Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials

Clin Gastroenterol Hepatol. 2017 Mar;15(3):339-348. doi: 10.1016/j.cgh.2016.08.007. Epub 2016 Aug 12.


A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of nonceliac gluten sensitivity (NCGS) in patients without celiac disease who respond to a gluten-free diet. To determine the accuracy of this approach, we analyzed data from 10 double-blind, placebo-controlled, gluten-challenge trials, comprising 1312 adults. The studies varied in the duration of the challenge (range, 1 d to 6 wk), daily doses for the gluten challenge (range, 2-52 g; 3 studies administered <8 g/d), and composition of the placebo (gluten-free products, xylose, whey protein, rice, or corn starch containing fermentable carbohydrates). Most of the studies found gluten challenge to significantly increase symptom scores compared with placebo. However, only 38 of 231 NCGS patients (16%) showed gluten-specific symptoms. Furthermore, 40% of these subjects had a nocebo response (similar or increased symptoms in response to placebo). These findings reveal heterogeneity and potential methodology flaws among studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of the nocebo effect in these types of studies.

Keywords: Celiac Disease; Gluten-Free Diet; Irritable Bowel Syndrome; Wheat Allergy.

MeSH terms

  • Controlled Clinical Trials as Topic
  • Diagnostic Tests, Routine / methods*
  • Food Hypersensitivity / diagnosis*
  • Glutens / administration & dosage*
  • Humans


  • Glutens