A Review of Calcium Supplements and Cardiovascular Disease Risk

Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE.
Advances in Nutrition (Impact Factor: 4.71). 11/2012; 3(6):763-71. DOI: 10.3945/an.112.002899
Source: PubMed


A group of academic and industry experts in the fields of nutrition, cardiology, epidemiology, food science, bone health, and integrative medicine examined the data on the relationship between calcium supplement use and risk of cardiovascular events, with an emphasis on 4 of the Bradford Hill criteria for causal inference: strength, consistency, dose-response, and biological plausibility. Results from 2 epidemiological studies and a meta-analysis of randomized, controlled clinical trials, including a subgroup analysis from the Women's Health Initiative, have prompted concern about a potential association between calcium supplement use and a small increase in the risk of adverse cardiovascular events. However, a number of issues with the studies, such as inadequate compliance with the intervention, use of nontrial calcium supplements, potential bias in event ascertainment, and lack of information on and adjustment for known cardiovascular risk determinants, suggest that bias and confounding cannot be excluded as explanations for the reported associations. Findings from other cohort studies also suggest no detrimental effect of calcium from diet or supplements, with or without vitamin D, on cardiovascular disease risk. In addition, little evidence exists for plausible biological mechanisms to link calcium supplement use with adverse cardiovascular outcomes. The authors do not believe that the evidence presented to date regarding the hypothesized relationship between calcium supplement use and increased cardiovascular disease risk is sufficient to warrant a change in the Institute of Medicine recommendations, which advocate use of supplements to promote optimal bone health in individuals who do not obtain recommended intakes of calcium through dietary sources.

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    • "In addition, AE case reports in a case reporting system such as VAERS can be analysed statistically using methods such as filtering based on a case number cutoff, proportional reporting ratio (PRR) [33], and Chi-square test, in order to screen for possible causal AEs [8]. To make more convincing causality assessment using a statistical method, randomized, well-controlled experimental design for evaluating a causality hypothesis is typically required [34,35]. These statistical methods can be used to address any possible ‘causal adverse event hypothesis’. "
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