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
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OBJECTIVES: To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women's Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk. DESIGN: Reanalysis of WHI CaD Study limited access dataset and incorporation in meta-analysis with eight other studies. Data source WHI CaD Study, a seven year, randomised, placebo controlled trial of calcium and vitamin D (1g calcium and 400 IU vitamin D daily) in 36,282 community dwelling postmenopausal women. Main outcome measures Incidence of four cardiovascular events and their combinations (myocardial infarction, coronary revascularisation, death from coronary heart disease, and stroke) assessed with patient-level data and trial-level data. RESULTS: In the WHI CaD Study there was an interaction between personal use of calcium supplements and allocated calcium and vitamin D for cardiovascular events. In the 16,718 women (46%) who were not taking personal calcium supplements at randomisation the hazard ratios for cardiovascular events with calcium and vitamin D ranged from 1.13 to 1.22 (P = 0.05 for clinical myocardial infarction or stroke, P = 0.04 for clinical myocardial infarction or revascularisation), whereas in the women taking personal calcium supplements cardiovascular risk did not alter with allocation to calcium and vitamin D. In meta-analyses of three placebo controlled trials, calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.21 (95% confidence interval 1.01 to 1.44), P = 0.04), stroke (1.20 (1.00 to 1.43), P = 0.05), and the composite of myocardial infarction or stroke (1.16 (1.02 to 1.32), P = 0.02). In meta-analyses of placebo controlled trials of calcium or calcium and vitamin D, complete trial-level data were available for 28,072 participants from eight trials of calcium supplements and the WHI CaD participants not taking personal calcium supplements. In total 1384 individuals had an incident myocardial infarction or stroke. Calcium or calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.24 (1.07 to 1.45), P = 0.004) and the composite of myocardial infarction or stroke (1.15 (1.03 to 1.27), P = 0.009). CONCLUSIONS: Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.
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Intakes of calcium in excess of 1200 to 1500 mg/day may increase the risk of developing kidney stones, cardiovascular disease, and stroke.
“Intakes in excess of 1200 to 1500 mg/day may increase the risk of developing kidney stones, cardiovascular disease, and stroke.”
From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [33]
The Patient-level data and Discussion sections report increased risks of myocardial infarction and stroke with calcium supplements, with or without vitamin D. They do not establish that total calcium intakes above 1200–1500 mg/day are the threshold for these risks, and our copy does not report an increased risk of kidney stones. Page numbers are not supplied for these passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCalcium supplements with or without vitamin D may significantly increase risk of MI in long-term randomized trials.
“However, calcium supplements with or without vitamin D may significantly increase risk of MI in long-term randomized trials.328, 329”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [328]
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- Authors
- Bolland, M. J., Grey, A., Avenell, A., Gamble, G. D., & Reid, I. R.
- Affiliations
- University of Auckland (NZ)
- University of Aberdeen (GB)
- Corresponding author
- Reid, I. R.
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2011-04-19
- Volume
- 342
- Issue
- apr19 1
- Pages
- d2040-d2040
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC3079822
- OpenAlex
- W2085977362
- Cited by
- 851
- References
- 45
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 17 · 2023: 32 · 2022: 25 · 2021: 40 · 2020: 46 · 2019: 60 · 2018: 44 · 2017: 58 · 2016: 59 · 2015: 87 · 2014: 83 · 2013: 114 · 2012: 94
- FWCI
- 13.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Funders
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Health Research Council of New Zealand
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
- Keywords
- calcium supplements, vitamin D supplementation, cardiovascular events, myocardial infarction, stroke, coronary revascularization, coronary heart disease mortality, postmenopausal women, Women's Health Initiative, meta-analysis reanalysis, cardiovascular risk reduction, calcium intake
- MeSH terms
- Aged, Calcium, Dietary, Cardiovascular Diseases, Coronary Disease, Drug Therapy, Combination, Female, Humans, Middle Aged, Myocardial Infarction, Myocardial Revascularization, Risk Factors, Vitamin D, Osteoporosis, Postmenopausal, Randomized Controlled Trials as Topic, Dietary Supplements, Stroke, Bone Density Conservation Agents
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