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Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis
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OBJECTIVE: To investigate whether calcium supplements increase the risk of cardiovascular events. DESIGN: Patient level and trial level meta-analyses. DATA SOURCES: Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010. STUDY SELECTION: Eligible studies were randomised, placebo controlled trials of calcium supplements (>or=500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self reports, hospital admissions, and death certificates. RESULTS: 15 trials were eligible for inclusion, five with patient level data (8151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11 921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02 to 1.67, P=0.035). Non-significant increases occurred in the incidence of stroke (1.20, 0.96 to 1.50, P=0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, P=0.057), and death (1.09, 0.96 to 1.23, P=0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01 to 1.59, P=0.038). CONCLUSIONS: Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.
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“Conjugated linoleic acid and calcium were proposed as potential mediators, but RCTs have demonstrated very small benefits or even adverse cardiometabolic effects of these factors.78–84”
From Components of a Cardioprotective Diet: New Insights (2011) · cites this paper as [84]
In the citing paper
“Evidence has accrued that most of these supplements have little CVD benefit, and that certain supplements including beta-carotene, calcium, and vitamin E may even be harmful.105-108, 111-113”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [113]
In the citing paper
“Evidence has accrued that most of these supplements have little CVD benefit, and that certain supplements including beta-carotene, calcium, and vitamin E may even be harmful.105-108, 111-113”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [113]
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Metadata
- Authors
- Bolland, M. J., Avenell, A., Baron, J. A., Grey, A., MacLennan, G. S., Gamble, G. D., & Reid, I. R.
- Affiliations
- University of Auckland (NZ)
- University of Aberdeen (GB)
- Dartmouth College (US)
- Corresponding author
- Reid, I. R.
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2010-07-29
- Volume
- 341
- Issue
- jul29 1
- Pages
- c3691-c3691
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC2912459
- OpenAlex
- W2143921117
- Cited by
- 1,099
- References
- 68
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 25 · 2023: 35 · 2022: 29 · 2021: 34 · 2020: 53 · 2019: 55 · 2018: 59 · 2017: 59 · 2016: 73 · 2015: 81 · 2014: 114 · 2013: 134 · 2012: 112
- FWCI
- 17.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion, cc-by-nc)
- Funders
- Scottish Government
- University of Auckland
- Fonterra Co-Operative Group
- Shire
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Health Research Council of New Zealand
- National Cancer Institute (R01CA098286)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- calcium supplements, myocardial infarction, cardiovascular events, stroke, sudden death, mortality, vitamin D, older adults, cardiovascular risk, individual patient data, risk of bias assessment, subgroup analysis
- MeSH terms
- Adult, Aged, Calcium, Dietary, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Myocardial Infarction, Osteoporosis, Risk Factors, Vitamin D, Randomized Controlled Trials as Topic, Dietary Supplements, Stroke, Bone Density Conservation Agents
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