Soy-Based Natural S-Equol Supplements Improve Crow's Feet Skin Wrinkles in Menopausal Women

S-Equol Study simultaneously published in MENOPAUSE and presented at North American Menopause Society Annual Meeting

WASHINGTON, Sept. 21, 2011 /PRNewswire-USNewswire/ -- A soy germ-based nutritional supplement containing Natural S-equol significantly improved the appearance of crow's feet skin wrinkles of the outer corner of the eyes in Japanese menopausal women, suggesting that supplements containing Natural S-equol have potential to slow skin aging, according to data from a controlled pilot study simultaneously published online in the peer-review journal MENOPAUSE and presented in a poster session at the North American Menopause Society (NAMS) annual meeting.

"While earlier studies have documented the beneficial effects of the Natural S-equol supplement on menopausal symptoms in postmenopausal women, this is the first study to examine its effects on menopausal skin, which were quite remarkable," said Belinda H. Jenks, Ph.D., Director of Scientific Affairs & Nutrition Education at Pharmavite LLC., and coauthor of the NAMS poster.  "However, other larger studies using a longer treatment period and in menopausal women of different ethnicities are warranted to confirm and further characterize the effects of the Natural S-equol supplement on skin aging."

S-equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is a compound resulting -- when certain bacteria are present in the digestive tract -- from the natural metabolism, or conversion, of daidzein, an isoflavone found in whole soybeans.  Not everyone can produce S-equol after soy consumption, as the production depends on the types of bacteria present in the large intestine and may be influenced by the amount of soy consumed.  About 50 percent of Asians and 20 to 30 percent of North Americans and Europeans, who in general consume less soy than Asians, have the ability to produce high levels of S-equol naturally.  Preliminary evidence from observational studies suggests that among Japanese women, those who produce S-equol naturally may have fewer menopausal symptoms.  Controlled clinical trials have documented that a supplement containing Natural S-equol reduces the frequency of hot flashes as well as muscle discomfort associated with menopause, both in Japan and the United States.

S-equol binds to the same estrogen receptors as naturally occurring, endogenous estrogen, but with a stronger affinity for the estrogen beta receptor.  On binding to these receptors, S-equol mimics some, but not all, activities of endogenous estrogen.  Because of these actions, it has been proposed that S-equol may alleviate some of the symptoms caused by diminished estrogen production during menopause, such as skin aging.  Some studies in postmenopausal women have shown that hormone therapy increases skin's collagen content, elasticity, thickness and hydration, while reducing wrinkles. Approximately 30 percent of the collagen fibers of the skin's middle dermal layer are diminished during the first five years after menopause.

Effects of Natural S-Equol Supplements on Skin Aging in Postmenopausal Women

"Our data suggest that doses of either 10 or 30 milligrams of Natural S-equol daily may have beneficial effects on crow's feet wrinkles.  Crow's feet wrinkles are degenerative changes seen in postmenopausal women," said Ayuko Oyama, first author of the MENOPAUSE article and Researcher at the Saga Nutraceuticals Research Institute of Otsuka Pharmaceutical Co., Ltd, which is conducting the development and ongoing research of the Natural S-equol supplement, SE5-OH.

In the study, the 34 women in the placebo group experienced a 20.2 +/- 5.1 percent average increase in their average wrinkle area after 12 weeks of treatment.  In comparison, the 34 women receiving 10 mg of Natural S-equol had a significantly smaller average increase of just 8.9 +/- 4.3 percent (P=0.029).  In contrast, the 33 women receiving 30 mg of Natural S-equol experienced a 3.4 +/- 4.9 decrease in their wrinkle area at week 12, a significant change compared the placebo group (P= 0.004).  

Also, the average depth of the maximum largest wrinkle increased in the placebo group by 6.5 +/- 2.8 percent after 12 weeks of treatment.  In contrast, the 30 mg group had an average decrease in wrinkle depth of 4.5 +/- 2.6 percent, significantly different than the placebo group (P=0.015).  The 10 mg group had no significant changes to its average wrinkle depth, experiencing an average increase of just 0.3 +/- 2.9 percent by week 12, which did not statistically differ from the placebo group.

Investigators made measurements of the women's skin without cosmetics under standardized room temperature and humidity levels at the study start and at weeks four, eight and 12 during the treatment period.

No statistically significant differences occurred between the three groups in skin elasticity, skin hydration or transepidermal water loss, a measurement of how much water passes from inside the body through the skin's outer, epidermal layer, such as by evaporation.

The study showed no serious adverse events on uterine or breast tissues.  No significant changes occurred in the levels of hormones estradiol, follicle-stimulating hormone, thyroid-stimulating hormone, free triiodothyronine and free thyroxin occurred.  The investigators also examined the women's endometrial thickness, cells of vaginal tissue and mammograms before and after treatment. Levels of sex and thyroid hormones were tested at the same time as skin measurements. There were no significant differences in clinical laboratory results, body mass index and vital signs among the groups, and all levels were within the normal range.  This further supports the findings in prior studies in regard to the safety profile of S-equol.

All of the women in the study were aged 45 to 65, were S-equol non-producers, had experienced the onset of menopause within the past five years before the study began and did not differ significantly in their wrinkle area or largest wrinkle depth at the study start.

How SE5-OH is Made

SE5-OH is the product of fermentation of whole soy germ by the bacterial strain Lactococcus 20-92 using a patented and proprietary process by the Otsuka Pharmaceutical Co., Ltd.  The process results in the conversion of the daidzein to Natural S-equol.  SE5-OH is created under current Good Manufacturing Practices. Following fermentation, the bacteria undergo heat denaturation and are deactivated.  The process is designed to produce a Natural S-equol rich product, or nutraceutical ingredient.  The ingredient has self-affirmed GRAS (Generally Recognized As Safe) status.

Development and ongoing research of the supplement SE5-OH containing Natural S-equol is conducted by the Saga Nutraceuticals Research Institute of Otsuka Pharmaceutical Co., Ltd.  Pharmavite LLC, the makers of Nature Made® vitamins and minerals and a subsidiary of Otsuka, is studying SE5-OH containing Natural S-equol in supplement form for the management of menopausal symptoms.  More information about SE5-OH containing Natural S-equol, including results of studies, is at http://www.naturalequol.com.

Otsuka Pharmaceutical Co. Ltd. supported the studies.

MENOPAUSE 19(2) February 2012
DOI: 10.1097/GME.0b013e318227427b
http://journals.lww.com/menopausejournal/toc/9000/00000
The effects of natural S-equol supplementation on skin aging in postmenopausal women: A pilot randomized placebo-controlled trial
Ayuko Oyama, Tomomi Ueno, MS, and Shigeto Uchiyama, MS, of the Saga Nutraceuticals Research Institute of Otsuka Pharmaceutical Co., Ltd, in Japan; Tomohiko Aihara, MD, Ph.D., of the Breast Center of Aihara Hospital in Osaka, Japan;
Akira Miyake, MD, Ph.D. of the Miyake Gynecology and Internal Medicine Clinic in Osaka, Japan; Sumio Kondo, MD of the Kensyokai Medical Corporation in Osaka, Japan; and Kayoko Matsunaga, MD, Ph.D. of the Department of Dermatology at Fujita Health University School of Medicine in Toyoake, Japan.

NAMS Presentation
Thursday, Sept. 22, 2011 5:15 to 6:15 p.m. EDT
Poster Presentation 1116615
The effects of natural S-equol supplementation on skin aging in postmenopausal women: A pilot randomized placebo-controlled trial.
Tomomi Ueno, Atsuko Onoda and Shigeto Uchiyama of Otsuka Pharmaceutical Co., Ltd. in Saga, Japan; Belinda H. Jenks, Soh Iwashita and James Brooks of Pharmavite LLC in Northridge, Calif.; Takeshi Aso of the Tokyo Medical and Dental University in Japan; and Kayoko Matsunaga of the Fujita Health University School of Medicine in Aichi, Japan.  Iwashita also has an appointment at Otsuka Pharmaceutical.

About Pharmavite LLC: For 40 years, Pharmavite has earned and maintained the trust of healthcare professionals, consumers, and retailers by manufacturing high-quality vitamins, minerals, herbs and other dietary supplements that are safe, effective and science-based.  Nature Made® is the number one selling dietary supplement brand in the food, drug, club and mass channels.  The dietary supplement industry is regulated by the U.S.  Food and Drug Administration and the Federal Trade Commission, as well as by government agencies in each of the 50 states.

About Otsuka Pharmaceutical Co., Ltd.: Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and consumer products for the maintenance of everyday health.  Otsuka is committed to being a corporation that creates global value, adhering to the high ethical standards required of a company involved in human health and life, maintaining a dynamic corporate culture, and working in harmony with local communities and the natural environment.  Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The Otsuka Group has business operations in 23 countries and regions around the world, with consolidated sales of 1,090.2 billion yen for fiscal year 2010. Visit Otsuka Pharmaceutical Co., Ltd.  at http://www.otsuka.co.jp/en/.

SOURCE Pharmavite LLC