• The Challenges of the Single Micronutrient Study

     
     
     
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    The Challenges of the Single Micronutrient Study Commentary on Calcium Supplements and Cardiovascular Events

    June 8, 2011

    This review presents a position paper on behalf of the ASBMR Professional Practice Committee on the current controversy regarding calcium supplement use and the possible association with increased cardiovascular events. Data from randomized controlled trials, large cohort studies and three recently published meta-analyses are discussed.

    While earlier publications reported a significant proportion of the adult population with very low calcium intakes, the 2010 NHANES report  showed that a much greater percentage of people are meeting and some, in fact, exceeding daily recommended intakes for calcium and vitamin D.

    Recently, controversy has arisen based on reports of an increased risk of cardiovascular events associated with calcium supplementation. Publications with the opposing view that calcium supplementation does not increase cardiovascular events have also been recently published, including a meta-analysis and a randomized controlled trial with long term follow-up.  This leads to the question of whether calcium supplementation is beneficial for bone but deleterious for the cardiovascular system. 

    Four recent publications, one a randomized controlled trial, one a prospective cohort study and two meta-analyses have suggested that there is an increased risk for adverse cardiovascular events in elderly adult men and women on calcium supplements. But, how convincing is the evidence for cardiovascular harm?  The two "positive meta-analyses" use an unusual retrospective collection of patient level data, and select subpopulations of the original studies. A conventional and recent meta-analysis that included only original study data, in which compliance of >80% and outcomes were formally collected, reported no increase in adverse cardiovascular events.  A RCT with an equivalent number of patients, nine and a half years of  follow-up for cardiovascular outcomes and firm documentation of supplement compliance reported no evidence of increased adverse cardiovascular outcome.  Several cohort studies found no evidence of cardiovascular harm.

    The following lessons have come from this review: True placebo-controlled randomization in a trial of a single, readily available nutrient such as calcium is often difficult to achieve. Compliance with study parameters must be maintained, probably to levels well above 80% to provide confidence in a verifiable outcome, and it is important to monitor the intake of other dietary nutrients that might alter calcium effects. Clear, definable adjudicated endpoints must be utilized. The most appropriate and stringent methods of statistical analysis must be applied.  Based on these criteria, the weight of evidence is insufficient to conclude that calcium supplements cause adverse cardiovascular events; however, the debate continues. 

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