Calcium Intake and Cardiovascular Disease Risk An Updated Systematic Review and Meta-analysis

Background: Conflicting evidence exists regarding potential cardiovascular risks associated with high levels of calcium intake. Purpose: To update and reanalyze 2 systematic reviews to examine the effects of calcium intake on cardiovascular disease (CVD) among generally healthy adults. Data Sources: MEDLINE; Cochrane Central Register of Controlled Trials; Scopus, including EMBASE; and previous evidence reports from English-language publications from 1966 to July 2016. Study Selection: Randomized trials and prospective cohort and nested case-control studies with data on dietary or supplemental intake of calcium, with or without vitamin D, and cardiovascular outcomes. Data Extraction: Study characteristics and results extracted by 1 reviewer were confirmed by a second reviewer. Two raters independently assessed risk of bias. Data Synthesis: Overall risk of bias was low for the 4 randomized trials (in 10 publications) and moderate for the 27 observational studies included. The trials did not find statistically signifi-cant differences in risk for CVD events or mortality between groups receiving supplements of calcium or calcium plus vitamin D and those receiving placebo. Cohort studies showed no consistent dose-response relationships between total, dietary, or supplemental calcium intake levels and cardiovascular mortality and highly inconsistent dose-response relationships between calcium intake and risks for total stroke or stroke mortality. Limitations: CVD disease outcomes were secondary end points in all trials. Dose-response metaregression analysis of cohort studies was limited by potential confounding, ecological bias, and imprecise measures of calcium exposures. Data were scarce regarding very high calcium intake-that is, beyond recommended tolerable upper intake levels. Conclusion: Calcium intake within tolerable upper intake levels (2000 to 2500 mg/d) is not associated with CVD risk in generally healthy adults.