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

A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of non-celiac 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 (ranging from 1 day to 6 weeks), daily doses for the gluten challenge (ranging from 2 g to 52 g; 3 studies administered less than 8 g/day), 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 38/231 of 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 among and potential methodology flaws in studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of nocebo effect in these types of studies