The calcium scare—what would Austin Bradford Hill have thought?
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Detailed consideration of the suggested association between calcium supplementation and heart attacks has revealed weakness in the evidence which make the hypothesis highly implausible.
The aim of this study was to evaluate the strength of the evidence that calcium supplementation increases the risk of myocardial infarction.
This study used critical examination of a meta-analysis of the effects of calcium supplements on heart attacks in five prospective trials on 8,016 men and women, and consideration of related publications by the same author.
The meta-analysis was found to be subject to several limitations including non-adherence to the clinical protocol, multiple endpoint testing and failure to correctly adjust for endpoint ascertainment. The main risk factors for myocardial infarction were not available for 65% of the participants, and none of the trials had cardiovascular disease as its primary endpoint. There were more overweight participants, more subjects on thyroxine and more men on calcium than on placebo. In particular, over 65% of all the heart attacks were self-reported. When the evidence was considered in the light of Austin Bradford Hill's six main criteria for disease causation, it was found not to be biologically plausible or strong or to reflect a dose–response relationship or to be consistent or to reflect the relationship between the trends in calcium supplementation and heart attacks in the community or to have been confirmed by experiment. The addition of a more recent trial on 1,460 women over 5 years reduced the relative risk to 1.23 (P = 0.0695).
Present evidence that calcium supplementation increases heart attacks is too weak to justify a change in prescribing habits.
- Report of a joint FAO/WHO expert consultation. Human vitamin and mineral requirements. Rome 2002
- Abrahamsen B (2010) DIPART Group. Patient level pooled analysis of 68500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 340:b5463 CrossRef
- Daly RM, Ebeling P (2010) Is excess calcium harmful to health? Nutrients 2:505–522 CrossRef
- Bolland MJ, Barber PA, Doughty RN et al (2008) Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 336(7638):262–266 CrossRef
- Bolland MJ, Avenell A, Baron JA et al (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691 CrossRef
- Bischoff-Ferrari HA, Rees JR, Grae MV, Barry E, Gui J, Baron JA (2008) Effect of calcium supplementation on fracture risk: a double-blind randomized controlled trial. Am J Clin Nutr 87(6):1945–1951
- Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC et al (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (randomised evaluation of calcium or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 365:1621–1628 CrossRef
- Barr EL, Tonkin AM, Welborn TA, Shaw JE (2009) Validity of self-reported cardiovascular disease events in comparison to medical record adjudication and a statewide hospital morbidity database: the AusDiab study. Intern Med J 39(1):49–53 CrossRef
- Fruergaard P, Launbjerg J, Hesse B et al (1996) The diagnoses of patients admitted with acute chest pain but without myocardial infarction. Eur Heart J 17(7):1028–1034
- Hill AB (1965) The environment and disease: association or causation? Proc R Soc Med 58:295–300
- Le Fanu J (1999) The rise and fall of modern medicine. Abacus 58.
- Fleisch H, Neuman WF (1961) Mechanisms of calcification: role of collagen, polyphosphates, and phosphatase. Am J Physiol 200:1296–1300
- McDowell H, Brown WE, Sutter JR (1971) Solubility study of calcium hydrogen phosphate. Ion-pair formation. Inorg Chem 10:1638 CrossRef
- Wang TK, Bolland MJ, Pelt NC et al (2011) Relationships between vascular calcification, calcium metabolism, bone density, and fractures. J Bone Miner Res 25:2777–2785 CrossRef
- Almqvist EG, Bondeson AG, Bondeson L, Svensson J (2011) Increased markers of inflammation and endothelial dysfunction in patients with mild primary hyperparathyroidism. Scand J Clin Lab Invest 71:139–144
- Schuijf J, van der Wall EE, Bax JJ (2010) Lesions without calcium: lessons from CT angiography. Heart 95:1038–1040 CrossRef
- Reid IR, Bolland MJ, Avenell A, Grey A (2011) Cardiovascular effects of calcium supplementation. Osteoporos Int 22:1649–1658. doi:10.1007/s00198-011-1599-9 CrossRef
- Lewis JR, Calver J, Zhu K, Flicker L, Prince RL (2011) Calcium supplementation and the risks of atherosclerotic vascular disease in older women: result of a 5-year RCT and a 4.5-year follow-up. J Bone Miner Res 26:35–41 CrossRef
- Australian Institute of Health and Welfare (2011) A snapshot of osteoporosis in Australia 2011. Arthritis series no.15. Cat. no. PHE137. Canberra, Australia
- Australian Institute of Health and Welfare (2010) Australia's health 2010. Australia's health series no. 12. Cat. no. AUS 122. Canberra, Australia
- The calcium scare—what would Austin Bradford Hill have thought?
Volume 22, Issue 12 , pp 3073-3077
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Calcium supplements
- Cardiovascular disease
- Myocardial infarction
- Industry Sectors
- Author Affiliations
- 1. Endocrine and Metabolic Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia
- 2. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia
- 3. School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC, 3125, Australia
- 4. Cardiology Unit, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia
- 5. School of Mathematical Sciences, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia
- 6. Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia
- 7. School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia