S-equol, a potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora

Kenneth D.R. Setchell, Carlo Clerici, Edwin D. Lephart, Sidney J. Cole, Claire Heenan, Danilo Castellani, Brian E. Wolfe, Linda Nechemias-Zimmer, Nadine M. Brown, Trent D. Lund, Robert J. Handa, James E. Heubi

Research output: Contribution to journalArticle

315 Scopus citations

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. Design: 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 exc lusive 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 β (Ki = 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 β.

Original languageEnglish (US)
Pages (from-to)1072-1079
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume81
Issue number5
StatePublished - Dec 12 2005
Externally publishedYes

Keywords

  • Bacteria
  • Equol
  • Humans
  • Pharmacokinetics
  • Soy isoflavones

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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    Setchell, K. D. R., Clerici, C., Lephart, E. D., Cole, S. J., Heenan, C., Castellani, D., Wolfe, B. E., Nechemias-Zimmer, L., Brown, N. M., Lund, T. D., Handa, R. J., & Heubi, J. E. (2005). S-equol, a potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. American Journal of Clinical Nutrition, 81(5), 1072-1079.