To investigate whether vitamin D with or without calcium supplementation has any effect on clinical outcomes of cancer and fractures in adults, researchers searched MEDLINE and Cochrane for controlled studies reporting incidence of, or death, from cancer and fracture outcomes.

A total of 19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) met the inclusion criteria. The following findings were reported:

• Limited data from RCTs suggested that high-dose (1000 IU/d) vitamin D supplementation can reduce the risk for total cancer, and data from observational studies suggested that higher blood 25-hydroxyvitamin D (25-[OH]D) concentrations might be associated with increased risk for cancer.

• Mixed-effects dose–response meta-analyses showed that each 10-nmol/L increase in blood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to 9%) reduced risk for colorectal cancer but no statistically significant dose–response relationships for prostate and breast cancer.

• Random-effects model meta-analysis showed that combined vitamin D and calcium supplementation reduced fracture risk (pooled relative risk, 0.88 [CI, 0.78 to 0.99]) in older adults, but the effects differed according to study setting: institution (relative risk, 0.71 [CI, 0.57 to 0.89]) versus community-dwelling (relative risk, 0.89 [CI, 0.76 to 1.04]).

• One RCT showed adverse outcomes associated with supplementation, including increased risk for renal and urinary tract stones.

The researchers concluded that there is not sufficient robust evidence to clarify the role of vitamin D supplementation for the prevention of cancer. Combined vitamin D and calcium supplementation can reduce fracture risk, but the effects appear to be smaller among community-dwelling older adults than among institutionalized elderly persons.