Tools for Practice


#87 Daily multivitamins to reduce mortality, cardiovascular disease, and cancer


CLINICAL QUESTION
Does daily multivitamin supplementation reduce mortality, cardiovascular disease (CVD), and/or cancer?

BOTTOM LINE
Present evidence does not support the routine use of multivitamins to reduce mortality, cardiovascular disease, or cancer for people in developed countries.


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EVIDENCE
A meta-analysis and one Randomized Controlled Trial (RCT). Meta-analysis1 of 21 RCTs (including RCT below) with 91,074 patients (54% males) randomized to multivitamins or placebo for 3.5 years. Most are primary prevention studies from Europe or North America
  • No effect on overall mortality: Relative Risk (RR)=0.98 (0.94-1.02).
    • No effect on cancer mortality: RR=0.96 (0.88-1.04).
    • No effect on CVD mortality: RR=1.01 (0.93-1.09).
    • Multiple subgroup testing found no differences.
  • No evidence of publication bias or meaningful heterogeneity.
Physicians’ Health Study II: Heavily publicized RCT2,3 of 14,641 men (mean age 64.3) randomized to Centrum Silver™ or placebo, followed 11.2 years.
  • No effect on overall mortality: Hazard Ratio (HR)=0.94 (0.88-1.02).
    • No effect on cancer mortality: HR=0.88 (0.77-1.01).
    • No effect on CVD mortality: HR=0.95 (0.83-1.09).
    • No effect on CVD events: HR=1.01 (0.91-1.10).
    • Reduced cancer incidence: HR=0.92 (0.86-0.998).
      • These were adjusted (for unclear reasons).
      • Unadjusted is not significant RR=0.94 (0.87-1.003).
  • Multiple issues: Lots of exclusion including run-in to remove non-compliant patients, adjustments (without clear reason) always in favor of multivitamins.
Context:
  • Multiple cohort studies have found no mortality reduction with multivitamins.
  • Vitamin supplementation may help reduce overall mortality in undernourished populations (like rural China). 8
    • However, in this RCT8 of four different vitamin interventions, only one reduced mortality RR=0.91 (0.84-0.99).
  • Meta-analyses of different vitamin components on mortality:
    • B-Vitamins:9 No effect.
    • Anti-oxidants:10 Increase mortality RR=1.04 (1.01-1.07).
      • Increase with vitamin E, beta-carotene and high-dose vitamin A.
      • No effect from vitamin C and selenium.
    • Vitamin D:11 Decrease mortality RR=0.97 (0.94-1.00)
    • Increases and decreases are small [Numbers Needed to Harm (NNH) or treat around 200 over five years].
April 15, 2013

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Author(s):

  • G. Michael Allan MD CCFP
  • Mayank Singal MD CCFP

1. Macpherson H, Pipingas A, Pase MP. Am J Clin Nutr. 2012 Dec 19. [Epub ahead of print]

2. Gaziano JM, Sesso HD, Christen WG, et al. JAMA. 2012; 308:1871-80.

3. Sesso HD, Christen WG, Bubes V, et al. JAMA. 2012; 308:1751-60.

4. Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al. Arch Intern Med. 2009; 169:294-304.

5. Park SY, Murphy SP, Wilkens LR, et al. Am J Epidemiol. 2011; 173:906-14.

6. Li K, Kaaks R, Linseisen J, et al. Eur J Nutr. 2012; 51:407-13.

7. Watkins ML, Erickson JD, Thun MJ, et al. Am J Epidemiol. 2000; 152:149-62.

8. Blot WJ, Li JY, Taylor PR, et al. J Natl Cancer Inst. 1993; 85:1483-92.

9. Clarke R, Halsey J, Lewington S, et al. Arch Intern Med. 2010; 170:1622-31.

10. Bjelakovic G, Nikolova D, Gluud LL, et al. Cochrane Database Syst Rev. 2012; 3:CD007176.

11. Bjelakovic G, Gluud LL, Nikolova D, et al. Cochrane Database Syst Rev. 2011; 7:CD007470.

Authors do not have any conflicts of interest to declare.