Antioxidant supplements no good?

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Hi All,

How good are antioxidant supplements? The Ann Intern Med paper is and the Cochrane Database Syst Rev paper is not pdf-availed.

Ann Intern Med 16 Sep 2008; Vol. 149, No. 6TherapeuticsReview: Antioxidant supplements do not reduce all-cause mortality in primary and secondary prevention.

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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 Syst Rev. 2008 Apr 16;(2):CD007176. Review.PMID: 18425980

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.

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Clinical impact ratings: GM 5 G 6

Question

Do antioxidant supplements reduce all-cause mortality in primaryor secondary prevention?

Review scope

Included studies compared antioxidant supplements (â-carotene,vitamin A, vitamin C, vitamin E, or selenium) with placebo or nointervention in healthy participants (primary prevention) or inpatients with any disease (secondary prevention) who were =/>18years of age. Studies of patients with acute, infectious, or malignantdiseases except nonmelanoma skin cancer, or of children orpregnant women, were excluded. Outcome wasall-cause mortality.

Review methods

MEDLINE, EMBASE/Excerpta Medica, and Science CitationIndex Expanded (all to Oct 2005); Cochrane Library (Issue 3,2005); reference lists; and pharmaceutical companies were searchedfor randomized controlled trials (RCTs). 67 RCTs (n = 232 550,mean age 62 y, 55% men, based on 63 RCTs) met the selectioncriteria: 21 RCTs (n = 164 439) included healthy participants, and46 RCTs (n = 68 111) included patients with various diseases.47 RCTs had low risk for bias.

Main results

Random-effects meta-analysis showed that groups did not differfor all-cause mortality, but fixed-effects meta-analysis showedthat antioxidants increased risk for mortality more than didplacebo or no intervention (Table).

Conclusion

Antioxidant supplements do not reduce all-cause mortality inprimary or secondary prevention.

Commentary

The meta-analysis by Bjelakovic and colleagues showed no benefitof consuming supposed antioxidant supplements compared withplacebo or no intervention. Normal diets may have adequateamounts of these vitamins and compounds, and further supplementationadds very little. These micronutrients may even bebetter absorbed in the course of eating whole foods, rather than asisolated supplements. The review supports counseling patients onthe value of a well-balanced diet and only using supplements whena true need arises. Patients may be falsely reassured by supplementsand neglect important nutritional needs in their diets. A majorlimitation of the study is that the authors did not mentionwhether supplements were independently tested for contentbefore being studied. That labels on many over-the-counter supplementsdo not reflect actual content and often have much lessactive ingredient than what is touted has

been well-documented.

A.Green

16 September 2008 ACP Journal Club Volume 149, Number 3 2008 American College of Physicians JC3-9

Table. Antioxidant supplements vs placebo or no intervention (control) in primary and secondary prevention*==============================================Outcome at 1 mo to 14 y Number of trials (n)---Weighted event rates---Type of meta-analysis RRI (95% CI) NNH (CI) ---Antioxidant Control---==============================================All-cause mortality 67 (232 550)---10.7% 10.5% Random-effects model 2% (-1 to 6) Not significant - - ---10.9% 10.5% Fixed-effects model 4% (2 to 6) 239 (159 to

477)============================================== * Abbreviations defined in Glossary. Weighted event rates, RRI, NNH, and CI calculated from control event rates and relative risks in article.

-- Al Pater, alpater@...