Calcium plus vitamin D supplementation and the risk of colorectal cancer.

This was a randomized, placebo-controlled trial in healthy postmenopausal women aged 50 to 79 years enrolled at 40 Women's Health Initiative centers in the United States. For the calcium plus vitamin D group, 18,176 participants were randomized.

Active treatment was oral calcium carbonate providing 500 mg elemental calcium plus 200 IU vitamin D3 per tablet, taken twice daily for a total daily dose of 1000 mg elemental calcium and 400 IU vitamin D3. The regimen was given for an average of 7 years and was compared with placebo.

Calcium plus vitamin D did not reduce colorectal cancer incidence in this trial. Invasive colorectal cancer occurred in 168 women in the calcium plus vitamin D group versus 154 in the placebo group (hazard ratio 1.08, 95% CI 0.86 to 1.34; P = 0.51). Death from colorectal cancer was also not reduced (34 vs 41; hazard ratio 0.82, 95% CI 0.52 to 1.29; P = 0.39), and intestinal polyps were unchanged (2983 vs 2997; hazard ratio 0.99, 95% CI 0.94 to 1.04; P = 0.71). Kidney stones were more common with supplementation (449 vs 381; hazard ratio 1.17, 95% CI 1.02 to 1.34; P = 0.02).

The main outcome was null despite a long follow-up of about 7 years, which may still be too short for a cancer endpoint with long latency. Baseline calcium and vitamin D intake was already substantial, many participants used personal calcium supplements, and supplementation outside the trial was not restricted, all of which could dilute any effect. Generalizability is limited to relatively healthy postmenopausal women in the Women's Health Initiative.