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LPI's Response to the EPIC-Heidelberg Study on Calcium Supplements and Cardiovascular Disease

News outlets are abuzz about a recently published prospective study that reported an association between calcium supplement use and the risk of myocardial infarction (MI) (also known as a heart attack). As is often the case when confronted with alarming headlines in the media, a closer look at the experimental details of the research study presents a different picture.

The European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg) evaluated the association between dietary and supplemental calcium intake with risk of subsequent cardiovascular events in a group of adults living in Heidelberg, Germany.

Calcium intake was assessed in 23,980 men and women (aged 35-64 at baseline) from self-administered questionnaires. Self-reported calcium use was then related to the incidence of MI, stroke, and death due to cardiovascular disease (CVD) that occurred over the next 11 years of follow-up.

The authors reported that users of mixed calcium supplements had an 86% increased risk of having an MI (Hazard Ratio (HR) = 1.86) that was also statistically significant in those who used single-ingredient calcium supplements (HR = 2.39). Notably, these risk estimates are based on very small numbers of cases: after 11 years of follow-up, 20 out of 851 (2.4%) mixed calcium supplement users had an MI compared to 256 out of 15,959 (1.6%) non-supplement users. For users of single-ingredient calcium supplements, seven out of 256 (2.7%) individuals suffered an MI. No statistically significant association was found between calcium supplementation and risk of stroke or death due to CVD.

This study provides justification to conduct larger studies addressing this topic, but it does not provide conclusive evidence that calcium supplements increase the risk of MI. There are a number of additional study limitations that warrant mention:

  • Calcium supplement use was assessed by asking participants if they had regularly taken vitamin/mineral supplements in the past four weeks. This method is subject to measurement error and recall bias, and intake habits may change over 11 years. Additionally, no data on calcium dose were collected.
  • The association between calcium supplement use and MI is no longer significant when the effect of cumulative supplementation is considered. In other words, the association weakens as the assessment of calcium supplementation becomes more accurate.
  • Only 3.6% of the cohort reported use of calcium supplements. This prevalence is lower than reported supplement use in other German populations (e.g., 8% and 27% in elderly men and women, respectively). This underreporting may lead to misclassification of study participants and influence the accuracy of the results.
  • Baseline characteristics differed between supplement users and non-users. For instance, calcium supplement users took more non-steroidal anti-inflammatory drugs (NSAIDS) and other medications, had a longer duration of smoking history, had a lower body mass index (BMI), and were mostly women.
  • Inconsistencies throughout the publication (e.g., information included in the Methods section vs. data presented in table form, ambiguity of what confounders were included in the statistical model) make the data difficult to evaluate.

Therefore, this study suffers from serious limitations, including flawed study design, small number of supplement users, lack of quantitative information about calcium supplement intake, and lack of dose response. Given the accumulated evidence from many other studies in the scientific literature, we do not think that the results of this single study compel special concern about the use of calcium supplements, which have known benefits for bone health. It remains to be further investigated whether calcium supplements are not indicated in individuals with preexisting risk factors for CVD. In the meantime, if you are not getting the recommended 1,0001,200 mg/day of calcium from your diet, LPI recommends taking an extra calcium supplement (combined with magnesium) with a meal to make up the difference.