Does Equol production determine soy endocrine effects?

European Journal of Nutrition

Volumn 51, Issue 4, 2012, Pages 389-398

  Shor, Dana ^a   Sathyapalan, Thozhukat ^a   Atkin, Stephen L ^a   Thatcher, Natalie J ^b,c  

^a UNIVERSITY OF HULL   (United Kingdom)

^b Michael White Diabetes Centre   (United Kingdom)

^c FOOD STANDARDS AGENCY   (United Kingdom)

Author keywords

Breast cancer; Cardiovascular disease; Equol; Isoflavone; Osteoporosis; Phytoestrogen; Soy

Indexed keywords

AGLYCONE; ANDROGEN RECEPTOR; ANDROSTANOLONE; CHOLESTEROL; COUMESTAN DERIVATIVE; DAIDZEIN; EQUOL; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR BETA; GENISTEIN; GLUCOSIDE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; ISOFLAVONE DERIVATIVE; LIGNAN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PHYTOESTROGEN; SEX HORMONE BINDING GLOBULIN; STILBENE DERIVATIVE; UNCLASSIFIED DRUG;

AGE DISTRIBUTION; ANDROPAUSE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ANXIETY DISORDER; ASIAN; BINDING AFFINITY; BIOTRANSFORMATION; BLOOD LEVEL; BONE DENSITY; BONE REMODELING; BREAST CANCER; CANCER STAGING; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CHOLESTEROL BLOOD LEVEL; DEPRESSION; DIET SUPPLEMENTATION; EARLY CANCER; ENDOCRINE DISEASE; FOOD INTAKE; GENE OVEREXPRESSION; GENOTOXICITY; HEART PROTECTION; HIGH RISK PATIENT; HORMONAL REGULATION; HORMONE SUBSTITUTION; HOT FLUSH; HUMAN; HYPERCHOLESTEROLEMIA; JOINT STIFFNESS; LACTOCOCCUS; LIFESTYLE; MAMMOGRAPHY; MENOPAUSE; NONHUMAN; OSTEOPOROSIS; POSTMENOPAUSE OSTEOPOROSIS; PREMENOPAUSE; PROSTATE CANCER; RECEPTOR BINDING; REVIEW; RISK BENEFIT ANALYSIS; RISK FACTOR; RISK REDUCTION; SOYBEAN; URINE LEVEL; VASODILATATION; VASOMOTOR DISORDER; VEGETARIAN;

ANIMALS; DIETARY SUPPLEMENTS; ENDOCRINE SYSTEM DISEASES; EQUOL; FEMALE; FUNCTIONAL FOOD; HUMANS; ISOFLAVONES; MALE; PHYTOESTROGENS; SOY FOODS;

EID: 84864721538     PISSN: 14366207     EISSN: 14366215     Source Type: Journal    
DOI: 10.1007/s00394-012-0331-7     Document Type: Review

References (132)

1. Yamori Y (2006) Food factors for atherosclerosis prevention: Asian perspective derived from analyses of worldwide dietary biomarkers. Exp Clin Cardiol 11:94-98 (Pubitemid 44018286)
2. Cornwell T, Cohick W, Raskin I (2004) Dietary phytoestrogens and health. Phytochemistry 65:995-1016 (Pubitemid 38542736)
3. Cassidy A, Albertazzi P, Lise Nielsen I, Hall W, Williamson G, Tetens I, Atkins S, Cross H, Manios Y, Wolk A et al (2006) Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women. Proc Nutr Soc 65:76-92 (Pubitemid 43259987)
4. Setchell KD, Brown NM, Lydeking-Olsen E (2002) The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. J Nutr 132:3577-3584 (Pubitemid 35435031)
5. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139:4252-4263 (Pubitemid 28513713)
6. Izumi T, Piskula MK, Osawa S, Obata A, Tobe K, Saito M, Kataoka S, Kubota Y, Kikuchi M (2000) Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. J Nutr 130:1695-1699 (Pubitemid 30451055)
7. Evans BA, Griffiths K, Morton MS (1995) Inhibition of 5 alphareductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol 147:295-302
8. Zava DT, Duwe G (1997) Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutr Cancer 27:31-40 (Pubitemid 26424313)
9. Mitchell JH, Gardner PT, McPhail DB, Morrice PC, Collins AR, Duthie GG (1998) Antioxidant efficacy of phytoestrogens in chemical and biological model systems. Arch Biochem Biophys 360:142-148 (Pubitemid 29010923)
10. Day AJ, Du Pont MS, Ridley S, Rhodes M, Rhodes MJ, Morgan MR, Williamson G (1998) Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver betaglucosidase activity. FEBS Lett 436:71-75 (Pubitemid 28454609)
11. Heinonen S, Wahala K, Adlercreutz H (1999) Identification of isoflavone metabolites dihydrodaidzein, dihydrogenistein, 6'-OH-O-dma, and cis-4-OH-equol in human urine by gas chromatography-mass spectroscopy using authentic reference compounds. Anal Biochem 274:211-219 (Pubitemid 29489491)
12. Chang YC, Nair MG (1995) Metabolism of daidzein and genistein by intestinal bacteria. J Nat Prod 58:1892-1896 (Pubitemid 26071145)
13. Setchell KD, Borriello SP, Hulme P, Kirk DN, Axelson M (1984) Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr 40:569-578 (Pubitemid 14035518)
14. Axelson M, Setchell KD (1981) The excretion of lignans in rats-evidence for an intestinal bacterial source for this new group of compounds. FEBS Lett 123:337-342 (Pubitemid 11148771)
15. Atkinson C, Berman S, Humbert O, Lampe JW (2004) In vitro incubation of human feces with daidzein and antibiotics suggests interindividual differences in the bacteria responsible for equol production. J Nutr 134:596-599 (Pubitemid 38298502)
16. Atkinson C, Frankenfeld CL, Lampe JW (2005) Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp Biol Med (Maywood) 230:155-170 (Pubitemid 40293689)
17. Setchell KD, Clerici C (2010) Equol: history, chemistry, and formation. J Nutr 140:1355S-1362S
18. Setchell KD, Cole SJ (2006) Method of defining equol-producer status and its frequency among vegetarians. J Nutr 136:2188-2193 (Pubitemid 44156823)
19. Song KB, Atkinson C, Frankenfeld CL, Jokela T, Wahala K, Thomas WK, Lampe JW (2006) Prevalence of daidzeinmetabolizing phenotypes differs between Caucasian and Korean American women and girls. J Nutr 136:1347-1351
20. Akaza H, Miyanaga N, Takashima N, Naito S, Hirao Y, Tsukamoto T, Fujioka T, Mori M, Kim WJ, Song JM, Pantuck AJ (2004) 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 34:86-89 (Pubitemid 43115325)
21. Morton MS, Arisaka O, Miyake N, Morgan LD, Evans BA (2002) Phytoestrogen concentrations in serum from Japanese men and women over forty years of age. J Nutr 132:3168-3171
22. Fujimoto K, Tanaka M, Hirao Y, Nagata Y, Mori M, Miyanaga N, Akaza H, Kim WJ (2008) Age-stratified serum levels of isoflavones and proportion of equol producers in Japanese and Korean healthy men. Prostate Cancer Prostatic Dis 11:252-257
23. Atkinson C, Newton KM, Bowles EJ, Yong M, Lampe JW (2008) 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 87:679-687 (Pubitemid 351364550)
24. Hoey L, Rowland IR, Lloyd AS, Clarke DB, Wiseman H (2004) 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 91:607-616 (Pubitemid 38584785)
25. Vedrine N, Mathey J, Morand C, Brandolini M, Davicco MJ, Guy L, Remesy C, Coxam V, Manach C (2006) One-month exposure to soy isoflavones did not induce the ability to produce equol in postmenopausal women. Eur J Clin Nutr 60:1039-1045 (Pubitemid 44340401)
26. Mathey J, Lamothe V, Coxam V, Potier M, Sauvant P, Bennetau-Pelissero C (2006) Concentrations of isoflavones in plasma and urine of post-menopausal women chronically ingesting high quantities of soy isoflavones. J Pharm Biomed Anal 41:957-965
27. Minamida K, Tanaka M, Abe A, Sone T, Tomita F, Hara H, Asano K (2006) Production of equol from daidzein by grampositive rod-shaped bacterium isolated from rat intestine. J Biosci Bioeng 102:247-250 (Pubitemid 44537867)
28. Minamida K, Ota K, Nishimukai M, Tanaka M, Abe A, Sone T, Tomita F, Hara H, Asano K (2008) Asaccharobacter celatus gen. nov., sp. nov., isolated from rat caecum. Int J Syst Evol Microbiol 58:1238-1240
29. Yu ZT, Yao W, Zhu WY (2008) Isolation and identification of equol-producing bacterial strains from cultures of pig faeces. FEMS Microbiol Lett 282:73-80 (Pubitemid 351473561)
30. Wang XL, Shin KH, Hur HG, Kim SI (2005) Enhanced biosynthesis of dihydrodaidzein and dihydrogenistein by a newly isolated bovine rumen anaerobic bacterium. J Biotechnol 115:261-269
31. Rafii F, Hotchkiss C, Heinze TM, Park M (2004) Metabolism of daidzein by intestinal bacteria from rhesus monkeys (Macaca mulatta). Comp Med 54:165-169 (Pubitemid 38590831)
32. Matthies A, Clavel T, Gutschow M, Engst W, Haller D, Blaut M, Braune A (2008) Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Appl Environ Microbiol 74:4847-4852
33. Jin JS, Nishihata T, Kakiuchi N, Hattori M (2008) Biotransformation of C-glucosylisoflavone puerarin to estrogenic (3S) - equol in co-culture of two human intestinal bacteria. Biol Pharm Bull 31:1621-1625
34. Hur HG, Lay JO Jr, Beger RD, Freeman JP, Rafii F (2000) Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin. Arch Microbiol 174:422-428 (Pubitemid 32001683)
35. Tamura M, Tsushida T, Shinohara K (2007) Isolation of an isoflavone-metabolizing, Clostridium-like bacterium, strain TM-40, from human faeces. Anaerobe 13:32-35 (Pubitemid 46274434)
36. Maruo T, Sakamoto M, Ito C, Toda T, Benno Y (2008) 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 58:1221-1227
37. Wang XL, Kim HJ, Kang SI, Kim SI, Hur HG (2007) Production of phytoestrogen S-equol from daidzein in mixed culture of two anaerobic bacteria. Arch Microbiol 187:155-160
38. Kim M, Kim SI, Han J, Wang XL, Song DG, Kim SU (2009) Stereospecific biotransformation of dihydrodaidzein into (3S) - equol by the human intestinal bacterium Eggerthella strain Julong 732. Appl Environ Microbiol 75:3062-3068
39. Yokoyama S, Suzuki T (2008) Isolation and characterization of a novel equol-producing bacterium from human feces. Biosci Biotechnol Biochem 72:2660-2666
40. Matthies A, Blaut M, Braune A (2009) Isolation of a human intestinal bacterium capable of daidzein and genistein conversion. Appl Environ Microbiol 75:1740-1744
41. Jin JS, Kitahara M, Sakamoto M, Hattori M, Benno Y (2010) Slackia equolifaciens sp. nov., a human intestinal bacterium capable of producing equol. Int J Syst Evol Microbiol 60:1721-1724
42. Tsuji H, Moriyama K, Nomoto K, Miyanaga N, Akaza H (2010) Isolation and characterization of the equol-producing bacterium Slackia sp. strain NATTS. Arch Microbiol 192:279-287
43. Decroos K, Vanhemmens S, Cattoir S, Boon N, Verstraete W (2005) Isolation and characterisation of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions. Arch Microbiol 183:45-55 (Pubitemid 40142881)
44. Decroos K, Eeckhaut E, Possemiers S, Verstraete W (2006) Administration of equol-producing bacteria alters the equol production status in the Simulator of the Gastrointestinal Microbial Ecosystem (SHIME). J Nutr 136:946-952
45. Ishiwata N, Melby MK, Mizuno S, Watanabe S (2009) New equol supplement for relieving menopausal symptoms: randomized, placebo-controlled trial of Japanese women. Menopause 16:141-148
46. Marrian GF, Haslewood GA (1932) Equol, a new inactive phenol isolated from the ketohydroxyoestrin fraction of mares' urine. Biochem J 26:1227-1232
47. Setchell KD, Clerici C, Lephart ED, Cole SJ, Heenan C, Castellani D, Wolfe BE, Nechemias-Zimmer L, Brown NM, Lund TD et al (2005) 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. Am J Clin Nutr 81:1072-1079 (Pubitemid 41724948)
48. Muthyala RS, Ju YH, Sheng S, Williams LD, Doerge DR, Katzenellenbogen BS, Helferich WG, Katzenellenbogen JA (2004) 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 12:1559-1567 (Pubitemid 38304880)
49. Setchell KD, Zhao X, Shoaf SE, Ragland K (2009) The pharmacokinetics of S-(-) equol administered as SE5-OH tablets to healthy postmenopausal women. J Nutr 139:2037-2043
50. Nagel SC, vom Saal FS, Welshons WV (1998) The effective free fraction of estradiol and xenoestrogens in human serum measured by whole cell uptake assays: physiology of delivery modifies estrogenic activity. Proc Soc Exp Biol Med 217:300-309
51. Fanti P, Sawaya BP, Custer LJ, Franke AA (1999) Serum levels and metabolic clearance of the isoflavones genistein and daidzein in hemodialysis patients. J Am Soc Nephrol 10:864-871 (Pubitemid 29149538)
52. Lund TD, Munson DJ, Haldy ME, Setchell KD, Lephart ED, Handa RJ (2004) Equol is a novel anti-androgen that inhibits prostate growth and hormone feedback. Biol Reprod 70:1188-1195 (Pubitemid 38387732)
53. Rimbach G, De Pascual-Teresa S, Ewins BA, Matsugo S, Uchida Y, Minihane AM, Turner R, VafeiAdou K, Weinberg PD (2003) Antioxidant and free radical scavenging activity of isoflavone metabolites. Xenobiotica 33:913-925 (Pubitemid 37255402)
54. Hedlund TE, Johannes WU, Miller GJ (2003) Soy isoflavonoid equol modulates the growth of benign and malignant prostatic epithelial cells in vitro. Prostate 54:68-78 (Pubitemid 36043838)
55. Jackman KA, Woodman OL, Chrissobolis S, Sobey CG (2007) Vasorelaxant and antioxidant activity of the isoflavone metabolite equol in carotid and cerebral arteries. Brain Res 1141:99-107 (Pubitemid 46365641)
56. Blay M, Espinel AE, Delgado MA, Baiges I, Blade C, Arola L, Salvado J (2010) Isoflavone effect on gene expression profile and biomarkers of inflammation. J Pharm Biomed Anal 51:382-390
57. Hall WL, Formanuik NL, Harnpanich D, Cheung M, Talbot D, Chowienczyk PJ, Sanders TA (2008) A meal enriched with soy isoflavones increases nitric oxide-mediated vasodilation in healthy postmenopausal women. J Nutr 138:1288-1292 (Pubitemid 351930991)
58. Chacko BK, Chandler RT, Mundhekar A, Khoo N, Pruitt HM, Kucik DF, Parks DA, Kevil CG, Barnes S, Patel RP (2005) Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions. Am J Physiol Heart Circ Physiol 289:H908-H915 (Pubitemid 41129409)
59. Brink E, Coxam V, Robins S, Wahala K, Cassidy A, Branca F (2008) Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study. Am J Clin Nutr 87:761-770 (Pubitemid 351364559)
60. Verheus M, van Gils CH, Kreijkamp-Kaspers S, Kok L, Peeters PH, Grobbee DE, van der Schouw YT (2008) Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17:2632-2638
61. Hodgson JM, Puddey IB, Beilin LJ, Mori TA, Croft KD (1998) Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. J Nutr 128:728-732 (Pubitemid 28158487)
62. Simons LA, von Konigsmark M, Simons J, Celermajer DS (2000) Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. Am J Cardiol 85:1297-1301 (Pubitemid 30314660)
63. Nikander E, Kilkkinen A, Metsa-Heikkila M, Adlercreutz H, Pietinen P, Tiitinen A, Ylikorkala O (2003) A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstet Gynecol 101:1213-1220 (Pubitemid 36694346)
64. Sehmisch S, Uffenorde J, Maehlmeyer S, Tezval M, Jarry H, Stuermer KM, Stuermer EK (2010) Evaluation of bone quality and quantity in osteoporotic mice-the effects of genistein and equol. Phytomedicine 17:424-430
65. Sehmisch S, Erren M, Kolios L, Tezval M, Seidlova-Wuttke D, Wuttke W, Stuermer KM, Stuermer EK (2010) Effects of isoflavones equol and genistein on bone quality in a rat osteopenia model. Phytother Res 24(Suppl 2):S168-S174
66. Braidman IP, Hainey L, Batra G, Selby PL, Saunders PT, Hoyland JA (2001) Localization of estrogen receptor beta protein expression in adult human bone. J Bone Miner Res 16:214-220 (Pubitemid 32105402)
67. Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH, Manson JE, Stefanick ML, Ockene J, Sarto GE et al (2010) Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 304:1684-1692
68. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T (2000) Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72:844-852 (Pubitemid 30667108)
69. Mei J, Yeung SS, Kung AW (2001) High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 86:5217-5221 (Pubitemid 33070238)
70. Alekel DL, Van Loan MD, Koehler KJ, Hanson LN, Stewart JW, Hanson KB, Kurzer MS, Peterson CT (2010) The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr 91:218-230
71. Wong WW, Lewis RD, Steinberg FM, Murray MJ, Cramer MA, Amato P, Young RL, Barnes S, Ellis KJ, Shypailo RJ et al (2009) Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. Am J Clin Nutr 90:1433-1439
72. Ricci E, Cipriani S, Chiaffarino F, Malvezzi M, Parazzini F (2010) Soy isoflavones and bone mineral density in perimenopausal and postmenopausal Western women: a systematic review and meta-analysis of randomized controlled trials. J Womens Health (Larchmt) 19:1609-1617
73. Wu J, Oka J, Higuchi M, Tabata I, Toda T, Fujioka M, Fuku N, Teramoto T, Okuhira T, Ueno T et al (2006) Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metabolism 55:423-433
74. Wu J, Oka J, Ezaki J, Ohtomo T, Ueno T, Uchiyama S, Toda T, Uehara M, Ishimi Y (2007) 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 14:866-874 (Pubitemid 47517585)
75. Frankenfeld CL, McTiernan A, Thomas WK, La Croix K, McVarish L, Holt VL, Schwartz SM, Lampe JW (2006) Postmenopausal bone mineral density in relation to soy isoflavonemetabolizing phenotypes. Maturitas 53:315-324 (Pubitemid 43163067)
76. Uesugi S, Watanabe S, Ishiwata N, Uehara M, Ouchi K (2004) Effects of isoflavone supplements on bone metabolic markers and climacteric symptoms in Japanese women. BioFactors 22:221-228 (Pubitemid 40921794)
77. Dewell A, Hollenbeck CB, Bruce B (2002) The effects of soyderived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. J Clin Endocrinol Metab 87:118-121 (Pubitemid 34084680)
78. Goodman-Gruen D, Kritz-Silverstein D (2001) Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women. J Nutr 131:1202-1206 (Pubitemid 32275100)
79. Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, Watanabe S (2010) Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: metaanalysis of randomized controlled trials. Asia Pac J Clin Nutr 19:33-42
80. Howes JB, Sullivan D, Lai N, Nestel P, Pomeroy S, West L, Eden JA, Howes LG (2000) The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia. Atherosclerosis 152:143-147
81. Samman S, Lyons Wall PM, Chan GS, Smith SJ, Petocz P (1999) The effect of supplementation with isoflavones on plasma lipids and oxidisability of low density lipoprotein in premenopausal women. Atherosclerosis 147:277-283 (Pubitemid 29512259)
82. Clerici C, Setchell KD, Battezzati PM, Pirro M, Giuliano V, Asciutti S, Castellani D, Nardi E, Sabatino G, Orlandi S et al (2007) Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk. J Nutr 137:2270-2278 (Pubitemid 47529589)
83. Tormala RM, Appt S, Clarkson TB, Tikkanen MJ, Ylikorkala O, Mikkola TS (2007) Individual differences in equol production capability modulate blood pressure in tibolone-treated postmenopausal women: lack of effect of soy supplementation. Climacteric 10:471-479 (Pubitemid 350211298)
84. Hall WL, Vafeiadou K, Hallund J, Bugel S, Reimann M, Koebnick C, Zunft HJ, Ferrari M, Branca F, Dadd T et al (2006) Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr 83:592-600 (Pubitemid 44699204)
85. Thorp AA, Howe PR, Mori TA, Coates AM, Buckley JD, Hodgson J, Mansour J, Meyer BJ (2008) Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers. Am J Clin Nutr 88:298-304
86. Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SR (2003) Phytoestrogen supplements for the treatment of hot flashes: the isoflavone clover extract (ICE) study: a randomized controlled trial. JAMA 290:207-214 (Pubitemid 37430059)
87. Bolanos R, Del Castillo A, Francia J (2010) Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis. Menopause 17:660-666
88. Jou HJ, Wu SC, Chang FW, Ling PY, Chu KS, Wu WH (2008) Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynaecol Obstet 102:44-49
89. Aso T (2010) Equol improves menopausal symptoms in Japanese women. J Nutr 140:1386S-1389S
90. Niculescu MD, Pop EA, Fischer LM, Zeisel SH (2007) 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 18:380-390 (Pubitemid 46727040)
91. Wu AH, Wan P, Hankin J, Tseng CC, Yu MC, Pike MC (2002) Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis 23:1491-1496 (Pubitemid 35012429)
92. Wu AH, Yu MC, Tseng CC, Twaddle NC, Doerge DR (2004) Plasma isoflavone levels versus self-reported soy isoflavone levels in Asian-American women in Los Angeles County. Carcinogenesis 25:77-81 (Pubitemid 38128620)
93. Ingram D, Sanders K, Kolybaba M, Lopez D (1997) Casecontrol study of phyto-oestrogens and breast cancer. Lancet 350:990-994 (Pubitemid 27421108)
94. Nagata C (2010) Factors to consider in the association between soy isoflavone intake and breast cancer risk. J Epidemiol 20:83-89
95. Messina M, Hilakivi-Clarke L (2009) Early intake appears to be the key to the proposed protective effects of soy intake against breast cancer. Nutr Cancer 61:792-798
96. Kumar NB, Cantor A, Allen K, Riccardi D, Cox CE (2002) The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer 94:1166-1174 (Pubitemid 34150873)
97. Pino AM, Valladares LE, Palma MA, Mancilla AM, Yanez M, Albala C (2000) Dietary isoflavones affect sex hormone-binding globulin levels in postmenopausal women. J Clin Endocrinol Metab 85:2797-2800 (Pubitemid 32269154)
98. Duncan AM, Merz-Demlow BE, Xu X, Phipps WR, Kurzer MS (2000) Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer. Cancer Epidemiol Biomarkers Prev 9:581-586 (Pubitemid 30396180)
99. Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS (2005) Short-term soy and probiotic supplementation does not markedly affect concentrations of reproductive hormones in postmenopausal women with and without histories of breast cancer. J Altern Complement Med 11:1067-1074 (Pubitemid 43134056)
100. Bonorden MJ, Greany KA, Wangen KE, Phipps WR, Feirtag J, Adlercreutz H, Kurzer MS (2004) Consumption of Lactobacillus acidophilus and Bifidobacterium longum do not alter urinary equol excretion and plasma reproductive hormones in premenopausal women. Eur J Clin Nutr 58:1635-1642 (Pubitemid 40028526)
101. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR, Kurzer MS (2000) Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 85:3043-3048
102. Xu X, Duncan AM, Merz BE, Kurzer MS (1998) Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women. Cancer Epidemiol Biomarkers Prev 7:1101-1108 (Pubitemid 29001666)
103. Atkinson C, Skor HE, Dawn Fitzgibbons E, Scholes D, Chen C, Wahala K, Schwartz SM, Lampe JW (2003) Urinary equol excretion in relation to 2-hydroxyestrone and 16alpha-hydroxyestrone concentrations: an observational study of young to middle-aged women. J Steroid Biochem Mol Biol 86:71-77 (Pubitemid 37025751)
104. Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS (2005) The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in postmenopausal women depends on equol production status but is not influenced by probiotic consumption. J Nutr 135:603-608 (Pubitemid 40365225)
105. Frankenfeld CL, McTiernan A, Tworoger SS, Atkinson C, Thomas WK, Stanczyk FZ, Marcovina SM, Weigle DS, Weiss NS, Holt VL et al (2004) Serum steroid hormones, sex hormonebinding globulin concentrations, and urinary hydroxylated estrogen metabolites in post-menopausal women in relation to daidzein-metabolizing phenotypes. J Steroid Biochem Mol Biol 88:399-408 (Pubitemid 38625605)
106. Atkinson C, Newton KM, Aiello Bowles EJ, Lehman CD, Stanczyk FZ, Westerlind KC, Li L, Lampe JW (2009) Daidzeinmetabolizing phenotypes in relation to mammographic breast density among premenopausal women in the United States. Breast Cancer Res Treat 116:587-594
107. Fuhrman BJ, Teter BE, Barba M, Byrne C, Cavalleri A, Grant BJ, Horvath PJ, Morelli D, Venturelli E, Muti PC (2008) Equol status modifies the association of soy intake and mammographic density in a sample of postmenopausal women. Cancer Epidemiol Biomarkers Prev 17:33-42 (Pubitemid 351196271)
108. Maskarinec G, Williams AE, Carlin L (2003) Mammographic densities in a one-year isoflavone intervention. Eur J Cancer Prev 12:165-169 (Pubitemid 36543431)
109. Frankenfeld CL, McTiernan A, Aiello EJ, Thomas WK, La Croix K, Schramm J, Schwartz SM, Holt VL, Lampe JW (2004) Mammographic density in relation to daidzein-metabolizing phenotypes in overweight, postmenopausal women. Cancer Epidemiol Biomarkers Prev 13:1156-1162 (Pubitemid 38917904)
110. Boyd NF, Stone J, Martin LJ, Jong R, Fishell E, Yaffe M, Hammond G, Minkin S (2002) The association of breast mitogens with mammographic densities. Br J Cancer 87:876-882 (Pubitemid 35252963)
111. Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ (1998) Mammographic densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev 7:1133-1144 (Pubitemid 29001671)
112. Hooper L, Madhavan G, Tice JA, Leinster SJ, Cassidy A (2010) Effects of isoflavones on breast density in pre-and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update 16:745-760
113. Nagata Y, Sonoda T, Mori M, Miyanaga N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A et al (2007) Dietary isoflavones may protect against prostate cancer in Japanese men. J Nutr 137:1974-1979 (Pubitemid 47292748)
114. Yan L, Spitznagel EL (2009) Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr 89:1155-1163
115. Jian L (2009) Soy, isoflavones, and prostate cancer. Mol Nutr Food Res 53:217-226
116. Ozasa K, Nakao M, Watanabe Y, Hayashi K, Miki T, Mikami K, Mori M, Sakauchi F, Washio M, Ito Y et al (2004) Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men. Cancer Sci 95:65-71 (Pubitemid 38208409)
117. Hamilton-Reeves JM, Rebello SA, Thomas W, Slaton JW, Kurzer MS (2007) Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptorbeta expression or serum hormonal profiles in men at high risk of prostate cancer. J Nutr 137:1769-1775 (Pubitemid 47037705)
118. Rannikko A, Petas A, Rannikko S, Adlercreutz H (2006) Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation. Prostate 66:82-87 (Pubitemid 43005951)
119. Pendleton JM, Tan WW, Anai S, Chang M, Hou W, Shiverick KT, Rosser CJ (2008) Phase II trial of isoflavone in prostatespecific antigen recurrent prostate cancer after previous local therapy. BMC Cancer 8:132
120. Hussain M, Banerjee M, Sarkar FH, Djuric Z, Pollak MN, Doerge D, Fontana J, Chinni S, Davis J, Forman J et al (2003) Soy isoflavones in the treatment of prostate cancer. Nutr Cancer 47:111-117 (Pubitemid 38590881)
121. Kumar NB, Cantor A, Allen K, Riccardi D, Besterman-Dahan K, Seigne J, Helal M, Salup R, Pow-Sang J (2004) The specific role of isoflavones in reducing prostate cancer risk. Prostate 59:141-147 (Pubitemid 38481225)
122. Ohno S, Nakajima Y, Inoue K, Nakazawa H, Nakajin S (2003) Genistein administration decreases serum corticosterone and testosterone levels in rats. Life Sci 74:733-742 (Pubitemid 37494900)
123. Weber KS, Setchell KD, Stocco DM, Lephart ED (2001) Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats. J Endocrinol 170:591-599 (Pubitemid 32834325)
124. Hamilton-Reeves JM, Vazquez G, Duval SJ, Phipps WR, Kurzer MS, Messina MJ (2010) Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil Steril 94:997-1007
125. Nagata C, Takatsuka N, Shimizu H, Hayashi H, Akamatsu T, Murase K (2001) Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men. Cancer Epidemiol Biomarkers Prev 10:179-184 (Pubitemid 34288527)
126. Hamilton-Reeves JM, Rebello SA, Thomas W, Slaton JW, Kurzer MS (2007) Soy protein isolate increases urinary estrogens and the ratio of 2:16alpha-hydroxyestrone in men at high risk of prostate cancer. J Nutr 137:2258-2263 (Pubitemid 47529587)
127. Farnsworth WE (1996) Roles of estrogen and SHBG in prostate physiology. Prostate 28:17-23 (Pubitemid 26035438)
128. Kumar NB, Krischer JP, Allen K, Riccardi D, Besterman-Dahan K, Salup R, Kang L, Xu P, Pow-Sang J (2007) A Phase II randomized, placebo-controlled clinical trial of purified isoflavones in modulating steroid hormones in men diagnosed with localized prostate cancer. Nutr Cancer 59:163-168 (Pubitemid 350230733)
129. Tanaka M, Fujimoto K, Chihara Y, Torimoto K, Yoneda T, Tanaka N, Hirayama A, Miyanaga N, Akaza H, Hirao Y (2009) Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers. Prostate Cancer Prostatic Dis 12:247-252
130. Akaza H, Miyanaga N, Takashima N, Naito S, Hirao Y, Tsukamoto T, Mori M (2002) Is daidzein non-metabolizer a high risk for prostate cancer? A case-controlled study of serum soybean isoflavone concentration. Jpn J Clin Oncol 32:296-300 (Pubitemid 43102798)
131. Kurahashi N, Iwasaki M, Inoue M, Sasazuki S, Tsugane S (2008) Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center. J Clin Oncol 26:5923-5929
132. Magee PJ, Raschke M, Steiner C, Duffin JG, Pool-Zobel BL, Jokela T, Wahala K, Rowland IR (2006) 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 54:232-242 (Pubitemid 44316306)