title: The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers.
abstract: BACKGROUND
  The nonsteroidal estrogen equol occurs as diastereoisomers, S-(-)equol and R-(+)equol, both of which have significant biological actions. S-(-)equol, the naturally occurring enantiomer produced by 20-30% of adults consuming soy foods, has selective affinity for estrogen receptor-beta, whereas both enantiomers modulate androgen action. Little is known about the pharmacokinetics of the diastereoisomers, despite current interest in developing equol as a nutraceutical or pharmaceutical agent.
  
  
  OBJECTIVE
  The objective was to compare the pharmacokinetics of S-(-)equol and R-(+)equol by using [13C] stable-isotope-labeled tracers to facilitate the optimization of clinical studies aimed at evaluating the potential of these diastereoisomers in the prevention and treatment of estrogen- and androgen-dependent conditions.
  
  
  METHODS
  A randomized, crossover, open-label study in 12 healthy adults (6 men and 6 women) compared the plasma and urinary pharmacokinetics of orally administered enantiomeric pure forms of S-(-)[2-13C]equol, R-(+)[2-13C]equol, and the racemic mixture. Plasma and urinary [13C]R-equol and [13C]S-equol concentrations were measured by tandem mass spectrometry.
  
  
  RESULTS
  Plasma [13C]equol concentration appearance and disappearance curves showed that both enantiomers were rapidly absorbed, attained high circulating concentrations, and had a similar terminal elimination half-life of 7-8 h. The systemic bioavailability and fractional absorption of R-(+)[2-13C]equol were higher than those of S-(-)[2-13C]equol or the racemate. The pharmacokinetics of racemic (+/-)[2-13C]equol were different from those of the individual enantiomers: slower absorption, lower peak plasma concentrations, and lower systemic bioavailability.
  
  
  CONCLUSIONS
  The high bioavailability of both diastereoisomers contrasts with previous findings for the soy isoflavones daidzein and genistein, both of which have relatively poor bioavailability, and suggests that low doses of equol taken twice daily may be sufficient to achieve biological effects.
authors.affiliation: Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. kenneth.setchell@cchmc.org
authors.forename: Kenneth Dr
authors.initials: KD
authors.lastname: Setchell
authors.forename: Xueheng
authors.initials: X
authors.lastname: Zhao
authors.forename: Pinky
authors.initials: P
authors.lastname: Jha
authors.forename: James E
authors.initials: JE
authors.lastname: Heubi
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Brown
mesh_terms: D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D060754:Equol; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007529:Isoflavones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D048789:Phytoestrogens / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D045730:Soy Foods; D013025:Glycine max; D013237:Stereoisomerism; D055815:Young Adult
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D060754:Equol