Taking calcium supplements appears to raise the risk of death from cardiovascular disease among men but not women, according to a report published online Feb. 4 in JAMA Internal Medicine.
In contrast, the intake of dietary calcium has no apparent effect on cardiovascular disease (CVD) mortality in either sex, said Qian Xiao, Ph.D., of the division of cancer epidemiology and genetics, National Cancer Institute, and her associates.
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Calcium tablets
These findings from a large prospective study that followed 388,229 adults for 12 years are not definitive but provide further support for the controversial idea that supplemental calcium may have adverse effects on cardiovascular health. However, calcium also "is widely involved in many aspects of human physiology" and is known to benefit some aspects of cardiovascular health, such as lowering blood pressure and improving lipid profiles, so further study is warranted.
"Given the extensive use of calcium supplements in the population, it is of great importance to assess the effect of supplemental calcium use beyond bone health," Dr. Xiao and her colleagues wrote.
The investigators examined this issue using data from the National Institutes of Health–AARP Diet and Health Study, which assessed adults who were aged 50-71 years in 1995 and resided in California, Florida, Louisiana, New Jersey, North Carolina, Pennsylvania, Atlanta, and Detroit. For this study, the investigators followed 219,059 men and 169,170 women participants, correlating their calcium intake at baseline with cumulative mortality from heart disease, cerebrovascular disease, and other forms of CVD.
A total of 23% of the men and 56% of the women took calcium supplements, and 56% of the men and 58% of the women took multivitamins containing calcium. During follow-up there were 7,904 CVD deaths in men and 3,874 in women.
The use of calcium supplements correlated with a significantly elevated risk of total CVD mortality, heart disease mortality, and cerebrovascular disease mortality in men. In addition, men taking the highest quintile of calcium supplementation showed an increased risk of CVD death, which was mainly driven by heart disease death, Dr. Xiao and her associates said (JAMA Intern. Med. 2013 [doi:10.1001/jamainternmed.2013.3283]).
In women, null associations were seen between calcium supplements and all of these outcomes.
Dietary calcium showed no relationship with any mortality outcome in men or women.
These findings remained robust in a sensitivity analysis that excluded data on all deaths that occurred during the first 2 years of follow-up.
In analyses that categorized subjects by age, smoking status, BMI, hypertension, hypercholesterolemia, magnesium intake, and alcohol consumption, the positive association between calcium supplements and increased mortality persisted in most of these subgroups among men. It remained null among women except in three notable subgroups: In women who were former smokers, who did not have hypertension, and who had hypercholesterolemia, calcium supplements were linked to an increase in CVD mortality.
One possible mechanism by which calcium supplements could exert an adverse effect on CVD is the deposition of calcium phosphate in cardiovascular structures, in the form of vascular calcification. Increased blood coagulation and arterial stiffness also have been linked to high serum calcium levels, the investigators noted.
The significant interaction by sex was an "intriguing" finding that also deserves further investigation. "It may be reasonable to assume that, on average, male users started taking calcium supplements at an older age. Therefore women were more likely to have achieved calcium balance and stable calcium levels long before the study, and the effect of calcium supplements became less profound," the investigators wrote.
This study was supported by the National Institutes of Health, the National Cancer Institute, and the National Institute on Aging. No financial conflicts of interest were reported.