Genistein

What Is It?

Genistein is structurally classified as an isoflavone. It is a phytoestrogen naturally derived from plants, and has a structure similar to estrogens$^1$. Genistein can bind to estrogen receptors to activate or inhibit downstream signaling cascades depending on the context$^2$. Genistein is known to have several anticancer effects, functioning as a tyrosine kinase inhibitor$^3$, an angiogenesis inhibitor$^4$, and antioxidant/anti-inflammatory nutrient$^5$.

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-one$^1$.

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 foods$^{6,7}$. Legumes also contain genistein. Vegetables have been found to contain trace amounts of genistein$^8$. A summary of the average genistein quantity in common foods is as follows:

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 effects$^9$. Anticancer effects are also related to genistein’s role as a tyrosine kinase inhibitor$^3$. Genistein also prevents cancer through antioxidant and anti-inflammatory effects$^5$. In addition, researchers found that genistein can provide postmenopausal symptom relief, such as alleviating hot flashes$^{1,10}$. Genistein is known for its ability to maintain cardiovascular and bone health$^{10}$.

What Are Its Main Drawbacks?

At normal dietary doses, very few side effects or drawbacks of genistein consumption have been identified to date$^{11,12}$. When consumed in high doses, however, genistein might damage DNA, adversely affecting healthy cells (via apoptosis or cell cycle arrest)$^{13}$. 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 normal$^{14}$. 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 context$^{12}$. 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 tissue$^{15}$. Some studies suggest that genistein can inhibit the activity of estrogen receptors and block estrogen signaling$^{12}$, 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 cancer$^{16}$. Without this cell growth signaling mechanism in the tumor, cancer cells may undergo apoptosis$^{17}$.
2. Tyrosine Kinase Inhibitor: Genistein acts as a tyrosine kinase inhibitor to block numerous downstream signaling pathways$^3$. 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 lung$^{18,19}$, head and neck$^{20}$, colorectal$^{21}$, pancreatic$^{22}$, breast$^{23}$, and brain$^{24}$ cancers). A study also found that it can inhibit cancer cell proliferation and migration through Akt and MAPK signaling pathways$^{25,26}$.
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 inhibitor$^4$. Genistein can interrupt the vascular endothelial growth factor (VEGF) signaling pathway, which is crucial for angiogenesis$^{27}$. Other molecular targets for genistein’s anti-angiogenesis effects are under investigation$^{28}$.
4. Antioxidant and Anti-Inflammatory Properties: Research shows genistein has antioxidant and anti-inflammatory properties$^{5}$ 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 enzymes$^{29}$. It has been suggested that these mechanisms make genistein useful for treating or preventing cancer$^{30}$, as well as age-related diseases such as Alzheimer’s disease$^{31,32}$.

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 genistein$^{1}$. For comparison, for soy-based diets, the typical genistein content is 0.25-1 mg/kg/day.$^{33}$ 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 PubMed$^{33-57}$. A summary of the results for each cancer type is as follows:

📄 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
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• Genistein
• What Is It?
• What Are Its Other Names?
• What Foods Have It?
• What Are Its Main Benefits?
• What Are Its Main Drawbacks?
• What Are Its Mechanisms of Action?
• What Are Typical Doses and Durations?
• Summary of Data
• References
• About This Article
• Disclaimer