The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids

At a population level there is growing evidence for the beneficial effects of dietary flavonoids on health. However there is extensive heterogeneity in the response to increased intake, which is likely mediated via wide inter-individual variability in flavonoid absorption and metabolism. Flavonoids are extensively metabolized by phase I and II- (which occurs predominantly in the gastrointestinal tract and liver) and colonic microbial- metabolism. A number of factors, including age, gender and genotype may impact on these metabolic processes. In addition food composition and flavonoid source is likely to affect bioavailability and emerging data suggest a critical role for the microbiome. This review will focus on the current knowledge for the main sub-classes of flavonoids, including anthocyanins, flavonols, flavan-3-ols and flavanones, where there is growing evidence from prospective studies for beneficial effects on health. Identifying key factors governing metabolism, and understanding if differential capacity to metabolize these bioactive compounds impacts on health outcomes, will help establish how to optimize intakes of flavonoids for health benefits and in specific subgroups. We identify research areas which need to be addressed in order to further understand important determinants of flavonoid bioavailability and metabolism and to advance the knowledge base required to move towards the development of dietary guidelines / recommendations for flavonoids and flavonoid-rich foods.