Consuming the equivalent of two slices of bread a day for just 1 week significantly worsened abdominal pain, bloating, foggy mind, depression, and aphthous stomatitis among patients with self-diagnosed gluten intolerance, according to a double-blind, placebo-controlled, crossover study reported in the September issue of Clinical Gastroenterology and Hepatology.
The study is unique because its patients were referred for intestinal and extraintestinal symptoms of gluten sensitivity, rather than irritable bowel syndrome, said Dr. Antonio Di Sabatino at the University of Pavia (Italy) and his associates. The study also used gluten capsules that had been shown to be indistinguishable from placebo, excluded patients with minimal baseline symptoms, and used global response as the primary outcome measure because that is patients’ major concern, the investigators said.
The existence and definition of nonceliac gluten sensitivity (NCGS) remains debatable even as patients in “crowded online forums” diagnose themselves with it, the researchers noted.
To test if NCGS exists and if so, the amount of gluten needed to cause symptoms, they conducted a randomized, double-blind, placebo-controlled trial of 61 self-diagnosed patients with no history of wheat allergy or celiac disease. Patients ingested either 4.375 g of gluten – the equivalent of two slices of wheat bread – or placebo rice starch in capsule form every day for 1 week. Then they followed a gluten-free diet for a week before crossing over to the other study arm. Each day, patients were asked to grade 15 intestinal symptoms and 13 extraintestinal symptoms on a scale of 0 (absent) to 3 (severe and interfering with daily activities). The group averaged 39 years of age, and 87% were female, the investigators said (Clin Gastroenterol Hepatol. 2015 doi: 10.1016/j.cgh.2015.01.029).
Among 59 patients who finished the trial, gluten intake was tied to significantly higher overall symptom scores, compared with placebo (median score, 55 vs. 33; P = .034), said the researchers. Patients also reported significantly worse abdominal bloating (P = .04), abdominal pain (P = .047), aphthous stomatitis (P = .025), foggy mind (P = .019), and depression (P = .02) when they ingested gluten, compared with placebo.
“The observation that short-term exposure to gluten induced depression is remarkable,” Dr. Di Sabatino and his associates commented. “This result was supported by a recent double-blind, placebo-controlled, crossover study in which depression was assessed by an ad hoc psychiatric score (Aliment Pharmacol Ther. 2014 May;39:1104-12). The direct, highly significant correlation between symptom score and symptom prevalence at both the intestinal and extraintestinal levels is indirect proof of the validity of our findings.”
The study did not yield data on identifiable biomarkers, nor did it pinpoint pathogenic mechanisms for NCGS, the investigators acknowledged.
“Self-prescription of gluten withdrawal is becoming increasingly common, but this behavior should be strongly discouraged because it may lead to the consequent preclusion of a proper diagnosis of celiac disease and to a high and unjustified economic burden,” they emphasized. “Because a reliable marker of NCGS is not readily available at present, double-blind, placebo-controlled trials are mandatory to ascertain this condition.” Their laboratory is working to identify cytokines in the duodenal mucosa of patients in the trial, and early results have not implicated innate or adaptive immune mechanisms for NCGS, they said.
St. Matteo Hospital Foundation supported the research, and Giuliani Pharma provided the capsules used in the study. The investigators reported having no conflicts of interest.
