ArticlesAntioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis
Introduction
Oxidative stress can cause cancer.1, 2 The human diet is a complex mixture of oxidants and antioxidants. The gastrointestinal tract is thought to be the major site of antioxidant action.3 The question of whether antioxidant supplements might protect against cancer has drawn much attention.4, 5
Oxidative injury might induce gene mutation and promote carcinogenesis.6 In addition to the deleterious effects of reactive oxygen species on human cells, oxidative injury can lead to cell death (apoptosis).7 Dysregulation of apoptosis has a role in gastrointestinal diseases, including cancer.8 Oxidative stress can modulate the apoptotic programme9, 10 and could cause gastro-intestinal cancer.11, 12 Many observational epidemiological studies have shown that a high intake of fruit and vegetables (rich in antioxidants) is associated with a lower cancer incidence.13, 14 However, results of randomised trials looking at the possible preventive effects of dietary supplementation with one or more selected antioxidants have been contradictory.15, 16, 17, 18 In this systematic review, including meta-analyses, we assess the beneficial and harmful effects of such antioxidant supplementation in the prevention of gastro-intestinal cancers.
Section snippets
Methods
We did this review by following the Cochrane Collaboration methodology19 on the basis of our predefined, peer-reviewed, published Cochrane Hepato-Biliary Group protocol.20 We included all trials that randomised participants to supplementation with antioxidants (β-carotene, vitamins A, C, E, and selenium, as different combinations or separately) versus placebo, and reported the incidence of gastrointestinal cancers.20 We included participants from the general population, mainly with
Role of the funding source
The funding sources had no role in the collection, analyses, interpretation of data, writing of the report, or decision to publish. The authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Results
We identified 681 references through database searches. After exclusion of duplicate and irrelevant references, we retrieved 116. Additionally, we identified 81 through scanning reference lists. Of these 197 references, we excluded 36 non-randomised trials, 11 describing six continuing trials, and 13 describing five trials that did not contain relevant data. The remaining 137 references, describing 14 trials,15, 16, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 fulfilled our inclusion criteria
Discussion
Our systematic review contains several major findings. β-carotene, vitamin A, vitamin C, and vitamin E supplements given alone or in combinations do not seem to have much effect in the prevention of gastrointestinal cancers. Further, these antioxidant supplements seem to increase overall mortality. Selenium might be an exception, potentially leading to reduction of gastrointestinal cancers, but this result might be biased because of low methodological quality in three of four trials. Compared
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