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Nonceliac Gluten Intolerance?

Gluten caused gastrointestinal symptoms in some individuals without celiac disease.

Many people without celiac disease actively follow gluten-free diets and insist that gluten produces symptoms. Some of these individuals believe that they have celiac disease, despite negative test results, and many cannot be adequately tested because they are following a gluten-free diet. Can gluten cause gastrointestinal symptoms in people without celiac disease, and — if so — by what mechanism? To answer these questions, researchers in Australia conducted a double-blind, randomized, placebo-controlled, dietary rechallenge trial involving individuals with irritable bowel syndrome who were proven not to have celiac disease and whose symptoms were under control on a gluten-free diet.

Participants were recruited through advertisements. Proof that celiac disease was not present required either absence of the HLA-DQ2 and HLA-DQ8 haplotypes or a normal duodenal biopsy at endoscopy while the person was on a gluten-containing diet. Of the 39 individuals who met the inclusion criteria and were enrolled, 5 were excluded (4 because of inadequate symptom control during the 2-week baseline period and 1 because of acute psychiatric illness). All participants followed a gluten-free diet; in addition, they were asked to eat two slices of bread and one muffin daily (these foods contained gluten for the gluten group but were gluten free for the placebo group). Preliminary testing showed that the taste and texture of the gluten-free and gluten-containing products were identical.

Nine participants stopped the study diet prematurely because of intolerable symptoms (6 in the gluten group after a median of 7 days and 3 in the placebo group after a median of 16 days). Poorly controlled symptoms were reported during more than half of the 6-week study period by more gluten-group participants than placebo-group participants (68% vs. 40%; P=0.001). During the entire study period, scores for pain, satisfaction with stool consistency, and tiredness were significantly worse in the gluten group than in the placebo group. Neither group showed significant changes in levels of fecal lactoferrin or celiac antibodies or in measures of intestinal permeability. Responses to gluten were similar between participants who had HLA-DQ2, HLA-DQ8, or both, and those who did not.

Comment: Although this study does not identify a mechanism for nonceliac gluten intolerance, it provides the most convincing evidence yet for the existence of this condition. Certainly, getting tested for celiac disease before a gluten-free trial is still optimal, given the implications of a celiac diagnosis — including the necessity of strict adherence to a gluten-free diet, an increased cancer risk, and the need to screen family members.

— Douglas K. Rex, MD

Published in Journal Watch Gastroenterology April 8, 2011

Citation(s):

Biesiekierski JR et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: A double-blind randomized placebo-controlled trial. Am J Gastroenterol 2011 Mar; 106:508.

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