Abstract
Objective To investigate the associations of blood cadmium levels and smoking status with all-cause and cause-specific mortality and to evaluate whether magnesium intake modifies these associations in two large population-based cohorts. Design Prospective cohort study. Setting US National Health and Nutrition Examination Survey (NHANES, 2003-2018) and UK Biobank (UKB). Participants 35 197 adults from NHANES and 209 615 participants from UKB. Exposures Blood cadmium concentration (NHANES only), self-reported smoking status, dietary magnesium intake and magnesium supplement use. Main outcome measures The main outcomes were all-cause, cardiovascular disease (CVD) and cancer mortality, which were obtained through linkage to national death registries. Results NHANES documented 4412 deaths over a median follow-up of 9.3 years and UKB documented 12 633 deaths over a median follow-up of 13.4 years. In NHANES, compared with adults in the lowest quartile of blood cadmium, those in the highest quartile had higher risks of all-cause (HR (95% CI)1.62 (1.41 to 1.87)), CVD (1.54 (1.19 to 1.98)) and cancer mortality (1.53 (1.14 to 2.05)). Cadmium mediated 31.1% of the effect of smoking on all-cause mortality. High dietary magnesium intake was associated with lower mortality risks, particularly among individuals with high cadmium exposure (HR for all-cause mortality in adults with cadmium ≥median vs <median: 0.81 (0.72 to 0.90) vs 0.91 (0.79 to 1.06); p for additive interaction=0.02) or who smoked (HR for all-cause mortality in smokers vs non-smokers: 0.78 (0.69 to 0.88) vs 0.90 (0.79 to 1.02); p for additive interaction=0.003). No protective association was observed for magnesium supplements. Findings were consistent in UKB, where higher dietary magnesium intake was inversely associated with mortality among smokers. Conclusion Magnesium intake from food, but not supplements, is associated with reduced mortality risk linked to cadmium exposure and smoking. Public health strategies promoting adequate dietary magnesium intake may help mitigate toxicant-related premature mortality. </p>