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Intervention Review

Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

  1. Goran Bjelakovic1,*,
  2. Dimitrinka Nikolova2,
  3. Lise Lotte Gluud2,
  4. Rosa G Simonetti3,
  5. Christian Gluud2

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 23 APR 2008

Assessed as up-to-date: 19 FEB 2008

DOI: 10.1002/14651858.CD007176

How to Cite

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.

Author Information

  1. 1

    Medical Faculty, University of Nis, Department of Internal Medicine - Gastroenterology and Hepatology, Nis, Serbia

  2. 2

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

  3. 3

    Ospedale V.Cervello, Divisione di Medicina, Palermo, Italy

*Goran Bjelakovic, Department of Internal Medicine - Gastroenterology and Hepatology, Medical Faculty, University of Nis, Boulevard Dr Zorana Djindjica 81, Nis, 18000, Serbia. goranb@junis.ni.ac.rs.

Publication History

  1. Publication Status: Edited (no change to conclusions), comment added to review
  2. Published Online: 23 APR 2008

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This is not the most recent version of the article. View current version (14 MAR 2012)

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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 methods

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.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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

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.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

抗氧化補充劑用於預防健康受試者和各種疾病病人之死亡

動物和生理學研究以及觀察研究指出抗氧化補充劑有助於提高存活率。

目標

以初級預防或次級預防隨機臨床試驗來評估使用抗氧化補充劑對死亡率產生的作用。

搜尋策略

我們搜尋Cochrane Library(2005年第3期)、MEDLINE (1966年到2005年10月)、EMBASE (1985年到 2005年10月)和cience Citation Index Expanded (1945年到2005年10月)。我們掃描了相關出版物的書目,並寫信給製藥公司,以獲取更多的試驗。

選擇標準

我們收納所有抗氧化補充劑(β胡蘿蔔素、維他命A、維他命C、維他命E和硒)對照安慰劑或無干預療法用於初級預防或次級預防的隨機臨床試驗。 包括健康的受試者(初級預防)和患有各種疾病的受試者(次級預防)。

資料收集與分析

三位作者摘錄數據。若隨機方法恰當,採用盲法及追蹤的試驗被認為具有較低的偏誤風險。根據隨機效果和固定效果模式,實施統合分析。並以隨機效果統合回歸分析來評估試驗間來源的異質性。

主要結論

共包括67個隨機試驗,232,550位受試者。47個試驗包括180,938位受試者,其偏誤風險較低。21個試驗包括164,439位健康受試者。46個試驗包括68,111位患有各種疾病的受試者(包括胃腸、心血管、神經學、視覺、皮膚、類風濕、腎、內分泌或不明原因的疾病)。總體來看,隨機效果的統合分析(相對風險度[RR] 1.02, 95% 信賴區間 [CI] 0.99 1.06),顯示抗氧化補充劑對死亡率沒有顯著作用,但是在固定效果模式 (RR 1.04, 95% CI 1.02 1.06)裏,明顯增加死亡率。在統合回歸分析中,偏誤風險和抗氧化補充劑類型是檢驗試驗間異質性的唯一顯著指標。在偏誤風險低的試驗裏,抗氧化補充劑明顯增加死亡率 (RR 1.05, 95% CI 1.02 1.08)。單獨評估各種抗氧化劑時,對偏誤風險低且排除硒試驗的試驗分析指出,維他命A (RR 1.16, 95% CI 1.10 1.24)、β胡蘿蔔素 (RR 1.07, 95% CI 1.02 1.11)和維他命E (RR 1.04, 95% CI 1.01 1.07)能夠明顯增加死亡率,但是維他命C (RR 1.06, 95% CI 0.94 1.20)沒有顯著有害的療效。偏誤風險低的硒試驗發現對死亡率沒有顯著影響 (RR 0.91, 95% CI 0.76 1.09)。

作者結論

我們發現沒有證據支持抗氧化補充劑對於初級或次級預防有幫助。維他命A、β胡蘿蔔素和維他命E可能會增加死亡率。未來需要進一步實施隨機試驗來評估維他命C和硒用於初級和次級預防的潛在療效。此類試驗均須密切監測其有害作用。需要把抗氧化補充劑視為藥物,一般經過充分的評估之後才能上市行銷。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

沒有證據支持抗氧化補充劑能夠預防健康人群或患各種疾病的病人的死亡。 過去對動物和生理模式的研究指出,抗氧化補充劑對於延長生命具有有益的作用。一些觀察研究建議,抗氧化補充劑可以延長生命,但是另外一些研究指出抗氧化補充劑具有中性或有害效果。大部份的隨機試驗屬於中性效果。我們需要從隨機試驗中提供證據以確定是否抗氧化補充劑應用於預防。目前系統性文獻回顧包括67 個隨機臨床試驗,包括232,550位受試者被分配使用抗氧化補充劑(β胡蘿蔔素、維他命A、維他命C、維他命E和硒) 並對照安慰劑或無干預法。21個試驗包括164,439 位健康受試者。46個試驗包括 68,111位患有各種疾病的受試者(包括胃腸、心血管、神經學、視覺、皮膚、類風濕、腎、內分泌或不明原因的疾病)。總體來看,抗氧化補充劑看似不能降低死亡率。 在136,023位受試者中,17,880 人(13.1%) 接受抗氧化補充劑死亡,96,527位接受安慰劑或無干預法的受試者中有10,136 人(10.5%)死亡。在分析偏誤風險低的試驗中,β胡蘿蔔素、維他命A和維他命E明顯增加死亡率。抗氧化補充劑對健康受試者(初級預防)或患有各種疾病的受試者 (次級預防)的療效沒有顯著差異。偏誤控制恰當的隨機試驗發現維他命C沒有顯著作用。 在我們的某些分析中,硒看似可以降低死亡率。 目前沒有支持證據抗氧化補充劑用於一般人群或患有各種疾病的病人。合併後的證據指出需要對抗氧化補充劑進行深入研究。維他命C和硒的證據則尚不能定論。未來試驗應關注維他命C和硒,評估其潛在利弊。對於維他命A、β胡蘿蔔素和維他命E導入用於額外的初級和次級預防的試驗,至少在試驗的劑量範圍之內而言,似乎沒有必要。目前文獻回顧沒有評估抗氧化補充劑用於治療具體的疾病(三級預防),抗氧化補充劑用於對抗氧化劑有特殊需求的病人,或者水果或蔬菜中所含的抗氧化劑的療效。針對這些治療方式進一步的研究和系統性的文獻回顧是有需要的。