Abstract Objectives There is a debate on the association between the circulating manganese (Mn) levels and mortality. The aim of this study was to explore the nonlinear association between the serum Mn levels and all-cause or cause-specific mortality. Methods We included 8,145 adults from the United States (US) and their serum Mn concentrations obtained from the National Health and Nutrition Examination Survey (NHANES 2011–2014). We retrieved their survival information from baseline until 2019 using the national death index. Multivariable Cox proportional hazards models were used to show the risk of all-cause or cause-specific mortality according to the baseline serum Mn concentrations. Smooth curve fitting and threshold effect analyses were used to clarify the potential nonlinearity. Results During a median follow-up of 6.2 years, there were 716 deaths from all causes, 224 of which were due to cardiovascular disease (CVD) and 165 due to cancer. The serum Mn levels exhibited a U-shaped relationship with all-cause or CVD-associated mortality. Serum Mn levels lower than the threshold value (7.32 μg/L) were negatively associated with all-cause (fully adjusted HR: 0.86, 95% CI: 0.80–0.94) and CVD (fully adjusted HR: 0.82, 95% CI: 0.71–0.94) mortality. In contrast, serum Mn levels higher than the threshold value (7.32 μg/L) were positively associated with all-cause (fully adjusted HR: 1.04, 95% CI: 1.02–1.06) and CVD (fully adjusted HR: 1.05, 95% CI: 1.02–1.08) mortality. Conclusions The serum Mn concentrations showed a U-shaped relationship with all-cause and CVD-associated mortality among NHANES participants.
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