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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S-equol is classified as a selective estrogen receptor modulator (SERM) with high affinity for ERβ.
“Thus, S-equol is classified as a selective estrogen receptor modulator (SERM) with high affinity for ERβ.”
S-equol binds ERβ approximately 1/5 as well as 17β-estradiol, while having low affinity for ERα.
“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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Cites
Cloning of a novel receptor expressed in rat prostate and ovary.
Kuiper, G. G. J. M., Enmark, E., Pelto‐Huikko, M., Nilsson, S., & Gustafsson, J.-Α. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5925 · Cited by 4,792 · see citing works
Kuiper, G. G. J. M., Carlsson, B., Grandien, K., Enmark, E., Häggblad, J., Nilsson, S., & Gustafsson, J.-A. (1997) · Endocrinology · doi:10.1210/endo.138.3.4979 · Cited by 4,442 · see citing works
Setchell, K. D. R., Brown, N. M., & Lydeking-Olsen, E. (2002) · The Journal of Nutrition · doi:10.1093/jn/132.12.3577 · Cited by 1,209 · see citing works
Dietary Isoflavones: Biological Effects and Relevance to Human Health
Setchell, K. D. R., & Cassidy, A. (1999) · Journal of Nutrition · doi:10.1093/jn/129.3.758s · Cited by 1,158 · see citing works
Setchell, K. D. R., Brown, N. M., Desai, P. B., Zimmer-Nechemias, L., Wolfe, B., Brashear, W. T., Kirschner, A. S., Cassidy, A., & Heubi, J. E. (2001) · Journal of Nutrition · doi:10.1093/jn/131.4.1362s · Cited by 974 · see citing works
Exposure of infants to phyto-oestrogens from soy-based infant formula
Setchell, K. D. R., Zimmer-Nechemias, L., Cai, J., & Heubi, J. E. (1997) · The Lancet · doi:10.1016/s0140-6736(96)09480-9 · Cited by 704 · see citing works
A SPECIFIC BREEDING PROBLEM OF SHEEP ON SUBTERRANEAN CLOVER PASTURES IN WESTERN AUSTRALIA
Bennetts, H. W., Uuderwood, E. J., & Shier, F. L. (1946) · Australian Veterinary Journal · doi:10.1111/j.1751-0813.1946.tb15473.x · Cited by 671 · see citing works
Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease
Setchell, K. D. R., Borriello, S. P., Hulme, P., KIRK, D. N., & Axelson, M. (1984) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/40.3.569 · Cited by 619 · see citing works
Setchell, K. D. R., Brown, N. M., Zimmer-Nechemias, L., Brashear, W. T., Wolfe, B., Kirschner, A. S., & Heubi, J. E. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.2.447 · Cited by 618 · see citing works
Interaction of Phytoestrogens with Estrogen Receptors .ALPHA. and .BETA..
Morito, K., HIROSE, T., Kinjo, J., Hirakawa, T., Okawa, M., Nohara, T., Ogawa, S., Inoue, S., Muramatsu, M., & Masamune, Y. (2001) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.24.351 · Cited by 615 · see citing works
Rowland, I. R., Wiseman, H., Sanders, T. A. B., Adlercreutz, H., & Bowey, E. A. (2000) · Nutrition and Cancer · doi:10.1207/s15327914nc3601_5 · Cited by 583 · see citing works
Equol, a natural estrogenic metabolite from soy isoflavones
Muthyala, R. S., Ju, Y. H., Sheng, S., Williams, L. D., Doerge, D. R., Katzenellenbogen, B. S., Helferich, W. G., & Katzenellenbogen, J. A. (2004) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2003.11.035 · Cited by 441 · see citing works
Watanabe, S., Yamaguchi, M., Sobue, T., Takahashi, T., Miura, T., Arai, Y., Mazur, W., Wähälä, K., & Adlercreutz, H. (1998) · Journal of Nutrition · doi:10.1093/jn/128.10.1710 · Cited by 423 · see citing works
Urinary Equol Excretion with a Soy Challenge: Influence of Habitual Diet
Lampe, J. W., Karr, S. C., Hutchins, A. M., & Slavin, J. L. (1998) · Experimental Biology and Medicine · doi:10.3181/00379727-217-44241 · Cited by 401 · see citing works
STEROID AND PHYTO-OESTROGEN BINDING TO SHEEP UTERINE RECEPTORS IN VITRO
Shutt, D. A., & Cox, R. I. (1972) · Journal of Endocrinology · doi:10.1677/joe.0.0520299 · Cited by 389 · see citing works
Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life
Setchell, K. D. R., Zimmer-Nechemias, L., Cai, J., & Heubi, J. E. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/68.6.1453s · Cited by 388 · see citing works
Setchell, K. D. R., Faughnan, M. S., Avades, T. Y., Zimmer-Nechemias, L., Brown, N. M., Wolfe, B., Brashear, W. T., Desai, P., Oldfield, M. F., Botting, N. P., et al. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.2.411 · Cited by 320 · see citing works
Setchell, K. D. R., Brown, N. M., Desai, P. B., Zimmer-Nechemias, L., Wolfe, B., Jakate, A. S., Creutzinger, V., & Heubi, J. E. (2003) · Journal of Nutrition · doi:10.1093/jn/133.4.1027 · Cited by 302 · see citing works
Metabolites of dietary (soya) isoflavones in human urine
KELLY, G. E., Nelson, C., Waring, M., Joannou, G. E., & Reeder, A. Y. (1993) · Clinica Chimica Acta · doi:10.1016/0009-8981(93)90058-c · Cited by 299 · see citing works
Brown, N. M., & Setchell, K. D. R. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780282 · Cited by 297 · see citing works
Kostelac, D., Rechkemmer, G., & Briviba, K. (2003) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf034427b · Cited by 294 · see citing works
Axelson, M., & Setchell, K. D. R. (1981) · FEBS Letters · doi:10.1016/0014-5793(81)80322-5 · Cited by 291 · see citing works
Hur, H.-G., Lay, J. O., Beger, R. D., Freeman, J. P., & Rafii, F. (2000) · Archives of Microbiology · doi:10.1007/s002030000222 · Cited by 271 · see citing works
Equol Is a Novel Anti-Androgen that Inhibits Prostate Growth and Hormone Feedback1
Lund, T. D., Munson, D. J., Haldy, M. E., Setchell, K. D. R., Lephart, E. D., & Handa, R. J. (2004) · Biology of Reproduction · doi:10.1095/biolreprod.103.023713 · Cited by 250 · see citing works
Akaza, H. (2004) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyh015 · Cited by 246 · see citing works
Axelson, M., KIRK, D. N., Farrant, R. D., Cooley, G., Lawson, A. M., & Setchell, K. D. R. (1982) · Biochemical Journal · doi:10.1042/bj2010353 · Cited by 244 · see citing works
Phytoestrogen content of purified, open- and closed-formula laboratory animal diets.
Thigpen, J. E., Setchell, K. D. R., Ahlmark, K. B., Locklear, J., Spahr, T., Caviness, G. F., Goelz, M. F., Haseman, J. K., Newbold, R. R., & Forsythe, D. B. (1999) · PubMed · Cited by 237 · see citing works
Tsangalis, D., Ashton, J., McGill, A. E. J., & Shah, N. P. (2002) · Journal of Food Science · doi:10.1111/j.1365-2621.2002.tb08866.x · Cited by 234 · see citing works
(2000) · PubMed · Cited by 190 · see citing works
Nagel, S. C., Saal, F. S. V., & Welshons, W. V. (1998) · Experimental Biology and Medicine · doi:10.3181/00379727-217-44236 · Cited by 186 · see citing works
Soymilk or progesterone for prevention of bone loss
Lydeking-Olsen, E., Jensen, J. B., Setchell, K. D. R., & Holm–Jensen, T. (2004) · European Journal of Nutrition · doi:10.1007/s00394-004-0497-8 · Cited by 179 · see citing works
Heinonen, S., Wähälä, K., & Adlercreutz, H. (1999) · Analytical Biochemistry · doi:10.1006/abio.1999.4279 · Cited by 168 · see citing works
Setchell, K. D. R., & Cole, S. J. (2003) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf026199b · Cited by 161 · see citing works
Ohta, A., Sakai, K., Takasaki, M., Uehara, M., Adlercreutz, H., Morohashi, T., & Ishimi, Y. (2002) · Journal of Nutrition · doi:10.1093/jn/132.7.2048 · Cited by 158 · see citing works
Atkinson, C., Humbert, O., Lampe, J. W., & Berman, S. H. (2004) · Journal of Nutrition · doi:10.1093/jn/134.3.596 · Cited by 137 · see citing works
Equol, a new inactive phenol isolated from the ketohydroxyoestrin fraction of mares' urine
Marrian, G. F., & Haslewood, G. A. D. (1932) · Biochemical Journal · doi:10.1042/bj0261227 · Cited by 131 · see citing works
TANG, B. Y., & Adams, N. R. (1980) · Journal of Endocrinology · doi:10.1677/joe.0.0850291 · Cited by 125 · see citing works
Identification of lignans and phytoestrogens in urine of chimpanzees
Adlercreutz, H., Musey, P. I., Fotsis, T., Bannwart, C., Wähälä, K., Mäkelä, T., Brunow, G., & Hase, T. (1986) · Clinica Chimica Acta · doi:10.1016/0009-8981(86)90230-5 · Cited by 113 · see citing works
Transient elevation of estrogen receptors in the neonatal rat hippocampus
O’Keefe, J. A., & Handa, R. J. (1990) · Developmental Brain Research · doi:10.1016/0165-3806(90)90191-z · Cited by 110 · see citing works
Handa, R. J., Reid, D. L., & Resko, J. A. (1986) · Biology of Reproduction · doi:10.1095/biolreprod34.2.293 · Cited by 108 · see citing works
Shutt, D., & Braden, A. (1968) · Australian Journal of Agricultural Research · doi:10.1071/ar9680545 · Cited by 107 · see citing works
Blair, R. M., Appt, S. E., Clarkson, T. B., & Franke, A. A. (2003) · Journal of Nutrition · doi:10.1093/jn/133.7.2262 · Cited by 99 · see citing works
Steer, T. E., Johnson, I. T., Gee, J. M., & Gibson, G. R. (2003) · British Journal Of Nutrition · doi:10.1079/bjn2003949 · Cited by 72 · see citing works
Bonorden, M. J. L., Greany, K. A., Wangen, K. E., Phipps, W. R., Feirtag, J. M., Adlercreutz, H., & Kurzer, M. S. (2004) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602020 · Cited by 71 · see citing works
Tsangalis, D., Ashton, J., McGill, A. E. J., & Shah, N. P. (2003) · Journal of Food Science · doi:10.1111/j.1365-2621.2003.tb05721.x · Cited by 64 · see citing works
Nettleton, J. A., Greany, K. A., Wangen, K. E., Kurzer, M. S., Thomas, W. T. B., & Adlercreutz, H. (2004) · Journal of Nutrition · doi:10.1093/jn/134.8.1998 · Cited by 64 · see citing works
STEROIDS AND OTHER LIPIDS OF PREGNANT COW'S URINE
Klyne, W., & WRIGHT, A. A. (1959) · Journal of Endocrinology · doi:10.1677/joe.0.0180032 · Cited by 41 · see citing works
Identification of phytoestrogens in the urine of male dogs
Juniewicz, P. E., Morell, S. P., Moser, A. B., & EWING, L. L. (1988) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(88)90343-3 · Cited by 37 · see citing works
Atkinson, C., Skor, H. E., Fitzgibbons, E. D., Scholes, D., Chen, C., Wähälä, K., Schwartz, S. M., & Lampe, J. W. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00259-0 · Cited by 35 · see citing works
Verbeke, W., Moriaux, S., & Viaene, J. (2001) · Ghent University Academic Bibliography (Ghent University) · Cited by 30 · see citing works
Identification of equol in the urine of the domestic fowl
Common, R. H., & AINSWORTH, L. (1961) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(61)90452-8 · Cited by 26 · see citing works
Prolongation of the Life Span of Rats by Bulk-Formers in the Diet
Carlson, A. J., & Hoelzel, F. (1948) · Journal of Nutrition · doi:10.1093/jn/36.1.27 · Cited by 25 · see citing works
Suginome, H. (1966) · Bulletin of the Chemical Society of Japan · doi:10.1246/bcsj.39.1544 · Cited by 22 · see citing works
Monfort, S. L., Thompson, M., Czekala, N. M., Kasman, L. H., Shackleton, C. H. L., & Lasley, B. L. (1984) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(84)90398-4 · Cited by 21 · see citing works
Clark-Lewis, J., Dainis, I., & Ramsay, G. C. (1965) · Australian Journal of Chemistry · doi:10.1071/ch9651035 · Cited by 21 · see citing works
KUROSAWA, K., Ollis, W. D., Redman, B. T., Sutherland, I. O., Gottlieb, O. R., & Alves, H. M. (1968) · Chemical Communications (London) · doi:10.1039/c19680001265 · Cited by 16 · see citing works
The oestrogenicity of equol in sheep
Kaziro, R., Kennedy, J., Cole, E. R., & SOUTHWELL‐KEELY, P. T. (1984) · Journal of Endocrinology · doi:10.1677/joe.0.1030395 · Cited by 12 · see citing works
Tamura, M., Hirayama, K., Itoh, K., Suzuki, H., & Shinohara, K. (2002) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.48.225 · Cited by 10 · see citing works
Chemical Synthesis of [ 13 C]Daidzein
Baraldi, P. G., Spalluto, G., Cacciari, B., Romagnoli, R., & Setchell, K. D. R. (1999) · Journal of Medicinal Food · doi:10.1089/jmf.1999.2.99 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- Uchiyama S, Ueno T, Shirota T. The relationship between soy isofla- vones and the menopausal symptoms in Japanese perimenopausal women. Ann Nutr Metab 2001;45:113 (abstr).
- Lund TD, Munson DJ, Haldy ME, Setchell KDR, Lephart ED, Handa RJ. The phytoestrogen equol acts as an anti-androgen to inhibit prostate growth and hormone feedback. Biol Reprod 2004;70:1188 -95.
- Clark-Lewis JW. Configurations of optically active flavonoid com- pounds. Rev Pure Appl Chem 1962;12:96 -116.
- Baraldi PG, Spalluto G, Cacciari B, Romangnoli R, Setchell KDR. Chemical synthesis of [13C]daidzein. J Med Food 1999;2:99 -102.
- Morito K, Hirose T, Kinjo J, et al. Interaction of phytoestrogens with estrogen receptors ␣ and . Biol Pharm Bull 2001;24:351-6.
- Ueno T, Uchiyama S. Identification of the specific intestinal bacteria capable of metabolising soy isoflavone to equol. Ann Nutr Metab 2001; 45:114 (abstr).
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Dietary phenolics: chemistry, bioavailability and effects on health
Crozier, A., Jaganath, I. B., & Clifford, M. N. (2009) · Natural Product Reports · doi:10.1039/b802662a · Cited by 2,002 · see citing works
Bioavailability of the polyphenols: Status and controversies
D’Archivio, M., Filesi, C., Varì, R., Scazzocchio, B., & Masella, R. (2010) · International Journal of Molecular Sciences · doi:10.3390/ijms11041321 · Cited by 950 · see citing works
Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review
Duda-Chodak, A., Tarko, T., Satora, P., & Sroka, P. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-0852-y · Cited by 599 · see citing works
Equol: History, Chemistry, and Formation
Setchell, K. D. R., & Clerici, C. (2010) · The Journal of Nutrition · doi:10.3945/jn.109.119776 · Cited by 519 · see citing works
Flavonoid metabolism: the interaction of metabolites and gut microbiota
Murota, K., Nakamura, Y., & Uehara, M. (2018) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2018.1444467 · Cited by 487 · see citing works
Mayo, B., Vázquez, L., & Flórez, A. B. (2019) · Nutrients · doi:10.3390/nu11092231 · Cited by 416 · see citing works
Microbial metabolism of dietary phenolic compounds in the colon
Aura, A. (2008) · Phytochemistry Reviews · doi:10.1007/s11101-008-9095-3 · Cited by 412 · see citing works
Method of Defining Equol-Producer Status and Its Frequency among Vegetarians
Setchell, K. D. R., & Cole, S. J. (2006) · Journal of Nutrition · doi:10.1093/jn/136.8.2188 · Cited by 351 · see citing works
Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms
Lephart, E. D. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.001 · Cited by 325 · see citing works
Self-citationYuan, J., Wang, J., & Liu, X. (2007) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200600262 · Cited by 324 · see citing works
The Biochemistry, Chemistry and Physiology of the Isoflavones in Soybeans and their Food Products
Barnes, S. (2010) · Lymphatic Research and Biology · doi:10.1089/lrb.2009.0030 · Cited by 278 · see citing works
The chemistry of gut microbial metabolism of polyphenols
Stevens, J. F., & Maier, C. S. (2016) · Phytochemistry Reviews · doi:10.1007/s11101-016-9459-z · Cited by 244 · see citing works
The Influence of Gonadal Hormones on Neuronal Excitability, Seizures, and Epilepsy in the Female
Scharfman, H. E., & MacLusky, N. J. (2006) · Epilepsia · doi:10.1111/j.1528-1167.2006.00672.x · Cited by 232 · see citing works
Botanicals and Their Bioactive Phytochemicals for Women’s Health
Dietz, B. M., Hajirahimkhan, A., Dunlap, T. L., & Bolton, J. L. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.010843 · Cited by 226 · see citing works
Equol: Pharmacokinetics and Biological Actions ,
Setchell, K. D. R., & Clerici, C. (2010) · Journal of Nutrition · doi:10.3945/jn.109.119784 · Cited by 212 · see citing works
Bioactivation of Phytoestrogens: Intestinal Bacteria and Health
Landete, J. M., Arqués, J. L., Médina, M., Gaya, P., Rivas, B. D. L., & Múñoz, R. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.789823 · Cited by 204 · see citing works
Zhang, Y., Chen, R., Zhang, D., Qi, S., & Liu, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114295 · Cited by 209 · see citing works
Emerging evidence of the health benefits of S-equol, an estrogen receptor β agonist
Jackson, R. L., Greiwe, J. S., & Schwen, R. J. (2011) · Nutrition Reviews · doi:10.1111/j.1753-4887.2011.00400.x · Cited by 195 · see citing works
Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review
Domínguez‐López, I., Yago-Aragón, M., Salas‐Huetos, A., Tresserra‐Rimbau, A., & Hurtado‐Barroso, S. (2020) · Nutrients · doi:10.3390/nu12082456 · Cited by 204 · see citing works
Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review
Fritz, H., Seely, D., Flower, G., Skidmore, B., Fernandes, R., Vadeboncoeur, S., Kennedy, D., Cooley, K., Wong, R., Sagar, S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081968 · Cited by 188 · see citing works
A Brief Historical Overview of the Past Two Decades of Soy and Isoflavone Research
Messina, M. J. (2010) · Journal of Nutrition · doi:10.3945/jn.109.118315 · Cited by 185 · see citing works
Mann, G. E., Rowlands, D. J., Li, F., deWinter, P., & Siow, R. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.04.004 · Cited by 181 · see citing works
Analytical and compositional aspects of isoflavones in food and their biological effects
Mortensen, A., Kulling, S. E., Schwartz, H., Rowland, I. R., Ruefer, C. E., Rimbach, G. H., Cassidy, A., Magee, P. J., Millar, J., Hall, W. L., et al. (2009) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200800478 · Cited by 167 · see citing works
Barnes, S., PRASAIN, J. K., D'Alessandro, T. L., Arabshahi, A., Botting, N. P., Lila, M. A., Jackson, G. S., Janle, E. M., & Weaver, C. M. (2011) · Food & Function · doi:10.1039/c1fo10025d · Cited by 166 · see citing works
Mann, G. E., Bonacasa, B., Ishii, T., & Siow, R. C. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2008.12.012 · Cited by 158 · see citing works
Ju, Y. H., Fultz, J., Allred, K. F., Doerge, D. R., & Helferich, W. G. (2006) · Carcinogenesis · doi:10.1093/carcin/bgi320 · Cited by 157 · see citing works
Phytoestrogen Metabolism by Adult Human Gut Microbiota
Gaya, P., Médina, M., Sánchez‐Jiménez, A., & Landete, J. M. (2016) · Molecules · doi:10.3390/molecules21081034 · Cited by 150 · see citing works
The role of soy isoflavones in menopausal health
Clarkson, T. B., Utian, W. H., Barnes, S., Gold, E. B., Basaria, S. S., Asô, T., Kronenberg, F., Frankenfeld, C. L., Cline, J. M., Landgren, B., et al. (2011) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e31821fc8e0 · Cited by 148 · see citing works
Estrogen receptor β ligands: Recent advances and biomedical applications
Minutolo, F., Macchia, M., Katzenellenbogen, B. S., & Katzenellenbogen, J. A. (2009) · Medicinal Research Reviews · doi:10.1002/med.20186 · Cited by 147 · see citing works
Matthies, A., Clavel, T., Gütschow, M., Engst, W., Haller, D., Blaut, M., & Braune, A. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.00555-08 · Cited by 141 · see citing works
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Joy, S., Siow, R. C. M., Rowlands, D. J., Becker, M., Wyatt, A. W., Aaronson, P. I., Coen, C. W., Kalló, I., Jacob, R., & Mann, G. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602803200 · Cited by 141 · see citing works
Grünz, G., Haas, K., Soukup, S. T., Klingenspor, M., Kulling, S. E., Daniel, H., & Spanier, B. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.11.005 · Cited by 142 · see citing works
Usui, T., Tochiya, M., Sasaki, Y., Muranaka, K., Yamakage, H., Himeno, A., Shimatsu, A., Inaguma, A., Ueno, T., Uchiyama, S., et al. (2012) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2012.04400.x · Cited by 138 · see citing works
Liu, T., Li, N., Yan, Y., Liu, Y., Xiong, K., Liu, Y., Xia, Q., Zhang, H., & Liu, Z. (2019) · Phytotherapy Research · doi:10.1002/ptr.6538 · Cited by 138 · see citing works
Diverse Effects of Phytoestrogens on the Reproductive Performance: Cow as a Model
Wocławek-Potocka, I., Mannelli, C., Boruszewska, D., Kowalczyk‐Zieba, I., Waśniewski, T., & Skarzynski, D. J. (2013) · International Journal of Endocrinology · doi:10.1155/2013/650984 · Cited by 135 · see citing works
(ANS), E. P. O. F. A. A. N. S. A. T. F. (2015) · EFSA Journal · doi:10.2903/j.efsa.2015.4246 · Cited by 130 · see citing works
Nakatsu, C. H., Armstrong, A. P., Clavijo, A. P., Martin, B. R., Barnes, S., & Weaver, C. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108924 · Cited by 129 · see citing works
Isolation and Characterization of a Novel Equol-Producing Bacterium from Human Feces
Yokoyama, S., & Suzuki, T. (2008) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.80329 · Cited by 128 · see citing works
Toi, M., Hirota, S., Tomotaki, A., Sato, N., Hozumi, Y., Anan, K., Nagashima, T., Tokuda, Y., Masuda, N., Ohsumi, S., et al. (2013) · Current Nutrition & Food Science · doi:10.2174/15734013113099990001 · Cited by 127 · see citing works
Clavel, T., Lepage, P., & Charrier, C. (2014) · Springer eBooks · doi:10.1007/978-3-642-30138-4_343 · Cited by 126 · see citing works
Methods of analysis and separation of chiral flavonoids
Yáñez, J. A., Andrews, P. K., & Davies, N. M. (2006) · Journal of Chromatography B · doi:10.1016/j.jchromb.2006.10.052 · Cited by 126 · see citing works
Galea, G. L., Meakin, L. B., Sugiyama, T., Zebda, N., Sunters, A., Taipaleenmäki, H., Stein, G. S., van Wijnen, A. J., Lanyon, L. E., & Price, J. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.405456 · Cited by 124 · see citing works
Schröder, C., Matthies, A., Engst, W., Blaut, M., & Braune, A. (2013) · Applied and Environmental Microbiology · doi:10.1128/aem.03693-12 · Cited by 124 · see citing works
Kurahashi, N., Iwasaki, M., Inoue, M., Sasazuki, S., & Tsugane, S. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.8807 · Cited by 119 · see citing works
Dietary Phenolic Compounds: Their Health Benefits and Association with the Gut Microbiota
Matsumura, Y., Kitabatake, M., Kayano, S.-I., & Ito, T. (2023) · Antioxidants · doi:10.3390/antiox12040880 · Cited by 123 · see citing works
PRASAIN, J. K., & Barnes, S. (2007) · Molecular Pharmaceutics · doi:10.1021/mp700116u · Cited by 114 · see citing works
A review of the role of estrogen in dermal aging and facial attractiveness in women
Lephart, E. D. (2018) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.12508 · Cited by 114 · see citing works
Microbiota and cancer: host cellular mechanisms activated by gut microbial metabolites
Tsvetikova, S. A., & Koshel, E. I. (2020) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2020.151425 · Cited by 111 · see citing works
Setchell, K. D. R., Brown, N. M., Zhao, X., Galandi, S. L., Heubi, J. E., King, E. C., & Messina, M. J. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.019638 · Cited by 110 · see citing works
Cho, K. W., Lee, O., Banz, W. J., Moustaïd‐Moussa, N., Shay, N. F., & Kim, Y. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2009.06.012 · Cited by 107 · see citing works
Kenny, R. A., Mangano, K. M., Abourizk, R. H., Bruno, R. S., Anamani, D. E., Kleppinger, A., Walsh, S. J., Prestwood, K. M., & Kerstetter, J. E. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27600 · Cited by 106 · see citing works
Improving natural product research translation: From source to clinical trial
Sorkin, B. C., Kuszak, A. J., Bloss, G., Fukagawa, N. K., Hoffman, F. A., Jafari, M., Barrett, B. P., Brown, P. N., Bushman, F. D., Casper, S. J., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201902143r · Cited by 104 · see citing works
Kumari, N., KUMARI, R. R., Dua, A., Singh, M., Kumar, R., Singh, P., Duyar‐Ayerdi, S., Pradeep, S., Ojesina, A. I., & Kumar, R. (2024) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202300688 · Cited by 113 · see citing works
Isoflavone supplements containing predominantly genistein reduce hot flash symptoms
Williamson-Hughes, P. S., Flickinger, B. D., Messina, M. J., & Empie, M. W. (2006) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000227330.49081.9e · Cited by 105 · see citing works
Cognitive Effects of Soy Isoflavones in Patients with Alzheimer’s Disease
Gleason, C. E., Fischer, B. L., Dowling, N. M., Setchell, K. D. R., Atwood, C., Carlsson, C. M., & Asthana, S. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142958 · Cited by 100 · see citing works
Steinshamn, H., Purup, S., Thuen, E., & Hansen-Møller, J. (2008) · Journal of Dairy Science · doi:10.3168/jds.2007-0857 · Cited by 99 · see citing works
Setchell, K. D. R., Zhao, X., Jha, P., Heubi, J. E., & Brown, N. M. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27981 · Cited by 95 · see citing works
Pawlowski, J. W., Martin, B. R., McCabe, G. P., McCabe, L. D., Jackson, G. S., Peacock, M., Barnes, S., & Weaver, C. M. (2015) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.114.093906 · Cited by 91 · see citing works
Jin, J., Nishihata, T., Kakiuchi, N., & Hattori, M. (2008) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.31.1621 · Cited by 88 · see citing works
Toma, L., Sanda, G. M., Niculescu, L. S., Deleanu, M., Sima, A. V., & Stancu, C. S. (2020) · Biomolecules · doi:10.3390/biom10040641 · Cited by 87 · see citing works
Estrogenic flavonoids and their molecular mechanisms of action
Kiyama, R. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109250 · Cited by 82 · see citing works
Rowlands, D. J., Chapple, S. J., Siow, R. C. M., & Mann, G. E. (2011) · Hypertension · doi:10.1161/hypertensionaha.110.162198 · Cited by 82 · see citing works
Effect of Bifidobacterium on osteoclasts: TNF-α/NF-κB inflammatory signal pathway-mediated mechanism
Wu, Y., Yang, Y., Wang, L., Chen, Y., Han, X., Sun, L., Chen, H., & Chen, Q. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1109296 · Cited by 83 · see citing works
Dietary Factors Influence Production of the Soy Isoflavone Metabolite S-(-)Equol in Healthy Adults
Setchell, K. D. R., Brown Nadine, M., Summer, S. S., King Eileen, C., Heubi James, E., Cole, S. J., Trish, G., & Hokin, B. D. (2013) · Journal of Nutrition · doi:10.3945/jn.113.179564 · Cited by 81 · see citing works
Magee, P. J., Allsopp, P. J., Samaletdin, A., & Rowland, I. R. (2013) · European Journal of Nutrition · doi:10.1007/s00394-013-0520-z · Cited by 80 · see citing works
Isolation and characterization of the equol-producing bacterium Slackia sp. strain NATTS
Tsuji, H., Moriyama, K., Nomoto, K., Miyanaga, N., & Akaza, H. (2010) · Archives of Microbiology · doi:10.1007/s00203-010-0546-z · Cited by 78 · see citing works
Anti-obesity molecular mechanism of soy isoflavones: weaving the way to new therapeutic routes
Wang, S., Wang, Y., Pan, M., & Ho, C.-T. (2017) · Food & Function · doi:10.1039/c7fo01094j · Cited by 78 · see citing works
Cavallini, D., Manzoni, M. S. J., Bedani, R., Roselino, M. N., Celiberto, L. S., Vendramini, R. C., de Valdez, G., Abdalla, D. S. P., Pinto, R. A., Rosetto, D., et al. (2016) · Nutrients · doi:10.3390/nu8010052 · Cited by 80 · see citing works
Gopaul, R., Knaggs, H. E., & Lephart, E. D. (2012) · BioFactors · doi:10.1002/biof.191 · Cited by 72 · see citing works
Equol an isoflavonoid: potential for improved prostate health, in vitro and in vivoevidence
Lund, T. D., Blake, C., Bu, L., Hamaker, A., & Lephart, E. D. (2011) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-9-4 · Cited by 73 · see citing works
Jackman, K. A., Woodman, O. L., Chrissobolis, S., & Sobey, C. G. (2007) · Brain Research · doi:10.1016/j.brainres.2007.01.007 · Cited by 71 · see citing works
Niculescu, M. D., POP, E. A., Fischer, L. M., & Zeisel, S. H. (2006) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2006.06.002 · Cited by 71 · see citing works
Liu, B., Qin, L., Liu, A., Uchiyama, S., Ueno, T., Li, X., & Wang, P. (2010) · Journal of Epidemiology · doi:10.2188/jea.je20090185 · Cited by 71 · see citing works
The Pharmacokinetics of S-(-)Equol Administered as SE5-OH Tablets to Healthy Postmenopausal Women ,
Setchell, K. D. R., Zhao, X., Shoaf, S. E., & Ragland, K. (2009) · Journal of Nutrition · doi:10.3945/jn.109.110874 · Cited by 71 · see citing works
Feng, X., Li, Y., Oppong, M. B., & Qiu, F. (2018) · Drug Metabolism Reviews · doi:10.1080/03602532.2018.1485691 · Cited by 71 · see citing works
Regulation of estrogen receptor beta activity and implications in health and disease
Swedenborg, E., Power, K. A., Cai, W., Pongratz, I., & Rüegg, J. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0118-z · Cited by 69 · see citing works
Handayani, R., Rice, L. P., Cui, Y., Medrano, T. A., Samedi, V. G., Baker, H. V., Szabo, N. J., & Shiverick, K. T. (2006) · Journal of Nutrition · doi:10.1093/jn/136.1.75 · Cited by 69 · see citing works
Equol in milk of dairy cows is derived from forage legumes such as red clover
Mustonen, E., Tuori, M., Saastamoinen, I., Taponen, J., Wähälä, K., Saloniemi, H. S., & Vanhatalo, A. (2009) · British Journal Of Nutrition · doi:10.1017/s0007114509990857 · Cited by 68 · see citing works
Jenks, B. H., Iwashita, S., Nakagawa, Y., Ragland, K., Lee, J., Carson, W. H., Ueno, T., & Uchiyama, S. (2012) · Journal of Women s Health · doi:10.1089/jwh.2011.3153 · Cited by 67 · see citing works
Microbiome impact on metabolism and function of sex, thyroid, growth and parathyroid hormones.
Kunc, M., Gabrych, A., & Witkowski, J. M. (2015) · Acta Biochimica Polonica · doi:10.18388/abp.2015_1093 · Cited by 66 · see citing works
A role for estrogen in skin ageing and dermal biomechanics
Wilkinson, H. N., & Hardman, M. J. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111513 · Cited by 71 · see citing works
Isolation and identification of equol-producing bacterial strains from cultures of pig faeces
Yu, Z., Yao, W., & Zhu, W. (2008) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2008.01108.x · Cited by 66 · see citing works
Brown, N. M., Belles, C. A., Lindley, S. L., Zimmer-Nechemias, L., Zhao, X., Witte, D. P., Kim, M., & Setchell, K. D. R. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq025 · Cited by 65 · see citing works
Pop, E. A., Fischer, L. M., Coan, A. D., Gitzinger, M., Nakamura, J., & Zeisel, S. H. (2008) · Menopause · doi:10.1097/gme.0b013e318167b8f2 · Cited by 62 · see citing works
Bioavailability of Dietary Polyphenols and the Cardiovascular Diseases
Shivashankara, K. S., & Acharya, S. N. (2010) · The Open Nutraceuticals Journal · doi:10.2174/1876396001003010227 · Cited by 66 · see citing works
Barnes, S., Benton, H. P., Casazza, K., Cooper, S. J., Cui, X., Du, X., Engler, J. A., Kabarowski, J. H. S., Li, S., Pathmasiri, W., et al. (2016) · Journal of Mass Spectrometry · doi:10.1002/jms.3780 · Cited by 64 · see citing works
The history and basic science development of soy isoflavones
Setchell, K. D. R. (2017) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001018 · Cited by 65 · see citing works
Yamagata, K., & Yamori, Y. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000757 · Cited by 64 · see citing works
Boronat, A., Rodríguez-Morató, J., Serreli, G., Fitó, M., Tyndale, R. F., Deiana, M., & de la Torre, R. (2021) · Advances in Nutrition · doi:10.1093/advances/nmab085 · Cited by 65 · see citing works
Magee, P. J., Raschke, M., Steiner, C., Duffin, J. G., Pool-Zobel, B. L., Jokela, T., Wähälä, K., & Rowland, I. R. (2006) · Nutrition and Cancer · doi:10.1207/s15327914nc5402_10 · Cited by 61 · see citing works
Yao, J., Zhao, L.-Q., Mao, Z.-S., Chen, S.-H., Wong, K., To, J., & Brinton, R. (2013) · Brain Research · doi:10.1016/j.brainres.2013.02.021 · Cited by 61 · see citing works
The Use of Metabolising Systems for In Vitro Testing of Endocrine Disruptors
Jacobs, M. N., Janssens, W., Bernauer, U., Brandon, E. F. A., Coecke, S., Combes, R. D., Edwards, P. M., Freidig, A. P., Freyberger, A., Kolanczyk, R. C., et al. (2008) · Current Drug Metabolism · doi:10.2174/138920008786049294 · Cited by 61 · see citing works
Nutritional Genomics, Polyphenols, Diets, and Their Impact on Dietetics
Barnes, S. (2008) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2008.08.014 · Cited by 60 · see citing works
Insights into the Role of Estrogen Receptor β in Triple-Negative Breast Cancer
Sellitto, A., D’Agostino, Y., Alexandrova, E., Lamberti, J., Pecoraro, G., Memoli, D., Rocco, D., Coviello, E., Giurato, G., Nassa, G., et al. (2020) · Cancers · doi:10.3390/cancers12061477 · Cited by 60 · see citing works
Polyphenols in Farm Animals: Source of Reproductive Gain or Waste?
Hashem, N. M., Gonzalez‐Bulnes, A., & Simal‐Gándara, J. (2020) · Antioxidants · doi:10.3390/antiox9101023 · Cited by 60 · see citing works
Metabolism of Daidzein and Genistein by Gut Bacteria of the Class Coriobacteriia
Soukup, S. T., Stoll, D., Danylec, N., Schoepf, A., Kulling, S. E., & Huch, M. (2021) · Foods · doi:10.3390/foods10112741 · Cited by 60 · see citing works
Gou, Z., Jiang, S., Zheng, C., Tian, Z., & Lin, X. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000430124 · Cited by 59 · see citing works
Estrogen receptor signaling protects against immune suppression by UV radiation exposure
Widyarini, S., Domanski, D., Painter, N., & Reeve, V. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603642103 · Cited by 58 · see citing works
Effects of Isoflavones on the Skin of Postmenopausal Women: A Pilot Study
Neto, A. C. A., Haidar, M. A., Simões, R. S., Simões, M. D. J., Soares, J. M., & Baracat, E. C. (2009) · Clinics · doi:10.1590/s1807-59322009000600004 · Cited by 58 · see citing works
Mattison, D. R., Karyakina, N. A., Goodman, M. G., & LaKind, J. S. (2014) · Critical Reviews in Toxicology · doi:10.3109/10408444.2014.930813 · Cited by 57 · see citing works
- 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 › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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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