Regular Use of Proton Pump Inhibitors May Increase Risk for Inflammatory Bowel Diseases

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Investigators evaluated the association between regular proton pump inhibitor use and the risk for inflammatory bowel disease and its subtypes.

Increased risk for inflammatory bowel disease (IBD) was associated with regular use of proton pump inhibitors (PPIs), according to results of a study published in Gastroenterology.

Data from the Nurses’ Health Study (NHS; n=82,869), NHS II (n=95,141), and United Kingdom (UK) Biobank (n=469,397) were pooled for this analysis. Self-reported use of PPIs and diagnoses of Crohn disease (CD) or ulcerative colitis (CD) were recorded. Results were validated in an analysis using a 1:4 nearest neighbor caliper propensity score-matched subset of data from the UK Biobank (n=142,606).

A total of 578 (NHS and NHS II: n=112; UK: n=466) and 1189 (NHS and NHS II: n=159; UK: n=1030) participants reported CD and UC, respectively.

Stratified by PPI use, regular users were more likely to have obesity, be less physically active, to smoke, to never drink, to be post-menopausal, use menopausal hormones, and to report higher rates of ulcers, upper gastrointestinal tract bleeding, and gastroesophageal reflux disease.

In the fully adjusted model, regular use of PPIs increased risk for IBD (adjusted hazard ratio [aHR], 1.42; 95% CI, 1.22-1.65), CD (aHR, 1.62; 95% CI, 1.27-2.09), and UC (aHR, 1.36; 95% CI, 1.02-1.81).

These findings were not affected by age, sex, obesity, smoking, drinking, dietary quality, physical activity, gastroesophageal reflux disease, aspirin use, non-steroidal anti-inflammatory drug use, or H2 receptor antagonist use.

Similar findings were reported in the propensity-matched cohort, in which PPI use increased risk for IBD (HR, 1.53; 95% CI, 1.29-1.82), CD (HR, 1.77; 95% CI, 1.33-2.36), and UC (HR, 1.44; 95% CI, 1.17-1.77).

In order to verify that these patterns were robust, the investigators performed a falsification analysis relating PPI use with increased risk for refraction and accommodation disorders, uterine corpus cancer, or death by transportation. No significant trends were observed.

This study could have been limited by the differing definitions of regular PPI use among the 3 cohorts and by the fact that the UK Biobank participants were only evaluated on 1 occasion.

These data indicated that regular PPI users may be at increased risk for IBD. Additional studies are needed to determine the biological mechanism for these overserved patterns.


Xia B, Yang M, Nguyen LH, et al. Regular use of proton pump inhibitor and the risk of inflammatory bowel disease: pooled analysis of three prospective cohorts. Gastroenterol. Published online August 10, 2021. doi: 10.1053/j.gastro.2021.08.005