Potential Role of Vitamin C in the Associations of Serum Per- and Polyfluoroalkyl Substances with Bilirubin and Albumin in U.S. Adolescents and Young Adults: NHANES 2011–2018

Research on per- and polyfluoroalkyl substances (PFAS) and biomarkers potentially related to oxidative stress in adolescents is limited. We investigated associations between serum PFAS and total bilirubin and albumin among 1474 participants aged 12–20 years using National Health and Nutrition Examination Survey 2011–2018 data. Six primary PFAS and two secondary measures, summed branched perfluorooctanesulfonic acid (Sm-PFOS) and total PFOS, were assessed. Survey-weighted linear regression with multiple imputation for missing covariates was used to assess associations and potential vitamin C effect modification. Bayesian kernel machine regression was used to evaluate PFAS mixture associations. After adjustment for multiple comparisons, perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorodecanoic acid (PFDeA) were positively associated with bilirubin, and seven PFAS measures were positively associated with albumin. Albumin associations for PFOA, perfluorononanoic acid (PFNA), and PFDeA were stronger among vitamin C-deficient participants (<11.4 µmol/L), with significant interactions. For example, the PFOA–albumin association was stronger among vitamin C-deficient than non-deficient participants (β = 2.276 vs. 0.544; interaction q = 0.013). Mixture associations were positive for both biomarkers and consistent with the primary analysis. These findings suggest PFAS are associated with bilirubin and albumin; vitamin C findings are exploratory and limited by the small deficient group.