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Probiotic supplementation seems to provide beneficial effects in the prevention and treatment of radiation-induced diarrhea. We performed a systematic review and meta-analysis to estimate the efficacy of probiotic supplementation for prevention and treatment of radiation-induced diarrhea.Two reviewers independently searched PubMed, EMBASE, Cochrane Library, Google Scholar and on-line clinical trials registers (up to January 2009) for randomized controlled trials that evaluated the efficacy of probiotic supplementation for the prevention and treatment of radiation-induced diarrhea. Each clinical trial was separately evaluated for study characteristics, methodologic quality and outcomes. Results of the randomized controlled trials were pooled in a meta-analysis.Four randomized controlled trials were included. Three clinical trials, with a total of 632 subjects, evaluated the preventive effects of probiotic supplementation and 1 study evaluated the therapeutic role. Random effects meta-analysis of the preventive trials did not show significant differences between probiotic supplementation and control groups (odds ratio 0.47; 95% confidence interval: 0.13-1.67). However, the few available trials and the presence of significant clinical and statistical heterogeneity limited the analysis. Similarly, the therapeutic clinical trial did not show significant differences between active and placebo groups. No major adverse events owing to probiotic supplementation were reported in any study.Probiotic supplementation showed beneficial effect in the prevention and treatment of radiation-induced diarrhea in experimental animal studies. Encouraging results have been observed in humans; however, the few available clinical studies do not allow firm conclusions. More well-performed, randomized placebo-controlled studies are needed.