Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10‐Year Follow‐up of the Multi‐Ethnic Study of Atherosclerosis (MESA)



Recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, we assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC).

Methods and Results

We studied 5448 adults free of clinically diagnosed CVD (52% female; aged 45–84 years) from the Multi‐Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles. Baseline CAC was measured by computed tomography, and CAC measurements were repeated in 2742 participants ≈10 years later. At baseline, mean calcium intakes across quintiles were 313.3, 540.3, 783.0, 1168.9, and 2157.4 mg/day. Women had higher calcium intakes than men. After adjustment for potential confounders, among 1567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake, were 1 (reference), 0.95 (0.79–1.14), 1.02 (0.85–1.23), 0.86 (0.69–1.05), and 0.73 (0.57–0.93). After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR=1.22 [1.07–1.39]). No relation was found between baseline calcium intake and 10‐year changes in log‐transformed CAC among those participants with baseline CAC >0.


High total calcium intake was associated with a decreased risk of incident atherosclerosis over long‐term follow‐up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC.

Excessive dietary calcium intake, particularly from overconsumption of calcium supplements taken to prevent or treat osteoporosis, may have unintended health consequences. The well‐known “milk”‐alkali syndrome1 has been increasing in incidence attributed to the widespread use of over‐the‐counter calcium supplements.2 Supplements contribute to calcium loading (ie, excessive calcium amounts in a single dose or bolus), which leads to an increase in urinary calcium excretion in adults with normal renal function, with or without hypercalcemia, and possibly to soft tissue or ectopic calcification.3 Gallagher et al recently found that 9% of women taking calcium supplements had evidence of hypercalcemia and 31% had hypercalcuria.4

A direct relationship between total calcium intake (diet plus supplements) and cardiovascular disease (CVD), however, has not been established, and this issue remains controversial.5, 6, 7, 8, 9, 10, 11, 12, 13 Recent evidence derived from randomized, controlled trials, including the Women’s Health Initiative, have raised a concern for an association between calcium supplement use and increased risk for CVD events.12, 13, 14 Among calcium supplement users, a high intake of calcium greater than 1400 mg/day has been reported to be associated with higher death rates from all causes, including from CVD.15

The purported CVD risk associated with total calcium intake may depend on the source of calcium intake.3 Intake of calcium from food sources has not been shown to increase CVD risk, whereas a signal for increased risk of myocardial infarction (MI) among calcium supplement users has been reported.7 In a similar fashion, dietary calcium intake may decrease risk of kidney stones, whereas calcium supplementation may increase risk.16 One explanation for this apparent paradox may be that large boluses of calcium intake through supplements may transiently elevate serum calcium concentrations,17, 18 which, in turn, may lead to vascular calcification and other adverse health effects.

One potential mechanism underlying the association between calcium intake and CVD risk may be through progression of atherosclerosis. The coronary artery calcium (CAC) score is a well‐established surrogate marker for burden of atherosclerosis and is prognostic for CVD risk.19 A few published reports have not demonstrated any association between calcium intake and a single evaluation of CAC.5, 20 However, little is known about the association of calcium intake with incident CAC or CAC progression, particularly in a population‐based cohort, and whether any associations with CAC differ by source of calcium intake (diet vs supplements).

In a multiethnic cohort of men and women, we hypothesized that no associations would be found between dietary calcium intake and CAC progression over 10 years of follow‐up. We also hypothesized that calcium supplement use would be associated with increased CAC progression attributed to unfavorable calcium balance.


Study Design

The Multi‐Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study investigating risk factors and progression of subclinical CVD, whose study design has previously been reported on.21 Briefly, the MESA baseline information was collected between 2000 and 2002 from 6814 individuals (52% women), aged ≥45 to 84, of 4 race/ethnicities (non‐Hispanic white, non‐Hispanic black, Hispanic, and Chinese), who were enrolled at 6 US field centers: Baltimore City and County, Maryland, Chicago, Illinois, Forsyth County, North Carolina, New York City, New York, Los Angeles County, California, and St. Paul, Minnesota. The study was conducted under the guidelines of the Declaration of Helsinki and approved by the institutional review boards at each site. Written informed consent of all participants was obtained.


Of the 6814 participants enrolled at baseline, participants were excluded from this analysis if complete information on dietary intake (n=283) was not available. Those with implausibly high calcium intakes (>5000 mg/day) were excluded (n=347). Participants with abnormal renal function, that is, estimated glomerular filtration rate (eGFR) values of 60 mL/min or less, were also excluded (n=622) given that impaired renal function could influence calcium metabolism. In addition, participants with daily energy intakes <600 or >6000 kcal/day were excluded (n=114). This left 5448 participants available for cross‐sectional analysis at the baseline exam (2000–2002).

There were 3305 subjects who participated in the MESA Air ancillary study and were eligible for a second computed tomography (CT) scan 10 years later. Of these participants, 2742 (83%) had complete covariate data and returned for a second follow‐up CAC scan at MESA Exam 5 (2010–2012) enabling them to be included in longitudinal analysis. Of these, 1567 were free of CAC at baseline and included in the incident CAC analysis, and 1175 had a baseline CAC >0 and were included in the change in CAC score analysis.

A flow diagram of participant inclusion/exclusion of our substudy is shown in Figure. Additionally, Table 1 compares the baseline characteristics of the overall MESA cohort (n=6814), the MESA Air participants with CAC measured at Exam 1 and Exam 5 (n=3305), and the sample used for longitudinal analyses in this article (n=2742).


Sources: John J.B. Anderson, Bridget Kruszka, Joseph A.C. Delaney, Ka He, Gregory L. Burke, Alvaro Alonso, Diane E. Bild, Matthew Budoff, and Erin D. Michos


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