Associations between serum per- and polyfluoroalkyl substances and serum metabolomic profiles in elite athletes: a cross-sectional multi-sport study

Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals linked to adverse health outcomes in the general population and occupationally exposed groups. However, PFAS exposure in elite athletes remains poorly characterized despite potential sport-related exposure media. We investigated serum PFAS concentrations and associated metabolomic profiles in 242 elite athletes across 19 sport disciplines classified into six environment-based groups. Serum concentrations of 45 endocrine-disrupting chemicals and 304 metabolites were measured using targeted LC-MS/MS. Serum PFOA and PFHxS concentrations were 1.7- and 2.1-fold higher than KoNEHS cycle 5 adult reference values, and the sum of seven PFAS exceeded the NASEM clinical follow-up threshold of 20 ng/mL in 90.1% of athletes. PFAS levels differed significantly among sport environment groups (p < 0.001), with the highest levels in the Synthetic/Outdoor group. After adjustment for sex and correction for multiple comparisons, 27 metabolites were significantly associated with PFOS, including an inverse association with serotonin and positive associations with branched-chain amino acids, acylcarnitines, and glycerophosphocholine. Pathway analysis indicated enrichment of branched-chain amino acid metabolism. Consistent associations were observed for PFOS, PFOA, and PFHxS, and post hoc weighted quantile sum (WQS) analysis showed mixture associations with serotonin and acetylcholine. This study provides an initial characterization of PFAS exposure and associated serum metabolomic profiles in elite athletes. These cross-sectional findings support further longitudinal studies with detailed exposure assessment in athlete populations.