Meta-analysiscited by the Tayebat archivefull text checked★ key study A-SUP-01 in-depth review
Calcium pills and heart attacks
Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis.
Overview
Bolland MJ et al.. BMJ 2010 · PMID 20671013 · DOI 10.1136/bmj.c3691
In trials, people taking calcium had 31% more heart attacks than with placebo (143 vs 111 events).
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
CV risk of calcium.
- How was the study done?
Meta-analysis of RCTs.
- How many people, animals or samples were studied?
~20,000.
- What was actually found?
More MIs.
- How large was the observed effect?
HR 1.31.
- What do the results mean in everyday life?
Possible small risk.
- What are the study's limitations?
Secondary outcomes.
- What does it say about Elawady's specific claim?
Partly supports.
- Do the results apply to Germany and Europe?
Applicable.
- What can explicitly not be concluded from this study?
Certainty of harm.
Scientific in-depth review
1. Full reference
- Authors
- Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR
- Journal
- BMJ
- Year
- 2010
- Identifier
- PMID 20671013 DOI 10.1136/bmj.c3691 · PMC2912459
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- full text
- Conflicts of interest and funding
Health Research Council of New Zealand and University of Auckland School of Medicine Foundation; Scottish Chief Scientist Office (one author); funders had no role. One author received research support from and consulted for Fonterra (dairy); several authors had calcium study drugs supplied by Wyeth, Mission Pharmacal, Shire and Nycomed; several authors were investigators of included trials.
2. Research question
Do calcium supplements increase cardiovascular events?
3. Study design and population
- Study design
- Meta-analysis – Systematic review with patient-level (5 trials) and trial-level (11 trials) meta-analyses of double-blind placebo-controlled RCTs of calcium supplements; cardiovascular outcomes were secondary/non-prespecified in the original trials
- Population
Mostly older women (patient-level median age 74.5 y, ~78% women, 97% white) in trials of calcium >=500 mg/day, >=100 participants, mean age >40, >1 year; calcium+vitamin D vs placebo trials excluded
- Country
Multinational (New Zealand, UK, USA, Australia, Europe)
- Period
Searches Nov 2007, updated March 2010 (Medline 1966-, Embase 1980-, CENTRAL, two trial registries)
- Sample size
15 eligible trials; patient-level data from 5 trials (8151 participants, median follow-up 3.6 y); trial-level data from 11 trials (11,921 participants, mean 4.0 y); no CV data for 4 trials
- Inclusion and exclusion criteria
Randomised double-blind placebo-controlled; calcium >=500 mg/day; excluded calcium+vitamin D vs placebo, dietary or complex supplements, and populations with major systemic disease
4. Methods and endpoints
- Exposure / intervention
Calcium supplements (without vitamin D)
- Comparator
Placebo
- Endpoints
Time to first MI, stroke, composite MI/stroke/sudden death (primary); all-cause death (secondary); events from self-report, hospital admissions and death certificates, adjudicated blind in some trials
- Statistical methods
Cox models stratified by study (patient level), covariate-adjusted sensitivity, prespecified subgroups (dietary calcium, age, sex, vitamin D, supplement type), Poisson GEE for recurrent events; random-effects pooling at trial level; Egger test
5. Actual results
- Results
Patient level: MI 143 (calcium) vs 111 (placebo), HR 1.31 (95% CI 1.02-1.67), P=0.035; stroke 167 vs 143, HR 1.20 (0.96-1.50); composite 293 vs 254, HR 1.18 (1.00-1.39); death 519 vs 487, HR 1.09 (0.96-1.23). Including recurrent events: MI RR 1.32 (1.02-1.71); composite 1.27 (1.07-1.51). Increased MI risk only with dietary calcium above median 805 mg/day (HR 1.85, 1.28-2.67) vs below (0.98, 0.69-1.38), P interaction 0.01. Trial level: MI 166 vs 130, RR 1.27 (1.01-1.59), P=0.038; no significant effect on stroke, composite or death; no heterogeneity or publication bias.
- Absolute risks
Number needed to harm over 5 years: 69 for MI, 100 for stroke, 61 for composite, 77 for death; per 1000 people treated for 5 years: about 14 additional MIs, 10 strokes and 13 deaths versus 26 fractures prevented (authors' estimate; stroke and death increases not statistically significant)
- Authors' conclusion
Calcium supplements without coadministered vitamin D are associated with an increased risk of MI; a reassessment of their role in osteoporosis management is warranted; results may not apply to calcium plus vitamin D.
6. Strengths
- Restricted to double-blind placebo-controlled RCTs
- Patient-level data with time-to-event analysis
- Consistent direction across trials; no heterogeneity
- Absolute harms weighed against fracture benefit
7. Weaknesses
- CV events were not primary endpoints and were collected non-uniformly; blinded adjudication in only some trials
- Borderline significance (P=0.035/0.038); stroke, composite and death not significant
- CV data missing for ~15% of participants (4 trials none)
- Excludes calcium+vitamin D vs placebo trials, so it cannot address the vitamin D part of the claim
- Protocol not registered; initial search by one investigator
- Investigator overlap with included trials and industry/dairy ties
8. Risk of bias
- Orienting tool
- AMSTAR 2
- Type of assessment
- structured assessment based on the full text by a single reviewer (no formal double review)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Single-reviewer structured AMSTAR 2 appraisal from full text; not formal (needs two independent reviewers). Main threat is non-standardised, secondary outcome ascertainment in the primary trials and post-hoc-like question.
| Domain | Judgement | Rationale |
|---|---|---|
| Item 1 PICO components | low | Clearly defined. |
| Item 2 Protocol a priori (critical) | some concerns | Protocol drafted with prespecified endpoints but not registered. |
| Item 3 Explanation of included designs | low | Placebo-controlled RCTs only. |
| Item 4 Comprehensive search (critical) | low | Three databases, registries, reference lists; no language limits. |
| Item 5 Duplicate selection | low | Two investigators reviewed potentially relevant studies. |
| Item 6 Duplicate extraction | some concerns | Data supplied by lead authors or extracted by one investigator; event adjudication duplicated. |
| Item 7 Excluded studies justified (critical) | some concerns | Flow chart counts; detailed list not in text. |
| Item 8 Description of included studies | low | Tables 1-2. |
| Item 9 RoB assessment (critical) | some concerns | Randomisation/concealment described narratively; no formal tool. |
| Item 10 Funding of included studies | high | Not reported per trial. |
| Item 11 Appropriate meta-analytic methods (critical) | low | Patient-level Cox and random-effects pooling appropriate. |
| Item 12 Impact of RoB on results | some concerns | Not formally assessed. |
| Item 13 RoB considered in interpretation (critical) | some concerns | Limitations discussed but conclusion framed firmly on borderline results. |
| Item 14 Heterogeneity | low | None detected. |
| Item 15 Publication bias (critical) | low | Funnel plots and Egger test. |
| Item 16 Conflicts of interest | low | Declared. |
Full-text review (25 October 2026): Added NNH and per-1000 absolute estimates, dietary-calcium interaction (HR 1.85 above vs 0.98 below median), recurrent-event analysis, population (median age 74.5, 78% women), non-standardised outcome ascertainment, funding/COI details; AMSTAR 2 item-level appraisal (overall unchanged).
9. Assessment of the statistical interpretation
Borderline-significant relative increase in MI (HR 1.31, lower CI 1.02) corresponding to roughly 14 extra MIs per 1000 treated over 5 years; effect confined to those with higher dietary calcium (subgroup finding). Fragile evidence; later analyses disagree.
10. Relevance to the specific claim
11. Independent contrary findings
Chung 2016 (I-SUP-06); Jenkins 2018 (A-SUP-29) found no effect of calcium.
12. Transferability to Germany and Europe
High: biology and trial populations comparable to European adults.
13. Overall methodological judgement
Influential but contested signal.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | inconsistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | essentially correct but incomplete |
14. Open questions
15. Linked fact checks
Use by the Tayebat archive
Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.
- What the archive says about the study
Calcium supplements without vitamin D raised MI risk by about 31% (HR 1.31, P=0.035).
- A. What was actually studied?
Calcium vs placebo and CV events.
- B. What did the authors find?
HR 1.31 (1.02-1.67) for MI, about 14 extra MIs per 1000 over 5 years; non-significant for stroke, composite and death; excess only in those with dietary calcium >805 mg/day.
- C. What conclusions do the authors themselves draw?
Associated with increased MI.
- D. What does the archive derive from it?
Presented as established harm, with WHI reanalysis said to 'confirm' that vitamin D does not erase it.
- E. Is this derivation scientifically justified?
Essentially correct numbers; incomplete - the analysis excluded calcium+vitamin D vs placebo trials and so cannot support the claim's statement about vitamin D; the absolute risk is small and the finding is contested by later reviews.
- Adequacy of the interpretation (by the archive)
- essentially correct but incomplete