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    Study Shows Gluten Intolerance Without Celiac Disease


    Jefferson Adams
    Image Caption: New study on gluten intolerance without celiac disease appears in the latest AJG.

    Celiac.com 02/14/2011 - In what may seem for some like an obvious finding, a team of Australian researchers has shown that people can suffer gluten intolerance without having celiac disease. Their study is published in The American Journal of Gastroenterology.


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    I say obvious, because many in the celiac and surrounding community have long understood and accepted the concept of gluten-intolerance as distinct from celiac disease. Surprisingly, there has been very little scientific research to establish the existence of gluten-intolerance as distinct from celiac disease. That is changing, and the recent Australian study offers some support for gluten-intolerance as distinct from celiac disease.

    For their study, a team of researchers led by Peter Gibson, professor of medicine at Eastern Health Clinical School at Monash University in Australia, recruited 34 people with irritable bowel syndrome, but who were clinically proven to be free of celiac disease. All participants had previously benefited from a gluten-free diet.

    The 34 volunteers were all fed bread and muffins, half of which contained gluten, half of which were gluten-free. Nearly 70 per cent of the volunteers who ate the gluten reported pain, bloating, toilet problems and extreme tiredness.

    ''Gluten is indeed a trigger of gut symptoms and tiredness,'' the researchers concluded. Professor Gibson said: ''These symptoms have a big impact on quality of life. But conservative medicine has not been so good at dealing with this because we haven't had any evidence.''

    A number of the volunteers had sought help from alternative health practitioners, a fact that impaired recruitment of volunteers, as many of these folks had adopted a gluten-free diet without proving or disproving celiac disease via colonoscopy and biopsy.

    It was important for the team to exclude celiac disease for several reasons, including the fact that although it was safe to use gluten to test people who may have an intolerance, it could harm people with celiac disease.

    "If you go back on gluten while you have celiac disease - even if you only eat a few pieces of bread - you will damage your body and undo many months of healing," Professor Gibson said.

    For that reason, and also to prove gluten intolerance alone was the symptom cause, the team recruited people  clinically proven to be free of celiac disease, and who were already on gluten-free diets.

    For those patients with irritable bowel syndrome, excluding celiac disease, who were symptomatically controlled on a gluten-free diet, the team crafted a double-blind, randomized, placebo-controlled re-challenge trial.

    Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. The team evaluated symptoms using a visual analog scale and markers of intestinal inflammation, injury, and immune activation monitoring.

    A total of 4 men and 30 women between the ages of 29–59-years old completed the study as per protocol. Overall, 56% showed human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high.

    Of 19 patients (68%) in the gluten-consuming group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation).

    On a visual analog scale, patients were significantly worse within one week of consuming gluten for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001).

    In no cases did gluten-consumption trigger anti-gliadin antibodies. Moreover, there where were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with the DQ2/DQ8 and those without.

    Gibson calls the general lack of research into gluten intolerance "almost unbelievable." He plans to now investigate the prevalence of non-celiac gluten intolerance, why it occurs and whether low levels of gluten can be eaten safely.


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    Guest Steve Rose

    Posted

    So here we have more questions. Can our allergic community have more unknown facts about food allergies and sensitivities? There seems to be more research into foods as triggers for non-life threatening reactions. It just seems that instead of looking at the reactions, some one should be looking at the foods. Where are the food products coming from and how well regulated are they? Are the regulations in the best interest of our health too?

    At least we are now seeing more gluten-free and allergy friendly foods to help us through this uncertainty.

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    5 stars for the presentation by Jefferson Adams. 2 stars for the actual researchers. Why? Because anyone who has ever been on a gluten-free diet can tell the difference between regular bread and gluten-free bread, and this may influence their complaints. So, if the researchers really wanted this to be double-blind and placebo controlled, they should have given gluten in a capsule to the experimental group, and an identical capsule containing something like rice flour to the control group.

     

    This was bad experimental design!

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    Guest Nancy Lindsey

    Posted

    Here is my concern. I have no idea which I am - celiac or gluten intolerant. For 7 months I suffered with stomach issues and lost 20 pounds. A GI doctor tested me for everything BUT celiac. I lived on noodle soup and crackers and was often violently ill. After my sister suggested I try a gluten free diet (which I had never heard of 10 years ago), I did so and became well immediately. When I attempted to see a celiac specialist, I had to wait 2 months. I was told to continue the diet until I saw the specialist. Once I saw the specialist, he told me that I had return to a gluten diet to accurately diagnose me. I told him to dig a hole and throw me in as I would not touch gluten. He then charted me as "celiac" but I truly don't know. I think the medical world in America still has a long way to go in researching possible treatment/antidote for celiac disease and gluten intolerance.

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    Guest Karen Kritchen

    Posted

    5 stars for the presentation by Jefferson Adams. 2 stars for the actual researchers. Why? Because anyone who has ever been on a gluten-free diet can tell the difference between regular bread and gluten-free bread, and this may influence their complaints. So, if the researchers really wanted this to be double-blind and placebo controlled, they should have given gluten in a capsule to the experimental group, and an identical capsule containing something like rice flour to the control group.

     

    This was bad experimental design!

    As soon as I read the article I said uh-oh, don't they know we gluten-free's can taste the difference!

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    Guest betsy frahm

    Posted

    I am gluten intolerant and because I do not get sick after ingesting gluten, it makes it easier for me to cheat. I can stay gluten-free only so long and my craving for a good sandwich just takes over.It would be very nice to know that cheating occasionally isn't doing the same damage as if I were a true celiac. I agree with Hallie's comment. So far there is no gluten-free bread or muffin that tastes the same as that made from wheat. I would agree that a pill would have been the way to go. But keep on trying with the research. I have hope that there will be something like Lactaid for milk intolerance.

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    Guest Barbara Irlbeck

    Posted

    Interesting article.

     

    I call myself gluten intolerant though have never had an 'official' diagnosis. I tried gluten free diet three years ago, upon recommendation from my internist , as a help for peripheral neuropathy in my feet. I never tested for gluten intolerance. However, about two years after adopting the gluten free diet, I did have the test for HLA-DQ2 and HLA-DQ8 and found I was negative for being celiac. It was important to me to know because I have children and grand children.

     

    Last summer when I was not settling in to sleep because I felt like a supplement I had taken was 'stuck in my throat', I got up and ate one piece of toast from loaf of bread that was labeled "flourless." I found out the next day that it contained wheat sprouts instead of the usual flour. After eating it, I returned to bed and fell asleep. About a half to one hour after consuming the bread, I awoke very nauseated and ended up spending the next half hour or so hanging over the toilet as I vomited up everything in my stomach. I have no real explanation for this, but decided it proved that I am definitely gluten intolerant. I now read labels more thoroughly.

     

    The flourless bread was shelved with gluten free breads at the store and thus I did not questions it as I should have. This incident happened in the night and I was not the least sick when went to bed that night, nor was I when I got up the next morning.

     

    By the way, I no longer have any burning in my feet and not much parastheia either. I am committed to staying on a gluten free diet.

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    Guest Barbara Ross

    Posted

    Am I understanding that if you are gluten intolerant, without celiac disease, there would be no antibodies present (in blood, stool or otherwise)?

    Also, agree with Hallie. Even people who have never been on gluten free diets would realize that gluten free bread is different. Those sausages with wheat fillers would have done the trick!

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    5 stars for the presentation by Jefferson Adams. 2 stars for the actual researchers. Why? Because anyone who has ever been on a gluten-free diet can tell the difference between regular bread and gluten-free bread, and this may influence their complaints. So, if the researchers really wanted this to be double-blind and placebo controlled, they should have given gluten in a capsule to the experimental group, and an identical capsule containing something like rice flour to the control group.

     

    This was bad experimental design!

    Actually, there are gluten-free breads which are very similar to French bread, and gluten-free muffins which are essentially indistinguishable from regular ones. Perhaps they made the regular muffins and bread more similar to the gluten-free controls. We'd have to read the whole article to find out.

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    Guest Jo Fick

    Posted

    I am gluten intolerant and because I do not get sick after ingesting gluten, it makes it easier for me to cheat. I can stay gluten-free only so long and my craving for a good sandwich just takes over.It would be very nice to know that cheating occasionally isn't doing the same damage as if I were a true celiac. I agree with Hallie's comment. So far there is no gluten-free bread or muffin that tastes the same as that made from wheat. I would agree that a pill would have been the way to go. But keep on trying with the research. I have hope that there will be something like Lactaid for milk intolerance.

    I can so identify with this. At this point, I'm still waiting for results of the biopsy. But an EGD showed flattening of the duodenum, which had never shown up before. I didn't even know what it meant. I have no typical celiac symptoms. In fact, I am overweight. I don't notice any ill effects from ingesting gluten. And I am a carb/bread lover from way back. Oddly enough, my brother was just diagnosed with severe celiac. He had been untreated for years, and was very ill; it was thought he had cancer. He's doing worlds better now; he is extremely cautious after having a bad reaction that left him sick for more than a week. Seems I read somewhere they are working on developing a vaccine for celiac. Wouldn't that be wonderful?

    No doubt there will be a laundry list of other foods to avoid coming after they do blood testing. And every gluten-free bread I've tried is yuck. I thought the same thing when I read about that study. I can always tell a gluten-free product. It doesn't help that they douse a lot of the baked goods with sugar to disguise the taste. Eating gluten-free doesn't mean eating healthy.

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    I am glad someone is at last taking this subject seriously. My four year old grandson has been tested for celiac disease but it was confirmed that he did not have it. However, we (his family) know that if he eats gluten products he becomes twitchy (really mild spasms); especially in his sleep, his intestines grumble really badly, he becomes more hyperactive and naughty and when he drinks milk it hurts his stomach. If, however, we maintain his gluten-free diet, he is calm, not at all twitchy, you never hear his stomach grumble and when he drinks milk, he is fine. It is annoying that the doctors do recognise gluten intolerance if celiac is not present. So I say well done for the research. Much more is needed, especially with children and gluten intolerance to convince the medical world.

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    Guest Eugenia Rodgers

    Posted

    Interesting. I have severe systematic shin splints, tumor knots behind both knees and both sides of groin area, and extreme exhaustion whenever I eat gluten. This reaction has been going on since Spring 2009. Also, I deal with IBS and have been diagnosed with Rocky Mountain Spotted Fever last week. I have been looking since 2009 for someone to listen to me. Thank you.

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Jefferson Adams
    Patients Diagnosed in Childhood Might Evolve toward Latency on a Normal Diet
    Celiac.com 05/23/2007 - The results of a study recently published in the journal Gut indicate that some people who suffer from celiac disease might not need to remain on a gluten free diet for their entire lives, and that some celiac patients might be able to safely introduce gluten containing foods without suffering a relapse.
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    Several studies have shown that some patients diagnosed with celiac disease in childhood were able to remain on a gluten-containing diet after gluten challenge without suffering a relapse. However, most of these studies included a small number of patients, or followed the patients for only a short period after gluten was reintroduced into their diets.
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    Determining Long-term Response to Gluten Consumption in Celiac Disease Patients
    A research team made up of doctors Tamara Matysiak-Budnik (1), Georgia Malamut (1,2), Natacha Patey-Mariaud de Serre (3), Etienne Grosdidier (2), Sylvie Seguier (3), Nicole Brousse (3), Sophie Caillat-Zucman (4), Nadine Cerf-bensussan (1), Jacques Schmitz (5) and Christophe Cellier (1,2), set out to determine whether children diagnosed with celiac disease must follow a gluten free diet for life.
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    Results Show 20% Long-term Latency in Celiac Patients who Eat Normal Diet
    Of those studied, 61 patients had returned to a normal diet, and were asymptomatic. 48 showed various degrees of villous atrophy (silent celiac disease), and 13 had no detectable atrophy (latent celiac disease) on duodenal biopsies. Compared to those with silent celiac disease, patients with latent celiac disease showed markedly less osteopenia/osteoporosis [1/9 (11%) versus 23/33 (70%), p<0.001)], and lower TcR- + intraepithelial T cell counts (38±20 vs. 55±15, p<0.01).
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    Compared to the seven control patients on a long-term gluten free diet, the latent patients did not differ significantly, except for a higher frequency of celiac disease-specific serum antibodies. However, a follow-up found that two of the patients with latent celiac disease had suffered a clinical and histological relapse.
    Results showed that of those patients who remained asymptomatic after the reintroduction of gluten, 20% showed long-term latency.
    The study concludes that some patients with celiac disease may not need to remain on a life-long gluten free diet, and that some may indeed be able to safely reintroduce gluten into their diets with no adverse effects. However, the latency patients may experience may be transient, and therefore a regular follow-up is necessary. Also, patients with silent celiac disease should remain on a gluten free diet.
    Participating hospitals:
    (1) INSERM, U793, Faculté de Médecine René Descartes, IFR94, Paris, France.
    (2) AP-HP, H&OCIRC;pital Européen Georges Pompidou, Department of Hepato-Gastroenterology,
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    (3) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pathology, Paris, France.
    (4) INSERM, Equipe Avenir, Faculté de Médecine René Descartes, Paris, France.
    (5) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pediatric Gastroenterology, Paris, France.
    Gut 2006;13(10).
    Comments on this Study by Ron Hoggan
    This is dressed up like a new finding, but it isn't. There are a number of studies that show similar findings. Part of that problem lies in the interpretation of the biopsies, and part of the problem arises out of failing to recognize the variable nature of the disease. It has long been known to wax and wane for reasons beyond our ken. Samuel Gee (1888) and Gibbons (1889) both reported the cyclic nature of their patients symptoms. They cited a study to support the idea of a two year rule saying that relapse would usually occur within two years, yet Kuitunen P, Savilahti E, Verkasalo M., in Late mucosal relapse in a boy with coeliac disease and cows milk allergy. Acta Paediatr Scand. 1986 Mar;75(2):340-2. reported one patient who at 4.3 years on a normal diet showed normal villous architecture. It was not until a follow-up biopsy at more than 8 years of eating a gluten-containing diet that he showed villous atrophy. These findings, along with all the other studies that have shown long delays in some patients before relapsing, argue strongly for Michael N. Marsh's position that we should concentrate on treating any immune system that is sensitized to gluten with a gluten-free diet. His rectal challenge is an excellent tool for identifying such sensitized immune systems. Dr. Fines fecal antibody test probably fits into the same category. The underlying assumption is that the biopsy will identify all cases of intestinal lesion regardless of the possibility of patchy lesions that are well documented in the literature. They deal with increased IEL counts as if they were a feature of latent celiac disease when that is not the case. There are several other points on which this study falters. They admit that the latency can be transient. Unfortunately, they have not exchanged emails with people where they have returned to eating gluten and have developed an abdominal cancer. I exchanged emails with such a young man who blamed himself for having killed himself with his carelessness about his diet. How awful that was for him! Yet these authors seem to think it is quite acceptable for patients to indulge during their latency periods and only consider a diet if there is a relapse of intestinal lesion.
     

    Jefferson Adams
    Celiac.com 10/26/2010 - A recent study shows that, since 1974, the rate of celiac disease has doubled every fifteen years, and that celiac rates increase as people grow older, with many developing the disease in their 50s or 60s.
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    SOURCE:
    Annals of Medicine: October 2010, Vol. 42, No. 7 , Pages 530-538
    doi:10.3109/07853890.2010.514285



    Jefferson Adams
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    Source:

    BMC Medicine 2011, 9:23 doi:10.1186/1741-7015-9-2

    Jefferson Adams
    Celiac.com 09/28/2012 - Two researchers recently set out to study gluten sensitivity in people without celiac disease. The study was conducted by A. Di Sabatino A, and G.R. Corazza of the Centro per lo Studio e la Curia della Mallatia Celiaca at the Fondazione IRCCS Policlinico San Matteo at the University of Pavia in Italy.
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    Source:
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    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.