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

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).

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 (As^III), and arsenate (As^V) 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.

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, As^III, and As^V yielded several nominal associations.

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.