896
Views
23
CrossRef citations to date
0
Altmetric
Original Articles

Metabolism and health effects of phyto-estrogens

, , , , &

References

  • Adlercreutz, H. (1998). Epidemiology of phytoestrogens. Baillière's Clin. Endoc. Metab. 12:605–623.
  • Aedin, Cassidy, Paola, Albertazzi, Inge, Lise Nielsen, Wendy, Hall, et al. (2006). Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women. Proc. Nutr. Soc. 65:76–92.
  • Alcantara, E. H., Shin, M.-Y., Sohn, H.-Y., Park, Y.-M., Kim, T., Lim, J.-H., et al. (2011). Diosgenin stimulates osteogenic activity by increasing bone matrix protein synthesis and bone-specific transcription factor Runx2 in osteoblastic MC3T3-E1 cells. J. Nutr. Biochem. 22:1055–1063.
  • Alekel, D. L., Van Loan, M. D., Koehler, K. J., Hanson, L. N., Stewart, J. W., Hanson, K. B., et al. (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.
  • Anderson, J. W., Johnstone, B. M. and Cook-Newell, M. E. (1995). Meta-analysis of the effects of soy protein intake on serum lipids. New Engl. J. Med. 333:276–282.
  • Anderson, K. M., Odell, P. M., Wilson, P. W. and Kannel, W. B. (1991). Cardiovascular disease risk profiles. Am. Heart J. 121:293–298.
  • Anderson, L. N., Cotterchio, M., Boucher, B. A. and Kreiger, N. (2013). Phytoestrogen intake from foods, during adolescence and adulthood, and risk of breast cancer by estrogen and progesterone receptor tumor subgroup among Ontario women. Int. J. Cancer. 132:1683–1692.
  • Atkinson, C., Compston, J. E., Day, N. E., Dowsett, M. and Bingham, S. A. (2004). The effects of phytoestrogen isoflavones on bone density in women: A double-blind, randomized, placebo-controlled tria1-3. Am. J. Clin. Nutr. 79:326–333.
  • Atkinson, C., Frankenfeld, C. L. and Lampe, J. W. (2005). Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. Exp. Biol. Med. 230:155–170.
  • Atkinson, C., Warren, R., Sala, E., Dowsett, M., Dunning, A. M., Healey, C. S., et al. (2004). Red-clover-derived isoflavones and mammographic breast density: A double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res. 6:R170–R179.
  • Atteritano, M., Marini, H., Minutoli, L., Polito, F., Bitto, A., Altavilla, D., et al. (2007). Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: A two-year randomized, double-blind, placebo-controlled study. J. Clin. Endoc. Metab. 92:3068–3075.
  • Axelson, M., Sjövall, J., Gustafsson, B. E., and Setchell, K. D. R. (1982). Origin of lignans in mammals and identification of a precursor from plants. Nature. 298(5875):659–660.
  • Bandyopadhyay, S., Lion, J.-M., Mentaverri, R., Ricupero, D. A., Kamel, S., Romero, J. R., et al. (2006). Attenuation of osteoclastogenesis and osteoclast function by apigenin. Biochem. Pharmacol. 72:184–197.
  • Barnes, S. (2003). Phyto-oestrogens and osteoporosis: what is a safe dose?[J]. Brit. J. Nutr. 89(S1):S101–S108.
  • Bateman, H. L. and Patisaul, H. B. (2008). Disrupted female reproductive physiology following neonatal exposure to phytoestrogens or estrogen specific ligands is associated with decreased GnRH activation and kisspeptin fiber density in the hypothalamus. Neurotoxicology. 29:988–997.
  • Beavers, D. P., Beavers, K. M., Miller, M., Stamey, J. and Messina, M. J. (2012). Exposure to isoflavone-containing soy products and endothelial function: A Bayesian meta-analysis of randomized controlled trials. Nutr. Metab. Cardiovasc. Dis. 22:182–191.
  • Beral, V. (2007). Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 369:1703–1710.
  • Bingham, S., Atkinson, C., Liggins, J., Bluck, L. and Coward, A. (1998). Phyto-oestrogens: Where are we now? Brit. J. Nutr. 79:393–406.
  • Bolaños, R., Del Castillo, A. and Francia, J. (2010). Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis[J]. Menopause. 17(3):660–666.
  • Boucher, B. A., Cotterchio, M., Anderson, L. N., Kreiger, N., Kirsh, V. A. and Thompson, L. U. (2013). Use of isoflavone supplements is associated with reduced postmenopausal breast cancer risk. Int. J. Cancer. 132:1439–1450.
  • Branca, F. (2003). Dietary phyto-oestrogens and bone health. Proc. Nutr. Soc. 62:877–887.
  • Briese, V. (2000). Phytoöstrogene [J]. Der Gynäkologe. 33(1):28–35.
  • Brink, E, Coxam, V, Robins, S, Wahala, K, Cassidy, A and 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.
  • Brössner, C., Petritsch, K., Fink, K., et al. (2006). Prostatic phyto-oestrogen tissue levels in different Austrian regions[J]. Urol. Int. 76(4):327–331.
  • Buteau-Lozano, H., Velasco, G., Cristofari, M., Balaguer, P. and Perrot-Applanat, M. (2008). Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism. J. Endoc. 196:399–412.
  • Caan, B. J., Natarajan, L., Parker, B., Gold, E. B., Thomson, C., Newman, V., et al. (2011). Soy food consumption and breast cancer prognosis. Cancer Epidem. Biomar. Prev. 20:854–858.
  • Campbell, S. C., Khalil, D. A., Payton, M. E. and Arjmandi, B. H. (2010). One-year soy protein supplementation does not improve lipid profile in postmenopausal women. Menopause. 17:587–593.
  • Cano, A., Dapia, S., Noguera, I., Pineda, B., Hermenegildo, C., Del, Val R., et al. (2008). Comparative effects of 17β-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice. Osteoporos. Int. 19:793–800.
  • Cassidy, A., Albertazzi, P., Nielsen, I. L., et al. (2006). Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women[J]. Proc. Nutr. Soc. 65(01):76–92.
  • Castoria, G., Migliaccio, A., Bilancio, A., Di Domenico, M., de Falco, A., Lombardi, M., et al. (2001). PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. EMBO J. 20:6050–6059.
  • Chen, C. L., Weiss, N. S., Newcomb, P., et al. (2002). Hormone replacement therapy in relation to breast cancer[J]. JAMA. 287(6):734–741.
  • Chen, J., Hui, E., Ip, T. and Thompson, L. U. (2004). Dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen-dependent human breast cancer (MCF-7) in nude mice. Clin. Cancer Res. 10:7703–7711.
  • Chen, J., Lin, H. and Hu, M. (2005). Absorption and metabolism of genistein and its five isoflavone analogs in the human intestinal Caco-2 model. Cancer Chemoth. Pharmaco. 55:159–169.
  • Chen, Y.-M., Ho, S. C., Lam, S. S..H., Ho, S. S. S. and Woo, J. L. F. (2004). Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: A double-blind, randomized, controlled trial. Menopause. 11:246–254.
  • Chen, J., and Liu, X. (2014). Effects on blood fat and bone density of postmenopausal women fed by soy protein with isoflavone. Zhonghua yi Xue za Zhi. 94(3):215–217.
  • Cheng, G., Wilczek, B., Warner, M., Gustafsson, J. Å., and Landgren, B. M. (2007). Isoflavone treatment for acute menopausal symptoms. Menopause. 14(3):468–473.
  • Clavel, T., Henderson, G., Engst, W., Doré, J. and Blaut, M. (2006). Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside. FEMS Microbiol. Ecol. 55:471–478.
  • Clifton-Bligh, P. B., Nery, M. L., Clifton-Bligh, R. J., Visvalingam, S., Fulcher, G. R., Byth, K., and Baber, R. (2015). Red clover isoflavones enriched with formononetin lower serum LDL cholesterol – a randomized, double-blind, placebo-controlled study. Eur. J. Clin. Nutr. 69(1):134–142.
  • Cohen, L., Zhao, Z., Pittman, B. and Scimeca, J. (2000). Effect of intact and isoflavone-depleted soy protein on NMU-induced rat mammary tumorigenesis. Carcinogenesis. 21:929–935.
  • Colacurci, N., Chiantera, A., Fornaro, F., de Novellis, V., Manzella, D., Arciello, A., et al. (2005). Effects of soy isoflavones on endothelial function in healthy postmenopausal women. Menopause. 12:299–307.
  • Cole, Z, Dennison, E. and Cooper, C. (2008). Update on the treatment of post-menopausal osteoporosis. Brit. Med. Bull. 86:129–143.
  • Collins-Burow, B. M., Antoon, J. W., Frigo, D. E., Elliott, S., Weldon, C. B., Boue, S. M., et al. (2012). Antiestrogenic activity of flavonoid phytochemicals mediated via the c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha. J. Steroid Biochem. Mol. Biol. 132:186–193.
  • Come, S. E., Buzdar, A. U., Arteaga, C. L., Brodie, A. M., Davidson, N. E., Dowsett, M., et al. (2003). Second international conference on recent advances and future directions in endocrine manipulation of breast cancer summary consensus statement. Clin. Cancer Res. 9:443s–446s.
  • Constantinou, A. I., Lantvit, D., Hawthorne, M., Xu, X., van Breemen, R. B. and Pezzuto, J. M. (2001). Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague–Dawley rats. Nutr. Cancer. 41:75–81.
  • Cotterchio, M, Boucher, B. A., Kreiger, N., Mills, C. A. and Thompson, L. U. (2008). Dietary phytoestrogen intake – lignans and isoflavones – and breast cancer risk (Canada). Cancer Causes Contr. 19:259–272.
  • Crespy, V., Morand, C., Manach, C., Besson, C., Demigne, C. and Remesy, C. (1999). Part of quercetin absorbed in the small intestine is conjugated and further secreted in the intestinal lumen. Am. J. Physiol. Gastrointest. Liver Physiol. 277(1):G120–G126.
  • Crisafulli, A., Marini, H., Bitto, A, Altavilla, D., Squadrito, G., Romeo, A., et al. (2004). Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT and placebo-controlled study. Menopause. 11:400–404.
  • Davis, D. D., Díaz-Cruz, E. S., Landini, S., Kim, Y.-W. and Brueggemeier, R. W. (2008). Evaluation of synthetic isoflavones on cell proliferation, estrogen receptor binding affinity, and apoptosis in human breast cancer cells. J. Steroid Biochem. Mol. Biol. 108:23–31.
  • Davis, D. D., Díaz-Cruz, E. S., Landini, S., Kim, Y.-W. and Brueggemeier, R. W. (2008). Evaluation of synthetic isoflavones on cell proliferation, estrogen receptor binding affinity, and apoptosis in human breast cancer cells. J. Steroid Biochem. Mol. Biol. 108:23–31.
  • Day, A. J., DuPont, M. S., Ridley, S., Rhodes, M., Rhodes, M. J., Morgan, M. R., et al. (1998). Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver β-glucosidase activity. FEBS Lett. 436:71–75.
  • Day, A. J., Cañada, F. J., Díaz, J. C., Kroon, P. A., Mclauchlan, R., Faulds et al. (2000). Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 468(2):166–170.
  • de Boer, V. C., Dihal, A. A., van der Woude, H., Arts, I. C., Wolffram, S., Alink, G. M., et al. (2005). Tissue distribution of quercetin in rats and pigs. J. Nutr. 135:1718–1725.
  • de Lemos, M. L. (2001). Effects of soy phytoestrogens genistein and daidzein on breast cancer growth. Ann. Pharmacother. 35:1118–1121.
  • Decroos, K., Vanhemmens, S., Cattoir, S., Boon, N. and 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.
  • D'Mello, J. F. (1997). Handbook of Plant and Fungal Toxicants. CRC Press, Boca Raton, Florida, pp. 117–137.
  • Donovan, J. L., Manach, C., Faulks, R. M., and Kroon, P. A. (2006). Absorption and metabolism of dietary plant secondary metabolites. In: Plant Secondary Metabolites: Occurrence, Structure and Role in the Human Diet, pp. 303–351. A. Crozier., M. N. Clifford and H. Ashihara., eds., Blackwell Publishing Ltd, Oxford, UK.
  • Engel, N., Lisec, J., Piechulla, B., and Nebe, B. (2012). Metabolic profiling reveals sphingosine-1-phosphate kinase 2 and lyase as key targets of (phyto-) estrogen action in the breast cancer cell line mcf-7 and not in mcf-12a. Plos One. 7(10):576–576.
  • Farina, H. G., Pomies, M., Alonso, D. F. and Gomez, D. E. (2006). Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol. Rep. 16:885–891.
  • Faure, C., Linossier, M.-T., Malaval, L., Lafage-Proust, M.-H., Peyroche, S., Vico, L, et al. (2008). Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation. Bone. 42:1092–1101.
  • Feinleib, M., Garrison, R., Fabsitz, R., Christian, J., Hrubec, Z., Borhani, N., et al. (1977). The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results. Am. J. Epidemiol. 106:284–295.
  • Ferenc, P., Solár, P., Kleban, J., Mikeš, J. and Fedoročko, P. (2010). Down-regulation of Bcl-2 and Akt induced by combination of photoactivated hypericin and genistein in human breast cancer cells. J. Photochem. Photobio. B. 98:25–34.
  • Filipović, B., Šošić-Jurjević, B., Ajdžanović, V., Brkić, D., Manojlović-Stojanoski, M., Milošević, V., et al. (2010). Daidzein administration positively affects thyroid C cells and bone structure in orchidectomized middle-aged rats. Osteoporos. Int. 21:1609–1616.
  • Food and Drug Administration. (1999). Food labeling: health claims; soy protein and coronary heart disease. Food and Drug Administration, HHS. Final rule. Fed Regist. 64:57700–57733.
  • Foster, W. G., Younglai, E. V., Boutross-Tadross, O., Hughes, C. L. and Wade, M. G. (2004). Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein. Toxicol. Sci. 77:91–100.
  • Foti, P., Erba, D., Spadafranca, A., Ciappellano, S., Bresciani, J. and Testolin, G. (2006). Daidzein is absorbed by passive transport in isolated small intestine of rats. Nutr. Res. 26:284–288.
  • Frankenfeld, C. L., McTiernan, A., Thomas, W. K., LaCroix, K., McVarish, L., Holt, V. L., et al. (2006). Postmenopausal bone mineral density in relation to soy isoflavone-metabolizing phenotypes. Maturitas. 53:315–324.
  • Frasor, J., Stossi, F., Danes, J. M., Komm, B., Lyttle, C. R. and Katzenellenbogen, B. S. (2004). Selective estrogen receptor modulators discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells. Cancer Res. 64:1522–1533.
  • French, M. R., Thompson, L. U. and Hawker, G. A. (2007). Validation of a phytoestrogen food frequency questionnaire with urinary concentrations of isoflavones and lignan metabolites in premenopausal women. J. Am. Coll. Nutr. 26:76–82.
  • Fujioka, M., Uehara, M., Wu, J., Adlercreutz, H., Suzuki, K. and Kanazawa, K., et al. (2004). Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice. J. Nutr. 134:2623–2627.
  • Gallo, D., Giacomelli, S., Cantelmo, F., Zannoni, G. F., Ferrandina, G., Fruscella, E., et al. (2001). Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy. Breast Cancer Res. Treat. 69:153–164.
  • Gao, Y. H. and Yamaguchi, M. (1999). Inhibitory effect of genistein on osteoclast-like cell formation in mouse marrow cultures. Biochem. Pharmacol. 58:767–772.
  • Gee, J. M., DuPont, M. S., Day, A. J., Plumb, G. W., Williamson, G. and Johnson, I. T. (2000). Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. J. Nutr. 130:2765–2771.
  • Gee, J. M., DuPont, M. S., Rhodes, M. J. C. and Johnson, I. T. (1998). Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radical Biol. Med. 25:19–25.
  • Go, A. S., Mozaffarian, D., Roger, V. L., Benjamin, E. J., Berry, J. D., Borden, W. B., et al. (2013). Executive summary: Heart disease and stroke statistics – 2013 update. A report from the American Heart Association. Circulation. 127:143–152.
  • González-Granillo, M, Steffensen, K., Granados, O., Torres, N., Korach-André, M., Ortíz, V., et al. (2012). Soy protein isoflavones differentially regulate liver X receptor isoforms to modulate lipid metabolism and cholesterol transport in the liver and intestine in mice. Diabetologia. 55:2469–2478.
  • Goodman, M. T., Shvetsov, Y. B., Wilkens, L. R., Franke, A. A., Le Marchand, L., Kakazu, K. K., et al. (2009). Urinary phytoestrogen excretion and postmenopausal breast cancer risk: The multi-ethnic cohort study. Cancer Prev. Res. 2:887–894.
  • Goodman-Gruen, D and Kritz-Silverstein, D. (2001). Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women. J. Nutr. 131:1202–1206.
  • Gossell-Williams, M., Hyde, C., Hunter, T., Simms-Stewart, D., Fletcher, H., McGrowder, D., and Walters, C. A. (2011). Improvement in HDL cholesterol in postmenopausal women supplemented with pumpkin seed oil: pilot study. Climacteric. 14(5):558–564.
  • Gottstein, N., Ewins, B. A., Eccleston, C., Hubbard, G. P., Kavanagh, I. C., Minihane, A. M., et al. (2003). Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function. Brit. J. Nutr. 89:607–615.
  • Guengerich, F. P. (2003). Cytochromes P450, drugs, and diseases. Mol. Interv. 3(4):194.
  • Guha, N., Kwan, M. L., Quesenberry Jr, C. P., Weltzien, E. K., Castillo, A. L., and Caan, B. J. (2009). Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: The life after cancer epidemiology study. Breast Cancer Res. Treat. 118(2):395–405.
  • Guo, A. J., Choi, R. C., Cheung, A. W., Chen, V. P., Xu, S. L., Dong, T. T., et al. (2011). Baicalin, a flavone, induces the differentiation of cultured osteoblasts an action via the Wnt/β-catenin signaling pathway. J. Biol. Chem. 286:27882–27893.
  • Hall, W. L., Vafeiadou, K., Hallund, J., Bugel, S., Reimann, M., Koebnick, C., 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.
  • Hertrampf, T., Schleipen, B., Offermanns, C., Velders, M., Laudenbach, U. and Diel, P. (2009). Comparison of the bone protective effects of an isoflavone-rich diet with dietary and subcutaneous administrations of genistein in ovariectomized rats. Toxicol. Lett. 184:198–203.
  • Ho, S. C., Chen, Y.-M., Ho, S. S. and Woo, J. L. (2007). Soy isoflavone supplementation and fasting serum glucose and lipid profile among postmenopausal Chinese women: A double-blind, randomized, placebo-controlled trial. Menopause. 14:905–912.
  • Horn-Ross, P. L., John, E. M., Lee, M., Stewart, S. L., Koo, J., Sakoda, L. C., et al. (2001). Phytoestrogen consumption and breast cancer risk in a multiethnic population the Bay Area Breast Cancer Study. Am. J. Epidemiol. 154:434–441.
  • Hsieh, C. Y, Santell, R. C., Haslam, S. Z. and Helferich, W. G. (1998). Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 58:3833–3838.
  • Hu, M., Krausz, K., Chen, J., Ge, X., Li, J, Gelboin, H. L., et al. (2003). Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. Drug Metab. Dispos. 31:924–931.
  • Huh, J.-E., Nam, D.-W., Baek, Y.-H., Kang, J. W., Park, D.-S., Choi, D.-Y., et al. (2011). Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways. Int. Immunopharm. 11:46–54.
  • Hur, H. G. and Rafii, F. (2006). Biotransformation of the isoflavonoids biochanin A, formononetin, and glycitein by Eubacterium limosum. FEMS Microbiol. Lett. 192:21–25.
  • Hutchins, A. M., Martini, M. C., Olson, B. A., Thomas, W., and Slavin, J. L. (2000). Flaxseed influences urinary lignan excretion in a dose-dependent manner in postmenopausal women. Cancer Epidemiol. Biomarkers Prev. 9:1113–1118.
  • Iwasaki, M., Inoue, M., Otani, T., Sasazuki, S., Kurahashi, N, Miura, T., et al. (2008). Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: A nested case-control study from the Japan Public Health Center-based prospective study group. J. Clin. Oncol. 26:1677–1683.
  • Jaganath, I. B. and Crozier, A. L. A. N. (2010). Dietary flavonoids and phenolic compounds. In: Plant Phenolics and Human Health: Biochemistry, Nutrition, and Pharmacology, pp. 1–49. Fraga CG., ed., JohnWiley & Sons, Hoboken, New Jersey.
  • Jawaid, K., Crane, S. R., Nowers, J. L., Lacey, M. and Whitehead, S. A. (2010). Long-term genistein treatment of MCF-7 cells decreases acetylated histone 3 expression and alters growth responses to mitogens and histone deacetylase inhibitors. J. Steroid Biochem. Mol. Biol. 120(4):164–171.
  • Jiang, X., Patterson, N. M., Ling, Y., Xie, J., Helferich, W. G. and Shapiro, D. J. (2008). Low concentrations of the soy phytoestrogen genistein induce proteinase inhibitor 9 and block killing of breast cancer cells by immune cells. Endocrinology. 149:5366–5373.
  • Jin, Z. and MacDonald, R. S. (2002). Soy isoflavones increase latency of spontaneous mammary tumors in mice. J. Nutr. 132:3186–3190.
  • Ju, Y. H., Allred, C. D., Allred, K. F., Karko, K. L., Doerge, D. R. and Helferich, W. G. (2001). Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J. Nutr. 131:2957–2962.
  • Ju, Y. H., Fultz, J., Allred, K. F., Doerge, D. R. and Helferich, W. G. (2006). Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice. Carcinogenesis. 27:856–863.
  • Juan, H. X., Xie, M. and Diel, P. (2013). The phytoestrogen Genistein inhibits the anti-tumor activity of cisplatin in MCF-7 breast and HT29 colon cancer cells. Exp. Clin. Endocrinol. Diab. 121(3).
  • Kano, M., Takayanagi, T., Harada, K., Sawada, S. and Ishikawa, F. (2006). Bioavailability of isoflavones after ingestion of soy beverages in healthy adults. J. Nutr. 136:2291–2296.
  • Karieb, S. and Fox, S. W. (2011). Phytoestrogens directly inhibit TNF-α-induced bone resorption in RAW264. 7 cells by suppressing c‐fos-induced NFATc1 expression. J. Cell. Biochem. 112:476–487.
  • Keinan-Boker, L., van Der Schouw, Y. T., Grobbee, D. E. and Peeters, P. H. (2004). Dietary phytoestrogens and breast cancer risk. Am. J. Clin. Nutr. 79:282–288.
  • Kenny, A. M., Mangano, K. M., Abourizk, R. H., Bruno, R. S., Anamani, D. E., Kleppinger, A., et al. (2009). Soy proteins and isoflavones affect bone mineral density in older women: A randomized controlled trial. Am. J. Clin. Nutr. 90:234–242.
  • Ketron, A. C., and Osheroff, N. (2014). Phytochemicals as anticancer and chemopreventive topoisomerase II poisons. Phytochem. Rev. 13(1):19–35.
  • Khan, S. A., Chatterton, R. T., Michel, N., Bryk, M, Lee, O., Ivancic, D., et al. (2012). Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial. Cancer Prev. Res. 5:309–319.
  • Khovidhunkit, W and Shoback, D. M. (1999). Clinical effects of raloxifene hydrochloride in women. Ann.Int. Med. 130:431.
  • Kilkkinen, A., Stumpf, K., Pietinen, P., Valsta, L. M., Tapanainen, H. and Adlercreutz, H. (2001). Determinants of serum enterolactone concentration. Am. J. Clin. Nutr. 73:1094–1100.
  • Kim, T.-H., Jung, J. W., Ha, B. G., Hong, J. M., Park, E. K., Kim, H.-J., et al. (2011). The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss. J. Nutr. Biochem. 22:8–15.
  • Kirkman, L. M., Lampe, J. W., Campbell, D. R., Martini, M. C. and Slavin, J. L. (1995). Urinary lignan and isoflavonoid excretion in men and women consuming vegetable and soy diets. Nutr Cancer. 24:1–12.
  • Knowlden, J. M., Gee, J. M., Robertson, J. F., Ellis, I. O. and Nicholson, R. I. (2000). A possible divergent role for the oestrogen receptor alpha and beta subtypes in clinical breast cancer. Int. J. Cancer. 89:209–212.
  • Kobayashi, S., Nagai, T., Konishi, Y., Tanabe, S., Morimoto, K. and Ogihara, T. (2012). Transport mechanisms of flavanone aglycones across Caco-2 cell monolayers and artificial PAMPA membranes. J. Pharm. Pharmacol. 64:52–60.
  • Korde, L. A., Wu, A. H., Fears, T., Nomura, A. M. Y, West, D. W., Kolonel, L. N., et al. (2009). Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol. Biomarkers Prev. 18:1050–1059.
  • Kuiper, G. G., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., et al. (1998). Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology. 139:4252–4263.
  • Kurzer, M. (2008). Soy consumption for reduction of menopausal symptoms. Inflammopharmacology. 16:227–229.
  • Labeling, F. (1999). Health claims; soy protein and coronary heart disease. Food Drug Admin. 21.
  • Lamartiniere, C. A., Cotroneo, M. S., Fritz, W. A., Wang, J., Mentor-Marcel, R. and Elgavish, A. (2002). Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. J.Nutr. 132:552S–558S.
  • Lambe, M., Wigertz, A., Holmqvist, M., Adolfsson, J., Bardage, C., Fornander, T., et al. (2010). Reductions in use of hormone replacement therapy: Effects on Swedish breast cancer incidence trends only seen after several years. Breast Cancer Res. Treat. 121:679–683.
  • Lampe, J. W., Karr, S. C., Hutchins, A. M. and Slavin, J. L. (1998). Urinary equol excretion with a soy challenge: Influence of habitual diet. In: Proceedings of the Society for Experimental Biology and Medicine, Society for Experimental Biology and Medicine, pp. 335–339. Royal Society of Medicine. New York, NY.
  • Le Bail, J., Varnat, F., Nicolas, J. and Habrioux, G. (1998). Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids. Cancer Lett. 130:209–216.
  • Lee, R. J., Albanese, C., Stenger, R. J., Watanabe, G., Inghirami, G., Haines, G. K., et al. (1999). pp60v- src Induction of cyclin D1 requires collaborative interactions between the extracellular signal-regulated kinase, p38, and Jun kinase pathways: A role for cAMP response element-binding protein and activating transcription factor-2 in pp60v-src signaling in breast cancer cells. J. Biol. Chem. 274:7341–7350.
  • Lee, S. A., Shu, X. O., Li, H., Yang, G., Cai, H., Wen, W., et al. (2009). Adolescent and adult soy food intake and breast cancer risk: Results from the Shanghai Women's Health Study. Am. J. Clin. Nutr. 89:1920–1926.
  • Levine, J. P. (2007). Effective strategies to identify postmenopausal women at risk for osteoporosis[J]. Geriatrics. 62(11):22–30.
  • Li, S.-H., Liu, X.-X., Bai, Y.-Y., Wang, X.-J., Sun, K., Chen, J.-Z., et al. (2010). Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials. Am. J. Clin. Nutr. 91:480–486.
  • Li, Y., Kong, D., Ahmad, A., et al. (2013). Antioxidant function of isoflavone and 3, 3′-diindolylmethane: are they important for cancer prevention and therapy?[J]. Antioxidants Redox Signaling. 19(2):139–150.
  • Li, Y.-Q., Xing, X.-H., Wang, H., Weng, X.-L., Yu, S.-B. and Dong, G.-Y. (2012). Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone. Acta Pharmacol. Sin. 33:66–74.
  • Liao, Mei-Hsiu, et al. (2014). Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases/NF-κB/activator protein-1 and promotes cell mineralisation. Br. J. Nutr. 111.01:55–63.
  • Limer, J. L and Speirs, V. (2004). Phyto-oestrogens and breast cancer chemoprevention. Breast Cancer Res. 6(3):119–127.
  • Lindahl, G., Saarinen, N., Abrahamsson, A. and Dabrosin, C. (2011). Tamoxifen, flaxseed, and the lignan enterolactone increase stroma-and cancer cell–derived IL-1Ra and decrease tumor angiogenesis in estrogen-dependent breast cancer. Cancer Res. 71:51–60.
  • Linseisen, J., Piller, R., Hermann, S. and Chang-Claude, J. (2004). Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study. Int. J. Cancer. 110:284–290.
  • Liu, B., Edgerton, S, Yang, X., Kim, A., Ordonez-Ercan, D., Mason, T, et al. (2005). Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Cancer Res. 65:879–886.
  • Liu, X. X., Li, S. H., Chen, J. Z., Sun, K., Wang, X. J., Wang, X. G., et al. (2012). Effect of soy isoflavones on blood pressure: A meta-analysis of randomized controlled trials. Nutr. Metab. Cardiovas. Dis. 22:463–470.
  • Liu, Y and Hu, M. (2002). Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model. Drug Metab. Dispos. 30:370–377.
  • Liu, Z.-M., Chen, Y.-M., Ho, S. C., Ho, Y. P. and Woo, J. (2010). Effects of soy protein and isoflavones on glycemic control and insulin sensitivity: A 6-MO double-blind, randomized, placebo-controlled trial in postmenopausal Chinese women with prediabetes or untreated early diabetes. Am. J. Clin. Nutr. 91:1394–1401.
  • Liu, Z.-M, Chen, Y.-M. and Ho, S. C. (2011). Effects of soy intake on glycemic control: A meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 93:1092–1101.
  • Lowcock, E. C., Cotterchio, M. and Boucher, B. A. (2013). Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk[J]. Cancer Causes Control. 24(4):813–816.
  • Lucki, N. C. and Sewer, M. B. (2011). Genistein stimulates MCF-7 breast cancer cell growth by inducing acid ceramidase (ASAH1) gene expression. J. Biol. Chem. 286:19399–19409.
  • Lydeking-Olsen, E., Jensen, J. E. B., Setchell, K. D. R., Damhus, M., and Jensen, T. H. (2002, March). Isoflavone-rich soymilk prevents bone loss in the lumbar spine of postmenopausal women: A two-year study. J. Nutr. 132(3):581S–581S. ( Amer. Inst. Nutrition, Rockville Pike, Bethesda, MD)
  • MacLennan, A., Lester, S. and Moore, V. (2001). Oral oestrogen replacement therapy versus placebo for hot flushes. Cochrane Database of Systematic Reviews, 55(1):295–296.
  • Magee, P., Allsopp, P., Samaletdin, A. and Rowland, I. (2013). Daidzein, R-(+) equol and S-(−) equol inhibit the invasion of MDA-MB-231 breast cancer cells potentially via the downregulation of matrix metalloproteinase-2. Eur. J. Nutr. 53(1):345–350.
  • Maggiolini, M., Vivacqua, A., Fasanella, G., Recchia, A. G., Sisci, D., Pezzi, V., et al. (2004). The G Protein-coupled Receptor GPR30 mediates c-fos upregulation by 17β-estradiol and phytoestrogens in breast cancer cells. J. Biol. Chem. 279:27008–27016.
  • Mai, Z., Blackburn, G. L. and Zhou, J. R. (2007). Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Mol. Carcinog. 46:534–542.
  • Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schutz, G., Umesono, K., et al. (1995). The nuclear receptor superfamily: The second decade. Cell. 83:835–839.
  • Manna, S. K. (2012). Double-edged sword effect of biochanin to inhibit nuclear factor kappaB: Suppression of serine/threonine and tyrosine kinases. Biochem. Pharmacol. 83:1383–1392.
  • Marino, M., Pallottini, V. and Trentalance, A. (1998). Estrogens cause rapid activation of IP3-PKC-α signal transduction pathway in HEPG2 cells. Biochem. Biophys. Res. Commun. 245:254–258.
  • Markiewicz, L., Garey, J., Adlercreutz, H. and Gurpide, E. (1993). In vitro bioassays of non-steroidal phytoestrogens. J. Steroid Biochem. Mol. Biol. 45:399–405.
  • Maskarinec, G., Takata, Y., Franke, A. A., Williams, A. E. and Murphy, S. P. (2004). A 2-year soy intervention in premenopausal women does not change mammographic densities. J. Nutr. 134:3089–3094.
  • Maskarinec, G., Williams, A. and Carlin, L. (2003). Mammographic densities in a one-year isoflavone intervention. Eur. J. Cancer Prev. 12:165–169.
  • Mason, J. K., and Thompson, L. U. (2013). Flaxseed and its lignan and oil components: Can they play a role in reducing the risk of and improving the treatment of breast cancer? 1. App. Physiol. Nutr. Metab. 39(6):663–678.
  • Matvienko, O. A., Alekel, D. L., Genschel, U., Ritland, L., Van Loan, M. D. and Koehler, K. J. (2010). Appetitive hormones, but not isoflavone tablets, influence overall and central adiposity in healthy postmenopausal women. Menopause (New York) 17:594.
  • Mazur, W., Uehara, M., Wähälä, K. and Adlercreutz, H. (2000). Phyto-oestrogen content of berries, and plasma concentrationsand urinary excretion of enterolactone after asingle strawberry-meal in human subjects. Brit. J. Nutr. 83:381–387.
  • McMichael-Phillips, D. F., Harding, C., Morton, M., Roberts, S. A., Howell, A., Potten, C. S., et al. (1998). Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am. J. Clin. Nutr. 68:1431S–1435S.
  • Migliaccio, A., Di Domenico, M., Castoria, G., De Falco, A., Bontempo, P., Nola, E., et al. (1996). Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO J. 15:1292.
  • Molzberger, A. F., Vollmer, G., Hertrampf, T., Möller, F. J., Kulling, S. and Diel, P. (2012). In utero and postnatal exposure to isoflavones results in a reduced responsivity of the mammary gland towards estradiol. Mol. Nutr. Food Res. 56:399–409.
  • Morand, C., Crespy, V., Manach, C., Besson, C, Demigné, C. and Rémésy, C. (1998). Plasma metabolites of quercetin and their antioxidant properties. Am. J. Physiol. Regul. Integr. Comp. Physiol. 275:R212–R219.
  • Mousavi, Y. and Adlercreutz, H. (1992). Enterolactone and estradiol inhibit each other's proliferative effect on MCF-7 breast cancer cells in culture. J. Steroid Biochem. Mol. Biol. 41:615–619.
  • Muir, A., Westcott, N., Ballantyne, K. and Northrup, S. (2000). Flax lignans – Recent developments in the analysis of lignans in plant and animal tissues. Proc. Flax Inst. 58:23–32.
  • Muir, A., Westcott, N. and Prasad, K. (1997). Extraction, purification and animal model testing of an anti-atherosclerotic lignan secoisolariciresinol diglucoside from flaxseed (Linum usitatissimum). In: II WOCMAP Congress on Medicinal and Aromatic Plants, Part 2: Pharmacognosy, Pharmacology, Phytomedicine, Toxicology, Vol. 501, pp. 245–248.
  • Murota, K and Terao, J. (2003). Antioxidative flavonoid quercetin: Implication of its intestinal absorption and metabolism. Arch. Biochem. Biophys. 417:12–17.
  • Muthyala, R. S., Ju, Y. H., Sheng, S., Williams, L. D., Doerge, D. R., Katzenellenbogen, B. S., et al. (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. Bioorgan. Med. Chem. 12:1559.
  • Nagata, C., Takatsuka, N., Kurisu, Y. and Shimizu, H. (1998). Decreased serum total cholesterol concentration is associated with high intake of soy products in Japanese men and women. J. Nutr. 128:209–213.
  • Naragoni, S., Sankella, S., Harris, K. and Gray, W. G. (2009). Phytoestrogens regulate mRNA and protein levels of guanine nucleotide-binding protein, beta-1 subunit (GNB1) in MCF-7 cells. J. Cell. Physiol. 219:584–594.
  • Nesbitt, P. D., Lam, Y. and Thompson, L. U. (1999). Human metabolism of mammalian lignan precursors in raw and processed flaxseed. Am. J. Clin. Nutr. 69:549–555.
  • Nielsen, T. S., Purup, S., Wärri, A., Godschalk, R. W. and Hilakivi-Clarke, L. (2011). Effects of maternal exposure to cow's milk high or low in isoflavones on carcinogen-induced mammary tumorigenesis among rat offspring. Cancer Prev. Res. 4:694–701.
  • Nishio, K., Niwa, Y., Toyoshima, H., Tamakoshi, K., Kondo, T, Yatsuya, H., et al. (2007). Consumption of soy foods and the risk of breast cancer: Findings from the Japan collaborative cohort (JACC) study. Cancer Causes Control. 18:801–808.
  • Ohtomo, T., Uehara, M., Peñalvo, J. L., Adlercreutz, H., Katsumata, S.-I. and Suzuki, K. (2008). Comparative activities of daidzein metabolites, equol and O-desmethylangolensin, on bone mineral density and lipid metabolism in ovariectomized mice and in osteoclast cell cultures. Eur. J. Nutr. 47:273–279.
  • Ono, M., Koga, T., Ueo, H. and Nakano, S. (2012). Effects of dietary genistein on hormone-dependent rat mammary carcinogenesis induced by ethyl methanesulphonate. Nutr. Cancer. 64:1204–1210.
  • Padilla-Banks, E., Jefferson, W. N. and Newbold, R. R. (2006). Neonatal exposure to the phytoestrogen genistein alters mammary gland growth and developmental programming of hormone receptor levels. Endocrinology. 147:4871–4882.
  • Paech, K., Webb, P., Kuiper, G. G., Nilsson, S., Gustafsson, J.-Å., Kushner, P. J., et al. (1997). Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science. 277:1508–1510.
  • Palacios, V. G., Robinson, L. J., Borysenko, C. W., Lehmann, T., Kalla, S. E. and Blair, H. C. (2005). Negative regulation of RANKL-induced osteoclastic differentiation in RAW264. 7 cells by estrogen and phytoestrogens. J. Biol. Chem. 280:13720–13727.
  • Pavese, J., Farmer, R. and Bergan, R. (2010). Inhibition of cancer cell invasion and metastasis by genistein. Cancer Metast. Rev. 29:465–482.
  • Pei, R. J., Sato, M., Yuri, T., Danbara, N., Nikaido, Y. and Tsubura, A. (2003). Effect of prenatal and prepubertal genistein exposure on N-methyl-N-nitrosourea-induced mammary tumorigenesis in female Sprague–Dawley rats. In vivo (Athens Greece) 17:349–357.
  • Peng, J.-H., Zhu, J.-D., Mi, M.-T., Li, F.-J., Cai, L., Dong, J.-Z., et al. (2010). Prepubertal genistein exposure affects erbB2/Akt signal and reduces rat mammary tumorigenesis. Eur. J. Cancer Prev. 19:110–119.
  • Petrakis, N. L., Barnes, S., King, E. B., Lowenstein, J., Wiencke, J., Lee, M. M., et al. (1996). Stimulatory influence of soy protein isolate on breast secretion in pre-and postmenopausal women. Cancer Epidemiol. Biom. Prev. 5:785–794.
  • Pietinen, P., Stumpf, K., Männistö, S., Kataja, V., Uusitupa, M. and Adlercreutz, H. (2001). Serum enterolactone and risk of breast cancer a case-control study in eastern Finland. Cancer Epidem. Biom. Prev. 10:339–344.
  • Pillow, P. C., Duphorne, C. M., Chang, S., Contois, J. H., Strom, S. S., Spitz, M. R., et al. (1999). Development of a database for assessing dietary phytoestrogen intake. Nutrition & Cancer. 33(1):3–19.
  • Pipe, E. A., Gobert, C. P., Capes, S. E., Darlington, G. A., Lampe, J. W. and Duncan, A. M. (2009). Soy protein reduces serum LDL cholesterol and the LDL cholesterol:HDL cholesterol and apolipoprotein B:apolipoprotein A-I ratios in adults with type 2 diabetes. J. Nutr. 139:1700–1706.
  • Piskula, M. K. and Terao, J. (1998). Accumulation of (−)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues. J. Nutr. 128:1172–1178.
  • Piskula, M. K., Yamakoshi, J. and Iwai, Y. (1999). Daidzein and genistein but not their glucosides are absorbed from the rat stomach. FEBS Lett. 447:287–291.
  • Quella, S. K., Loprinzi, C. L., Barton, D. L., Knost, J. A., Sloan, J. A., LaVasseur, B. I., et al. (2000). Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. J. Clin. Oncol. 18:1068–1068.
  • Riesco, E., Aubertin-Leheudre, M., Maltais, M. L., Audet, M. and Dionne, I. J. (2010). Synergic effect of phytoestrogens and exercise training on cardiovascular risk profile in exercise-responder postmenopausal women: A pilot study. Menopause. 17:1035–1039
  • Riggs, B. L. and Hartmann, L. C. (2003). Selective estrogen-receptor modulators – Mechanisms of action and application to clinical practice. New Engl. J. Med. 348:618–629.
  • Ronis, M. J., Chen, Y., Badeaux, J. and Badger, T. M. (2009). Dietary soy protein isolate attenuates metabolic syndrome in rats via effects on PPAR, LXR, and SREBP signaling. J.Nutr. 139:1431–1438.
  • Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M., et al. (2002). Writing group for the women's health initiative investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the women's health initiative randomized controlled trial. JAMA. 288:321–333.
  • Rowland, I., Faughnan, M. and Hoey, L. (2003). Bioavailability of phyto-oestrogens[J]. Br. J. Nutr. 89(S1):S45–S58.
  • Rüfer, C. E., Bub, A., Möseneder, J., Winterhalter, P., Stürtz, M. and Kulling, S. E. (2008). Pharmacokinetics of the soybean isoflavone daidzein in its aglycone and glucoside form: A randomized, double-blind, crossover study. Am. J. Clin. Nutr. 87:1314–1323.
  • Saad, H. E. S, Meduri, G., Phrakonkham, P., Bergès, R., Vacher, S, Djallali, M., et al. (2011). Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin. Reprod. Toxicol. 32:15–25.
  • Saarinen, N. M., Abrahamsson, A. and Dabrosin, C. (2010). Estrogen-induced angiogenic factors derived from stromal and cancer cells are differently regulated by enterolactone and genistein in human breast cancer in vivo. Int. J. Cancer. 127:737–745.
  • Sacks, F. M., Lichtenstein, A., Van Horn, L., Harris, W., Kris-Etherton, P. and Winston, M. (2006). Soy protein, isoflavones, and cardiovascular health. Circulation. 113:1034–1044.
  • Safe, S. (2001). Transcriptional activation of genes by 17β-estradiol through estrogen receptor-Sp1 interactions. Vitam. Horm. 62:231–252.
  • Sakamoto, T., Horiguchi, H., Oguma, E. and Kayama, F. (2010). Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. J. Nutr. Biochem. 21:856–864.
  • Schairer, C., Lubin, J., Troisi, R., Sturgeon, S., Brinton, L. and Hoover, R. (2000). Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA. 283:485–491.
  • Schmitt, E., Dekant, W. and Stopper, H. (2001). Assaying the estrogenicity of phytoestrogens in cells of different estrogen sensitive tissues. Toxicol. in Vitro. 15:433–439.
  • Schwanck, B., Behrendt, M., Naim, H. and Blaschek, W. (2011). Deglycosylation of individual flavonoids and flavonoid containing plant extracts by purified human intestinal lactase-phlorizin hydrolase (LPH). Planta Med. 77:PA22.
  • Seo, H.-S., DeNardo, D. G., Jacquot, Y., Laïos, I., Vidal, D. S., Zambrana, C. R., et al. (2006). Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha. Breast Cancer Res. Treat. 99:121–134.
  • Seo, H.-S., Ju, J.-H., Jang, K. and Shin, I. (2011). Induction of apoptotic cell death by phytoestrogens by upregulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor α-negative breast cells. Nutr. Res. 31:139–146.
  • Setchell, K. D. (2001). Soy isoflavones – Benefits and risks from nature's selective estrogen receptor modulators (SERMs). J. Am. Coll. Nutr. 20:354S–362S.
  • Setchell, K. D., Brown, N. M., Desai, P., Zimmer-Nechemias, L., Wolfe, B. E., Brashear, W. T., et al. (2001). Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J. Nutr. 131:1362S–1375S.
  • Setchell, K. D., Brown, N. M., Desai, P. B., Zimmer-Nechimias, L., Wolfe, B, Jakate, A. S., et al. (2003). Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes. J. Nutr. 133:1027–1035.
  • Setchell, K. D., Brown, N. M. and 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.
  • Setchell, K. D., Brown, N. M., Zimmer-Nechemias, L., Brashear, W. T., Wolfe, B. E., Kirschner, A. S., et al. (2002). Evidence for lack of absorption of soy isoflavone glycosides in humans, supporting the crucial role of intestinal metabolism for bioavailability. Am. J. Clin. Nutr. 76:447–453.
  • Shang, Y and Brown, M. (2002). Molecular determinants for the tissue specificity of SERMs. Science. 295:2465–2468.
  • Sheu, S. Y., Tsai, C. C. and Sun, J. S. (2012). Stimulatory effect of puerarin on bone formation through co-activation of nitric oxide and bone morphogenetic protein-2/mitogen-activated protein kinases pathways in mice[J]. Chin. Med. J. 125(20):3646–3653.
  • Shu, X. Z. Y. C. H., et al. (2009). Soy food intake and breast cancer survival. JAMA. 302:2437–2443.
  • Shu, X. O., Jin, F., Dai, Q., Wen, W., Potter, J. D., Kushi, L. H., et al. (2001). Soy food intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol. Biomarkers Prev. 10:483–488.
  • Simbalista, R. L., Sauerbronn, A. V., Aldrighi, J. M. and Arêas, J. A. (2010). Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women. J. of Nutr. 140:293–297.
  • Sirtori, C. R., Arnoldi, A. and Johnson, S. K. (2005). Phytoestrogens: End of a tale? Ann. Med. 37:423–438.
  • Sirtori, C. R. (2001). Risks and benefits of soy phytoestrogens in cardiovascular diseases, cancer, climacteric symptoms and osteoporosis. Drug Safety. 24:665–682.
  • Stalmach, A., Steiling, H. and Williamson, G., et al. (2010). Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy[J]. Arch. Biochem. Biophys. 501(1):98–105.
  • Takumi, H., Mukai, R. and Ishiduka, S. (2011). Tissue distribution of hesperetin in rats after a dietary intake[J]. Biosci. Biotechnol. Biochem. 75(8):1608–1610.
  • Tew, B. Y., Xu, X., Wang, H. J., Murphy, P. A. and Hendrich, S. (1996). A diet high in wheat fiber decreases the bioavailability of soybean isoflavones in a single meal fed to women. J. Nutr. 126:871–877.
  • Tham, D. M., Gardner, C. D. and Haskell, W. L. (1998). Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J. Clin. Endocrinol. Metab. 83:2223–2235.
  • Thanos, J., Cotterchio, M., Boucher, B. A., Kreiger, N. and Thompson, L. U. (2006). Adolescent dietary phytoestrogen intake and breast cancer risk (Canada). Cancer Causes Contr. 17:1253–1261.
  • This, P., De La Rochefordi, A., Clough, K., Fourquet, A. and Magdelenat, H. (2001). Phytoestrogens after breast cancer. Endocr. Relat. Cancer. 8:129–134.
  • Thompson, L. U., Chen, J. M., Li, T., Strasser-Weippl, K. and Goss, P. E. (2005). Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin. Cancer Res. 11:3828–3835.
  • Thompson, L. U. (1999). Role of lignans in carcinogenesis. In: Phytochemicals in Human Health Protection, Nutrition, and Plant Defense, pp. 51–65. Romeo J., ed., Springer, New York, NY.
  • Tophkhane, C., Shihe, Y., Bales, W., Archer, L., Osunkoya, A., Thor, A. D., et al. (2007). Bcl-2 overexpression sensitizes MCF-7 cells to genistein by multiple mechanisms. Int. J. Oncol. 31:867–874.
  • Touré, A and Xueming, X. (2010). Flaxseed lignans: Source, biosynthesis, metabolism, antioxidant activity, bioactive components, and health benefits. Compr. Rev. Food Sci. Food Saf. 9:261–269.
  • Tovar, A. R., Murguía, F, Cruz, C., Hernández-Pando, R., Aguilar-Salinas, C. A., Pedraza-Chaverri, J., et al. (2002). A soy protein diet alters hepatic lipid metabolism gene expression and reduces serum lipids and renal fibrogenic cytokines in rats with chronic nephrotic syndrome. J. Nutr. 132:2562–2569.
  • Travis, R. C., Allen, N. E., Appleby, P. N., Spencer, E. A., Roddam, A. W. and Key, T. J. (2008). A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women. Int. J. Cancer. 122:705–710.
  • Trock, B. J., Hilakivi-Clarke, L. and Clarke, R. (2006). Meta-analysis of soy intake and breast cancer risk. J. Natl. Cancer Inst. 98:459–471.
  • Ueda, M., Niho, N., Imai, T., Shibutani, M., Mitsumori, K., Matsui, T., et al. (2003). Lack of significant effects of genistein on the progression of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in ovariectomized Sprague–Dawley rats. Nutr. Cancer. 47:141–147.
  • Valaciiovicova, T., Slivova, V., Bergman, H., Shuherk, J. and Sliva, D (2004). Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-κB/AP-1-dependent and-independent pathways. Int. J. Oncol. 25:1389–1395.
  • van de Weijer, P. H. M. and Barentsen, R. (2002). Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo[J]. Maturitas. 42(3):187–193.
  • van Duursen, M. B., Nijmeijer, S., de Morree, E., de Jong, P. C. and van den Berg, M. (2011). Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model. Toxicology. 289:67–73.
  • Vanden Berghe, W., De Naeyer, A., Dijsselbloem, N., David, J.-P., De Keukeleire, D. and Haegeman, G. (2011). Attenuation of ERK/RSK2-Driven NFB gene expression and cancer cell proliferation by Kurarinone, a Lavandulyl flavanone isolated from Sophora flavescens AIT. roots. Endocr. Metab. Immun. Dis. Drug Targets 11:247–261.
  • Vantyghem, S. A., Wilson, S. M., Postenka, C. O., Al-Katib, W., Tuck, A. B. and Chambers, A. F. (2005). Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model. Cancer Res. 65:3396–3403.
  • Verheus, M., Van Gils, C. H., Keinan-Boker, L., Grace, P. B., Bingham, S. A. and Peeters, P. H. (2007). Plasma phytoestrogens and subsequent breast cancer risk. J. Clin. Oncol. 25:648–655.
  • Verheus, M., van Gils, C. H., Kreijkamp-Kaspers, S., Kok, L., Peeters, P. H. M, Grobbee, D. E., et al. (2008). Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Cancer Epidemiol. Biomarkers Prev. 17:2632–2638.
  • Verkasalo, P. K., Appleby, P. N., Allen, N. E., Davey, G., Adlercreutz, H. and Key, T. J. (2001). Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European Prospective Investigation into Cancer and Nutrition). Br. J. Nutr. 86:415–421.
  • Walker, H., Dean, T., Sanders, T., Jackson, G., Ritter, J. and Chowienczyk, P. (2001). The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17β-estradiol. Circulation 103:258–262.
  • Wang, C. and Kurzer, M. S. (1997). Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutrition & Cancer, 28(3):236–247.
  • Wang, L.-Q. (2002). Mammalian phytoestrogens: Enterodiol and enterolactone. J. Chromatogr. B. 777:289–309.
  • Wang, S. F., Jiang, Q., Ye, Y. H., Li, Y. and Tan, R. X. (2005). Genistein derivatives as selective estrogen receptor modulators: Sonochemical synthesis and in vivo anti-osteoporotic action. Bioorgan. Med. Chem. 13:4880–4890.
  • Wangen, K. E., Duncan, A. M., Merz-Demlow, B. E., Xu, X., Marcus, R., Phipps, W. R., et al. (2000). Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J. Clin. Endocrinol. Metab. 85:3043–3048.
  • Ward, H. A., Kuhnle, G. G. C., Mulligan, A. A., Lentjes, M. A. H., Luben, R. N. and Khaw, K. T. (2010). Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition – Norfolk in relation to phytoestrogen intake derived from an improved database. Am. J. Clin. Nutr. 91:440–448.
  • Warri, A., Saarinen, N., Makela, S. and Hilakivi-Clarke, L. (2008). The role of early life genistein exposures in modifying breast cancer risk. Br. J. Cancer. 98:1485–1493.
  • Watson, K. L., Stalker, L. and Jones, R. A. (2015). High levels of dietary soy decrease mammary tumor latency and increase incidence in MTB-IGFIR transgenic mice[J]. BMC Cancer. 15(1):37.
  • Weggemans, R. and Trautwein, E. (2003). Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: A meta-analysis. Eur. J. Clin. Nutr. 57:940–946.
  • Wu, A. H., Wan, P., Hankin, J., Tseng, C. C., Yu, M. C. and Pike, M. C. (2002). Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis. 23:1491–1496.
  • Wu, A. H., Ziegler, R. G., Horn-Ross, P. L., Nomura, A., West, D. W., Kolonel, L. N., et al. (1996). Tofu and risk of breast cancer in Asian-Americans. Cancer Epidemiol. Biomarkers Prev. 5:901–906.
  • Wu, J., Oka, J., Higuchi, M., Tabata, I., Toda, T., Fujioka, M., et al. (2006). Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metab. Clin. Exp. 55:423–433.
  • Wu, J., Wang, X. X., Takasaki, M., Ohta, A., Higuchi, M. and Ishimi, Y. (2001). Cooperative effects of exercise training and genistein administration on bone mass in ovariectomized mice. J. Bone Miner. Res. 16:1829–1836.
  • Yeung, J., and Yu, T. F. (2003). Effects of isoflavones (soy phyto-estrogens) on serum lipids: A meta-analysis of randomized controlled trials. Nutr. J. 2(1):15.
  • Yin, J., Han, N., Liu, Z., Song, S. and Kadota, S. (2010). The in vitro antiosteoporotic activity of some glycosides in Dioscorea spongiosa. Biol. Pharm. Bull. 33:316–320.
  • Yuan, J., Wang, Q., Ross, R., Henderson, B. and Yu, M. (1995). Diet and breast cancer in Shanghai and Tianjin, China. Br. J. Cancer. 71:1353.
  • Yuan, J. P., Wang, J. H. and Liu, X. (2007). Metabolism of dietary soy isoflavones to equol by human intestinal microflora – Implications for health. Mol. Nutr. Food Res. 51:765–781.
  • Zhan, S. and Ho, S. C. (2005). Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am. J. Clin. Nutr. 81:397–408.
  • Zhang, G. P., Han, D., Liu, G., et al. (2012). Effects of soy isoflavone and endogenous oestrogen on breast cancer in MMTV-erbB2 transgenic mice[J]. J. Int. Med. Res. 40(6):2073–2082.
  • Zhang, X., Shu, X. O., Gao, Y.-T., Yang, G., Li, Q., Li, H, et al. (2003). Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J. Nutr. 133:2874–2878.
  • Zhang, Y.-B., Chen, W.-H., Guo, J.-J., Fu, Z.-H., Yi, C, Zhang, M., et al. (2013). Soy isoflavone supplementation could reduce body weight and improve glucose metabolism in non-Asian postmenopausal women – A meta-analysis. Nutrition. 29:8–14.
  • Zhou, S., Hu, Y., Zhang, B, Teng, Z, Gan, H, Yang, Z, et al. (2008). Dose-dependent absorption, metabolism, and excretion of genistein in rats. J. Agr. Food Chem. 56:8354–8359.
  • Zhuo, X.-G., Melby, M. K. and Watanabe, S. (2004). Soy isoflavone intake lowers serum LDL cholesterol: A meta-analysis of 8 randomized controlled trials in humans. J. Nutr. 134:2395–2400.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.