Calcium Supplements Linked to Mortality Risk in Men, But Not Women

February 04, 2013

BETHESDA, Maryland — The debate over the safety of calcium supplements has been muddied with the publication of a new analysis showing that a high intake of supplemental calcium increases the risk of cardiovascular disease (CVD) death in men but not in women [1]. Compared with individuals who took no calcium, men who consumed 1000 mg or more of supplemental calcium per day had a significant 20% increased risk of CVD death, a risk that was driven by a significant 19% increased risk of heart-disease death.

For women, however, there was no association between calcium intake and the risk of death.

"We found a significant interaction by sex," write Dr Qian Xiao (National Cancer Institute, Bethesda, MD) and colleagues in their paper, published online February 4, 2013 in JAMA: Internal Medicine. "Elevated CVD mortality with increasing supplemental calcium intake was observed only in men; however, we cannot rule out the possibility that supplemental calcium intake may be associated with cardiovascular mortality in women." The group calls the difference in risk between men and women "intriguing," adding that further studies are needed to determine whether such differential risks are real.

In an editorial [2], Dr Susanna Larsson (Karolinska Institute, Stockholm, Sweden) said the lack of association between calcium supplementation in women is "perplexing," especially given the results of a reanalysis of the WHI study conducted by Dr Mark Bolland (University of Auckland, New Zealand) and colleagues. In the original WHI analysis on the risks associated with calcium use, investigators found no adverse cardiovascular effects in women taking calcium and vitamin D when compared with those not taking the supplements. However, Bolland et al reexamined the WHI data because 54% of women were already taking calcium and vitamin D by personal choice at the start of the WHI study and were not told to stop if they were randomized to placebo. When the data were reanalyzed, the researchers observed a significant association between calcium intake, as well as vitamin D, with the risk of MI.

New Report From NIH Data

The latest report is taken from an analysis of the National Institutes of Health--AARP Diet and Health Study, a study that included 388 229 men and women 50 to 71 years of age from six US states. Individuals self-reported frequency of food intake and portion size during a one-year period and answered questions about the frequency in which they consumed multivitamins, calcium-containing antacids, or calcium supplements alone.

During a mean follow-up of 12 years, there were 7904 and 3874 CVD deaths in men and women, respectively. Dietary intake of calcium was initially associated with total CVD and heart-disease death in men and women, but the association was no longer significant after adjustment for CVD risk factors. Supplemental calcium intake (1000 mg/day vs no calcium supplementation), on the other hand, increased the risk of CVD death and heart-disease death by 20% and 19%, respectively, in men, but there was no association in women. In an analysis that looked only at those taking calcium supplements and not multivitamins, the risk of CVD death and heart-disease death was 24% and 37% higher in men who took 1000 mg/day of calcium compared with those who took no supplements. Again, no association was observed in women who took calcium supplements alone.

There is currently a debate surrounding the benefits and risks of supplemental calcium in men and women. In 2010, researchers published a meta-analysis in BMJ showing that the use of calcium supplements without coadministered vitamin D is associated with an increased risk of MI. This increased risk was later confirmed in an analysis of the patients participating in the European Prospective Investigation into Cancer and Nutrition Study (EPIC).

In the editorial, Larsson concludes that the available evidence is suggestive of an adverse cardiovascular effect with excessive use of calcium supplements. Published as part of JAMA: Internal Medicine's series on "less is more" in medicine, the editorial states that more calcium, which is promoted because of its proposed benefits on bone health, does translate into health benefits. The best source of calcium, says Larsson, remains diet and the consumption of calcium-rich foods such as low-fat dairy, beans, and green leafy vegetables.