Calcium Supplements, but Not Dietary Calcium, Linked to Higher Long-term Risk of Atherosclerosis: MESA

Adults free of heart disease who get high levels of calcium from their diet rather than from supplements have a lower 10-year risk of atherosclerotic disease, as evidenced by changes in coronary artery calcium (CAC), according to a new analysis of data from the Multi-Ethnic Study of Atherosclerosis (MESA). Echoing earlier reports, researchers also found that excessive use of supplements can increase the risk of disease.

Starting nearly a decade ago, data derived from randomized trials including the Women’s Health Initiative and others “kept showing this possible signal of harm with calcium supplementation” in terms of increased CVD events, senior author Erin D. Michos, MD, MHS (Johns Hopkins University School of Medicine, Baltimore, MD), told TCTMD.

“The reason why we think it’s different than diet is that when you’re taking calcium by food, you’re taking it in small amounts with other nutrients throughout the day. But if you take a big bolus of calcium all at once, pharmacological studies have shown there are transient elevations in the serum calcium level. . . . Calcium is one of the components needed for clotting, so it can trigger clotting, which can lead to heart attacks. Or that excess calcium can accumulate in soft tissues, like blood vessels.”

Independent From Traditional Risk Factors

For their paper published online October, 11, 2016, in the Journal of the American Heart Association, Michos et al studied 5,448 individuals (52% women) who were free of clinically diagnosed cardiovascular disease. Calcium intake was assessed at baseline using food frequency questionnaires and medication inventory, with subjects being divided into quintiles. CAC was also measured by computed tomography at baseline and, in 2,742 participants, approximately 10 years later.

Mean calcium intake per day across quintiles was 313.3 mg, 540.3 mg, 783.0 mg, 1,168.9 mg, and 2,157.4 mg. Women tended to get more calcium than men (mean 1,080.5 vs 907.9 mg daily), a difference driven by higher use of supplements.

In their analyses, researchers adjusted for a spate of traditional risk factors for atherosclerosis including age, sex, blood pressure, smoking, activity level, and caloric intake. Among the 1,567 individuals with no baseline CAC, and after adjusting for supplement use, the relative risk of developing CAC over 10 years was not significantly related to calcium intake for the lowest 4 quintiles. However, those who got the highest amount of calcium were 27% less likely to show signs of atherosclerotic disease (RR 0.73; 95% CI 0.57-0.93) and those taking supplements had a 22% higher risk of incident CAC at 10 years (RR 1.22; 95% CI 1.07-1.39).

For those with CAC at baseline, calcium intake was not associated with an increase in CAC progression.

Greens, Dairy, and Grains

In an email to TCTMD, Alice Lichtenstein, DSc (Tufts University, Boston, MA), put the levels of calcium consumption in perspective, pointing out that the recommended daily allowance for calcium is 1,000 to 1,200 mg per day, with an upper limit of 2,000 to 2,500 mg.

An important consideration, she said, is that the individuals who met the recommended level were, “in general, healthier and appeared to engage in more favorable lifestyle behaviors. The data were statistically corrected for this issue but there is always the concern about residual confounding.”

The current findings gel with the usual advice, which is that people should “get their nutrients from foods rather than supplements,” Lichtenstein noted. “Exceeding recommended intakes, as more frequently happens when supplements are used, was associated with an adverse health outcome likely because [the supplements] brought people up above that which is recommended. Hence, the study findings are important and consistent with prior work.”

Data in the literature are mixed, Michos said, but more studies than not have suggested excess CV risk with calcium supplements. Given that findings are also inconsistent over whether the supplements can aid bone health, physicians need to take care when advising their patients, she stressed. “With such weak data on fracture, there are [still] all these people taking [calcium] thinking they are doing something for their bones and they may be putting themselves at risk. We already know that calcium supplements increase the risk of kidney stones.”

Patients and their doctors should discuss whether supplements are necessary and at what dose. “There may be some subgroups that may benefit, such as people who have really low dietary calcium,” she acknowledged, adding that most individuals can obtain enough through leafy greens, low-fat dairy, and fortified grains.