Breast health study advances safety profile for soy-based natural S-equol supplement designed to manage menopause symptoms

Northridge, Calif. (Sept. 13, 2011) –Consuming the soy germ-based compound Natural S-equol and the supplement SE5-OH containing Natural S-equol did not increase the risk of estrogen-sensitive breast cancer, according to a study in the September issue of the peer-reviewed journal Food and Chemical Toxicology. SE5-OH containing Natural S-equol reduced menopause symptoms in postmenopausal women in previously reported controlled trials in the United States and in Japan.

"A major concern of health care professionals and women in managing menopausal symptoms is that a treatment might increase the risk of developing or progressing breast cancer," said 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. "This study is the first to directly examine the effects of Natural S-equol alone and SE5-OH containing Natural S-equol, which we are developing to reduce menopause symptoms, directly on the growth of human breast cancer cells in an established mouse model as well as in directly in cell cultures. The study documented that Natural S-equol itself, as well as SE5-OH, did not increase or stimulate the growth of these breast cancer cells."

The safety of SE5-OH containing Natural S-equol previously was confirmed by standard animal testing. Also, studies involving postmenopausal women who consumed SE5-OH containing Natural S-equol have not observed any safety problems, including analysis of breast and reproductive tissues and of hormone levels, and have documented significant reductions in hot flashes frequency, in muscle and joint discomfort. More information about S-equol and SE5-OH, including study results, is at http://www.naturalequol.com.

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. Because of the actions that S-equol has that mimic some but not all activities of naturally occurring estrogen, it is important for us to explore the effects of S-equol as well as of SE5-OH containing Natural S-equol on human breast cancer cells," explains Jenks.

About 60 to 70 percent of human breast cancers are estrogen-positive, in which estrogen, the main sex hormone in women, acts with high affinity to these receptors and increases the number of cancer cells.

No significant differences in the size of human breast tumors occurred between mice that ate diets for 25 weeks containing Natural S-equol, SE5-OH, genistein (an isoflavone that occurs naturally in soy) or a soy-free diet.

For the study, investigators implanted 71 healthy female mice - from which the ovaries had been surgically removed - with pellets containing 2 milligrams (mg) of 17-beta estradiol, a form of estrogen. One week later, the researchers injected the mice with MCF-7-E10 cells, which are estrogen-dependent, human breast cancer cells that have both alpha and beta estrogen receptors. When the cells had grown to tumors that averaged 34 square millimeters (mm2) in size, nine of the mice continued unaltered, as a control, while the rest of the mice had their estrogen pellets removed.

The 62 mice without estrogen then received one of four diets daily for 25 weeks: either 250 or 500 parts-per-million (ppm) of the soy isoflavone genistein, SE5-OH or purified S-equol or no soy isoflavones. The researchers measured the size of the implanted tumors, total body weight and food intake weekly.

At 25 weeks, the tumor sizes did not significantly differ and for the 250 or 500 ppm groups, respectively, averaged 61 mm2 in the estrogen pellet-free control group, 96 and 79 mm2 in the genistein groups, 65 and 80 mm2 in the SE5-OH groups, and 62 and 56 mm2 in the S-equol groups. In comparison, by week 10, the mice had estrogen pellets had tumors that averaged 269 ± 72.1 mm2.

In other studies, doses of the supplement SE5-OH containing Natural S-equol ranging from 10 to 30 mg daily were effective in reducing menopausal symptoms without significant adverse events.

In tests using laboratory cultures of MCF-7-E10 cells, Natural S-equol and SE5-OH containing Natural S-equol did not stimulate estrogen receptor activity or the multiplication of MCF-7-E10 cells unless given at concentrations that were 10,000 to one million times larger than the levels needed to induce comparable activity with 17-beta estradiol (0.05 ± 0.00 to 0.16 ± 0.13 pico moles,).

Authors of the study are Atsuko Onoda, M.S., Tomomi Ueno, M.S., and Shigeto Uchiyama, M.S. of Otsuka Pharmaceutical Co, LTD, Saga, Japan; and Kiyoko Kato, Ph.D., M.D., and Norio Wake, Ph.D., M.D., of the Department of Obstetrics and Gynecology at the Graduate School of Medical Sciences of Kyushu University, Fukuoka, Japan. An initial report on the study data was presented in a poster at the Women's Health Congress 2011 in April.

How SE5-OH Ingredient 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 SE5-OH containing Natural S-equol is conducted by the Saga Nutraceuticals Research Institute of Otsuka Pharmaceutical Co., Ltd.

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 for fiscal year 2010. Visit Otsuka Pharmaceutical Co., Ltd. at http://www.otsuka.co.jp/en/.