The association of serum manganese concentrations with all-cause, cardiovascular disease and cancer mortality:A cohort study based on the 2011–2014 National Health and Nutrition Examination Survey(NHANES)

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 al-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 al 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(ful y 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.