Association Between Serum per- and Polyfluoroalkyl Substances and Iron Status Biomarkers in a Representative Sample of U.S. Adults: NHANES 2013–2018

<b>Purpose:</b> Per- and polyfluoroalkyl substances (PFAS) comprise a class of man-made compounds widely utilized in manufacturing everyday consumer products. Experimental studies indicate that PFAS may interfere with iron regulation by hindering absorption or inducing oxidative stress. Nonetheless, epidemiological studies examining the association between PFAS exposure and a broad spectrum of iron-related biomarkers remain scarce. <b>Approach and Results:</b> In this study, data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed, which included 5050 adults aged 18 and older. The relationships between six PFAS compounds, oral iron intake, and a comprehensive set of markers of iron homeostasis, including serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin saturation, ferritin, and transferrin receptor levels, were examined. Our findings revealed a negative association between both individual and total PFAS (sum of six PFAS) levels and oral iron intake. Additionally, serum iron and transferrin saturation levels exhibited significant positive correlations with all PFAS compounds, whereas ferritin was positively correlated with all PFAS compounds except <i>n</i>-perfluorooctanoic acid (<i>n</i>-PFOA). UIBC and transferrin receptor showed significant negative correlations with all PFAS compounds, while TIBC was significantly negatively correlated with <i>n</i>-perfluorooctane sulfonic acid (<i>n</i>-PFOS), perfluoromethylheptane sulfonic acid isomers (<i>sm</i>-PFOS), perfluorohexane sulfonic acid (PFHxS), and the total PFAS. <b>Conclusions:</b> Higher PFAS exposure was associated with altered iron status biomarkers While this cross-sectional study cannot establish causality, the observed associations raise the possibility that PFAS exposure may influence iron absorption. These findings emphasize the need for additional research into the potential impact of PFAS exposure on iron homeostasis.