Dr. Ron Hoggan, Ed.D.

Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia. So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9). With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection. Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal. There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments. My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question. Sources: 1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44. 2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15. 3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454. 4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23. 5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26. 6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11. 7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454. 8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48 9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4. 10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/ 13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29. 14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

Celiac.com 04/14/2018 - There is a revolutionary new book about gluten sensitivity and celiac disease, written by Dr. Gordon Heinrichs, D.C. (whose article appears in this issue). His careers as a medical laboratory technologist, then a chiropractor, have uniquely located him to see gluten's impact on health in an entirely new way. His book critiques relevant scientific explorations and discoveries and the ensuing clinical practices. Titled "Celiac Disease & Gluten Sensitivity: A troubled past, but a promising future", this exciting book is a breath of fresh air in the field of gluten sensitivity and celiac disease. Dr. Heinrichs' thoughtful analysis of relevant data combined with the application of practical common sense explodes some of the common medical myths that claim to distinguish gluten sensitivity from celiac disease. He also explores conventional wisdom around dietary experimentation, and offers a rational approach to diagnosing gluten sensitivity. The evidence Heinrichs provides raises questions about the view that we should continue to eat gluten until we can visit a gastroenterologist and get a biopsy taken. He also challenges the belief that HLA analysis is beneficial for those who are aware that gluten causes some or all of their health problems. After a preview of the final draft, I can confidently predict that anyone who is interested in thoughtful, objective, and health promoting insights into gluten's impact on human health will be intrigued and motivated by the offerings of this inexpensive, powerful new ebook. I recommend it without reservation. It is very well researched and written and is now available on Amazon. I hope it will become the new best seller among books that explore the gluten syndrome.

Celiac.com 03/16/2018 - Celiac awareness has increased exponentially over the last decade among physicians and the general public alike. Increasing numbers of research publications and very active support groups and individuals have contributed to this growing awareness. Knowledge of the many and varied manifestations is also growing rapidly although some individuals continue to cling to the notion that celiac disease is characterized by malabsorption and that nutrient deficiency is the dominant feature of this ailment. This misses the broader understanding of the many ways in which gluten grains negatively impact on human health. From toes to head, any and all of our human body systems may be harmed by ingesting gluten under some circumstances. Although the wide range of signs and symptoms of celiac disease is impressive, a similar, even broader range of impacts may be attributed to gluten in the context of non-celiac gluten sensitivity. Those with celiac disease only comprise a small portion of the population of people who are afflicted by non celiac gluten sensitivity. Dr. Rodney Ford has offered the all encompassing term of 'gluten syndrome' to identify everyone whose health is compromised by gluten consumption (1). From Dr. Fasano's most conservative estimate that 6% of the population is afflicted by non-celiac gluten sensitivity (2), to Dr. Rodney Ford's estimate that 10% is afflicted (3), to Dr. Kenneth Fine's finding that IgG class anti-gliadin antibodies are found in about 11% of the population (4), to this writer's assertion that non-celiac gluten sensitivity includes well more than 20% of the population, the paucity of research in this area offers a wide range of estimates without a solid basis for refuting any of them. Nonetheless, it is clear that those with non-celiac gluten sensitivity outnumber those with celiac disease by a ratio of somewhere between 6 to 1 and more than 20 to 1. The gluten syndrome may therefore include from seven percent to more than twenty percent of the population. The importance of these percentages and ratios is that we are seeing growth in the diagnosis of celiac disease, and in the number of people who have celiac disease (4). It has been argued that a similar trend may be seen across the spectrum of the gluten syndrome, attributing that trend to the genetic modifications that have been made to grains, and the increased consumption of these foods (5). But this is just the tip of the iceberg. Dr. Fasano bases his estimate of non-celiac gluten sensitivity on those who mount an innate immune reaction to gluten grains. While there is likely some overlap between innate immune reactions and selective antibody reactions, most estimates of non-celiac gluten sensitivity are based on IgG class antibodies against one of the proteins of several protein families found in gluten. It makes eminent sense to me that when our bodies are mounting a measurable immune response against the most common food in our diets, whether the reaction is by the innate immune system or by creating selective antibodies, that food might be harmful to our health. I do not quarrel with the basis on which these sensitivities are identified. I simply argue that they are only identifying a sub-fraction of many more possible cases of non-celiac gluten sensitivity. To put this issue into sharper focus, there are several protein families to be found in each of the gluten grains. In wheat, for instance, each family, glutelin, gliadin, and glutenin contains a number of individual proteins. The antibody test for gliadin ignores possible reactions to proteins in either of the other two families. Further, IgG class antibodies are the most common and widespread class of selective antibody we produce. But they form only one of five types of selective antibodies (known as immunoglobulins). Further, as is obvious from Dr. Fasano's conservative approach to identifying non-celiac gluten sensitivity, there are other facets of the immune system that do not involve selective antibodies, and can also be enlisted in a reaction against gluten grains. Thus, when we test for IgG anti-gliadin antibodies, the most common test for non-celiac gluten sensitivity, positive results are identifying reactions against only one of the several protein families found in gluten, and only one of the five possible selective antibody reactions against this single protein family. It therefore seems wholly improbable that testing for reactions against a single protein family in only a single class of selective antibody would identify all or even most cases of gluten sensitivity. Admittedly, some researchers test for IgA antibodies but those investigators usually do not test for IgG antibodies. However, even with testing for both classes of selective antibodies, which most published reports on this issue have not done, it is clear that many possible immune reactions to any other protein fractions of gluten might well be overlooked, either in the form of other selective antibodies or as other immune reactions and various innate reactions against gluten grains. I'm sure that, by now, the reader will see that there are many possible immune reactions against this most common food, and that most of these reactions will go undetected, both in the context of standard medical testing and in most research conducted in this venue. On a more practical plane, when Dr. Curtis Dohan identified significant improvements among patients with schizophrenia patients eating a gluten-free, dairy-free diet (6), and Singh and Kay replicated their findings (7), many looked for celiac disease among patients with schizophrenia and found only a small increase. Dohan and Singh's publications were followed by several sloppy studies that ignored the guiding principles expressed in this pioneering work. These weak studies further undermined acceptance of the connection between gluten and schizophrenia. The net result was a growing belief that Dohan had erred and his heroic work was widely dismissed. Yet, more than twenty years after his death, one of Dohan's most vigorous critics is listed among the authors of a paper that reports an immune reaction against gluten that, while different from the reaction seen in celiac disease, is common among people with schizophrenia (8). Similarly, I think that we can expect, sometime in the future, to see research that identifies immune reactions and damaging dynamics caused by gluten consumption among people with learning disabilities. There is, for instance, one newspaper report of an informal study conducted at the Nunnykirk School in Northumberland, a school that serves only children with dyslexia, a condition that is reported to afflict about 10% of children in the United Kingdom. After six months of eating a gluten free diet, more than 80% of these children improved their reading at a rate of at least twice that of normal children. Some leaped ahead, in their reading skills, by as much as 2.5 years over this six month period (9). Relatedly, I had the privilege of working with Dr. Rodney Ford on a retrospective analysis of indicators of school readiness among children who had celiac disease, non-celiac gluten sensitivity (as measured by selective antibody testing) and children who showed no signs of either reaction to gluten. A large majority of those who reacted to gluten improved dramatically. There was a small but significant sub-group whose school readiness improved following a gluten free diet, and these improvements happened within 6 months of avoiding gluten (unpublished data). Autism, especially where normal development was curtailed after one or several years, is another condition in which excluding gluten seems to provide substantial improvements even in the absence of celiac disease. Some research in this area suggests that toxins (generated by bacteria resident in the intestines) are allowed access to the bloodstream and the brain (10). Perhaps exclusion of dietary gluten is the factor that limits access to the bloodstream through reducing zonulin production. Similarly, although not as well supported, there is some evidence to suggest that gluten contributes to bi-polar disorder. Just how frequent and significant the contribution may be is still open to debate, but I have observed some evidence to support this hypothesis in my own family. A range of types of epilepsy have been found in association with celiac disease, many of which are mitigated by the gluten free diet (11). The manifestations of undetected non-celiac gluten sensitivity are not limited to brain function. We know that celiac disease is much more frequent in the context of other autoimmune diseases. We also know that antibody tests show even higher rates of non-celiac gluten sensitivity. Since we are only identifying a fraction of those who may be reacting to gluten, it seems reasonable to suggest that everyone with an autoimmune disease, or antibodies suggesting that an autoimmune disease is imminent, should begin a strict gluten free diet and follow it for at least one year. If there is any reduction of auto-antibodies or symptoms of autoimmunity, the diet should be continued. Although difficult in the early stages, it is an entirely benign intervention/treatment. There are no unwanted side effects or hazards. There are more than 200 autoimmune and other medical conditions reported in association with gluten and are listed in Appendix D of Dangerous Grains (12). In each case, a lengthy trial of a gluten free diet would be well advised. Again, there are no negative side effects of the gluten free diet. It is an entirely benign intervention. A significant proportion of those who suffer from IBS, Crohn's or any of the various types of colitis have also been reported to benefit from a gluten free diet on various websites. Similarly, many people with MS and a host of other neurological diseases have been shown to benefit from a gluten free diet (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23). Even many AIDS patients are helped by a gluten free diet. It reduces their diarrhea and improves nutrient absorption (24). This is an important discovery that can be harnessed in conjunction with the improved treatments now available for this very serious illness. Overweight, obesity, and weight loss are contentious issues with regard to the gluten free diet. Until quite recently, there were two reports of small studies of changes in body mass index in the USA and one report from Ireland, following institution of a gluten free diet. The two American studies showed weight loss among overweight subjects on a gluten free diet. The study from Ireland showed only weight gain among overweight subjects after following a gluten free diet. In November of 2011, another small study was published. Their conclusion states "The GFD (gluten free diet) has a beneficial effect upon the BMI (body mass index) of overweight children with celiac disease" (25), which is congruent with the earlier two American studies. I have previously suggested that the discrepancy between the findings may be due to the acceptance of wheat starch as part of the gluten free diet in the United Kingdom. However, regardless of the cause, the preponderance of evidence supports the notion that a gluten free diet can be used as an effective weight loss strategy in some cases of celiac disease. Other evidence suggests it may be a more broadly effective weight loss tool. Thus, my estimate of the prevalence of non-celiac gluten sensitivity includes the 6% who show signs of innate immune reactions to gluten, in addition to those who show IgG antibodies against gluten, at about 11% of the population (although there may be some overlap between these 6% and 11% groups). My estimate also includes many of those with schizophrenia who number about 1% of the general population, and a portion of those with autism who are quickly approaching 1% of the population. I am also including 80% of the approximately 10% of the population with some degree of dyslexia. Because of overlaps between groups, and because gluten's impact is often only demonstrable through a gluten free diet, I only assert that non-celiac gluten sensitivity is a factor in more than 20% of the general population. However, I remain open to findings that will show a much greater negative impact from eating foods derived from gluten grains. The portion of the human population that may be negatively impacted by gluten consumption can range as high as the 80% portion that produce haptaglobin 2, for which zonulin is the precursor. The take away point here is that the gluten free diet may aid overall health for up to as much as 80% of the general population. In that context, my estimate that 20+% of the population is showing signs that they are variously mounting immune reactions against gluten or are otherwise harmed by gluten appears modest. The overlapping symptoms make it extremely difficult to narrow my estimate further. Nonetheless, gluten is one of the most harmful substances in our diet. Yet it is the most ubiquitous factor in our diets. Sources: 1. www.doctorgluten.com 2. Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Cartenì M, Riegler G, de Magistris L, Fasano A. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011 Mar 9;9:23. 3. personal communication 4. personal communication 5. Wheat Belly 6. Dohan FC, Grasberger JC. Relapsed schizophrenics: earlier discharge from the hospital after cereal-free, milk-free diet. Am J Psychiatry. 1973 Jun;130(6):685-8. 7. Singh & Kay 8. 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. 9. Blair, Alexandra. Wheat-free diet gives food for thought. http://www.timesonline.co.uk/tol/news/uk/article444290.ece 10. Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Väisänen ML, Nelson MN, Wexler HM. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000 Jul;15(7):429-35. 11. Ribaldone DG, Astegiano M, Fagoonee S, Rizzetto M, Pellicano R. Epilepsy and celiac disease: review of literature. Panminerva Med. 2011 Dec;53(4):213-6. 12. Braly J, Hoggan R, Dangerous Grains. Avery, New York, 2002. 13. Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D. Gluten sensitivity: from gut to brain. Lancet Neurol. 2010 Mar;9(3):318-30. 14. Turner MR, Chohan G, Quaghebeur G, Greenhall RC, Hadjivassiliou M, Talbot K. A case of celiac disease mimicking amyotrophic lateral scl Nat Clin Pract Neurol. 2007 Oct;3(10):581-4. 15. Hadjivassiliou M, Chattopadhyay AK, Grünewald RA, Jarratt JA, Kandler RH, Rao DG, Sanders DS, Wharton SB, Davies-Jones GA. Myopathy associated with gluten sensitivity. Muscle Nerve. 2007 Apr;35(4):443-50. 16. Hadjivassiliou M, Grünewald RA, Kandler RH, Chattopadhyay AK, Jarratt JA, Sanders DS, Sharrack B, Wharton SB, Davies-Jones GA. Neuropathy associated with gluten sensitivity. J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1262-6. Epub 2006 Jul 11. 17. Hadjivassiliou M, Sanders DS, Grünewald RA. Multiple sclerosis and occult gluten sensitivity. Neurology. 2005 Mar 8;64(5):933-4; author reply 933-4. 18. Hadjivassiliou M, Williamson CA, Woodroofe N. The immunology of gluten sensitivity: beyond the gut. Trends Immunol. 2004 Nov;25(11):578-82. Review. 19. Hadjivassiliou M, Sanders DS, Grünewald RA, Akil M. Gluten sensitivity masquerading as systemic lupus erythematosus. Ann Rheum Dis. 2004 Nov;63(11):1501-3. 20. Hadjivassiliou M, Grünewald RA, Davies-Jones GA. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry. 2002 May;72(5):560-3. 21. Hadjivassiliou M, Grünewald RA, Lawden M, Davies-Jones GA, Powell T, Smith CM. Headache and CNS white matter abnormalities associated with gluten sensitivity. Neurology. 2001 Feb 13;56(3):385-8. 22. Hadjivassiliou M, Grünewald RA, Davies-Jones GA. Gluten sensitivity: a many headed hydra. BMJ. 1999 Jun 26;318(7200):1710-1. 23. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71. 24. Quiñones-Galvan A, Lifshitz-Guinzberg A, Ruíz-Arguelles GJ. Gluten-free diet for AIDS-associated enteropathy. Ann Intern Med. 1990 Nov 15;113(10):806-7. 25. Reilly NR, Aguilar K, Hassid BG, Cheng J, Defelice AR, Kazlow P, Bhagat G, Green PH. Celiac disease in normal-weight and overweight children: clinical features and growth outcomes following a gluten-free diet. J Pediatr Gastroenterol Nutr. 2011 Nov;53(5):528-31. 26. Cheng J, Brar PS, Lee AR, Green PH. Body mass index in celiac disease: beneficial effect of a gluten-free diet. J Clin Gastroenterol. 2010 Apr;44(4):267-71. 27. Murray JA, Watson T, Clearman B, Mitros F. Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. Am J Clin Nutr. 2004 Apr;79(4):669-73.

Celiac.com 02/02/2018 - An opinion article by Dr. Di Sabatino and Dr. Corazza in the February 2012 issue of Annals of Internal Medicine (1) has unleashed a storm of opinion articles in the popular media that decry the gluten-free diet. The article by these two physicians is mostly reasonable and thoughtful but there are a couple of problems with it. The authors devalue patients' participation in their own health care and implicitly assert that gluten is a healthy food for most people. They do so through a protocol they have devised and by stating that they wish to prevent "a gluten preoccupation from evolving into the conviction that gluten is toxic for most of the population" (1). This statement, and the media claims that followed, reflect several deeply flawed assumptions and perspectives that are not only unscientific, they elevate the physician's observations over the individual's insights into her/his own health. The first assumption, of course, is that gluten is a healthy food for all those without celiac disease. Yet in the very same article, Di Sabatino and Corazza offer a list of afflictions that, in the absence of celiac disease, improve or completely disappear when gluten is withdrawn. Thus, while they acknowledge the existence of these illnesses, they simultaneously assert that a condition of gluten preoccupation exists and that gluten is not toxic for most of the population. They go on to bemoan the absence of clear diagnostic criteria for these non-celiac, gluten-induced illnesses, calling for an individualized approach to diagnosis that would involve patients following a single-blinded gluten challenge test for subjective symptoms and an open test for objective signs and symptoms. In a nutshell, they want patients to undergo a gluten challenge, without knowing (the patient is the one who is blinded) when they are or are not gluten-free, to confirm, for the physician, the patient's claim that her/his symptoms are legitimately linked to gluten ingestion. The gluten challenge is for the sole benefit of the physician. If she/he observes that the signs and/or symptoms worsen with gluten exposure and/or improve after excluding gluten then the physician will be reassured that the patient's self-report is accurate. Does that strike anyone else as a trifle offensive? Of course, this assumes that the physician's tests and observations are somehow more valid than the patient's complaints. I don't want to be too cranky about this. After all, I'm a pretty skeptical person and I think it is important to resist random claims, especially about dietary restrictions, without supporting evidence. But honestly, when an individual is seeking medical advice and reports on their signs and symptoms, there seems little cause to doubt that patient's word. After all, if they misrepresent the facts they are only hurting themselves. Patients can, of course, be mistaken. And those who are interested in a physician's diagnosis might want to subject themselves to such a paternalistic gluten challenge. I have no quarrel with patients making that informed choice. Perhaps some patients will have conditions imposed by their insurance company. Or maybe they will have some other reason to accept this protocol. However, it should not be overlooked that, at its root, this protocol is the antithesis of encouraging patients to take responsibility for their own health care. Further, despite their implied disdain for patients, Doctors Di Sabatino and Corazza don't seem to have considered some of the risks involved in their newly hatched diagnostic protocol which is aimed at pushing back against what they seem to believe is a growing idea that "gluten is toxic for most of the population". In brief, they advocate patients resuming gluten consumption, thus incurring several serious risks to the health and welfare of the patient so physicians may stem the growing tide of gluten-free patients who have undertaken the diet without the blessing of a gastroenterologist or physician. Please take a moment to consider this proposition. The gluten-free diet is restrictive, inconvenient, and expensive. Why would anyone choose to follow such a diet without being convinced that it was valuable to them? Di Sabatino and Corazzo freely acknowledge that there is a dearth of diagnostic tests and protocols for diagnosing or excluding non-celiac gluten sensitivity (although they do overlook some basic tests that I'll discuss shortly). The inconvenience of a gluten-free diet should disabuse critics and skeptics of much of their doubt. However, even if this huge factor is ignored, there are issues of opioid addiction, appetite manipulation, and the risks of triggering allergies, chronic inflammation, autoimmune disease, and psychiatric illness, any or all of which can accompany ingestion of gluten in some individuals. All of these costs and risks are ignored by these two innovators in their Brave New World of non-celiac gluten sensitivity. Addiction to Gluten-derived Opioids Most of the people I know who follow a gluten-free diet are well aware of how addictive gluten can be. Once a person has broken away from an addictive substance, it seems very questionable, to say the least, to persuade them, ostensibly in the interests of their health, to ingest that addictive substance again. Since 1979, we have had solid evidence of the morphine-like peptides of gluten grains (2). Many subsequent reports have replicated the findings first reported by Christine Zioudrou and her colleagues (3, 4, 5, 6) so there is little cause to question the addictive potential of gluten grains and the foods derived from them. How wise would it be to ask a former smoker to do a trial of smoking cigarettes for a few weeks? Or to ask an alcoholic to return to alcohol to reassure his physician of the correctness of the patient's choice to quit? Appetite Manipulation Relatedly, an opioid blocker, Naloxone, was given to a group of binge eaters who experienced reduced "duration and magnitude of binge eating episodes" (7). Another group, of healthy volunteers, showed 28% reductions in food intake on days when they were given the same opioid blocker (8). Although gluten opioids were not the intended target of the Naloxone, it may be that this was exactly what this drug was doing in both of these studies. As the obesity epidemic spreads, it is increasingly important to exercise care with respect to foods that cause abnormal and unwarranted increases in appetite. Other researchers have also reported reductions in food intake after administration of opioid blocking medications (9, 10). Autoimmunity Although obesity is an important health concern, autoimmune disease may be of at least equal concern. The loss of integrity of the mucosal barrier of the small intestine is now considered an important factor in the development of many cases of autoimmunity (11, 12). This group of ailments currently plagues the western world with their serious, sometimes lethal consequences. Especially among those who report symptoms in association with gluten consumption, it seems only prudent to proceed with an abundance of caution. When there may be an increased risk of developing one or more autoimmune diseases, a return to gluten consumption seems a very poor choice. In susceptible individuals, gluten consumption triggers zonulin production. Zonulin mediates the tight junctions between the epithelial cells that form the protective barrier between the digesting food in our intestines, and our bloodstreams (11). Thus, ingesting gluten , for those at risk, invites leakage of undigested and partly digested proteins into the bloodstream. The immune system sees these foreign substances as invaders and attacks them in the same manner it would attack a viral or bacterial invader. These same antibodies sometimes attack self tissues with similar protein structures. Because gluten is ingested each day, several times a day, this leaky gut and flood of antibodies can quickly become chronic. Why would a caring health-care professional advise someone who is reporting symptoms associated with gluten consumption to return to eating this substance when the patient may well be reporting early signs and symptoms of a developing autoimmune disease? Allergies and Inflammation Similarly, a compromised intestinal mucosa has been connected to allergies and chronic inflammation. It seems irresponsible to bring one's professional authority to bear on the patient, encouraging them to return to eating gluten so the physician may be persuaded that the patient is accurately reporting their responses to gluten. At the Department of Neurology at the Royal Hallamshire Hospital in Sheffield, U.K., a group of researchers have been reporting, since the mid 1990s, the identification of elevated serum IgG antibodies against one of the proteins in gluten among a majority of patients with a variety of neurological diseases of unknown origins (13). They also report that the prognosis is quite poor for these people. I attended a presentation by the lead researcher of this group, Dr. Marios Hadjivassiliou, in 2005. He repeatedly stated that these individuals require an exceedingly strict gluten-free diet to have any chance of improving their prognosis. Yet doctors Di Sabatino and Corazza's approach would further compromise these patients' chances of recovery to satisfy the doubts held by physicians. The research group at the Royal Hallamshire Hospital, and many other researchers, continue to use testing for IgG and IgA class antibodies against gliadin, a sub-group of gluten proteins, as an indicator of gluten sensitivity (13). It may be imperfect, but any time a particular food protein is triggering an abnormal immune response in our bodies, it seems reasonable to assert that this individual is sensitive to that food protein. When celiac disease has been ruled out, positive IgG and/or IgA anti-gliadin antibodies clearly indicate a condition of non-celiac gluten sensitivity. There are other forms of non-celiac gluten sensitivity that may be missed by these tests, but it is clear that IgG and IgA testing for anti-gliadin antibodies is identifying some, perhaps most, cases of non-celiac gluten sensitivity. About 12% of the general population shows elevated levels of IgG antibodies against gluten (13, 14). Notwithstanding Di Sabatino and Corazza's assertion that there are no tests for non-celiac gluten sensitivity, IgG and IgA anti-gliadin antibody tests are certainly one means of identifying gluten sensitivity, whether in the blood or in fecal matter. Additional markers may well arise from current and future research. Psychiatric Illnesses Some forty years ago, Dr. Curtis Dohan and his colleagues established a clear connection between gluten and dairy proteins and schizophrenia (15). Doctors Singh and Kay replicated those findings (16). The issue was hotly debated on the basis of several other studies of sloppy design that followed. For a long time, the connection with gluten was dismissed because of the contradictory reports in the medical literature. In the last fifteen years, another spate of research has emerged showing that Dr. Dohan, Dr. Singh, and both of their research groups had unearthed a compelling connection with serious implications for the effective treatment of a sub-group of patients with schizophrenia and other mental illnesses. Some of these findings were capricious, as in the case of a long-term schizophrenic who was placed on a ketogenic diet. After 53 years of battling her symptoms she experienced complete relief from her schizophrenia (17). Genetic studies and investigations of schizophrenic patients and bi-polar patients have also shown that gluten may be an important factor in these conditions (18, 19, 20, 21, 22, 23, 24, 25 ) which are both common and debilitating. A subset of autistic patients have also experienced symptom improvement on a gluten-free diet (25, 26, 27). Thus, there is compelling evidence across a number of specialty areas of human illness in which gluten plays a role as an important contributor to symptoms and/or it lies at the root of these conditions. I must therefore question how Dr. Di Sabatino and Dr. Corazza can assert that gluten is not toxic to most people? Their implicit claim to that effect is questionable given the wide range illnesses that it contributes to or causes. We now know that increased production of zonulin, the mediator of intestinal barrier integrity, discovered at the University of Maryland in 2000 (28), is triggered, in some people, by gluten ingestion (29). Subsequent research has revealed that zonulin is the precursor of haptoglobin 2 which is found in about 80% of the human population (11). In the absence of further research, there may well be cause to suspect that gluten grains are a healthy food for only about 20% of the population. So these two physicians would have us continue to consume gluten until such time as we develop full-blown illness or signs and symptoms acceptable to our physicians. Surely that has put the cart before the horse. Their patients do not visit them for the sole benefit of the physician. Nonetheless that is the central thrust of this protocol. This published opinion has spawned a number of articles online and in the popular press, all of which (that I've seen) seem to ignore all of the concessions to non-celiac gluten sensitivity mentioned in the article by doctors Di Sabatino and Corazza . Some of these spin-off commentaries even use the original article to support their suggestions that a gluten-free diet is inappropriate even for those with symptoms that are relieved by the diet. This blatantly contravenes the opinions expressed by Di Sabatino and Corazza but these journalists don't let the facts get in the way of their over-simplified, august opinions. While I take exception to their implied distrust of patients, at least Di Sabatino and Corazza concede that the gluten-free diet is appropriate for those who experience symptom mitigation or remission when avoiding gluten. These reporters make no such concession. One article from the LA Times, states: "That hasn't stopped many people from declaring they are gluten sensitive, even though they may not be" (30). This journalist seems to imagine that he/she is in a better position to judge whether there is benefit in a gluten-free diet than the people who choose to follow it. Given Di Sabatino and Corazza's flagrant disrespect for patients, I suppose similar disparagement by the journalists who mindlessly follow should not surprise us. They, too, dispense medical advice that could prove very harmful. The quality of that advice is about what one might expect under the circumstances. Doctors Di Sabatino and Corazza not only acknowledge non-celiac gluten sensitivity as a cause for symptoms very similar to those of celiac disease, they call for further research to develop and codify diagnostic protocols that will help clinicians better recognize and treat this newly recognized ailment. They go on to acknowledge that conditions including "headache, lethargy, attention-deficit/hyperactivity disorder, ataxia, or recurrent oral ulceration" in the absence of celiac disease often improve or resolve on a gluten-free diet. Their unfortunate denial of gluten as toxic seems to have invited much of the spin-off, journalistic conjecture under such titles as "Gluten-free diets not always necessary, study suggests" (31). Even the characterization of this opinion article as a study is misleading in the extreme. These journalists and medical opinion authors also seem oblivious to the strong connection between learning disabilities and gluten consumption (32, 33). My own professional experience echoes Blair's report in which 70% to 90% of children with dyslexia accelerated their reading and writing skills more rapidly than mainstream children not afflicted with dyslexia during a six month trial of the gluten-free diet (33). This is startling! In most cases, children with dyslexia work very hard to reduce the gap by which they are falling behind in their studies. In my work it is often difficult to persuade parents of a child who struggles with learning disabilities to undertake a six month trial of a gluten-free diet. Yet the positive results are often quite astounding. The medical opinion expressed by Di Sabatino and Corazza and the subsequent spin-off in the popular press have just made this task substantially more difficult. Who wants to be characterized as a radical nut case? Who wants to risk their child's learning and welfare on a fad diet? These are the accusations implicit in the Di Sabatino and Corazza characterization of "gluten preoccupation" and the journalistic frenzy that followed. One article in The Toronto Star claims that the gluten-free diet is dangerous. Anyone who has followed it knows that claim to be pure nonsense. The article is based on an interview with Dr. Corazza so it is difficult to tell whether the journalist got it wrong or Dr. Corazza actually made this silly claim. The dangers that Dr. Corazza is quoted about are that it will be more difficult to get a diagnosis of celiac disease and that the diet will cost more money (34). Yet the title says " Gluten-free diets could be dangerous, doctors say" (34). What these journalists and physicians missed is the rapidly growing body of evidence showing that increasing numbers of ailments among escalating numbers of people are driven by this ubiquitous food (2-35) . Gluten may or may not be toxic for most of the population. We don't know. We can't know that without more research. Neither can Di Sabatino and Corazza or any of the journalistic lemmings who leaped off that same cliff, asserting that those who take up a gluten-free lifestyle are the ones who are misguided. Regardless of whether gluten is toxic to most of us, a gluten-free diet certainly is not. Just how do Dr. Corazza and/or these journalists imagine that humans survived and thrived before gluten grains were first cultivated about 10,000 years ago? And most of the world's populations survived and thrived without gluten for many more millennia without gluten grains. The growing numbers of people who are willing to accept the inconvenience and expense of a gluten-free diet because of the benefits they experience should incite curiosity and discourse - not contempt and dismissal. Gluten may be toxic to many more people than are currently identifiable by limited available testing. Asserting one side or the other of this argument is at least premature. At most it could prove very harmful to those individuals who listen and obey the voices of experts and journalistic hucksters using devious methods to promote their own pet ideas. Sources: 1. Di Sabatino A, Corazza G. Nonceliac Gluten Sensitivity: Sense or Sensibility? Ann Intern Med. 2012;156:309-311. 2. Zioudrou C, Streaty RA, Klee WA. Opioid peptides derived from food proteins. The exorphins. J Biol Chem. 1979 Apr 10;254(7):2446-9. 3. Fukudome S, Jinsmaa Y, Matsukawa T, Sasaki R, Yoshikawa M. Release of opioid peptides, gluten exorphins by the action of pancreatic elastase. FEBS Lett. 1997 Aug 4;412(3):475-9. 4. Fukudome S, Yoshikawa M. Gluten exorphin C. A novel opioid peptide derived 5. from wheat gluten. FEBS Lett. 1993 Jan 18;316(1):17-9. Fukudome S, Yoshikawa M. Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett. 1992 Jan 13;296(1):107-11. 6. Huebner FR, Lieberman KW, Rubino RP, Wall JS. Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates. Peptides. 1984 Nov-Dec;5(6):1139-47. 7. Drewnowski A, Krahn DD, Demitrack MA, Nairn K, Gosnell BA. Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters. Am J Clin Nutr. 1995 Jun;61(6):1206-12. 8. Cohen MR, Cohen RM, Pickar D, Murphy DL. Naloxone reduces food intake in humans. Psychosom Med. 1985 Mar-Apr;47(2):132-8. 9. Wolkowitz OM, Doran AR, Cohen MR, Cohen RM, Wise TN, Pickar D. Single-dose naloxone acutely reduces eating in obese humans: behavioral and biochemical effects. Biol Psychiatry. 1988 Aug;24(4):483-7. 10. Trenchard E, Silverstone T. Naloxone reduces the food intake of normal human volunteers. Appetite. 1983 Mar;4(1):43-50. 11. Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS,Antalis TM, Vogel SN, Zhao A, Yang S, Arrietta MC, Meddings JB, Fasano A. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16799-804. Epub 2009 Sep 15. 12. Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8. 13. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71. 14. Fine K. Enterolabs. Private communication. 15. Dohan FC, Grasberger JC, Lowell FM, Johnston HT Jr, Arbegast AW. Relapsed schizophrenics: more rapid improvement on a milk- and cereal-free diet. Br J Psychiatry. 1969 May;115(522):595-6. 16. Singh MM, Kay SR. Wheat gluten as a pathogenic factor in schizophrenia. Science. 1976 Jan 30;191(4225):401-2. 17. 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. 18. Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Leister F, Yang S, Krivogorsky B, Alaedini A, Yolken R. Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry. 2010 Jul 1;68(1):100-4. Epub 2010 May 14. 19. 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. Epub 2009 Sep 11. 20. Cascella NG, Kryszak D, Bhatti B, Gregory P, Kelly DL, Mc Evoy JP, Fasano A, Eaton WW. Prevalence of celiac disease and gluten sensitivity in the United States clinical antipsychotic trials of intervention effectiveness study population. Schizophr Bull. 2011 Jan;37(1):94-100. 21. Kalaydjian AE, Eaton W, Cascella N, Fasano A. The gluten connection: the association between schizophrenia and celiac disease. Acta Psychiatr Scand. 2006 Feb;113(2):82-90. 22. Wei J, Hemmings GP. Gene, gut and schizophrenia: the meeting point for the gene-environment interaction in developing schizophrenia. Med Hypotheses. 2005;64(3):547-52. 23. 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. 24. Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Yolken R. Markers of gluten sensitivity in acute mania: A longitudinal study. Psychiatry Res. 2012 Mar 2. 25. Millward C, Ferriter M, Calver S, Connell-Jones G. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev. 2004;(2):CD003498. 26. Shattock P, Whiteley P. Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets. 2002 Apr;6(2):175-83. 27. Knivsberg AM, Reichelt KL, Høien T, Nødland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002 Sep;5(4):251-61. 28. Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000 Apr 29;355(9214):1518-9. 29. Clemente MG, De Virgiliis S, Kang JS, Macatagney R, Musu MP, Di Pierro MR, Drago S, Congia M, Fasano A. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut. 2003 Feb;52(2):218-23. 30. http://www.latimes.com/health/boostershots/la-heb-gluten-sensitivity-20120221,0,4517592.story 31. http://www.cbsnews.com/8301-504763_162-57381966-10391704/gluten-free-diets-not-always-necessary-study-suggests/ 32. Knivsberg AM. Urine patterns, peptide levels and IgA/IgG antibodies to food proteins in children with dyslexia. Pediatr Rehabil. 1997 Jan-Mar;1(1):25-33. 33. http://www.timesonline.co.uk/tol/news/uk/article444290.ece 34. http://www.thestar.com/living/article/1146787--gluten-free-diets-could-be-dangerous-doctors-say#article 35. Hoggan R. Considering wheat, rye, and barley proteins as aids to carcinogens. Med Hypotheses. 1997 Sep;49(3):285-8.

Celiac.com 11/23/2017 - Many theories have been fielded about autism. Some research careers have been made by investigating autism, while other careers have been seriously damaged when that research threatened some sacred cows of allopathic medicine. Yet despite all of this active research exploring the world of autism, we continue to experience exponential increases in rates at which autism is diagnosed. And debate continues unabated regarding the causes and appropriate treatments. Part of this increasing trend is, doubtless, because we have gotten better at recognizing the various manifestations of this debilitating condition. However, the evidence indicates that there is a dramatic increase in the absolute incidence of autism. Although frightening, this trend may offer some insight into several of the factors that contribute to this condition. That is the crux of my argument here. Since most prior theories have been tested in isolation, as is the norm in medical investigations, measurement of changes induced by individual contributing factors may either be so mild as to escape notice, or may not have been sufficient to induce symptom mitigation. Similarly, if preconceived notions shape resistance to some of these hypotheses, we may miss the most salient characteristics of autism. I have therefore chosen to combine several findings to form a testable hypothesis. I'll let posterity and the reader be the judges of whether this speculation is worthy of further investigation. We begin with Dr. Kalle Reichelt, who sought to understand autism and other psychiatric illnesses through the prism suggested by Dr. Curtis Dohan's work investigating schizophrenic patients. While Dohan et al reported positive results among schizophrenics from a gluten free, dairy free diet, Reichelt and his colleagues identified unique peptides in the urinary excretions from patients on the autistic spectrum and explored their possible connections with gluten and dairy proteins(1). A leaky gut appeared to be a precondition for autism. In 1996, D'Eufemia and others reported increased intestinal permeability in almost half of their autistic patients, using synthetic sugars that can be measured in the urine (2). Gardner has reported disturbed gastrointestinal function in autism. Reichelt and Knivsberg have also published reports of improved social interaction and communication among some children with autism following institution of a gluten-free, casein-free diet (4). However, their investigations reveal that the diet must be consistent, strict, and long-lasting to allow the gradual dissipation of the psychoactive peptides from these foods. Others have reported that this dissipation process can take up to 12 months (5). It is important to note that, while the work indicating that the symptoms of autism can often be mitigated by the strict, long-term avoidance of gluten and dairy, none of these investigators claimed that this diet can cure autism or even eliminates all of its symptoms. The diet simply helped children improve to the point where they could function better in school and society by mitigating their most severe and limiting symptoms (4). Many of these researchers postulate that improved integrity of the intestinal barrier and reduced ingestion of psychoactive peptides in the diet are a likely root of these improvements. Against this backdrop of widespread recognition of gastrointestinal dysfunction, excessive intestinal permeability, and symptom mitigation through dietary restriction in many autistic children, Dr. Andrew Wakefield, along with 12 other researchers, published their discovery of a pattern of intestinal inflammation and compromised barrier function in 11 of 12 subjects with pervasive developmental disorders, including 9 children with autism. Based on histories provided by parents, health visitors, and general practitioners, a pattern of behavioral/autistic symptom onset was seen within 14 days of combined vaccination for measles, mumps, and rubella. The average time to symptom onset was about 6 days. In the same report, Wakefield et al state "We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described." Later on the same page, they state "If there is a causal link between measles, mumps, and rubella vaccine and this syndrome, a rising incidence might be anticipated after the introduction of this vaccine in the UK, in 1988." [my emphasis] Wakefield et al identify several reports connecting vaccine-strain measles virus with Crohn's disease and autoimmune hepatitis. They also hearken to earlier work that implicates inflamed or dysfunctional intestines in the behavior changes seen in some children. They point to other factors that suggest a genetic predisposition may also be a precondition of developing autism, along with markers of vitamin B12 deficiency (which many readers will recognize as a common finding in celiac disease and non-celiac gluten sensitivity). Clearly this group was not attacking the MMR vaccine or its importance to public health. Nonetheless, in the same issue of The Lancet, no less than six letters, written by a combined total of 21 authors, attacked Wakefield et al because of the impact that their findings might have on public health. Over the ensuing months and years, Wakefield's methods were criticized and denigrated. One of the more emotional attacks alleged academic fraud on Wakefield's part (7). He has been vilified in the public and professional media as a brigand. Yet he and his research group were careful to avoid making any claims beyond having found a form of bowel disease (lymphoid hyperplasia) in 9 of their subjects, and non-specific colitis in 11 of their subjects, along with reporting the close temporal association of onset of behavioral symptoms and MMR vaccines as reported by parents, health visitors, and general practitioners. They would have been remiss had they failed to report this association. Further, there were 12 other researchers who put their names to this research. Surely we cannot suspect that all 13 of these professionals would risk their careers to perpetrate a fraud! Meanwhile, as these attacks were ginning up, a research group at the University of Maryland reported that, in genetically susceptible individuals, a protein they dubbed "zonulin" can, when gluten is ingested, induce changes to intestinal permeability (8, 9). Does the gluten free, dairy free diet reduce excessive intestinal permeability? We know it does in people with celiac disease (8), but what impact would or could it have on children with the lymphoid hyperplasia and/or non-specific colitis identified by Wakefield et al? And does reduced zonulin production due to restriction of these foods explain the benefit experienced by many children with autism? Perhaps these questions are also relevant to another area of autism research reflected by identification of specific strains of clostridium infection in autism, first postulated by Bolte (10). Dr. S. Finegold and his colleagues demonstrated that 8 of 10 children with late onset autism showed transient reductions of symptoms of autism in response to oral vancomycin which returned when vancomycin was withdrawn (11). This is an antibiotic that is usually used in cases of antibiotic-resistant infections. Because this group identified an unusually large number and variety of strains of clostridium in their autistic subjects, as compared with controls, and because many clostridium variants excrete neurotoxic substances, their use of vancomycin was given to target clostridium. However, elements of Finegold's work and Wakefield's work may be taken to suggest some overlap. For instance, could the added clostridium load in autistic children contribute to the intestinal inflammation and permeability seen in Wakefield's report? Or could the MMR vaccinations produce conditions that are more hospitable to antibiotic resistant, neurotoxic strains of clostridia? Or could symptoms induced by MMR lead to administration of antibiotics that provide favorable conditions in the gut for proliferation of clostridium? To further complicate this issue, Dr. Stephanie Seneff has identified vitamin D deficiency, and popular use of statin drugs, in combination with reduced dietary consumption of cholesterol and fats as possible factors in autism. She implicates these deficiencies as arising either in utero or in infancy and she specifically cites work demonstrating that cholesterol, fats, and vitamin D are important components of healthy immune function (14). Putting it all together The hypothesis embodied herein asserts that at some stage the autistic child has: some predisposition to autism; a multi-dimensionally compromised immune system; been exposed to multiple and uncommon strains of clostridium which lead to the colonization of the gut by these antibiotic-resistant bacteria; are suffering from some degree of vitamin D deficiency and are eating a diet that is deficient in fats and cholesterol. Further, as the child develops one or more of the symptoms or sequelae of clostridium colonization or other infection, antibiotics are administered to provide relief from these or other symptoms of infection, sometimes including chronic ear infections. Thus, the competing gut bacteria that might otherwise keep these strains of clostridia in check are wiped out, permitting broader proliferation of multiple strains of clostridia. Similarly, the MMR vaccine, which, by design, engages and taxes the immune system. In the immune system's weakened state resulting from vaccination and dietary opioids (13), increased numbers of unusual strains of clostridium, abnormal gut biome, cholesterol deficiency, vitamin D deficiency, and perhaps, other nutrient deficiencies, also reduces systemic surveillance for, and antibody combat with, the clostridia and/or remnants of MMR vaccine. The neurotoxic excreta from clostridia and MMR are released into the intestinal lumen and by zonulin's action to widen the junctions between epithelial cells, these toxins are thus given access to the bloodstream. By the same pathway, opioids, other psychoactive peptides from gluten and dairy, along with other undigested and partly digested proteins, which may be harmful, also reach the bloodstream. From there, they travel to the BBB where zonulin again opens gaps in this barrier and allows the clostridium-derived toxins, opioids, and other impurities access to the brain where they alter blood-flow patterns, damage neurological tissues, and perhaps do other damage that has not yet been recognized. Ultimately, this damage and dynamics lead to impeded social performance, intellectual performance, and sometimes, induce startlingly abnormal behaviors. Although this picture appears bleak, and much of it simply reflects the several dietary miscues of the last and our current century, there are corrective steps that can sometimes improve these children's lives. Vitamin D, vitamin B12, and other supplements can be administered to address deficiencies. Because of the associated gut problems, sub-lingual vitamins, and exposure to sunlight without sun screen may both be good starting points. A strict, long-term gluten free, dairy free diet should also be on the menu, even if the whole family has to follow it to ensure that the autistic child does not rebel due to feeling deprived. High levels of cholesterol, saturated and mono-unsaturated fats should also comprise a large part of the diet. One or more courses of vancomycin may also be worth trying. In isolation, the benefits of antibiotics alone will likely be short-lived, as reported by Finegold, but in combination with these other strategies, may extend the benefits of this drug. New developments in antibiotics research may lead to isolation of protective substances from hens' egg shells that may provide more appropriate antibiotic relief and therefore benefit these children even more (15). Most of the research, to date, has focused on one of these factors in isolation. However, if an immune system is compromised by any or all of cholesterol deficiency, vitamin D deficiency, vitamin B12 deficiency, dietary shortages of cholesterol and fats, lingering, chronic sequelae of MMR vaccination, opioids from gluten and/or dairy, and an unusual and wide variety of clostridia, then it seems unreasonable to expect to reverse this condition through implementing only one of the interventions suggested by the above. Each and all of these other components should be addressed when attempting to remediate autism. In the context of these dietary and lifestyle changes, appropriate antibiotics may lead to more permanent improvements for the autistic child. This would be the greatest gift that a physician, parent, or caretaker could give to these children. One may hope. References: Reichelt KL, Hole K, Hamberger A, Saelid G, Edminson PD, Braestrup CB, Lingjaerde O, Ledaal P, Orbeck H. Biologically active peptide-containing fractions in schizophrenia and childhood autism. Adv Biochem Psychopharmacol. 1981;28:627-43. D'Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagnini M, Cardi E, Giardini O. Abnormal intestinal permeability in children with autism. Acta Paediatr. 1996 Sep;85(9):1076-9. Gardner MLG (1994) in Physiology of the gastrointestinal tract (Johnson LR : edit) Rave Press, NY pp 1795-1820 Knivsberg AM, Reichelt KL, Høien T, Nødland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002 Sep;5(4):251-61. Paul, K., Henker, J., Todt, A., Eysold, R. (1985) Zoeliaki- Kranken Kindern in Abhaengigkeit von der Ernaehrung Seitschrift der Klinische Medizin 40; 707-709. as reported in Reichelt K (1990). The Effect of Gluten-Free Diet on Urinary Peptide Excretion and Clinical State in Schizophrenia. Journal of Orthomolecular Medicine. 5(4): 223-239. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 2004 Mar 6;363(9411):750. Flaherty DK. The vaccine-autism connection: a public health crisis caused by unethical medical practices and fraudulent science. Ann Pharmacother. 2011 Oct;45(10):1302-4. Epub 2011 Sep 13. Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000 Apr 29;355(9214):1518-9. Clemente MG, De Virgiliis S, Kang JS, Macatagney R, Musu MP, Di Pierro MR, Drago S, Congia M, Fasano A. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut. 2003 Feb;52(2):218-23. Bolte ER. Autism and Clostridium tetani. Med Hypotheses. 1998 Aug;51(2):133-44. Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, McTeague M, Sandler R, Wexler H, Marlowe EM, Collins MD, Lawson PA, Summanen P, Baysallar M, Tomzynski TJ, Read E, Johnson E, Rolfe R, Nasir P, Shah H, Haake DA, Manning P, Kaul A. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002 Sep 1;35(Suppl 1):S6-S16. http://stephanie-on-health.blogspot.ca/2008/11/sunscreen-and-low-fat-diet-recipe-for.html Hoggan R. Considering wheat, rye, and barley proteins as aids to carcinogens. Med Hypotheses. 1997 Sep;49(3):285-8 Seneff S, Davidson R, Mascitelli L. Might cholesterol sulfate deficiency contribute to the development of autistic spectrum disorder? Med Hypotheses. 2012 Feb;78(2):213-7. Epub 2011 Nov 17. Wellman-Labadie O, Lakshminarayanan R, Hinckeemail MT Antimicrobial properties of avian eggshell-specific C-type lectin-like proteins. FEBS Letters Volume 582, Issue 5 , Pages 699-704, 5 March 2008

Celiac.com 09/15/2017 - In Pennsylvania, there is a six-year-old little girl (we'll call her Amy) who has not been allowed to see her mother (we'll call her Cindy) since June 21st because Amy's dad takes issue with a diet that excludes gluten and other allergenic foods. You might think that this is due to a dispute arising out of the dissolution of a marriage, but that is not the case. However, I'm getting ahead of myself. I need to start describing this situation as it began about six years ago, when her father was arrested for public drunkenness, resisting arrest, and creating a public disturbance, when Amy was less than a year old. Dad (we'll call him Steve) struggled with unemployment and part-time employment as a truck driver, falling further and further into arrears on his child support payments. Cindy had primary custody, and every second weekend, Steve took care of Amy. Conflicts between Cindy and Steve quickly arose over the dietary restrictions mentioned above. Cindy wanted Amy to be healthy and she thought she could achieve that goal by allowing her to eat only wholesome foods, excluding cow's milk, gluten, soy, tree nuts, and refined sugar. She made these choices partly because she observed better behavior in Amy when she excluded these foods, partly because she observed gastrointestinal symptoms, including abdominal bloating, when Amy ate these foods, and partly because Amy tested positive for IgE antibodies against tree nuts, and other testing, conducted after Amy was on a diet that had already excluded these foods, showed mildly positive results for gluten, cow milk, and soy. Who can say how strongly Amy would react to these foods if she were eating them on a daily basis? However, Steve apparently does not believe in such diets or testing. He refused to cooperate with the prescribed dietary restrictions despite a court ordering him to do so. This court order had been in place for four years, yet when he testified in court, asserting that he had been following the diet for Amy, he could not even say what gluten is, or what foods contain gluten. Not surprisingly, despite the court's provision of visitation rights for Cindy, Steve has found one excuse after another to refuse Cindy access to their daughter, since gaining full custody based on a deeply flawed claim that Cindy has Munchausen's syndrome by proxy (MSBP). My comments, of course, only represent one side of the story. However, most of us who follow a gluten free diet have, at some point, had to deal with similarly resistant attitudes, although they are not usually taken to such extremes. After years of support payment delinquency and non-compliance with court orders, Steve showed up in court on June 21st, with legal counsel, a psychiatrist's report asserting that Cindy has MSBP, and claiming that he has a full-time job and is therefore able to support Amy, despite long standing arrears on his child support payments to Cindy. Where did all this money come from to pay for these expensive representatives and expert reports? And how is it that Steve overlooked bringing his child support payments up to date before paying these other expenses? Further, Steve is demanding child support payments when he has yet to pay up his own arrears. The court took away her daughter based on a flimsy report that accused Cindy of Munchausen's Syndrome by Proxy. At that time, Cindy was not allowed to defend herself or speak on her own behalf. She was not even allowed to read the report that accused her of MSBP! The judge has also sealed the record so Cindy cannot get a copy of it! It appears that she doesn't have a right to face her accuser. One of Steve's experts ignored the fact that Amy was only getting gluten on every second weekend, at the time she was tested, and asserted that Amy's mildly positive test results for food sensitivities to gluten, soy, and cow's milk were somehow meaningless. (This may also be rooted in the currently contested value of IgG food allergy testing, which would fill another article.) The psychiatrist asserted that Cindy's dietary restrictions for Amy indicate that Cindy has Munchausen's syndrome by proxy and that Cindy is therefore abusing Amy with this diet. The most insane part of this whole scenario is that any of the many Paleodiet advocates, including S. Boyd Eaton, M.D., professor Loren Cordain, Ph.D., professor Melvin Konner, M.D., Ph.D., and professor Staffan Lindeberg, M.D., Ph.D. would endorse this diet as almost universally healthful. Many low carbohydrate advocates, such as professor Stephen Phinney, M.D., Ph.D., professor Jeff Volek Ph.D., R.D., and professor Jay Wortman, M.D., would similarly approve this diet as providing a much more healthful start for this child than the conventional American diet that most American children her age are eating. Some of these Paleodiet and low carbohydrate experts have raised their own children on similar diets because of the health benefits such eating habits confer. Do they have Munchausen's syndrome by proxy too? Let's take a look at this diet, one element at a time. Cindy wants her daughter to avoid refined sugar. Not only is it unhealthy, Cindy believes that Amy's behavior deteriorates when consuming refined sugar, and the work of all of the above scientists supports Cindy's concerns. One research group, Fiorito et al, showed that sweetened beverage consumption at age five predicts lifelong elevated sugar consumption, and both current and future adiposity (1). With obesity looming as one of the greatest health challenges facing Americans today, it is little wonder that Cindy is concerned. Relatedly, the Center for Science in the Public Interest (CSPI) quotes Marion Nestle, chair of the Department of Nutrition and Food Studies at New York University, as saying, "Because sugary foods often replace more healthful foods, diets high in sugar are almost certainly contributing to osteoporosis, cancer, and heart disease" (2). Similarly, Mohammad Akhter, the executive director of the American Public Health Association stated that "Health officials must take prudent action to stem the dilution of the American diet with sugar's empty calories" (2). The CSPI offered these and other statements from a number of health experts and organizations in their petition asking the U.S. government's Food and Drug Administration (FDA) to require labeling that would specify the sugar content of beverages and processed foods. They also want the FDA to provide guidelines that will recommend a limit on daily consumption of refined sugars, just as they do with vitamins. There can be little doubt that refined sugar is an important and pervasive health threat to Americans. Certainly the reduction or exclusion of refined sugars provides no basis for legitimate criticism of Cindy's exclusion of this harmful food substance from Amy's diet. Cindy also wants Amy to avoid soy. Some evidence suggests that chronic ingestion of soy-derived genestein induces chromosomal imbalances in epithelial cells of human breast tissues, thereby increasing one's risk of developing breast cancer later in life (3). Further, soy, as with many other legumes, contain high concentrations of several types of anti-nutrients. Soy protein isolate, a very common processed food additive, has the highest saponin content of all legumes, at 10,600 mg/kg (4). These saponins can damage and penetrate the membranes of almost all human cell lines. This is the means by which they penetrate the intestinal mucosal barrier, enter the circulation, and damage red blood cells, inhibiting their capacity to carry oxygen (4). Soy is also very high in phytate content. Phytates bind to iron, calcium, zinc, and magnesium, forming a bond that cannot be broken by human digestive processes or enzymes. The net result is that when soy is consumed, much of the important trace minerals from other foods consumed at the same time are wasted in one's fecal matter rather than being absorbed through the gut enterocytes (5). The impact of soy-derived phytates alone may not be sufficient to induce deficiency in the context of a mineral-rich diet. However, children often experience trace mineral deficiencies during growth spurts, and soy consumption would serve to accentuate these deficiency states (5). Similarly, the approximately 20% of the protease inhibitors in soy that survive cooking (assuming that all soy is cooked prior to consumption) incite the pancreas to increase production and excretion of protease enzymes, particularly trypsin. This particular protease induces increased intestinal permeability. Soybean lectin also increases intestinal permeability. Both combine to cause a leaky gut and an increased risk of developing additional food sensitivities. Also, soy isoflavones impair iron metabolism (4). Clearly, there is no good reason to question Cindy's dietary choices for Amy based on her exclusion of soy. Cindy also wants to protect her daughter from the health hazards of cow's milk, which is both a very common allergen and has long been reported to induce iron deficiency in infants and young children (5). This latter may be the result of the high levels of bio-available calcium in milk. Calcium competes for the absorptive mechanisms that also moves, zinc, magnesium, and iron into our circulation (5). Zinc is critical to healthy function of the innate immune system. Magnesium serves in a wide range of processes that aid the healthy development of a child's body. And iron is critical to a child's intellectual development and wellbeing (5). Milk has also been implicated in causing or raising insulin resistance, acne, and a host of hormonal abnormalities. Some evidence suggests that these problems are caused by the hormones in cow's milk and their impact on our hormonal receptors and our own hormonal production (4). These harmful hormones from cow milk include bovine insulin, insulin-like growth factor 1, and estrogen, all of which have been shown to impact on human health (4). Further, soy and dairy proteins are both numbered among the eight most allergenic foods in the U.S. food supply, along with tree nuts and wheat (4). Cow milk allergy alone is estimated to afflict "from 2 to 3 percent of children between the ages of one and three" (4). Milk has also been implicated in some cases of asthma. Others argue that the health benefits of dairy consumption outweigh the detriments. However, "a 2007 meta analysis from the Harvard School of Public Health reported that high calcium intake had no therapeutic effect on hip fractures in 170,000 women and 68,000 men" (4) p. 102. Now let's look at gluten. Most research regarding the impact of a gluten free diet has only examined its impact on children with celiac disease, who almost universally benefit in learning and behavior from gluten avoidance. However, a gluten free diet has also been shown, in the context of a test group of 533 children, to improve school readiness among 100% of children with celiac disease, 86% of those with non-celiac gluten sensitivity (as measured by IgG and/or IgA antibodies against gliadin) and among at least 43% of gluten insensitive patients who attended a pediatric gastroenterology practice in New Zealand, between 2001 and 2005 (6). Others have reported, in the absence of celiac disease, significant reductions in the number and severity of learning disabilities following a six months trial of a gluten free diet (7). Still others are now reporting that non-celiac gluten sensitivity is an important clinical condition (8) and that this newly recognized clinical condition may be accompanied by consequences as dire as those found in untreated celiac disease (9). Long standing evidence, and considerable new research combine to support dietary exclusion of gluten for from 12% to 40%+ of the U.S. Population (10, 11). We are forced to wonder exactly which facet of the diet Cindy is trying to keep Amy on could suggest a condition of Munchausen's syndrome by proxy? This is a condition that is defined by the fabrication of symptoms or symptoms induced by the caregiver. I can understand someone who is not well versed in recent nutritional research claiming that this is a harsh and restrictive diet. However, the health benefits such a diet confers are far greater than the inconvenience it imposes. It is a completely benign diet that only offers benefit to the child. And, after repeated demonstrations that he has little regard for court orders that do not suit him, Steve now has custody of this young child, and he is blocking her mother and Amy from spending time together. That behavior alone says a great deal about just how concerned he is about the welfare of this child. The MSBP diagnosis is largely based on Steve's claims that he never saw any symptoms related to the foods to which Cindy believes Amy is allergic/sensitive when Amy was with him. However, in the short term it is quite likely that she did not display any signs or symptoms, especially for those symptoms caused by the opioids in gluten and dairy (12). Cindy would be dealing with the withdrawal symptoms in the first week or so after Amy returned home from a weekend with her dad, but not while being fed those opioid-containing foods (13, 14, 15). I understand that MSBP mothers can cause their children a great deal of harm. I also understand that such a diet would be a huge undertaking for someone like Steve, who doesn't believe in such things. However, for those of us who have experienced the miraculous improvements that come with the kind of healthy diet that Cindy is insisting on for Amy, this harmless diet only offers improved health and development. To suggest MSBP on the basis of this diet reflects a gross level of ignorance on a dietary level. It also says a great deal about the current state of Medicine and the field of Psychiatry that a practitioner could construe such a diet as suggestive of any mental illness, unless independent thinking is now a diagnostic characteristic of one of the maladies defined in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV). Sources: Fiorito LM, Marini M, Francis LA,Smiciklas-Wright H,Birch LL. Beverage intake of girls at age 5 y predicts adiposity and weight status in childhood and adolescence1,2,3 Am J Clin Nutr. 2009 October; 90(4): 935–942. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744622/ http://www.cspinet.org/new/sugar.html Kim YM, Yang S, Xu W, Li S, Yang X. Continuous in vitro exposure to low-dose genistein induces genomic instability in breast epithelial cells. Cancer Genet Cytogenet. 2008 Oct 15;186(2):78-84. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2590788/ Cordain L, The Paleo Answer. Wiley & Sons. Hoboken, NJ, 2012 p. 72 -147 Hoggan R, The Iron Edge . Waterside Works. Calgary, Canada. 2008. Ford R, Hoggan R, Fung T, Marini A. School readiness paper - unpublished data Blair A, Wheat-free diet gives food for thought: A school claims dyslexic children show astonishing improvements with special meals The Times, June 12, 2004 http://www.timesonline.co.uk/tol/news/uk/article444290.ece Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity. Am J Gastroenterol. 2012 Jul 24. Anderson LA, McMillan SA, Watson RG, Monaghan P, Gavin AT, Fox C, Murray LJ. Malignancy and mortality in a population-based cohort of patients with coeliac disease or "gluten sensitivity". World J Gastroenterol. 2007 Jan 7;13(1):146-51. Braly J, Hoggan R, Dangerous Grains. Penguin/Avery, NY. 2002 Davis W, Wheat Belly. Rodale, NY. 2011 Fanciulli G, Dettori A, Demontis MP, Tomasi PA, Anania V, Delitala G. Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier. Life Sci. 2005 Feb 25;76(15):1713-9. Epub 2004 Dec 20. Yoshikawa M, Takahashi M, Yang S. Delta opioid peptides derived from plant proteins. Curr Pharm Des. 2003;9(16):1325-30. Horváth K, Gráf L, Walcz E, Bodánszky H, Schuler D. Naloxone antagonises effect of alpha-gliadin on leucocyte migration in patients with coeliac disease. Lancet. 1985 Jul 27;2(8448):184-5. Schick R, Schusdziarra V. Physiological, pathophysiological and pharmacological aspects of exogenous and endogenous opiates. Clin Physiol Biochem. 1985;3(1):43-60.

Celiac.com 06/30/2017 - Dear attending physician: If you are reading this it is because your patient either expects you to refuse or you have refused to test them for celiac disease. You may believe, in keeping with prior training, that this patient does not display the signs or symptoms associated with celiac disease. However, the symptom complex of celiac disease has recently undergone dramatic changes, beginning with the understanding that celiac disease is a systemic, rather than an intestinal ailment. World renowned researchers have weighed in on this issue, with peer reviewed reports that repeatedly establish the protean manifestations of celiac disease. They defy prior algorithms for symptom assessment toward diagnosing celiac disease. In the past, undiagnosed celiac patients were often identified as asymptomatic because their symptoms were simply not diarrhea, abdominal bloating, and muscle wasting. However, the Celiac Disease Center at the University of Chicago lists more than 300 presenting symptoms of celiac disease (1). The same group also offers a list of symptoms that demonstrate the wide range of apparently unrelated symptoms that can indicate celiac disease, only the first two of which represent these classical symptoms (2). Recurring abdominal bloating and pain Chronic or recurrent diarrhea Constipation Nausea or emesis Liver and biliary tract disorders (increased serum transaminases, primary sclerosing cholangitis) Weight loss Pale, foul-smelling stool Iron-deficiency anemia unresponsive to iron therapy Fatigue Failure to thrive or short stature Delayed puberty Arthralgia Tingling numbness in the legs Pale sores inside the mouth Dermatitis herpetiformis Abnormal dentition (tooth discoloration, loss of enamel) Unexplained infertility or recurrent miscarriage Osteopenia or osteoporosis Peripheral neuropathy Psychiatric disorders (anxiety or depression) Please remember that any one or more of the above symptoms and/or ailments may indicate untreated celiac disease, so testing for celiac disease is an important, inexpensive step toward assisting a patient to resolve these troubling, sometimes debilitating, symptoms. Overweight and obesity may also indicate underlying celiac disease. Today's affluence and accompanying food surpluses permit people who are not absorbing nutrients efficiently to eat enough to more than compensate for otherwise calorically deficient diets. Thus, only a minority of celiac disease cases present with classical symptoms in most of the first world. In fact, some reports indicate that overweight patients with celiac disease are as common as those who are underweight ( 3, 4, 5). This is why researchers have long employed the iceberg metaphor to describe the mass of people with celiac disease. The vast majority these people with celiac disease remain undiagnosed (6). Until sensitive and specific serological screening tools became available, very few cases were diagnosed and celiac disease was erroneously considered rare. In addition to alleviating quite a lot of human suffering, early detection offers some rather large economies for the health care system, as many of the more serious ailments that often befall those with untreated celiac disease may be averted through these inexpensive serological tests and subsequent prescription of a strict gluten free diet. Prior to the therapeutic use of a gluten free diet, mortality was reported at 36% among 73 children with celiac disease (7). Admittedly, it is likely that these were the more serious cases and perhaps some cases of misdiagnosis. However, even as recently as 1989, adult celiac patients experienced almost double the early mortality rate seen in the general population (8), so an early diagnosis and treatment of celiac disease is not just helpful in mitigating current symptoms, it is a powerful form of preventive medicine that is coincidental to the appropriate diagnosis and treatment of celiac disease. Let me expand on that last comment a little further. Chronic depression (9), ADHD (10), neurological (11) and neuromuscular disorders(12) treatment-resistant iron deficiency (13, 14), impaired lung function (15, 16) a variety of lymphomas including B cell and T cell (17, 18, 19) and adenocarcinomas (20, 21) dental enamel defects (22, 23) autoimmune thyroid disease (24, 25 ) autoimmunity in general (26) type 1 diabetes (27, 28) kidney disease (29) liver disease (30, 31) skin disease (32, 33) seizure disorders (34) gait disorders (35) obesity (36) fatigue (37) anxiety (38) infertility (39) osteoporosis (40) learning disorders (41, 42) aphasia (43) and many more such sequels to untreated celiac disease (44) impose an enormous economic burden on our health system and education system. This burden weighs on most levels of government, private insurance companies, families, and individuals. Much of this unnecessary cost is ultimately passed along to taxpayers and/or are incorporated into insurance premiums. We all pay. And the human costs are even greater. Attention deficits and learning disabilities impose life-long inhibitions on success and are corrosive to self esteem. Depression robs us of individual, economic and social achievements, as well as denying us the day-to-day pleasures of life. Similarly, anxiety and infertility are socially isolating and heartbreaking, each in their own ways. Neurological and seizure disorders, including gait disorders, can inhibit our mobility and/or our safe function in this increasingly complex and fast-paced society. Impaired lung function can prohibit or interfere with normal, desirable activities ranging from pleasant walks, sports, and even having sex. Lymphomas and adenocarcinomas can have rapidly fatal consequences. The individual and familial consequences are often devastating. Type 1 diabetes tethers us to insulin injections and requires that we maintain a careful balance between carbohydrate intake and insulin injections. The challenges of this diet dwarfs the inconvenience of a gluten free diet, and a late celiac diagnosis may require that some people comply with both sets of dietary constraints. Skin disease can also exact an enormous social toll, and this is ignores the discomfort and embarrassment of constant itching and scratching, as well as the pain associated with the most common skin diseases connected to celiac disease. Similarly, obesity is not only socially excluding, it poses its own sets of health hazards and life shortening penalties. As osteoporosis becomes more and more common, we can see that society's increasing nutritional dependence on gluten grains may well have set the stage for this degenerative condition, often requiring painful and expensive joint replacement surgeries as our bones gradually crumble and shrink. The dramatic loss of our ability to produce intelligible speech, called aphasia, is by no means the least of this list. The horrific nightmare of being unable to speak to others and have them understand us has been the lived experience of at least one individual. His speech slowly returned after his celiac diagnosis and some time on a gluten free diet. Too many of us are not so lucky. Many of us see ourselves, and our symptoms, in the many posts, blog comments, listservs and websites that discuss celiac disease. Yet outdated medial training can create barriers to patients seeking testing. However, given the above, peer reviewed data and expert opinions, it is difficult to imagine any reasonable argument for refusing to test a patient who requests serological testing for celiac disease. The cost is minimal and the potential benefits to those who are diagnosed, and our society, are enormous. Current data suggest a prevalence of celiac disease in the general population at somewhere around 1%, based on serological testing for selective antibodies. However, newly emerging data suggest that a portion of the population that is at least six or seven times the size of the group with celiac disease mounts an innate immune response to gluten grains. The careful characterization of one pathway for activating intestinal inflammation by non-gluten components of these grains, leaves open the possibility of "gliadin-dependent signaling pathways that still remain to be characterized" (45). Other forms of non-celiac gluten sensitivity, as signaled by IgG class antibodies against gliadin, are seen in 10% to 12% of the general population. Whether these segments of the population with non-celiac gluten sensitivity overlap or are distinct has yet to be determined, so it remains unclear whether they form 10% of our population, or as much as 19% of our culture. Finally, based on a new book by the world renowned pediatric gastroenterologist and allergist, Dr. Rodney Ford, titled Gluten: Zero Global, there is considerable evidence to suggest that, with their many other anti-nutrient, addictive, allergenic, and blood-glucose altering features, gluten grains are a questionable macronutrient food source for humans (46). Thus, testing for non-celiac gluten sensitivity, may offer many of the benefits that testing for celiac disease offers. Your patient and I are asking that you heed the above data from your professional literature and the first dictum of your profession, by 'first doing no harm', and ordering testing for celiac disease and non-celiac gluten sensitivity. Sincerely, Dr. Ron Hoggan, Ed. D. Sources: 1. http://www.cureceliacdisease.org/wp-content/uploads/2011/09/CDCFactSheets10_SymptomList.pdf 2. http://www.cureceliacdisease.org/medical-professionals/guide/symptoms 3. Dickey W, Kearney N. Overweight in celiac disease: prevalence, clinical characteristics, and effect of a gluten-free diet. Am J Gastroenterol. 2006 Oct;101(10):2356-9 4. Tucker E, Rostami K, Prabhakaran S, Al Dulaimi D. Patients with coeliac disease are increasingly overweight or obese on presentation. J Gastrointestin Liver Dis. 2012 Mar;21(1):11-5 5. Cheng J, Brar PS, Lee AR, Green PH. Body mass index in celiac disease: beneficial effect of a gluten-free diet. J Clin Gastroenterol. 2010 Apr;44(4):267-71. 6. Katz KD, Rashtak S, Lahr BD, Melton LJ 3rd, Krause PK, Maggi K, Talley NJ, Murray JA. Screening for celiac disease in a North American population: sequential serology and gastrointestinal symptoms. Am J Gastroenterol. 2011 Jul;106(7):1333-9. doi: 10.1038/ajg.2011.21. Epub 2011 Mar 1. 7. Hardwick C. 1989, as described in Holmes GKT. Non-malignant complications of coeliac disease. Acta Paediatr Suppl. 412: 68-75. 1996. 8. Logan RF, Rifkind EA, Turner ID, Ferguson A. Mortality in celiac disease. Gastroenterology. 1989 Aug;97(2):265-71. 9. Zipser RD, Farid M, Baisch D, Patel B, Patel D. Physician awareness of celiac disease: a need for further education. J Gen Intern Med. 2005 Jul;20(7):644-6. 10. ADHD (10),Niederhofer H. Association of attention-deficit/hyperactivity disorder and celiac disease: a brief report. Prim Care Companion CNS Disord. 2011;13(3). 11. neurological and neuromuscular disorders (11, 12,) Currie S, Hadjivassiliou M, Clark MJ, Sanders DS, 12. Wilkinson ID, Griffiths PD, Hoggard N. Should we be 'nervous' about coeliac disease? Brain abnormalities in patients with coeliac disease referred for neurological opinion. J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1216-1221. 13. Hadjivassiliou M, Chattopadhyay AK, Davies-Jones GA, Gibson A, Grünewald RA, Lobo AJ. Neuromuscular disorder as a presenting feature of coeliac disease. J Neurol Neurosurg Psychiatry. 1997 Dec;63(6):770-5. 14. Fayed SB, Aref MI, Fathy HM, Abd El Dayem SM, Emara NA, Maklof A, Shafik A. Prevalence of celiac disease, Helicobacter pylori and gastroesophageal reflux in patients with refractory iron deficiency anemia. J Trop Pediatr. 2008 Feb;54(1):43-53. 15. Cekın AH, Cekın Y, Sezer C. Celiac disease prevalence in patients with iron deficiency anemia. Turk J Gastroenterol. 2012 Oct;23(5):490-5. 16. Robertson DA, Taylor N, Sidhu H, Britten A, Smith CL, Holdstock G. Pulmonary permeability in coeliac disease and inflammatory bowel disease. Digestion. 1989;42(2):98-103. 17. Edwards C, Williams A, Asquith P. Bronchopulmonary disease in coeliac patients. J Clin Pathol. 1985 Apr;38(4):361-7. 18. Bautista-Quach MA, Ake celiac disease, Chen M, Wang J. Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features. J Gastrointest Oncol. 2012 Sep;3(3):209-25. 19. Leslie LA, Lebwohl B, Neugut AI, Gregory Mears J, Bhagat G, Green PH. Incidence of lymphoproliferative disorders in patients with celiac disease. Am J Hematol. 2012 Aug;87(8):754-9. 20. Elfström P, Granath F, Ekström Smedby K, Montgomery SM, Askling J, Ekbom A, Ludvigsson JF. Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease. J Natl Cancer Inst.2011 Mar 2;103(5):436-44. 21. Benhammane H, El M'rabet FZ, Idrissi Serhouchni K, El Yousfi M, Charif I, Toughray I, Mellas N, Riffi Amarti A, Maazaz K, Ibrahimi SA, El Mesbahi O. Small bowel adenocarcinoma complicating coeliac disease: a report of three cases and the literature review. Case Rep Oncol Med. 2012;2012:935183. 22. Vecchio R, Marchese S, Gangemi P, Alongi G, Ferla F, Spataro C, Intagliata E. Laparoscopic treatment of mucinous adenocarcinoma of jejunum associated with celiac disease. Case report. G Chir. 2012 Apr;33(4):126-8. 23. El-Hodhod MA, El-Agouza IA, Abdel-Al H, Kabil NS, Bayomi KA. Screening for celiac disease in children with dental enamel defects. ISRN Pediatr. 2012;2012:763783. 24. Erriu M, Sanna S, Nucaro A, Orrù G, Garau V, Montaldo C. HLA-DQB1 Haplotypes and their Relation to Oral Signs Linked to Celiac Disease Diagnosis. Open Dent J. 2011;5:174-8. 25. Cats EA, Bertens AS, Veldink JH, van den Berg LH, van der Pol WL. Associated autoimmune diseases in patients with multifocal motor neuropathy and their family members. J Neurol. 2012 Jun;259(6):1137-41. 26. Bardella MT, Elli L, De Matteis S, Floriani I, Torri V, Piodi L. Autoimmune disorders in patients affected by celiac sprue and inflammatory bowel disease. Ann Med. 2009;41(2):139-43 27. Nass FR, Kotze LM, Nisihara RM, de Messias-Reason IT, Utiyama SR. Autoantibodies in relatives of celiac disease patients: a follow-up of 6-10 years. Arq Gastroenterol. 2012 Jul-Sep;49(3):199-203. 28. Saadah OI, Al-Agha AE, Al Nahdi HM, Bokhary RY, Bin Talib YY, Al-Mughales JA, Al Bokhari SM. Prevalence of celiac disease in children with type 1 diabetes mellitus screened by anti-tissue transglutaminase antibody from Western Saudi Arabia. Saudi Med J. 2012 May;33(5):541-6. 29. Van den Driessche A, Eenkhoorn V, Van Gaal L, De Block C. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Neth J Med. 2009 Dec;67(11):376-87. 30. Welander A, Prütz KG, Fored M, Ludvigsson JF. Increased risk of end-stage renal disease in individuals with coeliac disease. Gut. 2012 Jan;61(1):64-8. 31. Drastich P, Honsová E, Lodererová A, Jarešová M, Pekáriková A, Hoffmanová I, TuÄková L, Tlaskalová-Hogenová H, SpiÄák J, Sánchez D. Celiac disease markers in patients with liver diseases: A single center large scale screening study. World J Gastroenterol. 2012 Nov 21;18(43):6255-62. 32. Massironi S, Rossi RE, Fraquelli M, Bardella MT, Elli L, Maggioni M, Della Valle S, Spampatti MP, Colombo M, Conte D. Transient elastography in patients with celiac disease: a noninvasive method to detect liver involvement associated with celiac disease. Scand J Gastroenterol. 2012 Jun;47(6):640-8 33. Caproni M, Bonciolini V, D'Errico A, Antiga E, Fabbri P. Celiac disease and dermatologic manifestations: many skin clue to unfold gluten-sensitive enteropathy. Gastroenterol Res Pract. 2012;2012:952753. 34. Criado PR, Criado RF, Aoki V, Belda W Jr, Halpern I, Landman G, Vasconcellos C. Dermatitis herpetiformis: relevance of the physical examination to diagnosis suspicion. Can Fam Physician. 2012 Aug;58(8):843-7. 35. Maniar VP, Yadav SS, Gokhale YA. Intractable seizures and metabolic bone disease secondary to celiac disease. J Assoc Physicians India. 2010 Aug;58:512-5. 36. Hadjivassiliou M, Grünewald R, Sharrack B, Sanders D, Lobo A, Williamson C, Woodroofe N, Wood N, Davies-Jones A. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003 Mar;126(Pt3):685-91. 37. Balamtekin N, Demir H, Baysoy G, Uslu N, Yüce A. Obesity in adolescents with celiac disease: two adolescents and two different presentations. Turk J Pediatr. 2011 May-Jun;53(3):314-6. 38. Greenfield JR, Samaras K. Evaluation of pituitary function in the fatigued patient: a review of 59 cases. Eur J Endocrinol. 2006 Jan;154(1):147-57 39. Smith DF, Gerdes LU. Meta-analysis on anxiety and depression in adult celiac disease. Acta Psychiatr Scand. 2012 Mar;125(3):189-93. 40. Choi JM, Lebwohl B, Wang J, Lee SK, Murray JA, Sauer MV, Green PH. Increased prevalence of celiac disease in patients with unexplained infertility in the United States. J Reprod Med. 2011 May-Jun;56(5-6):199-203. 41. Rastogi A, Bhadada SK, Bhansali A, Kochhar R, Santosh R. Celiac disease: A missed cause of metabolic bone disease. Indian J Endocrinol Metab. 2012 Sep;16(5):780-5 42. Knivsberg AM. Urine patterns, peptide levels and IgA/IgG antibodies to food proteins in children with dyslexia. Pediatr Rehabil. 1997 Jan-Mar;1(1):25-33. 43. Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004 Jun;113(6):1672-6. 44. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48. 45. Norström F, Sandström O, Lindholm L, Ivarsson A. A gluten-free diet effectively reduces symptoms and health care consumption in a Swedish celiac disease population. BMC Gastroenterol. 2012 Sep 17;12:125 46. Junker Y, Zeissig S, Kim SJ, Barisani D, Wieser H, Leffler DA, Zevallos V, Libermann TA, Dillon S, Freitag TL, Kelly CP, Schuppan D. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012 Dec 17;209(13):2395-408 47. Ford R. Gluten: Zero Global. YfoodX Ltd. Christchurch, New Zealand. 2012.

Celiac.com 02/14/2017 - In 1999, Loren Cordain, the renowned professor of Exercise Physiology at Colorado State University who has since popularized the Paleodiet, published an extensive exploration of why our cultivation and consumption of cereal grains has been disastrous for the human race, resulting in many autoimmune, nutrient deficiency, and other modern diseases (1). Previously, in 1987, the famous physiologist, Jared Diamond characterized humanity's shift to agriculture as "The Worst Mistake in the History of the Human Race" (2). A year later, medical doctor and professor of Anthropology, S. Boyd Eaton and colleagues suggested a mismatch between the human genome and our current agricultural diet/lifestyle (3). And more than a decade prior to that, gastroenterologist, Walter L. Voegtlin, M.D., self published a book apparently asserting, based on his treatments and observations of patients, that dietary avoidance of cereal grains and sugars, offset by increased consumption of meats and animal fats, is an effective treatment regimen for a variety of intestinal ailments including Crohn's disease, colitis, irritable bowel syndrome, and indigestion (4). Each of these perspectives was informed by a different but solidly scientific approach to human health. The academic field of each of these authors varied from Exercise Physiology to Physiology, to Gastroenterology, to Anthropology. Yet each of these specialist researchers arrived at the very similar conclusion that cereal grains are not healthful foods for humans. Their strident declarations to that effect leave little room for doubt. Dr. Cordain acknowledges that the roots of some of his thinking lie with Dr. Eaton and his colleagues. Nonetheless, there is a convergence here, of ideas and insights drawn from separate bodies of data and investigative approaches. While there is some overlap between these scientific disciplines, they all lead to a clear indictment of cereal grains as little more than a starvation food for humans. These scientists point to myriad signs of illness that arise more commonly when populations make the transition to eating diets dominated by grains, especially when the grains are refined and when they are combined with sugar. One critic of this paradigm is the evolutionary biologist, Dr. Marlene Zuk of the University of California at Riverside. According to Alison George at New Scientist, Zuk asserts that the 10,000 years that humans have been cultivating and consuming cereal grains is an adequate time period for humans to evolve an adaptation to these foods (5). But surely this is a Eurocentric view. Simply because some Europeans have been cultivating and consuming cereal grains for ten or more thousands of years does not mean that the entire world's population, or even all Europeans, would or could have adapted to consuming these foods. Let's look back to see what we currently know about our human roots and how those early humans spread all over the world. A group thought to number about 200 humans left Africa sometime between 85,000 and 70,000 years ago, during a glacial maximum that lowered worldwide sea levels by about 300 feet below current levels. The enormous glaciers of the time so depleted the oceanic barriers we see today, that these bodies of water were made navigable even with very primitive flotation devices. The progeny of this relatively small group of early modern people multiplied and went on to parent almost all of today's non-African people of the world with some 1% to 4% of today's human, non-African genes having been derived from the Neanderthal branch of the hominid tree (6). This predominantly early modern human group's progeny would quickly find its way to Australia, the South Pacific, across Asia, to China, east to the Americas and west across India, finally arriving in Europe, where they would supplant the long-time Neanderthal residents who had survived some of Europe's harsh and inhospitable glaciations but apparently could not survive having our forebears as neighbors. While specific paths and dates for exiting Africa, and worldwide patterns and timing of human distribution remain controversial, most experts now accept that indigenous Australians had arrived there at least 60,000 years ago (6). A similarly recent finding places people in the Americas by at least 55,000 years ago, long prior to the date at which the Bering Land Bridge was thought to be available for human movement from Siberia into the Americas (8). This newer, admittedly controversial date raises the likely possibility that people arrived in the Americas, from Asia, by boats or rafts on which they followed the shoreline east to what is now Alaska, then south of the glaciated wastelands of much of what is now Canada. (Or perhaps they arrived by some other means that we have not yet imagined.) But only a small portion of these early Americans would eat wheat, rye, oats, or barley before the last 200 years or so, especially those living on the Great American Plains, or in the frigid north, the dense jungles or places that were otherwise isolated from the encroaching wave of "immigrants" from Europe and beyond. And none of those aboriginal peoples of the Americas were eating these grains prior to 1492. The epidemics of autoimmunity and obesity that may be seen among indigenous Americans are clear reflections of their recent shift to the gastronomic wonders of foods derived from these European grains. Further, even among Europeans, grain cultivation and consumption had not uniformly spread across most of Europe until, at most, less than half of the 10,000 years that Zuk says would be sufficient for human adaptation. In Britain, for instance, grain farming was only getting under way about 4,000 years ago, and availability of grains varied according to local geographies and economies. Also, in parts of Scandanavia, wheat bread was a rare treat until after World War II. Some Europeans are thought to have been cultivating grains for even longer than the 10,000 years ago suggested by Cordain, but the evidence is contradictory and accompanied by a range of expert opinions. Further, the health consequences of this nutritional path are consistently seen in the skeletal remains of those early farmers, many of which can now be seen reflected among indigenous peoples of the Americas, as they assimilate our grain and sugar dominated diet. Adaptation to eating grains is not a gentle, joyful process. Early farmers may have produced many more children than their hunting and gathering neighbors, but their lives were shorter, their bodies were less robust, with substantial reductions in stature, and they experienced widespread infectious diseases and ailments driven by nutritional deficiencies. By the time grains became a cash crop for many European farmers, cereals were disproportionately consumed by affluent urbanites. Those who were large consumers of cereal grains did not include all Europeans, even where yields were prodigious. In more remote, northerly, or mountainous areas, cereal grains, or foods made from them, were likely a rare treat rather than a daily staple. Jared Diamond points out, that in addition to "..... malnutrition, starvation, and epidemic diseases, farming helped bring another curse upon humanity: deep class divisions." He goes on to argue that only with farming and the storage and accumulation of food can Kings "and other social parasites grow fat on food seized from others". He also presents evidence that farming led to inequality between men and women. Conversely, contemporary hunter-gatherers have repeatedly been shown to be quite egalitarian, both regarding gender and political leadership (9). Roger Lewin is another critic of the health impact of European grain cultivation on humans. He points out that even in the very heart of the Fertile Crescent, where agriculture got its start, there was not a uniform adoption of farming. One agricultural center at Abu Hureyra, experienced two cycles of abandonment, one at 8,100 B.C.E., lasting about 500 years, and another at 5,000 B.C.E. These periods when agriculture at this locale was abandoned are "thought to be related to climatic change that became less and less conducive to agriculture" (10). Lewin also harkens to Mark Nathan Cohen's collation of "physical anthropological data that appear to show increasingly poor nutritional status coincident with the beginnings of agriculture.... " (10) suggesting, again, that grains were a starvation food. Eaton et al also approach grain cultivation from an anthropological perspective, suggesting that increased dietary protein and fats from animal/meat sources likely gave rise to increased stature of earlier humans, along with providing the necessary fatty acids for building larger brains, and allowing smaller gut sizes over the past 2.5 million years. It seems reasonable to assume that if it took our pre-historic ancestors that long to adapt to eating meats and animal fats, the very irregular adaptation period of between less than one hundred years and about 10,000 years that various world populations have been cultivating and consuming wheat, rye, barley and oats would be insufficient to allow full adaptation to eating these immune sensitizing cereal grains. Dr. Zuk's perspective might be tempered a bit if she considers that Europeans and their descendants do not comprise the entirety of the world's populations. There are several Asian populations that are not insignificant when compared with European populations and their progeny, including the residents of China, India, Pakistan, and South-East Asia. Even among those of us who appear quite European, there may be a mixture of genes derived from peoples of any of the other five populated continents. The approximately 10,000 year maximum period since humans began to cultivate cereal grains would have little adaptive impact on populations that have only been exposed to these grains for a period of somewhere between four or five centuries and seven or eight decades, as is the case among the indigenous people of the Americas, Australia, New Zealand, and much of Asia (6). Even if all humans had been cultivating and consuming cereal grains for the 10,000 years since this practice was first begun in the Middle East, the high frequency of intestinal, autoimmune, and other diseases that can be mitigated by a gluten free diet, even among descendants of Europeans, leaves little room to doubt that Dr. Zuk's projected adaptation simply has not occurred. The current prevalence of celiac disease and non-celiac gluten sensitivity identifies, at a bare minimum, between 7% and 12% of the American population that has not adapted to cereal grain consumption. While a few research projects suggest that molecular mimicry and the opioids from cereal grains contribute to autoimmunity, obesity, type 2 diabetes and cardio-vascular disease, current research does not provide any clear sense of how many cases or to what degree these health conditions are driven by gluten consumption. We know that foods derived from cereal grains are often laced with refined sugar, but the insulin stimulating properties of gluten alone are such that their role in these conditions cannot, reasonably, be denied. I feel vindicated by these many experts who decry the folly in humanity's embrace of the European grains. I wonder how long it will take for this information to filter into, and be acknowledged by, those who claim that science has led them to advocate cereal grain consumption for everyone without celiac disease and, more recently, non celiac gluten sensitivity? Sources: Cordain, Loren. Simopoulos AP (ed): Evolutionary Aspects of Nutrition and Health. Diet, Exercise, Genetics and Chronic Disease. World Rev Nutr Diet. Basel, Karger, 1999, vol 84, pp 19–73 http://thepaleodiet.com/wp-content/uploads/2012/08/Cerealgrainhumanitydoublesword.pdf Jared Diamond, "The Worst Mistake in the History of the Human Race," Discover Magazine, May 1987, pp. 64-66. http://www.ditext.com/diamond/mistake.html Eaton SB, Konner M, Shostak M. Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med. 1988 Apr;84(4):739-49. Voegtlin, Walter L. (1975). The stone age diet: Based on in-depth studies of human ecology and the diet of man. Vantage Press. ISBN 0-533-01314-3 George, A. " The Paleo Diet Is a Paleo Fantasy" New Scientist. April 7, 2013. http://www.slate.com/articles/health_and_science/new_scientist/2013/04/marlene_zuk_s_paleofantasy_book_diets_and_exercise_based_on_ancient_humans.single.html Oppenheimer, Stephen. The Real Eve: Modern Man's Journey Out of Africa. Basic Books, NY, NY. 2004 Fagan, Brian. Cro-Magnon: How the Ice Age Gave Birth to the First Modern Humans. Bloomsbury Press, New York. 2011 http://www.utep.edu/leb/Pleistnm/sites/pendejocave.htm Brody, Hugh. The Other Side of Eden: Hunters, Farmers and the Shaping of the World. Douglas 7 McIntyre Ltd., Vancouver, B.C., Canada. 2000 Lewin, Roger. A Revolution of Ideas in Agricultural Origins. Science. vol 240, May 20, 1988

Celiac.com 01/24/2017 - Diabetes is a condition in which blood glucose rises high enough to cause: damage to blood vessel walls, neurological injury, vision loss, and a host of other maladies. Most currently recognized cases of diabetes fall into one of two categories which are identified as type 1 and type 2 diabetes. While these two types of diabetes share many symptoms, the underlying causes are, in most cases, quite distinct, although there is also some overlap which will be explored shortly. There are also cases of gestational diabetes and some researchers are now suggesting that type 3 diabetes may be yet another entity that causes accelerating cell death in the brain, resulting dementia (1) but these latter two types of this condition are not included in the current discussion. All but one of these forms of diabetes involves cellular resistance to the action of insulin, although there is some gray area between type 1 and type 2 diabetes. Type 1 diabetes is the result of an autoimmune attack on a specific group of pancreatic cells called islets of Langerhans. These are the cells that produce insulin, a hormone that moves glucose out of the bloodstream and into various cells. About 14% of type 2 diabetics are also thought to experience a late-onset, slowly developing damage to pancreatic islet cells, which results in reduced insulin production in combination with their insulin resistance(2). This may be caused by autoimmunity, similar to type 1 diabetes, or it may be damage induced by other factors. Nonetheless, while type 2 diabetes can often be controlled either during weight loss or by reduced carbohydrate consumption alone, type 1 diabetes is not typically viewed as a condition that can be remedied by a change in eating habits. Yet there are some hints in the literature suggesting that dietary interventions may be therapeutically useful, especially if begun early enough in the disease process. Researchers Amanda MacFarlane and Fraser Scott report that there are several environmental factors, including specific foods, as well as viral, bacterial, and chemical agents that have been hypothesized to incite an autoimmune attack on the islet cells (2). They also report that about half of the animals that develop type 1 diabetes are mounting an immune response to wheat, which may also be involved in the attack on the insulin producing cells of the pancreas by either or both of two pathways they outline (2, 3). These hypothesized biological processes are identified as molecular mimicry or bystander activation and cell death. While these authors favor bystander activation, either or both of these pathways may lead to an autoimmune attack on pancreatic islet cells. Regardless of the specific biological route, type 1 diabetes can be induced in a significant portion of genetically susceptible rats and mice, simply by feeding them a diet dominated by wheat gluten. Further, the severity of their disease varies directly with the proportion of wheat gluten in the diet (2). These investigators go on to say that "These similarities between coeliac disease in humans and diabetes in BB rats, NOD mice and type 1 diabetic patients are consistent with the idea that wheat is involved in diabetes pathogenesis, possibly by inducing a subclinical, gut inflammation in many individuals that develop this form of diabetes" (2). They go on to report that: "Our data suggest that dietary modulation has effects at two (or more) levels: At the target cells before classic insulitis, changing the growth pattern of insulin-producing cells, enhancing islet mass and changing metabolism and insulin reserves . Dampening an ongoing inflammatory condition in the gut." (2) Scott's work (4, 5) along with investigations conducted by several groups of his colleagues (6-10) indicate that significant numbers of diabetes patients show immune reactions to the prolamins which are storage proteins in wheat, rye, and barley. Further, investigators have long understood that there is significant overlap between celiac disease and type 1 diabetes, with estimates ranging between 5% and 12% in each disease group (2, 11). MacFarlane and Scott point out that 33% to 40% of patients with type 1 diabetes show transglutaminase autoantibodies which are similar to those found in celiac patients but usually at lower levels (2). Low concordance rates in monozygotic (identical) twins also suggest that environmental factors play a large role in causing type 1 diabetes (2). Again, the most compelling evidence indicates that dietary consumption of wheat gluten and similar prolamins is an important factor in the autoimmune attack that destroys the pancreatic capacity to produce insulin, in genetically susceptible individuals. Indirect support for this perspective is offered by animal research published in July of 2011. It shows that gamma-Aminobutryic acid (GABA) supplements not only inhibit the autoimmune attack on islet cells, GABA also incites regeneration of insulin producing cells (12). GABA is a non-toxic substance that is produced by the beta cells of the pancreas (13). It plays an inhibitory role throughout the nervous system which may be significant when taken in conjunction with Rodney Ford's identification of gluten as the agent which, directly and indirectly, induces neurological damage in those with celiac disease and those with non-celiac gluten sensitivity. One pathway Ford identifies is gluten-induced neuronal excitation leading to cellular self-destruction. In light of Ford's hypothesis, the inhibitory role of GABA on neuronal tissues, both at and near synapses, offers an inviting new window for envisioning the process that incites, and therefore may reverse, type 1 diabetes. Clearly there is considerable cause to suspect gluten grain consumption as an important factor in the onset and perpetuation of many cases of type 1 diabetes. While genetically coded HLA markers predispose to the disease, and a number of other environmental factors may play a role in its pathogenesis, prolamins from wheat and its close relatives are clearly a frequent and important contributor to this life-long condition in which exogenous insulin (injection with hypodermic needles) is necessary for maintaining optimal health (12) while living with this malady. However, given the insights offered by the above, the following case history may offer insights that might otherwise incite only scepticism. MacFarlane and Scott suggest the following: "One approach to achieving this [prevention] is to understand and modify the environmental factors that induce disease or equip those at risk with better means of avoiding or handling these agents"(2). Case Study: On January 18, 2008, three year old K and her anxious mother were taken to a hospital emergency department in Gilbert, AZ, where the attending physician concluded that the child had experienced a febrile seizure of about 5 minutes' duration. At examination, she had a 102.5 degree temperature. In addition to fevers, K complained of abdominal pain and showed abdominal bloating. During this examination of K, she vomited. Laboratory tests showed elevated glucose (133 mg/dl) and an elevated white blood cell count (19,000). Tylenol was used to bring K's temperature down and she was discharged with instructions for the parents to administer more Tylenol as needed, and to follow up with her regular health care provider within two days. By February 29, K experienced more fevers, ranging between 101 and 104, intermittently over 24 hours. Every four hours, when the effects of the previous dose of Tylenol wore off, the fever would, again, spike to 103-104. K was taken to see her regular physician the following day and urinalysis revealed ketone bodies. K and her parents were then sent to the emergency department of Banner Children's Hospital. At the hospital, testing showed elevated urinary ketone bodies in the Large category, and blood showed elevated glucose at 193 mg/dL. Type 1 diabetes was diagnosed and K was admitted to hospital where she stayed for four days. Her condition was stabilized with ½ unit of Novalog and 4 units of Lantus. Meanwhile parents were educated about type 1 diabetes, insulin measurement and injection. They were taught to inject 1 unit of insulin for every 20 grams of carbohydrates consumed (20:1 ratio). K's parents repeatedly wondered, in the presence of the diagnosing endocrinologist, just how much insulin K was producing and how many carbohydrates a thirty pound child needed to be healthy? * K's father has a history of joint pain when consuming gluten grains. K was still experiencing abdominal bloating and because of the overlap between type 1 diabetes and celiac disease (2) serum IgA antibody tests were undertaken and both transglutaminase and gliadin antibody tests were negative. However, the parents observed that variations in the types of food K ate seemed to have a greater impact on blood glucose than a specific food's putative sugar content. In keeping with their observations that different foods, despite their equal sugar content, produced different blood glucose results, the father's history of joint pain when eating gluten, K's abdominal bloating, and the widely documented connection between gluten grains and type 1 diabetes, these foods and several others were eliminated from her diet. K's parents were quickly able to adjust the insulin therapy to a 40:1 ratio while K typically maintained a blood glucose range of between 80 and 95 mg/dl, which is well within the reference range for a healthy, non-diabetic person. In fact, this is a far narrower range than is prescribed by the American Diabetes Association which is 70-120 mg/dl for diabetic patients. K's family continued to target and achieve the 80-95 mg/dl range. After a few months of lower than normal blood sugars, still on insulin therapy, with the carbohydrate ratio now 40/1, the parents sought permission from the endocrinologist to take K off insulin completely, on the condition that her blood sugar continued within the normal range of 85-95 mg/dl. This was monitored on a daily basis. The first 24 hours were a success and another day was granted. After six months of following a strict and intense food therapy diet for K, the family started reintroducing foods. Some foods were reintroduced without a rise in blood sugar. She was also able to eat a larger amount of carbohydrate each meal with the same blood sugar control. Clearly, the pancreas was producing increasing quantities of insulin. On August 21, 2008, six months into this intensive and individualized food therapy, the patient's blood test results indicated a regeneration of the pancreas and a complete reversal of her type 1 diabetes. Her A1C was 4.8, well within the normal range for a non-diabetic person. Today, more than three years later, the patient is still insulin free and is using food therapy alone to maintain healthy and normal glucose control. Signs of pancreatic inflammation were also absent. Each of these findings echo MacFarlane and Scott on the issue of dietary intervention in animal studies. The intensive food therapy has now been replaced with a maintenance program. The variety of foods the patient can eat is vast. However, grain and casein continue to be avoided. It appears that, in this case, these foods may have contributed to K's Type 1 diabetes. It may also be that the underlying cause of the fever K experienced early in this process was a factor in the onset of her type 1diabetes, and the transient nature of this fever, and its cause, may be at the root of her recovery from this ailment. Nonetheless, given the many converging research findings indicting grains and dairy proteins, along with K's suggestive signs and symptoms, and her father's reactions to gluten, continued avoidance of these foods seems a more likely explanation. Thoughtful readers may also wonder just how much insulin K was producing, at the time of her diagnosis, and just how many carbohydrates a thirty pound child needs to be healthy? It may be that GABA supplements and other chemical miracles will be unnecessary for large numbers of children who suffer from type 1 diabetes. Perhaps early diagnosis and permanent dietary adjustments will be what is needed to facilitate complete recovery for many, perhaps most, children afflicted by this insidious condition. Perhaps this case history will provide the necessary impetus to encourage undertaking controlled studies of dietary factors early in the disease process of type 1 diabetes. * While there are no carbohydrates that are essential to good health, there are essential amino acids and essential fats. Sources: de la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol. 2008 Nov;2(6):1101-13. http://www.medicine.uottawa.ca/Students/MD/BlockOrientation/assets/documents/e_inf_week05.pdf http://www.elements4health.com/type-1-diabetes-patients-have-immune-response-to-wheat-proteins.html Scott FW, Sarwar G, Cloutier HE. Diabetogenicity of various protein sources in the diet of the diabetes-prone BB rat. Adv Exp Med Biol 1988; 246: 277–85. Scott F. Dietary initiators and modifiers of BB rat diabetes. In:Shafrir E, Renold AE, eds. Frontiers in Diabetes Research:Lessons from Animal Diabetes. London: Libbey, 1988: 34–9. Hoorfar J, Buschard K, Dagnaes-Hansen F. Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Br J Nutr 1993; 69: 597–607. Funda DP, Kaas A, Bock T, Tlaskalova-Hogenov H, Buschard K. Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev 1999; 15: 323–7. Bao F, Yu L, Babu S et al. One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies. J Autoimmun 1999; 13:143–8. Lampasona V, Bonfanti R, Bazzigaluppi E et al. Antibodies to tissue transglutaminase C in type I diabetes. Diabetologia 1999; 42: 1195–8. Pocecco M, Ventura A. Coeliac disease and insulin-dependent diabetes mellitus: a causal association? Acta Paediatr 1995; 84: 1432–3. Hansen D, Brock-Jacobsen B, Lund E, Bjørn C, Hansen LP, Nielsen C, Fenger C, Lillevang ST, Husby S. Clinical Benefit of a Gluten-Free Diet in Type 1 Diabetic Children With Screening-Detected Celiac Disease A population-based screening study with 2 years' follow-up Diabetes Care 29:2452-2456, 2006 Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes.Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11692-7. Epub 2011 Jun 27. Bouzane B, Postmedia News June 28, 2011 Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.

Celiac.com 12/21/2016 - I have previously criticized the use of a single blind test protocol for a gluten-free diet. In past issues of The Journal of Gluten Sensitivity I have also been critical of some double blind research protocols for investigating dietary variables for a variety of reasons not relevant to the current topic. However, there are good reasons that the double blind protocol continues to be favored, especially among medical researchers. Single blind testing is where the research subjects are not aware of the intervention being used whereas, in a double blind test, both the subjects and the researchers are kept in the dark about the intervention until the end of the trial. Sometimes that requires the use of placebos. In other protocols, it involves masking the intervention. The primary merit of double blind, over single blind tests is that the former eliminates something called "confirmation bias". Single blind testing was first developed because patients' and other experimental subjects' expectations were thought to skew results. Under some circumstances, this problem is called a placebo effect. We can see the placebo effect in action when research subjects are split into two groups. One group is given the medical treatment or drug being investigated, while the other group is given a placebo. This placebo may be a sugar pill or some other substance or treatment that should have no significant or measurable medical impact on the subject. The placebo is given to subjects/patients as if it could provide medicinal properties. Because the patient expects to feel better with this placebo intervention, some subjects do start feeling better. That's the placebo effect. Single blind testing does reduce this problem. Especially for drug treatments, blinding subjects does make sense. However, another confounding variable was soon recognized as arising from single blind tests. It turns out that, in addition to patients' reporting health benefits from sugar pills and other placebos, the physicians and other scientists were skewing the results in another fashion. This is where confirmation bias comes in. The term identifies a situation where researchers miss signs of a problem with gluten. (A fascinating book titled The Structure of Scientific Revolutions (1962), by Thomas Kuhn provides detailed explanations of this phenomenon in his descriptions of several experiments that clearly show this tendency.) To some extent we all have a tendency to confirm our expectations in what we see. This confirmation bias can have an impact on research results in two ways. First, it can lead researchers who are interacting with the test subjects to communicate, either through body language, or verbal "slips" to indicate that they expect a given patient to improve following the intervention or drug being investigated, leading to more of the placebo effect. It can also lead researchers to interpret their results in ways that confirm what they expected to see, rather than in a more objective light. Placebo effect and confirmation bias can be nullified in a double blind study when researchers subtract the portion of the placebo group who are feeling better on the placebo from the number who report feeling better in the experimental group. (The experimental group is the group that was given the actual drug or medical treatment under investigation.) This simple arithmetic eliminates the number of people in the experimental group who were likely to report feeling better even though they were only given the placebo. The remaining number of experimental subjects who report feeling better after the medical intervention are thought to reflect the number of people who actually experience a benefit induced by the treatment. My concern with physicians running single blind tests on patients who believe that they feel healthier on a gluten-free diet is that the physician is likely to see what she/he expects to see (confirmation bias). So skeptical physicians who would request that their patients do a gluten challenge in the form of a single blind test are most likely to see what they expect to see. This may be why more than 95% of people with celiac disease remain undiagnosed in the USA. Confirmation bias seems to afflict many physicians practicing in the USA. Judging from my years of exchanging correspondence with gluten sensitive people from all over the world, similar dynamics seem to be at work, to varying degrees, in many other countries as well. A protocol that requires the patient to undergo a gluten challenge in a single blind test format is offensive in its implications. It denies the limitations of the very physicians who would be charged with conducting these tests, making observations, and treating patients accordingly. I sincerely believe that physicians are intelligent, hard-working individuals who have pursued a career that is dedicated to helping people. I also believe that they are equally fallible in their judgments and pre-conceived notions about others, especially when it comes to dietary interventions. If physicians cannot accept the observations of their patients, why should their patients be willing to accept their physicians' observations and conclusions? Who has more at stake in this relationship? And who is in a better position to observe even very subtle responses to gluten ingestion? As a culture, we seem to have lost track of why we consult physicians. Although we are all subject to confirmation bias, most of us are not seeking insulting instructions that disparage our honesty, integrity and reliability. When I visit my family physician, I want her to act as my guide to the science she is familiar with, and render the best guidance she can offer based on her expertise and paying careful attention to what I report. If my problem is beyond her knowledge or experience, I expect to be referred to a specialist in my area of concern. I usually consult her, on a collaborative level, when she has some relevant expertise that will compliment my own expertise. I can not foresee a set of circumstances in which I would allow her to conduct a single blind trial on me. I do not accept the premise that she is less susceptible to her confirmation bias than I am to the placebo effect. Thus, my expectation of my physician is that we work together to solve any health problems that arise. I must say that both my current physician, whom I have been seeing for the last five years, and my previous physician who worked with me for the previous eleven years, have consistently exceeded my expectations. In both cases, they seem very happy that I am trying to take responsibility for my own health care and that I consider their advice to be a resource rather than the final word in the matter. I'm very grateful for these relationships, as they, and the gluten-free, dairy-free, diet, along with reduced soy and refined sugar consumption, have helped me achieve a much better state of health than I previously considered possible.

Celiac.com 11/10/2016 - So far, 2014 has been a challenging new year for me. I was reminded of some events that happened almost fifty years ago. Based on that reminder, I resolved to contact a former girlfriend, both to suggest that she get testing for celiac disease, and to apologize for some insensitive things I said and did when I was 17. She was a year younger than me and one grade behind me in school. She was very slender and exceedingly self-conscious about having what she called "a chest like a boy". (She may have been experiencing delayed development, as is sometimes seen in celiac disease.) Every new place we visited, she went looking for the washroom as soon as she could. Movie theatres, restaurants, libraries, everywhere we went, she found the washroom first. She even did that the first time she was at my mother's house, which occasioned an uncharitable comment from my mom. Pat was also troubled by some microscopic hair that was growing on her upper lip. It sounds silly now, but these things were important to her at the time. I remember telling her that nobody could see her "moustache" without a magnifying glass. Nonetheless, she put Nair on it and, for at least one day, had the brightest red upper lip I have ever seen. She said it was too sore to put makeup on, so it really drew a lot of unwanted attention. Until meeting my wife, I never knew anyone who was as honest about who she was. I regret that I didn't appreciate her as much as I should have, but that was partly due to my age. Time passed, way led onto way, and life happened. Forty nine years later, there I was, looking for her on Facebook and other social media. I tracked her through old phone numbers, family members, and I even searched the title on her parents' home. I was full of excitement about re-connecting with my old friend, a person with whom I had shared those last innocent days of adolescence. Our friendship had been cut short because her dad was transferred to a city more than 600 miles away, and she was annoyed with me because I had said and done some insensitive things. We never even wrote to each other. I used to talk about her with my students, explaining our mutual fascination with literature. I thought about her often, but never, until this year, considered contacting her. After about a month of searching, I eventually found her. Much to my dismay, I was almost a year too late. She had passed away on March 10th of 2013, at the age of 64. At the time of her death, she was in the process of being evaluated for Parkinson's disease. She was at home when she experienced her last, massive seizure, which resulted in brain death. Both of her daughters are heartbroken over Pat's sudden, unexpected passing. Already a widow, Pat had left this world before I took the time and made the effort to be in touch with her again. I was filled with sadness, disappointment, and regret when I first reached one of her daughters and confirmed that she was the person I had known. I still wonder, if I had gotten in touch a decade earlier, would she still be alive? Would a gluten-free diet have helped her? I'll never know, but the relevant literature does seem to suggest that a gluten-free diet may have helped (1, 2). Then, a week or so ago, I received an email from a concerned mom. Her athletic, teen-aged son was recovering from a brain concussion he had sustained. His friends who had sustained similar concussions, at other times, reported having recovered more quickly. His mom began to wonder if her son's slow recovery could be the result of his celiac disease, despite more than a decade of strict compliance with the diet. I didn't know. I could only offer the suggestions that he try daily supplementation with medium chain triglycerides, and a ketogenic diet, as they seem to have stopped my life-long tremors. I also suggested that he try avoiding dairy and soy as well, based on research I did 14 years ago for my grandson. This concerned mom also mentioned, "I generally find doctors are dismissive of the idea that celiac is linked to any issues outside the digestive tract, unless it's malnutrition-related, and they tend to think everything should be hunky-dory if you just follow the gluten-free diet." She went on to say that "It gets kind of old being thought of as the silly, overprotective mom." Neurological researchers have long known about a correlation between a variety of neurological ailments and gluten sensitivity, with or without celiac disease (3). We also know that neurological symptoms are commonly found among more than half of patients with celiac disease (4). Also, despite modern diagnostic protocols and technology, we are still seeing some overlap between celiac disease and both amyotrophic lateral sclerosis (5) and multiple sclerosis (6) as well as other neurological illnesses. For instance, the increased presence of the gene named Parkinson's disease 7 (PARK7) has been found in the duodenal mucosa of untreated children with celiac disease and may be implicated in the alteration of the permeability of their intestinal barriers (7). This further suggests an important link between gluten sensitivity and Parkinson's disease. This gene may predispose to the appearance of this most distressing disease later in life. Many people with celiac disease continue to experience neurological symptoms, despite compliance with a gluten-free diet. This may suggest that the neurodegenerative dynamics, once initiated by gluten ingestion, may continue, either in the absence of gluten or in response to trace amounts of gluten (10). I also started to wonder if the cellular and immune system clean-up processes that follow brain injuries might initiate some of the same damaging autoimmune processes in the brain? They might also occur in response to other dietary factors which may trigger autoimmune dynamics that mimic reactions to gluten, or maybe there is some other, unknown factor that triggers the brain damage. One research group on the leading edge of the investigation of gluten sensitivity in relation to neurological illnesses reports that, "Incomplete elimination of gluten from the diet may be enough to abolish gastrointestinal symptoms with recovery of the small bowel mucosa but is insufficient to arrest the state of heightened immunological responsiveness resulting in neuronal injury" (10). So, when it comes to even tiny amounts of gluten, they may be enough to perpetuate gluten induced neurological illnesses. There may also an agent in the environment that is causing a cross reaction. This area really needs more investigation, as baby boomers threaten alarmingly increased rates of all forms of dementia. We already know that people with celiac disease are at much greater risk of developing neurological diseases than the general population (13). These ailments range from headaches to learning disabilities to movement disorders to tic disorders, to seizures, to sensory disorders (4) and many who have non-celiac gluten sensitivity also experience a high rate of neurological disease (3). Does that also mean that young athletes with celiac disease will take longer to recover from head injuries? Does it also mean, given the slow acceptance of gluten as a factor in many common neurological illnesses (11) that people like my former high school flame will never be told about the neuro-protective benefits of a gluten-free diet or a ketogenic diet? Surely, resistance to the well established data showing neurological manifestations of gluten sensitivity as a scientific fact (12) is more emotional than rational. A gluten-free diet and/or a ketogenic diet should be offered to those people regardless of whether their neurologist is either resistant to, or not staying current with, his/her professional literature. But they cannot offer what they do not know or have developed some bias against. Dr. David Perlmutter has done an excellent job of getting the word out to the general public, with his recent book titled Grain Brain, but there is much more work to do. People who are gluten sensitive, and are therefore at greater risk of developing neurological disease, might be well advised to look carefully at the benefits of a high fat, ketogenic diet, and the benefits of supplementing with medium chain triglycerides and Omega 3 fatty acids (14). Equally, they might be well advised to avoid the pro-inflammatory omega 6 and omega 9 fatty acids, as well as limiting the amounts of polyunsaturated fats they eat, which are also pro-inflammatory 14). I find that I feel my best when I am in mild, diet-induced ketosis (about 15 mg/dl as measured in morning urine, with Ketostix, which are inexpensive and available at most drug stores). There are a number of good books that explore the fine points of a high fat, ketogenic diet. These include The Art and Science of Low Carbohydrate Living by Volek and Phinney, The Ketogenic Diet by Lyle McDonald, and many others. Finally, when considering a gluten-free diet for neurological ailments, it is important to recognize that 20 parts per million may be far too much gluten to consume. The maximum threshold to qualify as gluten-free under the United Nations Codex Alimentarius Commission and many other regulatory agencies, including the FDA, is 20 parts per million. Without further research, especially in the field of neurology and gluten sensitivity, we will never know what, if any, levels of gluten are safe to consume. Regardless of the nature of your neurological ailment, whether it is Parkinson's disease, or seizures, or multiple sclerosis, or amyotrophic lateral sclerosis, or brain cancer, or almost any other kind of cancer (15), or even if you are just slow recovering from a neurological injury, the positive results of dietary interventions might offer you a whole new lease on life. Sources: http://www.medscape.com/viewarticle/770593 Currie S, Hadjivassiliou M, Clark MJ, Sanders DS, Wilkinson ID, Griffiths PD, Hoggard N. Should we be ‘nervous' about coeliac disease? Brain abnormalities in patients with coeliac disease referred for neurological opinion. J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1216-21. Matheson NA. Letter: Food faddism. Am J Clin Nutr. 1975 Oct;28(10):1083. Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004 Jun;113(6):1672-6. Brown KJ, Jewells V, Herfarth H, Castillo M, White matter lesions suggestive of amyotrophic lateral sclerosis attributed to celiac disease. AJNR Am J Neuroradiol. 2010 May;31(5):880-1 Batur-Caglayan HZ, Irkec C, Yildirim-Capraz I, Atalay-Akyurek N, Dumlu S. A case of multiple sclerosis and celiac disease. Case Rep Neurol Med. 2013;2013:576921. Vörös P, Sziksz E, Himer L, Onody A, Pap D, Frivolt K, Szebeni B, Lippai R, GyÅ‘rffy H, Fekete A, Brandt F, Molnár K, Veres G, Arató A, Tulassay T, Vannay A. Expression of PARK7 is increased in celiac disease. Virchows Arch. 2013 Sep;463(3):401-8. Hadjivassiliou M, Grünewald RA, Lawden M, Davies-Jones GA, Powell T, Smith CM. Headache and CNS white matter abnormalities associated with gluten sensitivity. Neurology. 2001 Feb 13;56(3):385-8. Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D. Gluten sensitivity: from gut to brain. Lancet Neurol. 2010 Mar;9(3):318-30 Hadjivassiliou M, Grünewald RA, Davies-Jones GA. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry. 2002 May;72(5):560-3. Tengah P, AJ Wills. Questions and Answers About the Neurology of Gluten Sensitivity. Pract Neurol 2003;3:354-357 Hadjivassiliou M, Grünewald R. The Neurology of Gluten Sensitivity: science Vs conviction. Pract Neurol 2004;3:4, 124-126. Hadjivassiliou M, Grünewald R. Gluten sensitivity as a neurological illness. Neurol Neurosurg Psychiatry. May 2002; 72(5): 560–563. http://www.omegascience.org/product_ingredients/coconut_oil.aspx Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013 Aug;67(8):789-96

Celiac.com 10/04/2016 - Several years ago, Dr. Levinovitz contacted me by telephone, asking if he could interview me then, and in subsequent calls, for a book he was writing about gluten consumption. Assuming he, as an academic employed by a university, had an open mind, I was happy to share my own anti-gluten paradigm and the sources of my angst about these harmful foods. Dr. Levinovitz mentioned that he was involved in religious studies, but since I had earned my doctorate in the field of Education, I didn't feel any particular concern about answering his questions or his qualifications to write about gluten. As the interviews proceeded (he called back for further information and/or clarification at least once more but I think it was twice) I was most anxious to help with his project as I see gluten as a food source that fosters a great deal of illness. Because he used a poor, static laden Internet phone (VOIP) for these interviews, I missed much of what he was saying, but when I got the gist of his questions, I did my best to answer as fully and honestly as I could. However, when I mentioned that several of my former students had benefitted academically from excluding gluten from their diets, he wanted their names and contact information. That is when I began to feel uneasy. I told him that I would get back to him with that information if my former students were willing to be interviewed. After some thought, I decided that I would not expose these people to Dr. Levinovitz's questions without their prior permission and without a clear understanding of what he was trying to accomplish. He was quite forthcoming when I asked for some specifics about his book project. He said that he planned to attack the whole gluten-free "fad". He said that he saw it as silly and unscientific. Please remember that I'm paraphrasing something that was said several years ago, over a poor telephone connection, so I am open to correction on the specific words he used, although his meaning was crystal clear. I realized that he was determined to undermine much of the work I had done to sound the alarm about the human health hazards posed by gluten consumption. I speculated aloud that he had used the VOIP to make it more difficult for me to detect his duplicity when not telling me what his book project was about during that first call when he asked to interview me. I ended the call and did not respond to the two phone messages he subsequently left for me. He hadn't lied. He just hadn't told the whole truth. He claims, in his book, that exaggeration or distortion is a lie when it comes to science (p. 18). What is it when the distortion is aimed at getting an interview? Is that a lie too? I don't know. On the other hand, readers of his book will not suffer any confusion about its author's bias. The title gives adequate forewarning. He begins with the anti-MSG movement, which he describes in detail, beginning in 1968 and extending to a 2013 edition of a reference book where MSG is exonerated as a harmful additive, except in "rare" cases. The implication is clear. Americans condemned and avoided this Japanese flavor enhance for a period of 45 years without what Dr. Levinovitz considers to be good reason. Perhaps some Americans continue to avoid MSG. Dr. Levinovitz says that "Today, food allergy experts believe the overwhelming majority of reactions to MSG are psychological, not physiological." (1 p. 4) I saw this type of statement repeatedly when reading his book. Dr. Levinovitz makes sweeping generalizations for experts in "food allergy" and other such specialist practitioners without any apparent desire to provide a source for these statements of opinion. If his approach is correct, my training has me suffering under the faulty illusion that citing sources is a very important part of science. But "what," you may ask, "does MSG have to do with gluten?" Well, it seems that Dr. Levinovitz wants us to conclude that the anti-MSG fad is the same as the shift away from eating gluten grains. He also tells his readers a story about Horace Fletcher and his "theory of mastication," in which a low protein diet is consumed, chewing the food hundreds of times. This, according to Levinovitz, was what led Fletcher to make claims of weight loss and improved health. Levinovitz names several prominent individuals who followed Fletcher's prescription. Then, Dr. Levinovitz discusses epidemiology. Quoting an authority on the subject, who attributes the causal connection of lung cancer to smoking to this type of study. This authority also states that it is exceedingly difficult to establish "credible linkages" in these studies. There is a very good reason for that. Epidemiology may have pointed researchers at smoking as a candidate for causing lung cancer, but this kind of study cannot be used to establish causal relationships. That approach to dietary research is a major source of the many dietary misconceptions that Dr. Levinovitz decries. Levinovitz fails to explain just what epidemiology is. It is the study of correlations. During my first year of university, in the 1960s, I was taught that "correlation ‰ causation". This means that simply because two things happen at the same time and place does not mean that they are linked in a causal relationship. For example, drowning deaths can be shown to rise and fall with ice cream sales, and victims of auto accidents usually wear white underwear. Does that mean that ice cream causes drowning deaths? Or that white underwear causes car accidents? Most of us recognize these as foolish claims. Yet that is the type of study that is at the very heart of the epidemiology or "science" that Dr. Levinovitz offers his readers under the heading of "What Real Experts Say about Gluten". He claims that "..... after I reveal the myths and superstitions behind fears of gluten, fat, sugar, and salt, you will be less afraid of these vilified foods - and food in general." (1 p.22) He also says that: "..... exaggeration in science is nothing less than a lie" (1 p. 18). Lest you begin to fear that Dr. Levinovitz becomes more timid as the book progresses, the first sub-heading in chapter two is "The Gluten Liars" (1 p. 23). He very briefly explains that there are about one percent of Americans, or about 3 million have celiac disease and only 17% have been diagnosed. Thus, 2 and 1/2 million Americans with active celiac disease are, as yet, undiagnosed. He goes on to say that "a slightly larger number of Americans" have a condition called non celiac gluten sensitivity, but says that this malady or set of maladies is a "matter of considerable debate". Yet some of the world's foremost experts in gluten sensitivity research (2, 3) publishing in a wide array of journals, have estimated that between 0.5% and 6% of Americans have non celiac gluten sensitivity (2, 3). They define it as a condition in which the person's innate immune system reacts to gluten and causes symptoms similar to those seen in celiac disease. Although it defines a range, it is a number that could stretch to something north of 18 million individuals in the USA alone. Where I come from, that's more than just "a slightly larger number". As Dr. Levinovitz repeatedly admonishes, 'remember, in science, any exaggeration is a lie' (1 p 18). But there's more. Levinovitz acknowledges celiac disease (he is unclear about the diagnostic criteria) and non celiac gluten sensitivity (NCGS) diagnosed on the basis of innate immune reactions to gluten, but he really is missing quite a few people who are gluten sensitive and would, and sometimes do, benefit from a gluten free diet. For instance, when IgG antibodies against gliadin are measured, they show that 10% to 12% of the population is mounting an identifiable, measurable immune reaction to gluten grains. However, these findings are non-specific, so they are not popular with doctrinaire writers such as Dr. Levinovitz. There is also a sub-group of people with schizophrenia who show an immune reaction to transglutaminase 6, another grain-related reaction that is also implicated in some brain disorders (3). Dr. Levinovitz presents both Grain Brain by David Perlmutter, M.D., and Wheat Belly, by William Davis, M.D., as irresponsible and alarmist. He then claims that reading such books can "make people physically and mentally ill". That claim falls well short of the scientific standards set by these two anti-grain authors. Levinovitz apparently doesn't see any harm in his sensationalist rhetoric attacking these two physicians for writing within their areas of specialty, yet Dr. Levinovitz's field quite far removed from the laboratory. There is something terribly incongruent here. But what, exactly, does Levinovitz have to teach us about science? He wants us to listen to statements he attributes to several authorities. For instance, he quotes Dr. Stefano Guandalini, as an expert in nutrition, saying that the gluten free diet "is not a healthier diet for those who don't need it" p. 29 and later in the same paragraph, Guandalini is quoted as saying "these people are following a fad, essentially" but the reader is left wondering if Dr. Guandalini defined who does or does not need the diet? Such selected quotes can sometimes fail to accurately communicate the meaning of the speaker's comment. When I conducted an Internet search for this statement along with Dr. Guandalini's name, I found an article from the New York Times in 2013. The statement appeared to be exactly the one Dr. Levinovitz attributed to Guandalini (p. 29). However, in the NYT article, Dr. Guandalini goes on to say "And that's my biased opinion." That small addition makes a huge difference to the meaning of Dr. Guandalini's statement. I had only read to page 29 of The Gluten Lie when I discovered this deception. And Dr. Levinovitz has the nerve to go around calling others liars? He deliberately withheld the part of Dr. Guandalini's statement that qualified it as his own bias. Dr. Levinovitz is certainly teaching us something about gluten lies, but his lessons may not carry the message he wants to disseminate. Levinovitz mentions me in his acknowledgements. At the time of the interview, I told him repeatedly that I had earned a doctoral degree in Education, shortly after the publication of Dangerous Grains. Yet he represents me as having gone back to university to get a Master's degree. I had already accomplished that well before the time Dangerous Grains was published. I now wonder if he made this omission intentionally, especially given his other "oversights" outlined above. He also mentions me at several points in his book. He does grant that undiagnosed celiac disease in connection with fibromyalgia, irritable bowel syndrome, diabetes, atopic eczema, and "other related conditions." p. 43 But he insists that only those with these conditions in the context of undiagnosed celiac disease will benefit from a gluten free diet. That's a pretty strong statement. It appears that Dr. Levinovitz has not experienced the challenges of getting appropriate testing for celiac disease, so he doesn't understand. Perhaps he missed all the twists and turns that researchers have experienced on their way to choosing villous atrophy as the defining characteristic of celiac disease? He may not realize that the "gold standard" intestinal biopsy was a retrofit added to the diagnostic criteria for celiac disease to counter the widespread resistance to Dr. Dicke's claim that dietary gluten was the cause of celiac disease. Gastroenterologists simply wouldn't believe that gluten could cause celiac disease without some rigorous testing that ultimately excluded many of the folks who were previously diagnosable with this ailment, many of whom died from it. So the diagnostic criteria began with a constellation of gut symptoms, then it relied on an intestinal biopsy showing damage that was reversed by a gluten free diet. Now, those who have the same symptoms, which also respond to a gluten free diet, and who might previously been diagnosed with celiac disease, are now thought to have non-celiac gluten sensitivity. The rude dismissal of Dr. Dickie's ideas by American gastroenterologists, signals a dynamic in science that was originally outlined by Thomas S. Kuhn, which Dr. Levinovitz seems to have overlooked. Kuhn's book, The Structure of Scientific Revolutions (7) outlines the process by which scientific revolutions take place. To oversimplify and paraphrase the process, it begins with scientists in that field ignoring the new idea. Then, as it gains credence, the scientists laugh at it. With gaining momentum, the new idea is vigorously opposed. Finally, once widespread acceptance has been gained, the scientists give the impression that they had known this all along. Apparently, Elaine Gottshall wrote two books about gluten. I haven't read them. I have heard of them, and some folks swear by them. I don't know about the quality of information she provides. But I know that the information I provided in Dangerous Grains was accurate and it was mostly drawn from the peer reviewed medical and scientific literature, and supported by personal anecdotes from individuals on the celiac listserv. Further, every one of the more than 200 correlations between celiac disease and other ailments was drawn directly from the peer reviewed medical literature. Yet, Dr. Levinovitz lumps us together, saying that "Gottshall and Hoggan deserve our sympathy....." and in the next paragraph: "Sure, they distort the evidence and overstate the dangers of gluten. But is there any harm in that? You bet there is" (1 p. 48). So what did I distort? What did I overstate? Does he base his refutation of our ideas on science? His evidence looks a lot less scientific to me. For instance, he claims that "rumors of illness can make you sick" (1 p.50). So it isn't much of a stretch for him to depict specialist physicians such as William Davis, MD, David Perlmutter, MD, and myself (not a physician) as purveyors of illness. Dr. Levinovitz's "science" is made up of the personal bias of Dr. Guandalini, as quoted in the New York Times, gossip from an endocrinologist, more personal opinions from scientists, consensus opinions, and even some opinion statements published in medical journals. For instance, he quotes Jennifer Thomas, a professor of psychology at Harvard Medical School as saying "There are no studies, but anecdotally we see this all the time". She is then quoted as saying "Of course most of my patients are reading these types of books and it definitely concerns me. People can't typically stick to these rigid diets" (1 p. 54). So, if there aren't any studies are we supposed to accept her pronouncements instead? And what harm do these rigid diets do if people can't stick to them? Dr. Thomas does grant that "Eating disorders have been around, with or without these food fads, But I still believe that these diets can be a gateway to an eating disorder, and that they can help you maintain it" (1 p. 55). If there aren't any studies, what does she base this belief on? Isn't this the very heart of Levinovitz's argument? Doesn't he say that we should use science, not personal beliefs, to inform our views about diet? Then Dr. Levinovitz attacks Dr. Robert Lustig, MD, an endocrinologist. Levinovitz quotes, in his chapter about sugar, gossip from another, nameless endocrinologist who calls Lustig "extreme and opinionated" (1 p.94). Perhaps he is. I don't know Dr. Lustig. However, I do know that Dr. Levinovitz has presented this gossip as "evidence" to further his attack on a group of not just physicians, but specialist physicians who have conducted studies and have done extensive work in their specialty fields. Levinovitz relies primarily on epidemiological studies (the ones that can be used to blame drowning on ice cream sales) expressions of personal bias, published opinion statements, and consensus opinions. I believe that Dr. Levinovitz should attack any idea that he believes to be faulty. I believe that he is entitled to believe whatever he believes and shout it from the rooftops if he wishes. But I hope that his readers recognize that he needs more than personal opinions, gossip, sweeping generalizations, and the hyperbole he accuses others of wielding to effectively counter the work of dedicated people who have found answers for themselves and are trying to share them with others. His attack on salt misses the more important point that we should be consuming sea salt, not just sodium chloride, to get the salt taste and the nutritional benefits of salt without the possible hazards of too much sodium for those who are sodium sensitive. Are there other deceptions in The Gluten Lie? Perhaps. Is there anything of value here? I don't know. I think that we all need to take more responsibility for our own health. I don't know how most of us can do it through reading peer reviewed research articles. They are available but difficult to read without a strong educational background, especially in statistics. Dr. Levinovitz seems like a nice enough fellow except for his tendency to do exactly what he criticizes me and others for... hyperbolizing and twisting the facts to fit his own narrative. He may even have good intentions. It's hard to say. Although his omissions are misleading, I'm not sure whether he really means to mislead, or if his personal bias is so powerful that he is confused about the difference between gossip and evidence; the difference between opinion and data, and; the difference between epidemiology and the various other forms of research designs that can be brought to bear on questions about human nutrition. Whatever the source of his views on the gluten free diet, there doesn't seem to be much actual scientific insight there. Sources: Levinovitz A. The Gluten Lie And other myths about what you eat. Regan Arts, 65 Bleeker Street, NY, NY 2015. Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013 Sep 26;5(10):3839-53. Lebwohl B, Ludvigsson JF, Green PH. Celiac disease and non-celiac gluten sensitivity. BMJ. 2015 Oct 5;351:h4347 Cascella NG, Santora D, Gregory P, Kelly DL, Fasano A, Eaton WW. increased prevalence of transglutaminase 6 antibodies in sera from schizophrenia patients. Schizophr Bull. 2013 Jul;39(4):867-71. Leonard MM, Vasagar B. US perspective on gluten-related diseases. Clin Exp Gastroenterol. 2014 Jan 24;7:25-37. http://well.blogs.nytimes.com/2013/02/04/gluten-free-whether-you-need-it-or-not/?_r=0 Kuhn Thomas S. The Structu5re of Scientific Revolutions. University of Chicago. 1962. Aziz I, Lewis NR, Hadjivassiliou M, et al. A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care. Eur J Gastroenterol Hepatol 2014;26:33-9.

Celiac.com 09/20/2016 - A surprising research report from Australia that explores non celiac gluten sensitivity (1) has given rise to a number of journalistic offerings that range between offensive and downright silly, while the reporters who wrote them appear to have somewhat compromised reading skills (3, 4). That is not to say that the research report is without problems. However, at least that report requires a close reading to identify its most troubling elements (1). Specifically, it suggests that patients who claim to feel better on a gluten free diet are either deluded or confused. The research implies that these patients may actually feel better because they have reduced their consumption of the starch in the gluten grains they are avoiding. That doesn't qualify as justification for either "fake" or "b$#@@#$$" (2, 3) as stated in the titles of the above journalistic offerings. The central thrust of the research report is that their investigations showed no evidence of benefits for patients who follow a gluten free diet due to the patients' belief that they are sensitive to gluten. These researchers could have said something indicating that a low FODMAPs diet might work better to help the person with NCGS [non celiac gluten sensitivity], as it not only eliminates gluten, but it also eliminates the associated starches, and a host of other sugars and starches that may also be contributing to their digestive symptoms. But they didn't. They said, instead, that they found ".....no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed on a low FODMAPs diet" (1). First, let's be clear about what the acronym FODMAP means. It stands for fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols. They are groups of sugars and starches that can induce or exacerbate gastrointestinal symptoms. But most of the gluten grains are made up of such starches (which are quickly turned to sugar as soon as we ingest them). The protein content is relatively small. Flours made from all forms of wheat and rye are high in FODMAPs (4). These people were not masquerading as having celiac disease. Neither were they trying to mislead anyone. They simply found that they feel better when avoiding gluten grains. So why the profanity and accusations embedded in the headlines of these articles (2, 3)? Avoidance of these foods will often help those with digestive problems. But this can happen for a variety of reasons. For instance, in a person with lactose intolerance, that individual has stopped or reduced production of the brush border enzymes (lactase) that are needed to break apart the two constituent sugars that form lactose (galactose and glucose) the sugar found in milk. The lactose molecule, a disaccharide (di = two and saccharide = sugar) is too large to be absorbed through the cells (enterocytes) that line the intestinal wall, and then into the bloodstream. While humans may not be able to digest these larger molecules of lactose, many of the bacteria that live in our intestines do so with little problem. These microscopic residents of our GI tracts multiply rapidly in the presence of so much available food. The enormous and growing numbers of these microbes, combined with their rapid digestion of lactose, produces considerable quantities of methane gas. The resulting symptoms we experience include gut pain, flatulence, smelly stools, and diarrhea. The low FODMAP diet excludes or limits oligosaccharides (from 3 to 6 units of simple sugars) disaccharides, and monosaccharides. It also excludes sugar alcohols and fermentable foods which can produce acids, gases and/or alcohols. Thus, only the gluten family of proteins should have been used to "challenge" the research subjects in this study (1) that is causing all the fuss. But that wasn't done. As may be very quickly ascertained from the interview with Sachin Rustgi, in the spring issue of this journal, there are many structural variations in each of the families of glutens and in specific gluten structures of each strain of each of the gluten-containing grains (5). In fact, Biesiekierski et al openly acknowledge that they purchased the refined gluten they used in their study from a different supplier than was used in a previous study, conducted by some of the same researchers, that confirmed the presence of non celiac gluten sensitivity (6). The later study used a form of gluten that may not have diverged much from the original, as the research group was able to state that the glutens from both studies were similar. However, they also acknowledged that they did not characterize the other, non-gluten components of the gluten they used, either. Thus, there are two possible confounding factors just in the gluten component used in this study. Small differences in the gluten protein structures may have been sufficient to cause the dramatically different result, or some added or missing non-gluten component of the gluten purchased may have caused the different result. We have no way of telling if, or to what extent, either of these factors may have played in the different findings. Without more careful work, neither could the Biesiekierski et al research group (1). It is not news to many of us who are gluten sensitive that differing families of gluten can produce differing symptoms and will sometimes elicit no symptoms at all. Some of us, including those with celiac disease, also react to corn and/or rice glutens, despite very clear medical statements that this is not part of our gluten-induced disease. So some of us have a more generalized reaction to gluten, while others are reacting only to sub-groups of gluten. Still others may cross react with similar proteins from other foods. Yet I can't help but believe that when such foods cause virtually identical digestive symptoms, there is some kind of connection to our problem with digesting and metabolizing gluten. Narrow medical definitions notwithstanding, each individual who struggles with this digestive issue must find her or his best answers through trial and error. Rigid journalists who genuflect at the altar of allopathic medicine will be unable to help us navigate this hazardous swamp. Neither will researchers with pre-conceived notions, who try to conduct dietary studies in a manner developed for pharmaceutical trials. For instance, Sachin Rustgi acknowledged that some biopsy-diagnosed celiacs will not react to a given strain of gluten grains while others with celiac disease will mount an immune reaction against the same strain (5). So each of us may be sensitized to different short strings of amino acids that form part of one or more of the family of gluten proteins or one or more of its sub-groups. This is wholly congruent with the science that explains and depicts selective antibody formation and activation. And that is only one part of the complexity here. Research that tries to formulate a strain of wheat that will not trigger gluten-induced illnesses must eliminate all sensitizing agents that each person with celiac disease may respond to with selective antibody production, while trying to retain the characteristics that produce the desired taste, smell, and nutrient content. Also, few of us with gluten issues need to be told that other foods can cause us to experience similar symptoms, or exacerbate, or vary, our symptoms. It can sometimes be a very confusing quagmire where it is difficult to identify the source of our symptoms. Further, Biesiekierski and colleagues overtly acknowledge that their focus on fatigue might have produced better insight into NCGS by revealing "why those who follow a GFD feel better" if they had asked their question differently (1). They also acknowledge the possibilities that gluten may only cause symptoms in combination with FODMAPs, or that FODMAPs cause gut problems which result in a gluten-induced loss of a sense of wellness. Their comments in this regard commendably reflect a willingness to look beyond the surface in this matter. I would go further, based on Scott Adams' interview of Sachin Rustgi (5) and assert that not all genetic strains of wheat gluten will elicit symptoms of celiac disease in a given individual with biopsy-proven celiac disease, never mind those with NCGS. So the researchers' failure to account for patient-to-patient variability, as is seen in celiac disease, along with specific wording of questions about symptoms are yet two more confounding factors in this study. Perhaps a mixture of several forms of gluten, bereft of contaminants, would have been a better choice for Biesiekierski's group. And other precautions in formulating their questions might have been useful. But there are many more problems with this report. Extensive Review by Expert Panel Dr. Carlo Catassi and a large group of widely recognized celiac experts published a comprehensive review of the medical literature on the topic of non-celiac gluten sensitivity in September of last year. Therein, they state that: " Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders" (7). Conversely, the Australian group led by Biesiekierski, asserts in their report which was published the previous month, that "Generally, NCGS is viewed as a defined illness, much like celiac disease, where gluten is the cause and trigger for symptoms" (6). At least one of these groups is confused about whether or not non celiac gluten sensitivity is well defined and well understood. As a student of this literature myself, I would assert that the consensus view is that this form of gluten sensitivity is far from being either well defined or well understood. In fact, there is still a great deal that is not understood even about celiac disease. Non celiac gluten sensitivity has only recently begun to be widely recognized in circles of gastrointestinal researchers. Further, the Biesiekierski group's extensive use of celiac-related antibody tests appears to ignore the widely held view that biomarkers are one of the great impediments to understanding non celiac gluten sensitivity. I would also add that while I have often argued for the use of IgG class anti-gliadin antibodies as a marker of many cases gluten sensitivity (also see Jean Duane's article in this issue) with or without symptoms, I have also maintained that there are many cases in which these antibodies are not found, yet the patient will frequently benefit from removal of gluten from her/his diet. A further weakness of the Biesiekierski et al study is that each of the intervals during which the low FODMAP diet (2 weeks), the gluten-containing diet at 16 grams/day (for 1 week), the low gluten diet at 2 grams /day (for 1 week), and the whey-containing diet 16 grams/day ( for 1 week) all ran for periods of time that were just too short to produce measurable serological findings in people with celiac disease. Even the washout period of 2 weeks was a minimal duration. Also, the three days allotted for the re-challenge trial was certainly too brief to produce meaningful results. Some celiac disease researchers report that only about 50% of their research subjects, all of whom had biopsy diagnosed celiac disease, produced celiac-associated antibodies after a two week challenge: "Antibody titres increased slightly from baseline to day 14 of GC [gluten challenge] but markedly by day 28" (8). This puts the one week duration of the Biesiekierski study into perspective - it is a choice that may have been directed at a specific research result. By day 28 of the Leffler et al study, 75% of the celiac patients showed markedly increased celiac associated antibodies. Thus, a single week of gluten challenge, as was used in the Biesiekierski et al study would be unlikely to produce any measureable changes in serum antibodies, even among people with celiac disease, who should reasonably be expected to react most quickly and strongly to gluten ingestion. Those with biopsy diagnosed celiac disease form the group that is currently thought to mount a much more serious and vigorous immune reaction to gluten than that seen in those with non celiac gluten sensitivity. While I do not necessarily agree with that perspective, it is wholly unreasonable to expect a reaction from a group of NCGS patients in one quarter of the time it is seen in only 75% of celiac patients. This Leffler et al study (8) also indicates that these celiac patients were reporting symptoms within three days of beginning the gluten challenge. Thus, it seems especially surprising that self-diagnosed gluten sensitivity would be such a contentious issue that would incite such rancorous responses as those mentioned earlier (2, 3). Because NCGS is not well characterized or understood, allowing only one week for gluten ingestion to cause symptoms, if that is our only measurement of gluten's impact on their health, might work with about three quarters of celiac patients, if antibodies are measured after 28 days, but how can anyone say that it is appropriate for NCGS? Further, the use of tests, especially serological antibodies, takes the focus off of symptoms and undermines the patients' reports of symptoms, suggesting that their claims of gluten sensitivity are either misguided or duplicitous. Meanwhile, the ~25% of those with biopsy diagnosed celiac disease had not yet produced celiac associated serum antibodies, even after four weeks of gluten challenge. We do not need physicians to tell us how we feel. While most of the limitations to the Biesiekierski et al study were actually mentioned in their report, those journalists who formulated articles and inflammatory titles that included the terms "fake" (2) and "b$#@@#$$" (3) seem to have missed reading those parts of this report. Further, they took such statements as "These data suggest that NCGS, as currently defined, might not be a discrete entity or that this entity might be confounded by FODMAP restriction" to mean that there is no such thing as NCGS. However, those of us with reading skills above the middle-school level will recognize that Biesiekierski and colleagues qualified their statement in several important ways, suggesting that FODMAP restriction could be a confounding variable or that the current definition of NCGS may need to be adjusted, or the possibility that the gluten they used may not have been appropriate. One must wonder whether these journalists are that challenged when it comes to reading? Or are they trying to raise readership? Perhaps their ads sell according to how many hits and responses their websites garner. Thus, it may make sense to offend groups that are likely to post responses to their site, as a strategy aimed at raising their advertising revenue. I can't see what other limitation or motivation there might be to so dramatize these research findings with little regard for what the researchers actually said. On another level, I hope that the field of Journalism has not become so crass that they don't bother to exercise even a modicum of critical thought when reading reports of research results. That, after all, is their function in democratic societies. They are supposed to offer insightful commentaries on current trends in politics, science, education, law enforcement, and various other facets of our democratic cultures. It is difficult to find thoughtfulness or insight in the terms "fake" and "b$#@@#$$". It is also difficult to see such reports being published when a retrospective study I was involved in remains unpublished. Perhaps that is due to the finding that the gluten free diet had a very positive impact on the behavior and scholastic performance of many children. The gluten sensitive community has come a long way, but many biased journalists, physicians, and researchers continue to resist the notion that gluten is a food that harms many people. Sources: Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology. 2013 Aug;145(2):320-8.e1-3. https://ca.shine.yahoo.com/gluten-intolerance-is-fake-093131285.html http://kitchenette.jezebel.com/gluten-sensitivity-is-apparently-b$#@@#$$-1577905069 http://stanfordhospital.org/digestivehealth/nutrition/DH-Low-FODMAP-Diet-Handout.pdf Adams S. Discussion with Assistant Resident Research Professor Sachin Rustgi on the Genetic Modification of Wheat to Make it Safe for Celiacs. Jrnl Glut Sens. 2014. Spring; 13 (2): 11-13. Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD,Shepherd SJ, Muir JG, Gibson PR. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011 Mar;106(3):508-514. Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013 Sep 26;5(10):3839-53. Leffler D, et al. (2013) Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut 62(7):996–1004.

Celiac.com 07/19/2016 - We know that celiac disease afflicts almost 1% of the general population (1). We also know that about 12% of the general population has non-celiac gluten sensitivity, as indicated by elevated IgG class anti-gliadin antibodies in their blood (2). Although elevated antibodies identified by this test are often dismissed as "non-specific", they are clear evidence that the immune system is mounting a reaction against the most common food in our western diet. It is also true that many people who produce these antibodies and have then excluded gluten from their diets have also experienced improved health. Unfortunately, most of the individuals who have elevated IgG anti-gliadin antibodies and might benefit from avoiding gluten do not know that they are gluten sensitive and/or have celiac disease. Thus, we really don't know how many, or which, school children should be avoiding gluten to optimize their academic potential as they work their way through the education system. Approaching this issue from a different angle, we know that between 10% and 15% of the U.S. population has dyslexia (3). About 60% of those with ADHD have dyslexia (3). If we calculate the prevalence of ADHD, at 8.8% of the population (4), then just the ADHD component, it should give us 5.28% of the population with dyslexia. But we can't tell how much overlap there is between this group and the group that constitutes between 10% and 15% of the population that are reported as having dyslexia. These disabilities have been given considerable attention and have been studied for some time, yet we really know little about their causes, except in cases of traumatic brain injury. However, there is a startling study, reported in The Times ten years ago, from the Nunnykirk School in Northumberland, U.K. (5). The astounding results of this study continue to cry out for further research and possible replication. After 6 months on a gluten-free diet, testing showed that 11 of the 12 (92%) live-in students had improved their reading and comprehension at more than twice the rate at which regular students are expected to improve. Among the 22 students living in the community and attending this special school for dyslexic students during the day, 17 of them (77%) showed similar improvements (5). To put these results in perspective, special needs teachers are often very proud when they can help students achieve at rates similar to regular students. Doubling the rates of improvement is an astonishingly positive result! And a few of these students leaped ahead at six times the rate of normal students! The numbers of students involved in this study are too small to allow us to extrapolate to other dyslexic populations. And, given that the research was done in the United Kingdom, where definitions of learning disabilities, and other factors may be dissimilar, and that the work was reported in a newspaper instead of a peer reviewed journal, and the startlingly positive nature of these results, we really need further, carefully designed studies to explore this phenomenon. The Nunnykirk findings are consistent with the extensive brain and neurological research that has been done at the Royal Hallamshire Hospital at the University of Sheffield, over the last two decades, by Marios Hadjivassiliou and his colleagues. They have found that a strict gluten-free diet can often relieve central and peripheral neurological symptoms. Further, many prominent researchers who work with children and adults who have dyslexia characterize it as a neurobiological condition, and can demonstrate, with MRI, altered brain function in dyslexia (8). It is also clear that many cases of dyslexia are at least partly genetically conferred (8, 9). Neither are learning disabilities limited to dyslexia. Although some practitioners lump two or more learning disabilities together, the literature distinguishes between dyslexia, dysgraphia, dyspraxia, dyscalculia, dysphasia/aphasia, auditory processing disorders, visual processing disorders, etc. Some such practitioners not only differentiate between types of learning disabilities, they also differentiate between sub-types of disabilities. For instance, motor dysgraphia (where fine motor speed is impaired), dyslexic dysgraphia (where normal fine motor speed allows them to draw or copy but impairs spontaneous writing) and spatial dysgraphia (where handwriting is illegible due to distortion) can each be identified based on symptoms (10). Similar sub-types are seen in other learning disabilities. But what if the findings at Nunnykirk School are broadly applicable to all of these types of learning problems? Or perhaps further research can tell us which types and sub-types of learning disabilities can often be alleviated by a gluten-free diet. My own professional observations suggest that the number of students helped by a gluten-free diet would be similar to the proportions seen at Nunnykirk School. I have also observed that as the strictness of the diet increases, so does the number of students who improve. However, the diagnosing professionals are becoming reluctant to differentiate, even between general types of learning disabilities such as dyslexia and dysgraphia. As teachers, we were told that a child had learning disabilities and then, if not specified in the documents we were given, we had to figure out exactly what type of disability they had, then devise or research effective ways of teaching these students. I have done a little of both, but my experience is that this choice varies from one teacher to the next, and one situation to the next. Unfortunately, depending on the individual teacher's workload, teaching background, and personal biases, these children can sometimes be neglected or under-served, a choice that is often dictated by excessive workloads and demands on teachers' time to perform other tasks, especially extensive reporting and supervising sports and other extra-curricular activities. Please recall the overlap between dyslexia and ADHD mentioned earlier (3), and consider that there are ten reports of connections between attention deficit disorders and celiac disease published in the peer reviewed medical literature. Now, please recall that about 60% of these ADHD children will have dyslexia (3). Since the current, and past issues, of the Diagnostic and Statistical Manual of Mental Disorders, require that ADHD and learning disorders each be differentiated from any medical condition that might be causing the same symptoms and be alleviated by resolution of the medical condition in question. On that basis alone, almost every child being considered for a diagnosis of learning disorders or ADHD should be thoroughly tested for celiac disease and non-celiac gluten sensitivity. Yet, I would be very surprised to learn that this is commonly being done. Thus, we have a situation in which we are forced to rely upon a study conducted by a group of teachers, in cooperation with parents and students, that was published in The Times (5) and we must take action on our own because, as yet, celiac disease and non-celiac gluten sensitivity are not yet being differentiated from ADHD and/or learning disabilities. The really tragic part of this story is that a gluten-free diet, if started early enough, can reduce or completely eliminate all of these problems with learning disabilities and attention deficits, when gluten is the underlying problem. If you or your spouse are gluten sensitive, or have celiac disease, do you also have children who struggle in school? Based on the data from Nunnykirk School, current blood tests are probably not sufficient to rule out those who would benefit from a gluten-free diet. For the moment, you may need to institute a trial of a gluten-free diet, as mentioned above, while we await further research in this area. But wouldn't it be valuable for succeeding generations to know, or have a pretty clear idea whether the diet could help? And with what types and/or sub-types of learning disorders? That's where more research could really help. We already know that there is an association between gluten sensitivity and seizure disorders, ataxia and cerebellar degeneration, neuropathy (damage to peripheral nervous system), schizophrenia, depression, migraine, anxiety disorders, autism, multiple sclerosis, myasthenia gravis (an autoimmune neuromuscular disease), and white matter lesions in the brain (11). It should not be surprising if gluten underlies many or most cases of learning disorders and attention deficits. And if research can tell us which cases would be most likely to benefit from the diet, that will be a huge step forward for parents, students, teachers, and government agencies that provide funding for the education of those who are afflicted with these ailments. In the meantime, we only have the information that we have. So, despite its many weaknesses, the Nunnykirk investigation of dyslexic children argues for experimental implementation, on a trial basis. I would suggest at least a six-months-long period of strict gluten avoidance to determine whether it will help individuals who suffer from dyslexia and/or other learning disabilities. Sources: 1. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003 Feb 10;163(3):286-92. 2. Hadjivassiliou M, Grünewald R A, Davies-Jones G A B. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 2002;72:560-563. 3. Dyslexia Research Institute http://www.dyslexia-add.org/ 4. National Resource Center on ADHD http://www.help4adhd.org/about/statistics 5. Blair http://www.thetimes.co.uk/tto/news/uk/article1924736.ece 6. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71. 7. Aziz I, Hadjivassiliou M. Coeliac disease: noncoeliac gluten sensitivity--food for thought. Nat Rev Gastroenterol Hepatol. 2014 Jul;11(7):398-9. 8. Shaywitz SE, Shaywitz BA. The Neurobiology of Reading and Dyslexia. Focus on Basics - Connecting Research & Practice, Volume 5,A: Aug. 2001. http://www.ncsall.net/index.html@id=278.html 9. Eicher JD, Powers NR, Miller LL, Mueller KL, Mascheretti S, Marino C, Willcutt EG, DeFries JC, Olson RK, Smith SD, Pennington BF, Tomblin JB, Ring SM, Gruen JR. Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ. Hum Genet. 2014 Jul;133(7):869-81. 10. About Education http://specialed.about.com/od/readingliteracy/a/Dyslexia-And-Dysgraphia.htm 11. Jackson JR, Eaton WW, Cascella NG, Fasano A, Kelly DL.Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatr Q. 2012 Mar;83(1):91-102. 12. Diaconu G, Burlea M, Grigore I, Anton DT, Trandafir LM. Celiac disease with neurologic manifestations in children. Rev Med Chir Soc Med Nat Iasi. 2013 Jan-Mar;117(1):88-94. PubMed PMID: 24505898. 13. Niederhofer H. Association of attention-deficit/hyperactivity disorder and celiac disease: a brief report. Prim Care Companion CNS Disord. 2011;13(3). pii: PCC.10br01104PMCID: PMC3184556. 14. Niederhofer H, Pittschieler K. A preliminary investigation of ADHD symptoms in persons with celiac disease. J Atten Disord. 2006 Nov;10(2):200-4. 15. Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004 Jun;113(6):1672-6. 16. KozÅ‚owska ZE. [Evaluation of mental status of children with malabsorption syndrome after long-term treatment with gluten-free diet (preliminary report)]. Psychiatr Pol. 1991 Mar-Apr;25(2):130-4. Polish. 17. Diaconu G, Burlea M, Grigore I, Anton DT, Trandafir LM. Celiac disease with neurologic manifestations in children. Rev Med Chir Soc Med Nat Iasi. 2013 Jan-Mar;117(1):88-94. PubMed PMID: 24505898. 18. Niederhofer H. Association of attention-deficit/hyperactivity disorder and celiac disease: a brief report. Prim Care Companion CNS Disord. 2011;13(3). pii: PCC.10br01104. PMCID: PMC3184556. 19. Niederhofer H, Pittschieler K. A preliminary investigation of ADHD symptoms in persons with celiac disease. J Atten Disord. 2006 Nov;10(2):200-4. 20. 4: Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004 Jun;113(6):1672-6. 21. KozÅ‚owska ZE. [Evaluation of mental status of children with malabsorption syndrome after long-term treatment with gluten-free diet (preliminary report)]. Psychiatr Pol. 1991 Mar-Apr;25(2):130-4. Polish.

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 Google.com. 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. 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. 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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. 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