Cochrane Review - Antioxidant Supplements

Cochrane Review - Antioxidant Supplements for Prevention of Mortality in Healthy Participants and Patients with Various Diseases.
Cochrane Library March 2008
www.cochrane.org/reviews/en/ab007176.html

This detailed review looked at the effect of antioxidant supplements on the mortality of those people who partook in primary or secondary prevention randomised clinical trials.  Forty-seven low bias risk involving 180,938 people were assessed.
All primary and secondary prevention randomised clinical trials that satisfied certain criteria for accuracy and used supplements of beta-carotene, vitamin A, vitamin C, vitamin E and selenium were included in the analysis. Some twenty other trials were excluded from the analysis because they were not considered to be of good enough quality.
 
Overall, the antioxidant supplements had no significant effect on mortality in a random-effects meta-analysis (relative risk [RR] 1.02, 95% confidence interval [CI] 0.99 to 1.06), but significantly increased mortality in a fixed-effect model (RR 1.04, 95% CI 1.02 to 1.06). 

In the trials with a low risk of bias, the antioxidant supplements significantly increased mortality (RR 1.05, 95% CI 1.02 to 1.08).  When the different antioxidants were assessed separately, analyses including trials with a low risk of bias and excluding selenium trials found significantly increased mortality by

• vitamin A (RR 1.16, 95% CI 1.10 to 1.24)
• beta-carotene (RR 1.07, 95% CI 1.02 to 1.11)
• vitamin E (RR 1.04, 95%CI 1.01 to 1.07)
  but
• no significant detrimental effect of vitamin C (RR 1.06, 95% CI 0.94 to 1.20)

The low-bias risk trials on selenium found

• no significant effect on mortality (RR 0.91, 95% CI 0.76 to 1.09).

Authors’conclusions

“We found no evidence to support antioxidant supplements for primary or secondary prevention.  Vitamin A, beta-carotene and vitamin E may increase mortality.  Future randomised trials could evaluate the potential effects of vitamin C and selenium for primary and secondary prevention.  Such trials should be closely monitored for potential harmful effects.  Antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.”

There is now accumulating evidence that vitamin A and beta-carotene may be particularly harmful for some people and the risk factors for harm are slowly being identified [Are Your Supplements Safe for You?]