The association between exposure to per- and polyfluoroalkyl substances and the risk of metabolic syndrome in adults: A systematic review and meta-analysis.

BACKGROUND: Evidence regarding the association between per- and polyfluoroalkyl substances (PFAS) and metabolic syndrome (MetS) across adult subgroups remains limited. This study aimed to examine PFAS exposure and MetS risk in adults, focusing on potential susceptibility factors. METHODS: We searched PubMed, CINAHL, Embase, MEDLINE and Web of Science from inception to December 2025 for studies reporting associations between four legacy PFAS-perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS)-and the risk of MetS. Pooled effect sizes were synthesized using random-effects models. To explore potential sources of heterogeneity, subgroup analyses were conducted according to geographic region, participant mean age, MetS prevalence, and study sample size. RESULTS: A total of 10 studies comprising 32,597 participants, including 5437 cases of MetS, were included. No significant associations between legacy PFAS exposure and MetS risk were observed in the general adult population. Age-stratified analyses demonstrated that elevated PFOS and PFNA levels were associated with an increased risk of MetS in study populations with a mean age ≥ 50 years (Odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.26-2.22; Pinteraction <0.01; OR: 1.88, 95% CI: 1.40-2.53, Pinteraction <0.01, respectively). Geographical stratification further delineated regional heterogeneity, with the metabolic impacts of PFNA being localized to the Asian region (OR: 1.86, 95% CI: 1.37-2.52, Pinteraction = 0.02). CONCLUSION: PFOS and PFNA may contribute to MetS risk among older adults, while PFNA-related risk may be more pronounced in Asian populations, suggesting potential age- and region-related effect modification of PFAS-associated metabolic risk.