Could This Patient Have 'Non-Celiac Gluten Sensitivity'?

William F. Balistreri, MD


February 11, 2013


I frequently see patients who don't test negatively for celiac disease, yet they are convinced that their symptoms are caused by gluten. Is "non-celiac gluten sensitivity" real?

Response from William F. Balistreri, MD
Professor of Medicine, University of Cincinnati College of Medicine; Staff Physician, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Gluten intolerance in people without celiac disease is a controversial issue, as shown in a recent New York Times article, "Should We All Go Gluten-Free?"[1] 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 negative for celiac disease, and whose symptoms were under control on a gluten-free diet.[2] 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). Participants were randomly assigned to a "gluten" or "non-gluten" (placebo) group. During the trial, they were asked to eat 2 slices of bread and 1 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 = .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.

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