Tools for Practice

#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.  

CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

Join Now

Already a CFPCLearn Member? Log in

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

Latest Tools for Practice

#348 How to Slow the Flow III: Tranexamic acid for heavy menstrual bleeding (Free)

In premenopausal heavy menstrual bleeding due to benign etiology, does tranexamic acid (TXA) improve patient outcomes?
Read 0.25 credits available

#347 Chlorthali-D’OH!: What is the best thiazide diuretic for hypertension?

Which thiazide diuretic is best at reducing cardiovascular events in hypertension?
Read 0.25 credits available

#346 Stress Urinary Incontinence: Pelvic floor exercises or pessary? (Free)

How effective are pelvic floor exercises or pessaries for stress urinary incontinence?
Read 0.25 credits available

This content is certified for MainPro+ Credits, log in to access


  • 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.