Share This Article:

Review: Anti-Oxidant and Anti-Aging Properties of Equol in Prostate Health (BPH)

DOI: 10.4236/ojemd.2014.41001    4,646 Downloads   7,567 Views   Citations

ABSTRACT

Benign prostatic hyperplasia (BPH) is the pathological cellular progression of glandular proliferation associated with aging. The primary changes in prostate disorders are mediated by the conversion of the principle androgen, testosterone, to its more potent metabolite, 5α-dihydrotestosterone (5α-DHT). However, recent evidence suggests that estrogen hormonal actions via estrogen receptor subtypes also play an important role in BPH. Current pharmaceutical options for BPH have advantages, limitations and adverse effects. Complementary and Alternative Medicine (CAM) treatments for BPH include botanicals such as polyphenols and isoflavones. Equol is a polyphenolic/isoflavonoid molecule derived from intestinal metabolism, dairy and dietary plant sources. Equol has potent anti-oxidant and anti-aging properties to decrease prostatic irritation and potentially neoplastic growth. It has the unique characteristic to bind specifically 5α-DHT by sequestering 5α-DHT from the androgen receptor (AR), thus decreasing androgen hormone actions to improve prostate health by acting as a selective androgen modulator (SAM). It also has affinity for estrogen related receptor gamma (ERR-γ) and estrogen receptor beta (ER-β) within the prostate that is known to improve male health via selective estrogen receptor modulatory (SERM) activities to decrease inflammation, cellular proliferation and carcinogenesis. The possible clinical efficacy of equol on the symptoms associated with BPH is presented and the reviewed findings suggest that equol may provide a well-tolerated and rapid beneficial therapy for BPH that can be used alone or in combination with current pharmaceutical therapies. The beneficial clinical efficacy of equol observed may be due to the multiple positive biological actions that are not present in current pharmaceutical treatments.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Lephart, E. (2014) Review: Anti-Oxidant and Anti-Aging Properties of Equol in Prostate Health (BPH). Open Journal of Endocrine and Metabolic Diseases, 4, 1-12. doi: 10.4236/ojemd.2014.41001.

References

[1] J. T. Wei, E. A. Calhoun and S. J. Jacobsen, “Benign Prostatic Hyperplasia,” In: M. S. Litwin and C. S. Saigal, Eds., Urologic Disease in America, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, US Government Publishing Office, Washington DC, NIH Publication No. 04-5512, 2004, pp. 43-69.
[2] A. Gravas and M. Oelke, “Current Status of 5α-Reductase Inhibitors in the Management of Lower Urinary Tract Symptoms and BPH,” World Journal of Urology, Vol. 28, No. 1, 2010, pp. 9-15.
http://dx.doi.org/10.1007/s00345-009-0493-y
[3] T. Fujimura, S. Takahashi, T. Urano, N. Ijichi, K Ikeda, J. Kumagai, et al., “Differential Expression of EstrogenRelated Receptors β and γ (ERRβ and ERRγ) and Their Clinical Significance in Human Prostate Cancer,” Cancer Science, Vol. 101, No. 3, 2010, pp. 646-651.
http://dx.doi.org/10.1111/j.1349-7006.2009.01451.x
[4] S. J. Ellem and G. P. Risbridger, “The Dual, Opposing Role of Estrogens in the Prostate,” Annals New York Academy of Science, Vol. 1155, 2009, pp. 174-186.
http://dx.doi.org/10.1111/j.1749-6632.2009.04360.x
[5] S. J. Berry, D. S. Coffey, P. C. Walsh and L. L. Ewing, “The Development of Human Benign Prostatic Hyperplasia with Age,” Journal of Urology, Vol. 132, No. 3, 1984, pp. 474-479.
[6] J. T. Wei, E. Calhoun and S. J. Jacobsen, “Urologic Diseases in America Project: Benign Prostatic Hyperplasia,” Journal of Urology, Vol. 179, No. 5, 2008, pp. S75-S80.
http://dx.doi.org/10.1016/j.juro.2008.03.141
[7] J. Sausville and M. Naslund, “Benign Prostatic Hyperplasia and Prostate Cancer: An Overview for Primary Care Physicians,” International Journal of Clinical Practice, Vol. 64, No. 13, 2010, pp. 174-1745.
http://dx.doi.org/10.1111/j.1742-1241.2010.02534.x
[8] K, Kijvikai, “Digital Rectal Examination, Serum Prostatic Specific Antigen or Transrectal Ultrasonography: The Best Tool to Guide the Treatment of Men with Benign Prostatic Hyperplasia,” Current Opinion in Urology, Vol. 19, No. 1, 2009, pp. 44-48.
http://dx.doi.org/10.1097/MOU.0b013e32831743d0
[9] M. Emberton, E. B. Cornel, P. F. Bassi, R. O. Fourcade, J. M. F. Gómez and R. Castro, “Benign Prostatic Hyperplasia as a Progressive Disease: A Guide to the Risk Factors and Options for Medical Management,” International Journal of Clinical Practice, Vol. 62, No. 7, 2008, pp. 1076-1086. http://dx.doi.org/10.1111/j.1742-1241.2008.01785.x
[10] W. D. Tilley, M. Marcelli and M. J. Phaul, “Recent Studies of the Androgen Receptor—New Insights into Old Questions,” Molecular Cellular Endocrinology, Vol. 68, No. 2-3, 1990, pp. C7-C10.
http://dx.doi.org/10.1016/0303-7207(90)90178-B
[11] K. P. DeJésus-Tran, P.-L. Cöté, L. Cantin, J. B. Blanchet, F. Labrie and R. Breton, “Comparison of Crystal Structures of Human Androgen Receptor Ligand-Binding Domain Complexed with Various Agonists Reveal Molecular Determinants Responsible for Binding Affinity,” Protein Science, Vol. 15, No. 5, 2006, pp. 987-999.
http://dx.doi.org/10.1110/ps.051905906
[12] D. Simon, K. Nahoul and M. A. Charles, “Sex Hormones, Aging, Ethnicity and Insulin Sensitivity in Men: An Overview of the TELECOM Study,” In: A. Vermeulen and B. J. Oddens, Eds., Androgens and the Aging Male, Parthenon Publishing, New York, 1996, pp. 85-102.
[13] D. Schulthesiss, S. Machtens and U. Jonas, “Testosterone Therapy in the Aging Male: What about the Prostate?” Andrologia, Vol. 36, No. 6, 2004, pp. 355-365.
http://dx.doi.org/10.1111/j.1439-0272.2004.00630.x
[14] J. M. Kaufman and A. Vermeulen, “The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications,” Endocrine Reviews, Vol. 26, No. 6, 2005, pp. 833-876.
http://dx.doi.org/10.1210/er.2004-0013
[15] G. R. Cunningham and S. M. Toma, “Why Is Androgen Replacement in Males Controversial?” Journal Clinical Endocrinology Metabolism, Vol. 96, No. 1, 2011, pp. 38-52. http://dx.doi.org/10.1210/jc.2010-0266
[16] B. B. Yeap, H. Alfonso, S. A. P. Chubb, D. J. Handelsman, G. J. Hankey, J. Golledge, et al., “Lower Plasma Testosterone or Dihydrotestosterone, but No Estradiol, Is Associated with Symptoms of Intermittent Claudication in Older Men,” Clinical Endocrinology, Vol. 79, No. 1, 2013, pp. 725-732.
[17] Y.-S. Zhu and J. L. Imperato-McGinely, “5α-Reductase Isozymes and Androgen Actions in the prostate,” Annals of the New York Academy of Sciences, Vol. 1155, 2009, pp. 43-56.
http://dx.doi.org/10.1111/j.1749-6632.2009.04115.x
[18] L. N. Thomas, R. C. Douglas, C. B. Lazier, C. K. L. Too, R. S. Rittmaster and D. J. Tindall, “Type 1 and Type 2 5α-Reductase Expression in the Development and Progression of Prostate Cancer,” European Urology, Vol. 53, No. 1, 2008, pp. 244-252.
http://dx.doi.org/10.1016/j.eururo.2007.10.052
[19] G. Androle, N. Bruchovsky, L. W. K, Chung, A. M. Matsumoto, R. Rittimaster, C. Roehrborn, et al., “Dihydrotestosterone and the Prostate: The Scientific Rationale for 5α-Reductase Inhibitors in the Treatment of Benign Prostatic Hyperplasia,” Journal Urology, Vol. 172, No. 4, 2004, pp. 1399-1408.
http://dx.doi.org/10.1097/01.ju.0000139539.94828.29
[20] C. L. Smith, “Estrogens, Overview,” In: E. Knobil and J. D. Neill, Eds., Encyclopedia of Reproduction, Vol. 2, Academic Press, New York, 1999, pp. 119-126.
[21] K. D. R. Setchell, C. Clerici, E. D. Lephart, S. J. Cole, C. Heenan, D. Castellani, et al., “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,” American Journal Clinical Nutrition, Vol. 81, No. 5, 2005, pp. 1072-1079.
[22] D. L. Hemsell, J. M. Grodin, P. K, Siiteri and P. C. McDonald, “Plasma Precursors of Estrogen II. Correlation of the Extent of Plasma Androstenedione to Estrone with Age,” Journal Clinical Endocrinology Metabolism, Vol. 38, No. 3, 1974, pp. 476-479.
http://dx.doi.org/10.1210/jcem-38-3-476
[23] S. E. Bulun and E. R. Simpson, “Competitive RT-PCR Analysis Indicates Levels of Aromatase Cytochrome P450 transcripts in Adipose Tissue of Buttocks, Thighs and Abdomen of Women Increase with Advancing Age,” Journal Clinical Endocrinology Metabolism, Vol. 78, No. 2, 1994, pp. 428-432.
http://dx.doi.org/10.1210/jc.78.2.428
[24] S. M. Haffner, R. A. Valdez, M. P. Stern and M. S. Katz, “Obesity, Body-Fat Distribution and Sex-Hormones in Men,” International Journal Obesity, Vol. 17, No. 11, 1993, pp. 643-649.
[25] A. Gautier, F. Bonnet, S. Dubois, C. Massart, C. Grosheny, A. Bachelot, C. Aube, B. Balkau and P.-H. Ducluzeau, “Associations between Visceral Adipose Tissue, Inflammation and Sex Steroid Concentrations in Men,” Clinical Endocrinology, Vol. 78, No. 3, 2013, pp. 373378.
[26] V. Giguère, “To ERR in the Estrogen Pathway,” Trends Endocrinology Metabolism, Vol. 13, No. 5, 2002, pp. 220-225. http://dx.doi.org/10.1016/S1043-2760(02)00592-1
[27] E. A. Ariazi, G. M. Clark and J. E. Mertz, “EstrogenRelated Receptor α and Estrogen-Related Receptor β Associate with Unfavorable and Favorable Biomarkers, Respectively, in Human Breast Cancer,” Cancer Research, Vol. 62, No. 22, 2002, pp. 6510-6518.
[28] S. Yu, X. Wang, C. F. Ng, S. Chen and F. L. Chan, “EER-Gamma Suppresses Cell Proliferation and Tumor Growth of Androgen-Sensitive and Androgen-Insensitive Prostate Cancer Cells and Its Implication as a Therapeutic Target for Prostate Cancer,” Cancer Research, Vol. 67, No. 10, 2007, pp. 4909-4914.
http://dx.doi.org/10.1158/0008-5472.CAN-06-3855
[29] S. Yu, Y. C. Wong, M. T. Ling, C. F. Ng, S. Chen and F. L. Chen, “Orphan Nuclear Receptor Estrogen-Related Receptor-Gamma Suppresses in Vitro and in Vivo Growth of Prostate Cancer Cells via p21WAF1/CIP1 Induction and as a Potential Therapeutic Target in Prostate Cancer,” Oncogene, Vol. 27, No. 23, pp. 3313-3328.
http://dx.doi.org/10.1038/sj.onc.1210986
[30] M. Emberton, N. Zinner, M. C. Michel, M. Gittelman, M.-K. Chung and S. Madersbacher, “Managing the Progression of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: Therapeutic Options for the Man at Risk,” British Journal of Urology International, Vol. 100, No. 2, 2007, pp. 249-253.
http://dx.doi.org/10.1111/j.1464-410X.2007.07056.x
[31] M. J. Barry and C. G. Roehrborn, “Benign Prostatic Hyperplasia,” British Medical Journal, Vol. 323, No. 7320, 2001, pp. 1042-1046.
http://dx.doi.org/10.1136/bmj.323.7320.1042
[32] K. T. McVary, C. G. Roehrborn, A. Avins, M. J. Barry, R. C. Bruskewitz, R. F. Donnell, et al., “Guideline on the Management of Benign Prostatic Hyperplasia (BPH),” American Urological Association Education and Research, Inc., Baltimore, 2010, pp. 1-134.
[33] C. Manach, G. Williamson, C. Morand, A. Scalbert and C. Rémésy, “Bioavailability and Bioefficacy of Polyphenols in Humans, I. Review of 97 Bioavailability Studies,” American Journal Clinical Nutrition, Vol. 81, Supplement 1, 2005, pp. 230S-242S.
[34] H. Adlercreutz and W. Mazur, “Phyto-Estrogens and Western Diseases,” Annuals of Medicine, Vol. 29, No. 2, 1997, pp. 95-120.
http://dx.doi.org/10.3109/07853899709113696
[35] C. Brössner, K. Petritsch, K. Fink, M. Auprich, S. Madersbacher and H. Adlercreutz, et al., “ Phytoestrogen Tissue Levels in Benign Prostatic Hyperplasia and Prostate Cancer and Their Association with Prostate Diseases,” Urology, Vol. 64, No. 4, 2004, pp. 707-711.
http://dx.doi.org/10.1016/j.urology.2004.04.046
[36] V. U. Kumar, “Phyto-Oestrogens and Prostatic Growth,” National Medical Journal of India, Vol. 17, No. 1, 2004, pp. 22-26.
[37] K. Griffiths, L. Denis, A. Turkes and S. Morton, “Phytoestrogens and Diseases of the Prostate Gland,” Bailliere’s Clinical Endocrinology and Metabolism, Vol. 12, No. 4, 1998, pp. 625-647.
http://dx.doi.org/10.1016/S0950-351X(98)80008-6
[38] K. D. Setchell and C. Clerici, “Equol: History, Chemistry, and Formation,” Journal of Nutrition, Vol. 140, No. 7, 2010, pp. 1355S-1362S.
http://dx.doi.org/10.3945/jn.109.119776
[39] C. Manach, A. Scalbert, C. Morand, C. Rémésy and L. Jime’nez, “Polyphenols: Food Sources and Bioavaiability,” American Journal Clinical Nutrition, Vol. 79, No. 5, 2004, pp. 727-747.
[40] H. Adlercreutz, M. Yaghoob and K. Höckerstedt, “Diet and Breast Cancer,” Acta Oncologica, Vol. 31, No. 2, 1992, pp. 175-181.
http://dx.doi.org/10.3109/02841869209088899
[41] H. Adlercreutz, “Phytoestrogen: Epidemiology and a Possible Role in Cancer Protection,” Environmental Health Perspectives, Vol. 103, Supplement 7, 1995, pp. 103-112.
[42] K. D. Setchell, S. P. Borriello, P. Hulme, D. N. Kirk and M. Axelson, “Nonsteroidal Estrogens of Dietary Origin: Possible Roles in Hormone-Dependent Disease,” American Journal of Clinical Nutrition, Vol. 40, No. 3, 1984, pp. 569-578.
[43] J. M. Smoliga, J. A. Baur and H. A. Hausenblas, “Resveratrol and Health—A Comprehensive Review of Human Clinical Trials,” Molecular Nutrition & Food Research, Vol. 55, No. 8, 2011, pp. 1129-1141.
http://dx.doi.org/10.1002/mnfr.201100143
[44] K. F. Kiple and K. C. Ornelas, “Soybean,” In: The Cambridge World History of Food, Vol. 1, Cambridge University Press, New York, 2000, pp. 422-427.
[45] USDA, “USDA—Iowa State University Database on the Isoflavone Content of Foods, Release 1.4,” Agricultural Research Service, Beltsville Human Nutrition Research Center, Nutrient Data Laboratory, Beltsville, 2007.
[46] K. D. R. Setchell, N. M. Brown and E. Lydeking-Olson, “The Clinical Importance of the Metabolite Equol—A Clue to the Effectiveness of Soy and Its Isoflavones,” Journal of Nutrition, Vol. 132, No. 12, 2002, pp. 3577-3584.
[47] C. Atkinson, C. L. Frankenfeld and J. W. Lampe, “Gut Bacterial Metabolism of the Soy Isoflavone Daidzein: Exploring the Relevance to Human Health,” Experimental Biology & Medicine, Vol. 230, No. 3, 2005, pp. 155170.
[48] I. R. Rowland, T. A. Sanders, H. Adlercreutz and E. A. Bowey, “Inter-Individual Variation in Metabolism of Soy Isoflavones and Lignans: Influence of Habitual Diet on Equol Production by the Gut Flora,” Nutriton and Cancer, Vol. 36, No. 1, 2000, pp. 27-32.
http://dx.doi.org/10.1207/S15327914NC3601_5
[49] J.-P. Yuan, J.-H. Wang and X. Liu, “Metabolism of Dietary Soy Isoflavones to Equol by Human Intestinal Microflora-Implications for Health,” Molecular Nutrition & Food Research, Vol. 51, No. 7, 2007, pp. 765-781.
http://dx.doi.org/10.1002/mnfr.200600262
[50] K. Ozasa, M. Nakao, Y. Watanabe, K. Hayaski, T. Miki, K. Mikami, et al., “Association of Serum Phytoestrogen Concentration and Dietary Habits in a Sample Set of the JACC Study,” Journal of Epidemiology, Vol. 15, Supplement 2, 2005, pp. S196-S202.
http://dx.doi.org/10.2188/jea.15.S196
[51] J. W. Lampe, “Isoflavonoid and Lignan Phytoestrogens as Dietary Biomarkers,” Journal of Nutrition, Vol. 133, Suppl. 3, 2003, pp. 956S-964S.
[52] H. Adlercreutz, H. Honjo, A. Higashi, T. Fotsis, E. Hamalainen, T. Hasegawa, et al., “Urinary Excretion of Lignans and Isoflavonoids Phytoestrogens in Japanese Men and Women Consuming a Traditional Japanese Diet,” American Journal of Clinical Nutrition, Vol. 54, No. 6, 1991, pp. 1093-1100.
[53] T. E. Hedlund, P. D. Maroni, P. G. Ferucci, R. Dayton, S. Barnes, K, Jones, et al., “Long-Term Dietary Habits Affect Soy Isoflavone Metabolism and Accumulation in Prostatic Fluid in Causasian Men,” Journal Nutrition, Vol. 135, No. 6, 2005, pp. 1400-1406.
[54] L. Valentin-Blasini, M. A. Sadowski, D. Walden, L. Caltabiano, L. L. Needhan and D. B. Barr, “Urinary Phytoestrogen Concentrations in the U.S. Population (1999-2000),” Journal Exposure Analysis and Environmental Epidemiology, Vol. 15, No. 3, 2005, pp. 509-523.
http://dx.doi.org/10.1038/sj.jea.7500429
[55] A. Hoikkälä, S. Mustonen, I. Saastamoinen, T. Jokela, J. Taponen, H. Saloniemi, et al., “High Levels of Equol in Organic Skimmed Finnish Cow Milk,” Molecular Nutrition & Food Research, Vol. 51. No. 7, 2007, pp. 782-786. http://dx.doi.org/10.1002/mnfr.200600222
[56] C. Bannwart, H. Adlercreutz, T. Fotsis, K, Wähälä, T. Hare and G. Barrow, “Identification of Isoflavonic Phytoestrogens and Lignans in Urine of Human and in Cow Milk by GC/MS,” Advances in Mass Spectrometry, Vol. 10, No. 4, 1986, pp. 661-622.
[57] R. A. King, M. M. Mano and R. J. Head, “Assessment of Isoflavonoid Concentrations in Australian Bovine Milk Samples,” Journal of Dairy Research, Vol. 65, No. 3, 1998, pp. 479-489.
http://dx.doi.org/10.1017/S0022029998002891
[58] T. J. O. Lundh, H. I. Petersson and K. A. Martinsson, “Comparative Levels of Free and Conjugated Plant Estrogens in Blood Plasma of Sheep and Cattle Fed Ostrogenic Silage,” Journal of Agriculture and Food Chemistry, Vol. 38, No. 7, 1990, pp. 1530-1534.
http://dx.doi.org/10.1021/jf00097a022
[59] R. H. Common and L. Ainsworth, “Identification of Equol in the Urine of the Domestic Fowl,” Biochimica et Biophysica Acta, Vol. 53, No. 2, 1961, pp. 403-404.
http://dx.doi.org/10.1016/0006-3002(61)90452-8
[60] J. M. Hamilton-Reeves, G. Vazque, S. J. Duval, W. R. Phipps, M. S. Kurzer and M. J. Messian, “Clinical Studies Show no Effects of Soy Protein or Isoflavones on Reproductive Hormones in Men: Results of a Meta-Analysis,” Fertility and Sterility, Vol. 94, No. 3, 2010, pp. 997-1007.
http://dx.doi.org/10.1016/j.fertnstert.2009.04.038
[61] J. H. Mitchell, E. Cawood, D. Kinniburgh, A. Provan, A. R. Collins and D. S. Irvine, “Effect of a Phytoestrogen Food Supplement on Reproductive Health in Normal Males,” Clinical Science (London), Vol. 100, No. 6, 2001, pp. 613-618. http://dx.doi.org/10.1042/CS20000212
[62] A. Andres, M. A. Cleves, J. B. Bellando, R. T. Pivik, P. H. Casey and T. M. Badger, “Developmental Status of 1Year-Old Infants Fed Breast Milk, Cow’s Milk Formula, or Soy Formula,” Pediatrics, Vol. 129, No. 6, 2012, pp. 1134-1140. http://dx.doi.org/10.1542/peds.2011-3121
[63] J. M. Gilchrist, M. B. Moore, A. Andres, J. A. Estroff and T. M. Badger, “Ultrasonographic Patterns of Reproductive Organs in Infants Fed Soy Formula: Comparisons to Infants Fed Breast Milk and Milk Formula,” Journal of Pediatrics, Vol. 156, No. 2, 2010, pp. 215-220.
http://dx.doi.org/10.1016/j.jpeds.2009.08.043
[64] T. M. Badger, J. M. Gilchrist, R. T. Pivik, A. Andres, K. Shandar, J.-R. Chen and M. J. Ronis, “The Health Implications of Soy Infant Formula,” American Journal of Nutrition, Vol. 89, No. 5, 2009, pp. 1668S-1672S.
http://dx.doi.org/10.3945/ajcn.2009.26736U
[65] M. Axelson, D. N. Kirk, R. D. Farrant, G. Cooley, A. M. Lawson and K. D. R. Setchell, “The Identification of Equol [7-Hydroxy-3-(4’-Hydroxy Phenyl) Chroman] in Human Urine,” Biochemical Journal, Vol. 201, No. 2, 1982, pp. 353-357.
[66] K. D. R. Setchell, N. M. Brown, L. Zimmer-Nechemias, W. T. Brashear, B. E. Wolf, A. S. Kirschner, et al., “Evidence for Lack of Absorption of Soy Isoflavone Glycosides in Humans, Supporting the Crucial Role of Intestinal Metabolism for Bioavailability,” American Journal of Clinical Nutrition, Vol. 76, No. 2, 2002, pp. 447-453.
[67] K. D. R. Setchell and S. J. Cole, “Method of Defining Equol-Producer Status and Its Frequency among Vegetarians,” Journal of Nutrition, Vol. 136, No. 8, 2006, pp. 2188-2193.
[68] E. D. Lephart, “Isoflavones and prenatal Exposure to Equol, Chapter 29,” In: V. R. Preedy, Ed., Isoflavones: Chemistry, Analysis, Function and Effects, The Royal Society of Chemistry, Thomas Graham House, Cambridge, England, 2013, pp. 480-499.
[69] E. D. Lephart, J. P. Porter, D. W. Hedges, T. D. Lund and K. D. R. Setchell, “Phytoestrogens: Implications in Neurovascular Research,” Current Neurovascular Research, Vol. 1, No. 5, 2004, pp. 455-464.
http://dx.doi.org/10.2174/1567202043361974
[70] L. W. Gu, S. E. House, R. L. Prior, N. Fang, M. J. J. Ronis, T. B. Clarkson, et al., “Metabolic Phenotypes of Isoflavones Differ among Female Rats, Pigs, Monkeys, and Women,” Journal of Nutrition, Vol. 136, No. 5, 2006, pp. 1215-1221.
[71] C. C. Hoerger, F. E. Wettstein, H. J. Bachmann, K. Hungerbübler and T. D. Bucheli, “Occurrence and Mass Balance of Isoflavones on an Experimental Grassland Field,” Environmental Science & Technology, Vol. 45, No. 16, 2011, pp. 6752-6760.
http://dx.doi.org/10.1021/es200567b
[72] G. H. Degen, M. Balaszkewicz, L. J. Shi, A. E. Buyken and T. Remer, “Urinary Isoflavone Phytoestrogens in German Children and AdolescentsA Longitudinal Examination in the DONALD Cohort,” Molecular Nutrition Food Research, Vol. 55, No. 3, 2011, pp. 359-367.
http://dx.doi.org/10.1002/mnfr.201000325
[73] E. A. Mustonen, M. Tuori, I. Saastamoinen, J. Taponen, K. Wähälä, H. Saloniemi and A. Vanhatalo, “Equol in Milk of Dairy Cows Is Derived from Forage Legumes such as Red Clover,” British Journal of Nutrition, Vol. 102, No. 11, 2009, pp. 1552-1556.
http://dx.doi.org/10.1017/S0007114509990857
[74] C. L. Frankenfeld, “Dairy Consumption Is a Significant Correlate of Urinary Equol Concentration in Representative Sample of US Adults,” American Journal of Clinical Nutrition, Vol. 93, No. 5, 2011, pp. 1109-1116.
http://dx.doi.org/10.3945/ajcn.111.011825
[75] A. Höjer, S. Alder, S. Purup, J. Hansen-Møller, K. Martinsson, H. Steinshamn and A.-M. Gustavsson, “Effects of Feeding Dairy Cows Different-Legume-Grass Silages on Milk Phytoestrogen Concentration,” Journal of Dairy Science, Vol. 95, No. 8, pp. 4526-4540.
http://dx.doi.org/10.3168/jds.2011-5226
[76] N. Hounsome, B. Hounsome, D. Tomos and G. EdwardsJones, “Changes in Antioxidant Compounds in White Cabbage during Winter Storage,” Postharvest Biology & Technology, Vol. 52, No. 2, 2009, pp.173-179.
http://dx.doi.org/10.1016/j.postharvbio.2008.11.004
[77] N. Hounsome, B. Grail, A. D. Tomos, B. Hounsome and Edwards-Jones, “High-Throughput Anti-Oxidant Profiling in Vegetables by Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry,” Functional Plant Science and Biotechnology, Vol. 4, No. 1, 2010, pp. 1-10.
[78] Y. Abiru, M. Kumenura, T. Ueno, S. Uchiyama and K. Masaki, “Discovery of an S-Equol Rich Food Stinky Tofu, a Traditional Fermented Soy Product in Taiwan,” International Journal of Food Science and Nutrition, Vol. 63, No. 8, 2012, pp. 964-970.
http://dx.doi.org/10.3109/09637486.2012.687369
[79] H. J. Jou, P. J. Tsai, J. H. Tu and W. H. Wu, “Stinky Tofu as a Rich Source of Bioavailable S-Equol in Asian Diets,” Journal of Functional Foods, Vol. 5, No. 2, 2013, pp. 651-659.
http://dx.doi.org/10.1016/j.jff.2013.01.006
[80] J. H. Mitchell, P. T. Gardner, D. B. McPhail, P. C. Morrice, A. R. Collins and G. C. Duthie, “Antioxidant Efficacy of Phytoestrogens in Chemical and Biological Model Systems,” Archives of Biochemistry and Biophysics, Vol. 360, No. 1, 1998, pp. 142-148.
http://dx.doi.org/10.1006/abbi.1998.0951
[81] A. Arora, M. G. Nair and G. M. Strasburg, “Antioxidant Activities of Isoflavones and Their Biological Metabolites in a Liposomal Dystem,” Archives of Biochemistry and Biophysics, Vol. 356, No. 2, 1998, pp. 133-141.
http://dx.doi.org/10.1006/abbi.1998.0783
[82] C. E. Rüfer and S. E. Kulling, “Antioxidant Activity of Isoflavones and Their Major Metabolites Using Different in Vitro Assays,” Journal of Agriculture and Food Chemistry, Vol. 54, No. 8, 2006, pp. 2926-2931.
http://dx.doi.org/10.1021/jf053112o
[83] R. Gopaul, H. E. Knaggs and E. D. Lephart, “Biochemical Investigation and Gene Analysis of Equol: A Plant and Soy-Derived Isoflavonoid with Anti-Aging and Antioxidant Properties with Potential Human Skin Applications,” BioFactors, Vol. 38, No. 1, 2012, pp. 44-52.
http://dx.doi.org/10.1002/biof.191
[84] E. D. Lephart, “Protective Effects of Equol and Their Polyphenolic Isomers against Dermal Aging: Mircoarray/Protein Evidence with Clinical Implications and Unique Delivery into Human Skin,” Pharmaceutical Biology, Vol. 51, No. 11, 2013, pp. 1393-1400.
http://dx.doi.org/10.3109/13880209.2013.793720
[85] K. D. R. Setchell, X. Zhao, P. Jha, J. E. Heubi and N. M. Brown, “The Pharmacokinetic Behavior of the Soy Isoflavone Metabolite S-Equol and Its Diastereoismer R-Equol in Healthy Adults Determined by Using Stable-IsotopeLabeled Tracers,” American Journal of Clinical Nutrition, Vol. 90, No. 4, 2009, pp. 1029-1037.
http://dx.doi.org/10.3945/ajcn.2009.27981
[86] T. D. Lund, D. J. Munson, M. E. Hadley, K. D. R. Setchell, E. D. Lephart and R. J. Handa, “Equol Is a Novel Anti-Androgen that Inhibits Prostate Growth and Hormone Feedback,” Biology Reproduction, Vol. 70, No. 4, 2004, pp. 1188-1195.
http://dx.doi.org/10.1095/biolreprod.103.023713
[87] T. D. Lund, L. Blake, L. Bu, A. N. Hamaker and E. D. Lephart, “Equol an Isoflavonoid: Potential for Improved Prostate Health, in Vitro and in Vivo Evidence,” Reproductive Biology and Endocrinology, Vol. 9, 2011, p. 4.
[88] J. Hirvonen, A. M. Rajalin, G. Wohlfahrt, H. Adlercreutz, K. Wøhølø and P. Aarnisalo, “Transcriptional Activity of Estrogen-Related Receptor Gamma (ERRgamma) Is Stimulated by the Phytoestrogen Equol,” Journal of Steriod Biochemistry and Molecular Biology, Vol. 123, No. 1-2, 2011, pp. 46-57.
http://dx.doi.org/10.1016/j.jsbmb.2010.11.001
[89] T. Fujimura, S. Takahashi, T. Urano, et al., “Differential Expression of Estrogen-Related Receptors Beta and Gamma (ERRβ and ERRγ) and Their Clinical Significance in Human Prostate Cancer,” Cancer Science, Vol. 101, No. 3, 2010, pp. 646-651.
http://dx.doi.org/10.1111/j.1349-7006.2009.01451.x
[90] J. M. Hamilton-Reeves, S. A. Rebello, W. Thomas, J. W. Slaton and M. S. Kurzer, “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,” Journal of Nutrition, Vol. 137, No. 7, 2007, pp. 1769-1775.
[91] T. D. Lund, D. J. Munson, H. Adlercreutz, R. J. Handa and E. D. Lephart, “Androgen Receptor Expression in the Rat Prostate Is Down Regulated by Dietary Phytoestrogens,” Reproductive Biology and Endocrinology, Vol. 2, 2004, p. 5.
[92] C. D. Gardner, B. Oelrich, J. P. Liu, D. Feldmen, A. A. Franke and J. D. Brooks, “ Prostatic Soy Isoflavone Concentrations Exceed Serum Levels after Dietary Supplementation,” Prostate, Vol. 69, No. 7, 2009, pp. 719-726.
http://dx.doi.org/10.1002/pros.20922
[93] E. D. Lephart, “Severe and Moderate BPH Symptoms in Mid-Aged Men Improved with Isoflavonoid-Equol Treatment: Pilot Intervention Study,” Open Journal of Urology, Vol. 3, No. 1, 2013, pp. 21-27.
[94] E. D. Lephart, “Safety Assessment of R,S-Equol as a Dietary Supplement for Benign Prostatic Hyperplasia,” Proceedings Society of Toxicology, Phoenix, 2014, pbn. 1585, p. 244.
[95] H. Akaza, N. Miyanaga, N. Takashima, S. Naito, S. Hirao, Y. Tsukamoto, T. Fujloka, et al., “Comparisons of Percent Equol Producers between Prostate Cancer Patients and Controls: Case-Controlled Studies of Isoflavones in Japanese, Korean and American Residents,” Japanese Journal of Clinical Oncology, Vol. 34, No. 2, 2004, pp. 86-89. http://dx.doi.org/10.1093/jjco/hyh015
[96] P. J. Magee, M. Raschke, C. Steiner, J. G. Duffin, B. L. Pool-Zobel, T. Jokela, et al., “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,” Nutrition and Cancer, Vol. 54, No. 2, 2006, pp. 232-242.
http://dx.doi.org/10.1207/s15327914nc5402_10
[97] M. Tanaka, K. Fujimoto, Y. Chihara, K. Torimoto, T. Yoneda and N. Tanaka, “Isoflavone Supplements Stimulated the Production of Serum Equol and Decreased the Serum Dihydrotestosterone Levels in Healthy Male Volunteers,” Prostate Cancer and Prostatic Disease, Vol. 12, No. 3, 2009, pp. 247-252.
http://dx.doi.org/10.1038/pcan.2009.10
[98] C. C. Douglas, S. A. Johnson and B. H. Arjmandi, “Soy and Its Isoflavones: The Truth behind the Science in Breast Cancer,” Anti-Cancer Agents in Medicinal Chemistry, Vol. 13, No. 8, 2013, pp. 1178-1187.
http://dx.doi.org/10.2174/18715206113139990320
[99] D. Ingram, K, Sanders, M. Kolybaba and D. Lopez, “CaseControl Study of Phyto-Oestrogens and Breast Cancer,” Lancet, Vol. 350, No. 9083, 1997, pp. 990-994.
http://dx.doi.org/10.1016/S0140-6736(97)01339-1
[100] P. J. Magee, P. Allsopp, A. Samaletdin and I. R. Rowland, “Daidzein, R-equol and S-equol Inhibit the Invasion of MDA-MB-231 Breast Cancer Cells Potentially via the Down-Regulation of Matrix Metalloproteinase-2,” European Journal of Nutrition, Epub Ahead of Print, 2013.
[101] C. Charalambous, C. A. Pitta and A. I. Constantinou, “Equol Enhances Tamoxifen’s Anti-Tumor Activity by Induction of Caspase-Mediated Apoptosis in MCF-7 Breast Cancer Cells,” BMC Cancer, Vol. 13, 2013, p. 238.
[102] M. Minatoya, G. Kutomi, S. Asakura, S. Otokozawa, Y. Sugiyama, Y. Nagata, et al., “Equol, Adiponectin, Insulin Levels and Risk of Breast Cancer,” Asian Pacific Journal of Cancer Prevention, Vol. 14, No. 4, 2013, pp. 21912199. http://dx.doi.org/10.7314/APJCP.2013.14.4.2191
[103] V. Singh, P. Sharma and N. Capulash, “DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer,” Current Cancer Drug Targets, Vol. 13, No. 4, 2013, pp. 379-399.
http://dx.doi.org/10.2174/15680096113139990077
[104] W. Zheng, Y. Zhang, D. Ma, Y. Shi, C. Liu and P. Wang, “Equol Inhibits Invasion in Prostate Cancer DU145 Cells Possibly via Down-Regulation of Matrix Metalloproteinase-9, Matrix Metalloproteinase-2 and Urokinase-Type Plasmiogen Activator by Antioxidant Activity,” Journal of Clinical Biochemical Nutrition, Vol. 51, No. 1, 2012, pp. 61-67. http://dx.doi.org/10.3164/jcbn.11-54
[105] T. E. Richardson and J. W. Simpkins, “Rand S-Equol Have Equivalent Cytoprotective Effects in Friedreich’s Ataxia,” BMC Pharmacology and Toxicology, Vol. 13, 2012, p. 12.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.