Self-reported nonceliac gluten/wheat sensitivity (NCGWS) affects about 1 in 10 people worldwide, and the first comprehensive global study on its prevalence and clinical characteristics has found a strong association with female sex, psychological distress, and irritable bowel syndrome (IBS).

NCGWS may warrant classification within disorders of gut-brain interaction (DGBI), wrote authors, led by Mohamed G. Shiha, MBBCh, with the School of Medicine and Population Health at the University of Sheffield, Sheffield, England. Findings of the systematic review and meta-analysis were published in Gut.

“Recognizing NCGWS within the DGBI framework and the development of symptom-based diagnostic criteria are needed to guide a more tailored management approach focusing on individual symptom patterns and dietary triggers beyond gluten and to reduce unnecessary dietary restriction in this common condition,” the authors wrote.

Women Twice as Likely to Have NCGWS

The analysis included 25 studies comprising 49,476 participants from 16 countries. The researchers found that women were more than twice as likely as men to report NCGWS (odds ratio [OR], 2.29; P < .001).

Other findings associated with those reporting NCGWS include:

• About 40% adhered to a gluten-free diet.
• The most common symptoms were bloating (71.0%), abdominal discomfort (46.0%), abdominal pain (36.0%), and fatigue (32.1%).
• Respondents reporting the condition were almost three times as likely as controls to report anxiety (OR, 2.95) or depression (OR, 2.42) P < .001.
• They were almost five times as likely as controls to report IBS (OR, 4.78; P < .001).

Prevalence of NCGWS varied widely geographically and ranged from 0.7% in Chile to 35.8% in Saudi Arabia.

Interventions Needed Beyond Gluten-Free Diet

Shiha’s team writes that future research should center on identifying clinical NCGWS phenotypes, explore the role of the gut-brain axis and psychological comorbidities, and evaluate multidisciplinary interventions beyond the gluten-free diet. They note that many people with self-reported NCGWS continue to experience gastrointestinal and extraintestinal symptoms despite long-term adherence to a gluten-free diet.

It's important to remember that there are no biomarkers or specific tests for NCGWS, Christopher Cao, MD, told Medscape Medical News. Cao is a gastroenterologist and director of the Celiac Disease Program at Mount Sinai in New York City.

Based on studies seen in the past and anecdotal experiences at Mount Sinai, “it seems to be more than just a gluten-mediated process,” Cao said. “It seems it may be related to consumption of nonfermentable carbohydrates, or perhaps it could fall into the realm of disordered gut-brain interaction.”

When celiac has been ruled out and patients are classified as NCGWS, patients may stay on a gluten-free diet, as seen in this study, he said. “But a gluten-free diet is not necessarily healthy for people who don’t have celiac [disease] because it has a lot of nutritional deficiencies,” Cao said. “There’s a lot of psychosocial burden. And it’s more expensive.”

The findings have implications beyond gastroenterology, he said. “I do think our primary care providers are the first to screen for a lot of these symptoms. An important message for everyone is that patients on a gluten-free diet may not have celiac disease and may not benefit from a gluten-free diet.”

A UK survey has shown a more-than twofold increase in the prevalence of self-reported NCGWS over a 3-year period, while celiac disease prevalence was stable. “Therefore, the public perception of gluten may be driving the marked rise in the number of individuals who believe they are “gluten sensitive,” the authors wrote.

This study can’t answer many questions about NCGWS, Cao said. “It’s still not a well-defined diagnosis. We don’t have pathophysiology for what is going on. We don’t know if gluten is playing a role at all. Certainly, there needs to be a lot more data.”

Shiha and Cao reported having no relevant financial relationships.

Marcia Frellick is an independent, Chicago-based healthcare reporter and a regular contributor to Medscape Medical News.