Does calcium intake affect cardiovascular risk?
BackgroundTwo papers have recently been published [1,2], discussing the effect of calcium intake on cardiovascular risk. These papers describe the results of the MESA study (multi-ethnic study of atherosclerosis) with 10-years of follow-up and a thorough meta-analysis on calcium intake and CV risk. However, both studies show contradictive results.
Calcium is essential for maintaining bone health and moreover, a small proportion of calcium regulates vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signalling and hormonal secretion. If required, for example when preventing or treating osteoporosis, it is suggested to enhance calcium intake by increasing calcium-rich food intake or by taking calcium supplements.
However, the cardiovascular effect of enhanced dietary intake or calcium supplements is controversial. Inconsistent results of multiple studies done over the past years show either increased risk for myocardial infarction or stroke or no effect on coronary heart disease events or mortality. It has been suggested that the effect on cardiovascular risk may depend on the source of calcium intake; dietary or supplements. For example, a different effect may be evoked by supplements as a result of the transient sudden enhancement through the bolus intake, whereas dietary calcium may have a protective effect, which may also be an indirect effect of its presence in ‘healthy foods’.
To extend on some of these uncertainties, Anderson and co-workers investigated the effect of both dietary calcium intake and calcium supplements on coronary artery calcium (CAC) progression, over 10-years of follow-up during the MESA trial. Furthermore, Chung and co-workers performed a systemic review and meta-analysis on this same issue.
In this study, 5448 suitable, multi-ethnic participants without past history of clinical cardiovascular disease were enrolled. For these participants, the dietary intake over the previous year was assessed by a modified, validated 120-item quantitative food frequency questionnaire and the calcium supplement intake was assessed by recording all medications over the past 2 weeks and adding this to the dietary intake. Then, the total daily calcium intake was categorized into quintiles.
The results showed that the use of calcium supplements was greater in the higher quintiles. Analysis using a fully adjusted model correcting for other risk factors for CVD, including the use of calcium supplements, demonstrated that, among 1567 participants with a baseline CAC of zero, the highest calcium intake (>1453 mg) compared to the lowest intake (<434 mg) was associated with a 27% decreased risk for incident CAC after 10 years (RR=0.73, 95% CI: 0.57-0.93, P=0.01). This suggests a protective effect of total calcium intake in the highest consumers of overall calcium, which as described above, largely includes participants taking calcium supplements. However, similar analysis but now calculating the risk of incident CAC based on calcium supplement intake, revealed that the risk of developing incident CAC was 22% higher in those who used supplements than those who did not (RR=1.22, 95% CI: 1.07-1.39). Therefore, participants were stratified for supplement user or non-user. This showed that the highest risk for incident CAC was found among supplement users with the lowest intake of total calcium (quintile 1, RR=1.41, 95% CI 1.02-1.97, P=0.038 when compared to non-supplement users quintile 1), whereas the lowest risk of incident CAC was noted among non-users with the highest intake of total calcium (quintile 5, RR=0.74, 95% CI 0.51-1.07, P=0.11 when compared to non-supplement users quintile 1). Furthermore, among those with prevalent CAC at baseline, calcium intake was not associated with an increase in CAC progression over 10 years.
Systematic review and meta-analysis
Fifteen studies reported mortality risks based on total, dietary or supplementary calcium intake. Total calcium levels ranged from 400-2400 mg/day. Overall, no consistent dose-response relationships were seen between calcium intake levels and risks for CVD, cardiac or ischemic heart disease mortality. Furthermore, dose-response metaregression did not detect statistically significant linear or nonlinear relationships between levels of dietary or total calcium intake and risk for cardiovascular death.
Twenty cohort studies assessed the association between calcium intake and stroke risk. Total calcium levels ranged from 400-2400 mg/day. The dose-response relationships between calcium intake levels and risks for total stroke or stroke mortality were highly inconsistent, with some studies showing opposite trends for total stroke risk. Dose-response metaregression analyses did not find statistically significant linear or nonlinear relationships between levels of dietary or total calcium intake and the risk for total stroke or stroke mortality.
This means the trials did not find statistically significant differences in risk for CVD events or mortality between groups receiving calcium supplements or calcium plus vitamin D supplements and those receiving placebo. Although some studies did find increased risk with higher calcium intake, risk estimates in most of those studies were small (~10% RR) and not considered clinically important, even if they were statistically significant.
ConclusionInconsistency between data remains. The study by Anderson suggested a protective effect of high dietary calcium intake and an increased cardiovascular risk with calcium supplements. However, a systemic review and meta-analysis did not confirm these results and did not find any effect of dietary calcium or supplements.
1. Anderson JJB, Kruszka B, Delaney JAC et al, 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), J Am Heart Assoc. 2016 Oct 11;5(10)
2. Chung M, Tang AM, Fu Z, et al, Calcium intake and cardiovascular disease risk, an updated systematic review and meta-analysis, Ann Intern Med 2016; doi: 10.7326/M16-1165