Arsenic species and lipid metabolism under low-to-moderate arsenic exposure: evidence from NHANES and a Chinese adult population.

BACKGROUND: The relationship between low-to-moderate arsenic exposure and lipid metabolism remains unclear, particularly for different urinary arsenic species and the potential role of urinary albumin-to-creatinine ratio (UACR). METHODS: This cross-sectional study used NHANES 2009-2020 data and an adult population from Zhaodong, China. The NHANES analysis included 2,104 participants, representing 52,612,536 adults, and the Zhaodong analysis included 310 participants. Creatinine-adjusted urinary total arsenic (UTA) and dimethylarsinic acid (DMA) were designated as the principal exposure indicators, whereas monomethylarsonic acid (MMA), arsenite (AsIII), and arsenate (AsV) were evaluated in supplementary exploratory analyses. Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and UACR were examined as outcomes. Multivariable regression, restricted cubic spline, subgroup, and mediation analyses were performed. RESULTS: The median UTA concentrations were 3.73 μg/L in NHANES and 12.37 μg/L in the Zhaodong population. In NHANES, after multivariable adjustment, UTA and DMA were positively associated with LDL-C levels, with β values of 0.68 and 0.85, respectively, and both associations remained significant after FDR correction (q < 0.1). Restricted cubic spline analyses revealed a nonlinear association between DMA and LDL-C. In the Zhaodong population, the highest quartile of DMA was associated with lower odds of abnormal LDL-C compared with the lowest quartile. In NHANES, both UTA and DMA were positively associated with UACR. Mediation analyses did not support a meaningful mediating role of UACR, although small negative indirect effects were observed in the LDL-C models involving UTA and DMA. Supplementary exploratory analyses involving MMA, AsIII, and AsV yielded several nominal associations. CONCLUSIONS: Low-to-moderate urinary arsenic exposure may be associated with altered LDL-C levels and increased UACR, with species- and population-specific differences. The mediation analyses did not support a meaningful mediating role of UACR. Prospective studies are needed to confirm these findings.