|Grade||Level of Evidence|
|A||Multiple double-blind, controlled clinical trials.|
|B||1 double-blind, controlled clinical trial.|
|C||At least 1 controlled or comparative clinical trial.|
|D||Uncontrolled, observational, animal or in-vitro studies only.|
|Grade||Effect||Size of Effect||Comments|
Restores the thickness of the skin, presumably by increasing collagen synthesis and limiting its degradation.
Inhibits UV-induced DNA damage and photodamage to the skin.
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Table of contents:
Genistein is a phytoestrogen belonging to the class of organic compounds known as isoflavones. It and its glucoside, genistin, occurs naturally in many legumes, but is most commonly found in soy, where it is among the most active components.
The leaves of the Indian bread root contains remarkably high (over 2g/kg dry weight) concentrations of genistein. The stems of the fava bean and the roots of kudzu vine are also rich sources of genistein, containing over 1g/kg and 0.95g/kg dry weight, respectively.
Like most polyphenols, the solubility and intradermal delivery of genistein is limited. Systems have therefore been developed to improve its permeability into the skin.
In one study on hairless porcine skin, which has been suggested to be physiologically similar to human skin, water-in-oil type microemulsions consisting of isopropyl myristate (IPM), 150 mM NaCl solution, Tween 80 and ethanol, increased both the solubility and skin accumulation of genistein by orders of magnitude.
An in-vitro experiment in which genistein was formulated as a topical gel found that the incorporation of chemical penetration enhancers such as Menthol, Transcutol and Transcutol + Lauroglycol, led to as much as 5 to 13-fold increases in flux and 7 to 22-fold increases in skin retention. Unsurprisingly, administration of genistein in a liposomal gel also increased skin deposition of genistein, as liposomes are known to increase drug penetration across the skin tissue.
Nanoemulsions also appear to aid the delivery of genistein into the skin, with experiments using porcine ear skin mounted in Franz diffusion cells showing a slow permeation profile. In another study, genistein-loaded polylactide nanocapsules incorporated in a semi-solid gel formulation was found to increase penetration, enabling genistein to reach deeper skin layers.
Topically applied genistein reaches all layers of the skin when formulated as nanoemulsions or nanoemulsions incorporated into hydrogels, and is retained especially well in the epidermis. Lower concentrations of genistein are retained in the dermis, followed by the stratum corneum.
One study noted that genistein seems to have great affinity for the skin layers, for it did not permeate across the skin into the receptor solution over 24 hours in an in-vitro experiment on pig skin. This is advantageous as it ensures continued levels of the drug in the skin tissues. However, successful transdermal application leads to therapeutic concentrations in plasma. Repeated transdermal application also increases the retention of genistein, reducing its excretion rate from 7.7% after the first application to 0.7% after the second application.
Due to the lipophilic nature of the stratum corneum, genistein in its non-ionized form (pH 6) exhibits better skin deposition than its ionized form (pH 10.8).
3. Effects on the skin
Numerous studies show that genistein has a potent protective effect against solar UV radiation. Genistein has been demonstrated to protect against UVA-induced photodamage and inhibit UVB-induced skin carcinogenesis and cutaneous aging in mice. Topical genistein also protected against solar-simulated UV-induced photodamage in porcine skin and inhibited UVB-induced DNA damage in human reconstituted skin.
However, there have not been many clinical trials investigating genistein's photoprotective effects in human subjects. In one small study involving 6 men, genistein was topically applied 1 hour before and 5 minutes after UVB irradiation, and the skin was photographed and quantitated for erythema index by a chromometer. Prior, but not post-application of genistein was found to substantially block erythema, indicating that genistein effectively protects human skin against UVB-induced skin burns and photodamage.
It has been hypothesized that the possible mechanisms of genistein's photoprotective and anti-carcinogenic effects on the skin may involve scavenging or quenching of reactive oxygen species, blocking of oxidative and photodynamic damage to DNA, inhibition of tyrosine protein kinase, downregulation of EGF-receptor phosphorylation and MAPK activation, suppression of oncoprotein expression in UV-irradiated cells and blocking the induction of cJun protein and collagenase.
3.2 Improvement in postmenopausal skin
Several clinical trials have evaluated the effects of oral and topical genistein on the skin of postmenopausal women.
Oral daily intake of 40mg of soy isoflavone aglycones for 12 weeks statistically improved fine wrinkles and skin elasticity on the cheeks in a study on 26 women volunteers in their late 30s and early 40s. In another study, 30 postmenopausal women were treated with 100mg/day of an isoflavones-rich, concentrated soy extract. After 6 months, there an increase in epidermal thickness in 23 women, an increase in dermal collagen content in 25 women, an increase in the number of elastic fibers in 22 women, and an increase in the number of dermal blood vessels in 21 women. However, 21 women also had an increased number of dermal papillae and hence wrinkling. But it is not clear from these studies whether the improvements were due to genistein or other isoflavones such as daidzein, in the test food and soy extract.
2 randomized, double-blinded studies have compared the effects of topically administered genistein versus estradiol on postmenopausal women. Epidermal thickness was found to have increased by 20%, dermal papillae by 125% and the number of blood vessels by 36% after 24 weeks of treatment with 4% genistein in the first study. The follow-up study also found an increase in hyaluronic acid concentration after 24 weeks of treatment with 4% genistein gel. Both studies agreed that treatment with 0.01% estradiol was more effective in enhancing postmenopausal skin, however.
Estrogen levels decline during menopause, which leads to an acceleration of skin aging because adequate estrogen levels are required to control the structural integrity and functional capacity of the skin. As estrogen levels fall, collagen, elastin and glycosaminoglycans break down, causing sagging, wrinkling and a loss of skin tone and elasticity. Loss of estrogen also leads to skin thinning, reduced blood vessels and increased dryness, fragility and sensitivity to environmental irritants. Genistein is an estrogen receptor beta (ER-β) agonist, and hence probably improves postmenopausal skin via similar mechanisms as estrogen, though the exact mechanisms have yet to be discovered. In-vitro studies have shown, for example, that genistein increases collagen gene expression and de novo collagen synthesis in human fibroblasts.
3.3 Increased epidermal thickness
A consequence of skin aging is reduced skin thickness, which topical genistein has been shown to reverse. In one study, a cream containing 90mg/kg genistein increased skin thickness in female subjects aged 55-64 by an average of 11% after 2-3 months of twice daily application, compared to subjects using a control cream who did not witness significant changes. Treatment with 100mg/day of concentrated soy extract has also been found to increase epidermal thickness by an average of 9.46% in 23 out of 30 patients, in another study. A third study demonstrated an even greater improvement (20%) in epidermal thickness after 6 months of treatment with 4% genistein.
The effect of estrogens on skin thickness is well-known -- many studies have reported increases in epithelium thickness after treatment or therapy with estrogens. Estrogen restores skin thickness by increasing collagen synthesis while limiting excessive collagen degradation. As a phytoestrogen, it is possible that genistein improves skin thickness through similar mechanisms by binding to estrogen receptors.
4. Side Effects
The topical application of soy isoflavones, including genistein, has been shown to lead to negligible stratum corneum disruption and skin erythema. The clinical trials that have been performed so far have also not reported any adverse events associated with genistein.
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