Deaths doubled with high calcium intake plus supplements

Daniel M Keller

February 18, 2013

Uppsala, Sweden - Too much of a good thing may be just that: too much. That's the conclusion of yet another study—this time a prospective, longitudinal, population-based cohort of Swedish women—looking at calcium intake and cardiovascular mortality [1].

In the study, high rates of calcium intake were associated with higher all-cause and cardiovascular death rates, but not deaths from stroke, Dr Karl Micha ë lsson (Uppsala University, Sweden) and colleagues reported in an article published online February 13, 2013 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 of cardiovascular disease death in men but not women.

Higher CV deaths and ischemic heart disease, but not stroke

The Swedish mammography cohort, established in 1987-1990, followed 61 433 women born between 1914 and 1948 and used registry data to determine outcomes. During the median follow-up period of 19 years, there were 11 944 deaths from all causes, of which 3862 were from cardiovascular disease, 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 of death (after adjustment for age, total energy, vitamin-D and calcium-supplement intake, and other dietary, physical, and demographic factors) compared with intakes of 600-1000 mg/day (HR 1.40, 95% CI 1.17-1.67).

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

In an email, Michaëlsson said the association of calcium intake with 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) who used supplement tablets had a 2.5-times higher risk of all-cause death than women with similar total intakes not taking a supplement (HR 2.57, 95% CI 1.19-5.55).

The authors explained 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."

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

Supplements plus calcium-rich diet flagged

He advised that recommendations should not be made based on 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 by email, Dr John Cleland (Hull York Medical School, Kingston-upon-Hull, UK) 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 events were confined to those women taking supplements (total events n=23, of which 16 occurred among women taking any form of calcium supplement).

So, it's not the diet but the pills that are the problem .

Women with calcium intakes >1400 mg/day who were also 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 with similar daily intakes who were not taking supplements. "So, it's not the diet but the pills that are the problem," Cleland concluded, which is essentially in agreement with what Michaëlsson said.

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 (CKD) or osteoporosis. He said the paper did not provide such information but only referred to a previous paper.

In summary, he said 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 this advice "should definitely include those taking them for osteoporosis and should perhaps include those taking them for CKD." His recommendation? "Having a healthy, balanced diet and avoiding water filters that reduce calcium in drinking water is probably best."

The study received no commercial funding. Micha ë lsson reported no financial conflicts of interest. Cleland had no disclosures.


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