title: The pharmacokinetics of anthocyanins and their metabolites in humans.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A 500 mg oral bolus dose of 6,8,10,3',5'-(13)C5-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.
  
  
  RESULTS
  Seventeen (13)C-labelled compounds were identified in the serum, including (13)C5-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 2000 nM, between 2 and 30 h (tmax) 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
  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.
authors.affiliation: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: de Ferrars
authors.forename: C
authors.initials: C
authors.lastname: Czank
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: N P
authors.initials: NP
authors.lastname: Botting
authors.forename: P A
authors.initials: PA
authors.lastname: Kroon
authors.forename: A
authors.initials: A
authors.lastname: Cassidy
authors.forename: C D
authors.initials: CD
authors.lastname: Kay
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000872:Anthocyanins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors; D055815:Young Adult
chemical_list: D000872:Anthocyanins; D005960:Glucosides; C462279:cyanidin-3-O-beta-glucopyranoside
keywords: anthocyanins; ferulic acid; hippuric acid; metabolites; vanillic acid