In a White European population, all-cause mortality decreased on a steep, nonlinear, L-shaped curve with increasing levels of 25-hydroxyvitamin D (25-(OH)D) up to 50 nmol/L, a large-scale, prospective cohort trial shows. Mortality from cancer, cardiovascular disease (CVD), and respiratory disease decreased similarly.
Measurements of 25-(OH)D levels and genetic analyses were obtained for 307,601 U.K. Biobank participants recruited from Mar. 2006 to July 2010. Results through June 2020 show the following for 18,700 deaths during 14 years of follow-up: “The association of genetically predicted 25-(OH)D with all-cause mortality was L-shaped (P for nonlinearity < 0.001), and risk for death decreased steeply with increasing concentrations until 50 nmol/L. Evidence for an association was also seen in analyses of mortality from cancer, CVD, and respiratory diseases (P ≤ 0.033 for all outcomes). Odds of all-cause mortality in the genetic analysis were estimated to increase by 25% (odds ratio, 1.25 [95% CI, 1.16 to 1.35]) for participants with a measured 25-(OH)D concentration of 25 nmol/L compared with 50 nmol/L.”
Concluding that these data support a causal relationship between vitamin D deficiency and mortality, the authors write, “Additional research needs to identify strategies that meet the National Academy of Medicine’s guideline of greater than 50 nmol/L and that reduce the premature risk for death associated with low vitamin D levels.”