Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials
What this study found
Calcium supplements were associated with an increased risk of cardiovascular disease and coronary heart disease, while cerebrovascular disease was not significantly increased. The pooled relative risk was 1.15 (1.06-1.25) for cardiovascular disease and 1.16 (1.05-1.28) for coronary heart disease, with absolute risk differences of 8.6 per 1000 persons for CVD and 8.8 per 1000 persons for CHD. The signal was most concerning in healthy postmenopausal women, leading the authors to advise caution with calcium supplement use and to discourage supplementary calcium intakes. They called for further…
- Study & population
- Meta-analysis of 13 double-blind, placebo-controlled randomized trials, with 14 trials included in the final analysis because one study contributed two calcium arms.
- Intervention
- Calcium supplementation was given orally in daily doses ranging from 500 mg/d to 2000 mg/d across the included trials, using forms such as calcium citrate, citrate malate, carbonate, lactate-gluconate carbonate, or elemental calcium carbonate.
- Key limitation
- Most included trials were not designed with cardiovascular outcomes as primary endpoints, so event counts were relatively limited and outcome ascertainment was secondary in many studies.
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Open PDFOriginal abstract
Background: Recent systematic reviews and meta-analyses of randomized, double-blind, placebo-controlled trials (double-blind, placebo-controlled RCTs) have reported controversial findings regarding the associations between calcium supplements on the risk of cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between them. Methods: We searched PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles for double-blind, placebo-controlled RCTs in November, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) for the risk of cardiovascular disease were calculated using a random effects model. The main outcomes were CVD, coronary heart disease (CHD), and cerebrovascular disease. Results: A total of 13 double-blind, placebo-controlled RCTs (n = 28,935 participants in an intervention group and 14,243 in a control group)) were included in the final analysis. Calcium supplements significantly increased the risk of CVD (RR 1.15, 95% CI 1.06–1.25], I2 = 0.0%, n = 14) and CHD (RR 1.16, 95% CI 1.05–1.28], I2 = 0.0%, n = 9) in double-blind, placebo-controlled RCTs, specifically in healthy postmenopausal women. In the subgroup meta-analysis, dietary calcium intake of 700–1000 mg per day or supplementary calcium intake of 1000 mg per day significantly increased the risk of CVD and CHD. Conclusions: The current meta-analysis found that calcium supplements increased a risk of CVD by about 15% in healthy postmenopausal women.