The pharmacokinetics of anthocyanins and their metabolites in humans

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 500mg oral bolus dose of 6,8,10,3,5-13C5-C3G was fed to eight healthy male participants, followed by a 48h collection (0, 0.5, 1, 2, 4, 6, 24, 48h) 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 (Cmax) ranged from 10 to 2000nM, between 2 and 30h (tmax) post-consumption, with half-lives of elimination observed between 0.5 and 96h. The major phenolic metabolites identified were hippuric acid and ferulic acid, which peaked in the serum at approximately 16 and 8h 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.