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S-Equol, a potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora1–4,
Open accessAbstract
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 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.
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“Thus, S-equol is classified as a selective estrogen receptor modulator (SERM) with high affinity for ERβ.”
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“Remarkably, S-equol binds ERβ approximately 1/5, as well as 17β-estradiol, while having low affinity for ERα [2,78,80].”
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Metadata
- Authors
- Setchell, K. D., 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.
- Affiliations
- Brigham Young University (US)
- Corresponding author
- Setchell, Kenneth DR
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 81
- Issue
- 5
- Pages
- 1072-1079
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2118089000
- Cited by
- 471
- References
- 59
- Citations by year
- 2026: 21 · 2025: 19 · 2024: 14 · 2023: 24 · 2022: 25 · 2021: 26 · 2020: 22 · 2019: 15 · 2018: 22 · 2017: 16 · 2016: 19 · 2015: 27 · 2014: 21 · 2013: 31 · 2012: 26
- FWCI
- 13.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca073328-03, RR08084)
- National Cancer Institute (R01CA73328)
- National Center for Research Resources (M01RR008084, RR08084)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Phytoestrogen effects and research
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- S-equol, equol, daidzein, soy isoflavones, estrogen receptor beta, intestinal bacterial metabolism, gut microbiota, enantiomers, stereospecificity, bioavailability, pharmacokinetics, human urine, soy products
- MeSH terms
- Animals, Biological Availability, Chromatography, High Pressure Liquid, Female, Half-Life, Humans, Intestines, Isoflavones, Male, Gas Chromatography-Mass Spectrometry, Stereoisomerism, Rats, Sprague-Dawley, Area Under Curve, Phytoestrogens, Rats, Equol
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