Study Finds International Celiac Disease Prevalence Not Dependent on Grain Consumption Levels

An epidemiologic study by Cleveland Clinic researchers has found no connection between the amount of consumption of gluten-containing grain and celiac disease prevalence in numerous countries.

“We expected to find higher rates of celiac disease where consumption of wheat, rye and barley were more common, since the population would be consuming more gluten. But we did not find this,” says gastroenterologist Claire Jansson-Knodell, MD, first author of the study presented at the American College of Gastroenterology’s 2021 annual scientific meeting. “The lack of a dose-dependent relationship suggests that quantity of intake may not be a significant factor in disease development.”

This surprising finding underscores the complexity of celiac disease.

“Genetic susceptibility and gluten consumption are necessary to lose tolerance to gluten but may not be sufficient to develop celiac disease. Other triggers are likely needed,” says gastroenterologist Alberto Rubio-Tapia, MD, Director of Cleveland Clinic’s Celiac Disease Program and author of the American College of Gastroenterology’s Clinical Guidelines for the Diagnosis and Management of Celiac Disease. Dr. Rubio-Tapia is a co-author of the epidemiology study.

Quantity Proves Unimportant

In an effort to identify those triggers, the researchers considered a variety of environmental factors and decided to compare country-specific production and consumption of gluten-containing grains with celiac disease prevalence.

The study’s primary outcome was correlation between intake of gluten-containing grains and celiac disease prevalence.

Gluten production for wheat, rye and barley was determined using the United National food balance (grams per capita per day), which is the domestic food supply available for consumption.

The researchers conducted a literature review for articles on celiac disease epidemiology, focusing on studies where population-based serum screening with a confirmatory test was performed.

They obtained country-specific information on human leukocyte antigen (HLA) gene frequencies from the Allele Frequency Net Database. HLA data was available for 28 countries.

The analysis included 427,146 subjects from 41 countries. Celiac disease prevalence ranged from 0 to 3.1% in the general population. Domestic wheat supply ranged from 102 to 527 grams per capita per day.

Celiac disease development is strongly linked to the presence of the HLA-DQ2 allele. The researchers’ analysis found a mild but significant correlation between HLA-DQ2 frequencies and wheat consumption, but not between wheat consumption and celiac disease prevalence. There also was no correlation between barley and rye consumption and rates of celiac disease.

“It does not appear that the amount of gluten-containing grain consumed has an impact on the development of celiac disease, at least not on a population level,” says Dr. Jansson-Knodell.

What’s Next?

Undeterred by this finding, the researchers plan to investigate other options.

“One good thing about research is that a negative result like this leads to more hypotheses and ideas,” says Dr. Rubio-Tapia. “Our next step is to look more closely into potential environmental triggers at the population level, such as imbalances in the microbiome.”

According to Dr. Jansson-Knodell, the potential role of grains in worldwide variations in celiac disease prevalence merits continued investigation as well. “Further studies are needed on the quality or relative potency of gluten in grains,” she says.

Advice to Clinicians

As gluten-free diets become increasingly common, members of the public often see giving up gluten as a positive step. Dr. Rubio-Tapia offers a word of warning.

“Gluten-containing foods are very important for human nutrition,” he says. “It is a good practice to start a gluten-free diet only when clinical benefit is expected, such as in a patient with a proven diagnosis of celiac disease.”

“Testing for celiac disease is facilitated and more reliable when performed on an individual consuming a gluten-containing diet,” he adds.

In gluten-sensitive individuals, no amount of gluten consumption is safe. However, gluten can be difficult to avoid, since it is hidden in many foods, medications and products such as toothpaste.

“If you have patients who repeatedly return with symptoms of celiac disease, consider referring them to a dietitian,” Dr. Jansson-Knodell advises clinicians. “Dietitians do an excellent job at helping patients learn how to avoid gluten.”