Calcium supplements and cancer risk: a meta-analysis of randomised controlled trials

Some evidence suggests that Ca and vitamin D supplements affect cancer risk; however, it is uncertain whether the effects are due to Ca, vitamin D or the combination. We investigated the effect of Ca supplements without co-administered vitamin D on cancer risk. Medline, Embase and the Cochrane Central Register of Controlled Trials, reference lists of meta-analyses and two clinical trial registries were searched for randomised, placebo-controlled trials of Ca supplements (>= 500 mg/d), with >= 100 participants and duration.1 year. The lead authors of eligible trials supplied data on cancer outcomes. Trial-level data were analysed using random-effects meta-analyses and patient-level data using Cox proportional hazards models. A total of sixteen trials were eligible, six had no data available, ten provided trial-level data (n 10 496, mean duration 3.9 years), and of these, four provided patient-level data (n 7221, median duration 3.5 years). In the meta-analysis of trial-level data, allocation to Ca did not alter the risk of total cancer (relative risk 0.95, 95% CI 0.76, 1.18, P=0.63), colorectal cancer (relative risk 1.38, 95% CI 0.89, 2.15, P=0.15), breast cancer (relative risk 1.01, 95% CI 0.64, 1.59, P=0.97) or cancer-related mortality (relative risk 0.96, 95% CI 0.74, 124, P=075), but reduced the risk of prostate cancer (relative risk 0.54, 95% CI 0.30, 0.96, P=0.03), although there were few events. The meta-analysis of patient-level data showed similar results, with no effect of Ca on the risk of total cancer (hazard ratio 1.07, 95% CI 0.89, 1.28, P=0.50). Ca supplements without co-administered vitamin D did not alter total cancer risk over 4 years, although the meta-analysis lacked power to detect very small effects, or those with a longer latency.