Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Sarcopenia: The Mediating Role of Serum Albumin

Widespread exposure to per- and polyfluoroalkyl substances (PFAS) is a growing public health concern, but its link to muscle damage remains largely unexplored. As PFAS exposure is associated with liver dysfunction, which is an established risk factor for muscle damage, we examined their associations and potential mediating pathways. A total of 1261 participants were recruited from Guangdong province, China, from November 2018 to August 2019 and examined for muscle mass, strength, serum PFAS levels, and biomarkers of liver function. The key results demonstrated significant positive associations between serum PFAS exposure and sarcopenia risk. Specifically, a per ln ng/mL increase in linear perfluorooctane sulfonate (PFOS), branch PFOS, and perfluorooctanoic acid (PFOA) was associated with adjusted odds ratios of 2.32 (95% CI: 1.77 to 3.00), 2.18 (95% CI: 1.67 to 2.90) and 3.01 (95% CI: 1.96 to 4.70), respectively. Analysis of PFAS mixtures via the BKMR model revealed a linear dose-response relationship of sarcopenia, with PFOS and PFOA being the primary contributor. Importantly, mediation analyses showed that liver function biomarkers served as significant mediators of the PFAS-sarcopenia association. Notably, liver synthesis function markers (albumin and globin) mediated a substantial proportion of the association, ranging from 3.48% to 82.42%, whereas liver injury markers (aspartate aminotransferase and gamma-glutamyl transferase) accounted for only 1.54% to 15.44%. This study underscores the need to be aware of the increased risk of muscle damage associated with PFAS exposure, which may primarily operate through liver function abnormalities.