Unravelling the Link between Polyphenol Intake and the Risk of Digestive System Cancer: An Umbrella Review Using Meta-Analyses and Systematic Reviews

Abstract

Background Digestive system cancers (DSCs) constitute a significant number of cancer cases and are closely associated with modifiable risk factors.Objective This umbrella review synthesizes evidence from meta-analyses on the association between dietary polyphenol consumption and the risk of DSCs, addressing limitations in the literature and identifying optimal polyphenol types and doses.Methods Following Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Scopus and Web of Science until April 2025, using specific keywords related to polyphenols and DSCs. Eligible studies included meta-analyses that examined polyphenol intake and DSC risk. The quality was assessed via the AMSTAR 2 and GRADE framework. Statistical analyses were performed using RStudio, employing random-effects models based on the heterogeneity metrics.Results Data from six meta-analyses, encompassing 27 effect sizes, revealed a statistically significant 11% reduction in the risk of DSCs associated with polyphenol consumption (RR: 0.89; 95% CI: 0.85-0.93; I2: 63%). Subgroup analysis revealed significant risk reductions for specific polyphenol classes: flavonols (22%), quercetin (22%), anthocyanidins (16%), flavan-3-ols (12%) and isoflavones (9%). Publication bias was evident, but adjustments using the trim-and-fill method still indicated a 13% overall reduction in risk (RR: 0.87; 95% CI: 0.83-0.92; I2: 64%).Conclusions Our findings support the protective role of dietary polyphenols against DSCs, particularly flavonols and quercetin, suggesting that further investigations into the optimal intake levels and mechanisms of action are needed. These findings underscore the potential of dietary modification as a strategy for DSC prevention.