The relationship between PFAS exposure and dyslipidemia: an updated review, meta-analysis, and evaluation of bias

There is concern that widespread exposure to per- and polyfluoroalkyl substances (PFAS) may induce changes in serum lipids, however, current evidence is insufficient to establish causality in humans. This systematic review evaluated 69 articles examining exposure to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and alterations in adult serum lipid outcomes. The majority of associations for PFOA or PFOS with serum lipids were either not significant, significantly negative, or were mixed versus significantly positive findings, suggesting non-consensus of any associations. A subset of 37 studies were examined via meta-analysis and reviewed for biases. Using pooled estimates, PFOA and PFOS exposure were significantly positively associated with total cholesterol (TC) and low-density lipoprotein (LDL). PFOA was significantly positively associated with triglycerides (TG), whereas PFOS had a non-significant positive association with high-density lipoprotein (HDL). TC and LDL estimates demonstrated high heterogeneity, peaking within cross-sectional and non-occupational studies that comprised the majority of the meta-analysis. Conversely, pooled estimates from longitudinal investigations trended towards null and were not significant. Potential reasons for heterogeneity were identified in a bias analysis and primarily included inconsistent confounding controls and possible subject recruitment bias from regions with known PFAS contamination. These factors indicate inconsistencies in PFAS-lipid literature that require further prospective investigations.