title: No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.
abstract: OBJECTIVE
  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.
authors: Department of Gastroenterology, Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia.
authors: Jessica R
authors: JR
authors: Biesiekierski
authors: Simone L
authors: SL
authors: Peters
authors: Evan D
authors: ED
authors: Newnham
authors: Ourania
authors: O
authors: Rosella
authors: Jane G
authors: JG
authors: Muir
authors: Peter R
authors: PR
authors: Gibson
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018592:Cross-Over Studies; D055050:Diet, Gluten-Free; D004187:Disaccharides; D004311:Double-Blind Method; D005260:Female; D005983:Glutens / Q000009:adverse effects*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000139:chemically induced* / Q000178:diet therapy; D008297:Male; D008875:Middle Aged; D009005:Monosaccharides; D009844:Oligosaccharides; D055815:Young Adult
chemical_list: D004187:Disaccharides; D009005:Monosaccharides; D009844:Oligosaccharides; D005983:Glutens
keywords: Abdominal Pain; Clinical Trial; D-FIS; Daily-Fatigue Impact Scale; FODMAP; Food Allergy; GFD; IBS; NCGS; VAS; Wheat; fermentable, oligo-, di-, monosaccharides, and polyols; gluten-free diet; irritable bowel syndrome; non-celiac gluten sensitivity; visual analogue scale