Sex-Specific Association Between Urinary Metal and Serum Homocysteine Levels in Chinese Older Adults: A Study Based on the Yinchuan Community-Dwelling Elderly Cohort

The traditional single-metal model does not reflect the complexity of metal exposure, and there are fewer studies on sex-specific associations between metals and serum homocysteine (Hcy) levels. In this study, levels of 12 metals in the urine of 3279 study participants older than 60 years were measured using Inductively Coupled Plasma Mass spectrometry (ICP-MS). The Least Absolute Shrinkage and Selection Operator (LASSO) regression screened the metals. Multi-metal generalized linear models (GLMs) were constructed to explore the association between metals and Hcy levels. Weighted Quantile Sum (WQS) regression was used to explore the weight of each metal. Bayesian kernel machine regression (BKMR) was used to explore the joint effect of mixed metal exposure and interaction between metals. In this study, it was found that there were differences in serum Hcy levels and metal concentrations between male and female participants (p < 0.05). The GLM results showed that after adjusting for covariates, Fe [β (95% CI): − 0.24 (− 0.45, − 0.03)] and Se [− 3.98 (− 4.81, − 3.16)] were negatively associated with serum Hcy levels while Cu [0.94 (0.46, 1.42)], As [0.99 (0.45, 1.54)], Mo [1.00 (0.43, 1.57)], and Cd [1.00 (0.51, 1.48)] were positively associated with serum Hcy levels. WQS regression model results showed that Se was the most heavily weighted among the negative effects. BKMR results showed that the joint effect of multi-metal exposures showed a decreasing and then increasing trend as the metal quartile increased and found that Se interacted with the remaining five metals. After stratification by gender, the trend of mixed metal exposure in male and female participants was generally consistent with that of the total population, and Fe was more important in female participants. Se reduces the positive effects of Mo, Cu, As, and Cd on serum Hcy levels and enhances the negative effects of Fe on serum Hcy levels. There may be some sex-specific associations between combined multi-metal exposure and serum Hcy levels, and prospective studies with larger samples should be conducted in the future.