Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis

Re: Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis

5 February 2013

The BMJ has published a series of papers demonstrating an increased risk of cardiovascular events in individuals using calcium supplements.1-3 Annual world-wide sales of these supplements have been several billion dollars. The figure shows a 60% reduction in prescriptions for calcium supplements in New Zealand in response to the publications. Declining prescriptions and over-the-counter sales of calcium could decrease company revenues. This raises the question as to what responses are appropriate from companies affected in this way, and what the proper role of academics and scientific journals should be in such responses.

The Council for Responsible Nutrition (CRN) is “the leading trade association representing dietary supplement manufacturers and ingredient suppliers” whose mission is “to enhance and sustain a climate for our member companies to responsibly develop, manufacture and market dietary supplements and nutritional ingredients” (quotes from the CRN website). Statements previously on the website indicate that CRN instigated the writing of a review of the BMJ papers, and that this review was directed to a specific outcome (CRN ~ The Report, July 8, 2011; CRN ~ The Report, August 19, 2011):

CRN has formed a working group to evaluate emerging safety questions regarding calcium supplementation and an alleged relationship to cardiovascular events

The working group was formed earlier this year to ... address potential unwarranted negative media coverage regarding calcium supplementation that resulted from three studies published by a small group of researchers

CRN believes these articles have the potential to negatively influence consumers‘ views of the importance of calcium

The working group has recruited ... experts in addition to CRN scientists

The CRN group began reviewing the science and developing a plan on its initial July 5 strategy call

If calcium is key to your business, your company needs to participate in CRN’s Calcium Working Group as it plans a critical review that addresses recent concerns about calcium’s safety

It appears that the product of this call to arms is the recently published paper of Heaney et al,4 which was followed by press releases from organisations with similar commercial interests to the CRN. Of the six authors, two are employees of CRN, and a third consults for this organisation. It is interesting to note that only two academics took up the open invitation to join this group of experts. Presuming that the paper is in fact a direct product of the call to arms, we were surprised that the academic authors participated in, and Advances in Nutrition chose to publish the result of, a process that was explicitly established to protect the commercial interests of the sponsoring organisation. We believe it is important that individuals reading this review are aware of the context that surrounded its creation. If a pharmaceutical company were to fund and co-author a review that was highly critical of research showing adverse effects of that company's product, such a review would be viewed with great scepticism. We see little difference between that hypothetical situation and the Heaney review. Parenthetically, the issues raised in the review regarding our analyses of calcium supplement effects on cardiovascular endpoints have already been addressed in detail in the BMJ5 and elsewhere.6


1. Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, Gamble GD, Grey A, Reid IR. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008;336(7638):262-66.

2. Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:C3691.

3. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium/vitamin D supplements and cardiovascular events: a re-analysis of the Women’s Health Initiative limited-access dataset, and meta-analysis of calcium with or without vitamin D. BMJ 2011;342:d2040. doi:10.1136/bmj.d2040.

4. Heaney RP, Kopecky S, Maki KC, Hathcock J, MacKay D, Wallace TC. A review of calcium supplements and cardiovascular disease risk. Advances in Nutrition 2012;3:763–71.

5. Bolland MJ, Avenell A, Grey A, Gamble GD, Reid IR. Calcium, vitamin D, and cardiovascular events: further author response. BMJ;

6. Reid IR, Bolland MJ, Avenell A, Grey A. Cardiovascular effects of calcium supplementation. Osteoporos. Int. 2011:1-10.

Competing interests: None declared

Ian R Reid, Professor of Medicine

Mark Bolland, Andrew Grey

University of Auckland, Private Bag 92019, Auckland, New Zealand

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