The modifying role of selenium in the association between heavy metals exposure and mortality risk in adults: A cohort study based on NHANES

While cadmium (Cd) and lead (Pb) exposure are associated with increased mortality and selenium (Se) may mitigate these effects, large-scale epidemiological evidence remains limited and the underlying mechanisms unclear. To address this, this study utilized data from the National Health and Nutrition Examination Survey (NHANES, 2013-2017) and employed multivariate Cox models, restricted cubic splines, and interaction analyses to assess the associations of serum Se, Cd, and Pb with mortality, with mediation analysis conducted to explore the role of inflammatory pathways. Elevated blood levels of Cd (HR: 2.90, 95 % CI:1.72-4.88) and Pb (HR: 2.02, 95 % CI: 1.11-3.68) were associated with increased all-cause mortality risk. RCS analysis revealed positive linear dose-response relationships for Cd (P_overall< 0.001, P_nonlinear= 0.173) and Pb (P_overall< 0.001, P_nonlinear= 0.070), while a negative non-linear dose-response relationship was observed for Se (P_overall< 0.001, P_nonlinear< 0.001). Notably, under high Cd exposure, individuals with high Se levels had substantially lower all-cause mortality risk (HR: 1.32, 95 % CI:0.90-1.94) compared to those with low Se levels (HR: 3.43, 95 % CI:2.23-5.29). Similarly, under high Pb exposure, high Se levels (HR: 0.76, 95 % CI:0.31-1.84) were associated with a lower mortality risk compared to low Se levels (HR: 2.64, 95 % CI:1.13-6.16). Furthermore, mediation analyses indicated that neutrophil-to-lymphocyte ratio, albumin-to-creatinine ratio, and neutrophil percentage-to-albumin ratio partially mediated Se's protective effect, accounting for 16.10 %, 6.30 %, and 8.80 % of the total effect, respectively. In conclusion, Se may mitigate the detrimental effects of Cd and Pb exposure on mortality risk, potentially through the modulation of inflammatory responses.