title: Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma.
abstract: METHODS
  Genistein from foods or supplements is metabolized by the gut microbiota and the human body, thereby releasing many different metabolites into systemic circulation. The order of their appearance in plasma and the possible influence of food format are still unknown. This study compared the nutrikinetic profiles of genistein metabolites.
  
  
  RESULTS
  In a randomized cross-over trial, 12 healthy young volunteers were administered a single dose of 30 mg genistein provided as a genistein tablet, a genistein tablet in low fat milk, and soy milk containing genistein glycosides. A high mass resolution LC-LTQ-Orbitrap FTMS platform detected and quantified in human plasma: free genistein, seven of its phase-II metabolites and 15 gut-derived metabolites. Interestingly, a novel metabolite, genistein-4'-glucuronide-7-sulfate (G-4'G-7S) was identified. Nutrikinetic analysis using population-based modeling revealed the order of appearance of five genistein phase II metabolites in plasma: (1) genistein-4',7-diglucuronide, (2) genistein-7-sulfate, (3) genistein-4'-sulfate-7-glucuronide, (4) genistein-4'-glucuronide, and (5) genistein-7-glucuronide, independent of the food matrix.
  
  
  CONCLUSIONS
  The conjugated genistein metabolites appear in a distinct order in human plasma. The specific early appearance of G-4',7-diG suggests a multistep formation process for the mono and hetero genistein conjugates, involving one or two deglucuronidation steps.
authors.affiliation: Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands; Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Smit
authors.forename: Ewa
authors.initials: E
authors.lastname: Szymańska
authors.forename: Iris
authors.initials: I
authors.lastname: Kunz
authors.forename: Victoria
authors.initials: V
authors.lastname: Gomez Roldan
authors.forename: Marcel W E M
authors.initials: MW
authors.lastname: van Tilborg
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.forename: Kevin
authors.initials: K
authors.lastname: Prudence
authors.forename: Frans M
authors.initials: FM
authors.lastname: van der Kloet
authors.forename: John P M
authors.initials: JP
authors.lastname: van Duynhoven
authors.forename: Age K
authors.initials: AK
authors.lastname: Smilde
authors.forename: Ric C H
authors.initials: RC
authors.lastname: de Vos
authors.forename: Igor
authors.initials: I
authors.lastname: Bendik
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D015992:Body Mass Index; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008892:Milk / Q000737:chemistry; D041942:Soy Milk / Q000737:chemistry; D055815:Young Adult
chemical_list: C551847:genistein-4',7-diglucuronide; C551846:genistein-7-glucuronide-4'-sulfate; D019833:Genistein
keywords: Genistein; Nutrikinetic modeling; Phase II metabolites