Effect of Vitamin D and calcium supplementation on cancer incidence in older women: A randomized clinical trial

IMPORTANCE Evidence suggests that low vitamin D status may increase the risk of cancer. OBJECTIVE To determine if dietary supplementation with vitamin D₃ and calcium reduces the risk of cancer among older women. DESIGN, SETTING, AND PARTICIPANTS A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015 - the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years. INTERVENTIONS The treatment group (vitamin D₃ + calcium group) received 2000 IU/d of vitamin D₃ and 1500mg/d of calcium; the placebo group received identical placebos. MAIN OUTCOMES AND MEASURES The primary outcomewas the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D₃ + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D₃ + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95%CI, -0.06%to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95%CI, 0.032 to 0.056) in the vitamin D₃ + calcium group and 0.060 (95%CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95%CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D₃ + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D₃ + calcium group and 2 in the placebo group). CONCLUSIONS AND RELEVANCE Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D₃ and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.