Gluten Is Not the Culprit in Many Patients' Symptoms


Am Fam Physician. 2016 May 1;93(9):788.

Clinical Question

Can patients with nonceliac gluten sensitivity tell when they are exposed to gluten?

Bottom Line

Gluten may not be the cause of gastrointestinal symptoms in many patients with nonceliac gluten sensitivity. Only one-third of patients on a gluten-free diet experienced symptoms and correctly identified when they were given gluten-containing flour. Almost one-half (49%) of patients experienced symptoms even though they were given gluten-free flour. (Level of Evidence = 1b−)


Although the incidence of celiac disease—with resulting gluten sensitivity—is approximately 0.4%, many persons who do not have antibodies to gluten identify symptoms when they eat gluten-containing foods. The researchers enrolled 35 patients (86% female) from a celiac disease clinic who did not have celiac disease, but were using a gluten-free diet because of self-identified gluten-related symptoms. These patients had been using a gluten-free diet for at least six months and reported being asymptomatic or mildly symptomatic. The participants were randomized, using a crossover design, to receive gluten-containing flour or gluten-free flour for 10 days, followed by a two-week washout period, and then another 10 days of the other type of flour.

Only 34% (n = 12) of the participants correctly identified when they were given gluten-containing flour. These patients also had a significant increase in symptoms following the gluten challenge using the Gastrointestinal Symptoms Rating Scale. Seventeen participants (49%) believed the gluten-free flour contained gluten, and they had increased symptoms during the gluten-free period. Despite the small number of patients in this study, the crossover design (in which each participant serves as his or her own control) greatly increases the statistical power. However, this group may represent a specific subtype of patient; many patients approached to participate did not do so, because of no interest in the study, fear of symptom recurrence, or an uncertain diagnosis.

Study design: Crossover trial (randomized)

Funding source: Self-funded or unfunded

Setting: Outpatient (specialty)

Reference: Zanini B, Baschè R, Ferraresi A, et al. Randomised clinical study: gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity. Aliment Pharmacol Ther. 2015; 42( 8): 968– 976.

POEMs (patient-oriented evidence that matters) are provided by EssentialEvidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, Associate Deputy Editor.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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