Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis
- PMID: 17327526
- DOI: 10.1001/jama.297.8.842
Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis
Erratum in
- JAMA. 2008 Feb 20;299(7):765-6
Abstract
Context: Antioxidant supplements are used for prevention of several diseases.
Objective: To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. DATA SOURCES AND TRIAL SELECTION: We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.
Data extraction: We included 68 randomized trials with 232 606 participants (385 publications).
Data synthesis: When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.04[corrected]-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.
Conclusions: Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.
Comment in
-
Review: antioxidant supplements for primary and secondary prevention do not decrease mortality.ACP J Club. 2007 Jul-Aug;147(1):4. ACP J Club. 2007. PMID: 17608369 No abstract available.
-
Antioxidant supplements and mortality.JAMA. 2007 Jul 25;298(4):400-1; author reply 402-3. doi: 10.1001/jama.298.4.400-b. JAMA. 2007. PMID: 17652289 No abstract available.
-
Antioxidant supplements and mortality.JAMA. 2007 Jul 25;298(4):400; author reply 402-3. doi: 10.1001/jama.298.4.400-a. JAMA. 2007. PMID: 17652290 No abstract available.
-
Antioxidant supplements and mortality.JAMA. 2007 Jul 25;298(4):401-2; author reply 402-3. doi: 10.1001/jama.298.4.401-b. JAMA. 2007. PMID: 17652291 No abstract available.
-
Antioxidant supplements and mortality.JAMA. 2007 Jul 25;298(4):401; author reply 402-3. doi: 10.1001/jama.298.4.401-a. JAMA. 2007. PMID: 17652292 No abstract available.
-
The art of casting nets: fishing for the prize of personalized cancer prevention.Nutr Cancer. 2008;60(1):1-6. doi: 10.1080/01635580701806699. Nutr Cancer. 2008. PMID: 18444129
Similar articles
-
Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.Cochrane Database Syst Rev. 2012 Mar 14;2012(3):CD007176. doi: 10.1002/14651858.CD007176.pub2. Cochrane Database Syst Rev. 2012. PMID: 22419320 Free PMC article. Review.
-
Antioxidant supplements for liver diseases.Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007749. doi: 10.1002/14651858.CD007749.pub2. Cochrane Database Syst Rev. 2011. PMID: 21412909 Review.
-
Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements.Aliment Pharmacol Ther. 2008 Sep 15;28(6):689-703. doi: 10.1111/j.1365-2036.2008.03785.x. Aliment Pharmacol Ther. 2008. PMID: 19145725 Review.
-
Antioxidant supplements for preventing gastrointestinal cancers.Cochrane Database Syst Rev. 2008 Jul 16;(3):CD004183. doi: 10.1002/14651858.CD004183.pub3. Cochrane Database Syst Rev. 2008. PMID: 18677777 Review.
-
Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.Cochrane Database Syst Rev. 2008 Apr 16;(2):CD007176. doi: 10.1002/14651858.CD007176. Cochrane Database Syst Rev. 2008. Update in: Cochrane Database Syst Rev. 2012 Mar 14;(3):CD007176. doi: 10.1002/14651858.CD007176.pub2. PMID: 18425980 Updated. Review.
Cited by
-
Effects of primary or secondary prevention with vitamin A supplementation on clinically important outcomes: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.BMJ Open. 2024 May 30;14(5):e078053. doi: 10.1136/bmjopen-2023-078053. BMJ Open. 2024. PMID: 38816049 Free PMC article.
-
Protective Effects of Dietary Vitamin D3, Turmeric Powder, and Their Combination against Gasoline Intoxication in Rats.Pharmaceuticals (Basel). 2024 May 10;17(5):619. doi: 10.3390/ph17050619. Pharmaceuticals (Basel). 2024. PMID: 38794189 Free PMC article.
-
The aging lung: microenvironment, mechanisms, and diseases.Front Immunol. 2024 May 2;15:1383503. doi: 10.3389/fimmu.2024.1383503. eCollection 2024. Front Immunol. 2024. PMID: 38756780 Free PMC article. Review.
-
The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging.J Physiol Sci. 2024 May 11;74(1):29. doi: 10.1186/s12576-024-00922-7. J Physiol Sci. 2024. PMID: 38730366 Free PMC article. Review.
-
Distributive randomization: a pragmatic fractional factorial design to screen or evaluate multiple simultaneous interventions in a clinical trial.BMC Med Res Methodol. 2024 Mar 11;24(1):64. doi: 10.1186/s12874-024-02191-9. BMC Med Res Methodol. 2024. PMID: 38468221
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical