Calcium Levels and CV Risk: New Study Finds No Link

–But most agree dietary calcium is preferable to supplements

A new review concludes that a high level of calcium intake, whether from food or supplements, is not linked to increased cardiovascular risk, as long as the total calcium intake remains below the tolerable upper level of intake (2,000-2,500 mg/day).

The systematic review, published in Annals of Internal Medicine, forms the basis for an updated guideline recommendation from the National Osteoporosis Foundation and the American Society for Preventive Cardiology. The guideline concludes that there is moderate-quality evidence that calcium “from food or supplements has no relationship (beneficial or harmful) with the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality.”

Calcium in the diet, however, is considered to be preferable to calcium obtained from supplements, but the guideline states that “supplemental calcium can be safely used to correct any shortfalls in intake.” Further, “discontinuation of supplemental calcium for safety reasons is not necessary and may be harmful to bone health when intake from food is suboptimal.”

Although some trials and observational studies have found an increased risk with higher calcium intake, these increases were small “and not considered clinically important, even if they were statistically significant.”

The systematic review included 27 observational studies and four randomized trials. To prevent osteoporosis the Institute of Medicine recommends people 19 to 50 years of age consume at least 1,000 mg/day of calcium. The calcium recommendation increases to 1,200 mg/day for women over 50 and men older than 70.

In an accompanying editorial, Karen Margolis, MD, MPH, of HealthPartners Institute, Minneapolis, and JoAnn Manson, MD, DrPH, of Brigham and Women’s Hospital in Boston, agree that “the preponderance of evidence does not support cardiovascular adverse effects, dietary sources of calcium are preferable to supplements for other reasons.” But they note that calcium supplement appear to increase the risk of kidney stones while dietary calcium reduces the risk. Supplements, then, “may be used to make up but not exceed the gap between dietary intake and the recommended intake level.”

The Debate Over Supplements Is Not Over

The Annals review did not include a recently published analysis of participants in the MESA (Multi-Ethnic Study of Atherosclerosis) study. As I reported recently, that study also found no increase in risk based on total calcium intake, but it did find a troubling signal of harm from calcium supplements. I asked both the senior author of the MESA paper and a co-author of the Annals editorial for their responses to the new papers.

Responding to the new guideline, the senior author of the MESA study, Erin Michos, MD, MHS, of Johns Hopkins University, said she continues to be concerned about the use of supplements. Here is her lengthy response to the new guideline:

This meta-analysis by Chung et al, along with our recent MESA study, continues to show the lack of cardiovascular harm with dietary calcium intake, which should be reassuring to individuals who are following dietary calcium recommendations by eating high-calcium foods, that consuming calcium from diet alone does not appear to increase CVD risk.

However, there is a lack of evidence for a dose-response. In other words, there also was no evidence to support a “more calcium is better” attitude; or to push patients towards intakes beyond the recommended daily allowance.

So while dietary calcium continues to appear safe, I think the data for the safety of calcium supplementation and cardiovascular harm continues to remain inconclusive in my opinion. In this meta-analysis by Chung et al, they did not include studies that did not quantify the amount of calcium supplementation in the interventions or exposures. Thus, not all potentially relevant studies are included. For example, the observational study by Li et al from EPIC-Hiedelberg (Heart 2012) had shown that users of calcium supplements had an increased risk of myocardial infarction (HR 1.86; 95% CI 1.17-2.96), but this study showing harm of supplement use was not included in their pooled analysis in Figure 2 because it did not specify the dose of supplements (although the dietary calcium results from this paper were included). So again, all relevant studies might not have been included.

This review by Chung et al also predominantly focuses on their review of 27 observational studies. The pooled data shown in Figures 1-4 are from cohort studies only, not randomized clinical trials (RCTs), which are our best source of evidence. Although the RCTs are mentioned in the text of the review, the authors did not perform a meta-analysis of the clinical trials because they felt the trials were too heterogeneous. And again the RCTs of calcium supplement use (with or without vitamin D) that collected CVD outcomes were not designed to test for CVD outcomes (which were secondary outcomes).

The most recent meta-analysis of RCTs on calcium supplements and CVD outcomes, published by Lewis et al (JBMR 2015), showed overall null results for either harm or benefit. But this meta-analysis was largely driven by results from the largest calcium/vitamin D RCT to date, the Women’s Health Initiative (WHI) which included over 36,000 women. As acknowledged, WHI did not find a signal for cardiovascular risk with calcium supplements plus Vitamin D in the overall trial results. But the null finding in the overall WHI may be obscured because so many trial participants were taking personal supplements outside of the trial. In fact in WHI, 54% of women were taking personal calcium supplements outside of the trial! In a re-analysis of the WHI trial data, Bolland et al found that among women who were not taking personal supplements, there was an increased risk of myocardial infarction and stroke (BMJ 2011). But Bolland’s re-analysis has been somewhat controversial.

But let’s just say that in the best case scenario that calcium supplements do not increase CVD harm. Then the next real question we should be asking is whether they have any significant benefit to support their use, because they are not free of undesirable side effects such as bloating, constipation, and kidney stones. Their benefits on fracture reduction is also not very clear. Prior meta-analyses of RCTs on fracture outcomes have found that data for calcium supplements (with or without vitamin D) is only weak and inconsistent for fracture reduction. In fact the US Preventive Services Task Force concluded that there was insufficient evidence to either support (or recommend against) the use of calcium for fracture prevention. Patients at risk for osteoporosis and fracture may benefit from other medications like bisphosphonates for prevention instead. Of note, WHI, which again was the largest calcium RCT trial to date, actually failed to show a benefit for fracture reduction but did show a harm of kidney stones!!

So given the absence of strong benefit (and a signal for potential harm in some but not all studies), why are so many people taking these supplements when many well done trials have shown that calcium supplements and other types of supplements are often no better than placebo?

In their discussion, the authors (when discussing mechanisms for harm of CVD events with calcium supplements) state that “available data about calcification of vascular tissues associated with calcium supplementation are derived from persons with impaired renal function, not from the general population.” However our recently published JAHA paper now newly did find that calcium supplementation was independently associated with a 22% increased risk of incident coronary artery calcification in a general multi-ethnic community population – and this was after adjustment for renal function. Of note, the mechanisms for CVD risk may not solely be vascular calcification as evaluated in our study, but also from potentially triggering clotting with excess serum calcium, as calcium is a component of the coagulopathy cascade.

In summary, almost all generally agree that dietary calcium intake does not appear to cause harm. And in the absence of evidence suggesting more is better, I advise my patients to try to meet this IOM daily recommendation from healthy food sources such as leafy green vegetables, low-fat dairy, and so forth.

I asked JoAnn Manson if her position in her editorial would have been altered by the new paper from the MESA study. Here is her response:

The MESA study does not change my interpretation of the totality of evidence because it’s an observational study, not a randomized trial.

The randomized clinical trials, a more rigorous standard of evidence, do NOT support a link between calcium supplements and increased risk of heart disease or stroke. Moreover, we looked at coronary artery calcium (CAC) at the end of the WHI calcium/vitamin D randomized trial and found no difference in CAC between the active and placebo arms. This is consistent with the totality of evidence that calcium supplements do not increase cardiovascular risk.

Observational studies of calcium supplements can show associations but cannot prove causation. Women may take calcium supplements because they have osteoporosis or increased fracture risk; such risk factors are also linked to cardiovascular disease. Recent evidence suggests a strong link between bone health and heart health, which may be partially due to common risk factors (lack of exercise, smoking, suboptimal diet, chronic inflammatory conditions). Thus, a cause-and-effect relationship between calcium supplements and cardiovascular disease may be difficult to prove in an observational study – and the association may be due to shared risk factors.

Bottom line: the new comprehensive and up-to-date review of randomized clinical trials provides reassurance that calcium supplements do not adversely affect cardiovascular heath. However, in our editorial, we still recommend trying to meet daily requirements for calcium (1,000-1,200 mg/day) by dietary sources, whenever possible, and making up the gap with supplements. Dietary sources of calcium include milk, yogurt, cheese, canned oily fish with bones, tofu, calcium-fortified juice, and leafy greens (3 servings/day of these foods will come close to meeting requirements). It’s important to note that more is not necessarily better and moderate intake is best. We also emphasize that adequate vitamin D intake (recommended intake is 600 IU/day for adults up to age 70 and 800 IU/day for ages above 70) is essential.


  1. James Stein says:

    It’s really all old news. Calcium supplements have not been shown to definitively help anything in otherwise healthy people – even bone health. They might help BMD but “Osteopenia” is not a disease – its risk factor. Diets high in calcium tend to be healthy diets for heart disease, stroke, cancer, and osteoporosis. People who eat them tend to be healthy and have higher SES – unclear if calcium has anything or very much to do with it. Maybe its the exercise, dairy protein, fruits or veges.

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