Flavonoids are plant‐derived dietary components with a substantial impact on human health. Research has expanded massively since it began in the 1930s, and the complex pathways involved in bioavailability of flavonoids in the human body are now well understood. In recent years, it has been appreciated that the gut microbiome plays a major role in flavonoid action, but much progress still needs to be made in this area. Since the first publications on the health effects of flavonoids, their action is understood to protect against various stresses, but the mechanism of action has evolved from the now debunked simple direct antioxidant hypothesis into an understanding of the complex effects on molecular targets and enzymes in specific cell types. This review traces the development of the field over the past 8 decades, and indicates the current state of the art, and how it was reached. Future recommendations based on this historical analysis are (a) to focus on key areas of flavonoid action, (b) to perform human intervention studies focusing on bioavailability and protective effects, and (c) to carry out cellular in vitro experiments using appropriate cells together with the chemical form of the flavonoid found at the site of action; this could be the native form of compounds found in the food for studies on digestion and the intestine, the conjugated metabolites found in the blood after absorption in the small intestine for studies on cells, or the chemical forms found in the blood and tissues after catabolism by the gut microbiota.

Background: Evidence suggests that the consumption of anthocyanin-rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown.

Background: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD).

Background and Purpose: Anthocyanins are phytochemicals with reported vasoactive bioactivity. However, given their instability at neutral pH, they are presumed to undergo significant degradation and subsequent biotransformation. The aim of the present study was to establish the pharmacokinetics of the metabolites of cyanidin‐3‐glucoside (C3G), a widely consumed dietary phytochemical with potential cardioprotective properties.Experimental Approach: A 500 mg oral bolus dose of 6,8,10,3′,5′‐¹³C₅‐C3G was fed to eight healthy male participants, followed by a 48 h collection (0, 0.5, 1, 2, 4, 6, 24, 48 h) of blood, urine and faecal samples. Samples were analysed by HPLC‐ESI‐MS/MS with elimination kinetics established using non‐compartmental pharmacokinetic modelling.Key Results: Seventeen ¹³C‐labelled compounds were identified in the serum, including ¹³C₅‐C3G, its degradation products, protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), 13 metabolites of PCA and 1 metabolite derived from PGA. The maximal concentrations of the phenolic metabolites (C_max) ranged from 10 to 2000 nM, between 2 and 30 h (t_max) post‐consumption, with half‐lives of elimination observed between 0.5 and 96 h. The major phenolic metabolites identified were hippuric acid and ferulic acid, which peaked in the serum at approximately 16 and 8 h respectively.Conclusions and Implications: Anthocyanins are metabolized to a structurally diverse range of metabolites that exhibit dynamic kinetic profiles. Understanding the elimination kinetics of these metabolites is key to the design of future studies examining their utility in dietary interventions or as therapeutics for disease risk reduction.

Background: Dietary flavonoids have beneficial effects on blood pressure in intervention settings, but there is limited information on habitual intak