly selective for their sugar moieties. It is believed that wheat lectin, which binds to the monosaccharide N-acetyl glucosamine (NAG), provides defense against predation from bacteria, insects and animals. Bacteria have NAG in their cell wall, insects have an exoskeleton composed of polymers of NAG called chitin, and the epithelial tissue of mammals, e.g. gastrointestinal tract, have a “sugar coat” called the glycocalyx which is composed, in part, of NAG. The glycocalyx can be found on the outer surface (apical portion) of the microvilli within the small intestine.

There is evidence that WGA may cause increased shedding of the intestinal brush border membrane, reduction in surface area, acceleration of cell losses and shortening of villi, via binding to the surface of the villi. WGA can mimic the effects of epidermal growth factor (EGF) at the cellular level, indicating that the crypt hyperplasia seen in celiac disease may be due to a mitogenic reponse induced by WGA. WGA has been implicated in obesity and “leptin resistance” by blocking the receptor in the hypothalamus for the appetite satiating hormone leptin. WGA has also been shown to have an insulin-mimetic action, potentially contributing to weight gain and insulin resistance.15 And, as discussed earlier, wheat lectin has been shown to induce IgA mediated damage to the kidney, indicating that nephropathy and kidney cancer may be associated with wheat consumption.

5) WHEAT PEPTIDES EXHIBIT MOLECULAR MIMICRY

Gliadorphin and gluten exporphins exhibit a form of molecular mimicry that affects the nervous system, but other wheat proteins effect different organ systems. The digestion of gliadin produces a peptide that is 33 amino acids long and is known as 33-mer which has a remarkable homology to the internal sequence of pertactin, the immunodominant sequence in the Bordetella pertussis bacteria (whooping cough). Pertactin is considered a highly immunogenic virulence factor, and is used in vaccines to amplify the adaptive immune response. It is possible the immune system may confuse this 33-mer with a pathogen resulting in either or both a cell-mediated and adaptive immune response against Self.

6) WHEAT CONTAINS HIGH LEVELS OF EXCITO-TOXINS

John B. Symes, D.V.M. is responsible for drawing attention to the potential excitotoxicity of wheat, dairy, and soy, due to their exceptionally high levels of the non-essential amino acids glutamic and aspartic acid. Excitotoxicity is a pathological process where glutamic and aspartic acid cause an over-activation of the nerve cell receptors (e.g. NMDA and AMPA receptor) leading to calcium induced nerve and brain injury. Of all cereal grasses commonly consumed wheat contains the highest levels of glutamic acid and aspartic acid. Glutamic acid is largely responsible for wheat’s exceptional taste. The Japanese coined the word umami to describe the extraordinary “yummy” effect that glutamic acid exerts on the tongue and palate, and invented monosodium glutamate (MSG) to amplify this sensation. Though the Japanese first synthesized MSG from kelp, wheat can also be used due to its high glutamic acid content. It is likely that wheat’s popularity, alongside its opiate-like activity, has everything to do with the natural flavor-enhancers already contained within it. These amino acids may contribute to neurodegenerative conditions such as Multiple sclerosis, Alzhemier’s, Huntington’s disease, and other nervous disorders such as Epilepsy, Attention Deficit Disorder and Migraines.

CONCLUSION

In this article I have proposed that celiac disease be viewed not as a rare “genetically-determined” disorder, but as an extreme example of our body communicating to us a once universal, species-specific affliction: severe intolerance to wheat. Celiac disease reflects back to us how profoundly our diet has diverged from what was, until only recently a grain free diet, and even more recently, a wheat free one. We are so profoundly distanced from that dramatic Neolithic transition in cultural time that “missing is any sense that anything is missing.” The body, on the other hand, cannot help but remember a time when cereal grains were alien to the diet, because in biological time it was only moments ago.

Eliminating wheat, if not all of the members of the cereal grass family, and returning to dicotyledons or pseudo-grains like quinoa, buckwheat and amaranth, may help us roll back the hands of biological and cultural time, to a time of clarity, health and vitality that many of us have never known before. When one eliminates wheat and fills the void left by its absence with fruits, vegetables, high quality meats and foods consistent with our biological needs we may begin to feel a sense of vitality that many would find hard to imagine. If wheat really is more like a drug than a food, anesthetizing us to its ill effects on our body, it will be difficult for us to understand its grasp upon us unless and until we eliminate it from our diet. I encourage everyone to see celiac disease not as a condition alien to our own. Rather, the celiac gives us a glimpse of how profoundly wheat may distort and disfigure our health if we continue to expose ourselves to its ill effects. I hope this article will provide inspiration for non-celiacs to try a wheat free diet and judge for themselves if it is really worth eliminating.

1 Celiac disease: an emerging global problem Journal of Pediatric Gastroenterology and Nutrition 2002 Oct; 35 (4): 472-4
2 Richard Logan is responsible for first introducing the “Celiac Iceberg” metaphor in 1991
3 Antibody testing for gliadin, tissue transglutaminase and endomysium indicates that “silent” or “latent” celiac disease is up to a 100 times more frequent than represented by the classical form.
4 Frontiers in Celiac Disease by Alessio Fasano, R. Troncone, D. Branski Published by Karger Publishers, pg. 242
5 See: www.patienthealthyself.info/Cystic_Fibrosis.html for Medline citations.
6 Cystic Fibrosis: a perinatal manifestation of selenium deficiency. Wallach JD, Germaise B. In:
Hemphill DD, ed. Trace substances in environmental health. Columbia: University of Missouri Press, 1979; 469-76
7 Genetic dissection between silent and clinically diagnosed symptomatic forms of coeliac disease in multiplex families. Digestive and Liver Disease 2002 Dec;34(12):842-5.
8 “Coelionomics”: towards understanding the molecular pathology of coeliac disease. Clinical Chemistry and Laboratory Medicine 2005;43(7):685-95.
9 Is gliadin really safe for non-coeliac individuals? Gut 2007;56:889-890; doi:10.1136/gut.2006.
10 “Do Dietary Lectins cause disease?” David L J Freed, BMJ 1999;318:1023-1024
11 “Food groups and renal cell carcinoma: a case-control study from Italy.” International Journal of Cancer 2007 Feb 1;120(3):681-5.
12 Unglued: The Sticky Truth About Wheat, Dairy, Corn and Soy. Scott-Free Newsletter, Autumn 2008
13 Exploring the Plant Transcriptome through Phylogenetic Profiling. Plant Physiology Vol. 137, 2005; pg. 33
14 An Introduction to Genetic Engineering. By Desmond S. T. Nicholl, Cambridge University Press, 2002, pg. 24
15 Footnote 7, supra.
16 “Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.” Scandinavian Journal of Gastroenterology Apr;41(4):408-19.
17 “The origins of agriculture ? a biological perspective and a new hypothesis” by Greg Wadley & Angus Martin, Australian Biologist 6:96- 105, June 1993
18 In vivo responses of rat intestinal epithelium to intraluminal dietary lectins. Gastroenterology. 1982 May;82(5 Pt 1):838-48.
19 Elevated levels of serum antibodies to the lectin wheat germ agglutinin in celiac children lend support to the gluten-lectin theory of celiac disease. Pediatric Allergy Immunology 1995 May;6(2):98-102.
20 Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance BMC Endocrine Disorders 2005, 5:10
21 Insulin-mimetic actions of wheat germ agglutinin and concanavalin A on specific mRNA levels. Archives of Biochemistry and Biophysics 1987 Apr;254(1):110-5.

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