Relative oestrogenic activities

Compared with estrodiol, the affinity of genistein for estrogen receptors is 0.82% (around 100 times weaker binding ability than estradiol), while that of daidzein is 0.015% (around 6666 times weaker than estradiol) . The important molecules to consider for maximum beneficial effect on menopausal skin are therefore genistein, and genistin. Levels of these isoflavones in fermented soybean products are in the order of 38.5 to 229.1 μg/g genistein and 71.7 to 492.8 μg/g for genistin .

Transdermal Absorption

A paper looking at the ex-vivo human skin permeation of genistein and daidzen found that pure genistein can be effectively administered transdermally . 

An in-vivo study involved applying daidzein and genistein to the skin in olive oil. After administration, plasma concentrations of genistein rose 3 times higher than for daidzein . But urinary excretion of daidzen was twice as high as for genistein (15.9% versus 7.7% after first application). This suggests that both are absorbed but that daidzein is excreted more rapidly.  Excretion rates for both were significantly decreased after repeated application, dropping to 1.6% and 0.7% after the second application. The researchers suggested that both “daidzein and genistein are captured in the skin following repeated transdermal application”. This may be a good thing, perhaps providing a ‘depot’ prolonged release effect.

A recent paper investigated the effect of vehicles on absorption of genistein, daidzein and glycetin during in vitro topical delivery . Isoflavones in a non-ionised form (pH6) showed higher skin deposition than the ionised (pH10.8) form. Soybean oil reduced the amount retained in the skin, especially for genistein. Genistein showed greater skin absorption than daidzein, although daidzein penetration was enhanced when an aglycone mixture was used as the active ingredient. In vivo skin deposition showed a linear correlation with in vitro results. There was no or only negligible disruption of skin. The conclusion was that topical delivery may serve as a potent route for soy isoflavones against photoageing and photodamage. 

A recent paper describes the incorporation of genistein into topical nanoemulsions (droplet sizes 230-280nm) at a concentration of 1mg/ml .

A transdermal patch for administration of soybean isoflavones has also been patented .

QUOTE: “Because the isoflavone aglycones have good transdermal activity in their active form, there has been increasing use of red clover in cosmetic formulations. The skin is an oestrogen dependant organ, and isoflavones are believed to help work against aging and wrinkles resulting from the changes in hormone levels at menopause.” 

Dose

Average daily dietary intake of genistein and genistin by the Japanese is calculated as 1.5-4.1 and 6.3-8.3 mg/person, respectively . Total amount of soy isoflavones in Asian diets is estimated at 20mg – 80mg per day .  After absorption from the intestines, isoflavones are transported to the liver where they are removed from the portal blood – only a percentage escapes hepatic uptake to enter the peripheral circulation. The effectiveness of this hepatic first-pass clearance influences the amount which reaches peripheral tissues . Isoflavones are then eliminated via the kidneys as with endogenous oestrogens. According to Barnes et al (1990), “..based on simple pharmacokinetic calculations involving daily intake of isoflavones, absorption from the gut, distribution to peripheral tissues, and excretion, it is unlikely that blood isoflavone concentrations even in high soy consumers could be greater than 1-5 microM  As transdermal administration by-passes initial hepatic clearance, a lower dose can be administered via a skin cream to achieve these sort of levels.

Yin Yang Wild Yam & Soya Cream contains 5.98% soy protein by weight. If soy protein concentrate contains 40% isoflavones by weight then Yin Yan contains 40% x 5.98% = 2.39% isoflavones by weight.

Effect on photoprotection of skin

Pig skin was treated with one of five different isoflavones or an antioxidant solution for 4 days. After UV irradiation, topical application of 0.5% solutions of genistein, daidzein and biochanin A provided effective photoprotection, but was less than that obtained from the antioxidants (although these were given at much higher concentrations including 15% Vit C, 1% vit E) .

Effect on skin density
 

Apparently, a clinical study involving 20 postmenopausal women with twice daily application of a 3% Lipobelle Soyaglycone emulsion showed an 11% increase in skin density after 3 months. No reference is given, however, so this claim cannot be checked . They claim these results outclass the effect of conjugated oestrogen HRT which produced a 4% improvement in skin density after 6 months  .

Isoflavones and Breast cancer

Isoflavones may play an important role in protecting against breast cancer. Isoflavones reduce the activity of tumour growth factors in the laboratory, so that new blood vessels do not form in developing tumours and tumour cells fail to thrive. They also seem to protect genetic material from harmful mutations , . They also reduce the total amount of oestrogen stimulation the breasts receive by blocking oestrogen receptors so that stronger human oestrogens cannot stimulate them. 

In a study of 406 women aged 45–74 years, those with the highest soy intake were least likely to show changes on mammography that are associated with high breast cancer risk  . Those eating most soy were 60% less likely to have a high risk of breast cancer than those eating the least. Increased isoflavone intake may also reduce the risk of breast cancer in premenopausal women by altering steroid hormone concentrations and menstrual cycle length .  In a population based study of 21,852 Japanese women (aged 40-59 years), those with the highest consumption of miso soup and isoflavones were 54% less likely to develop breast cancer than those with the lowest intake, even after adjusting for reproductive history, family history, smoking, and other dietary factors. The protection was highest in postmenopausal women . 

There has been concern over a possible detrimental effect of isoflavone supplements in women with pre-existing breast cancer due to their oestrogen-like action. However, a recent study, just published, suggests that isoflavones protect against all tumour subtypes of breast cancer, whether they are oestrogen receptor positive or negative, or whether progesterone receptor positive or negative .

A recent study looked at almost 2000 women who were breast cancer survivors, diagnosed during 1997-2000. They were followed for 6 years, and 282 developed a recurrence. The researchers found that “Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of breast cancer recurrent in women receiving tamoxifen therapy, and that supplements  appear not to interfere with tamoxifen efficacy” .

Another recent study involved 35, 000 Singapore Chinese women, of whom 629  developed breast cancer between 1993 and 1998. Women with a high intake of soy isoflavones were 18% less likely to develop breast cancer than those with a low intake (less than 10mg daily). The protective effect was strongest in postmenopausal women and in those with a higher weight .

A review  concluded that, overall, there is no impressive data suggesting that adult consumption of soy/isoflavones affects the risk of developing breast cancer or that soy consumption affects the survival of breast cancer patients. The authors stated that, if women with breast cancer enjoy soy products, it seems reasonable for them to continue using them. 

We can never tell clients that it is OK to take soy isoflavones if they have a history of breast cancer. They must follow their own doctor’s advice.

However, there does not appear to be a cause for concern – if anything isoflavones appear to be protective.

Dr Sarah Brewer