No evidence to support antioxidant supplements to prevent mortality in healthy people or patients with various diseases

Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C

Published Online:

January 20, 2010

Previous research on animal and physiological models suggest that antioxidant supplements have beneficial effects that may prolong life. Some observational studies also suggest that antioxidant supplements may prolong life, whereas other observational studies demonstrate neutral or harmful effects. Randomised trials have largely been neutral. We need evidence from randomised trials to decide if antioxidant supplements should be used for prevention.

Abstract (click to read)

Background:

Animal and physiological research as well as observational studies suggest that antioxidant supplements may improve survival.

Objectives:

To assess the effect of antioxidant supplements on mortality in primary or secondary prevention randomised clinical trials.

Search strategy:

We searched The Cochrane Library (Issue 3, 2005), MEDLINE (1966 to October 2005), EMBASE (1985 to October 2005), and the Science Citation Index Expanded (1945 to October 2005). We scanned bibliographies of relevant publications and wrote to pharmaceutical companies for additional trials.

Selection criteria:

We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Included participants were either healthy (primary prevention trials) or had any disease (secondary prevention trials).

Data collection and analysis:

Three authors extracted data. Trials with adequate randomisation, blinding, and follow-up were classified as having a low risk of bias. Random-effects and fixed-effect meta-analyses were performed. Random-effects meta-regression analyses were performed to assess sources of intertrial heterogeneity.

Main results:

Sixty-seven randomised trials with 232,550 participants were included. Forty-seven trials including 180,938 participants had low risk of bias. Twenty-one trials included 164,439 healthy participants. Forty-six trials included 68111 participants with various diseases (gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified). 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 meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. 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), and 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). Low-bias risk trials on selenium found no significant effect on mortality (RR 0.90, 95% CI 0.80 to 1.01).

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.

This record should be cited as:

Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007176. DOI: 10.1002/14651858.CD007176

Assessed as up to date:

February 20, 2008

Find the research

Get full text at The Cochrane Library

Primary Review Group:

Hepato-Biliary Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are antioxidant supplements on mortality in primary and secondary prevention randomised clinical trials?

Bottom line:

Compared to placebo or no intervention, antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E and selenium) did not reduce mortality in trials involving healthy participants (primary prevention) or participants with various diseases (including gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological or unspecified disease). Indeed, vitamin A, beta-carotene, and vitamin E given singly or combined with other antioxidant supplements significantly increase mortality.

Caveat:

The review did not assess antioxidant supplements for treatment of specific diseases (tertiary prevention), antioxidant supplements for patients with demonstrated needs for antioxidants, or the effects of antioxidants contained in fruit and vegetables. These findings suggest that antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.

Context:

Oxidative stress may play a role in the pathogenesis of cancer and cardiovascular disease, the leading causes of death in middle- and high-income countries.¹ Several observational studies have shown a significant positive association between higher intake of fruits and vegetables and reduced risk of chronic disease.² Many people take antioxidant supplements in the belief that they will improve their health.³ 1. Halliwell B. Lancet 2000 ;344 :721-724. 2. Willcox JK et al. Critical Reviews in Food Science and Nutrition 2004 ;44 :275-295. 3. Nichter M et al. Culture, Medicine and Psychiatry 2006 ;30 :175-222.

Cochrane Systematic Review:

Bjelakovic G et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Reviews 2008, Issue 2. Art. No.: CD007176. DOI: 10.1002/14651858.CD007176. This review contains 67 trials involving 232,550 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

In the News

BBC News on study of vitamin supplements also cites Cochrane reviews on vitamin D and antioxidant supplementation

Reporting on new study findings that vitamin supplements can cause harm, the BBC News cites the Cochrane authors of reviews on vitamin D and antioxidant supplementation.

Ben Goldacre cites a Cochrane Review of antioxidant supplements in his Bad Science column

In a commentary on several studies of risk compensation behaviour for his Bad Science column in The Guardian, Ben Goldacre cites evidence from the 2008 Cochrane Review of antioxidant supplements.

Two Newsweek articles refer and link to Cochrane reviews

Two recent health articles in Newsweek refer and link to Cochrane evidence: Antioxidants Fall From Grace [read review] and Why Almost Everything You Hear About Medicine Is Wrong [read Statin review].

NY Times column on new vitamins Review

New York Times 'Vital Signs' column on the new vitamins review. Go to review

Guardian column

The Guardian's bad science column responds to criticism of recently updated Cochrane review on vitamins. Go to review

BBC article on vitamins Review

The BBC's first article on our vitamins review. Go to review Click here for more press coverage of this Review.

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

No evidence to support antioxidant supplements to prevent mortality in healthy people or patients with various diseases

More like this

Copyright © 2012 - The Cochrane Collaboration