This analysis examined the benefits and harms of vitamin D with or without calcium supplementation on clinical outcomes of cancer and fractures in adults.
Studies examined included randomized, controlled trials (RCTs), prospective cohort studies, and nested case–control studies reporting incidence of or death from cancer and fracture outcomes; 19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) were analyzed.
According to the study, 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.