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    Patients with Suspected Non-celiac Gluten Sensitivity React Adversely to Gluten


    Jefferson Adams

    Celiac.com 03/23/2015 - There's been a bit of ping-ponging going on about the status of non-celiac gluten sensitivity as a valid medical condition. Studies have yielded conflicting results, with some supporting, and others negating, the existence of non-celiac gluten-sensitivity. 


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    Photo: CC--JeffreyWSo what's the deal? Does non-celiac gluten sensitivity exist, or not? Researchers and clinicians continue to debate whether people without celiac disease or wheat allergy who consume gluten can experience intestinal and extra-intestinal symptoms attributable to non-celiac gluten sensitivity (NCGS).

    Taking the latest stab at the problem, a team of researchers recently conducted a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS. The research team included A. Di Sabatino, U. Volta, C. Salvatore, P. Biancheri, G. Caio, R. De Giorgio, M. Di Stefano, and G. R. Corazza. They are variously affiliated with the First Department of Internal Medicine at St Matteo Hospital Foundation at the University of Pavia in Pavia, Italy, and with the Department of Medical and Surgical Sciences at St Orsola-Malpighi Hospital at the University of Bologna in Bologna, Italy.

    For their study, the team enrolled 61 adults without celiac disease or wheat allergy, but who believe that eating gluten-containing food to be causing of their intestinal and extra-intestinal symptoms. The team randomly assigned participants to groups that received either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastro-soluble capsules. Study subjects spend one week on a gluten-free diet, and then switched groups.

    The primary outcome was the change in overall (intestinal and extra-intestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo.

    Per-protocol analysis of data from the 59 patients who completed the trial shows that intake of gluten significantly increased overall symptoms compared with placebo (P=.034). Among the intestinal symptoms, abdominal bloating (P=.040) and pain (P=.047) were significantly more severe when subjects received gluten than placebo. Among the extra-intestinal symptoms, foggy mind (P=.019), depression (P=.020), and aphthous stomatitis (P=.025) were also worse when subjects received gluten than placebo.

    In this cross-over trial, subjects with suspected NCGS saw significantly more severe symptoms during 1 week of intake of small amounts of gluten, compared with placebo. So, at least for now, the NGCS ball seems to be back in the court that considers it a valid medical condition.

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    I was on gluten 5 years ago, horrible symptoms (severe brain fog, diarrhea, fatigue), blood test for celiac negative. Since then 100% gluten free, feel a lot better. Now when I eat only 2-3 grains of wheat, I get a strong brain fog that can last up to 10 days. Seems that I have a strong case of NCGS.

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    The one major problem I see with this study is what we all know, really, and that is those classified as having non-celiac gluten sensitivity may in fact have celiac sprue and have not been properly diagnosed prior to study. This is only one of many reasons these studies may not be conclusive as to the existence of the entity physicians seem to have fudged because they are so inadept at making an affirmative diagnosis of celiac sprue.

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    The crazy thing is, you are only considered to have celiac disease if your positive antibody reading is greater than 10. Yet ANY antibody response to wheat proteins indicates an issue. Even a 0.1 response is a response (and many people can return a very low reading due to a suppressed immune system, not because they don't have celiac disease or their NCGS isn't actually more severe than it seems).

     

    You are only considered to have celiac disease if your level is greater than 10 and you have detected gut damage, but couldn't NCGS simply be, like 'Metabolic Syndrome' is to diabetes, a possible precursor to celiac?

     

    Not everyone with Metabolic issues goes on to develop diabetes, but many do. Similarly, not everyone with NCGS will go on to develop 'full blown' celiac disease, but many do.

     

    The Medical profession never looks for anything until it is 'full blown'. Getting anyone with ANY level of antibody response, regardless of the numbers, off the trigger foods ought to be a huge preventative, not to mention money and resource-saving commitment within the 'health' industry.

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    I have had an intestinal biopsy and blood tests that confirm that I do NOT have celiac disease but I definitely, positively, without a doubt have intestinal troubles and skin rashes when I eat wheat. I am sensitive to some other foods too so I don't view avoiding gluten as a cure-all for every ailment. I hope, Jeff, that you will continue to support the NCGS among us because I assure you that the condition is real.

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    Guest Nancy

    Posted

    I have biopsy diagnosed celiac disease. My son also has biopsy diagnosed celiac disease. My daughter's blood test for celiac disease was negative so she didn't have a biopsy. She had more physical symptoms of celiac that either of us, so she tried a gluten free diet. There was so much improvement in her overall health that she has stayed on that diet for almost 9 years now. Is it really non celiac gluten sensitivity or really celiac that had not really shown up all those years ago?

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    I was also on gluten/wheat about seven years ago. Had all the classic symptoms, but in my case, it was not celiac but thyroid related. My thyroid levels were a mess and I had even developed goiters on my thyroid. After the doctor had me eliminate wheat/gluten from my diet, all these problems resolved and I felt 100% better.

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    I was also on gluten/wheat about seven years ago. Had all the classic symptoms, but in my case, it was not celiac but thyroid related. My thyroid levels were a mess and I had even developed goiters on my thyroid. After the doctor had me eliminate wheat/gluten from my diet, all these problems resolved and I felt 100% better.

    I am sure that wheat/gluten proteins trigger a huge array of health problems, celiac disease being just one of them. The most obvious issue connected to gluten is celiac, but that is only because it is the one disease that has been proved beyond doubt to be connected.

     

    More and more diseases and health issues are beginning to be linked to modern grains, but research on them is still very much in its infancy.

     

    Sadly, whilst even many with celiac slip through the net because the testing procedure is so unreliable, those with one or some of the seemingly unrelated non-gut issues are even less likely to be advised to try a gluten-free diet.

     

    Since I first visited my doctor with my suspicion about having celiac disease (when I was only given one blood test which was almost inevitably negative despite my raging IBS, stomach pain, restless legs and neuropathy which all went away on gluten free), she has become 'enlightened' and now will send patients who return a negative result for further testing on more occasions. Several of the doctors there will recommend gluten-free, and one is gluten-free himself.

     

    To find a doctor who is aware of the links between gluten and health issues other than celiac is a very rare and precious thing. What a great doctor you have!

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    I am one of the many who gave up gluten without a celiac disease test. I will probably never get a diagnosis, because even an amount that I can not even see will cause me too much pain to want to go back on gluten long enough to get the test. It is good to know that someone is looking out for us.

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    I too have been in pain for going on 8 years now. I have been to 3 different doctors with the same issues, extreme stomach pain, bloating, gassy, lethargic, constipation to diarrhea. All 3 Doctors have automatically (due to age) thought it was my gall bladder. After CT scan(s). They decided it was nothing more than IBS...eat more fiber, drink more liquid etc...when I tell them the only way I could eat more fiber would be if I ate the bark off of trees, they laugh well not sure what to tell you. The point is that none of these doctors have even thought about celiac disease. One of my coworkers suggested I try a Gluten Free diet. I have now been on the gluten-free diet for 6 weeks and there has been a world of difference. No more stomach pain, no more bloating, no more diarrhea or constipation.

    I now seem to have more energy, at least after lunch I'm not fighting to keep my eye lids from closing. I'm not sure I will have the blood test...because to me it isn't important to know whether or not I have celiac disease....because as long as I am off dairy and Gluten....I FEEL SO MUCH BETTER!

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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
    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).
    In 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.
    Source:
    Scand J Gastroenterol. 2012 Apr 23.

    Jefferson Adams
    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 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.

    Jefferson Adams
    Celiac.com 07/25/2014 - People with non-celiac gluten sensitivity (NCGS) do not have celiac disease, but their symptoms improve when they are placed on gluten-free diets.
    A research team set out to study the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in subjects believed to have NCGS. The study team included J.R. Biesiekierski of the Department of Gastroenterology, Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia, and colleagues S.L. Peters, E.D. Newnham, O. Rosella, J.G. Muir, and P.R. Gibson.
    They conducted a double-blind cross-over trial on 31 women and 6 men, aged 24-61, with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Researchers randomly assigned participants to groups given a 2-week diet of reduced FODMAPs. Participants 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 team measured serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants were then given either gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days. The team evaluated symptoms using visual analogue scales.
    Every patient experienced significant improvement in gastrointestinal symptoms during reduced FODMAP intake. Conversely, every patient experienced significantly worse symptoms when their diets included gluten or whey protein. The team observed gluten-specific effects in just 8% of participants. 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.
    The end result for this placebo-controlled, cross-over re-challenge study showed no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed on diets low in FODMAPs. The translation is that the team saw no effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.
    Source:
    Gastroenterology. 2013 Aug;145(2):320-8.e1-3. doi: 10.1053/j.gastro.2013.04.051. Epub 2013 May 4.  

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    Source:
    PLoS Med. 2018 Feb; 15(2): e1002507. doi:  10.1371/journal.pmed.1002507

    Jefferson Adams
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    BMC Pediatrics

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