Legacy PFAS can promote dyslipidemia and disrupt liver function.

We show that some alternative/precursor PFAS are associated with higher cholesterol.

Mixtures of 7 PFAS were consistently associated with higher cholesterol.

Adding additional PFAS to the mixtures made estimates weaker or less precise.

Associations with GGT were apparent in sensitivity analyses only.

Legacy per- and polyfluoroalkyl substances (PFAS) can promote dyslipidemia; however, evidence is lacking for alternative and precursor PFAS. We investigated associations between serum concentrations of 31 PFAS and concurrently measured lipids and liver function biomarkers.

PFAS, lipids, and liver function biomarkers were analyzed in serum samples provided by 282 adult females participating in a 2018–2021 follow-up study of a Canadian pregnancy cohort. We examined percent differences in outcomes continuously for 17 PFAS with >50% detection and as detected vs. not detected for 14 PFAS with 10–50% detection. We also examined associations with the sum of 7 PFAS recommended by the National Academies of Sciences, Engineering, and Medicine guidance report on PFAS testing and 17 PFAS. We used weighted quantile sum (WQS) and quantile g-computation models to estimate joint associations.

Each two-fold increase in concentrations of PFHxS, PFOS, PFNA, PFDA, PFHpS, and Σ7PFAS were associated with up to 7% higher total and LDL cholesterol and the TC:HDL ratio. Individuals with detectable concentrations of N-EtFOSA, N-MeFOSA, PFBS, and 9Cl-PF3ONS had up to 17% higher total and LDL cholesterol and TC:HDL. Each one-quartile increase in the mixture of 7 PFAS was associated with up to 10% higher total and LDL cholesterol. Adding additional PFAS to the mixture (17 PFAS) made estimates less precise in WQS models and attenuated associations to the null in quantile g-computation models.

Alternative and precursor PFAS, including replacements for legacy PFAS, are associated with higher cholesterol levels; prospective studies are required to confirm these findings.

Hepatotoxicity

Perfluorinated compounds

Biomonitoring

Liver enzymes

Environmental chemicals

© 2025 His Majesty the King in Right of Canada, as represented by the Minister of Health, 2025. Published by Elsevier GmbH.