Low vitamin D levels up mortality risk in adults

08 Nov 2022
Low vitamin D levels up mortality risk in adults

A deficiency in vitamin D levels appears to increase the risk of death in adults, suggests a study.

Using the UK Biobank, the authors recruited 307,601 participants of White European ancestry (aged 37‒73 years at recruitment) with available measurements of 25-hydroxyvitamin D (25[OH]D) and genetic data between March 2006 and July 2010. They assessed genetic evidence for the causal or low vitamin D status in mortality through nonlinear Mendelian randomization analyses.

Thirty-five confirmed variants of 25(OH)D were used to estimate genetically predicted 25(OH)D. The authors then recorded all-cause and cause-specific mortality (ie, cardiovascular disease, cancer, and respiratory) up to June 2020.

A total of 18,700 deaths were recorded during 14 years of follow-up. An L-shaped association was observed between genetically predicted 25(OH)D and all-cause mortality (p<0.001 for nonlinearity); the risk of death dropped sharply with increasing concentrations until 50 nmol/L.

Analyses of specific causes also revealed associations between vitamin D deficiency and death from cardiovascular diseases, respiratory diseases, and cancer (p≤0.033 for all outcomes).

In the genetic analysis, the likelihood of all-cause mortality tended to increase by 25 percent (odds ratio, 1.25, 95 percent confidence interval, 1.16‒1.35) for participants with 25(OH)D concentration of 25 nmol/L compared to those with 50 nmol/L.

“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,” the authors said.

This study was limited by analyses restricted to a White European population.

A genetic approach is best suited to providing proof of principle on causality, whereas the strength of the association is approximate,” the authors said.

Ann Intern Med 2022;doi:10.7326/M21-3324