title: Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes.
abstract: The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.4 mg) and genistein (9.8, 19.6 and 39.2 mg). Peak serum daidzein and genistein concentrations were attained after 4-8 h, and elimination half-lives were 8.0 and 10.1 h, respectively. There were no differences in the pharmacokinetics of daidzein and genistein between pre- and postmenopausal women, indicating absorption and disposition of isoflavones to be independent of age or menopausal status. A curvilinear relationship was observed between the bioavailability of daidzein and genistein, apparent from the area under the curve to infinity (AUC(inf)) of the serum concentration-time profiles and the amount of isoflavones ingested. The mean fraction of the isoflavones excreted in urine decreased with increasing intake when expressed as a percentage of the administered dose (63.2 +/- 8.0, 54.4 +/- 8.1 and 44.0 +/- 4.3%, respectively, for daidzein, and correspondingly, 25.2 +/- 5.3, 13.4 +/- 2.1 and 15.8 +/- 2.7% for genistein), underscoring the trend toward nonlinear pharmacokinetics. Equol was identified as a metabolite in 30% of women; it was present consistently in urine and blood from the same subjects. Its delayed appearance was consistent with colonic synthesis. On the basis of the pharmacokinetics, optimum steady-state serum isoflavone concentrations would be expected from modest intakes of soy foods consumed regularly throughout the day rather than from a single highly enriched product.
authors.affiliation: Division of Clinical Mass Spectrometry, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, OH, USA. Kenneth.Setchell@cchmc.org
authors.forename: Kenneth D R
authors.initials: KD
authors.lastname: Setchell
authors.forename: Nadine Maynard
authors.initials: NM
authors.lastname: Brown
authors.forename: Pankaj B
authors.initials: PB
authors.lastname: Desai
authors.forename: Linda
authors.initials: L
authors.lastname: Zimmer-Nechimias
authors.forename: Brian
authors.initials: B
authors.lastname: Wolfe
authors.forename: Abhijeet S
authors.initials: AS
authors.lastname: Jakate
authors.forename: Vivian
authors.initials: V
authors.lastname: Creutzinger
authors.forename: James E
authors.initials: JE
authors.lastname: Heubi
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D012016:Reference Values; D013025:Glycine max / Q000737:chemistry*
chemical_list: D007529:Isoflavones; C004742:daidzein; D019833:Genistein