Level 1: Likely reliable evidence

Vitamin D deficiency is associated with increased risk of all-cause and cardiovascular mortality (Dobnig H et al. Arch Intern Med. 2008;168:1340-1349). Studies have suggested that vitamin D supplementation may reduce cancer and cardiovascular disease, but evidence for the effects of supplementation on mortality has been inconsistent.

A recent Cochrane review evaluated various forms of vitamin D supplements and found that different forms have different effects on mortality (Bjelakovic G et al. Cochrane Database Syst Rev. 2011;7:CD007470). The review included 50 randomized trials comparing any vitamin D supplement with placebo or no intervention in 94,148 patients. Most of the participants were women younger than age 70 years. The median treatment duration was two years.

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In an analysis of 32 trials with 74,789 patients, vitamin D3 (cholecalciferol) significantly decreased all-cause mortality (relative risk=0.94; 95%CI 0.91-0.98), with a number needed to treat of 161, assuming 10% mortality in controls (Level 1: Likely reliable evidence). Subgroup analyses revealed that this risk reduction was driven primarily by patients with insufficient levels of vitamin D.

There were no significant differences in mortality associated with other forms of vitamin D, including vitamin D2 (ergocalciferol) (12 trials), alfacalcidol (four trials), or calcitriol (three trials) (Level 2: Mid-level evidence).

Alfacalcidol and calcitriol, both active forms of vitamin D, were associated with increased risk of hypercalcemia. Vitamin D3 combined with calcium supplementation was associated with increased risk of renal calcium stone disease.

All electronic documents accessed October 28, 2011.