CALCIUM SUPPLEMENTS MAY INCREASE CARDIOVASCULAR MORTALITY 

Too much of a good thing may be just that: too much. That is the conclusion of yet another study, this time a prospective, longitudinal, population-based cohort of Swedish women, looking at calcium intake and cardiovascular mortality.

In this study, high rates of calcium intake were associated with higher all-cause and cardiovascular death rates but not with deaths from stroke, Karl Michaëlsson, MD, PhD, professor in medical epidemiology and senior consultant in orthopedic surgery at Uppsala University in Sweden, and colleagues report in an article published online February 13 in BMJ.

The study is the latest in a series of contentious analyses linking calcium intake and cardiovascular events. Earlier this month, a National Institutes of Health–sponsored study suggested that a high intake of supplemental calcium increased the risk for cardiovascular disease (CVD) death in men, but not women.

However, a commentator notes that the study results suggest that supplements, rather than the intake level, are the problem.

The Swedish mammography cohort, established between 1987 and 1990, followed up 61,433 women born between 1914 and 1948 for a median of 19 years and used registry data to determine outcomes. During that period, there were 11,944 deaths from all causes, of which 3862 were from CVD, 1932 from ischemic heart disease, and 1100 from stroke.

Dietary assessments from food frequency questionnaires at baseline and in 1997 were available for 38,984 women, from which the researchers estimated intakes of dietary and supplemental calcium.

The highest intakes of calcium (>1400 mg/day) were associated with higher all-cause risk for death (after adjustment for age, total energy, vitamin D, and calcium supplement intake, as well as other dietary, physical, and demographic factors) as compared with intakes of 600 to 1000 mg/day (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.17 - 1.67).

Disease-specific mortality risks were elevated for CVD (HR, 1.49; 95% CI, 1.09 - 2.02) and for ischemic heart disease (HR, 2.14; 95% CI, 1.48 - 3.09) at daily calcium intakes above 1400 mg. At calcium intakes less than 600 mg/day, these same mortality risks were also elevated. None of these patterns was apparent for mortality from stroke.

In an email exchange with Medscape Medical News, Dr. Michaëlsson said the association of calcium intake and all-cause and cardiovascular mortality "was especially strong if a high dietary intake of calcium was combined with calcium supplements."

Women with the highest intake of calcium (>1400 mg/day) and who used supplement tablets had an all-cause risk for death 2.5 times higher than women who had similar total intakes but were not taking a supplement.

The authors explain that serum calcium levels "are under tight homeostatic control" and do not normally correlate with the amount of calcium intake. However, low or very high intakes override this control, "causing changes in blood levels of calcium or calciotropic hormones."

Complex Study Results; Weak Findings?

Dr. Michaëlsson also noted that some previous studies have shown a similar relationship between calcium supplements and a higher risk for CVD but were not powered to look at mortality and did not assess the amount of dietary intake of calcium.

He advised that one should not make recommendations on the basis of a single study, but emerging evidence suggests caution about high calcium intake. He also noted that a meta-analysis of randomized trials has shown that calcium supplementation actually increased the rate of hip fracture. "My present recommendation is to avoid calcium supplement use if you have a normal varied diet," he said.

Commenting to Medscape Medical News by email, John Cleland, MD PhD, professor of cardiology at Hull York Medical School in Kingston-upon-Hull, United Kingdom, called the study results "extremely complex...with rather weak findings." He pointed out that in the study there were few patients or events in the group with high calcium intake (n = 1241; 2%), and the events were confined to those women taking supplements (total events, n = 23, of which 16 occurred among women taking any form of calcium supplement).

Women with calcium intakes greater than 1400 mg/day who were taking calcium tablets had an adjusted all-cause mortality rate of 2.57 (95% CI, 1.19 - 5.55) compared with 1.17 (95% CI, 0.97 - 1.41) among women who had similar daily intakes but were not taking supplements. "So, it's not the diet but the pills that are the problem," Dr. Cleland concluded, which is essentially in agreement with what Dr. Michaëlsson said.

Dr. Cleland raised the issues of what else may have been in the calcium pills and why the women were taking them; for example, if they had chronic kidney disease or osteoporosis. He said the article did not provide such information but just referred to a previous paper.

He also pointed out that calcium tablets "have not been shown to reduce fracture rates or improve any other patient outcome that I know of." He recommended that people stop taking calcium supplements "until efficacy/safety is shown," and that this advice "should definitely include those taking them for osteoporosis and should perhaps include those taking them for [chronic kidney disease]." His recommendation? "Having a healthy balanced diet and avoiding water filters that reduce calcium in drinking water is probably best."

This study was supported by the Swedish Research Council. The authors and Dr. Cleland have disclosed no relevant financial relationships.