Review: Cholecalciferol (vitamin D₃) reduces mortality in adults; other forms of vitamin D do not

Does vitamin D reduce mortality in adults? What are the harms?

Included studies compared supplemental vitamin D (cholecalciferol [vitamin D₃] or ergocalciferol [vitamin D₂]) or active forms of vitamin D (alfacalcidol or calcitriol), alone or combined with calcium, with placebo or no intervention in adults ≥ 18 years of age who were healthy or had stable disease or vitamin D deficiency. Trials that enrolled patients with secondary-induced osteoporosis or cancer or women who were pregnant or lactating were excluded. Primary outcomes were all-cause mortality and adverse events. Other outcomes included cardiovascular (CV) and cancer mortality.

MEDLINE, EMBASE/Excerpta Medica, Cochrane Library, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index—Science (all to Jan 2011); ongoing trial databases; and reference lists were searched for randomized controlled trials (RCTs). Investigators, experts, and manufacturers of vitamin D were contacted. 144 RCTs (n = 108 496) met the selection criteria: 84 did not report any deaths, 10 reported mortality for all groups combined, and 50 reported mortality by treatment group and were included in meta-analyses. Of those 50 RCTs (n = 94 148, mean age 74 y, 79% women), 26 had low risk for bias. 38 used placebo control, and 12 used no control intervention; 32 included a vitamin D plus calcium intervention group.

Meta-analysis showed that use of any vitamin D reduced all-cause mortality more than placebo or no intervention (Table). Meta-analysis by type of vitamin D showed that cholecalciferol reduced all-cause but not CV or cancer mortality; ergocalciferol, alfacalcidol, and calcitriol did not reduce all-cause mortality (Table). Active forms of vitamin D increased risk for hypercalcemia (3 RCTs, n = 710, relative risk increase [RRI] 218%, 95% CI 17 to 768), and cholecalciferol plus calcium increased risk for nephrolithiasis (4 RCTs, n = 42 876, RRI 17%, CI 2 to 34) more than placebo or no intervention; vitamin D did not increase risk for other reported adverse events.

Cholecalciferol (vitamin D₃) reduces mortality in adults more than placebo or no treatment; other forms of vitamin D do not.