Northridge, Calif. (October 16, 2014) - Post-menopausal women experienced improvements in vaginal atrophy, with no significant effect on hormone levels or genital bleeding, after 12 weeks of daily 10 milligram (mg) doses of an investigational fermented soy germ-based nutritional supplement previously shown to help relieve certain menopause symptoms, according to a new peer-reviewed pilot study reported in a poster at the North American Menopause Society (NAMS) annual scientific meeting.
"These data documented improved vaginal epithelium, without significant abnormalities in vaginal cells, endometrial thickening, hormone levels or genital bleeding, which adds to the known safety profile of this S-equol supplement," said coauthor Belinda H. Jenks, Ph.D., director of Scientific Affairs & Nutrition Education at Pharmavite LLC, the makers of Nature Made® vitamins and minerals and a subsidiary of Otsuka Pharmaceutical Co., Ltd., which supported the study.
In menopausal women, estrogen loss is the major cause of atrophy of the tissues of the reproductive and urinary systems, which usually is progressive (Calleja-Agius and Brincat, 2009) and includes vaginal dryness, itching, burning, dyspareunia (painful intercourse) and urinary incontinence. While estrogen replacement therapy can help manage these symptoms, some women do not use such hormone-based therapy because of side effect concerns (Uchiyama et al., 2014).
S-equol has the ability to bind to the same estrogen receptors as naturally occurring estrogen, with a stronger affinity to the beta receptor compared to the alpha receptor. On binding to the receptor, S-equol mimics some, but not all, activities of estrogen. Because of these actions at the receptor, it has been proposed that S-equol may alleviate some symptoms caused by diminished estrogen production during menopause. Daily doses of the supplement containing S-equol, a metabolite of the soy isoflavone daidzein, can relieve hot flash frequency and muscle and joint pain, as reported in previously published controlled clinical trials in both U.S. and Japanese postmenopausal women.
Vaginal and Reproductive Health Benefits
Daily 10 mg doses of S-equol for 12 weeks showed an improvement in vaginal epithelium in 105 post-menopausal Japanese women, who were not S-equol producers. The researchers used the percentage of superficial cells, to determine vaginal atrophy, as the disappearance of these cells is associated with dryness and increased risk of some conditions such as candida (yeast) infections, known to cause itch and inflammation.
Investigators examined three daily doses of S-equol, 2, 6 and 10 mg, and a placebo, with tissue evaluations at the study start and 12 weeks. Specifically, the 10 mg group showed a positive trend to superiority compared to the placebo group, respectively +6.3 vs. -4.4 percent change in superficial cells at 12 weeks, P=0.0507, while the 2 and 6 mg groups showed dose-related changes of -2.2 and +2.7 percent, (P=0.6350 and P=0.2011) respectively, which did not differ significantly from the placebo group. None of the groups displayed an increase in abnormal vaginal cells.
Likewise, the women's change in endometrial thickness after 12 weeks showed no significant differences between groups: 3.6±1.1 millimeter (mm) in the placebo group, 4.0±1.1 mm for the 2 mg group, 3.8±2.3 for the 6 mg group, and 4.6±2.4 mm for the 10 mg group. No treatment group showed significant genital bleeding. Additionally, no significant differences occurred in the groups based on measures of their blood levels of estrogen, follicle stimulating hormone, testosterone, thyroid-stimulating hormone, triiodothyronine (T3) and thyroxine (T4).
Complete data from the study will be submitted to a peer-review journal for publication.
S-equol is a compound resulting 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. 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 equol.
The safety of the supplement containing S-equol previously was confirmed by standard animal testing breast cancer model, including a study documenting that S-equol itself, as well as the supplement containing S-equol, did not increase or stimulate the growth of breast cancer cells. Studies involving postmenopausal women who consumed the supplement containing S-equol have not observed any safety problems, including analysis of breast and reproductive tissues and of hormone levels.
Development and ongoing research of a supplement containing S-equol is conducted by the Saga Nutraceuticals Research Institute of Otsuka Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd, along with Pharmavite LLC, a subsidiary of Otsuka, have and continue to study the supplement containing S-equol for the management of menopausal symptoms.
More information about S-equol, including results of studies, is at http://www.
How the S-equol Supplement is Made
The supplement 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 soy isoflavone daidzein to S-equol. The S-equol ingredient is created under current Good Manufacturing Practices. Following fermentation, the bacteria undergo heat denaturation and are deactivated. The process is designed to produce a S-equol rich product, or nutraceutical ingredient. The ingredient has self-affirmed GRAS (Generally Recognized As Safe) status.
NAMS Poster #P-107, October 16, 2014, 6:00 pm - 7:00 pm
A Pilot Study of S-equol Supplement (SE5-OH) on Reproductive Health in Postmenopausal Japanese Women
Shigeto Uchiyama, M.S., Tomomi Ueno, M.S., and Soh Iwashita, Ph.D., all of Saga Nutraceuticals Research Institute, Otsuka Pharmaceuticals Co., Ltd.,; Belinda H. Jenks, Ph.D., and James Brooks., Ph.D., both of Scientific Affairs of Pharmavite LLC; and Takeshi Aso, M.D., Ph.D., Professor and Chairman Emeritus, Department of Comprehensive Reproductive Medicine at the Tokyo Medical and Dental University and of Kyoundo Hospital in Tokyo, Japan. Iwashita also has an appointment with Scientific Affairs of Pharmavite LLC.
About Pharmavite LLC:
For more than 40 years, Pharmavite LLC has earned and maintained the trust of healthcare professionals, consumers, and retailers by manufacturing high-quality vitamins, minerals and other dietary supplements, and all-natural foods under its Nature Made® and SOYJOY® brand names. Based in Northridge, California, Pharmavite LLC operates as a subsidiary of Otsuka Pharmaceutical Co., Ltd. For more information, please visit Pharmavite.com.
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 25 countries and regions around the world, with consolidated sales of approximately USD 14.1 billion for fiscal year 2013 (4/1/2013-3/31/2014.) Otsuka Pharmaceutical welcomes you to visit its global website at https:/
Calleja-Agius J, Brincat MP. "Urogenital atrophy." Climacteric. 2009 Aug;12(4):279-85. doi: 10.1080/13697130902814751.
Uchiyama S, Ueno T, Iwashita S, Jenks BH, Brooks J, Aso T. A Pilot Study of S-equol Supplement (SE5-OH) on Reproductive Health in Postmenopausal Japanese Women, presented at North American Menopause Society 2014 Annual Meeting, October 16, 2014, Washington, D.C.