Calcium is the most abundant mineral in the body, mainly found in the bones, teeth, blood, and muscles. It is primarily sourced from daily dietary intake. Calcium supplementation is common in individuals with osteopenia, osteoporosis, and those at risk of deficiency, such as post-menopausal females and lactose-intolerant individuals.[
1] However, since the 1960s, associations have been identified linking calcium supplementation to cardiovascular events.[
1]
Studies have yielded mixed results, where factors, such as the route of intake and dosage, are correlated with cardiovascular risk.[
2] In a prospective cohort of 132,823 participants followed for 17.5 years, males taking a calcium supplement ≥1,000 mg had higher overall mortality (relative risk [RR], 1.17; 95% confidence interval [CI], 1.03–1.33). In females, an inverse dose-dependent relationship was observed, with lower risks at doses of 0.1 to <500, 500 to <1,000, and ≥1,000 mg/day (RR, 0.90; 95% CI, 0.87–0.94; RR, 0.84; 95% CI, 0.80–0.88, respectively).[
3] Another cohort study with 388,229 participants followed for 12 years reported higher cardiovascular mortality in males taking >1,000 mg/day (RR, 1.20; 95% CI, 1.05–1.36), but no increased risk in females (RR, 1.06; 95% CI, 0.96–1.18).[
4]
In contrast, Lewis et al.[
4] evaluated 1,460 females taking a calcium supplement at a dose of 1,200 mg/day for five years and did not identify an increase in the risk of atherosclerotic vascular disease. The daily dose limit for females aged 51 to 70 years and older people >70 years has been extended to 1,200 mg, due to the duration of the postmenopausal period and osteopenia/osteoporosis.[
1] Although the literature reports conflicting results, there is considerable evidence of an increase in cardiovascular risk with the use of high doses of calcium supplementation, particularly when the dose exceeds 1,200 mg/day. Furthermore, there is consensus among studies that dietary calcium is devoid of risks to cardiovascular health and should be encouraged.[
1–
5]
Moreover, vitamin D supplementation can increase intestinal absorption and renal calcium generating greater efficiency in the utilization of this element. Therefore, it is concluded that supplementary calcium should only be prescribed for patients whose dietary intake does not reach therapeutic targets, provided that the sum of dietary intake and supplementary intake does not exceed the safe daily targets.[
4]
The studies cited here have methodological limitations that should be considered. Most of these are observational studies, which imply associations but not causality. For example, in the study by Zarzour et al. [
3], confounding factors, such as diet and comorbidities were not fully controlled. The variability in the results between males and females also raises concerns about the generalizability of the findings, particularly considering the biological and behavioral differences between the sexes. Additionally, the study by Lewis et al.[
4], which found no increased cardiovascular risk with calcium supplementation, was limited by the homogeneous sample and short follow-up period. The lack of control over factors, such as medical history and diet, weakens the robustness of the conclusions. Therefore, to achieve a more precise analysis of the relationship between calcium supplementation and cardiovascular risk, randomized studies with more control over confounding variables and greater sample diversity are required.
It is important to emphasize that osteoporosis and cardiovascular diseases are highly prevalent in aging populations. Although cardiovascular events significantly contribute to mortality, severe osteoporotic fractures, such as those of the femur or spine, pose life-threatening risks. When considering calcium supplementation, physicians must carefully balance the risks of cardiovascular events and osteoporotic fractures.
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Funding
The authors received no financial support for this article.
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Ethics approval and consent to participate
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Conflict of interest
No potential conflict of interest relevant to this article was reported.
REFERENCES
- 1. Reid IR, Bolland MJ, Avenell A, et al. Cardiovascular effects of calcium supplementation. Osteoporos Int 2011;22:1649-58. https://doi.org/10.1007/s00198-011-1599-9.
- 2. Kittithaworn A, Toro-Tobon D, Sfeir JG. Cardiovascular benefits and risks associated with calcium, vitamin D, and antiresorptive therapy in the management of skeletal fragility. Womens Health (Lond) 2023;19:17455057231170059. https://doi.org/10.1177/17455057231170059.
- 3. Zarzour F, Didi A, Almohaya M, et al. Cardiovascular impact of calcium and vitamin D supplements: A narrative review. Endocrinol Metab (Seoul) 2023;38:56-68. https://doi.org/10.3803/EnM.2022.1644.
- 4. Lewis JR, Calver J, Zhu K, et al. Calcium supplementation and the risks of atherosclerotic vascular disease in older women: Results of a 5-year RCT and a 4.5-year follow-up. J Bone Miner Res 2011;26:35-41. https://doi.org/10.1002/jbmr.176.
- 5. Bolland MJ, Grey A, Avenell A, et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: Reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ 2011;342:d2040. https://doi.org/10.1136/bmj.d2040.
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