Diploma Thesis Title: Finding evidence of efficacy and safety of antioxidant supplements for preventing gastrointestinal cancers: systematic review approach Objectives: Finding the best available evidence of efficacy and safety of antioxidant supplements for preventing gastrointestinal cancers. Material and Methods: „Antioxidant supplements for preventing gastrointestinal cancers“ systematic review was found by searching the Cochrane Library website. Further, we searched MEDLINE (PubMed), DARE and CENTRAL databases in order to find new randomised controlled trials and systematic reviews, following the same criteria that were used in Cochrane systematic review. After the search for studies was done, we made quality assessment of all systematic reviews using R-AMSTAR tool. Results: According to Cochrane systematic review, antioxidant supplements were without significant effects on gastrointestinal cancers (RR 0.94, 95% CI 0.83 to 1.06). However, there was significant heterogeneity (I(2) = 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 highbias 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, I(2) = 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, I(2) = 0%). We found two more RCTs. In one study there were statistically non-significant reductions in colorectal (HR, 0.89; 95% CI, 0.68–1.17; P=0.39) and pancreatic cancer (HR, 1,19; 95% CI, 0.76-1.85; P=0.45). Total mortality was not significantly reduced (HR, 0.94; 95% CI, 0.88–1.02; P=0.13). Those taking the active versus placebo multivitamin use were more likely to have skin rashes (2,111 and 1,973 men in corresponding active and placebo multivitamin groups; HR, 1.08; 95% CI, 1.01–1.15; P=0.016). In the other study, there were nonsignificant increased risks of Type 2 diabetes mellitus in the selenium arm (p=0.16; RR=1.07; 99% CI, 0.94–1.22). However, this slight increase was diminished in the second report (HR: 1.04; 99% CI: 0.93–1.17) There were no significant differences among treatment groups for colorectal cancer for selenium, vitamin E or their combination. Total R-AMSTAR score for Cochrane systematic review was 40. Two more systematic reviews were found. R-AMSTAR total score for them was 29 and 24. These two systematic reviews give the same conclusions as the Cochrane systematic review, although they differ in quality. A systematic review evaluated with 29 points showed that antioxidant supplements had no effect in the prevention of esophageal cancer. A systematic review evaluated with 24 points showed that antioxidant supplements had no significant effect on the incidence of colorectal cancer or in total mortality. Conclusion: Based on the reviewed systematic reviews and randomised controlled trials, convincing evidence that antioxidant supplements prevent gastrointestinal cancers could not be found. 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 on appropriate type of population.