Objective: To provide an updated meta-analysis of the observational studies examining the association between proton pump use and Parkinson’s disease.

Background: The exact cause of Parkinson’s disease (PD) is unclear, but proton pump inhibitors (PPI) may trigger it. Patients with PD often experience gastrointestinal dysfunction, leading to increased PPI use. This can cause gut microbiota dysbiosis, affecting the gastrointestinal, enteric, and central nervous systems. The relationship between PPI therapy and PD is unclear due to limited evidence. The results from observational studies on this subject also remained controversial. The association between proton pump use and Parkinson’s disease has not been meta-analyzed in the literature before.

Method: We searched PubMed, Embase, Scopus, and Google Scholar databases from the inception of the publication until March 2024 for observational studies that measured the association of proton pump inhibitors with Parkinson’s disease. At least two authors extracted summary data. Between-study heterogeneity was assessed using the I² statistic. For each exposure-outcome pair, a random or fixed effect meta-analysis was conducted based on the degree of heterogeneity to pool the odds ratio (OR) with a 95% confidence interval from the individual studies.

Results: This meta-analysis included four eligible case-control studies involving 46083 PD patients and 175927 controls. There was a statistically significantly increased risk of PD in PPI users [OR 1.31 (95% confidence interval: 1.19-1.44, p <0.00001, I²= 91%]. Moreover, the association was significant even after subgrouping the studies based in Asia and Europe. In subgroup analysis, the odds ratio of Parkinson’s disease in proton pump inhibitor users was 1.30 (95% confidence interval: 1.11-1.52, p <0.00001, I²= 94%) in the Asia study, while the odds ratio of Parkinson’s disease in proton pump inhibitor users was 1.27 (95% confidence interval: 1.17-1.36, p <0.00001) in the Europe study.

Conclusion: The meta-analysis showed that proton pump inhibitor therapy might be associated with the risk of Parkinson’s disease. However, this only shows a statistical association. Hence, future studies should investigate the underlying mechanisms and confirm the cause-effect relationship between PPI therapy and PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/do-proton-pump-inhibitors-increase-the-risk-of-parkinsons-disease-a-systematic-review-and-meta-analysis/