title: S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora.
abstract: BACKGROUND
  The discovery of equol in human urine more than 2 decades ago and the finding that it is bacterially derived from daidzin, an isoflavone abundant in soy foods, led to the current nutritional interest in soy foods. Equol, unlike the soy isoflavones daidzein or genistein, has a chiral center and therefore can occur as 2 distinct diastereoisomers.
  
  
  OBJECTIVE
  Because it was unclear which enantiomer was present in humans, our objectives were to characterize the exact structure of equol, to examine whether the S- and R-equol enantiomers are bioavailable, and to ascertain whether the differences in their conformational structure translate to significant differences in affinity for estrogen receptors.
  
  
  METHODS
  With the use of chiral-phase HPLC and mass spectrometry, equol was isolated from human urine and plasma, and its enantiomeric structure was defined. Human fecal flora were cultured in vitro and incubated with daidzein to ascertain the stereospecificity of the bacterial production of equol. The pharmacokinetics of S- and R- equol were determined in 3 healthy adults after single-bolus oral administration of both enantiomers, and the affinity of each equol enantiomer for estrogen receptors was measured.
  
  
  RESULTS
  Our studies definitively establish S-equol as the exclusive product of human intestinal bacterial synthesis from soy isoflavones and also show that both enantiomers are bioavailable. S-equol has a high affinity for estrogen receptor beta (K(i) = 0.73 nmol/L), whereas R-equol is relatively inactive.
  
  
  CONCLUSIONS
  Humans have acquired an ability to exclusively synthesize S-equol from the precursor soy isoflavone daidzein, and it is significant that, unlike R-equol, this enantiomer has a relatively high affinity for estrogen receptor beta.
authors.affiliation: Division of Pathology, Clinical Mass Spectrometry, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati 45229, OH, USA. kenneth.setchell@cchmc.org
authors.forename: Kenneth D R
authors.initials: KD
authors.lastname: Setchell
authors.forename: Carlo
authors.initials: C
authors.lastname: Clerici
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Lephart
authors.forename: Sidney J
authors.initials: SJ
authors.lastname: Cole
authors.forename: Claire
authors.initials: C
authors.lastname: Heenan
authors.forename: Danilo
authors.initials: D
authors.lastname: Castellani
authors.forename: Brian E
authors.initials: BE
authors.lastname: Wolfe
authors.forename: Linda
authors.initials: L
authors.lastname: Nechemias-Zimmer
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Brown
authors.forename: Trent D
authors.initials: TD
authors.lastname: Lund
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Handa
authors.forename: James E
authors.initials: JE
authors.lastname: Heubi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D060754:Equol; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007422:Intestines / Q000382:microbiology; D007529:Isoflavones / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D048789:Phytoestrogens / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D007529:Isoflavones; D048789:Phytoestrogens; D060754:Equol