Context: Although an inverse association between vitamin D status and mortality has been reported in observational studies, the precise association shape and optimal vitamin D status remain undetermined.
Objective: To investigate the association between vitamin D status and risk of all-cause and cause-specific mortality and estimate optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations.
Design: Prospective cohort study.
Setting: UK Biobank.
Participants: 365 530 participants who had serum 25(OH)D measurements and no history of cardiovascular disease (CVD), cancer, or diabetes at baseline (2006-2010).
Main outcome measures: All-cause and cause-specific mortality.
Results: During a median follow-up of 8.9 (interquartile range: 8.3-9.5) years, 10 175 deaths occurred, including 1841 (18.1%) due to CVD and 5737 (56.4%) due to cancer. The multivariate analyses revealed nonlinear inverse associations, with a decrease in mortality risk appearing to level off at 60 nmol/L of 25(OH)D for all-cause and CVD deaths and at 45 nmol/L for cancer deaths. Compared to participants with 25(OH)D concentrations below the cutoffs, those with higher concentrations had a 17% lower risk for all-cause mortality (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.79-0.86), 23% lower risk for CVD mortality (HR: 0.77, 95% CI: 0.68-0.86), and 11% lower risk for cancer mortality (HR: 0.89, 95% CI: 0.84-0.95).
Conclusions: Higher 25(OH)D concentrations are nonlinearly associated with lower risk of all-cause, CVD, and cancer mortality. The thresholds of 45 to 60 nmol/L might represent an intervention target to reduce the overall risk of premature death, which needs further confirmation in large clinical trials.
Keywords: vitamin D; 25-hydroxyvitamin D; cancer; cardiovascular disease; mortality.
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