Regimen Lab Skincare Encyclopedia ?


Version 1.0

Ingredient Profile

Common Name: Genistein, 4,5,7-trihydroxyisoflavone
INCI: Genistein
Source: Soybeans, Fava beans
Genistein Molecule

kligman ingredient evaluation

Penetration: Good Penetration
Biochemical Mechanism: ROS scavenger, NF-kB inhibitor, Cytokine inhibitor
Level of Evidence: Good Quality, Level B

Regimen's Take

Genistein used to be a wonder drug, especially for alternative medicine. It is well known for its chemotherapeutic property and was once at the forefront of Cancer Research. It does have a significant anti-inflammatory property and some UV-B protective ability. However, it has a similar structure as Estradiol, which is why its maximum concentration was limited to 0.007%. 


  • Genistein is used for anti-aging, wound-healing and anti-inflammation
  • It is often present in skincare at 0.05-1%, but the new maximum recommendation is 0.007%
  • Use it at low-neutral pH for best penetration

What is Genistein?

Genistein is a naturally occurring compound abundantly found in soybeans, fava beans, and other lentils. It belongs to the class of isoflavones, which are polyphenolic compounds known for various clinical benefits.1 Genistein has a chemical structure similar to Estradiol and is a well-known phytoestrogen, a plant-based compound that mimics estrogen in the body.2,3 It is also a potent antioxidant that acts as a free radical scavenger and modulates processes in the skin to prevent the destruction of elastin, collagen, and hyaluronic acid. Thus, it is widely used in skin care formulations to improve wound healing and combat dryness and wrinkles.3

While Genistein can be isolated from a methanol extract of soybean meal, it is also obtained from its glycoside form, called sophoricoside, through a process called biotransformation.3 This form of Genistein is more abundant in some plants and has similar physiological functions to Genistein, but it exhibits lower potency in some activities. In fact, sophoricoside will only exhibit pharmacological activities after it is metabolized into Genistein in vivo.3 Biotransformation is a technique that uses microbial enzymes, β-glucosidase in this case, to hydrolyze sophoricoside into Genistein in-vitro. This method is thought to be suitable for scale-up production in the cosmetic and pharmaceutical industries. 


  • Antioxidant8,9,10
  • Anti-aging5,6,7,13,16
  • Anti-inflammatory3
  • Wound healing10,11,12


Usage Rate/ Effective Concentration:

Genistein has potent effects on wound healing and preventing dryness, inflammation, and UVB-induced photodamage. Topical gel formulations may contain a combination of several isoflavones with typically 4% genistein.5,6,7 When applied daily on facial skin, this significantly increases the production of type I and type III collagen and the concentration of hyaluronic acid in the extracellular matrix, which is linked to preventing dryness and anti-aging benefits.5,6 In mice, a topical formulation containing 5 μmol genistein applied on the skin 1 hour before UVB irradiation was able to prevent acute skin burns completely. A potent dose-dependent chemoprotective effect was also observed with topical Genistein, which inhibited skin carcinogenesis by >90%.9 In humans, topical Genistein can also protect the skin from UVB-induced photodamage. 

Other skin-related benefits, mainly wound healing properties in mice models, are also documented with subcutaneous injections and oral administration of Genistein. In streptozotocin-induced type 1 diabetic mice, excisional wounds were treated with injectable doses of Genistein at 0.2, 1, or 5 mg/kg/day. All doses were able to normalize reactive oxygen species (ROS) levels, which are usually elevated under diabetic conditions and during injury and inflammatory response.11 In a separate study using post-ovariectomy (OVX) rats, incisional wounds were treated with injectable Genistein at 1 or 10 mg/kg/day for 12 weeks. While the production of proteins that are important for cell survival and wound healing is normally decreased in OVX rats, both doses of Genistein were seen to counteract this effect on Days 7 and 14 of the healing process, with the lower dose being more effective.12 Oral dietary supplements containing 0.025 and 0.1% Genistein also demonstrate an increased wound healing rate in mice by altering inflammatory response and reducing oxidative stress.10 

Estrogen deprivation from menopause accelerates the loss of structural architecture, which makes it prone to damage, dryness, atrophy, and wrinkles.16 The wound healing and anti-inflammatory properties of Genistein make it a favorable candidate for psoriasis treatment in co-pharmacotherapy with other drugs, and in anti-aging skincare.13 

However, in January 2022, the Scientific Community on Consumer Safety (SCCS) released its assessment of Genistein and Daidzein. Based on toxicologic calculations, they concluded that the maximum concentration allowed for daily topical products should be 0.007% for Genistein. The data available for Daidzein was not sufficient to rule out genotoxicity. We’ve been researching this for quite a while, and Vitamin X is within this limit. We started with 1% Genistein in the earlier versions of Vitamin X, but we decided to decrease it to minimal levels as more research came in. 

Formulation Considerations:

Genistein is a white powder with a yellowish hue soluble in glycols but not in water. There are glycoside versions of Genistein available, but they do not have the same activity as the aglycone version. There are not a lot of special considerations when formulating it, aside from protecting it from heat and oxygen.

Biochemical Details:

Anti-inflammatory & Wound healing

When the structural integrity of the normal skin barrier is compromised during injury, our immune system immediately starts to initiate the wound healing process. The first major response is inflammation, a critical period where immune cells remove any damaged tissues, foreign debris, and dead tissues. Therefore, wound healing would be delayed without inflammation. While a spike in the production of pro-inflammatory cytokines and free radicals is part of the normal response, damaging effects are also possible from their sudden storm if left unmodulated. Clinical studies using mice models have found Genistein to play an important role in wound healing by generally altering inflammatory response and modulating the expression of pro-inflammatory cytokines, such as TNF-α, by the NF-κB pathway and reducing oxidative stress by increasing antioxidation capacity.10 The rate of wound healing in genistein-treated mice was significantly faster than in untreated mice. 

The anti-inflammatory activity of Genistein is also important for the treatment of psoriasis, which is linked to uncontrollably high levels of inflammatory cytokines and active immune cells. This overstimulation and dysregulation of the immune system plays a major role in preventing the formation of an intact skin barrier, and it is why skin lesions and flare-ups, which could be very painful, are common in people with psoriasis.17 An imbalance of the pro- and anti-inflammatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukins 12 (IL-12), 17 (IL-17), and 23 (IL-23) is thought to influence the pathophysiology of psoriasis. Elevated levels of pro-inflammatory IL-17 can cause hypertrophy of the epidermis and consequently excessive proliferation of keratinocytes and skin lesions. Overstimulation of TNF-α and IL-17 receptors on keratinocytes also synergistically results in increased gene expression of inflammatory products.13 Hence, treatment is focused on modulating cytokine release and TNF-α/IL-17 synergism. Cytokine profiling during genistein monotherapy showed improvement on healing and controlling flare-ups, accompanied by changes in pharmacodynamics and levels of IL-12, IL-17, IL-23, and TNF-α. 

 In vitro studies on psoriasis assessed the effect of Genistein on the MAPK pathway, which is responsible for activities such as cell proliferation, differentiation, inflammation, and apoptosis in response to physiological stimuli. MAPK signaling is involved in the release and activation of IL-17, TNF-α, a combination of IL-17 and TNF-α, and phosphorylation of ERK1/2, which is a protein that has cascade signaling characteristics and serves an important role in signal transduction pathways for regulating cell growth and differentiation, and the expression of transcription factors.15,18 Keratinocytes that were treated with Genistein significantly altered MAPK activity and ERK1/2 phosphorylation in IL-17-stimulated cultures, thereby reducing the inflammatory response that would normally be activated by IL-17.13 Pre-treatment with Genistein was also able to inhibit IL-17-induced P13K activation, another signaling pathway that stimulates cell growth and proliferation in which excessive activation of it contributes to the effects of psoriasis. Moreover, it was able to modulate IL-17, TNF-α, and IL-17/TNF-α-induced NF-κB pathway activation and mRNA expression of cellular signaling genes in the early inflammatory response, which prevented further production of pro-inflammatory cytokines that promote cell proliferation and differentiation.13 In other cell culture models, Genistein also has a potent anti-inflammatory effect by decreasing the secretion of IL-1β, IL-6, and IL-8 from TNF-α stimulion.15


Apoptosis, programmed cell death, is an important natural process that is part of our immune system to prevent tumorigenesis and cancer. Research in cell cultures has demonstrated the role of Genistein in the induction of apoptosis by upregulating the expression of various pro-apoptotic proteins. For example, Genistein was able to enhance the activities of protease enzymes caspase-3 and caspase 9 to induce apoptosis in human cervical cancer cells (HeLa cells).19 In the LoVo and HT-29 colon cancer cell lines, it could trigger apoptotic activity by inhibiting the NF-κB pathway and modulating the levels of anti-apoptotic protein BcI-2 and pro-apoptotic protein Bax.20 In addition, Genistein promoted apoptosis in HT-29 colon cancer cells by modulating caspase-3 and the p38 MAPK signaling pathway, which is responsible for controlling the release of cytokines by macrophages and neutrophils during apoptotic events.21 

Another mechanism of genistein-mediated apoptosis is through upregulation of the expression of ER stress-associated proteins, such as inositol-requiring enzymes, calpain 1, GRP78, DNA damage-inducible gene 153, caspase-7, and caspase-4.22 The increase of GRP78 activity consequently upregulates the activity protein kinase R-like ER kinase, which ultimately activates transcription factors that are involved in the expression of pro-apoptotic proteins.24 Genistein was also shown to enhance phosphorylation and activation of p53, a tumor suppressor gene.25 


Phytoestrogens contain properties to prevent the destruction of elastin, collagen, and hyaluronic acid. Therefore, Genistein is often formulated into anti-aging facial creams to combat fine wrinkles, dryness, elastic fiber degeneration, and reduction in epidermal thickness and collagen content, all of which are the result of hypoestrogenism in aging skin.26 Daily dietary intake of phytoestrogens through soy-based food products that contain at least 40 mg soy isoflavones is also shown to improve fine wrinkles and skin elasticity.27

Does it Penetrate?

The topical application of Genistein to the skin is moderately absorbed when formulated in an aqueous buffer at pH 6, in which Genistein exists in the non-ionized form.13 Skin deposition was less efficient in the ionized form at pH 10.8. 17

Clinical Trials

 Concentration Study Details Conclusion
4% genistein
Subjects: Human (postmenopausal women), n = 15
Route of administration: Topical, once daily for 24 weeks
Area tested: Face
Significant increase in hyaluronic acid concentration found in the skin’s extracellular matrix compared to baseline (before treatment)5
4% genistein
(topical gel)
Subjects: Human (women, 45-55 years old), n = 30
Route of Administration: topical, once per day for 24 weeks, in vivo
Area Tested: Facial skin (in vivo)
Comparison study to examine effects of genistein versus estrogen on the facial skin collagen of postmenopausal women: biopsy on facial skin from the preauricular area after 24 weeks showed increase in type I and type III facial collagen concentration, but to a higher extent using topical estrogen6
4% genistein
Subjects: Human (postmenopausal women)
Route of administration: Topical, once daily for 24 weeks
Area tested: Face
Increased epidermal thickness and number of vessels in isoflavone and estrogen groups, but to a greater extent in the latter; no significant increase in the number of dermal papillae and fibroblasts in the isoflavone group7
1-20 μmol genistein in 0.2 mL acetone (topical) Subjects: Mice
Route of administration: Topical, daily, in vivo
Area tested: skin
Pre-treatment with 10 μmol genistein for 1 week substantially inhibited DMBA-initiated and TPA-promoted skin tumorigenesis in a 2-stage carcinogenesis model, but inhibited tumor multiplicity (~50%) more potently than tumor incidence (~20%); pre-application with 10 μmol genistein also inhibited TPA-induced acute inflammatory response by reducing up to ~50-60% of edema and MPO activity8
1 and 5 μmol genistein (topical) Subjects: Mice, hairless
Route of Administration: topical, oral, in vivo
Area tested: back skin
Investigated the effect of genistein on UVB-induced photocarinogenesis: topical genistein had potent dose-dependent chemoprotective effect and inhibited skin carcinogenesis by >90%; 5 μmol genistein applied topically 60 minutes before UVB irradiation completely prevented acute skin burns;
oral supplement also prevented UVB-induced photocarcinogenesis, but to a lesser extent than topical dose;
topical genistein also protected human skin against UVB-induced photodamage9
0.025 and 0.1% genistein (oral) Subjects: Mice
Route of administration: oral (dietary supplement), in vivo
Area tested: skin
Rate of wound healing in genistein-treated mice was significantly faster than in untreated mice; genistein modulates wound healing in early stages by altering inflammatory response, such as modulating pro-inflammatory cytokine expression, and increasing antioxidant capacity to reduce oxidative stress10
0.2, 1, or 5 mg/kg/day of genistein
Subjects: Mice
Route of administration: Subcutaneous (in vivo), cultured endothelial cells (in vitro)
In vivo: Excisional wounds of streptozotocin-induced type 1 diabetic mice were treated with different doses of injectable genistein: all doses normalized reactive oxygen species (ROS) levels, which are usually elevated by diabetic conditions
In vitro: Genistein protected against high-glucose induced impairment of capillary tube formation11
1, 10 mg/kg genistein
Subjects: Rats, n = 96, including post-ovariectomy (OVX) and placebo (no surgery)
Route of Administration: Subcutaneous, daily for 12 weeks, in vivo
Incisional wounds were created after 12 weeks of pre-treatment with genistein, healing process was monitored on Days 7 and 14: the production of proteins that are involved in cell survival and wound healing is normally decreased in OVX rats, however, all treatments (estradiol, raloxifene, and genistein) significantly modified this decrease, with the lowest dose of genistein being most effective in improving skin healing12



  1. Křížová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules. 2019;24(6):1076. doi:10.3390/molecules24061076
  2. Irrera N, Pizzino G, D'Anna R, et al. (2017) Dietary Management of Skin Health: The Role of Genistein. Nutrients. 9(6):622. doi:10.3390/nu9060622
  3. Mei, J., Chen, X., Liu, J. et al. (2019). A Biotransformation Process for Production of Genistein from Sophoricoside by a Strain of Rhizopus oryza. Sci Rep. 9, 6564
  4. Walter, E. D. (1941). "Genistin (an Isoflavone Glucoside) and its Aglucone, Genistein, from Soybeans". Journal of the American Chemical Society. 63(12): 3273–3276. doi:10.1021/ja01857a013
  5. Patriarca MT, Goldman KZ, M. dos Santos J, Petri V, Simões RS, Soares JM, Simões MJ, Baracat EC. (2007). Effects of topical estradiol on the facial skin collagen of postmenopausal women under oral hormone therapy: A pilot study. European Journal of Obstetric & Gynecology and Reproductive Biology. 130(2): 202-205 ISSN 0301-2115.
  6. Lidia Aragão Silva, Adriana Aparecida Ferraz Carbonel, Andréa Regina Barbosa de Moraes, Ricardo S. Simões, Gisela Rodrigues da Silva Sasso, Lívia Goes, Winnie Nunes, Manuel Jesus Simões & Marisa Teresinha Patriarca. (2017). Collagen concentration on the facial skin of postmenopausal women after topical treatment with estradiol and genistein: a randomized double-blind controlled trial. Gynecological Endocrinology. 33:11, 845-848. doi: 10.1080/09513590.2017.1320708
  7. Moraes AB, Haidar MA, Soares JA, Simões MJ, Baracat EC, Patriarca MT. (2009). The effects of topical isoflavones on postmenopausal skin: Double-blind and randomized clinical trial of efficacy. European Journal of Obstetrics & Gynecology and Reproductive Biology. 146(2): 188-192. ISSN 188-192
  8. Wei H., Bowen R., Zhang X., Lebwohl M. (1998). Isoflavone genistein inhibits the initiation and promotion of two-stage skin carcinogenesis in mice. Carcinogenesis. 19:1509–1514. doi:10.1093/carcin/19.8.1509
  9. Wei H, Saladi R, Lu Y, Wang Y, Palep SR, Moore J, Phelps R, Shyong E, Lebwohl MG, (2003). Isoflavone Genistein: Photoprotection and Clinical Implications in Dermatology. The Journal of Nutrition. 133(11) 3811S–3819S
  10. Park E, Lee SM, Jung IK, Lim Y, Kim JH. (2011). Effects of genistein on early-stage cutaneous wound healing. Biochemical and Biophysical Research Communications. 410(3), 514-519. ISSN 0006-291X
  11. Tie, L, An Y, Han J, Xiao Y, Xiaokaiti Y, Fan S, Liu S, Chen AF, Li X. Genistein accelerates refractory wound healing by suppressing superoxide and FoxO1/iNOS pathway in type 1 diabetes. The Journal of Nutritional Biochemistry. 24(1), 88-96
  12. Marini, H., Polito, F., Altavilla, D., Irrera, N., Minutoli, L., Calò, M., Adamo, E. B., Vaccaro, M., Squadrito, F., & Bitto, A. (2010). Genistein aglycone improves skin repair in an incisional model of wound healing: a comparison with raloxifene and oestradiol in ovariectomized rats. British journal of pharmacology, 160(5), 1185–1194
  13. Bocheńska K, Moskot M, Smolińska-Fijołek E. et al. (2021). Impact of isoflavone genistein on psoriasis in in vivo and in vitro investigations. Sci Rep. 11, 18297.
  14. Morabito, N., Crisafulli, A., Vergara, C., Gaudio, A., Lasco, A., Frisina, N., D'Anna, R., Corrado, F., Pizzoleo, M. A., Cincotta, M., Altavilla, D., Ientile, R., & Squadrito, F. (2002). Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 17(10), 1904–1912.
  15. Tuli HS, Tuorkey MJ, Thakral F, Sak K, Kumar M, Sharma AK, Sharma U, Jain A, Aggarwal V, Bishayee A. (2019). Molecular Mechanisms of Action of Geinstein in Cancer: Recent Advances. Front. Pharmacol. 10. doi:10.3389/fphar.2019.01336
  16. Rzepecki AK, Murase JE, Juran R, Fabi SG, McLellan BN. (2019). Estrogen-deficient skin: The role of topical therapy. International Journal of Women’s Dermatology. 5(2): 85-90, ISSN 2352-6475.
  17. Huang, Z. R., Hung, C. F., Lin, Y. K., & Fang, J. Y. (2008). In vitro and in vivo evaluation of topical delivery and potential dermal use of soy isoflavones genistein and daidzein. International journal of pharmaceutics, 364(1), 36–44.
  18. Zou J, Lei T, Guo P, Yu J, Xu Q, Luo Y, Ke R, Huang D. (2018). Mechanisms shaping the role of ERK1/2 in cellular senescence (Review). Molecular Medicine Reports. 19(2): 759-770.
  19. Dhandayuthapani S, Marimuthu P, Hormann V, Kumi-Diaka J, Rathinavelu A. (2013). Induction of apoptosis in HeLa cells via caspase activation by resveratrol and genistein. J. Med. Food 16, 139–146. doi:10.1089/jmf.2012.0141
  20. Luo Y, Wang SX, Zhou ZQ, Wang Z, Zhang YG, Zhang Y, et al. (2014). Apoptotic effect of genistein on human colon cancer cells via inhibiting the nuclear factor-kappa B (NF-κB) pathway. Tumor Biol. 35, 11483–11488. doi:10.1007/s13277-014-2487-7
  21. Shafiee G, Saidijam M, Tavilani H, Ghasemkhani N, Khodadadi I. (2016). Genistein induces apoptosis and inhibits proliferation of HT29 colon cancer cells. Int. J. Mol. Cell Med. 5, 178–191
  22. Hsiao YC, Peng SF, Lai KC, Liao CL, Huang YP, Lin CC, et al. (2019). Genistein induces apoptosis in vitro and has antitumor activity against human leukemia HL-60 cancer cell xenograft growth in vivo. Environ. Toxicol. 34, 443–456. doi:10.1002/tox.22698
  23. Xia S, Wang J, Kalionis B, Zhang W, Zhao Y. (2019). Genistein protects against acute pancreatitis via activation of an apoptotic pathway mediated through endoplasmic reticulum stress in rats. Biochem. Biophys. Res. Commun. 509, 421–428. doi:10.1016/j.bbrc.2018.12.108
  24. Ouyang G, Yao L, Ruan K, Song G, Mao Y, Bao S. (2009). Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways. Cell Biol. Int. 33, 1237–1244. doi:10.1016/j.cellbi.2009.08.011
  25. Su S J, Yeh TM, Chuang WJ, Ho CL, Chang KL, Cheng HL, et al. (2005). The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem. Pharmacol. 69, 307–318. doi:10.1016/j.bcp.2004.09.025
  26. Liu, T, Li, N, Yan, Y, et al. (2020). Recent advances in the anti-aging effects of phytoestrogens on collagen, water content, and oxidative stress. Phytotherapy Research. 34:435– 447
  27. Izumi T, Saito M, Obata A, Arii M, Yamaguchi H, Matsuyama A. (2007). Oral intake of soy isoflavone aglycone improves the aged skin of adult women. J. Nutr. Sci. Vitaminol. 53:57–62. doi:10.3177/jnsv.53.57
  28. Scientific Committee on Consumer Safety. (2022). Opinion on Genistein and Daidzein. European Comission. SCCS/1641/22


The Skincare Encyclopedia aims to improve public understanding of the biology and chemistry of skincare. The Encyclopedia is rooted in core scientific principles and extensive research, in many cases in collaboration with the authors of the original studies referenced. This is a project of Regimen Lab, maintained by a group of multidisciplinary scientists, MDs, and researchers.