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#10 Antioxidant Vitamin Cure-Alls: Will Good Theories Ever Die?

Does daily supplementation of antioxidant vitamins (A, E, and C) decrease mortality in the general population?

The current evidence does not support the use of antioxidant supplementation, and patients should be dissuaded from using beta-carotene, vitamin E, and perhaps high-dose vitamin A, as they appear to increase mortality by about 1 in every 250 over ~5 years.  

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One Cochrane review1 of 78 Randomized Controlled Trials (RCTs) with 296,707 patients (~75% healthy participants, ~25% pre-existing condition):  
  • Focusing on high-quality RCTs: 
    • Antioxidants increased mortality with a Relative Risk (RR) of 1.04 (1.01-1.07), Number Needed to Harm (NNH)=238. 
    • Specifically: 
      • Beta-carotene (pro-vitamin A): RR 1.05 (1.01-1.09). 
      • Vitamin E: RR 1.03 (1.00-1.05). 
    • No statistically significant difference in mortality for: 
      • Vitamin A, all doses: RR 1.07 (0.97-1.18). 
        • High-dose vitamin A appears to increase mortality (p=0.002). 
        • High-dose not clearly defined, but appears to be >5000 IU. 
      • Vitamin C: RR 1.02 (0.98-1.07). 
      • Selenium: RR 0.97 (0.91-1.03). 
    • If baseline mortality risk were around 10% over 3.5 years, about one in every 100 to 250 people taking antioxidants would die because of the supplements. 
  • Other meta-analyses report similar results. Examples: 
    • Antioxidant vitamins do not reduce the incidence of cardiovascular disease or cancer when taken for primary prevention.2 
    • Beta-carotene: Statistically significant increased mortality (NNH=167-326).2-4 
    • Vitamin E: 
      • No difference in mortality in 101,343 healthy individuals: RR 1.01 (0.98-1.04).2 
      • High-dose (>400 IU): Statistically significant increased mortality (NNH=257).5,6
  • While theories and previous observational studies suggested potential benefit with antioxidant vitamins, this has been disproven by higher-level evidence. 
    • Theories of disease and treatment/prevention are common in medicine. We must guard against the superficial appeal of these theories and rely on evidence of benefit or harm to guide the care of our patients. 
updated aug 21 2016 by ricky

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

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

2. Fortmann SP, Burda BU, Senger C, et al. Ann Intern Med. 2013; 159:824-34.

3. Vivekananthan DP, Penn MS, Sapp SK, et al. Lancet. 2003; 361:2017-23.

4. Teo KK. ACP J Club. 2004; 140:45.

5. Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Ann Intern Med. 2005; 142:37-46.

6. Simon JA. ACP J Club. 2005; 143:1.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 21/08/2016

By: Ricky D. Turgeon BSc(Pharm) ACPR PharmD


Evidence Updated: New meta-analysis, moved Context references to Evidence; Bottom Line: No change.

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