The association between use of proton pump inhibitors and frailty index among middle‐aged and older adults

Aims This study aimed to investigate the association between use of proton pump inhibitors (PPI) and frailty index (FI), and to assess the causality relationship using Mendelian randomization (MR). Methods A total of 9756 middle‐aged and older adults from the National Health and Nutrition Examination Survey were included. The FI was evaluated using a previously validated 49‐item deficit model to assess frailty status, which is one of the common approaches to measure overall health burden. We performed weighted multivariable‐adjusted linear regression to assess the association between PPI use and FI, and conducted a two‐sample MR to evaluate causality, employing various sensitivity analyses for robustness. The inverse variance weighted (IVW) method was used as the primary analysis. Results Multiple linear regression analysis revealed a positive association between PPI use and FI (β = 0.048, 95% confidence interval [CI]: 0.042–0.054, P < .001). This association was observed in both short‐term (≤ 1 year) and long‐term (> 1 year) PPI users ( P for trend < 0.001). The MR study also revealed a positive association between PPI use and FI based on the IVW method (β = 1.183, 95% CI: 0.474–1.892, P = .001). Conclusions While our findings suggest a potential link between PPI use and FI, they should be interpreted with caution due to the study's limitations. Although the MR analysis suggests a causal relationship, further research, particularly longitudinal studies, is needed to confirm these findings and better establish temporality.