Abstract
BACKGROUND: The widespread presence of per-and polyfluoroalkyl substances (PFAS) has raised global health concerns. This study aims to determine the age-specific relationships of PFAS compounds with metabolic syndrome (MetS) and its components. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) in 2003-2018. Modified Poisson regression was employed to estimate associations between individual PFAS compounds and prevalence of MetS, as well as its components. Multiple linear regression analyses were performed to examine the associations between PFAS congeners and metabolic markers, including lipid and glucose homeostasis traits. Additionally, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were conducted to investigate the joint effects of PFAS mixtures on the prevalence of MetS and its components across different age groups. RESULTS: A total of 5850 participants were included for analysis. In the Modified Poisson regression model, ln-transformed perfluorononanoic acid (PFNA) level was positively correlated with MetS prevalence in adolescents (prevalence ratio [PR] = 1.42; 95% CI: 1.01-1.99). Conversely, ln-transformed perfluorohexanesulfonic acid (PFHxS) and ln-transformed 2-(N-Methylperfluorooctane sulfonamido) acetic acid (MeFOSAA) were negatively associated with the risks of MetS in young adults (PR = 0.86, 95% CI: 0.76-0.98) and middle-aged adults (PR = 0.88, 95% CI: 0.79-0.98), respectively. Notably, individual PFAS exposure was positively associated with levels of total cholesterol, low-density lipoprotein, non-high-density lipoprotein, and high-density lipoprotein in young and middle-aged adults. However, overall effect analyses using WQS and BKMR showed no significant associations of PFAS mixture with MetS in any age group. Nonetheless, in middle-aged adults, PFAS mixture was adversely correlated with hypertriglyceridemia and positively linked to a greater risk of hypertension and increased high-density lipoprotein cholesterol levels. CONCLUSIONS: Our study highlighted the complex relationships between PFAS exposure and the risks of MetS and its components across different age groups. Co-exposure to PFAS was particularly linked to dyslipidemia in young and middle-aged adults. Prospective studies are needed for better comprehension of the causative impact of PFAS on the risks of MetS.