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      Frequently Asked Questions About Celiac Disease   04/07/2018

      This Celiac.com FAQ on celiac disease will guide you to all of the basic information you will need to know about the disease, its diagnosis, testing methods, a gluten-free diet, etc.   Subscribe to Celiac.com's FREE weekly eNewsletter   What are the major symptoms of celiac disease? Celiac Disease Symptoms What testing is available for celiac disease?  Celiac Disease Screening Interpretation of Celiac Disease Blood Test Results Can I be tested even though I am eating gluten free? How long must gluten be taken for the serological tests to be meaningful? The Gluten-Free Diet 101 - A Beginner's Guide to Going Gluten-Free Is celiac inherited? Should my children be tested? Ten Facts About Celiac Disease Genetic Testing Is there a link between celiac and other autoimmune diseases? Celiac Disease Research: Associated Diseases and Disorders Is there a list of gluten foods to avoid? Unsafe Gluten-Free Food List (Unsafe Ingredients) Is there a list of gluten free foods? Safe Gluten-Free Food List (Safe Ingredients) Gluten-Free Alcoholic Beverages Distilled Spirits (Grain Alcohols) and Vinegar: Are they Gluten-Free? Where does gluten hide? Additional Things to Beware of to Maintain a 100% Gluten-Free Diet What if my doctor won't listen to me? An Open Letter to Skeptical Health Care Practitioners Gluten-Free recipes: Gluten-Free Recipes
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    WHY MEDICAL RESEARCHERS PREFER DOUBLE BLIND TESTING


    Dr. Ron Hoggan, Ed.D.


    • Journal of Gluten Sensitivity Winter 2014 Issue


    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.


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    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.


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    I especially liked how he described his relationship with his doctor and his expectations for a collaborative relationship.

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    Dr. Ron Hoggan, Ed.D.
    Celiac.com 10/16/2015 - Y Net News, under their "Health & Science" banner, published an article titled "Israeli researchers propose link between gluten and ALS", on April 17, 2015 (1). ALS refers to amyotrophic lateral sclerosis, or Lou Gehrig's disease, also known as motor neuron disease. Authorship of this article is attributed to the news agency, Reuters. The article refers to a study in which the investigators identify an autoimmune dynamic in the brain (2). The Y Net News article quotes one of these investigators as warning ALS patients against experimenting with a gluten-free diet: "Patients should not be tempted to use a gluten-free diet without clear evidence for antibodies, because an unbalanced diet might harm"(1). This is the kind of advice that frequently appears in the popular media. There can be little doubt that a gluten-free can be unhealthy, just as gluten containing diets can be unhealthy. When contacted on this issue, Dr. Drory said that "Patients with ALS tend to lose weight due to symptoms of their disease and it is well known that weight loss has a negative influence on disease progression and survival. Therefore it is very important for these patients not to lose weight" (3). Although Dr. Drory did not mean to impugn the gluten-free diet for the general population, she is legitimately concerned about the longevity and health of ALS patients, so she believes that only those with positive antibody tests should try the diet, and then only under the supervision of a dietitian. Reuters, on the other hand, have not responded to my request, through Y Net News, to contact the author of this article.
    While Dr. Drory's concerns are reasonable, I think that she has missed an important feature of the gluten-free diet and she puts too much faith in the connection between TG6 and ALS [an abbreviation for a recently discovered enzyme named tissue transglutaminase six] apparently believing that it will identify all ALS patients who might benefit from avoiding gluten. However, if we can judge based on those who have celiac disease, it is a diet that is more likely to increase the body mass of someone who is underweight. Dr. Drory also seems to have missed the sentiment expressed in the abstract of her own report. It says: "The data from this study indicate that, in certain cases, an ALS syndrome might be associated with autoimmunity and gluten sensitivity. Although the data are preliminary and need replication, gluten sensitivity is potentially treatable; therefore, this diagnostic challenge should not be overlooked" (1). Thus, when dealing with an otherwise irreversible and unstoppable disease, patients are cautioned not to try the diet without these marker antibodies which the authors identify as "preliminary" findings.
    Dr. Drory's caution also assumes that dietitians will generally be competent to guide the ALS patient in their gluten-free diet. However, it is important to recognize that the neurological patient needs to be even more strict with the diet than a person with celiac disease, and there are many uncertainties and debates around this diet. The average dietitian may not be up to date with the application of the gluten-free diet for such conditions, or the relevant controversies, or their application. Also, the beneficial results of a gluten-free diet are widespread across so many ailments and much medical research currently lags well behind patients' positive experiences. This is what has led to the continuing debate about the frequency and importance of non-celiac gluten sensitivity. Until very recently, it was usually given no attention at all. Further, since "gluten sensitivity is potentially treatable," and the current life expectancy for an ALS patient is about 2 years, it seems irresponsible to warn patients to wait for further research results before trying a gluten-free diet.
    This latter sentiment captures the essence of my current view of the gluten-free diet. Until I was diagnosed with celiac disease, more than twenty years ago, I would have ignored Dr. Drory, and subscribed to the bias inherent in the Y Net News article. Sadly, I used to dismiss people who talked about diet in the same way that I responded to those who talked about "astro travel" and Astrology. I viewed them as foolish concepts that were popular fads among drug-crazed hippies of the 1960s and 1970s, and other similarly deranged individuals. I still question many other diets, astro travel, and Astrology, but hope I do not do so with the same arrogant certitude of my youth.
    You see, I experienced a startling change of perspective shortly after I was diagnosed with celiac disease. Just three days after beginning the gluten-free diet, I awoke to an altered state of consciousness. The closest I can get to describing it is that I felt somewhat like I remember feeling as a kid when I awoke on Christmas morning. I felt optimistic, hopeful, and I looked forward to the day ahead. That was a big change. I was used to waking up feeling tired, depressed, and usually with a sense of foreboding about the coming day. I also found, after about the first six months or so of avoiding gluten, that my mind was becoming sharper, I was more aware of my surroundings, and my memory seemed to improve. My reflexes also seemed quicker. My sense of balance got better and my reaction time was faster. When I looked at others, I saw that many people were similarly challenged and didn't seem to be aware of their limitations—or perhaps they had just become used to them. Thus, I now believe that many people unknowingly suffer from the myriad harms induced or facilitated by gluten consumption. I also see, given the many venues in which the diet made a difference for me, why others might be skeptical.
    But how did Dr. Drory get from the notion that since gluten sensitivity is treatable, and should therefore be investigated as a potential factor in some cases of ALS, to the notion that ALS patients should be cautioned against experimenting with a gluten-free diet because it can cause weight loss? The gluten-free diet can be an effective weight loss strategy for some people. As I have mentioned in previous columns, the gluten-free diet seems to reduce the appetites of overweight individuals with celiac disease by about 400 calories per day. Equally, underweight celiac patients usually gain weight. Dr. Drory's concern about weight loss for those with ALS might be well founded if it was a universally good weight loss strategy. But it isn't. The data regarding weight loss on a gluten-free diet are only available, to my knowledge, with regard to celiac patients, where underweight patients almost always gain weight and about half of overweight patients lose weight. She also thinks that experimentation without a positive antibody test and the oversight of a dietitian might be risky. So her concerns may not be as valid as they first appear. If those ALS patients are gluten sensitive, then they might behave similarly to those with celiac disease, at least with regard to weight gain and loss. Further, how can anyone say, without trying it, that a gluten-free diet would not benefit those ALS patients who do not show TG6 antibodies?
    The Reuters article goes on from there to state: "It’s also worth remembering that an association is not the same as a cause. At least one earlier study concluded that there was no association between TG6 antibodies and either neurological disease or gluten itself" (1). The preceding comment refers to a retrospective research report in which the records of patients, on a Swedish data-base, who had been diagnosed with celiac disease, were further examined for an additional diagnosis of ALS (4). This is more than a little strange, since the very study the Reuters journalist used to distinguish between associations and causality, seeks only evidence of an association between the ALS and celiac disease. The notion that correlation is not causation is valid. However, using a study that looks for a correlation between celiac disease and ALS is not a reasonable basis for differentiating between correlation and causation. Neither is it a valid example of a causal relationship.
    Further, it is difficult to imagine a study design that would be less likely to reveal an association between transglutaminase TG6 and any other ailment, than one based on recorded data from a large number of patients who were diagnosed with celiac disease between 1969 and 2008. All, or almost all of these patients were diagnosed prior to the first published report of the discovery and diagnostic utility of transglutaminase 6 (5). So if one looks through records that predate the discovery of TG6 to find evidence of a connection between TG6 and any other disease, one is highly unlikely to find it.
    The abstract of the study that asserts there is no association between these ailments is based on a very weak design. It also ends with the statement: "Earlier reports of a positive association may be due to surveillance bias just after celiac disease diagnosis or expedited diagnostic work-up of ALS" (4). They are so confident of their own findings that they suggest that contrary findings are either due to bias or fast, careless work. I will leave it to the reader to infer whether there is bias among the authors of this report. Additionally, the Y Net News article, by one or more journalists at the Reuters News Agency, reports that this study found no association between TG6 antibodies and ALS, even though the study in question examines data that predates the use of TG6 antibody testing. While the study in question does appear to claim that there is no connection between celiac disease and ALS, the mention of TG6 and whether there is a connection between these antibodies and ALS appears to be information added by Reuters.
    Regardless of this possibly 'added' information, it really is quite a stretch to warn the public or ALS patients of the dangers of a gluten-free diet in reporting about research that has found evidence of a possible connection between ALS and gluten consumption. In a balanced report, the Reuters journalist would have mentioned the seven other research publications that have reported associations, and/or cause to suspect such associations, between gluten and ALS (5-11). It really isn't rocket science. It is just ethical, balanced reporting, which should serve as a minimum standard for an organization that is engaged in reporting the news. Since there are always at least two sides to almost any argument, both sides should at least have been acknowledged. Thus, in addition to the weak study reporting that they didn't find an association, the seven other reports of possible associations really should have been mentioned.
    It would also have been informative to their readers to mention Stephen Hawking, the longest living patient who was diagnosed with ALS. Dr. Hawking is still alive and has been on a gluten-free diet for the last 40+ years (12). He had already lived well beyond the two year life expectancy predicted by his doctors when, in 1963, Hawking's ALS had progressed to the point where he had begun to choke on his food. That is when he eliminated gluten, sugar, and plant oils from his diet. He has continued to avoid gluten for all these years and has also added several vitamins and supplements to his diet. Whether any or all of these measures have made "the" life extending difference, or if it is all of these measures combined that have allowed him to continue for so long, we can't know. Nonetheless, it may be that the gluten-free diet has been a determining factor in Dr. Hawking's longevity in the context of ALS. We also don't know if he would have tested positive for TG6 back when he was first diagnosed. However, he might not still be with us if he had opted to wait for this research to emerge and be confirmed.
    Since Hawking began his self-directed dietary experiment, researchers at the Royal Hallamshire Hospital in Sheffield, UK, have shown that the TG6 antibodies, while present in some celiac patients, are also found in some patients with non celiac gluten sensitivity and either neurological disease or an increased risk of developing one (5).
    Others, reporting a case study, had diagnosed ALS, then identified, diagnosed, and treated co-existing celiac disease with a gluten-free diet. They then retracted their ALS diagnosis saying: "Ultimately, improvement in the patient’s symptoms following treatment for celiac disease rendered the diagnosis of ALS untenable" (6). It would appear that any improvement in ALS symptoms obviates a diagnosis of ALS. It also raises the possibility that some cases of ALS can be effectively treated with a gluten-free diet.
    Similarly, in another case study report, the authors state: "ALS is a condition with relentless progression; for this reason, the simple observation of an improvement in symptoms is most pertinent in rendering the diagnosis of ALS untenable" (7). Again, the patient's ALS symptoms regressed following institution of a gluten-free diet.
    Yet another report that connects ALS with autoimmunity in general states: "The significance of increased premorbid celiac disease in those with ALS, and in family members of patients with MMN [multifocal motor neuropathy] remains unclear at present."(9). Still others have offered genetic evidence of connections between gluten sensitivity and ALS (10).
    Thus, the Reuters article raises an important question. Why are we seeing so many media attacks on those who are taking responsibility for their own health and experimenting with a gluten-free diet? It might come as a surprise to the Reuters journalist to learn that we humans had evolved and spread into most habitable areas of the world long before a few farmers began cultivating grains in regions of what are now known as Iraq and Iran. She/he might also be surprised to learn that we have known, for decades, that variants of wheat, rye, and barley have a deleterious impact on human neurological tissues (13, 14, 15) and that a variety of neurological ailments arise both in the context of celiac disease and non-celiac gluten sensitivity (14).
    The conclusion in the abstract of the 'no relationship' study dismisses reports of opposing findings as either due to "surveillance bias" or "expedited diagnostic work-up" (4). (This latter is a euphemistic statement suggesting that the work that led to these other reports was conducted too quickly and errors resulted.) Whatever your personal view of the attitude expressed there, the greater concern may be that the media continue to identify the gluten-free diet as potentially harmful (1) while researchers and individuals experimenting with a gluten-free diet have found evidence connecting gluten sensitivity with, at least, some cases of ALS (2).
    Over the years, I have heard many reasons for resisting this diet, but the one that is probably the least defensible is the assertion that it is potentially harmful. Almost any dietary regimen can be hazardous, of course, but the assertion that it might cause a harmful dietary imbalance fails to recognize that gluten has only been part of the Human experience for a very short time, in evolutionary terms. The simple fact is that we humans have spent far more of our evolutionary past eating a gluten-free diet than we have spent eating gluten. Some populations have only been eating these grains since European incursions over the last several hundred years. Some of these populations have only been eating it for less than one hundred years. Still others have been eating gluten for a few thousand years. In Israel, where Dr. Drory's study originated, grains were probably incorporated into the diet much earlier than in most of the rest of Europe, probably sometime between 15,000 and 10,000 years ago. It is difficult to imagine that after hundreds of thousands of years of eating a gluten-free diet, that avoiding gluten can pose a health hazard. The Reuters journalist appears to have another axe to grind, but I continue to wonder why we are seeing so many journalists on the attack against the gluten-free lifestyle?
    The driving force behind these journalists' attacks may well be similar to the perspective that I experienced before my diagnosis with celiac disease. Perhaps they suspect, whatever their reasons, that the gluten-free diet has little or no merit, and their only concession is to grudgingly allow that it may be helpful to those with celiac disease. My suspicion is that this attitude is driven by an insecurity. We want to believe conventional wisdom that gluten grains are healthy and that our medical professionals, and the institutions in which they serve, are above reproach. Nobel Laureate, Kary Mullis, is one highly vaunted physician's voice, among many, who dismiss most diets as fads, arguing that we are omnivores whose secret of successful adaptation to a wide variety of environments is the result of our flexibility in sources of nourishment (18). Many of us want to be able to rely on our physicians. We don't want the insecurity of knowing that our medical establishment is a flawed, human institution. The self-directed experimentation with a gluten-free diet poses a threat to that credibility, and hence, our sense of security, especially when it results in improved health. We don't want to feel the resulting uncertainty that comes from doubting the medical cornerstone of our civilization.
    It is not long ago that Don Wiss, myself, and others, argued extensively with physicians and researchers who insisted that the rate of celiac disease in the USA was variously one in 12,000 persons or one in 25,000 people. Sometimes these discussions became quite heated. Some of the people posting to these newsgroups were asking for suggestions for how they might proceed with various health complaints. When Don or I saw a post asking about symptoms that had been reported in the peer reviewed literature, in association with untreated celiac disease, we suggested a trial of a gluten-free diet. Some of the physicians and researchers contacted these individuals privately, saying things to discredit us. It seems doubtful that they would not have said such things where they were likely to be held accountable for what they said. Their reactions, I suspect, were driven by a sense of feeling threatened. As soon as controlled testing was done, it became clear that the rate of celiac disease, among Americans, is at least 1 in 133 Americans, and many of those individuals we advised to try a gluten-free diet might well have had celiac disease. Yet many journalists, physicians, and researchers have a great deal invested in the current status quo. Any threat to the established order is likely to incite the ire of many members of these groups.
    Thus, while others may consider it prudent to await the end of the current debate about ALS and a gluten-free diet, the ALS patient might be better advised to take dietary steps to ensure against weight loss, while trying a strict gluten-free diet. I know what I would do if were diagnosed with ALS...on second thought, since I've been gluten-free for more than twenty years, maybe I won't ever be diagnosed with ALS. I will continue to hope. In the meantime, Thomas Kuhn clearly outlined this stage of acceptance of new ideas in science (19). We appear to be in the "denial" stage, which is the last one before we can expect the emergence of widespread claims that 'we knew it all along'. If so, then broad acceptance is in the offing, and these nay-saying journalists will move on to some other controversial new discovery, and we can be spared the condescending remarks suggesting that the gluten-free diet is a mere placebo and a 'fad diet' for most of those who follow it.
    Sources:
    http://www.ynetnews.com/articles/0,7340,L-4647994,00.html Gadoth A, Nefussy B, Bleiberg M, Klein T, Artman I, Drory VE. Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis. JAMA Neurol. 2015 Apr 13. Drory V. Personal communication via email Ludvigsson JF, Mariosa D, Lebwohl B, Fang F. No association between biopsy-verified celiac disease and subsequent amyotrophic lateral sclerosis--a population-based cohort study. Eur J Neurol. 2014 Jul;21(7):976-82. Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders D, Woodroofe N, Aeschlimann D. Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 2008;64:332-343 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. 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. Ihara M, Makino F, Sawada H, Mezaki T, Mizutani K, Nakase H, Matsui M, Tomimoto H, Shimohama S. Gluten sensitivity in Japanese patients with adult-onset cerebellar ataxia. Intern Med. 2006;45(3):135-40. Turner MR, Goldacre R, Ramagopalan S, Talbot K, Goldacre MJ. Autoimmune disease preceding amyotrophic lateral sclerosis: an epidemiologic study. Neurology. 2013 Oct 1;81(14):1222-5. Auburger G, Gispert S, Lahut S, Omür O, Damrath E, Heck M, BaÅŸak N. 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? World J Diabetes. 2014 Jun 15;5(3):316-27. Bersano E, Stecco A, D'Alfonso S, Corrado L, Sarnelli MF, Solara V, Cantello R, Mazzini L. Coeliac disease mimicking Amyotrophic Lateral Sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2015 Feb 3:1-3. Hawking J. Travelling to Infinity: My Life with Stephen. Alma Books, Richmond, UK. 2014.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 01/26/2016 - One part of our natural protection from the microbes and toxins in our environment is the innate part of our immune systems. This includes everything from our skin, to the mucous we produce in various tissues which engulfs unwanted or harmful particles, isolating them and ultimately expelling them from the body in fecal matter and mucous, such as from our sinuses. While our immune systems have other components, it is the innate system that provides most of our protection from the world outside our bodies. The intestinal mucosa is very much a part of this system. Thus, since Hollon et al found that "Increased intestinal permeability after gliadin exposure occurs in all individuals" (1), there should be little doubt that humans are not well adapted to consuming these storage proteins from wheat, or gliadin's near relatives from rye and barley. Anyone eating these grains is opening a portal into their bloodstreams so toxins, microbes, along with undigested and partly digested proteins can enter their circulation. Without gliadin's impact, these various substances would probably not have entered the bloodstream and would have been wasted with feces.
    Just as few of us would ever consider putting fecal matter on an open wound, neither would we knowingly introduce this same material into the bloodstream through the intestinal wall. Yet, that is the net effect of humans consuming gluten grains. We are giving microbes access to our circulation. These harmful substances may be destroyed by other parts of our immune systems. Or perhaps we will develop episodic or chronic inflammation, leading to vascular damage where plaques can accumulate to cause atherosclerosis. Or the inflammation may use up available serotonin and its precursor, tryptophan, leading to depression. Or this they may cause one of the many other forms of damage that can be induced by inflammation. Or perhaps these infectious agents will manifest in other ailments, the causes of which will often remain obscure, as they degrade our health. Just one example of this risk can be found in a recent report in which antibiotic resistant staph infections were detected in 13% of pasteurized milk samples, and in 75% of raw milk samples (2). The acid in our stomachs, another part of the innate immune system, may provide some protection against this hazard. 

    On the other hand, microbes that have gained entrance into the circulation have also been implicated in some cases of arthritis, where the infectious agent binds to proteins in synovial fluid. Selective antibodies then target these complexes, causing damage to both the invader and the self tissues (3, 4).
    Toxins, especially those from insecticides and other chemicals likely to be found in or on our food supply are also cause for concern. Although most cases of organophosphate insecticide poisoning were the result of suicide attempts, these substances are widely used on a variety of food crops, and can be very dangerous (5). After all, both herbicides and pesticides are designed to kill small organisms. Because of our size, we may require more of these substances to get the job done but we, too, are organisms.
    One component of such substances is inorganic arsenic, which can also be found in natural rock deposits, some wood preservatives, rice, and sea foods, any or all of which can find its way to our bloodstreams (7) especially if we consume gluten grains. Of particular concern is that rice is often a staple of the gluten-free diet and it has been shown to have a strong affinity for inorganic arsenic, which "is a chronic, non-threshold carcinogen" (7). Thus, unlike smoking tobacco, even the smallest dose can result in cancer. Further, there are many areas of the United States where the groundwater is significantly contaminated with arsenic (8). Either drinking such water or excessive dietary reliance on rice grown in such a contaminated area can result in arsenic poisoning, as reported by Signes-Pastor et al (7) in a housewife in Saudi Arabia, who had celiac disease and relied heavily on rice. These authors first suspected dietary non-compliance until urine tests revealed an arsenic concentration at 46 times the highest value of the normal range (7). Her symptoms included: "progressive fatigue, profound watery diarrhea (12 times/d), palpitation, dry mouth, poor appetite, poor taste, sleeplessness, impaired concentration, and short-term memory" (7).

    Proteins from outside our bodies are eschewed by our selective immune systems, identifying them as foreign, and mount an attack against these "aliens". So any undigested proteins from the foods we eat, if they arrive in our bloodstream, are going to result in the mobilization of antibodies aimed at the destruction of these proteins. This sounds like a process for developing an allergic response against common foods.
    However, some proteins are worse than others. Gliadin, for instance, has long been recognized as harmful to many human cells (9). Humans also lack the necessary enzymes to fully digest it (10). Thus, after gliadin has caused increased zonulin production, leading to increased intestinal permeability, it can enter the bloodstream and travel to various tissues and organs where this undigested or partly digested family of proteins will induce one or more of their range of damaging impacts on the cells each molecule contacts. Dolfini et al have also reported that gliadin "induces an imbalance in the antioxidative mechanism of cells" (11) and it wreaks havoc on human cells by changing their shape, structure, and reducing their viability, as well as inhibiting enzyme production within the cell and/or inducing cell death (11).
    Since some humans have been consuming these grains for more than 10,000 years, one might expect that we would have evolved a digestive tract that could neutralize this threat to our wellness. Unfortunately, the issue isn't that simple. Only a small segment of the human population started cultivating gluten grains so long ago. The early development of this agriculture was also very localized and episodic. It would begin in one area then, for some unknown reason, the fields would be abandoned after some period of time. Then it would (excuse the pun) crop up in another, nearby area of the Fertile Crescent (what is now parts of Iraq, Iran, Kuwait, Syria, Lebanon, Jordan, Palestine, Israel, and Egypt). The net result was that it took some time before cereal agriculture was a thriving concern. This may be explained by the illnesses that are reflected in the bones of those early farmers (11). Gluten grains appear to have taken a much greater toll on their health than it does on us now, so some adaptation has probably occurred. Nonetheless, once grain cultivation got a good start, it spread fairly quickly across Europe, arriving in England by about 5,000 years ago.
    Populations living in environments that were not conducive to grain cultivation, either due to climate or soil conditions would wait much longer to incorporate gluten grains as a staple in their diets. Modern transportation systems were required to bring this crippling food to some doorsteps in Scandanavia, parts of Scotland and Ireland, and many other such environments throughout Europe. However, even in those halcyon days when the sun never set on the British Empire, Europeans really weren't the only people on the planet. They may have behaved as if they were, but that's an issue for another discussion. In the meantime, the bulk of the world's population had not eaten gluten grains until much more recently, when Europeans "shared" these grains almost everywhere they traveled. Most of the populations these Europeans met during their travels had also missed out on the many European plagues, including bubonic plague, smallpox, and typhoid fever, as well as the filthy living conditions that were common in Europe. These conditions had selected only those with the most vigorous immune systems to carry on as Europeans. When gifts such as smallpox-infected blankets were given to natives, these naive populations succumbed, in large numbers.
    Further, only a small percentage of these naive populations who were very recently introduced to gluten were developing celiac disease. For instance, only about 5.6% of Saharawi children of Northern Africa had developed celiac disease when tested by Dr. Catassi and colleagues some 50 years or so after they had begun to eat gluten (12).
    European "explorers" probably didn't really notice such illnesses among their grain-naive hosts. Nobody had the technology or the medical understanding to identify celiac disease or the many neurological ailments that gluten causes anyway. Many of us still deal with deep wells of medical ignorance, in the context of a very modern medical system, when it comes to our disease, so how could we expect anything more from those sea-faring Europeans of four or five centuries ago?
    Perhaps those gluten derived opioids probably felt pretty good to people who tried gluten. Whatever the reason, the rest of the world seems to have adopted Europe's dietary choices, pursuing the "comfort" of gluten grains while developing myriad forms of autoimmune disease, neurological dysfunction, gastrointestinal complaint, and a variety of other ailments. And most of the people I encounter would rather deny the health risks than give up donuts, cake, pie, and toast (13).
    Note: I'm proud to announce that I've been given the privilege of reviewing a new book that will be published early next year, under the Touchstone imprint, by Simon and Schuster. I will be writing about some interesting new insights this exciting book offers into the world of gluten sensitivity in the next issue of the Journal of Gluten Sensitivity.
    Sources:
    Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity. Nutrients 2015, 7, 1565-1576. Akindolire MA, Babalola OO, and Ateba CN. Detection of Antibiotic Resistant Staphylococcus aureus from Milk: A Public Health Implication. Int. J. Environ. Res. Public Health 2015, 12, 10254-10275. Li S, Yu Y, Koehn celiac disease, Zhang Z, Su K. Galectins in the Pathogenesis of Rheumatoid Arthritis. J Clin Cell Immunol. 2013 Sep 30;4(5). Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000 Mar;83(3):207-17. Coskun R, Gundogan K, Sezgin GC, Topaloglu US, Hebbar G, Guven M, Sungur M. A retrospective review of intensive care management of organophosphate insecticide poisoning: Single center experience. Niger J Clin Pract. 2015 Sep-Oct;18(5):644-50. Hasanato RM, Almomen AM. Unusual presentation of arsenic poisoning in a case of celiac disease. Ann Saudi Med. 2015 Mar-Apr;35(2):165-7. Signes-Pastor AJ, Carey M, Meharg AA. Inorganic arsenic in rice-based products for infants and young children. Food Chem. 2016 Jan 15;191:128-34. United States Geological Survey. 2005. Arsenic in ground water in the United States. http://water.usgs.gov/nawqa/trace/arsenic/ Last Modified: Thursday, 17-Nov-2011 Hudson DA, Purdham DR, Cornell HJ, Rolles CJ. Non specific cytotoxicity of wheat gliadin components towards cultured human cells. Lancet 1976; 1: 339-341. Kagnoff M. Private communication. 2005 Dolfini E, Elli L, Roncoroni L, Costa B, Colleoni MP, Lorusso V, Ramponi S,Braidotti P, Ferrero S, Falini ML, Bardella MT. Damaging effects of gliadin on three-dimensional cell culture model. World J Gastroenterol. 2005 Oct 14;11(38):5973-7. Rätsch IM, Catassi C. Coeliac disease: a potentially treatable health problem of Saharawi refugee children. Bull World Health Organ. 2001;79(6):541-5. Cordain L. Cereal grains: humanity's double-edged sword. World Rev Nutr Diet. 1999;84:19-73.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 04/26/2016 - Vice President Dan Quayle famously stated: "what a waste it is to lose one's mind, or not to have a mind is being very wasteful, how true that is," when speaking to people involved in the United Negro College Fund (1). While it is entertaining to read and ponder, this statement evokes some ideas I have about senility, which is increasing, along with many other modern diseases, at a frightening speed. The prospect of losing my mind, my memory, my sense of connection with friends and loved-ones, and even my sense of identity and personal hygiene is a frightening spectre. Can you separate your memories and experiences, along with what you think and feel, from who you are? I can't. I'm not sure I would want to be able to do so. My identity is tied to my memories, experiences, and how I responded and continue to respond to them. I remember looking at my son's tiny hands and feet when we first brought him home from the hospital. My daughter, born prematurely, had even smaller digits. They seemed impossibly tiny yet they were all perfectly formed and quite beautiful. It seemed miraculous to me. It still does. I can't imagine anything that I'd be willing to accept in exchange for those memories. Neither would I willingly surrender my memory of the joy I felt at my first convocation or my first car. Yet those lost memories form the prison in which many people already find themselves. It appears that many more will follow.
    One segment of this problem, the epidemic of Alzheimer's disease (AD), already effects 5.4 million Americans and 30 million people throughout the world (2). Parkinson's disease, which is a neurological ailment that, in its later stages is often accompanied by dementia, is a similar ailment that is rapidly increasing both in absolute numbers and as a percentage of the population (3). Vascular dementia is yet another condition in which brain mass and mental acuity wane with advancing years (4). Perhaps this trend is partly due to the large number of aging baby boomers from the World War II era. But the relevant research suggests otherwise. Although we may be living longer and that may contribute to a small part of the growth of these devastating ailments, the biggest contributors appear to be lifestyle choices that include low daily activity levels, consumption of highly glycemic and inflammation-promoting refined carbohydrates and grain products, inadequate sleep duration, and exposure to toxic substances.
    As most students of celiac disease have long been aware, there is a powerful and potentially devastating component of brain and neurological damage associated with this ailment as a result of gluten grain consumption. In addition to the behavioral changes identified by Gibbons in 1889 (5), attention deficits identified by Reichelt (6), Neiderhofer (7, 8), and others (9 - 11), subsequent reports have connected increased incidence of seizure disorders(12-17), reductions of brain size (17 -20), a variety of neurological movement disorders (21 -23), a range of mood disorders (24, 25), and several psychiatric ailments (26, 27) including schizophrenia (28, 29), and signs of learning disabilities have been reported to improve quite dramatically and quickly on a gluten-free diet (30). Sleep disorders are also common among people with celiac disease (31). With emerging research into non-celiac gluten sensitivity over the last two decades, we have also begun to see evidence of similar connections between gluten consumption and most of these neurological/brain ailments. This added dimension of non celiac gluten sensitivity and its impact on human neurological health, were previously obscure and, in the case of amyotrophic lateral sclerosis (ALS) (26, 32), was thought to be rapidly deadly and incurable (33). Most recently, Bredesen reported that the gluten-free diet, or a low grain diet, forms one significant part of their multi-modal protocol for reversing several dementias among a small group of those who experienced recent symptom onset, including Alzheimer's disease, objectively identified disruptions in memory function or subjective, self-reported symptoms of dementia (2). Of the ten subjects studied in this latter investigation, nine showed substantial recovery in the form of symptom reversal along with either a return to work or improved performance at work (2).
    Harnessing the gluten-free diet makes sense, of course, because of the many neurological dimensions of gluten's harmful impact on human neurological tissues. Over the last 20 years, Dr. Marios Hadjivassiliou and colleagues, at the University of Sheffield and the Royal Hallamshire Hospital, have been reporting a wide range of neurological ailments in association with elevated anti-gliadin antibodies ( both with and without celiac disease) afflicting a large portion of their patients with neurological diseases of unknown origin (34 -37). Further, Dr. Joe Murray and colleagues have also reported on a group of thirteen patients experiencing moderate cognitive decline, three of whom experienced stabilized or improved cognitive function on a gluten-free diet alone (38). However, the protocol reported by Bredesen is aimed at correcting a greater number and broader spectrum of converging metabolic processes that are shaped, in large part, by our modern lifestyle, and are increasingly thought to be at the root of the current epidemic of dementias, including Alzheimer's disease (2). Gluten is only an important part of the overall picture. Dr. Suzanne de la Monte and colleagues have also identified a dynamic which they call type 3 diabetes at work in the brains of many patients with Alzheimer's disease (39). Insulin resistance, in the brain and elsewhere, is also a multi-factorial condition (40) which mostly involves disrupted metabolic processes, either through depletion of insulin production or, more likely, increased cellular resistance to insulin's movement of glucose into the cell.
    Dr. Dale Bredesen has argued that "in the past decade alone, hundreds of clinical trials have been conducted for AD, at an aggregate cost of billions of dollars, without success. This has led some to question whether the approach taken to drug development for AD is an optimal one" (2) This is the rationale that underlies his enormously broad therapeutic approach employed in his protocol.
    Please consider each of the following facets of Bredesen's therapeutic protocol:
    1. Serum testing was conducted and subsequent supplement recommendations were made, aimed at improving vitamin, mineral, amino acid, and herb supplements to achieve optimal values. All of the foregoing is aimed at harnessing their putative anti-oxidant function, supporting various facets of metabolism, and making use of their reported anti-inflammatory properties. Chelation therapy was also used to correct heavy metal (mercury, lead, cadmium) toxicity. Non-farmed fish, vegetables, and fruits were emphasized, while meat consumption was either discouraged or patients were encouraged to eat only organic and free range meat.
    2. Patients were given their choice of several low glycemic, low inflammatory, low grain diets. By this description, such a diet would exclude or severely limit gluten consumption.
    3. Patients were encouraged to engage daily in strategies, including meditation and listening to music, toward reducing their stress levels, which would reduce their cortisol production. Cortisol is a hormone that triggers increased release of glucose into the bloodstream, suppresses the immune system, and inhibits bone formation. In addition to excluding or treating sleep apnea, patients were prescribed melatonin at 0.5 mg daily, toward achieving at least eight hours of sleep each night, thereby reducing production of hunger-inducing ghrelin hormones in the stomach and increasing hunger-suppressing leptin hormones which are produced in the fat cells. Each carries its message to the brain.
    Reductions in cortisol and ghrelin secretion in combination with increasing leptin production would have a net effect of reducing inflammation while aiding weight loss and reducing blood glucose levels to normal fasting levels and targeting reduction of hemoglobin A1c levels to below 5.5, further reducing inflammation. Optimum levels of thyroid hormones, along with progesterone and pregnenolone were also pursued, along with reductions of free homocysteine to below 7 mg/L by prescription of vitamin B6, B12, and folic acid supplements, to reduce vascular damage and blockage that can be caused by elevated free homocysteine levels.
    Twice daily dietary supplementation with medium chain triglycerides (MCTs) also provides strategy for altering hormone production aimed at improved cognitive function. In humans, medium chain fatty acids resist storage. They must either be converted to ketone bodies in the liver, or rapidly utilized for energy. Because MCTs can induce the liver to increase ketone production, it provides an alternative energy source for many of the brain's cells, without requiring insulin to usher these ketones into the cells, as glucose does. In essence, adequate ketone production provides an alternative fuel both for many brain and other cells throughout the body. The liver mostly produces the ketone called beta-hydroxybutyrate. This acts not only as a fuel source, but is also a powerful anti-oxidant that does not require insulin to enter the cell, unlike vitamin C, which does require insulin to enter cells.
    4. To further promote these values and other facets of wellness arising out of regular activity, patients were asked to exercise for 30 to 60 minutes per day, 4 to 6 days each week.
    Each and all of the above have been reported somewhere in the literature as valid and valuable as part of reversing dementias, which Bredesen's list of citations supports (2). However, while significant improvements in the dementia symptoms of nine of the ten subjects does argue for the validity of this protocol, wholesale acceptance of all of the concepts here would fail to narrow our focus on those factors that are most likely to contribute to causing the vast majority of the various dementias that are contributing to the emerging epidemic. Bredesen also acknowledges that study participants were encouraged to follow as many instructions as they could. They were not asked or expected to be fully compliant with the instructions they were given. Nonetheless, I would probably err on the side of caution, by implementing as many of these strategies as possible, were I dealing with a loved-one who struggled with dementia.
    Conversely, I would be most reluctant to accept the interdiction of meats, organic or otherwise. On the other hand, growth promotion using low doses of anti-biotics can result in delivering anti-biotic resistant microbes. Poultry, hogs, and cattle are all high risk meats. Further, grains, especially gluten grains and corn, combine to form the mainstay of feeds used to fatten these animals and birds for market, where weight is the determining factor in the price paid for these meats.
    Bredesen also pointed, quite rightly, to the small number of subjects as a weakness in his study. However, when 9 of their 10 subjects achieved such remarkable results, especially in the context of the common belief that dementia, at any stage, is irreversible, this study certainly suggests that exploring dementias as a group of metabolic illnesses is a potentially fruitful path.
    This is a perspective that is enjoying considerable support from a variety of sources. Many researchers have, for the past decade or so, thought of many dementias as type 3 diabetes, with a growing body of support for this perspective amassing in the peer reviewed literature (41). More recently, chronic sleep deprivation has been similarly implicated in several ways. The first is specific to Alzheimer's disease, where beta amyloid deposits or plaques characterize this ailment. New research has shown that during sleep, brain tissues shrink, while the fluids that surround the brain permeate these tissues and inter-cellular structures, assimilating amyloid, which is a group of protein fragments (peptides) that are waste products of daytime brain cell activities (42). Because there is no lymphatic system in the brain, it has long been believed that the brain did not dispose of its waste products. However, another field of brain research has shown that conduits of these fluids form surrounding the blood vessels, carrying waste products into the bloodstream and, ultimately, out of the brain for disposal (42). Since average nightly sleep duration has shortened from nine hours to seven hours, given the above research findings, this reduction in sleep decreases our nightly capacity to remove waste amyloid and other detritus, leading to the formation and growth of amyloid deposits, which characterize at least one form of dementia.
    This same culture-wide sleep deprivation also induces memory disturbances and memory losses. It does so by a circuitous route. Throughout the day, each of us encodes memories through our hippocampus, a small region of the brain that is also involved in spatial navigation and contributes, with other parts of the lymbic system, to the regulation of many body functions. During sleep, the day's memories are thought to be processed and integrated with prior knowledge, emotions, and impressions in the neo-cortex. Some researchers are now postulating that this integration process is what results in our dreams (43-45). Regardless of whether it is the author of our dreams, Dr. Robert Stickgold and colleagues have shown that sleep helps us to consolidate the day's learning experiences, thus improving our memory retention. He has also shown that inadequate sleep compromises learning (43). The net result is that we not only need sleep to permit the brain to clean out the day's wastes, we also need it to form and preserve learning.
    Although Bredesen made no mention of it, there is another complicating factor here. Statin drugs are aimed at reducing cholesterol. However, they have also been shown to induce memory problems. One friend of mine was prescribed a statin drug, and he stopped being able to recognize me. After discontinuing this medication, he told me that I looked familiar, but he couldn't even guess at my name or where he knew me from. He waves hello to me from across the street, but doesn't cross it to visit anymore. And that seems to be where the recovery of his memory is stalled. It is with heart-rending sadness that I occasionally see him in passing. I say hello. But if he doesn't notice me waving or hear me shouting, there isn't even an exchange of greetings. He seems happy enough. So perhaps the loss is mostly mine. But I don't imagine that he would willingly have chosen this "new" world of his.
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    6. Ziegler, A., Nødland, M., Tveiten, D. and Reichelt, K.L. (2016) The AD/HD Syndrome as a Group of Biological Disorders. Open Journal of Pediatrics, 6, 22-28. http://dx.doi.org/10.4236/ojped.2016.61005
    7. Niederhofer H. Association of attention-deficit/hyperactivity disorder and celiac disease: a brief report. Prim Care Companion CNS Disord. 2011;13(3). pii
    8. Niederhofer H, Pittschieler K. A preliminary investigation of ADHD symptoms in persons with celiac disease. J Atten Disord. 2006 Nov;10(2):200-4.
    9. Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004 Jun;113(6):1672-6.
    10. Welch E, Ghaderi A, Swenne I. A comparison of clinical characteristics between adolescent males and females with eating disorders. BMC Psychiatry. 2015 Mar 11;15:45.
    11. Kozłowska 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. (based on amateur translation)
    12. Parisi P, Principessa L, Ferretti A, D'Onofrio D, Del Giudice E, Pacchiarotti C, Villa MP. "EEG abnormalities" may represent a confounding factor in celiac disease: A 4-year follow-up family report. Epilepsy Behav Case Rep. 2014 Mar15;2:40-2.
    13. Korkmaz HA, Dizdarer C, Ecevit CO. Hypocalcemic seizure in an adolescent with Down syndrome: a manifestation of unrecognized celiac disease. Turk J Pediatr. 2013 Sep-Oct;55(5):536-8.
    14. Devinsky O, Schein A, Najjar S. Epilepsy associated with systemic autoimmune disorders. Epilepsy Curr. 2013 Mar;13(2):62-8.
    15. Vincent A, Crino PB. Systemic and neurologic autoimmune disorders associated with seizures or epilepsy. Epilepsia. 2011 May;52 Suppl 3:12-7.
    16. Das G, Baglioni P. Coeliac disease: does it always present with gastrointestinal symptoms? QJM. 2010 Dec;103(12):999-1000.
    17. Peltola M, Kaukinen K, Dastidar P, Haimila K, Partanen J, Haapala AM, Mäki M, Keränen T, Peltola J. Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitivity. J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):626-30.
    18. 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.
    19. Ryan AM, Ryan J, Wan-Ahmed M, Hardiman O, Farrell MA, McNamara B, Sweeney BJ. Vacuolar leucoencephalopathy and pulvinar sign in association with coeliac disease. BMJ Case Rep. 2009;2009. pii: bcr08.2008.0650.
    20. Kieslich M, Errázuriz G, Posselt HG, Moeller-Hartmann W, Zanella F, Boehles H. Brain white-matter lesions in celiac disease: a prospective study of 75 diet-treated patients. Pediatrics. 2001 Aug;108(2):E21.
    21. Caio G, De Giorgio R, Venturi A, Giancola F, Latorre R, Boschetti E, Serra M, Ruggeri E, Volta U. Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations. Gastroenterol Hepatol Bed Bench. 2015 Spring;8(2):146-52.
    22. Finsterer J, Leutmezer F. Celiac disease with cerebral and peripheral nerve involvement mimicking multiple sclerosis. J Med Life. 2014 Sep 15;7(3):440-4. Epub 2014 Sep 25.
    23. McKeon A, Lennon VA, Pittock SJ, Kryzer TJ, Murray J. The neurologic significance of celiac disease biomarkers. Neurology. 2014 Nov 11;83(20):1789-96.
    24. Zingone F, Swift GL, Card TR, Sanders DS, Ludvigsson JF, Bai JC. Psychological morbidity of celiac disease: A review of the literature. United European Gastroenterol J. 2015 Apr;3(2):136-45.
    25. Carta MG, Conti A, Lecca F, Sancassiani F, Cossu G, Carruxi R, Boccone A, Cadoni M, Pisanu A, Francesca Moro M, Demelia L. The Burden of Depressive and Bipolar Disorders in Celiac Disease. Clin Pract Epidemiol Ment Health. 2015 Dec 31;11:180-5.
    26. Catassi C. Gluten Sensitivity. Ann Nutr Metab. 2015;67 Suppl 2:16-26.
    27. Lionetti E, Leonardi S, Franzonello C, Mancardi M, Ruggieri M, Catassi C. Gluten Psychosis: Confirmation of a New Clinical Entity. Nutrients. 2015 Jul 8;7(7):5532-9
    28. Porcelli B, Verdino V, Bossini L, Terzuoli L, Fagiolini A. Celiac and non-celiac gluten sensitivity: a review on the association with schizophrenia and mood disorders. Auto Immun Highlights. 2014 Oct 16;5(2):55-61.
    29. 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.
    30. Blair A. Wheat-free diet gives food for thought. The Times (UK) June 12, 2004 http://www.timesonline.co.uk/tol/news/uk/article444290.ece
    31. Zingone F, Siniscalchi M, Capone P, Tortora R, Andreozzi P, Capone E, Ciacci C. The quality of sleep in patients with coeliac disease. Aliment Pharmacol Ther. 2010 Oct;32(8):1031-6.
    32. 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.
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    34. 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.
    35. 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 Feb 2.
    36. Hadjivassiliou M, Duker AP, Sanders DS. Gluten-related neurologic dysfunction. Handb Clin Neurol. 2014;120:607-19.
    37. Hadjivassiliou M, Rao DG, Wharton SB, Sanders DS, Grünewald RA, Davies-Jones AG. Sensory ganglionopathy due to gluten sensitivity. Neurology. 2010 Sep 14;75(11):1003-8.
    38. Hu WT, Murray JA, Greenaway MC, Parisi JE, Josephs KA. Cognitive impairment and celiac disease. Arch Neurol. 2006 Oct;63(10):1440-6.
    39. de la Monte SM. Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease. Curr Alzheimer Res. 2012 Jan;9(1):35-66
    40. de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol. 2014 Apr 15;88(4):548-59.
    41. de la Monte SM. Type 3 diabetes is sporadic Alzheimer's disease: mini-review. Eur Neuropsychopharmacol. 2014 Dec;24(12):1954-60.
    42. Nedergaard M, Goldman SA. Brain Drain. Scientific American. 2016 March; p. 44-49.
    43. Stickgold R. Parsing the role of sleep in memory processing. Curr Opin Neurobiol. 2013 Oct;23(5):847-53.
    44. Stickgold R. Early to bed: how sleep benefits children's memory. Trends Cogn Sci. 2013 Jun;17(6):261-2
    45. Stickgold R, Walker MP. Sleep-dependent memory triage: evolving generalization through selective processing. Nat Neurosci. 2013 Feb;16(2):139-45.
    46. Taheri S, Lin L, Austin D, Young T, Mignot E (2004) Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 1(3): e62. Sleep deprivation raises ghrelin & lowers leptin production.

    Dr. Ron Hoggan, Ed.D.
    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. Nutrients. 2015 Jul 8;7(7):5532-9.
    9. Dohan C. "Cereals and schizophrenia: data and hypothesis" Acta Psychiat Scand 1966; 42: 125-152
    10. Dohan FC, Grasberger JC, Lowell FM, Johnston HT Jr, Arbegast AW. Relapsed Schizophrenics: More Rapid Improvement on a Milk-and Cereal-free Diet" Brit J Psychiat 1969; 115: 595-596
    11. Singh MM, Kay SR. Wheat gluten as a pathogenic factor in schizophrenia. Science. 1976 Jan 30;191(4225):401-2.
    12. Zioudrou et. al. "Opioid peptides derived from food proteins. The exorphins" J Biol Chem 1979; 254:2446-2449
    13. Mycroft et. al. "MIF-like sequences in milk and wheat proteins" NEJM 1982; 307: 895
    14. Dohan et. al. "Is Schizophrenia Rare if Grain is Rare?" Biol Psychiat 1984; 19(3): 385-399
    15. Dohan "Is celiac disease a clue to pathogenesis of schizophrenia?" Mental Hyg 1969; 53: 525-529
    16. Ashkenazi et. al. "Immunologic reaction of psychotic patients to fractions of gluten" Am J Psychiat 1979; 136: 1306-1309
    17. Samaroo D, Dickerson F, Kasarda DD, Green PH, Briani C, Yolken RH, Alaedini A. Novel immune response to gluten in individuals with schizophrenia. Schizophr Res. 2010 May;118(1-3):248-55.
    18. Kraft BD, Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond). 2009 Feb 26;6:10. doi: 10.1186/1743-7075-6-10.
    19. De Santis A, Addolorato G, Romito A, Caputo S, Giordano A, Gambassi G, Taranto C, Manna R, Gasbarrini G. Schizophrenic symptoms and SPECT Abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med. 1997 Nov;242(5):421-3.
    20. Cordain L. The Paleo Diet. John Wiley & Sons. NY, 2002.
    21. Elli L, Rossi V, Conte D, Ronchi A, Tomba C, Passoni M, Bardella MT, Roncoroni L, Guzzi G. Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen. Gastroenterol Res Pract. 2015;2015:953042
    22. Meharg, A. A., Sun, G., Williams, P. N., Adomako, E., Deacon, C., Zhu, Y-G., Feldmann, J. & Raab, A. Inorganic arsenic levels in baby rice are of concern. Apr 2008 In : Environmental Pollution . 152, 3, p. 746-749.
    23. Hoggan R. How do you like your arsenic? Journal of Gluten Sensitivity, Spring 2009.
    24. Pigna, M., Cozzolino, V., Violante, A. & Meharg, A. A. Influence of phosphate on the arsenic uptake by wheat (Triticum durum L.) irrigated with arsenic solutions at three different concentrations Feb 2009 In : Water, Air, and Soil Pollution. 197, 1-4, p. 371-380.
    25. Hudson DA, Cornell HJ, Purdham DR, Rolles CJ. Non-specific cytotoxicity of wheat gliadin components towards cultured human cells. Lancet. 1976 Feb.
    26. Doherty, M., & Barry, R.(1981). Gluten-induced mucosal changes in subjects without overt small-bowel disease. The Lancet March 7, 517-520.
    27. de la Monte SM, Wands JR. Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed. J Diabetes Sci Technol. 2008 November; 2(6): 1101–1113.
    28. Jackson J, Eaton W, Cascella N, Fasano A, Santora D, Sullivan K, Feldman S, Raley H, McMahon RP, Carpenter WT Jr, Demyanovich H, Kelly DL. Gluten sensitivity and relationship to psychiatric symptoms in people with schizophrenia. Schizophr Res. 2014 Nov;159(2-3):539-42.
    29. Addolorato G, Di Giuda D, De Rossi G, Valenza V, Domenicali M, Caputo F, Gasbarrini A, Capristo E, Gasbarrini G. Regional cerebral hypoperfusion in patients with celiac disease. Am J Med. 2004 Mar 1;116(5):312-7.

  • Recent Articles

    Connie Sarros
    Celiac.com 04/21/2018 - Dear Friends and Readers,
    I have been writing articles for Scott Adams since the 2002 Summer Issue of the Scott-Free Press. The Scott-Free Press evolved into the Journal of Gluten Sensitivity. I felt honored when Scott asked me ten years ago to contribute to his quarterly journal and it's been a privilege to write articles for his publication ever since.
    Due to personal health reasons and restrictions, I find that I need to retire. My husband and I can no longer travel the country speaking at conferences and to support groups (which we dearly loved to do) nor can I commit to writing more books, articles, or menus. Consequently, I will no longer be contributing articles to the Journal of Gluten Sensitivity. 
    My following books will still be available at Amazon.com:
    Gluten-free Cooking for Dummies Student's Vegetarian Cookbook for Dummies Wheat-free Gluten-free Dessert Cookbook Wheat-free Gluten-free Reduced Calorie Cookbook Wheat-free Gluten-free Cookbook for Kids and Busy Adults (revised version) My first book was published in 1996. My journey since then has been incredible. I have met so many in the celiac community and I feel blessed to be able to call you friends. Many of you have told me that I helped to change your life – let me assure you that your kind words, your phone calls, your thoughtful notes, and your feedback throughout the years have had a vital impact on my life, too. Thank you for all of your support through these years.

    Jefferson Adams
    Celiac.com 04/20/2018 - A digital media company and a label data company are teaming up to help major manufacturers target, reach and convert their desired shoppers based on dietary needs, such as gluten-free diet. The deal could bring synergy in emerging markets such as the gluten-free and allergen-free markets, which represent major growth sectors in the global food industry. 
    Under the deal, personalized digital media company Catalina will be joining forces with Label Insight. Catalina uses consumer purchases data to target shoppers on a personal base, while Label Insight works with major companies like Kellogg, Betty Crocker, and Pepsi to provide insight on food label data to government, retailers, manufacturers and app developers.
    "Brands with very specific product benefits, gluten-free for example, require precise targeting to efficiently reach and convert their desired shoppers,” says Todd Morris, President of Catalina's Go-to-Market organization, adding that “Catalina offers the only purchase-based targeting solution with this capability.” 
    Label Insight’s clients include food and beverage giants such as Unilever, Ben & Jerry's, Lipton and Hellman’s. Label Insight technology has helped the Food and Drug Administration (FDA) build the sector’s very first scientifically accurate database of food ingredients, health attributes and claims.
    Morris says the joint partnership will allow Catalina to “enhance our dataset and further increase our ability to target shoppers who are currently buying - or have shown intent to buy - in these emerging categories,” including gluten-free, allergen-free, and other free-from foods.
    The deal will likely make for easier, more precise targeting of goods to consumers, and thus provide benefits for manufacturers and retailers looking to better serve their retail food customers, especially in specialty areas like gluten-free and allergen-free foods.
    Source:
    fdfworld.com

    Jefferson Adams
    Celiac.com 04/19/2018 - Previous genome and linkage studies indicate the existence of a new disease triggering mechanism that involves amino acid metabolism and nutrient sensing signaling pathways. In an effort to determine if amino acids might play a role in the development of celiac disease, a team of researchers recently set out to investigate if plasma amino acid levels differed among children with celiac disease compared with a control group.
     
    The research team included Åsa Torinsson Naluai, Ladan Saadat Vafa, Audur H. Gudjonsdottir, Henrik Arnell, Lars Browaldh, and Daniel Agardh. They are variously affiliated with the Institute of Biomedicine, Department of Microbiology & Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; the Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital and Division of Pediatrics, CLINTEC, Karolinska Institute, Stockholm, Sweden; the Department of Clinical Science and Education, Karolinska Institute, Sodersjukhuset, Stockholm, Sweden; the Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden; the Diabetes & Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden; and with the Nathan S Kline Institute in the U.S.A.
    First, the team used liquid chromatography-tandem mass spectrometry (LC/MS) to analyze amino acid levels in fasting plasma samples from 141 children with celiac disease and 129 non-celiac disease controls. They then crafted a general linear model using age and experimental effects as covariates to compare amino acid levels between children with celiac disease and non-celiac control subjects.
    Compared with the control group, seven out of twenty-three children with celiac disease showed elevated levels of the the following amino acids: tryptophan; taurine; glutamic acid; proline; ornithine; alanine; and methionine.
    The significance of the individual amino acids do not survive multiple correction, however, multivariate analyses of the amino acid profile showed significantly altered amino acid levels in children with celiac disease overall and after correction for age, sex and experimental effects.
    This study shows that amino acids can influence inflammation and may play a role in the development of celiac disease.
    Source:
    PLoS One. 2018; 13(3): e0193764. doi: & 10.1371/journal.pone.0193764

    Jefferson Adams
    Celiac.com 04/18/2018 - To the relief of many bewildered passengers and crew, no more comfort turkeys, geese, possums or other questionable pets will be flying on Delta or United without meeting the airlines' strict new requirements for service animals.
    If you’ve flown anywhere lately, you may have seen them. People flying with their designated “emotional support” animals. We’re not talking genuine service animals, like seeing eye dogs, or hearing ear dogs, or even the Belgian Malinois that alerts its owner when there is gluten in food that may trigger her celiac disease.
    Now, to be honest, some of those animals in question do perform a genuine service for those who need emotional support dogs, like veterans with PTSD.
    However, many of these animals are not service animals at all. Many of these animals perform no actual service to their owners, and are nothing more than thinly disguised pets. Many lack proper training, and some have caused serious problems for the airlines and for other passengers.
    Now the major airlines are taking note and introducing stringent requirements for service animals.
    Delta was the first to strike. As reported by the New York Times on January 19: “Effective March 1, Delta, the second largest US airline by passenger traffic, said it will require passengers seeking to fly with pets to present additional documents outlining the passenger’s need for the animal and proof of its training and vaccinations, 48 hours prior to the flight.… This comes in response to what the carrier said was a 150 percent increase in service and support animals — pets, often dogs, that accompany people with disabilities — carried onboard since 2015.… Delta said that it flies some 700 service animals a day. Among them, customers have attempted to fly with comfort turkeys, gliding possums, snakes, spiders, and other unusual pets.”
    Fresh from an unsavory incident with an “emotional support” peacock incident, United Airlines has followed Delta’s lead and set stricter rules for emotional support animals. United’s rules also took effect March 1, 2018.
    So, to the relief of many bewildered passengers and crew, no more comfort turkeys, geese, possums or other questionable pets will be flying on Delta or United without meeting the airlines' strict new requirements for service and emotional support animals.
    Source:
    cnbc.com

    admin
    WHAT IS CELIAC DISEASE?
    Celiac disease is an autoimmune condition that affects around 1% of the population. People with celiac disease suffer an autoimmune reaction when they consume wheat, rye or barley. The immune reaction is triggered by certain proteins in the wheat, rye, or barley, and, left untreated, causes damage to the small, finger-like structures, called villi, that line the gut. The damage occurs as shortening and villous flattening in the lamina propria and crypt regions of the intestines. The damage to these villi then leads to numerous other issues that commonly plague people with untreated celiac disease, including poor nutritional uptake, fatigue, and myriad other problems.
    Celiac disease mostly affects people of Northern European descent, but recent studies show that it also affects large numbers of people in Italy, China, Iran, India, and numerous other places thought to have few or no cases.
    Celiac disease is most often uncovered because people experience symptoms that lead them to get tests for antibodies to gluten. If these tests are positive, then the people usually get biopsy confirmation of their celiac disease. Once they adopt a gluten-free diet, they usually see gut healing, and major improvements in their symptoms. 
    CLASSIC CELIAC DISEASE SYMPTOMS
    Symptoms of celiac disease can range from the classic features, such as diarrhea, upset stomach, bloating, gas, weight loss, and malnutrition, among others.
    LESS OBVIOUS SYMPTOMS
    Celiac disease can often less obvious symptoms, such fatigue, vitamin and nutrient deficiencies, anemia, to name a few. Often, these symptoms are regarded as less obvious because they are not gastrointestinal in nature. You got that right, it is not uncommon for people with celiac disease to have few or no gastrointestinal symptoms. That makes spotting and connecting these seemingly unrelated and unclear celiac symptoms so important.
    NO SYMPTOMS
    Currently, most people diagnosed with celiac disease do not show symptoms, but are diagnosed on the basis of referral for elevated risk factors. 

    CELIAC DISEASE VS. GLUTEN INTOLERANCE
    Gluten intolerance is a generic term for people who have some sort of sensitivity to gluten. These people may or may not have celiac disease. Researchers generally agree that there is a condition called non-celiac gluten sensitivity. That term has largely replaced the term gluten-intolerance. What’s the difference between celiac disease and non-celiac gluten-sensitivity? 
    CELIAC DISEASE VS. NON-CELIAC GLUTEN SENSITIVITY (NCGS)
    Gluten triggers symptoms and immune reactions in people with celiac disease. Gluten can also trigger symptoms in some people with NCGS, but the similarities largely end there.

    There are four main differences between celiac disease and non-celiac gluten sensitivity:
    No Hereditary Link in NCGS
    Researchers know for certain that genetic heredity plays a major role in celiac disease. If a first-degree relative has celiac disease, then you have a statistically higher risk of carrying genetic markers DQ2 and/or DQ8, and of developing celiac disease yourself. NCGS is not known to be hereditary. Some research has shown certain genetic associations, such as some NCGS patients, but there is no proof that NCGS is hereditary. No Connection with Celiac-related Disorders
    Unlike celiac disease, NCGS is so far not associated with malabsorption, nutritional deficiencies, or a higher risk of autoimmune disorders or intestinal malignancies. No Immunological or Serological Markers
    People with celiac disease nearly always test positive for antibodies to gluten proteins. Researchers have, as yet, identified no such antobodies or serologic markers for NCGS. That means that, unlike with celiac disease, there are no telltale screening tests that can point to NCGS. Absence of Celiac Disease or Wheat Allergy
    Doctors diagnose NCGS only by excluding both celiac disease, an IgE-mediated allergy to wheat, and by the noting ongoing adverse symptoms associated with gluten consumption. WHAT ABOUT IRRITABLE BOWEL SYNDROME (IBS) AND IRRITABLE BOWEL DISEASE (IBD)?
    IBS and IBD are usually diagnosed in part by ruling out celiac disease. Many patients with irritable bowel syndrome are sensitive to gluten. Many experience celiac disease-like symptoms in reaction to wheat. However, patients with IBS generally show no gut damage, and do not test positive for antibodies to gliadin and other proteins as do people with celiac disease. Some IBS patients also suffer from NCGS.

    To add more confusion, many cases of IBS are, in fact, celiac disease in disguise.

    That said, people with IBS generally react to more than just wheat. People with NCGS generally react to wheat and not to other things, but that’s not always the case. Doctors generally try to rule out celiac disease before making a diagnosis of IBS or NCGS. 
    Crohn’s Disease and celiac disease share many common symptoms, though causes are different.  In Crohn’s disease, the immune system can cause disruption anywhere along the gastrointestinal tract, and a diagnosis of Crohn’s disease typically requires more diagnostic testing than does a celiac diagnosis.  
    Crohn’s treatment consists of changes to diet and possible surgery.  Up to 10% of Crohn's patients can have both of conditions, which suggests a genetic connection, and researchers continue to examine that connection.
    Is There a Connection Between Celiac Disease, Non-Celiac Gluten Sensitivity and Irritable Bowel Syndrome? Large Number of Irritable Bowel Syndrome Patients Sensitive To Gluten Some IBD Patients also Suffer from Non-Celiac Gluten Sensitivity Many Cases of IBS and Fibromyalgia Actually Celiac Disease in Disguise CELIAC DISEASE DIAGNOSIS
    Diagnosis of celiac disease can be difficult. 

    Perhaps because celiac disease presents clinically in such a variety of ways, proper diagnosis often takes years. A positive serological test for antibodies against tissue transglutaminase is considered a very strong diagnostic indicator, and a duodenal biopsy revealing villous atrophy is still considered by many to be the diagnostic gold standard. 
    But this idea is being questioned; some think the biopsy is unnecessary in the face of clear serological tests and obvious symptoms. Also, researchers are developing accurate and reliable ways to test for celiac disease even when patients are already avoiding wheat. In the past, patients needed to be consuming wheat to get an accurate test result. 
    Celiac disease can have numerous vague, or confusing symptoms that can make diagnosis difficult.  Celiac disease is commonly misdiagnosed by doctors. Read a Personal Story About Celiac Disease Diagnosis from the Founder of Celiac.com Currently, testing and biopsy still form the cornerstone of celiac diagnosis.
    TESTING
    There are several serologic (blood) tests available that screen for celiac disease antibodies, but the most commonly used is called a tTG-IgA test. If blood test results suggest celiac disease, your physician will recommend a biopsy of your small intestine to confirm the diagnosis.
    Testing is fairly simple and involves screening the patients blood for antigliadin (AGA) and endomysium antibodies (EmA), and/or doing a biopsy on the areas of the intestines mentioned above, which is still the standard for a formal diagnosis. Also, it is now possible to test people for celiac disease without making them concume wheat products.

    BIOPSY
    Until recently, biopsy confirmation of a positive gluten antibody test was the gold standard for celiac diagnosis. It still is, but things are changing fairly quickly. Children can now be accurately diagnosed for celiac disease without biopsy. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide.

    WHY A GLUTEN-FREE DIET?
    Currently the only effective, medically approved treatment for celiac disease is a strict gluten-free diet. Following a gluten-free diet relieves symptoms, promotes gut healing, and prevents nearly all celiac-related complications. 
    A gluten-free diet means avoiding all products that contain wheat, rye and barley, or any of their derivatives. This is a difficult task as there are many hidden sources of gluten found in the ingredients of many processed foods. Still, with effort, most people with celiac disease manage to make the transition. The vast majority of celiac disease patients who follow a gluten-free diet see symptom relief and experience gut healing within two years.
    For these reasons, a gluten-free diet remains the only effective, medically proven treatment for celiac disease.
    WHAT ABOUT ENZYMES, VACCINES, ETC.?
    There is currently no enzyme or vaccine that can replace a gluten-free diet for people with celiac disease.
    There are enzyme supplements currently available, such as AN-PEP, Latiglutetenase, GluteGuard, and KumaMax, which may help to mitigate accidental gluten ingestion by celiacs. KumaMax, has been shown to survive the stomach, and to break down gluten in the small intestine. Latiglutenase, formerly known as ALV003, is an enzyme therapy designed to be taken with meals. GluteGuard has been shown to significantly protect celiac patients from the serious symptoms they would normally experience after gluten ingestion. There are other enzymes, including those based on papaya enzymes.

    Additionally, there are many celiac disease drugs, enzymes, and therapies in various stages of development by pharmaceutical companies, including at least one vaccine that has received financial backing. At some point in the not too distant future there will likely be new treatments available for those who seek an alternative to a lifelong gluten-free diet. 

    For now though, there are no products on the market that can take the place of a gluten-free diet. Any enzyme or other treatment for celiac disease is intended to be used in conjunction with a gluten-free diet, not as a replacement.

    ASSOCIATED DISEASES
    The most common disorders associated with celiac disease are thyroid disease and Type 1 Diabetes, however, celiac disease is associated with many other conditions, including but not limited to the following autoimmune conditions:
    Type 1 Diabetes Mellitus: 2.4-16.4% Multiple Sclerosis (MS): 11% Hashimoto’s thyroiditis: 4-6% Autoimmune hepatitis: 6-15% Addison disease: 6% Arthritis: 1.5-7.5% Sjögren’s syndrome: 2-15% Idiopathic dilated cardiomyopathy: 5.7% IgA Nephropathy (Berger’s Disease): 3.6% Other celiac co-morditities include:
    Crohn’s Disease; Inflammatory Bowel Disease Chronic Pancreatitis Down Syndrome Irritable Bowel Syndrome (IBS) Lupus Multiple Sclerosis Primary Biliary Cirrhosis Primary Sclerosing Cholangitis Psoriasis Rheumatoid Arthritis Scleroderma Turner Syndrome Ulcerative Colitis; Inflammatory Bowel Disease Williams Syndrome Cancers:
    Non-Hodgkin lymphoma (intestinal and extra-intestinal, T- and B-cell types) Small intestinal adenocarcinoma Esophageal carcinoma Papillary thyroid cancer Melanoma CELIAC DISEASE REFERENCES:
    Celiac Disease Center, Columbia University
    Gluten Intolerance Group
    National Institutes of Health
    U.S. National Library of Medicine
    Mayo Clinic
    University of Chicago Celiac Disease Center