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Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.
Cochrane Database Syst Rev 2008; (2):CD007176CD

Abstract

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 0.91, 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.

Authors+Show Affiliations

Copenhagen University Hospital, Rigshospitalet, Department 3344,Copenhagen Trial Unit, Centre for Clinical Intervention Research, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. goranb@junis.ni.ac.yuNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

18425980

Citation

Bjelakovic, G, et al. "Antioxidant Supplements for Prevention of Mortality in Healthy Participants and Patients With Various Diseases." The Cochrane Database of Systematic Reviews, 2008, p. CD007176.
Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2008.
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2008). Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. The Cochrane Database of Systematic Reviews, (2), p. CD007176. doi:10.1002/14651858.CD007176.
Bjelakovic G, et al. Antioxidant Supplements for Prevention of Mortality in Healthy Participants and Patients With Various Diseases. Cochrane Database Syst Rev. 2008 Apr 16;(2)CD007176. PubMed PMID: 18425980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. AU - Bjelakovic,G, AU - Nikolova,D, AU - Gluud,L L, AU - Simonetti,R G, AU - Gluud,C, Y1 - 2008/04/16/ PY - 2008/4/22/pubmed PY - 2008/6/14/medline PY - 2008/4/22/entrez SP - CD007176 EP - CD007176 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 2 N2 - 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 0.91, 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/18425980/Antioxidant_supplements_for_prevention_of_mortality_in_healthy_participants_and_patients_with_various_diseases_ L2 - https://doi.org/10.1002/14651858.CD007176 DB - PRIME DP - Unbound Medicine ER -