Healthy pre-and post-menopausal Japanese women who took a supplement of SE5-OH containing Natural S-equol, a novel soy germ-based ingredient under development for the management of menopausal symptoms, had measures of reproductive hormones that stayed within normal limits throughout the study. These peer-reviewed safety data were presented at the American Medical Women's Association (AMWA) 2010 annual meeting.
A second safety study presented at AMWA documented that SE5-OH containing Natural S-equol consumption did not change the length of menstrual cycles in healthy pre-menopausal Japanese women. An earlier peer-review study in postmenopausal Japanese women documented that those receiving SE5-OH containing Natural S-equol reduced the frequency of hot flashes significantly compar ed to the women in the same study receiving a placebo>
"SE5-OH containing Natural S-equol may be an appropriate dietary supplement ingredient for women undergoing menopause, as it has recently been studied in clinical trials for its benefits for relief of hot flushes in U.S. and Japanese women. The new safety data documents that in healthy women SE5-OH containing Natural S-equol does not appear to influence the normal concentrations of endocrine hormones, the normal endometrium thickness or normal menstrual cycle length and appears to be well tolerated," said Belinda H. Jenks, Ph.D., director of Scientific Affairs & Nutrition Education at Pharmavite LLC, and an author of the study.
Pharmavite LLC, the makers of NatureMade- vitamins and minerals and a subsidiary of Otsuka Pharmaceutical Co., Ltd., is studying in clinical trials SE5-OH containing Natural S-equol in supplement form for the management of menopausal symptoms. Saga Nutraceuticals Research Institute of Otsuka Pharmaceutical Co., Ltd. developed the ingredient and has an ongoing research program to study SE5-OH containing Natural S-equol. Otsuka Pharmaceutical Co., Ltd., supported the research and data presented at AMWA, and complete reports of the data from both safety studies will be submitted for peer-review publication.
Soybeans contain a naturally occurring compound called daidzein that certain bacteria living within the human digestive tract can metabolize, or convert, into S-equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman]. 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 equol. Studies in Japan have documented an association between milder menopausal symptoms in equol producers as compared to non-producers.Endocrine hormones not influenced by SE5-OH containing Natural S-Equol in pre- and post-menopausal women
Moreover, the status of these hormones as well as of progesterone, luteinizing hormone (LH) and testosterone remained normal and did not differ between the Natural S-Equol group and the placebo group in a second study of 36 pre-menopausal Japanese women. In this study, the women's hormone status was measured during three specific menstrual cycle phases, the early follicular phase, the late follicular phase and the middle luteal phase, over the course of three cycles.
Both studies used a randomized, double-blind, placebo-controlled, parallel-group design. Both studies used the same formulation of SE5-OH containing Natural S-equol tablets and placebos. Endometrium thickness not influenced by SE5-OH containing Natural S-equol in post-menopausal women
As a normal part of the menstrual cycle, the hormone estrogen exerts influence to prompt the growth and thickening of the endometrium, to help create a receptive environment for a fertilized egg. When the ovary releases an unfertilized egg, it also produces the hormone progesterone. Progesterone also influences the endometrium to prepare for pregnancy. However, if fertilization does not occur, the progesterone level drops and the endometrium is shed from the uterus, a process called menstruation. The cycle repeats about every 28 days until menopause, when menstruation ceases. Menstrual cycle length in pre-menopausal women not influenced by SE5-OH containing Natural S-equol
In each of the two studies, the women in the placebo group did not differ from the women in the group receiving SE5-OH with Natural S-equol group in their reports of adverse effects, which included were diarrhea and feelings of fullness.About the two studies
During the 12-week post-menopausal study, the 27 women in the treatment group took Natural S-equol. The 54 women, aged 44 to 64, had reached menopause an average of five years prior to enrollment. None of the women naturally produced equol. The two treatment groups did not differ by average age or body mass index.
"These studies demonstrated that SE5-OH containing Natural S-equol is safe as measured and well tolerated in post-menopausal women fed the supplement for 12 weeks and in pre-menopausal women fed the supplement for one month. These studies were designed to better understand the impact and safety of SE5-OH with Natural S-equol in these two populations of women, and the findings indicate that there are no short-term safety concern based on the measures included in the study of certain hormone levels, endometrium thickness and menstrual cycle durations. These studies were conducted in preparation for the development of a women's health supplement designed to provide benefits for the management of menopausal symptoms. Further studies are needed to confirm whether or not fermented soy food containing Natural S-equol has influence when consumed for longer time periods or at higher doses," Jenks said.
SE5-OH for both studies was created under current Good Manufacturing Practices using the Lactic acid bacterial strain Lactococcus garvieae 20-92 in a patented and proprietary process by the Otsuka Pharmaceutical Co., Ltd. The patented fermentation process converts daidzein, a naturally occurring compound in soy germ, to Natural S-equol, steadily increasing the concentration of Natural S-equol until reaching a maximum concentration at 72 to 96 hours and decreasing daidzein by 95 percent. Following fermentation, the SE5-OH powder undergoes a sterilization process using heat denaturation that deactivates the bacteria. The process is designed to produce a product rich in Natural S-equol that can be used as a nutraceutical ingredient.
How SE5-OH is made
Friday, and Saturday March 26, 2010, Poster #39
Safety Assessment with Ingestion of Natural S-Equol in Pre- and Post-Menopausal Healthy Japanese Women
Belinda Jenks, Ph.D. , (Pharmavite LLC, Northridge, CA); Soh Iwashita, Ph.D., Tomomi Ueno, M.S., Atsuko Onoda, M.S., Yasuhiro Abiru, Ph.D., and Shigeto Uchiyama, M.S.,(Otsuka Pharmaceutical Co, LTD, Saga, Japan); Masaru Sakamoto, M.D., Ph.D., (Sasaki Institute Kyoundo Hospital, Tokyo, Japan); and Takeshi Aso, M.D., Ph.D., (Sasaki Institute and Tokyo Medical and Dental University, Tokyo, Japan).