Emerging evidence of the health benefits of S-equol, an estrogen receptor β agonist

Nutrition Reviews

Volumn 69, Issue 8, 2011, Pages 432-448

  Jackson, Richard L ^a   Greiwe, Jeffrey S ^a   Schwen, Richard J ^a  

^a Ausio Pharmaceuticals LLC   (United States)

Author keywords

Daidzein; Estrogen receptor ; S equol; Soy isoflavones

Indexed keywords

1,3,5 TRIS 4HYDROXYPHENYL 4PROPYL 1H PYRAZOLE; 3,4 DIHYDRO 3 (4 HYDROXYPHENYL) 2H 1 BENZOPYRAN 7 OL; ANTIBIOTIC AGENT; ANTINEOPLASTIC AGENT; ANTIOXIDANT; BENZOPYRAN DERIVATIVE; C REACTIVE PROTEIN; DAIDZEIN; DIARYLPROPIONITRILE; EFFISOY; ESTRADIOL; ESTRADIOL BENZOATE; ESTRADIOL CIPIONATE; ESTROGEN; ESTROGEN RECEPTOR BETA; FLUORENONE DERIVATIVE; GONADORELIN; ISOFLAVONE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MENERBA; MF 101; NALOXONE; OPIATE; PHYTOESTROGEN; PRINABEREL; RECEPTOR BLOCKING AGENT; S EQUOL; SOYASAPOGENOL A; TETRAHYDROFLUORENONE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; BACTERIAL STRAIN; BIOTRANSFORMATION; BLOOD LEVEL; BONE DENSITY; CANCER INHIBITION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHEMICAL STRUCTURE; CLINICAL TRIAL (TOPIC); DRUG BLOOD LEVEL; DRUG MEGADOSE; DRUG RECEPTOR BINDING; DRUG STRUCTURE; ESTROGEN THERAPY; GENE EXPRESSION PROFILING; HOT FLUSH; HUMAN; INTESTINE FLORA; ISCHEMIC HEART DISEASE; NEOPLASM; NONHUMAN; OSTEOPOROSIS; POSTMENOPAUSE; PROSTATE CANCER; PROSTATE HYPERTROPHY; SINGLE DRUG DOSE; VASOMOTOR DISORDER;

BIOLOGICAL MARKERS; BIOTRANSFORMATION; C-REACTIVE PROTEIN; CARDIOVASCULAR DISEASES; EQUOL; ESTROGEN RECEPTOR BETA; FEMALE; HUMANS; INTESTINES; ISOFLAVONES; LIPOPROTEINS, LDL; MALE; OSTEOPOROSIS; PHYTOESTROGENS; PROSTATIC NEOPLASMS; RISK FACTORS;

BACTERIA (MICROORGANISMS); GLYCINE MAX;

EID: 79960722812     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1111/j.1753-4887.2011.00400.x     Document Type: Article

References (116)

1. Yamori Y. Food factors for atherosclerosis prevention: Asian perspective derived from analyses of worldwide dietary biomarkers. Exp Clin Cardiol. 2006;11:94-98.
2. Setchell KDR, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite equol - a clue to the effectiveness of soy and its isoflavones. J Nutr. 2002;132:3577-3584.
3. Marrian GF, Haslewood GA. Equol, a new inactive phenol isolated from the ketohydroxyoestrin fraction of mares' urine. Biochem J. 1932;26:1227-1232.
4. Marrian GF, Beall D. The constitution of equol. Biochem J. 1935;29:1586-1589.
5. Axelson M, Kirk DN, Farrant RD, Cooley G, Lawson AM, Setchell KDR. The identification of the weak oestrogen equol [7-hydroxy-3-(4'-hydroxyphenyl)chroman] in human urine. Biochem J. 1982;201:353-357.
6. Setchell KDR, Clerici C, Lephart ED, etal. 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. Am J Clin Nutr. 2005;81:1072-1079.
7. Axelson M, Sjövall J, Gustafsson BE, Setchell KDR. Soya - a dietary source of the non-steroidal oestrogen equol in man and animals. J Endocr. 1984;102:49-56.
8. Setchell KDR, Borriello SP, Hulme P, Kirk DN, Axelson M. Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr. 1984;40:569-578.
9. Axelson M, Setchell KDR. The excretion of lignans in rats - evidence for an intestinal bacterial source for this new group of compounds. FEBS Lett. 1981;123:337-342.
10. Atkinson C, Berman S, Humbert O, Lampe JW. In vitro incubation of human feces with daidzein and antibiotics suggests interindividual differences in the bacteria responsible for equol production. J Nutr. 2004;134:596-599.
11. Rafii F, Davis C, Park M, Heinze TM, Beger RD. Variations in metabolism of the soy isoflavonoid daidzein by human intestinal microfloras from different individuals. Arch Microbiol. 2003;180:11-16.
12. Hur HG, Lay JO Jr, Beger RD, Freeman JP, Rafii F. Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin. Arch Microbiol. 2000;174:422-428.
13. Tamura M, Tsushida T, Shinohara K. Isolation of an isoflavone-metabolizing, Clostridium-like bacterium, strain TM-40, from human faeces. Anaerobe. 2007;13:32-35.
14. Maruo T, Sakamoto M, Ito C, Toda T, Benno Y. Adlercreutzia equolifaciens gen. nov., sp. nov., an equol-producing bacterium isolated from human faeces, and emended description of the genus Eggerthella. Int J Syst Evol Microbiol. 2008;58:1221-1227.
15. Wang XL, Hur HG, Lee JH, Kim KT, Kim SI. Enantioselective synthesis of S-equol from dihydrodaidzein by a newly isolated anaerobic human intestinal bacterium. Appl Environ Microbiol. 2005;71:214-219.
16. Wang XL, Kim HK, Kang SI, Kim SI, Hur HG. Prodution of phytoestrogen S-equol from daidzein in mixed culture of two anaerobic bacteria. Arch Microbiol. 2007;187:155-160.
17. Kim M, Kim SI, Han J, Wang XL, Song DG, Kim SU. Stereospecific biotransformation of dihydrodaidzein into (3S)-equol by the human intestinal bacterium Eggerthella strain Julong 732. Appl Environ Microbiol. 2009;75:3062-3068.
18. Uchiyama S, Ueno T, Suzuki T. Identification of a newly isolated equol-producing lactic acid bacterium from the human feces. J Intestinal Microbiol. 2007;21:217-220.
19. Ishiwata N, Melby MK, Mizuno S, Watanabe S. New equol supplement for relieving menopausal symptoms: randomized, placebo-controlled trial of Japanese women. Menopause. 2009;16:141-148.
20. Fujimoto K, Tanaka M, Hirao Y, etal. Age-stratified serum levels of isoflavones and proportion of equol producers in Japanese and Korean healthy men. Prostate Cancer Prostatic Dis. 2008;11:252-257.
21. Morton MS, Arisaka O, Miyake N, Morgan LD, Evans BA. Phytoestrogen concentrations in serum from Japanese men and women over forty years of age. J Nutr. 2002;132:3168-3171.
22. Lampe JW, Karr SC, Hutchins AM, Slavin JL. Urinary equol excretion with a soy challenge: influence of habitual diet. Proc Soc Exp Biol Med. 1998;217:335-339.
23. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006;55:1-12.
24. Adlercreutz H, Fotsis T, Heikkinen R, etal. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet. 1982;2:1295-1299.
25. Setchell KDR, Cole SJ. Method of defining equol-producer status and its frequency among vegetarians. J Nutr. 2006;136:2188-2193.
26. Atkinson C, Newton KM, Bowles EJ, Yong M, Lampe JW. Demographic, anthropometric, and lifestyle factors and dietary intakes in relation to daidzein-metabolizing phenotypes among premenopausal women in the United States. Am J Clin Nutr. 2008;87:679-687.
27. Gardana C, Canzi E, Simonetti P. The role of diet in the metabolism of daidzein by human faecal microbiota sampled from Italian volunteers. J Nutr Biochem. 2008;20:940-947.
28. Védrine N, Mathey J, Morand C, etal. One-month exposure to soy isoflavones did not induce the ability to produce equol in postmenopausal women. Eur J Clin Nutr. 2006;60:1039-1045.
29. Mathey J, Lamothe V, Coxam V, Potier M, Sauvant P, Bennetau-Pelissero C. Concentrations of isoflavones in plasma and urine of post-menopausal women chronically ingesting high quantities of soy isoflavones. J Pharm Biomed Anal. 2006;41:957-965.
30. Clavel T, Fallani M, Lepage P, etal. Isoflavones and functional foods alter the dominant intestinal microbiota in postmenopausal women. J Nutr. 2005;135:2786-2792.
31. Possemiers S, Bolca S, Eeckhaut E, Depypere H, Verstraete W. Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community. FEMS Microbiol Ecol. 2007;61:372-383.
32. Hoey L, Rowland IR, Lloyd AS, Clarke DB, Wiseman H. Influence of soya-based infant formula consumption on isoflavone and gut microflora metabolite concentrations in urine and on faecal microflora composition and metabolic activity in infants and children. Br J Nutr. 2004;91:607-616.
33. Atkinson C, Frankenfeld CL, Lampe JW. Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp Biol Med. 2005;230:155-170.
34. Lampe JW. Emerging research on equol and cancer. J Nutr. 2010;140:S1369-S1372.
35. Zhao L, Brinton RD. WHI and WHIMS follow-up and human studies of soy isoflavones on cognition. Expert Rev Neurother. 2007;7:1549-1564.
36. Cederroth CR, Nef S. Soy, phytoestrogens and metabolism: a review. Mol Cell Endocrinol. 2009;304:30-42.
37. Kronenberg F. Menopausal hot flashes: a review of physiology and biosociocultural perspective on methods of assessment. J Nutr. 2010;140:S1380-S1385.
38. Freedman RR. Physiology of hot flashes. Am J Hum Biol. 2001;13:453-464.
39. Rossouw JE, Anderson GL, Prentice RL, etal. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.
40. Bolaños R, Del Castillo A, Francia J. Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis. Menopause. 2010;17:660-666.
41. Jacobs A, Wegewitz U, Sommerfeld C, Grossklaus R, Lampen A. Efficacy of isoflavones in relieving vasomotor menopausal symptoms - a systematic review. Mol Nutr Food Res. 2009;53:1084-1097.
42. Tempfer CB, Bentz EK, Leodolter S, etal. Phyto-estrogens in clinical practice: a review of the literature. Fertil Steril. 2007;87:1243-1249.
43. Khaodhiar L, Ricciotti HA, Linglin L, etal. Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women. Menopause. 2008;15:125-132.
44. Jou HJ, Wu SC, Chang FW, Ling PY, Chu KS, Wu WH. Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynecol Obstet. 2008;102:44-49.
45. Thompson MA, Lasley BL, Rideout BA, Kasman LH. Characterization of the estrogenic properties of a nonsteroidal estrogen, equol, extracted from urine of pregnant macaques. Biol Reprod. 1984;31:705-713.
46. Morito K, Hirose T, Kinjo J, etal. Interaction of phytoestrogens with estrogen receptors α and β. Biol Pharm Bull. 2001;24:351-356.
47. Mueller SO, Simon S, Chae K, Metzler M, Korach KS. Phytoestrogens and their human metabolites show distinct agonistic and antagonistic properties on estrogen receptor α (ERα) and ERβ in human cells. Toxicol Sci. 2004;80:14-25.
48. Muthyala RS, Ju YH, Sheng S, etal. Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem. 2004;12:1559-1567.
49. Malamas MS, Manas ES, McDevitt RE, etal. Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-β ligands. J Med Chem. 2004;47:5021-5040.
50. Opas EE, Gentile MA, Kimmel DB, Rodan GA, Schmidt A. Estrogenic control of thermoregulation in ERαKO and ERβKO mice. Maturitas. 2006;53:210-216.
51. Opas EE, Scafonas A, Nantermet PV, etal. Control of rat tail skin temperature regulation by estrogen receptor-beta selective ligand. Maturitas. 2009;64:46-51.
52. Grady D, Sawaya GF, Johnson KC, etal. MF101, a selective estrogen receptor β modulator for the treatment of menopausal hot flushes: a phase II clinical trial. Menopause. 2009;16:458-465.
53. Paruthiyil S, Cvoro A, Zhao X, etal. Drug and cell type-specific regulation of genes with different classes of estrogen receptor β-selective agonists. PLoS One. 2009;4:1-14.
54. Meyers MJ, Sun J, Carlson KE, Marriner GA, Katzenellenbogen BS. Estrogen receptor-β potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J Med Chem. 2001;44:4230-4251.
55. Niculescu MD, Pop EA, Fischer LM, Zeisel SH. Dietary isoflavones differentially induce gene expression changes in lymphocytes from postmenopausal women who form equol as compared with those who do not. J Nutr Biochem. 2007;18:380-390.
56. Poulsen RC, Kruger MC. Soy phytoestrogens: impact on postmenopausal bone loss and mechanisms of action. Nutr Rev. 2008;66:359-374.
57. Vatanparast H, Chilibeck PD. Does the effect of soy phyto-estrogens on bone in postmenopausal women depend on the equol-producing phenotype? Nutr Rev. 2007;65:294-299.
58. Taku K, Melby MK, Kurzer MS, Mizuno S, Watanabe S, Ishimi Y. Effects of soy isoflavone supplements on bone turnover markers in menopausal women: systematic review and meta-analysis of randomized controlled trials. Bone. 2010;47:413-423.
59. Weaver CM, Legette LL. Equol, via dietary sources or intestinal production, may ameliorate estrogen deficiency-induced bone loss. J Nutr. 2010;140:S1377-S1379.
60. Ishimi Y. Dietary equol and bone metabolism in postmenopausal Japanese women and osteoporotic mice. J Nutr. 2010;140:S1373-S1376.
61. Zhang X, Shu XO, Li H, etal. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med. 2005;165:1890-1895.
62. Kreijkamp-Kaspers S, Kok L, Grobbee DE, etal. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. JAMA. 2004;292:65-74.
63. Lydeking-Olsen E, Beck-Jensen JE, Setchell KDR, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss. Eur J Nutr. 2004;43:246-257.
64. Wu J, Oka J, Higuchi M, etal. Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metabolism. 2006;55:423-433.
65. Wu J, Oka J, Ezaki J, etal. Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women: a double-blind, randomized, controlled trial. Menopause. 2007;14:1-9.
66. Kenny AM, Mangano KM, Abourizk RH, etal. Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Am J Clin Nutr. 2009;90:234-242.
67. Braidman IP, Hainey L, Batra G, Selby PL, Saunders PTK, Hoyland JA. Localization of estrogen receptor β protein expression in adult human bone. J Bone Miner Res. 2001;16:214-220.
68. Yu-Yahiro J, Ruff C, Parks B, etal. Effects of a new compound on mechanical properties of the femur and vertebrae in the rat model. Paper presented at the American Society for Bone and Mineral Research 31st Annual Meeting, Denver, CO, September 15-19, 2009.
69. Yan L, Spitznagel EL. Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr. 2009;89:1155-1163.
70. Travis RC, Spencer EA, Allen NE, etal. Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer. 2009;100:1817-1823.
71. Ward H, Chapelais G, Kuhnle GG, Luben R, Khaw KT, Bingham S. Lack of prospective associations between plasma and urinary phytoestrogens and risk of prostate or colorectal cancer in the European Prospective into Cancer - Norfolk study. Cancer Epidemiol Biomarkers Prev. 2008;17:2891-2894.
72. Park SY, Wilkens LR, Franke AA, etal. Urinary phytoestrogen excretion and prostate cancer risk: a nested case-control study in the Multiethnic Cohort. Br J Cancer. 2009;101:185-191.
73. Akaza H, Miyanaga N, Takashima N, etal. Is daidzein non-metabolizer a high risk for prostate cancer? A case-controlled study of serum soybean isoflavone concentration. Jpn J Clin Oncol. 2002;32:296-300.
74. Akaza H, Miyanaga N, Takashima N, etal. Comparisons of percent equol producers between prostate cancer patients and controls: case-controlled studies of isoflavones in Japanese, Korean and American residents. Jpn J Clin Oncol. 2004;34:86-89.
75. Ozasa K, Nakao M, Watanabe Y, etal. Serum phyto-estrogens and prostate cancer risk in a nested case-control study among Japanese men. Cancer Sci. 2004;95:65-71.
76. Kurahashi N, Iwasaki M, Inoue M, Sasazuki S, Tsugane S. Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center. J Clin Oncol. 2008;26:5923-5929.
77. Magee PJ, Raschke M, Steiner C, etal. Equol: a comparison of the effects of the racemic compound with that of the purified S-enantiomer on the growth, invasion, and DNA integrity of breast and prostate cells in vitro. Nutr Cancer. 2006;54:232-242.
78. Hedlund TE, Van Bokhoven A, Johannes WU, Nordeen SK, Ogden LG. Prostatic fluid concentrations of isoflavonoids in soy consumers are sufficient to inhibit growth of benign and malignant prostatic epithelial cells in vitro. Prostate. 2006;66:557-566.
79. Hedlund TE, Johannes WU, Miller GJ. Soy isoflavonoid equol modulates the growth of benign and malignant prostatic epithelial cells in vitro. Prostate. 2003;54:68-78.
80. Lund TD, Munson DJ, Adlercreutz H, Handa RJ, Lephart ED. Androgen receptor expression in the rat prostate is down-regulated by diet phyto-estrogens. Reprod Biol Endocrinol. 2004;2:1-5.
81. Hamilton-Reeves JM, Rebello SA, Thomas W, Slaton JW, Kurzer MS. Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-β expression or serum hormonal profiles in men at high risk of prostate cancer. J Nutr. 2007;137:1769-1775.
82. Norman BH, Dodge JA, Richardson TI, etal. Benzopyrnas are selective estrogen receptor β agonists with novel activity in models of benign prostatic hyperplasia. J Med Chem. 2006;49:6155-6157.
83. McPherson SJ, Ellem SJ, Simpson ER, Patchev V, Fritzemeier KH, Risbridger GP. Essential role for estrogen receptor beta in stromal-epithelial regulation of prostatic hyperplasia. Endocrinology. 2007;148:566-574.
84. Yamori Y. Cardiac study and dietary intervention study. In: Sugnao M, ed. Soy in Health and Disease Prevention. Boca Raton, FL: CRC Press; 2007:107-119.
85. Jackman KA, Woodman OL, Sobey CG. Isoflavones, equol and cardiovascular disease: pharmacological and therapeutic insights. Curr Med Chem. 2007;14:2824-2830.
86. Thorp AA, Howe PR, Mori TA, etal. Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers. Am J Clin Nutr. 2008;88:298-304.
87. Liu B, Qin L, Liu A, etal. Prevalence of the equol-producer phenotype and its relationship with dietary isoflavone and serum lipids in healthy Chinese adults. J Epidemiol. 2010;20:377-384.
88. Hall WL, Vafeiadou K, Hallund J, etal. Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr. 2005;82:1260-1268.
89. Clerici C, Setchell KD, Battezzati PM, etal. Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk. J Nutr. 2007;137:2270-2278.
90. Rüfer CE, Kulling SE. Antioxidant activity of isoflavones and their major metabolites using different in vitro assays. J Agric Food Chem. 2006;54:2926-2931.
91. Hwang J, Sevanian A, Hodis HN, Ursini F. Synergistic inhibition of LDL oxidation by phyto-estrogens and ascorbic acid. Free Radic Biol Med. 2000;29:79-89.
92. Hwang J, Wang J, Morazzoni P, Hodis HN, Sevanian A. The phytoestrogen equol increases nitric oxide availability by inhibiting superoxide production: an antioxidant mechanism for cell-mediated LDL modification. Free Radic Biol Med. 2003;34:1271-1282.
93. Kamiyama M, Kishimoto Y, Tani M, Utsunomiya K, Kondo K. Effects of equol on oxidized low-density lipoprotein-induced apoptosis in endothelial cells. J Atheroscler Thromb. 2009;16:239-249.
94. Siow RC, Li FY, Rowlands DJ, de Winter P, Mann GE. Cardiovascular targets for estrogens and phytoestrogens: transcriptional regulation of nitric oxide synthase and antioxidant defense genes. Free Radic Biol Med. 2007;42:909-925.
95. Mann GE, Bonacasa B, Ishii T, Sio RCM. Targeting the redox sensitive Nrf2-Keap 1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones. Curr Opin Pharmacol. 2009;9:139-145.
96. Jackson RL, Greiwe JS, Desai PB, Schwen RJ. Single-dose and steady-state pharmacokinetic studies of S-equol, a potent nonhormonal, estrogen receptor β-agonist being developed for the treatment of menopausal symptoms. Menopause. 2011;18:185-193.
97. Takahashi Y, Lavigne JA, Hursting SD, etal. Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study using DNA microarray. Mol Carcinog. 2006;45:943-956.
98. Cheng G, Wilczek B, Warner M, Gustafsson JA, Landgren BM. Isoflavone treatment for acute menopausal symptoms. Menopause. 2007;14:468-473.
99. Rossouw JE, Prentice RL, Manson JE, etal. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477.
100. Minamida K, Tanaka M, Abe A, etal. Production of equol from daidzein by gram-positive rod-shaped bacterium isolated from rat intestine. J Biosci Bioeng. 2006;102:247-250.
101. Minamida K, Ota K, Nishimukai M, etal. Asaccharobacter celatus gen. nov., sp. nov., isolated from rat caecum. Int J Syst Evol Microbiol. 2008;58:1238-1240.
102. Yu ZT, Yao W, Zhu WY. Isolation and identification of equol-producing bacterial strains from cultures of pig faeces. FEMS Microbiol Lett. 2008;282:73-80.
103. Wang XL, Shin KH, Hur HG, Kim SI. Enhanced biosynthesis of dihydrodaidzein and dihydrogenistein by a newly isolated bovine rumen anaerobic bacterium. J Biotechnol. 2005;115:261-269.
104. Rafii F, Hotchkiss C, Heinze TM, Park M. Metabolism of daidzein by intestinal bacteria from rhesus monkeys (Macaca mulatta). Comp Med. 2004;54:165-169.
105. Matthies A, Clavel T, Gütschow M, Engst W, Haller D, Blaut M. Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Appl Environ Microbiol. 2008;74:4847-4852.
106. Yokoyama S, Suzuki T. Isolation and characterization of a novel equol-producing bacterium from human feces. Biosci Biotechnol Biochem. 2008;72:2660-2666.
107. Matthies A, Blaut M, Braune A. Isolation of a human intestinal bacterium capable of daidzein and genistein conversion. Appl Environ Microbiol. 2009;75:1740-1744.
108. Jin JS, Nishihata T, Kakiuchi N, Hattori M. Biotransformation of C-glucosylisoflavone purerarin to estrogenic (3S)-equol in co-culture of two human intestinal bacteria. Biol Pharm Bull. 2008;31:1621-1650.
109. Jin JS, Kitahara M, Sakamoto M, Hattori M, Benno Y. Slackia equolifaciens sp. nov., a human intestinal bacterium capable of producing equol. Int J Syst Evol Microbiol. 2010;60:1721-1740.
110. Tsuji H, Moriyama K, Nomoto K, Miyanaga N, Akaza H. Isolation and characterization of the equol-producing bacterium Slackia sp. strain NATTS. Arch Microbiol. 2010;192:279-287.
111. Uchiyama S, Ueno T, Kumenura M, Imaizumi K, Masaki K, Shimizu S. Streptococcus and isoflavone-containing composition. US patent 6, 716, 424 B1. 2004.
112. Decroos K, Vanhemmens S, Cattoir S, Boon N, Verstraete W. Isolation and characterization of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions. Arch Microbiol. 2005;183:45-55.
113. Decroos K, Eeckhaut E, Possemiers S, Verstraete W. Administration of equol-producing bacteria alters the equol production status in the simulator of the gastrointestinal microbial ecosystem (SHIME). J Nutr. 2006;136:946-952.
114. Uesugi S, Watanabe S, Ishiwata N, Uehara M, Ouchi K. Effects of isoflavone supplements on bone metabolic markers and climacteric symptoms in Japanese women. Biofactors. 2004;22:221-228.
115. Murkies AL, Lombard C, Strauss BJG, Wilcox G, Burger HG, Morton MS. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas. 1995;21:189-195.
116. Setchell KDR, Zhao X, Shoaf SE, Ragland K. The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausal women. J Nutr. 2009;139:2037-2043.