Editorial

Calcium Supplements and Heart Attacks: a Follow-Up

In 2010, a meta-analysis of 15 randomized controlled trials found that participants who received calcium supplements as monotherapy (i.e., without other nutrients) had a 30% higher incidence of myocardial infarction, when compared with subjects who received a placebo.¹ When that study was published, I reviewed it in a Townsend Letter editorial and made the following points: First, the evidence was relatively weak, because it was derived from a secondary, post hoc analysis of studies (mainly osteoporosis studies) that were not designed to test the effect of calcium on heart disease risk. The increased incidence of heart attacks observed in the meta-analysis was only of borderline statistical significance (p = 0.035 to 0.038). Findings of borderline statistical significance from secondary analyses are more likely to be due to chance than are findings of borderline statistical significance from primary analyses. Second, if the reported adverse effect of calcium supplementation on the cardiovascular system is real, it might be due to calcium-induced magnesium depletion, and therefore might be preventable by coadministration of magnesium.

Recently, two other studies have been published that are relevant to the question of whether calcium causes heart disease. One of these studies suggests that giving vitamin D along with calcium might mitigate any potential deleterious effect of calcium monotherapy. The other study suggests that the reported increase in heart attacks among calcium supplement users is due at least in part to calcium-induced gastrointestinal side effects being incorrectly reported as myocardial infarctions.

The first new study was a meta-analysis of 24 randomized controlled trials in which vitamin D was given alone or with calcium. In studies in which vitamin D was given with calcium, there was a statistically significant 9% decrease in all-cause mortality compared with placebo. In trials in which vitamin D was given by itself, there was a nonsignificant 4% decrease in mortality compared with placebo.² While this meta-analysis did not address calcium supplementation by itself and did not report the incidence of heart attacks, the results support the concept that taking calcium in combination with vitamin D is not harmful, and is probably beneficial. Moreover, since the benefit of vitamin D plus calcium was greater than the benefit of vitamin D alone, the observed reduction in mortality may be due in part to the calcium.

The second new study was conducted because of earlier reports that patients hospitalized for symptoms consistent with acute myocardial infarction (MI) are frequently confused about the final diagnosis, particularly if they are admitted to the coronary care unit. For example, in both the Women’s Health Initiative and the Nurses’ Health Study, a 32% false-positive rate was found for self-reported MI. The new study reviewed 7 randomized controlled trials that examined adverse effects of calcium supplementation. In the pooled analysis, the incidence of gastrointestinal adverse events was 43% higher in the calcium group than in the placebo group (p < 0.001). Hospital discharge summaries indicated that the number of hospitalizations for acute abdominal pain was 82% higher in the calcium group than in the placebo group (4.0% vs. 2.2%). In a pooled analysis of two studies that compared the incidence of self-reported MI with that of clinically confirmed MI, the incidence of incorrectly classified self-reported MI was higher in the calcium group than in the placebo group (1.2% vs. 0.5%; p < 0.05). Although the incidence of confirmed MI was higher in the calcium group than in the placebo group (2.4% vs. 1.6%), the difference was not statistically significant (p = 0.15).³

The question of whether calcium monotherapy adversely affects the heart remains unresolved, but the issue is probably moot for practitioners trained in nutritional therapy, because we rarely prescribe calcium by itself. The available evidence, though circumstantial, suggests that calcium is safe when used in combination with magnesium and vitamin D. It has been clearly established that adequate calcium intake is important for achieving optimal peak bone mass and for preventing osteoporosis. Magnesium and vitamin D also play a role in promoting healthy bones, so for most patients there is no reason not to administer all three of these nutrients in combination.

Alan R. Gaby, MD

Notes

1. Bolland MJ et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010;341:c3691.

2. Rejnmark L et al. Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab. 2012;97:2670–2681.

3. Lewis JR et al. Adverse events from calcium supplementation: relationship to errors in myocardial infarction self-reporting in randomized controlled trials of calcium supplementation. J Bone Miner Res. 2012;27:719–722.