Two new studies contribute further to the debate over the cardiovascular risk associated with supplementary or dietary calcium, each decidedly coming down on the side of no significant risk — to men or women.
“[Based on these findings], clinicians should continue to evaluate calcium intake, encourage adequate dietary intake, and if necessary, use supplements to reach but not exceed recommended intakes,” Douglas C. Bauer, MD, from the University of California, San Francisco, the lead author of the first study, toldMedscape Medical News.
Results of both studies were reported at the recent American Society for Bone and Mineral Research (ASBMR) 2013 Annual Meeting.
Dr. Bauer’s observational trial is one of few contemporary studies to evaluate the level of risk among men, who are often poorly represented in calcium studies, he noted. The results showed no association between calcium dietary intake or supplementation and total or cardiovascular mortality. The second study was an updated meta-analysis of calcium supplementation among women and similarly demonstrated no increased risk for ischemic heart disease (with adjudicated outcomes) or total mortality in elderly women. It did draw some criticism for potential bias and contamination, however.
Nevertheless, says Robert Marcus, MD, a retired Stanford University bone specialist, the 2 studies are “powerful. The one involving men had very elegant, accurate reports of death and validated diagnosis of myocardial infarction, and the [study involving women] was also excellent work,” he commented.
“This field has been the subject of an enormous amount of controversy, ambiguity, and confusion for the past several years, and I think the most important thing is to help us come up with what is true,” he said. The quality of data to suggest an adverse effect of calcium is “very poor,” and there is now compelling evidence that there is little to substantiate this, he noted. But despite these reassuring new findings, public anxiety over a potential risk with calcium is unlikely to go away, he believes.
In recommendations issued in 2010, the ASBMR said that most adults 19 years of age and older require about 600 to 800 IUs of vitamin D daily and 1000 to 1200 mg of calcium daily through food and with supplements, if needed.
Contemporary Data on Calcium Intake in Men
The use of calcium supplements, predominantly with vitamin D, is an important therapy for the prevention of osteoporosis and its clinical consequences. But concerns about the cardiovascular safety of calcium have emerged periodically; in 2 alarming meta-analyses published in 2010 and 2011 by Dr. Mark Bolland and colleagues, for example, there was a 27% increase in MI among individuals allocated to calcium supplements in the first study and a 24% increased risk in the second.
More recently, a 40% increase in total mortality and up to a 50% increase in cardiovascular mortality was seenamong women from a Swedish mammography cohort with a calcium intake exceeding 1400 mg per day. In that study, the effect on mortality appeared to be especially strong if a high dietary intake of calcium was combined with calcium supplements.
In their new study, Dr. Bauer and his colleagues set out to assess rates of dietary calcium intake, use of supplements, and mortality in a prospective cohort of 5967 men over the age of 65 years in the Osteoporotic Fractures in Men (MrOS) study.
The participants completed extensive surveys at baseline on their dietary calcium intake, and supplementation was verified by a review of pill bottles by trained staff.
Mean dietary calcium intake was 1142 ± 590 mg/day, with more than half — 65% — of participants reporting use of calcium supplements.
Over the 10-year follow-up, among 2022 men who died, 687 deaths were caused by cardiovascular disease. The highest mortality for CVD was seen in the quartile with the lowest intake from calcium supplementation.
And in models that adjusted for age, energy intake, and calcium use, men in the lowest quartile of total calcium intake (less than 621 mg per day) had higher total mortality compared with those in the highest quartile (more than 1565 mg of calcium per day).
Adjustment for additional confounding factors showed no association between calcium dietary intake and total or cardiovascular mortality (P for trend .51 and .79, respectfully). Likewise, there was no association between calcium supplementation and total or cardiovascular mortality.
The authors also conducted an additional analysis of calcium intake and adjudicated cardiovascular disease events in a subcohort of the study, MrOS Sleep, involving 3120 patients who took part in a 7-year follow-up, and again there was no higher risk for cardiovascular events associated with calcium intake.
The study did have is limitations, Dr. Bauer acknowledged, including the observational design, calcium intake being assessed with a food frequency questionnaire, and cause of death not being formally adjudicated. Nevertheless, the findings are important in demonstrating the level of risk among men in a contemporary setting, he pointed out.
“Contrary to the Swedish study of women, we found no evidence that calcium supplementation is harmful to men, even among those with the highest dietary calcium intake,” he concluded, recommending that future studies should include adjudicated outcomes.
Study in Men as Expected, but Female Research Questioned
In the second study reported at the ASBMR meeting, Joshua Lewis, MD, PhD, from the University of Western Australia, Perth, and colleagues reported a meta-analysis of 19 randomized controlled trials involving women over the age of 50 years who had received calcium supplementation for more than a year.
Importantly, the analysis included reports of adjudicated cardiovascular outcomes, which the researchers note is important because gastrointestinal events can be misreported as cardiac ones. They also assessed all-cause mortality.
Among 59,844 participants in the studies, there were 4646 deaths, and the relative risk for death among those randomized to calcium supplements was 0.96 (P = .18).
The relative risk for 3334 ischemic heart disease events among 46,843 participants was 1.02 (P = .053), and the risk for 1097 MI events among 49,048 participants was 1.09 (P =.21).
“The data from this meta-analysis does not support the concept that calcium supplementation with or without vitamin D increases the risk of ischemic heart disease or total mortality in elderly women,” concluded Dr. Lewis.
But bone specialist Ian Reid, MD, from the University of Auckland, New Zealand, who was a coauthor on some of the Bolland studies, said this analysis essentially repeats previous ones, but with the inclusion of 20,000 patients from the Women’s Health Initiative (WHI), many of whom continued to take their own calcium tablets, regardless of whether they were randomized to calcium or placebo.
These “contaminated” WHI data have the potential to mask the effect of calcium, he told Medscape Medical News. In addition, in a study from Denmark also included in the meta-analysis, subjects were not properly blinded to treatment assignment and the calcium and control groups were not comparable at baseline for cardiovascular risk, which introduced “major potential bias,” he added.
Regarding the results from the study in men by Dr. Bauer and colleagues, Dr. Reid said they were not surprising to him. “Generally, people who take calcium supplements have more health-conscious behaviors than those who do not and so have a lower baseline risk of heart disease” that can “obscure small adverse effects of drugs such as calcium,” he observed.
An effect has to be “very substantial” before it can be picked up in an observational study, because of the many confounders that can obscure such an effect, he concluded.