Skiip the Calcium, Save the Patient
The Study
Xiao Q, Murphy RA, Houston DK, Harris TB, Chow W, Park Y. Dietary and supplemental calcium intake and cardiovascular disease mortality: The National Institutes of Health-AARP Diet and Health Study. JAMA Intern Med. 2013;1-8. [Epub ahead of print]
Introduction
Scant evidence supports the notion that calcium supplements alone significantly decrease the risk for osteoporotic fracture, yet these supplements remain one of the most popular treatments taken by adults in the United States. In addition, there is increasing evidence that calcium may contribute to a higher risk for cardiovascular disease (CVD). The current study uses a large cohort of adults to examine how dietary calcium and calcium supplements affect the risk for CVD among women and men.
Background
A new review of supplement use, based on data from the National Health and Nutrition Examination Survey,[1] concluded that nearly one half of adults in the United States use dietary supplements, but relatively few of these individuals take supplements on the recommendation of their physician or other healthcare provider. This study found that 49% of a sample of US adults had used of supplements in the past 30 days. Factors associated with a higher rate of supplement use included female sex, non-Hispanic white race, and a subjective measurement of health as very good or excellent.
Although the most popular reason for using supplements in this study was to improve or maintain health in general, "bone health" was cited by 25% of respondents as a reason for taking these agents. Products that contained calcium were the second most common supplements overall. However, only 23% of supplements were recommended by the individual's physician.
What is the evidence for supplement use, particularly when it comes to calcium? A meta-analysis of 29 studies found that calcium use alone was associated with a nonsignificant reduction in the risk for fracture.[2] However, the use of calcium with vitamin D reduced the risk for fracture by 12%. Vitamin D alone at doses of 800 IU or more daily also significantly reduced the risk for fracture (relative risk, 0.84; 95% confidence interval [CI], 0.75-0.94).
In another meta-analysis, total calcium intake did not alter the risk for hip or total nonvertebral fracture.[3] More disturbing was the finding that calcium supplementation was associated with a higherrisk for hip fracture compared with placebo.
Supplements are also frequently used to prevent poor health outcomes. There is limited evidence that high-dose treatment with vitamin D supplements can reduce the risk for incident cancer, particularly colorectal cancer.[4] However, little evidence suggests that treatment with calcium alone or calcium with vitamin D has an effect on the risk for cancer.
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Whereas the health benefits of calcium supplementation are questionable, growing evidence indicates that calcium supplementation may be associated with an increase in the risk for CVD. In a trial of over 1400 women who were randomly assigned to receive calcium citrate 1 g or placebo daily, the risk for the combined endpoint of myocardial infarction, stroke, or sudden death was nearly 50% higher in the calcium group during 5 years of treatment.[5] Although data from the Women's Health Initiative initially pointed to a lack of effect of calcium supplements on the risk for cardiovascular events, a separate analysis found that calcium supplements significantly increased the risk for these events, particularly myocardial infarction.[6,7] In a meta-analysis, the use of calcium supplements vs placebo was associated with a hazard ratio for myocardial infarction of 1.31 (95% CI, 1.02-1.67).[8] There were nonsignificant increases in the risks of stroke and a combined cardiovascular endpoint in women taking calcium vs placebo.
The data regarding any relationship between dietary calcium and the risk for CVD is weaker than that for calcium supplements.[9] However, a recent study found a significant increase in the risk for mortality outcomes associated with calcium consumption among a cohort of 61,000 women who were followed for a median of 19 years.[10] Compared with more modest consumption of dietary calcium, calcium intake of over 1400 mg/day was associated with a hazard ratio of 1.49 (95% CI, 1.09-2.02) for death from CVD, as well as a higher risk for death from any cause (hazard ratio, 1.40; 95% CI, 1.17-1.67).
The potential cardiovascular risk associated with calcium intake is an evolving field of inquiry. The current study uses a large database of older adults to add to the sum of evidence regarding this issue
Study Design and Results
Researchers analyzed data from the National Institutes of Health-American Association of Retired Persons (AARP) Diet and Health Study. This research enrolled AARP members between 50 and 71 years of age in 8 states. Participants were generally healthy at baseline, and individuals at the extremes of total energy and dietary calcium intake were excluded from study analysis.
A 124-item food-frequency questionnaire was used to assess participants' dietary calcium intake. This survey also queried the use of supplements, and participants completed a baseline questionnaire that included demographic, disease, anthropometric, and lifestyle information.
The main study outcome was the effect of calcium intake on the risk for CVD death, as defined by mortality caused by heart disease or stroke. National databases were used to access participants' vital status and causes of death. A previous study found that the accuracy of this method was 95%. Researchers adjusted their results to account for potential confounding variables.
The analysis included data from 388,229 adults. In all, 56% of women and 23% of men reported using calcium supplements; and the respective proportions of women and men who took multivitamins containing calcium were 58% and 56%. Participants who used calcium supplements were more likely to be non-Hispanic white persons, have a college education, have healthier lifestyle habits, and report better overall self-rated health.
During a mean of 12 years of follow-up, there were 7904 CVD deaths among men and 3874 CVD deaths among women in the study. A significant trend was seen toward a reduction in the risk for death due to heart disease with greater dietary calcium intake among men, but dietary calcium intake did not affect the risks for stroke death in either sex or any CVD death among women.
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Among men, daily supplemental calcium at a dosage of 1000 mg/day or more was associated with significant increases in the risks for overall CVD death (relative risk, 1.20; 95% CI, 1.05-1.36) and heart disease death (relative risk, 1.19; 95% CI, 1.03-1.37). There was a nonsignificant trend toward a higher risk for stroke death associated with the use of calcium supplements. The low number of deaths caused by stroke overall reduced the power of the study to evaluate this outcome.
Among women, calcium supplements did not independently affect the risks for death from CVD, heart disease, or stroke.
The risk for death among men who used calcium supplements appeared to be particularly high among smokers. There was a U-shaped curve relationship between total calcium intake and the risk for CVD mortality among men, but this was not found among women.
Commentary: The Gender Gap
No one should be more invested in the concept of wellness than the individual. Each patient has the autonomy to select health treatments, and clearly many adults use calcium to stay healthy. However, it is time for physicians to actively intercede of behalf of their patients' safety when they make this choice regarding calcium.
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The current study emphasizes the risk for CVD mortality associated with the use of calcium supplements among men, and any potential benefit of calcium supplementation is now outweighed by the risk for CVD in this group. The rate of osteoporosis among men is one-fifth that of women, and less than 40% of osteoporotic fractures occur among men.[11] Although we cannot discount the potential grave impact of fragility fractures among older men, calcium supplements do not seem to be the answer to reducing this risk, particularly given their association with CVD.
Among women, the current study suggests a neutral effect of both dietary calcium and calcium supplements on the risk for CVD. Physicians should keep in mind, however, that vitamin D and not calcium is principally responsible for preserving bone and preventing osteoporosis among women. Vitamin D at a dose of at least 800 IU/day should be the primary treatment for women at average risk for osteoporosis. Until the questions regarding the long-term safety of calcium supplements in both sexes are better understood, it is reasonable to withhold calcium among women receiving preventive treatment for bone health.
Clinical Pearls
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Calcium-containing compounds are the second most popular complementary treatment among adults in the United States, yet most supplements are taken without a recommendation from a physician.
It is questionable whether calcium supplements alone contribute to the prevention of fracture.
A growing body of evidence suggests that calcium supplements, and perhaps even dietary calcium, can increase the risk for CVD.
In the current study, the use of calcium supplements among men was associated with a higher risk for cardiovascular death and death related to heart disease.
Calcium supplements did not significantly affect the risk for CVD mortality among women.
Calcium supplements are unnecessary among men and should be evaluated critically among women at average risk for fracture.