Tools for Practice


#41 Does calcium supplementation increase the risk of MI?


CLINICAL QUESTION
Do calcium supplements increase risk of myocardial infarction (MI) and other cardiovascular disease (CVD)?

BOTTOM LINE
Evidence suggests that calcium supplementation might slightly increase the risk of MI and perhaps other CVD. Although there are limitations to the evidence and the increased CVD risk is likely <1%, the benefit-to-harm ratio might not favour calcium supplementation.


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EVIDENCE
Five recent systematic reviews had differing conclusions:
  • The first reviewed 15 Randomized Controlled Trials (RCTs) comparing calcium supplementation (≥500 mg/day) vs. placebo.1
    • Only one CVD outcome reached statistical significance:
      • Calcium increased MI risk, Relative Risk 1.27 (1.01-1.59).
      • Absolute risk was <1% and Number Needed to Harm (NNH) for one MI was 135 to 211 over four years.
  • Another examined 17 studies comparing vitamin D, calcium, or both vs. placebo:2
      • No comparisons reached statistical significance.
      • More than 99% of data for calcium and vitamin D vs. placebo were from the Women’s Health Initiative (WHI),3 and 54% of participants were taking extra calcium.4
  • A subgroup (similar to per-protocol) analysis of WHI data5 excluding those taking extra calcium found borderline significant increases in hazard ratios for MI [1.22 (1.00-1.50)] and MI or Stroke [1.16 (1.00-1.35)].
    • Updating the previous meta-analysis1 with this data, calcium (with or without vitamin D) significantly increased:5
      • MI NNH=240 over five years, p=0.004 and,
      • MI or stroke NNH=178 over five years, p=0.009.
  • A systematic review on a variety of calcium-related topics concluded there is no interaction between calcium and CVD risk.6
  • The newest systematic review of 11 RCTs (50,252 participants):7
    • Trends toward harm in odds ratios:
      • CVD [1.16 (0.97-1.68)],
      • MI [1.28 (0.97-1.68)],
      • Stroke [1.14 (0.90-1.46)].
  • Limitations: Over-interpretation of data (including calculating NNH for non-statistically significant outcomes),1 excluded relevant studies,2,7 small sample size,2 no analysis of different outcomes,2 large number of comparisons,5 sub-group analyses,5 possible conflict of interest,5 absolute numbers not reported.7
Context:
  • No RCT of calcium supplementation was designed to assess CVD outcomes.1,2
    • These meta-analyses1-3,7 represent post-hoc analyses of secondary or unplanned outcomes, possibly inadequately reported.8
  • Trials of vitamin D alone do not suggest CVD harm.9
  • Calcium (88% with vitamin D) reduces fracture (any type), Number Needed to Treat of 63 over 3.5 years.10
    • Calcium alone just failed to reach statistical significance.
    • Other studies suggest calcium alone does not reduce non-vertebral fracture and might increase hip fracture.11,12
February 7, 2011

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Author(s):

  • Christina Korownyk MD CCFP
  • G. Michael Allan MD CCFP

1. Bolland MJ, Avenell A, Baron JA, et al. BMJ. 2010; 341:c3691.

2. Wang L, Manson JE, Song Y, et al. Ann Intern Med. 2010; 152(5):315-23.

3. Hsia J, Heiss G, Ren H, et al. Circulation. 2007; 115(7):846-54.

4. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. N Engl J Med. 2006; 354(7):684-96.

5. Bolland MJ, Grey A, Avenell A, et al. BMJ. 2011; 342:d2040.

6. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.

7. Mao PJ, Zhang C, Tang L, et al. Int J Cardiol. 2013; 169:106-11.

8. Bolland MJ, Barber PA, Doughty RN, et al. BMJ. 2008; 336(7638):262-6.

9. Pittas AG, Chung M, Trikalinos T, et al. Ann Intern Med. 2010; 152(5):307-14.

10. Tang BM, Eslick GD, Nowson C, et al. Lancet. 2007; 370(9588):657-66.

11. Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, et al. Am J Clin Nutr. 2007; 86(6):1780-90.

12. Reid IR, Bolland MJ, Grey A. Osteoporos Int. 2008; 19(8):1119-23.

Authors do not have any conflicts of interest to declare.