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Genistein

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Genistein

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What Is It?

Genistein is structurally classified as an isoflavone. It is a phytoestrogen naturally derived from plants, and has a structure similar to estrogens1^11. Genistein can bind to estrogen receptors to activate or inhibit downstream signaling cascades depending on the context2^22. Genistein is known to have several anticancer effects, functioning as a tyrosine kinase inhibitor3^33, an angiogenesis inhibitor4^44, and antioxidant/anti-inflammatory nutrient5^55.

What Are Its Other Names?

Genistein is also known as genestein, prunetol, genisterin, genisteol, sophoric and bonistein (synthetic genistein). Its IUPAC name is 5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one1^11.

What Foods Have It?

Soy products such as soy milk, tofu, and fermented soy products are the primary food sources of genistein. Although food processing can lower genistein content, soy products still contain the highest genistein levels compared to all other foods6,7^{6,7}6,7. Legumes also contain genistein. Vegetables have been found to contain trace amounts of genistein8^88. A summary of the average genistein quantity in common foods is as follows:

Food Amount
Average Content (mg/100g)
Reference
Soybeans (mature seeds)
80.99
7
Tofu
1.63
6
Soy milk
0.41-6.07
6, 7
Miso
23.24
7
Red clover
10.00
7
Legumes (various)
0.062
8

What Are Its Main Benefits?

Genistein is mainly studied for its anticancer effects. Since genistein can bind to estrogen receptors, it might play a role in treating hormone-related cancers such as breast and prostate cancer. Metabolites of genistein are found to inhibit angiogenesis, endothelial cell proliferation, and play a role in DNA repair, contributing to its anti-cancer effects9^99. Anticancer effects are also related to genistein’s role as a tyrosine kinase inhibitor3^33. Genistein also prevents cancer through antioxidant and anti-inflammatory effects5^55. In addition, researchers found that genistein can provide postmenopausal symptom relief, such as alleviating hot flashes1,10^{1,10}1,10. Genistein is known for its ability to maintain cardiovascular and bone health10^{10}10.

What Are Its Main Drawbacks?

At normal dietary doses, very few side effects or drawbacks of genistein consumption have been identified to date11,12^{11,12}11,12. When consumed in high doses, however, genistein might damage DNA, adversely affecting healthy cells (via apoptosis or cell cycle arrest)13^{13}13. However, these effects have only been noted in cell and animal studies. Maternal genistein can be transferred to infants through breastmilk. When infants are fed soy formula, infant serum genistein concentration can increase by up to 100-fold higher than normal14^{14}14. No studies have explicitly stated any harm in having high serum genistein concentrations.

What Are Its Mechanisms of Action?

  1. Estrogen Agonist and Antagonist: Genistein is structurally similar to estrogen, so it can compete with endogenous estrogens for receptor binding, potentially activating or blocking them depending on the biological context12^{12}12. In terms of stimulating estrogenic effects, genistein has been shown to increase bone density in postmenopausal women (a known effect of estrogen), suggesting that it can stimulate estrogenic effects on bone tissue15^{15}15. Some studies suggest that genistein can inhibit the activity of estrogen receptors and block estrogen signaling12^{12}12, which may contribute to its potential anti-cancer effects in breast cancer. In hormone-related cancers, estrogen receptors are often overexpressed and play a major role in tumorigenesis through signalling cell growth. Estrogen receptors are major targets for hormone therapy in treating breast cancer16^{16}16. Without this cell growth signaling mechanism in the tumor, cancer cells may undergo apoptosis17^{17}17.
  2. Tyrosine Kinase Inhibitor: Genistein acts as a tyrosine kinase inhibitor to block numerous downstream signaling pathways3^33. Tyrosine kinases act as the initial site of activation in many signaling pathways. In particular, genistein is demonstrated to be an inhibitor of the epidermal growth factor receptor (EGFR), which is associated with tumor growth in a variety of cancers (e.g., some non-small cell lung18,19^{18,19}18,19, head and neck20^{20}20, colorectal21^{21}21, pancreatic22^{22}22, breast23^{23}23, and brain24^{24}24 cancers). A study also found that it can inhibit cancer cell proliferation and migration through Akt and MAPK signaling pathways25,26^{25,26}25,26.
  3. Anti-Angiogenesis: Angiogenesis is crucial for cancer growth as it allows the growth of new blood vessels. Genistein has been shown to prevent angiogenesis through its function as a tyrosine kinase inhibitor4^44. Genistein can interrupt the vascular endothelial growth factor (VEGF) signaling pathway, which is crucial for angiogenesis27^{27}27. Other molecular targets for genistein’s anti-angiogenesis effects are under investigation28^{28}28.
  4. Antioxidant and Anti-Inflammatory Properties: Research shows genistein has antioxidant and anti-inflammatory properties5^{5}5 both in vitro and in vivo. Its mechanisms of action depend on its ability to regulate signaling pathways, leading to an increased production of antioxidant enzymes29^{29}29. It has been suggested that these mechanisms make genistein useful for treating or preventing cancer30^{30}30, as well as age-related diseases such as Alzheimer’s disease31,32^{31,32}31,32.

What Are Typical Doses and Durations?

For clinical studies investigating the independent effects of genistein, the typical dosage varies from 20-60 mg/day. Some studies interested in high dose consumption used dosages as high as 450 mg/day. For studies on soy isoflavones, consisting of mostly genistein and daidzein, dosages also range from 20-60 mg/day. Individual amounts of genistein and daidzein may or may not be mentioned in these studies. Around half of the weight of standard soy isoflavones formulas is genistein1^{1}1. For comparison, for soy-based diets, the typical genistein content is 0.25-1 mg/kg/day.33^{33}33 Study durations are highly varied. Short term interventions range from a few weeks to 2 months, with long term studies up to 2 years.

Summary of Data

A total of 25 human clinical studies or randomized controlled trials were identified from PubMed33−57^{33-57}33−57. A summary of the results for each cancer type is as follows:

Cancer Type
General Effect (% based on number of studies with positive or negative effects)
Evidence (number of studies, participants)
General
100% reported beneficial effects
2 studies; 54 participants
Breast
44% reported beneficial effects 33% reported harmful effects 22% reported no significant effects
9 studies; 891 participants
Prostate
83% reported beneficial effects 17% reported no significant effects
12 studies; 613 participants
Bladder
100% reported beneficial effects
1 study, 59 participants
Colorectal
100% reported harmful effects
1 study, 140 participants

📄 Detailed Genistein human clinical trial study notes analyzed by Anticancer.ca

References

  1. PubChem. Genistein. pubchem.ncbi.nlm.nih.gov. Accessed March 10, 2023. https://pubchem.ncbi.nlm.nih.gov/compound/5280961
  2. Kim SH, Park MJ. Effects of phytoestrogen on sexual development. Korean J Pediatr. 2012;55(8):265. doi:10.3345/kjp.2012.55.8.265
  3. Nichols MR, Morimoto BH. Tyrosine Kinase-Independent Inhibition of Cyclic-AMP Phosphodiesterase by Genistein and Tyrphostin 51. Arch Biochem Biophys. 1999;366(2):224-230. doi:10.1006/abbi.1999.1200
  4. Varinska L, Gal P, Mojzisova G, Mirossay L, Mojzis J. Soy and Breast Cancer: Focus on Angiogenesis. Int J Mol Sci. 2015;16(12):11728-11749. doi:10.3390/ijms160511728
  5. Jaiswal KS, Malka O, Shauloff N, et al. Genistein carbon dots exhibit antioxidant and anti-inflammatory effects in vitro. Colloids Surf B Biointerfaces. 2023;223:113173. doi:10.1016/j.colsurfb.2023.113173
  6. Showing all foods in which the polyphenol Genistein is found - Phenol-Explorer. phenol-explorer.eu. Accessed March 10, 2023. http://phenol-explorer.eu/contents/polyphenol/396
  7. Bhagwat S, Haytowitz DB, Holden JM. USDA Database for the Isoflavone Content of Selected Foods, Release 2.0.; 2008. Accessed March 10, 2023. https://www.ars.usda.gov/arsuserfiles/80400525/data/isoflav/isoflav_r2.pdf
  8. Liggins J, Bluck LJC, Runswick S, Atkinson C, Coward WA, Bingham SA. Daidzein and genistein contents of vegetables. Br J Nutr. 2000;84(5):717-725. doi:10.1017/S0007114500002075
  9. Spagnuolo C, Russo GL, Orhan IE, et al. Genistein and Cancer: Current Status, Challenges, and Future Directions. Adv Nutr. 2015;6(4):408-419. doi:10.3945/an.114.008052
  10. Thangavel P, Puga-Olguín A, Rodríguez-Landa JF, Zepeda RC. Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases. Molecules. 2019;24(21):3892. doi:10.3390/molecules24213892
  11. Busby MG, Jeffcoat AR, Bloedon LT, et al. Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men. Am J Clin Nutr. 2002;75(1):126-136. doi:10.1093/ajcn/75.1.126
  12. Sharifi-Rad J, Quispe C, Imran M, et al. Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits. Oxid Med Cell Longev. 2021;2021:3268136. doi:10.1155/2021/3268136
  13. Sirtori CR. Risks and Benefits of Soy Phytoestrogens in Cardiovascular Diseases, Cancer, Climacteric Symptoms and Osteoporosis: Drug Saf. 2001;24(9):665-682. doi:10.2165/00002018-200124090-00003
  14. Cao Y, Calafat AM, Doerge DR, et al. Isoflavones in urine, saliva, and blood of infants: data from a pilot study on the estrogenic activity of soy formula. J Expo Sci Environ Epidemiol. 2009;19(2):223-234. doi:10.1038/jes.2008.44
  15. Wu Z, Liu L. The protective activity of genistein against bone and cartilage diseases. Front Pharmacol. 2022;13:1016981. doi:10.3389/fphar.2022.1016981
  16. Hua H, Zhang H, Kong Q, Jiang Y. Mechanisms for estrogen receptor expression in human cancer. Exp Hematol Oncol. 2018;7(1):24. doi:10.1186/s40164-018-0116-7
  17. Wang TTY, Sathyamoorthy N, Phang JM. Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis. 1996;17(2):271-275. doi:10.1093/carcin/17.2.271
  18. Bethune G, Bethune D, Ridgway N, Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010;2(1):48-51.
  19. Ohsaki Y, Tanno S, Fujita Y, et al. Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep. Published online May 1, 2000. doi:10.3892/or.7.3.603
  20. Kalyankrishna S, Grandis JR. Epidermal Growth Factor Receptor Biology in Head and Neck Cancer. J Clin Oncol. 2006;24(17):2666-2672. doi:10.1200/JCO.2005.04.8306
  21. Chan DLH, Segelov E, Wong RS, et al. Epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer. Cochrane Colorectal Cancer Group, ed. Cochrane Database Syst Rev. Published online June 27, 2017. doi:10.1002/14651858.CD007047.pub2
  22. Oliveira-Cunha M, Newman WG, Siriwardena AK. Epidermal Growth Factor Receptor in Pancreatic Cancer. Cancers. 2011;3(2):1513-1526. doi:10.3390/cancers3021513
  23. Masuda H, Zhang D, Bartholomeusz C, Doihara H, Hortobagyi GN, Ueno NT. Role of Epidermal Growth Factor Receptor in Breast Cancer. Breast Cancer Res Treat. 2012;136(2):10.1007/s10549-012-2289-9. doi:10.1007/s10549-012-2289-9
  24. Xu H, Zong H, Ma C, et al. Epidermal growth factor receptor in glioblastoma. Oncol Lett. 2017;14(1):512-516. doi:10.3892/ol.2017.6221
  25. Park SS, Kim YN, Jeon YK, et al. Genistein-induced apoptosis via Akt signaling pathway in anaplastic large-cell lymphoma. Cancer Chemother Pharmacol. 2005;56(3):271-278. doi:10.1007/s00280-004-0974-z
  26. Chen C, Wang Y, Chen S, et al. Genistein inhibits migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways. Taiwan J Obstet Gynecol. 2020;59(3):403-408. doi:10.1016/j.tjog.2020.03.012
  27. Yu X, Zhu J, Mi M, Chen W, Pan Q, Wei M. Anti-angiogenic genistein inhibits VEGF-induced endothelial cell activation by decreasing PTK activity and MAPK activation. Med Oncol. 2012;29(1):349-357. doi:10.1007/s12032-010-9770-2
  28. Su SJ, Yeh TM, Chuang WJ, et al. The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol. 2005;69(2):307-318. doi:10.1016/j.bcp.2004.09.025
  29. Park CE, Yun H, Lee EB, et al. The Antioxidant Effects of Genistein Are Associated with AMP-Activated Protein Kinase Activation and PTEN Induction in Prostate Cancer Cells. J Med Food. 2010;13(4):815-820. doi:10.1089/jmf.2009.1359
  30. Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and Antipromotional Effects of the Soybean Isoflavone Genistein. Exp Biol Med. 1995;208(1):124-130. doi:10.3181/00379727-208-43844
  31. Gong D k., Liu B h., Tan X h. Genistein Prevents Cadmium-induced Neurotoxic Effects through its Antioxidant Mechanisms. Drug Res. 2014;65(02):65-69. doi:10.1055/s-0034-1372595
  32. Mas-Bargues C, Borrás C, Viña J. The multimodal action of genistein in Alzheimer’s and other age-related diseases. Free Radic Biol Med. 2022;183:127-137. doi:10.1016/j.freeradbiomed.2022.03.021
  33. Xu L, Ding Y, Catalona WJ, et al. MEK4 Function, Genistein Treatment, and Invasion of Human Prostate Cancer Cells. JNCI J Natl Cancer Inst. 2009;101(16):1141-1155. doi:10.1093/jnci/djp227
  34. McMichael-Phillips DF, Harding C, Morton M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr. 1998;68(6):1431S-1436S. doi:10.1093/ajcn/68.6.1431S
  35. Hargreaves DF. Two-Week Dietary Soy Supplementation Has an Estrogenic Effect on Normal Premenopausal Breast. J Clin Endocrinol Metab. 1999;84(11):4017-4024. doi:10.1210/jc.84.11.4017
  36. Atkinson C, Warren RM, Sala E, et al. Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res. 2004;6(3):R170. doi:10.1186/bcr773
  37. Atteritano M, Pernice F, Mazzaferro S, et al. Effects of phytoestrogen genistein on cytogenetic biomarkers in postmenopausal women: 1 year randomized, placebo-controlled study. Eur J Pharmacol. 2008;589(1-3):22-26. doi:10.1016/j.ejphar.2008.04.049
  38. Qin W, Zhu W, Shi H, et al. Soy Isoflavones Have an Antiestrogenic Effect and Alter Mammary Promoter Hypermethylation in Healthy Premenopausal Women. Nutr Cancer. 2009;61(2):238-244. doi:10.1080/01635580802404196
  39. Bolca S, Urpi-Sarda M, Blondeel P, et al. Disposition of soy isoflavones in normal human breast tissue. Am J Clin Nutr. 2010;91(4):976-984. doi:10.3945/ajcn.2009.28854
  40. Khan SA, Chatterton RT, Michel N, et al. Soy Isoflavone Supplementation for Breast Cancer Risk Reduction: A Randomized Phase II Trial. Cancer Prev Res (Phila Pa). 2012;5(2):309-319. doi:10.1158/1940-6207.CAPR-11-0251
  41. Shike M, Doane AS, Russo L, et al. The Effects of Soy Supplementation on Gene Expression in Breast Cancer: A Randomized Placebo-Controlled Study. JNCI J Natl Cancer Inst. 2014;106(9):dju189-dju189. doi:10.1093/jnci/dju189
  42. Lu LJW, Chen NW, Brunder DG, et al. Soy isoflavones decrease fibroglandular breast tissue measured by magnetic resonance imaging in premenopausal women: A 2-year randomized double-blind placebo controlled clinical trial. Clin Nutr ESPEN. 2022;52:158-168. doi:10.1016/j.clnesp.2022.10.007
  43. Habito RC, Montalto J, Leslie E, Ball MJ. Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males. Br J Nutr. 2000;84(4):557-563. doi:10.1017/S0007114500001872
  44. Rannikko A, Petas A, Rannikko S, Adlercreutz H. Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation. The Prostate. 2006;66(1):82-87. doi:10.1002/pros.20315
  45. Vaishampayan U, Hussain M, Banerjee M, et al. Lycopene and Soy Isoflavones in the Treatment of Prostate Cancer. Nutr Cancer. 2007;59(1):1-7. doi:10.1080/01635580701413934
  46. Swami S, Krishnan AV, Moreno J, et al. Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patients. Int J Cancer. 2009;124(9):2050-2059. doi:10.1002/ijc.24161
  47. Gardner CD, Oelrich B, Liu JP, Feldman D, Franke AA, Brooks JD. Prostatic soy isoflavone concentrations exceed serum levels after dietary supplementation. The Prostate. 2009;69(7):719-726. doi:10.1002/pros.20922
  48. deVere White RW, Tsodikov A, Stapp EC, Soares SE, Fujii H, Hackman RM. Effects of a High Dose, Aglycone-Rich Soy Extract on Prostate-Specific Antigen and Serum Isoflavone Concentrations in Men With Localized Prostate Cancer. Nutr Cancer. 2010;62(8):1036-1043. doi:10.1080/01635581.2010.492085
  49. Lazarevic B, Boezelijn G, Diep LM, et al. Efficacy and Safety of Short-Term Genistein Intervention in Patients with Localized Prostate Cancer Prior to Radical Prostatectomy: A Randomized, Placebo-Controlled, Double-Blind Phase 2 Clinical Trial. Nutr Cancer. 2011;63(6):889-898. doi:10.1080/01635581.2011.582221
  50. Lazarevic B, Hammarström C, Yang J, et al. The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy. Br J Nutr. 2012;108(12):2138-2147. doi:10.1017/S0007114512000384
  51. Bilir B, Sharma NV, Lee J, et al. Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer. Int J Oncol. 2017;51(1):223-234. doi:10.3892/ijo.2017.4017
  52. Bosland MC, Huang J, Schlicht MJ, Enk E, Xie H, Kato I. Impact of 18-Month Soy Protein Supplementation on Steroid Hormones and Serum Biomarkers of Angiogenesis, Apoptosis, and the Growth Hormone/IGF-1 Axis: Results of a Randomized, Placebo-Controlled Trial in Males Following Prostatectomy. Nutr Cancer. 2022;74(1):110-121. doi:10.1080/01635581.2020.1870706
  53. Bosland MC, Schmoll J, Watanabe H, Randolph C, Kato I. Randomized, Placebo-Controlled Six-Month Intervention Study of Soy Protein Isolate in Men with Biochemical Recurrence after Radical Prostatectomy: A Pilot Study. Nutr Cancer. 2022;74(2):555-564. doi:10.1080/01635581.2021.1903949
  54. Messing E, Gee JR, Saltzstein DR, et al. A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients. Cancer Prev Res (Phila Pa). 2012;5(4):621-630. doi:10.1158/1940-6207.CAPR-11-0455
  55. Adams KF, Lampe PD, Newton KM, et al. Soy protein containing isoflavones does not decrease colorectal epithelial cell proliferation in a randomized controlled trial. Am J Clin Nutr. 2005;82(3):620-626. doi:10.1093/ajcn/82.3.620
  56. Wiseman H, O’Reilly JD, Adlercreutz H, et al. Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans,,. Am J Clin Nutr. 2000;72(2):395-400. doi:10.1093/ajcn/72.2.395
  57. van der Velpen V, Geelen A, Schouten EG, Hollman PC, Afman LA, van ’t Veer P. Estrogen Receptor–Mediated Effects of Isoflavone Supplementation Were Not Observed in Whole-Genome Gene Expression Profiles of Peripheral Blood Mononuclear Cells in Postmenopausal, Equol-Producing Women. J Nutr. 2013;143(6):774-780. doi:10.3945/jn.113.174037

About This Article

Last Updated
March 20, 2023
Author
Courtney Leung
Fact Checker and Co-Authors
Aria Panchal
Reviewer and Supervisor
Kenneth W. Yip

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  • What Is It?
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