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No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates

  • Jessica R. Biesiekierski
    Affiliations
    Department of Gastroenterology, Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia

    Department of Gastroenterology, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Victoria, Australia
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  • Simone L. Peters
    Affiliations
    Department of Gastroenterology, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Victoria, Australia
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  • Evan D. Newnham
    Affiliations
    Department of Gastroenterology, Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia
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  • Ourania Rosella
    Affiliations
    Department of Gastroenterology, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Victoria, Australia
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  • Jane G. Muir
    Affiliations
    Department of Gastroenterology, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Victoria, Australia
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  • Peter R. Gibson
    Correspondence
    Reprint requests Address requests for reprints to: Peter Gibson, MD, Department of Gastroenterology, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Victoria 3004, Australia. fax: +613 9076 2194.
    Affiliations
    Department of Gastroenterology, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Victoria, Australia
    Search for articles by this author

      Background & Aims

      Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated 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.

      Methods

      We 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. Participants were randomly assigned 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. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed over to groups given gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days. Symptoms were evaluated by visual analogue scales.

      Results

      In all participants, gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein. Gluten-specific effects were observed in only 8% of participants. There were no diet-specific changes in any biomarker. During the 3-day rechallenge, participants’ symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed.

      Conclusions

      In a placebo-controlled, cross-over rechallenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs. www.anzctr.org.au. ACTRN12610000524099

      Keywords

      Abbreviations used in this paper:

      D-FIS (Daily-Fatigue Impact Scale), FODMAP (fermentable, oligo-, di-, monosaccharides, and polyols), GFD (gluten-free diet), IBS (irritable bowel syndrome), NCGS (non-celiac gluten sensitivity), VAS (visual analogue scale)
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      Linked Article

      • Non-Celiac Wheat Sensitivity Is a More Appropriate Label Than Non-Celiac Gluten Sensitivity
        GastroenterologyVol. 146Issue 1
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          We have read with great interest the article by Biesiekirski et al,1 in which a double-blind, placebo-controlled (DBPC) rechallenge study demonstrated a lack of evidence of specific or dose-dependent effects of gluten in patients with non-celiac gluten sensitivity (NCGS) while on a low FODMAP diet. The authors themselves noted that these data are inconsistent with their previous study,2 and considered the strict control on the patients' diet throughout the entire study a pivotal difference. During the new study, all patients consumed a diet including foods with low FODMAP content and this led to an immediate improvement of the irritable bowel syndrome (IBS) symptoms, irrespective of the successive gluten challenges.
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