07.30.10
Calcium supplementation (without co-administered vitamin D) was associated with an increased risk of myocardial infarction, according to a meta-analysis published in the British Medical Journal.
Authors of the review concluded that since calcium supplements are widely used, these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. Therefore, they believe a reassessment of the role of calcium supplements in the management of osteoporosis is warranted.
Data sources included Medline, Embase and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010.
Eligible studies were randomized, placebo-controlled trials of calcium supplements (
500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year.
500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year.
The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self-reports, hospital admissions and death certificates.
Fifteen trials were eligible for inclusion—five with patient level data (8151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11,921 participants, mean duration 4 years).
In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo. Non-significant increases occurred in the incidence of stroke, the composite end point of myocardial infarction, stroke, or sudden death, and death. The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium.
The Council for Responsible Nutrition (CRN), Washington, D.C., responded to the study saying a broad range of scientific research has demonstrated that an adequate intake of calcium plays an important role in building and maintaining optimum bone mass, and that this meta-analysis should not cause consumers to doubt the value of calcium supplements for maintaining bone health.
“Adequate calcium intake is vital to building and maintaining healthy bones, and to preventing osteoporosis—which is caused by a failure to build adequate bone mass or by bone loss that occurs as we age,” said Andrew Shao, PhD, senior vice president, Scientific & Regulatory Affairs, CRN. “Most people do not get enough calcium from diet alone, and this is where a calcium supplement can be important to consumers of all ages. The results from this meta-analysis does not undermine the value calcium supplements offer to those concerned with maintaining or increasing bone density, as years of research shows these products do.”
According to CRN, the authors’ conclusions are dramatically overstated, considering the limitations of meta-analysis, in general, and this meta-analysis, specifically. For example, the analysis could have potentially included more than 300 scientific studies on calcium supplementation’s effect on bone, but only 15 randomized clinical trials were deemed “eligible for analysis.”
Further, seven of the 15 trials evaluated had no, or incomplete, data on cardiovascular outcomes, and only five of the 15 studies accounted for almost all of the cardiovascular outcomes. Further, because the researchers chose to exclude any trials administering calcium plus vitamin D, many large, important trials—including the Women’s Health Initiative, which found calcium plus vitamin D had no effect on the risk of coronary heart disease or stroke—were not included.
“The authors characterize these findings as though all of the selected studies suggest increased risk. In fact, the opposite is true: most of the studies do not suggest increased risk,” said Dr. Shao. “Bone health is one of the most common reasons why healthcare professionals recommend calcium supplements; there are other health benefits that may be associated with calcium supplementation, such as reduction of colon cancer risk. This is not even considered by the authors. It’s unfortunate that these researchers are making sweeping judgments about the value of calcium supplements by only assessing a handful of handpicked studies.”
Dr. Shao also pointed out that none of the original studies included in the meta-analysis were designed to evaluate cardiovascular outcomes. Additionally, the data on cardiovascular events was never previously published, so analysts had to track the information down separately, in some cases, 10 even 20 years after the original study was published.
“Meta-analysis can be a useful tool for scientific evaluation, but we have to recognize its limitations, and keep in mind that its findings are based on a collection of past studies that may have different designs, doses and study populations,” said Dr. Shao. “This analysis should not dissuade consumers, particularly young women, from taking calcium supplements. They should talk with their doctors about their current and long-term needs and determine how much calcium they are getting from their diets, and supplement accordingly—likely in combination with vitamin D.”
