Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials

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.

Calcium Supplementation, Risk of Cardiovascular Diseases, and Mortality: A Real-World Study of the Korean National Health Insurance Service Data

“…Furthermore, Michaëlsson et al found that a high calcium intake is related to high all-cause mortality [19]. Our findings are consistent with those of previous studies which showed that calcium supplementation is associated with an increased risk of myocardial infarction [7,10,17], ischemic stroke [8], and death [19] in other populations. Moreover, our findings suggest that calcium supplementation may increase the risk of myocardial infarction and ischemic stroke in Koreans, who are known to have little calcium intake.…”

“…While two previous meta-analyses by Bolland et al [7,17] reported an association between calcium supplementation and the risk of myocardial infarction, two other meta-analyses by Chung et al [18] and Lewis et al [9] showed no relationship between calcium supplementation and cardiovascular disease risk. However, a recent meta-analysis by Myung et al showed that calcium supplementation increased the risk of coronary heart disease [10]. Abajo et al suggested that calcium supplementation might increase the risk of ischemic stroke [8].…”

“…However, studies have reported negative cardiovascular effects of calcium supplement intake and stated that calcium intake might be related to an increased risk of myocardial infarction [7] and ischemic stroke [8]. Although a previous meta-analysis by Lewis et al showed no relationship between calcium supplementation and cardiovascular event risk [9], a recent meta-analysis of 13 randomized, double-blind, placebo-controlled trials showed that calcium supplementation increased the risk of cardiovascular diseases [10]. However, most studies were conducted in Western countries with high calcium intake, and evidence regarding populations with low calcium intake is rare.…”

Longitudinal Effects of Serum Calcium and Phosphate Levels and Their Ratio on Incident Ischemic Heart Disease among Korean Adults

“…In addition, calcium supplementation can be beneficial for bone health in children, older adults, and postmenopausal women [ 3 ]. However, there is also increasing concern regarding the possible link between serum calcium levels and cardiovascular events [ 4 , 5 ].…”

Global Variations in the Mineral Content of Bottled Still and Sparkling Water and a Description of the Possible Impact on Nephrological and Urological Diseases

“…High calcium waters may be a calorie-free nutritional supplement for those with low calcium levels as calcium supplements were thought to increase cardiovascular (CVD) risk [29,30]. However, although the relationship between calcium intake and bone formation is clear, controversy remains whether calcium intake affects the risk for CVD as the evidence is contradictory [31][32][33].…”