Assertions of Fact, Fiction and Fad that Drive Gluten-Free Diets

Celiac.com 07/07/2016 - Norelle R. Reilly, M.D., has offered several of her opinions regarding gluten-free diets in a commentary published in The Journal of Pediatrics, earlier this year (1). It is important to recognize the difference between this publication and a report of findings arising from a study. She didn't conduct a study. No ethical approval was cited or needed. Despite the inclusion of several tables and one graph, Dr. Reilly was only charting changes in the popular use of search terms between 2004 and 2015, on a single search engine, at Open Original Shared Link. Her tables simply provide explanations of several acronyms and a structure for her opinions, which may suggest more substance than her beliefs warrant. She simply formed a set of opinions that may or may not be supported by the research and other reports she cited. After all, Dr. Reilly had to interpret those studies so we aren't hearing from the investigators who actually conducted that research. We are just learning her interpretations of that research. Her clinical experience may or may not have factored into the opinions she offers, but since she failed to cite any such experience it seems most unlikely. She has also lumped all gluten-free diets into a single entity, which she labels GFD and which also poses several problems as you will see shortly.

Dr. Reilly has warned about the multiple hazards of the gluten free diet, especially for children. These hazards include its potential to cause harm due to its higher fat content, deficiencies in B vitamins and iron, as well as the increased costs of gluten-free food. She also points to social isolation and inconvenience as hazards of the gluten free diet, which would appear to include what she calls "a deterioration of their quality of life while on a GFD". She goes from there to say that the claim that "gluten is toxic" is a fiction for which there is no supporting evidence (1). She also says that those following a gluten free diet may be at greater risk from inorganic arsenic and/or mercury poisoning (1). She admonishes those who are at risk of developing celiac disease not to undertake a gluten-free diet "without first testing for celiac disease" and Dr. Reilly advises her readers that "there is no role for a GFD for children outside of treatment of celiac disease and wheat allergy" based on what she calls the "hazards" of this diet. She won't soon be going on my Christmas card list.

Celiac.com Sponsor (A12):
As many Journal of Gluten Sensitivity readers have heard before (from me), our pre-human line of primates split from our common primate ancestor with the bonobo chimpanzee sometime between 5 and 14 million years ago, depending on what source you read. Unlike our omnivorous, primate cousins, we humans have thrived in a wide range of habitats and have populated almost every part of our planet.

Some of us may have genes from ancestors who were cultivating and eating significant quantities of gluten grains as long as 10,000 to 15,000 years ago, in the Fertile Crescent of the Levant. Perhaps some human genes have been exposed to these grains for an even longer period. We really don't know. We can only judge based on the evidence we have. However, the evidence we have shows that most of the world's populations have had considerably less time to adapt to consuming these foods. Indigenous peoples of the Americas, Australia, as well as island dwellers from much of the Pacific Ocean, and even isolated groups of people in Europe and Asia have only consumed these foods for somewhere between 500 and about 5,000 years. A few of these populations, such as some groups of Canadian Inuit, some Pacific Islanders, etc. have only consumed gluten grains for less than 100 years. Yet Dr. Reilly would have us believe that the foods on which our forefathers thrived, while populating almost every habitable niche on earth, are somehow harmful. That seems a distinctly questionable perspective. She says that "The health and social consequences worthy of consideration in advance of starting a child on a GFD are not described adequately online or in books promoting an empiric GFD trial." Perhaps. That may simply result from the common awareness of the relatively short duration during which so many humans have consumed gluten-containing foods.

Further, Dr. Reilly's assertion that "This Commentary [sic] will provide an update on the current GFD fad ....." (1) suggests more than a small bias on her part. Has she undertaken to guide us through the facts, fiction, and fad of the GFD, while suffering the delusions of yet another fad herself? Is it possible that Dr. Reilly, in addition to eschewing some principles of natural selection and adaptation, is tending toward a paradigm that only counts gluten-induced disease when that ailment falls within her purview? This may be a trap set by today's trend toward the increasingly specialized study and practice of Medicine. Or it may reflect a less thoughtful resistance among these professionals, reminiscent of the 80 years' resistance to the germ theory.

Many neurologists, for instance, have been exploring a range of neurological ailments that are either triggered by gluten or are characterized by antigliadin antibodies found in the brain fluids of individuals afflicted by these neurological ailments (2). Some of these patients do have celiac disease but a majority do not(3). Yet their neurological ailments will often respond to a gluten free diet that must be more strict than is usually required to control celiac disease (4). In their work, Dr. Hadjivassiliou and colleagues have stated that "the neurological manifestations of celiac disease and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms" (5). Thus, although Dr. Reilly is correct when she says that non-celiac gluten sensitivity (NCGS) is not yet well understood, it is quite clear that there is more information on the connection between gluten consumption and at least some cases of a wide range of neurological diseases (6, 7) than Dr. Reilly would like to credit. And these findings don't seem to be having much impact on many gastrointestinal researchers or practitioners. What is going on there?

Further, regardless of the state of the intestinal mucosa, dermatitis herpetiformis (which Dr. Reilly did mention) is yet another form of NCGS in which it is clear that gluten exposure triggers the onset of this malady and a gluten free diet controls it. Yet she fails to mention that a subset of schizophrenia patients also experience symptom remission on a gluten-free diet, even among pre-pubescent children (8) and the association between schizophrenia and gluten has been repeatedly reported in the literature over the last half century (9 -19). The immune reaction to gluten is usually not the same as that seen in celiac disease (17). Nonetheless, for this group, the underlying trigger is gluten and its dietary restriction can produce startlingly positive results (18, 19). These psychiatric ailments can have a devastating impact on the victims' lives and their families when a simple diet can sometimes provide an effective treatment.

While there is still some debate about whether gluten is the trigger in some cases of intestinal NCGS ailments, considerable evidence has also accrued showing that gluten is the trigger in a wide range of conditions both in association with untreated celiac disease and in the absence of celiac disease . The added problem is that Dr. Reilly has lumped all gluten free diets into a single entity. Yet many of us who avoid eating gluten also avoid other Neolithic foods, believing them to drive much of the current increases in autoimmunity, cancer, obesity, diabetes, and a host of other modern diseases. Dr. Loren Cordain's books have given rise to a large number of adherents to the "Paleo-Diet" that Cordain advocates (20). Other gluten avoiders find themselves developing symptoms when consuming "replacement" grains such as rice, corn, or millet, and choose to avoid those grains as well. Still other gluten avoiders subscribe to vegetarian diets, while others eat only organically produced meats and/or vegetables. These dietary practices also vary according to geographic location, all while avoiding gluten consumption. For instance, these variations might include increased fish consumption near the seashore and increased beef consumption inland, increased yak milk consumption in the Himalayas and increased millet consumption in West Africa. Thus, it seems questionable to lump all gluten avoiders into a single group, then suggest that they are suffering social isolation, lower quality of life, arsenic and/or mercury poisoning, and a host of other hazards.

Dr. Reilly has argued that "The gluten-free diet (GFD) is a critical medical treatment for the millions of individuals worldwide with celiac disease (celiac disease), an autoimmune condition for which no other therapy is currently available" (1). That part is true. However, she then cites a study in which patients with celiac disease followed a gluten-free diet for an average of between 0 and 8.2 years and showed higher serum levels of mercury than either healthy controls eating a regular diet, or patients with celiac disease who were not following a gluten-free diet (21). There are several important things wrong here. The first is that Dr. Reilly has assumed that what is happening with the treated celiac patients may reasonably be assumed to be happening to those with NCGS who choose to follow a gluten-free diet. However, as she has so adroitly pointed out, people with celiac disease are different from those with NCGS. Thus, as was stated in the study of mercury and celiac disease that she cited (21), a person with celiac disease might have a genetic propensity for increased mercury absorption. Or they might experience a resurgence of those portions of the intestinal villi that are more likely to offer the primary point at which mercury is absorbed, or they might be more inclined to have mercury amalgam fillings that are degraded and absorbed due to grinding one's teeth, or chewing gum (21) or perhaps gastro-esophageal reflux is a factor in the degradation of mercury amalgam fillings. The authors of this study of mercury and celiac disease also acknowledge that their report is limited by the small number of participants. Dr. Reilly, on the other hand, fails to mention that only a small number of treated celiac patients participated in this study - only twenty of them. Neither does she seem to recognize that the study's results cannot legitimately be generalized from celiac patients on a gluten-free diet, to the non-celiac gluten sensitive population who may choose to avoid gluten. Further research might bridge that gap, but the study she cited does not (21) and such results should not be used to suggest a generalized risk that may be exclusive to those with celiac disease.

The same study also seems to include treated celiac patients who are very new to the diet but have shown diminished tissue transglutaminase antibody levels (21). The average duration of the gluten free diet is 8.2 years, but with a deviation of up to 8.2 years. It is difficult to understand how this could mean anything else. I have contacted the lead author for clarification and have not yet received a response.

With respect to high levels of inorganic arsenic in rice pablum, the celiac and gluten sensitive community has been aware of this problem since the 2009 publication of several articles, both in the popular and peer-reviewed scientific literature, arising out of studies conducted by professor Andy Meharg and his students the previous year (22). They found that samples of several brands of rice pablum purchased at supermarkets, commonly fed to babies, contained high levels of arsenic. Here in the Journal of Gluten Sensitivity, we also published a warning article (23). Some members of the same research group that exposed this problem with rice pablum have also published data showing that phosphorus fertilizer can mitigate uptake of arsenic in wheat (24). We continue to hope that rice farming practices will be similarly investigated and best practices will soon be prescribed for rice farmers, but Dr. Reilly has raised an important point here. Rice consumption should be limited by everyone, including those following a gluten-free diet.

Reilly has also asserted that "there are no data supporting the presumed health benefits of a GFD" (1). This bold statement is followed by a heading that reads "Fiction: Gluten is toxic", then " There are no data to support the theory of an intrinsically toxic property of gluten" (1). Yet gliadins have also been demonstrated to damage a variety of tissue cells. In an experiment conducted by Hudson and colleagues, simple exposure to this sub-group of proteins from wheat gluten resulted in damage to several lines of embryonic cells (25). Similarly, Doherty and colleagues showed that many persons who are fed large amounts of gluten will develop villous damage or other intestinal damage, even in the absence of celiac disease (26). Some gluten proteins will cause damage to a variety of cell lines, and people fed large amounts of gluten will experience intestinal damage, yet Dr. Reilly claims that there are no data to support what she calls the "fiction" that gluten is toxic (1).

Reilly also decries the higher fat content of the gluten-free diet. But dietary fats combine to make up a huge topic. Some promote inflammation. Others have anti-inflammatory properties. Some must be used as energy or they will prompt the liver to produce ketone bodies. These latter offer alternative fuels for the brain in the context of insulin resistance (27). Condemning its high fat content is a little like lumping all gluten-free diets into one group. It is a gross over-simplification that draws into question the writer's competence in the realm of Dietetics.

The same can be said about Reilly's identification of iron deficiency as the result of avoiding gluten grains. Until we have a better understanding of the proportions of the various minerals that are irreversibly bound by phytates and phenols in the human gastrointestinal tract, blaming gluten grain avoidance for iron deficiency in humans is, at best, inaccurate. While she does mention that many of these nutrients we will fail to get from gluten free foods are simply fortifications that have been added to processed, gluten-containing foods, she has failed to recognize or discuss the mineral binding and wasting that ensues from eating these foods and additives together.

Similarly, while some B vitamins are plentiful in processed, gluten-containing grains, others are not. However, the same B vitamins are abundantly available in other common food sources that do not contain the anti-nutrients common to cereal grains. Such deficiencies are not the result of a gluten free diet so much as they are the result of a poorly balanced diet, which can happen regardless of gluten exclusion.

Reilly goes on to admonish those who are at risk of developing celiac disease not to undertake a gluten-free diet "without first testing for celiac disease" (1). This is spoken like a person who is intimately familiar with the medical system and would have little or no difficulty getting adequate testing to rule out celiac disease on request. She has probably not spent much of the previous decade or so repeatedly undergoing repeated rounds of the same useless tests, such as barium swallow X-rays, barium enema X-rays along with repeated, often unnecessary, courses of various antibiotics, multiple courses of drugs to treat ulcers that fail to show up on the aforementioned tests, and taking supplements or drugs to correct blood test abnormalities, without considering the potential underlying causes. And none of the above strategies are likely to ever suggest celiac disease. Yet these are the stock-in -trade of the general practitioner who is often reluctant to refer to gastrointestinal specialists. This reluctance frequently escalates when the above symptoms are accompanied by psychiatric and/or neurological complaints, although such symptoms are reported in between 51% and 73% of newly diagnosed celiac patients (7, 8) and some cases of psychosis can be attributed to gluten intake alone (18, 19, 28). In the face of such evidence, the claim that gluten fractions are not toxic seems almost laughable. Yet her polemic "commentary" has spawned quite a number of spin-off articles that condemn the gluten-free diet as a fad or a hoax, and many innocent victims and their families continue to suffer from the psychiatric, neurological, and other extra-intestinal manifestations of non-celiac gluten sensitivity or celiac disease. I frequently observe school children with diagnosed learning disabilities who make huge strides forward when on a gluten free diet. And the explanation is really quite simple (29). And I am saddened by the certitude with which this diet is condemned by otherwise reasonable people.

Historically, the GFD has been contentious since it was introduced in 1937, when Dr. W.K. Dicke first began to treat his celiac patients with it. One may wonder why it has stirred so much controversy. I continue to be shocked when I read opinion articles such as Dr. Reilly's when they are included in peer-reviewed publications. I am not surprised by the many follow-up articles in the popular press that condemn the gluten free diet. This is the same resistance that I witnessed almost a quarter of a century ago, when I was diagnosed with celiac disease. I'm left wondering why so many supposedly objective professionals are so quick to oppose a diet that offers benefits to people with a wide range of maladies, many of which are, otherwise untreatable. What could motivate these vehement critics? I just don't understand.

Sources:
1. Reilly NR. The Gluten-Free Diet: Recognizing Fact, Fiction, and Fad. J Pediatr. 2016 May 10. pii: S0022-3476(16)30062-2.
2. Stenberg R, Hadjivassiliou M, Aeschlimann P, Hoggard N, Aeschlimann D. Anti-transglutaminase 6 antibodies in children and young adults with cerebral palsy. Autoimmune Dis. 2014;2014:237107.
3. Hadjivassiliou, M., Gibson, A., Davis-Jones, G., Lobo, A., Stephenson, T.,Milford-Ward, A. (1996). Does cryptic gluten sensitivity play a part in neurological illness? Lancet 347, 369-371.
4. Turner MR, Chohan G, Quaghebeur G, Greenhall RC, Hadjivassiliou M, Talbot K. A case of celiac disease mimicking amyotrophic lateral sclerosis. Nat Clin Pract Neurol. 2007 Oct;3(10):581-4.
5. Hadjivassiliou M, Rao DG, Grìnewald RA, Aeschlimann DP, Sarrigiannis PG, Hoggard N, Aeschlimann P, Mooney PD, Sanders DS. Neurological Dysfunction in Coeliac Disease and Non-Coeliac Gluten Sensitivity. Am J Gastroenterol. 2016 Apr;111(4):561-7.
6. Hadjivassiliou M, The Neuroimmunology of Gluten Intolerance. Textbook chapter. in press.
7. Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004 Jun;113(6):1672-6.
8. Lionetti E, Leonardi S, Franzonello C, Mancardi M, Ruggieri M, Catassi C. Gluten Psychosis: Confirmation of a New Clinical Entity. Nutrients. 2015 Jul 8;7(7):5532-9.
9. Dohan C. "Cereals and schizophrenia: data and hypothesis" Acta Psychiat Scand 1966; 42: 125-152
10. Dohan FC, Grasberger JC, Lowell FM, Johnston HT Jr, Arbegast AW. Relapsed Schizophrenics: More Rapid Improvement on a Milk-and Cereal-free Diet" Brit J Psychiat 1969; 115: 595-596
11. Singh MM, Kay SR. Wheat gluten as a pathogenic factor in schizophrenia. Science. 1976 Jan 30;191(4225):401-2.
12. Zioudrou et. al. "Opioid peptides derived from food proteins. The exorphins" J Biol Chem 1979; 254:2446-2449
13. Mycroft et. al. "MIF-like sequences in milk and wheat proteins" NEJM 1982; 307: 895
14. Dohan et. al. "Is Schizophrenia Rare if Grain is Rare?" Biol Psychiat 1984; 19(3): 385-399
15. Dohan "Is celiac disease a clue to pathogenesis of schizophrenia?" Mental Hyg 1969; 53: 525-529
16. Ashkenazi et. al. "Immunologic reaction of psychotic patients to fractions of gluten" Am J Psychiat 1979; 136: 1306-1309
17. Samaroo D, Dickerson F, Kasarda DD, Green PH, Briani C, Yolken RH, Alaedini A. Novel immune response to gluten in individuals with schizophrenia. Schizophr Res. 2010 May;118(1-3):248-55.
18. Kraft BD, Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond). 2009 Feb 26;6:10. doi: 10.1186/1743-7075-6-10.
19. De Santis A, Addolorato G, Romito A, Caputo S, Giordano A, Gambassi G, Taranto C, Manna R, Gasbarrini G. Schizophrenic symptoms and SPECT Abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med. 1997 Nov;242(5):421-3.
20. Cordain L. The Paleo Diet. John Wiley & Sons. NY, 2002.
21. Elli L, Rossi V, Conte D, Ronchi A, Tomba C, Passoni M, Bardella MT, Roncoroni L, Guzzi G. Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen. Gastroenterol Res Pract. 2015;2015:953042
22. Meharg, A. A., Sun, G., Williams, P. N., Adomako, E., Deacon, C., Zhu, Y-G., Feldmann, J. & Raab, A. Inorganic arsenic levels in baby rice are of concern. Apr 2008 In : Environmental Pollution . 152, 3, p. 746-749.
23. Hoggan R. How do you like your arsenic? Journal of Gluten Sensitivity, Spring 2009.
24. Pigna, M., Cozzolino, V., Violante, A. & Meharg, A. A. Influence of phosphate on the arsenic uptake by wheat (Triticum durum L.) irrigated with arsenic solutions at three different concentrations Feb 2009 In : Water, Air, and Soil Pollution. 197, 1-4, p. 371-380.
25. Hudson DA, Cornell HJ, Purdham DR, Rolles CJ. Non-specific cytotoxicity of wheat gliadin components towards cultured human cells. Lancet. 1976 Feb.
26. Doherty, M., & Barry, R.(1981). Gluten-induced mucosal changes in subjects without overt small-bowel disease. The Lancet March 7, 517-520.
27. de la Monte SM, Wands JR. Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed. J Diabetes Sci Technol. 2008 November; 2(6): 1101–1113.
28. Jackson J, Eaton W, Cascella N, Fasano A, Santora D, Sullivan K, Feldman S, Raley H, McMahon RP, Carpenter WT Jr, Demyanovich H, Kelly DL. Gluten sensitivity and relationship to psychiatric symptoms in people with schizophrenia. Schizophr Res. 2014 Nov;159(2-3):539-42.
29. Addolorato G, Di Giuda D, De Rossi G, Valenza V, Domenicali M, Caputo F, Gasbarrini A, Capristo E, Gasbarrini G. Regional cerebral hypoperfusion in patients with celiac disease. Am J Med. 2004 Mar 1;116(5):312-7.