TORONTO – Calcium supplements appear to cause more harm than good, according to a meta-analysis of 28,000 participants in nine trials that includes a new analysis of more than 16,000 participants in the Women’s Health Initiative, but the reanalysis has raised concerns among the WHI’s original investigators.

"We calculate that for every 1,000 people treated with calcium for 5 years, it will lead to four additional myocardial infarctions, four additional strokes, and two additional deaths, while preventing three fractures," Dr. Ian R. Reid said at the annual meeting of the American Society for Bone and Mineral Research.

"I don’t prescribe calcium supplements to anyone anymore for preventing bone fractures. People should get calcium from their diet," said Dr. Reid, a professor of medicine at the University of Auckland, New Zealand. "We believe there is a fundamental difference between dietary calcium and supplemental calcium." He speculated that a calcium supplement, even at a relatively modest dose of 500 mg, produces a "borderline hypercalcemia" that persists for several hours and raises the risk for MI or stroke, the same way that people in the highest quartile for normal blood calcium levels have an increased risk for cardiovascular disease events.

Dr. Ian R. Reid

But the researchers who ran the Women’s Health Initiative (WHI) study questioned the legitimacy of the new analysis beyond a hypothesis-generating exercise.

"The WHI investigators have concerns about the reanalysis and whether omitting the subgroups with favorable results is appropriate," commented Dr. JoAnn E. Manson, professor of medicine at Harvard University and chief of the division of preventive medicine at Brigham and Women’s Hospital, both in Boston, and a WHI coinvestigator.

Dr. Reid and his associates initially documented their finding that calcium supplements raise cardiovascular risk in a pair of meta-analyses published online last July (BMJ 2010;341:c3691). They reported that calcium supplement use was linked with a statistically significant 27% and 31% relatively increased risk for MI in two separate meta-analyses.

To further explore the impact of calcium supplements on cardiovascular risk, they received permission from the National Heart, Lung, and Blood Institute to reanalyze data collected in a WHI study of more than 36,000 postmenopausal women randomized to receive a daily supplement with 500 mg calcium plus vitamin D or placebo. The original report from the WHI investigators showed that the calcium plus vitamin D treatment did not significantly increase or decrease coronary or cerebrovascular risk in generally healthy postmenopausal women during 7 years of treatment. (Circulation 2007;115:846-54).

Photo credit:(c) Mary Hope/istockphoto

But the WHI study design allowed the participants to take more calcium supplements in addition to their study agent, if they wanted to do so. At baseline, more than 19,000 (54%) of the women in the study reported using a calcium supplement on their own, and at the end of the study 69% reported the practice, Dr. Reid said. To address the possible confounding this may have caused, he focused his analysis on the 16,718 women in the WHI study who reported not using a personal calcium supplement at entry into the study.

11/04/10  

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FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY FOR BONE AND MINERAL RESEARCH

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Vitals

Major Finding: People taking a calcium supplement showed a statistically significant 24% excess relative risk for MI, a 15% excess relative risk for stroke, and a 16% excess relative risk for MI or stroke.

Data Source: Meta-analysis of nine studies that compared calcium supplements with placebo in a total of more than 28,000 people.

Disclosures: Dr. Reid said that he had no relevant disclosures.

Links:

finding that calcium supplements raise cardiovascular risk

original report from the WHI investigators