The Lancet Gastroenterology & Hepatology recently published the results of a trial investigating how people with irritable bowel syndrome (IBS) who have self-perceived gluten sensitivity react to gluten, wheat, or sham challenges. This was a randomized and double-blind sham-controlled crossover design, in which participants who believed (prior to the study) that they’d experienced improvement on a gluten-free diet were assigned a random sequence of either receiving gluten, wheat, or sham (in various orders) for 1 week, with a 14 day washout followed by the next challenge, with each participant receiving all 3 possible substances. The food was provided as cereal bars, indistinguishable from each other. The primary outcome was a 50-point worsening in the IBS Symptom Severity Score (IBS-SSS); a total of 28 people completed all 3 challenge periods.
Twenty-nine percent of participants had a 50-point worsening in the IBS-SSS during the sham challenge, compared to 39% with the wheat challenge and 36% with the gluten challenge, but the results were not statistically significant from each other. Adverse events (none serious) were reported in over 90% of participants during each challenge, again not significantly different.
The authors concluded that in this subset of people with IBS, expectations play a major role in symptom generation, with gluten or wheat likely playing a lesser role. While this study highlights the possible importance of expectations, it also had a number of limitations, including a small sample size, a short challenge duration and washout period, and given the large percentage of people experiencing adverse effects even in the sham group, perhaps another aggravating substance that masked the benefit of a gluten-free challenge. For example, multiple other studies suggest that controlling for FODMAP intake is important in this population.