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    More Resistance to the Large Prevalence of Celiac Disease


    Dr. Ron Hoggan, Ed.D.

    This article originally appeared in the Spring 2011 edition of Celiac.com's Journal of Gluten-Sensitivity.


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    Celiac.com 09/07/2011 - Through the hard work and concerted efforts of many support groups and individuals throughout the US, along with the generosity of Instituto Di Ricerca in Italy, research funding was accumulated. Early in the Twenty-First Century, under the auspices of the Center for Celiac Disease Research, a new epoch in celiac disease awareness was born. Spearheaded by Dr. Alessio Fasano and several other prominent gastroenterologists, a large multi-center study was undertaken and the rate of celiac disease in the general U.S. population was determined to be at least 1 in 133 (1). This pains-taking, thorough, time-consuming and expensive research started a landslide of opinions that shifted the medical paradigm on the prevalence of celiac disease in the US, and caused ripples in medical thinking throughout the world. Celiac disease quickly became known as a very common ailment that is partly driven by a genetic predisposition, and is now thought to afflict about one percent of Americans. This increase in recognized prevalence is largely the result of studies that are conducted by testing blood from healthy blood donors to determine these numbers (more on this shortly). Yet a recent article from the medical literature asserts that current reports of the prevalence of celiac disease are over-estimating the actual portion of the population that is afflicted by this ailment. This article, published in the Annals of Medicine and Expert Opinion in December of 2010,  offers its own estimate the prevalence of celiac disease at about 1 in 160 (2).  What are we to believe? Is the rate of celiac disease really overestimated by many of the experts conducting research in this area? Or is there some other explanation?

    Photo: CC-RDECOMThere are actually several reasons that Biagi and colleagues have arrived at their reduced estimate of prevalence, and there is good cause to reject their claim in favor of the data indicating a prevalence of celiac disease that is close to 1% of American and other populations where gluten grains form a major part of the diet. The biases expressed by Biagi et al combine in this report to form what is probably the most glaring cause of their aberrant finding. These biases show up, both in their computations and in several emotion laden statements that appear in their report. There are also some indications to suggest that the statistical methods they employed are not appropriate for the data presented, especially when publishing an account that relies so heavily on statistical tools. For instance, they have failed to include some of the published data that fit within their inclusion criteria and would have significantly altered their results. There are also several confounding variables that were either overlooked or that warranted more attention than they were given by Biagi et al.  Finally, despite their acknowledgement of some of the weaknesses in the process by which they arrived at their estimate, they have chosen to impugn the work of other researchers who have reported a higher frequency of celiac disease rather than entertain the possibility that it is their own analyses and paradigm that are problematic. Even their choice of research method, the systematic review, is suspect, as it offers more opportunities for inclusion of the very errors they have made.

    Systematic reviews provide estimates based on averages of published research findings drawn from groups of studies of similar structure and design. The intent of this approach is to dampen the effects of extreme results, providing a more widely applicable and a more generally accurate perspective, eliminating variations driven by geographic location, accessibility of health care, research biases, etc. This is a useful tool that can be very helpful to busy clinicians by providing summaries that explain and clarify variations in findings as well as identifying mitigating factors in extreme findings. When done properly, these reviews reduce bias and other confounding factors, ultimately enhancing evidence-based optimal health care (3). However, Biagi and colleagues have fallen short of these ideals (2). They twice refer to their feelings in this report. Such expressions of the authors’ personal feelings reflect biases and preconceived notions that should not form any part of a scientific report. Yet they repeatedly do so. They go on to offer a rather snide parenthetic comment suggesting abuses of tissue transglutaminase testing. Such remarks demonstrate strong personal biases that interfere with the provision of objective information. Since bias reduction is an important, stated objective of the systematic review, this report by Biagi and colleagues should have been rejected by those who reviewed it.

    Biagi and colleagues do acknowledge that published research results vary so widely that they can not use the superior statistical method called a meta-analysis. (This is a method that can be especially useful with respect to celiac disease because when groups of research subjects are small, meta-analyses can be used to combine the findings from many small groups and provide more meaningful information.) The authors of the paper in question explain their choice of systematic review, yet this approach requires an exhaustive exploration of the relevant literature (3) which should have reached further than the small set of search terms they used.  In the interests of accuracy, it is important to find most or all of the relevant literature. Their limited search methods may explain why they missed several important studies, including the investigation of 989 Saharawi children by Catassi et al (4). Such studies would have altered their findings substantially which they side-step in a letter defending their original paper, published in the subsequent issue of the same journal (5). For instance, Catassi et al found a 5.6% prevalence of celiac disease among the sub-Saharan African children investigated (4). That is five and one half times as frequent as the prevalence figure that they have impugned. Surely they needed to at least acknowledge the existence of this report. They neither included it nor acknowledged it. In their letter of defence they assert that diagnoses were made on the basis of blood tests, not intestinal biopsies. However, many of the studies they did include in their data also offered diagnoses on the basis of blood tests in the absence of intestinal biopsies (5). 

    Biagi et al also assert over-estimation due to inclusion of “patients already known to be affected by celiac disease” (celiac disease). But how could their approach lead to an accurate tally of the percentage of all persons in a given population who have celiac disease? There appears to be some confusion about the meaning of the term “prevalence”. For instance, if a test group of 10,000 is identified and all participants are tested for celiac disease, yet several of them were previously diagnosed with celiac disease, Biagi and colleagues expect these previously diagnosed celiac patients to be excluded. Most of those who were previously diagnosed would test negative because they are now eating a gluten free diet. According to the Biagi paper, we should either exclude these people from our test group, or identify them as not having celiac disease. Either alternative is likely to produce much less accurate results than including them in the group that has celiac disease. (This approach alone would produce the faulty results they report in any population where there is reasonable access to modern health care.) Prevalence, after all, is a statement of the number of cases of a particular disease in a particular population. Excluding cases that were previously identified just doesn’t make any sense.

    Further, since IgA deficiency forms almost 2% of some populations (6) and the prevalence of celiac disease in IgA deficiency, in the same population is reported at 14% (4), such a significant confounding variable warrants attention. Yet Biagi et al do not even mention it. Let me explain. If total IgA was not measured in some, most, or all of the studies reviewed by Biagi et al, then IgA deficiency should reduce the reported prevalence by about 14%.  That difference alone would bridge most of the gap between the 1:133 and 1:160 prevalence findings.    

    But serology (blood testing) misses more than just IgA deficiency (7). This significant portion of the reports reviewed should therefore be expected to significantly under-estimate the prevalence of celiac disease. This is because, in these studies, case finding is often done with serological testing. Thus, these researchers will often fail to detect, and they will therefore have failed to biopsy, significant numbers of cases of seronegative celiac disease, both because of those excluded as blood donors due to their anaemia and/or malnourished condition and because of those who are seronegative, whether due to IgA deficiency or other reasons. 
    If any of the studies Biagi and colleagues reviewed used symptoms and signs for case finding, this is yet another source of underestimation, one that is probably the cause of current under-diagnosis of celiac disease that is estimated at above 95%.

    These authors point out that “anaemia or insufficient body weight are universally recognized as criteria that preclude enrolment as blood donors.” Since more than one quarter (13/41) of the studies they reviewed report rates based on case finding through the screening of healthy blood donors, the results of these studies must underestimate prevalence regardless of the authors’ feelings on the topic. Yet it is their feelings they harken to on this issue: “We feel that we did not find this difference because of the wide heterogeneity of the published papers which hampered a specific analysis focusing on this point.” I don’t much care what they feel. I want to know what evidence they can report. If they are interested in communicating about their feelings, there are many appropriate venues for such exchanges, but the medical research literature seems, at best, a very questionable choice.

    Much of the evidence they offered in support of their assertions that researchers are over-estimating celiac disease could more accurately be seen as inducing under-estimations of this common ailment.

    Finally, are the researchers who authored 41 separate reports failing so miserably at the diagnostic process that they miss the mark on a majority of marginal cases of celiac disease? This is the thrust of the Biagi et al statement:
    “Again, patients with minimal intestinal lesions and/or negative coeliac antibodies were always considered to be affected by celiac disease. Although these patients certainly exist, in our clinical experience they are very rare and most of the time they are not affected by celiac disease but are the result of diagnostic mistakes.“(2)
    In short, Biagi and colleagues claim to be so superior to the world leaders in celiac research that Biagi et al’s clinical experience is somehow more valid and accurate than the peer-reviewed, reported findings of most others working in this field (5).

    The proposition that the majority of celiac researchers are over-estimating the prevalence of celiac disease ignores variations due to IgA deficiency, seronegativity (negative blood tests), and ignores the variability of intestinal damage as shown by the Marsh system and other approaches for evaluating intestinal histology and/or diagnosing celiac disease without intestinal biopsies (8, 9, 10, 11, 12). Further, while many investigators have reported that potential or latent celiac disease often shows a similar constellation of signs and symptoms to those seen in celiac disease, Bertini et al have recently demonstrated that many cases of potential celiac disease show the same signatures of metabolic disturbances, both in the bloodstream and in urinary excretions, as those found in celiac disease (12). Such disturbances, whether in the context of celiac disease or potential celiac disease, normalize on a gluten free diet (13). In all, the Biagi et al article reflects the authors’ biases, serious limitations in the authors’ applications of the relevant statistical tools, and calls into question the quality of the process in this instance.

    Sources:

    1. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003 Feb 10;163(3):286-92
    2. Biagi F, Klersy C, Balduzzi D, Corazza GR. Are we not over-estimating the prevalence of coeliac disease in the general population? Ann Med. 2010 Dec;42(8):557-61. Epub 2010 Oct 1.
    3. Cook DJ, Mulrow celiac disease, Haynes RB.Systematic reviews: synthesis of best evidence for clinical decisions. Ann Intern Med. 1997 Mar 1;126(5):376-80.
    4. Catassi C, Rätsch IM, Gandolfi L, Pratesi R, Fabiani E, El Asmar R, Frijia M, Bearzi I, Vizzoni L. Why is coeliac disease endemic in the people of the Sahara? Lancet. 1999 Aug 21;354(9179):647-8.
    5. Hoggan, R. Comment on: Are we not over-estimating the prevalence of celiac disease in the general population? Annals of Medicine and Expert Opinion, 2011, 43: 164-65
    6. Bahari A, Karimi M, Sanei-Moghaddam I, Firouzi F, Hashemi M. Prevalence of celiac disease among blood donors in Sistan and Balouchestan Province, Southeastern Iran. Arch Iran Med. 2010 Jul;13(4):301-5.
    7. Sugai E, Hwang HJ, Vázquez H, Smecuol E, Niveloni S, Mazure R, Mauriño E, Aeschlimann P, Binder W, Aeschlimann D, Bai JC. New serology assays can detect gluten sensitivity among enteropathy patients seronegative for anti-tissue transglutaminase. Clin Chem. 2010 Apr;56(4):661-5. Epub 2009 Dec 18.
    8. Kurppa K, Ashorn M, Iltanen S, Koskinen LL, Saavalainen P, Koskinen O, Mäki M, Kaukinen K. Celiac disease without villous atrophy in children: a prospective study. J Pediatr. 2010 Sep;157(3):373-80, 380
    9. Salmi TT, Collin P, Reunala T, Mäki M, Kaukinen K. Diagnostic methods beyond conventional histology in coeliac disease diagnosis. Dig Liver Dis. 2010 Jan;42(1):28-32.
    10. Kaukinen K, Collin P, Mäki M.Latent coeliac disease or coeliac disease beyond villous atrophy? Gut. 2007 Oct;56(10):1339-40.
    11. Troncone R, Auricchio R, Granata V. Issues related to gluten-free diet in coeliac disease. Curr Opin Clin Nutr Metab Care. 2008 May;11(3):329-33.
    12. Bertini I, Calabrò A, De Carli V, Luchinat C, Nepi S, Porfirio B, Renzi D, Saccenti E, Tenori L. The metabonomic signature of celiac disease. J Proteome Res. 2009 Jan;8(1):170-7.
    13. Bernini P, Bertini I, Calabro A, la Marca G, Lami G, Luchinat C, Renzi D, Tenori L. Are Patients with Potential Celiac Disease Really Potential? The Answer of Metabonomics.  J Proteome Res. 2010 Dec.
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    Guest Celiac

    Posted

    Good article, but personally, as I celiac myself, I think gluten intolerance and celiac ARE over-diagnosed. Does there need to be more awareness? YES. Does there need to be diagnostics done for those ill with an unclear presentation of the disease or rare subtypes like gluten induced epilepsy? YES? Do high risk people (family history, Type 1 diabetics, autoimmune disease, etc.) need more screening? YES. But I think far too many other people think gluten is their problem when it is not. So many people cut out gluten with no proper diagnosis of Celiac (it's so common right?) only to not feel better. Then they cut out other foods. Either foods aren't why you are sick OR you are reacting to other foods, not gluten. I went undiagnosed for a long time in my 20s. I was very sick and I suspect near death. I was told I was "anxious", "stressed" or perhaps a hypochondriac. No doctor tested me for Celiac even though I have Type 1 diabetes and autoimmune thyroid disease. However, upon testing at my insistence, I had antibodies through the roof (EMA, Ttg, etc.) and a completely flat biopsy confirming the disease. My biopsy is now normal on a gluten-free diet. True Celiac that can cause severe health problems most definitely will show up on standard testing, it can't be missed if your doctor knows what to look for. Look at my case-if you really have Celiac, it can be tested for. Also, a crumb of gluten will make me sick/cause damage. Same with most Celiacs. Even if a culture only eats gluten 1x per week, that would be enough to still trigger the disease in most cases. If you actually have Celiac, you don't need to eat gluten in large amounts to trigger the disease. I think the new study is more accurate, and although I respect the old study, I do think Celiac has become the trendy disease du jour and may have caused a dis-service to us with the disease when the "fad" dies down. This I think was the issue the new study was trying to address. I hate that every time I visit a new doctor I have to bring my biopsy results with me to get him to write "celiac" on my chart...

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    Guest Elizabeth Mack

    Posted

    Good article but way, way, way too long, detailed and clinical for the average reader. Some previous article were the same way. I think it would be better if you had more layman's terms and covered what needed to be said in a few brief paragraphs or so. If this is taken directly from a medical journal or something can it be paraphrased for regular folks?

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    Guest Jerry Daily

    Posted

    I was misdiagnosed by a dermatologist in 2000. It took me 2 years before I went to another dermatologist, before I was diagnosed as a celiac. My youngest sister has had it for 50+ yrs. My older sister has had for 15+yrs.

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    Guest Grandma G

    Posted

    Good article, but personally, as I celiac myself, I think gluten intolerance and celiac ARE over-diagnosed. Does there need to be more awareness? YES. Does there need to be diagnostics done for those ill with an unclear presentation of the disease or rare subtypes like gluten induced epilepsy? YES? Do high risk people (family history, Type 1 diabetics, autoimmune disease, etc.) need more screening? YES. But I think far too many other people think gluten is their problem when it is not. So many people cut out gluten with no proper diagnosis of Celiac (it's so common right?) only to not feel better. Then they cut out other foods. Either foods aren't why you are sick OR you are reacting to other foods, not gluten. I went undiagnosed for a long time in my 20s. I was very sick and I suspect near death. I was told I was "anxious", "stressed" or perhaps a hypochondriac. No doctor tested me for Celiac even though I have Type 1 diabetes and autoimmune thyroid disease. However, upon testing at my insistence, I had antibodies through the roof (EMA, Ttg, etc.) and a completely flat biopsy confirming the disease. My biopsy is now normal on a gluten-free diet. True Celiac that can cause severe health problems most definitely will show up on standard testing, it can't be missed if your doctor knows what to look for. Look at my case-if you really have Celiac, it can be tested for. Also, a crumb of gluten will make me sick/cause damage. Same with most Celiacs. Even if a culture only eats gluten 1x per week, that would be enough to still trigger the disease in most cases. If you actually have Celiac, you don't need to eat gluten in large amounts to trigger the disease. I think the new study is more accurate, and although I respect the old study, I do think Celiac has become the trendy disease du jour and may have caused a dis-service to us with the disease when the "fad" dies down. This I think was the issue the new study was trying to address. I hate that every time I visit a new doctor I have to bring my biopsy results with me to get him to write "celiac" on my chart...

    "Celiac" much of what you say is true for YOU. Not so for many others. I would never have known I had celiac because I would never have been near death for a long time yet. I am a "Silent Celiac". Gluten does NOT make me sick in the normal way. I found it by studying the internet after being diagnosed with osteopenia at the age of 57.

    Yes there are those fad followers who have jumped on the gluten-free diet bandwagon. But do not dismiss all who suffer from "gluten intolerance" with such a sweeping accusation. My daughter is as sensitive to gluten as you describe you are, yet her blood test came in only 1 point above "normal". She has not been healthy for many years and could not afford the endoscopy but is a new person now that she has eliminated gluten from her life.

    It would appear that you think only those diagnosed "celiac" are entitled to live gluten-free without ridicule. It would be nice to live in such a cut and dried world as yours, then people who truly need to be gluten-free would know it.

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  • About Me

    As co-author of "Dangerous Grains" and "Cereal Killers", the study of the impact of gluten continues to be a driving passion in my life. I am fascinated by the way that gluten induces illness and impedes learning while it alters mood, behavior, and a host of other facets of our existence. Sure, the impact of gluten on health is an important issue, but that is only the most obvious area of impact. Mood disturbances, learning disabilities, and the loss of quality of life due to psychiatric and neurological illness are even more tragic than the plethora of physical ailments that are caused or worsened by gluten. The further I go down this rabbit hole, the more I realize that grains are a good food for ruminants - not people. I am a retired school teacher. Over the last decade, I have done some college and university level teaching, but the bulk of my teaching career was spent working with high school students. My Web page is: www.DangerousGrains.com

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    Jefferson Adams
    Celiac.com 03/23/2011 - A group of researchers in India recently conducted a community-based study on the prevalence of celiac disease in the northern part of India.
    The research group included Govind K Makharia, Anil K Verma, Ritvik Amarchand, Shinjini Bhatnagar, Prasenjit Das, Anil Goswami, Vidyut Bhatia, Vineet Ahuja, Siddhartha Datta Gupta and Krishnan Anand.
    They are affiliated with the Departments of Gastroenterology and Human Nutrition, and Pediatrics and Pathology at the Centre for Community Medicine of the All India Institute of Medical Sciences in New Delhi.
    Worldwide celiac disease rates are estimated at about 1%, but the disease is thought to be uncommon in both India and Asia. However, there has generally been a lack of study data on the actual prevalence of celiac disease in Asian nations.
    The research team set out to accurately estimate the prevalence of celiac disease in a specific Indian community. The team crafted a cross sectional study to estimate rates of celiac disease in urban and rural populations in the National Capital Region, Delhi, India.
    The team gathered data using a structured questionnaire administered via door-to-door visits. The questionnaire provided socio-demographic data and basic screening for features of celiac disease, such as chronic or recurrent diarrhea, and anemia.
    For children, the questionnaire included additional factors, namely short stature (linear height below 5th percentile for age) and failure to thrive/gain weight.
    All test subjects with positive screens and 10% of negative screen individuals were called for anti-tissue transglutaminase antibody blood test.
    All those with positive blood tests were invited to undergo endoscopic biopsy. The team diagnosed celiac disease on the basis of a positive blood screens, the presence of villous atrophy and/or response to gluten free diet.
    The team contacted 12,573 people in all. A total of 10,488 (83.4%) (50.6% male) agreed to participate. Screening showed 5,622 (53.6%) positive results. Of those who screened positive, 2167 (38.5%) submitted to anti-tissue transglutaminase antibody blood tests. The team also tested 712 (14%) subjects who had tested negative.
    The data showed an overall sero-prevalence of celiac disease was 1.44% (95% conï¬dence interval [CI] 1.22 1.69) and the overall prevalence of celiac disease was 1.04% (95% CI 0.85 1.25).
    Celiac disease in this north Indian community is 1 in 96, or about 1%. That means that celiac disease is more common than is recognized in India, and that rates are about the same as in other parts of the world, not lower, as conventional wisdom has held.
    Source:

    Journal of Gastroenterology and Hepatology, March 2011 / DOI: 10.1111/j.1440-1746.2010.06606.x

    Dr. Ron Hoggan, Ed.D.
    This article originally appeared in the Spring 2011 edition of Celiac.com's Journal of Gluten-Sensitivity.
    Celiac.com 09/07/2011 - Through the hard work and concerted efforts of many support groups and individuals throughout the US, along with the generosity of Instituto Di Ricerca in Italy, research funding was accumulated. Early in the Twenty-First Century, under the auspices of the Center for Celiac Disease Research, a new epoch in celiac disease awareness was born. Spearheaded by Dr. Alessio Fasano and several other prominent gastroenterologists, a large multi-center study was undertaken and the rate of celiac disease in the general U.S. population was determined to be at least 1 in 133 (1). This pains-taking, thorough, time-consuming and expensive research started a landslide of opinions that shifted the medical paradigm on the prevalence of celiac disease in the US, and caused ripples in medical thinking throughout the world. Celiac disease quickly became known as a very common ailment that is partly driven by a genetic predisposition, and is now thought to afflict about one percent of Americans. This increase in recognized prevalence is largely the result of studies that are conducted by testing blood from healthy blood donors to determine these numbers (more on this shortly). Yet a recent article from the medical literature asserts that current reports of the prevalence of celiac disease are over-estimating the actual portion of the population that is afflicted by this ailment. This article, published in the Annals of Medicine and Expert Opinion in December of 2010,  offers its own estimate the prevalence of celiac disease at about 1 in 160 (2).  What are we to believe? Is the rate of celiac disease really overestimated by many of the experts conducting research in this area? Or is there some other explanation?
    There are actually several reasons that Biagi and colleagues have arrived at their reduced estimate of prevalence, and there is good cause to reject their claim in favor of the data indicating a prevalence of celiac disease that is close to 1% of American and other populations where gluten grains form a major part of the diet. The biases expressed by Biagi et al combine in this report to form what is probably the most glaring cause of their aberrant finding. These biases show up, both in their computations and in several emotion laden statements that appear in their report. There are also some indications to suggest that the statistical methods they employed are not appropriate for the data presented, especially when publishing an account that relies so heavily on statistical tools. For instance, they have failed to include some of the published data that fit within their inclusion criteria and would have significantly altered their results. There are also several confounding variables that were either overlooked or that warranted more attention than they were given by Biagi et al.  Finally, despite their acknowledgement of some of the weaknesses in the process by which they arrived at their estimate, they have chosen to impugn the work of other researchers who have reported a higher frequency of celiac disease rather than entertain the possibility that it is their own analyses and paradigm that are problematic. Even their choice of research method, the systematic review, is suspect, as it offers more opportunities for inclusion of the very errors they have made.
    Systematic reviews provide estimates based on averages of published research findings drawn from groups of studies of similar structure and design. The intent of this approach is to dampen the effects of extreme results, providing a more widely applicable and a more generally accurate perspective, eliminating variations driven by geographic location, accessibility of health care, research biases, etc. This is a useful tool that can be very helpful to busy clinicians by providing summaries that explain and clarify variations in findings as well as identifying mitigating factors in extreme findings. When done properly, these reviews reduce bias and other confounding factors, ultimately enhancing evidence-based optimal health care (3). However, Biagi and colleagues have fallen short of these ideals (2). They twice refer to their feelings in this report. Such expressions of the authors’ personal feelings reflect biases and preconceived notions that should not form any part of a scientific report. Yet they repeatedly do so. They go on to offer a rather snide parenthetic comment suggesting abuses of tissue transglutaminase testing. Such remarks demonstrate strong personal biases that interfere with the provision of objective information. Since bias reduction is an important, stated objective of the systematic review, this report by Biagi and colleagues should have been rejected by those who reviewed it.
    Biagi and colleagues do acknowledge that published research results vary so widely that they can not use the superior statistical method called a meta-analysis. (This is a method that can be especially useful with respect to celiac disease because when groups of research subjects are small, meta-analyses can be used to combine the findings from many small groups and provide more meaningful information.) The authors of the paper in question explain their choice of systematic review, yet this approach requires an exhaustive exploration of the relevant literature (3) which should have reached further than the small set of search terms they used.  In the interests of accuracy, it is important to find most or all of the relevant literature. Their limited search methods may explain why they missed several important studies, including the investigation of 989 Saharawi children by Catassi et al (4). Such studies would have altered their findings substantially which they side-step in a letter defending their original paper, published in the subsequent issue of the same journal (5). For instance, Catassi et al found a 5.6% prevalence of celiac disease among the sub-Saharan African children investigated (4). That is five and one half times as frequent as the prevalence figure that they have impugned. Surely they needed to at least acknowledge the existence of this report. They neither included it nor acknowledged it. In their letter of defence they assert that diagnoses were made on the basis of blood tests, not intestinal biopsies. However, many of the studies they did include in their data also offered diagnoses on the basis of blood tests in the absence of intestinal biopsies (5). 
    Biagi et al also assert over-estimation due to inclusion of “patients already known to be affected by celiac disease” (celiac disease). But how could their approach lead to an accurate tally of the percentage of all persons in a given population who have celiac disease? There appears to be some confusion about the meaning of the term “prevalence”. For instance, if a test group of 10,000 is identified and all participants are tested for celiac disease, yet several of them were previously diagnosed with celiac disease, Biagi and colleagues expect these previously diagnosed celiac patients to be excluded. Most of those who were previously diagnosed would test negative because they are now eating a gluten free diet. According to the Biagi paper, we should either exclude these people from our test group, or identify them as not having celiac disease. Either alternative is likely to produce much less accurate results than including them in the group that has celiac disease. (This approach alone would produce the faulty results they report in any population where there is reasonable access to modern health care.) Prevalence, after all, is a statement of the number of cases of a particular disease in a particular population. Excluding cases that were previously identified just doesn’t make any sense.
    Further, since IgA deficiency forms almost 2% of some populations (6) and the prevalence of celiac disease in IgA deficiency, in the same population is reported at 14% (4), such a significant confounding variable warrants attention. Yet Biagi et al do not even mention it. Let me explain. If total IgA was not measured in some, most, or all of the studies reviewed by Biagi et al, then IgA deficiency should reduce the reported prevalence by about 14%.  That difference alone would bridge most of the gap between the 1:133 and 1:160 prevalence findings.    
    But serology (blood testing) misses more than just IgA deficiency (7). This significant portion of the reports reviewed should therefore be expected to significantly under-estimate the prevalence of celiac disease. This is because, in these studies, case finding is often done with serological testing. Thus, these researchers will often fail to detect, and they will therefore have failed to biopsy, significant numbers of cases of seronegative celiac disease, both because of those excluded as blood donors due to their anaemia and/or malnourished condition and because of those who are seronegative, whether due to IgA deficiency or other reasons. 
    If any of the studies Biagi and colleagues reviewed used symptoms and signs for case finding, this is yet another source of underestimation, one that is probably the cause of current under-diagnosis of celiac disease that is estimated at above 95%.
    These authors point out that “anaemia or insufficient body weight are universally recognized as criteria that preclude enrolment as blood donors.” Since more than one quarter (13/41) of the studies they reviewed report rates based on case finding through the screening of healthy blood donors, the results of these studies must underestimate prevalence regardless of the authors’ feelings on the topic. Yet it is their feelings they harken to on this issue: “We feel that we did not find this difference because of the wide heterogeneity of the published papers which hampered a specific analysis focusing on this point.” I don’t much care what they feel. I want to know what evidence they can report. If they are interested in communicating about their feelings, there are many appropriate venues for such exchanges, but the medical research literature seems, at best, a very questionable choice.
    Much of the evidence they offered in support of their assertions that researchers are over-estimating celiac disease could more accurately be seen as inducing under-estimations of this common ailment.
    Finally, are the researchers who authored 41 separate reports failing so miserably at the diagnostic process that they miss the mark on a majority of marginal cases of celiac disease? This is the thrust of the Biagi et al statement:
    “Again, patients with minimal intestinal lesions and/or negative coeliac antibodies were always considered to be affected by celiac disease. Although these patients certainly exist, in our clinical experience they are very rare and most of the time they are not affected by celiac disease but are the result of diagnostic mistakes.“(2)
    In short, Biagi and colleagues claim to be so superior to the world leaders in celiac research that Biagi et al’s clinical experience is somehow more valid and accurate than the peer-reviewed, reported findings of most others working in this field (5).
    The proposition that the majority of celiac researchers are over-estimating the prevalence of celiac disease ignores variations due to IgA deficiency, seronegativity (negative blood tests), and ignores the variability of intestinal damage as shown by the Marsh system and other approaches for evaluating intestinal histology and/or diagnosing celiac disease without intestinal biopsies (8, 9, 10, 11, 12). Further, while many investigators have reported that potential or latent celiac disease often shows a similar constellation of signs and symptoms to those seen in celiac disease, Bertini et al have recently demonstrated that many cases of potential celiac disease show the same signatures of metabolic disturbances, both in the bloodstream and in urinary excretions, as those found in celiac disease (12). Such disturbances, whether in the context of celiac disease or potential celiac disease, normalize on a gluten free diet (13). In all, the Biagi et al article reflects the authors’ biases, serious limitations in the authors’ applications of the relevant statistical tools, and calls into question the quality of the process in this instance.
    Sources:
    Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003 Feb 10;163(3):286-92 Biagi F, Klersy C, Balduzzi D, Corazza GR. Are we not over-estimating the prevalence of coeliac disease in the general population? Ann Med. 2010 Dec;42(8):557-61. Epub 2010 Oct 1. Cook DJ, Mulrow celiac disease, Haynes RB.Systematic reviews: synthesis of best evidence for clinical decisions. Ann Intern Med. 1997 Mar 1;126(5):376-80. Catassi C, Rätsch IM, Gandolfi L, Pratesi R, Fabiani E, El Asmar R, Frijia M, Bearzi I, Vizzoni L. Why is coeliac disease endemic in the people of the Sahara? Lancet. 1999 Aug 21;354(9179):647-8. Hoggan, R. Comment on: Are we not over-estimating the prevalence of celiac disease in the general population? Annals of Medicine and Expert Opinion, 2011, 43: 164-65 Bahari A, Karimi M, Sanei-Moghaddam I, Firouzi F, Hashemi M. Prevalence of celiac disease among blood donors in Sistan and Balouchestan Province, Southeastern Iran. Arch Iran Med. 2010 Jul;13(4):301-5. Sugai E, Hwang HJ, Vázquez H, Smecuol E, Niveloni S, Mazure R, Mauriño E, Aeschlimann P, Binder W, Aeschlimann D, Bai JC. New serology assays can detect gluten sensitivity among enteropathy patients seronegative for anti-tissue transglutaminase. Clin Chem. 2010 Apr;56(4):661-5. Epub 2009 Dec 18. Kurppa K, Ashorn M, Iltanen S, Koskinen LL, Saavalainen P, Koskinen O, Mäki M, Kaukinen K. Celiac disease without villous atrophy in children: a prospective study. J Pediatr. 2010 Sep;157(3):373-80, 380 Salmi TT, Collin P, Reunala T, Mäki M, Kaukinen K. Diagnostic methods beyond conventional histology in coeliac disease diagnosis. Dig Liver Dis. 2010 Jan;42(1):28-32. Kaukinen K, Collin P, Mäki M.Latent coeliac disease or coeliac disease beyond villous atrophy? Gut. 2007 Oct;56(10):1339-40. Troncone R, Auricchio R, Granata V. Issues related to gluten-free diet in coeliac disease. Curr Opin Clin Nutr Metab Care. 2008 May;11(3):329-33. Bertini I, Calabrò A, De Carli V, Luchinat C, Nepi S, Porfirio B, Renzi D, Saccenti E, Tenori L. The metabonomic signature of celiac disease. J Proteome Res. 2009 Jan;8(1):170-7. Bernini P, Bertini I, Calabro A, la Marca G, Lami G, Luchinat C, Renzi D, Tenori L. Are Patients with Potential Celiac Disease Really Potential? The Answer of Metabonomics.  J Proteome Res. 2010 Dec.

    Jefferson Adams
    Celiac.com 08/19/2012 - In an effort to assess rising rates of celiac disease, and an increasing popularity of gluten-free food products, a team of researchers recently conducted a survey. The research team included Alberto Rubio-Tapia, Jonas F. Ludvigsson, Tricia L Brantner, Joseph A. Murray and James E. Everhart.
    Their data indicate that about 1.8 million Americans have celiac disease, while another 1.4 million remain undiagnosed. Surprisingly, their results show that around 1.6 million people have adopted a gluten-free diet despite having no official diagnosis.
    Some of these people likely have celiac disease, while others likely belong to a large group of people who don't actually have celiac disease, but who suffer bloating and other celiac symptoms and seem to be helped by avoiding gluten; people many doctors are now officially describing as 'gluten sensitive.'
    Once a controversial term, the existence of gluten sensitivity has been supported by several studies, among them, a very small but often-cited Australian study.
    In that study, volunteers with gluten reaction symptoms received a gluten-free diet or a regular diet for six weeks, without knowing which one. At the end of the period, those who ate gluten-free had fewer problems with bloating, tiredness and irregular bowel movements.
    Clearly, the current data tell us that "there are patients who are gluten-sensitive," said Dr. Sheila Crowe, a San Diego-based physician on the board of the American Gastroenterological Association.
    The debate is now shifting to the question of how many people suffer from gluten sensitivity, she added. Because gluten sensitivity lacks the clinical markers of celiac disease, that question may not be answered anytime soon.
    Certainly, more and more people without any official diagnosis are turning to gluten-free diets as a way to lose weight, or as part of low carb and/or 'paleo' diets. Those people, together with celiacs and those with gluten intolerance are helping to drive the estimated $7 billion that will be spent on gluten-free.
    There has also been increasing concern among researchers that that many or most people have some kind of gluten sensitivity. Stay tuned for more news on this and other gluten and celiac-related topics.
    Source:
    The American Journal of Gastroenterology

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/21/2018 - Would you buy a house advertised as ‘gluten-free’? Yes, there really is such a house for sale. 
    It seems a Phoenix realtor Mike D’Elena is hoping that his trendy claim will catch the eye of a buyer hungry to avoid gluten, or, at least one with a sense of humor. D’Elena said he crafted the ads as a way to “be funny and to draw attention.” The idea, D’Elena said, is to “make it memorable.” 
    Though D’Elena’s marketing seeks to capitalizes on the gluten-free trend, he knows Celiac disease is a serious health issue for some people. “[W]e’re not here to offend anybody….this is just something we're just trying to do to draw attention and do what's best for our clients," he said. 
    Still, the signs seem to be working. D'elena had fielded six offers within a few days of listing the west Phoenix home.
    "Buying can sometimes be the most stressful thing you do in your entire life so why not have some fun with it," he said. 
    What do you think? Clever? Funny?
    Read more at Arizonafamily.com.

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    Bakery On Main started in the small bakery of a natural foods market on Main Street in Glastonbury, Connecticut. Founder Michael Smulders listened when his customers with Celiac Disease would mention the lack of good tasting, gluten-free options available to them. Upon learning this, he believed that nobody should have to suffer due to any kind of food allergy or dietary need. From then on, his mission became creating delicious and fearlessly unique gluten-free products that were clean and great tasting, while still being safe for his Celiac customers!
    Premium ingredients, bakeshop delicious recipes, and happy customers were our inspiration from the beginning— and are still the cornerstones of Bakery On Main today. We are a fiercely ethical company that believes in integrity and feels that happiness and wholesome, great tasting food should be harmonious. We strive for that in everything we bake in our dedicated gluten-free facility that is GFCO Certified and SQF Level 3 Certified. We use only natural, NON-GMO Project Verified ingredients and all of our products are certified Kosher Parve, dairy and casein free, and we have recently introduced certified Organic items as well! 
    Our passion is to bake the very best products while bringing happiness to our customers, each other, and all those we meet!
    We are available during normal business hours at: 1-888-533-8118 EST.
    To learn more about us at: visit our site.

    Jefferson Adams
    Celiac.com 06/20/2018 - Currently, the only way to manage celiac disease is to eliminate gluten from the diet. That could be set to change as clinical trials begin in Australia for a new vaccine that aims to switch off the immune response to gluten. 
    The trials are set to begin at Australia’s University of the Sunshine Coast Clinical Trials Centre. The vaccine is designed to allow people with celiac disease to consume gluten with no adverse effects. A successful vaccine could be the beginning of the end for the gluten-free diet as the only currently viable treatment for celiac disease. That could be a massive breakthrough for people with celiac disease.
    USC’s Clinical Trials Centre Director Lucas Litewka said trial participants would receive an injection of the vaccine twice a week for seven weeks. The trials will be conducted alongside gastroenterologist Dr. James Daveson, who called the vaccine “a very exciting potential new therapy that has been undergoing clinical trials for several years now.”
    Dr. Daveson said the investigational vaccine might potentially restore gluten tolerance to people with celiac disease.The trial is open to adults between the ages of 18 and 70 who have clinically diagnosed celiac disease, and have followed a strict gluten-free diet for at least 12 months. Anyone interested in participating can go to www.joinourtrials.com.
    Read more at the website for Australia’s University of the Sunshine Coast Clinical Trials Centre.

    Source:
    FoodProcessing.com.au

    Jefferson Adams
    Celiac.com 06/19/2018 - Could baking soda help reduce the inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease? Scientists at the Medical College of Georgia at Augusta University say that a daily dose of baking soda may in fact help reduce inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease.
    Those scientists recently gathered some of the first evidence to show that cheap, over-the-counter antacids can prompt the spleen to promote an anti-inflammatory environment that could be helpful in combating inflammatory disease.
    A type of cell called mesothelial cells line our body cavities, like the digestive tract. They have little fingers, called microvilli, that sense the environment, and warn the organs they cover that there is an invader and an immune response is needed.
    The team’s data shows that when rats or healthy people drink a solution of baking soda, the stomach makes more acid, which causes mesothelial cells on the outside of the spleen to tell the spleen to go easy on the immune response.  "It's most likely a hamburger not a bacterial infection," is basically the message, says Dr. Paul O'Connor, renal physiologist in the MCG Department of Physiology at Augusta University and the study's corresponding author.
    That message, which is transmitted with help from a chemical messenger called acetylcholine, seems to encourage the gut to shift against inflammation, say the scientists.
    In patients who drank water with baking soda for two weeks, immune cells called macrophages, shifted from primarily those that promote inflammation, called M1, to those that reduce it, called M2. "The shift from inflammatory to an anti-inflammatory profile is happening everywhere," O'Connor says. "We saw it in the kidneys, we saw it in the spleen, now we see it in the peripheral blood."
    O'Connor hopes drinking baking soda can one day produce similar results for people with autoimmune disease. "You are not really turning anything off or on, you are just pushing it toward one side by giving an anti-inflammatory stimulus," he says, in this case, away from harmful inflammation. "It's potentially a really safe way to treat inflammatory disease."
    The research was funded by the National Institutes of Health.
    Read more at: Sciencedaily.com

    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
    The research team included P Singh, A Arora, TA Strand, DA Leffler, C Catassi, PH Green, CP Kelly, V Ahuja, and GK Makharia. They are variously affiliated with the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Lady Hardinge Medical College, New Delhi, India; Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA; Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York; and the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
    For their review, the team searched Medline, PubMed, and EMBASE for the keywords ‘celiac disease,’ ‘celiac,’ ‘tissue transglutaminase antibody,’ ‘anti-endomysium antibody,’ ‘endomysial antibody,’ and ‘prevalence’ for studies published from January 1991 through March 2016. 
    The team cross-referenced each article with the words ‘Asia,’ ‘Europe,’ ‘Africa,’ ‘South America,’ ‘North America,’ and ‘Australia.’ They defined celiac diagnosis based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. The team used 96 articles of 3,843 articles in their final analysis.
    Overall global prevalence of celiac disease was 1.4% in 275,818 individuals, based on positive blood tests for anti-tissue transglutaminase and/or anti-endomysial antibodies. The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% in 138,792 individuals. That means that numerous people with celiac disease potentially remain undiagnosed.
    Rates of celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was 0.6% in female vs 0.4% males. Celiac disease was significantly more common in children than adults.
    This systematic review and meta-analysis showed celiac disease to be reported worldwide. Blood test data shows celiac disease rate of 1.4%, while biopsy data shows 0.7%. The prevalence of celiac disease varies with sex, age, and location. 
    This review demonstrates a need for more comprehensive population-based studies of celiac disease in numerous countries.  The 1.4% rate indicates that there are 91.2 million people worldwide with celiac disease, and 3.9 million are in the U.S.A.
    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.