The Evidence and Controversy Between Dietary Calcium Intake and Calcium Supplementation and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Cohort Studies and Randomized Controlled Trials

Objective: Our objective was to synthesize both trial and observational studies and undertake a meta-analysis to explore the associations between calcium from dietary and supplemental intakes and cardiovascular disease (CVD) risks. Methods: Data sources were from PubMed, Cochrane Central, Scopus, and Web of Science, published from the inception dates up to March 2019. Randomized controlled trials (RCTs) and prospective cohort studies with data on dietary or supplemental intake of calcium, with or without vitamin D, and cardiovascular outcomes, were included. Results: Of the 1,212 identified studies, 26 prospective cohort studies and 16 RCTs were included. Results of cohort studies reveled that dietary calcium intakes (DCIs) ranging from 200 to 1500?mg/d did not affect the risk of CVD, coronary heart disease (CHD), and stroke (relative risk (RR) RR (for CVD) = 0.96, 95% CI, 0.87?1.05; RR (for CHD) = 0.98, 95% CI, 0.88?1.08; RR (for stroke) = 0.94, 95% CI, 0.85?1.04). Pooled RR of RCTs showed that the risk of CHD due to calcium supplements (CSs) increased 8% (RR = 1.08, 95% CI, 1.02?1.22; I-2 = 0.0%) and increased 20% allocated to CSs alone (RR = 1.20, 95% CI, 1.08?1.33; I-2 = 0.0%). CSs increased the risk of myocardial infarction (MI) by 14% (RR = 1.14, 95% CI, 1.05?1.25; I-2 = 0.0%), and CSs alone increased the MI risk 21% (RR = 1.21, 95% CI, 1.08?1.35; I-2 = 0.0%). Conclusions: We concluded that calcium intake from dietary sources do not adequately increase the risk of CVD including CHD and stroke, while calcium supplements might raise CHD risk, especially MI.