Intervention Review

Antioxidant supplements for preventing gastrointestinal cancers

  1. Goran Bjelakovic2,*,
  2. Dimitrinka Nikolova3,
  3. Rosa G Simonetti4,
  4. Christian Gluud3

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 16 JUL 2008

Assessed as up-to-date: 11 NOV 2007

DOI: 10.1002/14651858.CD004183.pub3

How to Cite

Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD004183. DOI: 10.1002/14651858.CD004183.pub3.

Author Information

  1. 2

    Department 3344, Rigshospitalet, Copenhagen University Hospital,, Copenhagen Trial Unit, Centre for Clinical Intervention Research,, Copenhagen, Denmark

  2. 3

    Copenhagen Trial Unit, Centre for Clinical Intervention Research,, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

  3. 4

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

*Goran Bjelakovic, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Department 3344, Blegdamsvej 9, Copenhagen, DK-2100, Denmark.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 16 JUL 2008




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


Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory.


To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers.

Search methods

We identified trials through the trials registers of the four Cochrane Review Groups on gastrointestinal diseases, The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2007), MEDLINE, EMBASE, LILACS, SCI-EXPANDED, and The Chinese Biomedical Database from inception to October 2007. We scanned reference lists and contacted pharmaceutical companies.

Selection criteria

Randomised trials comparing antioxidant supplements to placebo/no intervention examining occurrence of gastrointestinal cancers.

Data collection and analysis

Two authors (GB and DN) independently selected trials for inclusion and extracted data. Outcome measures were gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were reported as relative risks (RR) with 95% confidence interval (CI) based on random-effects and fixed-effect model meta-analysis. Meta-regression assessed the effect of covariates across the trials.

Main results

We identified 20 randomised trials (211,818 participants), assessing beta-carotene (12 trials), vitamin A (4 trials), vitamin C (8 trials), vitamin E (10 trials), and selenium (9 trials). Trials quality was generally high. Heterogeneity was low to moderate. Antioxidant supplements were without significant effects on gastrointestinal cancers (RR 0.94, 95% CI 0.83 to 1.06). However, there was significant heterogeneity (I2 = 54.0%, P = 0.003). The heterogeneity may have been explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96 to 1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43 to 0.80; test of interaction P < 0.0005), and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). The antioxidant supplements had no significant effects on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97 to 1.07, I2 = 53.5%), but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02 to 1.07). Beta-carotene in combination with vitamin A (RR 1.16, 95% CI 1.09 to 1.23) and vitamin E (RR 1.06, 95% CI 1.02 to 1.11) significantly increased mortality. Increased yellowing of the skin and belching were non-serious adverse effects of beta-carotene. In five trials (four with high risk of bias), selenium seemed to show significant beneficial effect on gastrointestinal cancer occurrence (RR 0.59, 95% CI 0.46 to 0.75, I2 = 0%).

Authors' conclusions

We could not find convincing evidence that antioxidant supplements prevent gastrointestinal cancers. On the contrary, antioxidant supplements seem to increase overall mortality. The potential cancer preventive effect of selenium should be tested in adequately conducted randomised trials.


Plain language summary

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

Antioxidant supplements cannot be recommended for gastrointestinal cancer prevention

Our body cannot synthesize all compounds that are essential for health. Therefore such compounds must be taken through diet. Oxidative stress may cause cell damage that is implicated in chronic diseases like cancer. Gastrointestinal cancers are among the most common cancers worldwide. The poor prognosis of patients diagnosed with gastrointestinal cancers made primary prevention a potentially attractive approach. The evidence on whether antioxidant supplements are effective in decreasing gastrointestinal cancers is contradictory.

In this review prevention with antioxidant supplements of oesophageal, gastric, small intestinal, colorectal, pancreatic, liver, and biliary tract cancers is assessed. The review includes 20 randomised clinical trials. In total, 211,818 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo. Trial quality was exceptionally good.

Based on properly designed and conducted randomised clinical trials, convincing evidence that beta-carotene, vitamin A, vitamin C, and vitamin E or their combinations may prevent gastrointestinal cancers is not found. A total of 2057 of 95084 participants (2.2%) randomised to antioxidant supplements and 1548 of 78935 participants (2.0%) randomised to placebo developed gastrointestinal cancers. These antioxidant supplements even seem to increase mortality. A total of 17114 of 122,501 participants (14.0%) randomised to antioxidant supplements and 8799 of 78693 participants (11.2%) randomised to placebo died. Selenium alone may have preventive effects on gastrointestinal cancers. This finding, however, is based on trials with flaws in their design and needs confirmation in properly conducted randomised clinical trials.



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







作者經由四個對於胃腸道疾病的Cochrane Review Groups之試驗登錄, Cochrane Central Register of Controlled Trials on The Cochrane Library (2003年第一期), MEDLINE, EMBASE, LILACS及SCIEXPANDED資料庫(從開始到2003年2月),以及The Chinese Biomedical Database 2003年3月)等資料庫進行搜尋。我們瀏覽其中參考文獻和聯繫製藥公司。




兩名評論作者獨立地選擇納入試驗並提取數據。所評量結果為胃腸道癌的發病率,總死亡率和不良反應。結果以固定和隨機效應綜合分析的relative risks (RR)與95% confidence interval (CI)呈現。


我們納入14個隨機試驗(170525人參加),評估β胡蘿蔔素(9篇),維生素A(4篇),維生素C(4篇),維生素E(5篇),硒(6篇)。試驗的質量普遍較高。異質性低到中度。無論是固定效應(RR 0.96,95%CI 0.88至1.04)或隨機效應綜合分析(RR 0.90,95%CI 0.77至1.05)抗氧化輔助劑對預防胃腸道癌發病率都沒有顯著影響。在七個針對死亡率高品質的試驗(131727人參加),不像隨機效應(RR 1.06,95%CI 0.98至1.15), 固定效應綜合分析(RR 1.06,95%CI 1.02至1.10),抗氧化輔助劑顯著增加亡率。兩個低品質的試驗(32302人參加)沒有發現抗氧化輔助劑對死亡率有重大影響。高和低質量的試驗估計死亡率的差別,以相互作用檢測有顯著性的差異(z = 2.10,P = 0.04)。 β胡蘿蔔素加維生素A(RR 1.29,95%CI 1.14至1.45)和β胡蘿蔔素加維生素E(RR 1.10,95%CI 1.01至1.20),死亡率顯著增加,而單獨β胡蘿蔔素只有增加死亡率傾向(RR 1.05,95%CI 0.99至1.11)。增加皮膚發黃和打嗝是β胡蘿蔔素的非嚴重性不良影響。在四個試驗(三個實驗設計方法不明或不適當),硒對胃腸道癌發病率有顯著有益的效果。





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




Plain language summary

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

Nadomjesci antioksidanata za prevenciju probavnih karcinoma

Nadomjesci antioksidanata se ne mogu preporučiti za prevenciju probavnih karcinoma

Naše tijelo ne može stvoriti sve tvari koje su nam nužne za zdravlje. Stoga se takve tvari trebaju uzimati prehranom. Oksidativni stres može uzrokovati oštećenje stanice, za koje se smatra da je uključeno u razvoj kroničnih bolesti kao što je karcinom. Probavni karcinomi su među najčešćim karcinomima širom svijeta. Zbog loše prognoze osoba kojima je dijagnosticiran karcinom probavnog sustava, primarna prevencija ovih bolesti postala je izuzetno zanimljiva za istraživanja. Postojeći dokazi o tome je li dodavanje antioksidanata korisno za smanjenje broja probavnih karcinoma vrlo su proturječni.

Ovim sustavnim pregledom istraženo je preventivno djelovanje nadomjestaka antioksidanata na karcinom jednjaka, želuca, tankog crijeva, debelog crijeva, gušterače, jetre i žučnih vodova. U sustavni pregled je uključeno 20 randomiziranih kontroliranih pokusa, u kojima je sudjelovalo 211.818 ispitanika, od kojih je dio uzimao antioksidante (beta-karoten, vitamin A, vitamin C, vitamin E i selen) ili placebo. Kvaliteta istraživanja bila je vrlo visoka.

Ova istraživanja, koja su bila propisno osmišljena i ustrojena, nisu pokazala uvjerljive dokaze da beta-karoten, vitamin A, vitamin C i vitamin E, ili bilo koja njihova kombinacija, može spriječiti nastanak probavnih karcinoma. Ukupno 2057 od 95.084 (2,2%) ispitanika koji su dobivali antioksidante i 1.548 od 78.935 (2,0%) ispitanika koji su uzimali placebo razvilo je probavne karcinome u promatranom razdoblju. Štoviše, rezultati pokazuju da nadomjesci antioksidanata povećavaju smrtnost, jer je smrtnost u skupini koja je primala antioksidante iznosila 14%, a u skupini koja je uzimala placebo 11,2%. Ako se uzima sam, selen može imati preventivni učinak za probavne karcinome. Međutim, ovaj zaključak temelji se na istraživanjima koja nisu bila propisno ustrojena pa se stoga treba potvrditi u novim, propisno provedenim randomiziranim kontroliranim ispitivanjima.

Translation notes

Translated by: Croatian Branch of the Italian Cochrane Centre
Translation Sponsored by: Ministry of Education, Science and Sports