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    Gluten Challenge: Patients with Non-celiac Gluten Sensitivity Report More Symptoms than Those with Celiac Disease


    Jefferson Adams

    Celiac.com 06/13/2012 - In general, doctors and researchers know a good deal about how celiac disease works, and they are finding out more all the time. However, they know very little about non-celiac gluten sensitivity (NCGS).

    Photo: CC -- EmeraldimpIn an effort to learn more about non-celiac gluten sensitivity, a team of researchers recently carried out a study to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals, and to compare the results with celiac disease patients and healthy control subjects. They also compared the response to gluten challenge between patients with non-celiac gluten sensitivity and those with celiac disease.

    The research team included M. Brottveit, P.O. Vandvik, S. Wojniusz, A. Løvik, K.E. Lundin, and B. Boye, of the Department of Gastroenterology at Oslo University Hospital, Ullevål in Oslo, Norway.

    In all, the team looked at 22 patients with celiac disease and 31 HLA-DQ2+ NCGS patients without celiac disease. All patients were following a gluten-free diet.

    Over a three day period, the team challenged 17 of the celiac disease patients with orally ingested gluten. They then recorded the symptoms reported by those patients. They did the same with a group of 40 healthy control subjects.

    The team then had both patients and healthy control subjects complete questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life.

    Interestingly, patients with non-celiac gluten sensitivity reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after the gluten challenge than patients with celiac disease. The increase in symptoms in non-celiac gluten sensitivity patients was not related to personality.

    However, the two groups both reported similar responses regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. Responses for both groups were about the same as for healthy controls.

    The results showed that patients with non-celiac gluten sensitivity did not show any tendencies toward general somatization, as both celiac disease patients and those with non-celiac gluten sensitivity showed low somatization levels.

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    Guest Dr Charles Parker

    Posted

    Interesting report, coincides with our personal observations in the office. Some with the most pervasive psychological and biomedical challenges show almost no specific bowel symptoms - and we must work hard to chase down the details.

     

    In our work, with hundreds of IgG testing reviews: milk is even more prominent as a primary causality in immune dysregulation than wheat, and eggs join that triad at the top.

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    Guest SandraB

    Posted

    For us laymen, somatization is "the conversion of mental experiences into bodily symptoms" i.e., the pain in the body is real, but due to mental stress rather than having a physical cause. Known to the cynical as "It's all in the head."

    So it's not all in our heads. It's in our guts - which is where and how we knew it was.

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    Guest Laura

    Posted

    I am very happy to see this article and study! I am new to the gluten-free lifestyle. I was referred to a gastrointestinal doctor who thought my claims of having reactions to gluten other than digestive were crazy. I may be crazy, but I knew I was right!

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    Guest Laura Cunard

    Posted

    When I wrote out a full history of how gluten affects me, the GI I showed it to looked at me like I was nuts. He knew NOTHING about non-celiac gluten intolerance. I left the office rather depressed and went back to taking care of myself without help from any doctor. I'd sure like to find one nearby that does know something.

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    Hi Laura,

    My doctor also knew nothing about non-celiac gluten intolerance and I have since found out that they are not taught much about food intolerance at med school. I had symptoms for over 20 years and have found that the only person able to help me was, well, me! Dozens of doctors, no advice that was of any help, tired, fed up, unwell every single day all down to a tiny protein. Now if they had only told me that 20 years ago, life would have been so much better. I did, however, find a wonderful dietitian who specializes in food intolerance. That may be your best bet.

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    Guest Patricia

    Posted

    Having many of the symptoms for celiac disease (including many positive family members) I decided to go gluten-free 4 weeks ago and feel so much better. Of course, after 4 weeks of being gluten-free, my bloodwork came back negative. I'm now on a gluten challenge for one week (doc recommendation) and will have my blood retested. The first night of having gluten I was really sick (in and out of the bathroom for approximately 6 hours). In the next few days, the symptoms seem to be changing, i.e. constipation. Can anyone tell me if this is a direct result of consuming gluten again? I am extemely frustrated with the process. I'm also concerned that the bloodwork will again be negative and therefore be crazy to go back to a gluten-free diet if not necessary. But, am I correct in thinking that all blood tests can be negative and still have a gluten sensitive issue? I have not had the intestinal biopsy and probably should not have it done if all bloodwork is negative, right? ANY help would be appreciated.

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    By the time my daughter was 19 she was sick and had routinely been seeing specialists for 2 years who thought she might have Lupus, though she tested negative. She is 5'10" and when she finally hit 112 pounds, I said "Thats it!!". I took her to an alternative doctor who diagnosed her as food allergies/sensitivities. She was tested and found to have dairy, eggs, beef, gluten, soy, garlic, and pineapple. Non-Celiac Gluten Sensitivity has already caused so much damage to her GI that she has had 2 surgeries. She eats a very strict diet, which has helped greatly. She is retested annually because your sensitivities can change (which they have). Also... did you know that food sensitivities can cause you to be tired, give you arthritic problems, and skin issues like eczema and rashes? Taking supplements is a must for the rest of your life due to malabsorption and diet.

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    Having many of the symptoms for celiac disease (including many positive family members) I decided to go gluten-free 4 weeks ago and feel so much better. Of course, after 4 weeks of being gluten-free, my bloodwork came back negative. I'm now on a gluten challenge for one week (doc recommendation) and will have my blood retested. The first night of having gluten I was really sick (in and out of the bathroom for approximately 6 hours). In the next few days, the symptoms seem to be changing, i.e. constipation. Can anyone tell me if this is a direct result of consuming gluten again? I am extemely frustrated with the process. I'm also concerned that the bloodwork will again be negative and therefore be crazy to go back to a gluten-free diet if not necessary. But, am I correct in thinking that all blood tests can be negative and still have a gluten sensitive issue? I have not had the intestinal biopsy and probably should not have it done if all bloodwork is negative, right? ANY help would be appreciated.

    Hey Patricia

    I've had chronic constipation for years. My joints and lower back ached regularly, my iron counts were often low, low wbc, low end of B12, bloated, abdominal pain, foul smelling and fatty BM (very small... like almond-sized) and never relieved, gassy, fatigue, and my hair fell out more than normal in the shower. I did have a long list of food and seasonal allergies as a kid... nothing life-threatening, but take Aerius from April to first frost to manage my symptoms. I do get itchy skin and throat/ear canal, and a feeling of water in my ears... like hearing under water. On top of this I am having acid reflux, nausea, and indigestion, with a feeling of a fist in my stomach (which a prescription for Ranitidine is helping magnificently!) All this said...years of these complaints have been fluffed off by my doctor. Every year at the time of my physical I'd complain about these symptoms, and every year he'd put me on iron if blood tests showed low counts, and tell me to drink more water and eat more fiber! What he wasn't listening to is that I DO drink plenty of water, and my diet is VERY high in fruits/veggies and fiber! My mother-in-law calls me the walking Canada food guide!

     

    I was out of work in September when the kids returned to school and I decided to look into things myself. I found an interesting article online that suggested IBS symptoms could be linked to gluten intolerance. My mother-in-law IS celiac, so I am familiar with the diet and the label reading (because I do cook family meals). I always rolled my eyes at her when she suggested I get tested (hubby and kids were tested for celiac disease, but since I'm not in that blood line I didn't bother). After less than a week eating gluten-free, I began having regular bowel movements. After 2 weeks my joint pain was gone, the water in the ear feeling is mainly gone (had a few brief episodes) and pain in stomach gone. Most all of my symptoms are gone or greatly improved... it's been 5.5 weeks now. At 2 weeks gluten-free, I had a doctor's appt. His eyebrows shot up at my reports. He thinks my heartburn problems and my stomach issues may be connected, and I have been referred to a GI and an Alergist. In the meanwhile I had a genetic blood test for celiac disease since at the time of the requisition I'd already been gluten-free for 4 weeks and probably wouldn't show the necessary antibodies. BUT guess what? I got a call this week from the nurse saying I may, in fact, have celiac disease because it showed that my genetic make up supported a probability of Celiac!!! So, now I wait. I am not sure if I would consider going back to wheat in my diet just for a certain diagnosis. If things are working, I don't feel the need to be a "card-carrying Celiac"! I would, though, agree to the biopsies of the esophagus and intestines to rule out any growths or cancer.

     

    Sorry so long-winded. Hope this helps!

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    Guest Leen Coremans

    Posted

    When I wrote out a full history of how gluten affects me, the GI I showed it to looked at me like I was nuts. He knew NOTHING about non-celiac gluten intolerance. I left the office rather depressed and went back to taking care of myself without help from any doctor. I'd sure like to find one nearby that does know something.

    Your story is an exact copy of what I went through, Laura! Very frustrating indeed. Luckily we were both stubborn enough to do what we felt was right and go gluten-free. But a doctor who believes you would sure feel good, so I'm very happy to read these kinds of studies and am impatiently awaiting the day where NCGS will be just as well-known as celiac itself (and preferably receive a more suitable name).

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    Guest Lapinta59

    Posted

    Neither my spouse nor I have been tested for gluten sensitivity but my spouse has had stomach problems for years: bloating, gas, diarrhea, intestinal distress, etc. The docs always gave him Prilosec and Tums but nothing worked. He has other food allergies to oats, eggs, and red dye. We tried a completely gluten free diet and ALL of his symptoms disappeared. It has been nothing short of a miracle. I found on the gluten-free diet that my joint pain, fatigue, depression, blood sugar issues, and dermatitis disappeared. I had been told by my docs that I had osteoarthritis and had been prescribed massive doses of Ibuprofen....now I can say all that pain is gone, my skin in clear and I am no longer fatigued or depressed. Who new gluten could be so destructive!

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, and science. He previously served as Health News Examiner for Examiner.com, and provided health and medical content for Sharecare.com.

    Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book Dangerous Grains by James Braly, MD and Ron Hoggan, MA.

  • Popular Contributors

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    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.
    Previous Studies Showing Positive Response to Wheat Introduction in Patients with Celiac Disease are Promising, But Incomplete
    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.
    These previous studies also limited their evaluation largely to assessment of celiac disease serology and histology of duodenal biopsies, and did not attempt to identify what factors might predict the development of tolerance to gluten.
    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.
    To determine the effects of reintroducing gluten into the diets of celiac patients, the research team set out to monitor the clinical and physical progress of adult celiac patients who had been diagnosed as children, who underwent a gluten challenge, and who were asymptomatic.
    The study focused on a specific group of patients, all but two of whom were diagnosed as children and followed until adulthood in the Department of Pediatric Gastroenterology in Necker Hospital and thereafter at the Georges Pompidou European Hospital in Paris; after which, they were entered into a local register of adult celiac patients and were recruited for the study based on two criteria: celiac disease diagnosed in childhood; and adherence to a normal diet.
    The patients in the study were from 18 to 65 years old, and had been diagnosed with celiac disease in childhood. The research team recorded data in the following categories: biological parameters of malabsorption; bone mineral density; clinical celiac status; gluten intake; HLA genotype; serological markers of celiac disease; as well as histological and immuno-histochemical parameters in duodenal biopsies.

    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).
    Patients with latent celiac disease had a lower mean age at the time of their first gluten free diet compared to patients with silent celiac disease (14.4±5 vs 40.1±47 months, p<0.05).
    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,
    Paris, France.
    (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
    Blood Tests Different in Patients with Gluten Sensitivity Than in Those with Celiac Disease
    Celiac.com 12/03/2012 - Gluten sensitivity has recently been added to the spectrum of gluten-related disorders, but precise diagnostic markers do not yet exist. A research team recently set out to understand the blood test pattern of gluten sensitivity, and to compare it with the blood test pattern seen in celiac disease.
    The researchers included U. Volta, F. Tovoli, R. Cicola, C. Parisi, A. Fabbri, M. Piscaglia, E. Fiorini, G. Caio, of the Department of Clinical Medicine at University of Bologna's St. Orsola-Malpighi Hospital in Bologna, Italy.
    For their study, the researchers looked at blood samples from 78 patients with gluten-sensitivity and 80 patients with celiac disease. They assessed levels of immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA).
    They found positive readings for IgG AGA in 56.4% of patients with gluten-sensitivity, and in 81.2% of patients with celiac disease. Antibody levels for both groups were in the high range.
    They found IgA AGA in 7.7% of patients with gluten-sensitivity, and in 75% of patients with celiac disease, which shows lower enzyme-linked immunosorbent assay activities in gluten-sensitivity patients than in patients with celiac disease.
    Only 1 of the 78 patients with gluten-sensitivity tested positive for IgG DGP-AGA, which was found in nearly 90% of patients with celiac disease.
    All patients with gluten-sensitivity tested negative for IgA tTGA and IgA EmA, while 98.7% of patients with celiac disease tested positive for IgA tTGA, and 95% were positive for IgA EmA.
    Patients with gluten-sensitivity presented a variety of intestinal and extra-intestinal symptoms, including abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia. Small intestinal mucosa for these patients was either normal or only mildly abnormal.
    The data from these blood tests show that more than half of patients with gluten sensitivity will test positive for IgG AGA, and a small number will test positive for IgA AGA, but none will show positive results for EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.
    Source:
    J Clin Gastroenterol. 2012 Sep;46(8):680-5.

    Jefferson Adams
    Celiac.com 02/04/2013 - Ever wonder what happens to all those celiac disease patients who volunteer to do a gluten-challenge in the name of science? Well, the short answer is that they likely suffer, and may incur gut damage, at least in the short term.
    A team of researchers looking for ways to reduce or eliminate that problem recently conducted a study using larazotide acetate, a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated problems.
    The research team included C. P. Kelly, P. H. R. Green, J. A. Murray, A. DiMarino, A. Colatrella, D. A. Leffler, T. Alexander, R. Arsenescu, F. Leon, J. G. Jiang, L. A. Arterburner, B. M. Paterson, R. N. and Fedorak. They are affiliated with the Celiac Center of Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, the Celiac Disease Center at Columbia University in New York, NY, the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, MN, Thomas Jefferson University Hospital in Philadelphia, PA, the Pittsburgh Gastroenterology Associates in Pittsburgh, PA, with Gastrointestinal Specialists of Troy, MI, the Department of Internal Medicine at the University of Kentucky, in Lexington, KY, with Alba Therapeutics Corporation in Baltimore, MD, and with the Division of Gastroenterology at the University of Alberta in Edmonton, AB.
    The team wanted to find out how well larazotide acetate worked and how well it was tolerated by celiac disease patients undergoing a gluten challenge.
    To do this, the team conducted an exploratory, double-blind, randomized, placebo-controlled study that included 184 patients who maintained a gluten-free diet before and during the study.
    After a gluten-free diet run-in, the team randomly divided patients into groups and gave them either larazotide acetate in doses of 1, 4, or 8 mg three times daily, or a placebo. Both groups also received 2.7 grams of gluten daily for six weeks.
    The team then assessed ratios of lactulose-to-mannitol (LAMA), an experimental biomarker of intestinal permeability, and measured clinical symptoms by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels.
    They found no significant differences in LAMA ratios between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo).
    They did find that the average ratio of anti-tissue transglutaminase IgA levels was 19.0 over baseline in the placebo group compared with 5.78 (P = 0.010) in the 1mg larazotide acetate group, 3.88 (P = 0.005) in the 4mg larazotide acetate group, and 7.72 (P = 0.025) in the 8mg larazotide acetate group.
    Both the larazotide acetate and placebo groups showed similar rates of "adverse events."
    Overall, the team found that larazotide acetate reduced gluten-induced immune reactivity and symptoms in celiac disease patients undergoing gluten challenge and was generally well tolerated.
    However, the team found no significant difference in LAMA ratios between the larazotide acetate and placebo groups.
    Even though they did not find anything revolutionary, the results and design of their study will likely be helpful in shaping future gluten-challenge studies in patients with celiac disease.
    Source: 
    Aliment Pharmacol Ther. 2013;37(2):252-262.

    Jefferson Adams
    Celiac.com 09/23/2013 - Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease, but see an improvement in symptoms when they adopt gluten-free diets.
    A team of researchers recently investigated the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in patients with suspected NCGS.
    The research team included Jessica R. Biesiekierski, Simone L. Peters, Evan D. Newnham, Ourania Rosella, Jane G. Muir, and Peter R. Gibson.
    The team performed a double-blind cross-over trial of 37 subjects (aged 24−61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease.
    They assigned study participants randomly to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for 1 week, followed by a washout period of at least 2 weeks.
    The researchers then evaluated serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue.
    The team then crossed twenty-two participants over to groups receiving gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days, using visual analogue scales to evaluate symptoms.
    They found that gastrointestinal symptoms consistently and significantly improved for all patients during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein.
    The team saw gluten-specific effects in just 8% of study subjects. They saw no diet-specific changes in any biomarker. During the 3-day re-challenge, participants’ symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed.
    A placebo-controlled, cross-over re-challenge study showed no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs.
    Source:
    Gastroenterology, Volume 145, Issue 2, Pages 320-328.e3, August 2013. More info on the FODMAP diet from Stanford Univerisity.

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