Lack of Correlation Between Gluten Intake and Celiac Disease Prevalence: A Geo-Epidemiologic Analysis

Introduction: Celiac disease requires both genetic susceptibility and gluten exposure to trigger the immune-mediated disorder. Other factors that affect disease development are under investigation. We aimed to explore country-based gluten-containing grain production on a worldwide scale utilizing the United Nations database compared to celiac disease prevalence rates using a systematic literature review. Methods: We searched MEDLINE, Embase, Cochrane, and Scopus from inception to May 2021 for studies on celiac disease epidemiology. Studies were included if they performed population-based serum screening with a confirmatory test (either second serological study or small intestine biopsy). Studies were excluded if they sampled specific, high-risk, or referral populations. Country-specific gluten production was determined for wheat, barley, and rye using the United Nations food balance (grams/capita/day) which is the domestic food supply available for consumption. This figure was calculated as an average the year before, the year of, and the year after the prevalence study was performed. HLA frequencies were obtained from allelfrequencies.net database. The primary outcome was correlation between intake of gluten-containing grains and celiac disease prevalence. Correlations were analyzed with the Pearson correlation coefficient and conducted with SPSS. Results: We identified 5641 articles, and 121 met inclusion criteria. The analysis was conducted on 427,146 subjects from 41 different countries. Celiac disease prevalence ranged from 0 to 3.1% in the general population. Domestic wheat supply ranged from 102 to 527 g/capita/day. HLA data was available for 28 countries with frequencies ranging from 0.1 to 49.2%. There was a mild, but significant correlation between HLA DQ2 frequencies and wheat consumption (r = 0.41; P = 0.03), but not between wheat consumption and celiac disease prevalence (P = 0.45) [Figure]. Barley (P = 0.21) and rye (P = 0.60) consumption were not correlated with rates of celiac. Conclusion: In this epidemiologic study, gluten-containing grain consumption was not associated with celiac disease prevalence. The lack of a dose-dependent relationship suggests that quantity of intake may not be a significant factor in disease development. Further studies are needed to explore factors affecting variations in worldwide celiac prevalence, including quality of gluten or relative potency in grains that may impact celiac disease development.Figure.: Wheat Consumption and Celiac Disease Prevalence