News Release

Safety and influence on hormones and PSA examined in men taking novel soy germ-based dietary supplement, SE5-OH containing Natural S-equol

Peer-Reviewed Publication

Porter Novelli

Anaheim, Calif. (April 30, 2010) – Measures of reproductive and thyroid hormone levels remained within normal limits in healthy adult Japanese men who took either of two doses of a supplement of SE5-OH containing Natural S-equol, a novel soy germ-based ingredient under development for the management of prostate health, according to a new placebo-controlled study. In addition, measures of the men's prostate-specific antigen (PSA) levels were within normal limits. These peer-reviewed safety data were presented at the Experimental Biology (EB) 2010 annual meeting.

"The current study evaluated the safety and tolerance of SE5-OH containing Natural S-equol in healthy men. S-equol is under study to assist in the management of prostate health, as previous studies have indicated blood levels of equol are associated with reduced risk of prostate cancer in certain populations. This new safety study establishes that in healthy men, their concentrations of reproductive hormones as well as thyroid hormones remained within the normal range after 12 weeks of receiving SE5-OH containing Natural S-equol and the ingredient appears to be well tolerated. 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," 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 SE5-OH containing Natural S-equol in supplement form. 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 the Experimental Biology annual meeting, and a complete report of the data 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.

Earlier, controlled studies among men in Japan and Korea, countries where soy consumption is high, suggest equol is associated with reduced risk of prostate cancer. A 2002 study in Japan showed that equol producers tended to have more favorable prostate cancer disease stages and grades at diagnosis. A 2004 study documented that equol producers compared to nonequol producers consistently had lower rates of prostate cancer in Japanese and Korean men, but not in men living in America.

Hormone levels remain normal after SE5-OH containing Natural S-Equol ingestion

Levels of six hormones remained in the normal range and did not significantly differ between men receiving a placebo (12 men) or one of two daily doses of SE5-OH containing Natural S-equol, 10 milligrams (mg) (17 men) or 30 mg (17 men) for 12 weeks. Study investigators specifically measured total testosterone, free testosterone, estradiol, thyroid stimulating hormone (TSH), FreeT3 (a form of triiodothyronine) and FreeT4 (a form of thyroxine).

The men's average PSA levels were normal at the beginning of the study. After the study end, average PSA levels did not significantly differ between the men in the placebo or the two SE5-OH containing Natural S-equol groups. Both the hormones and PSA were measured at the study start and at four, eight, 12 and 16 weeks as part of the randomized, double-blind, placebo-controlled study of the 46 healthy Japanese men aged 22 to 64 years. PSA is a protein produced by prostate gland cells and the U.S. Food and Drug Administration has approved the use of the PSA test with a digital rectal exam to help detect prostate cancer in men age 50 and older.

Testosterone, an androgen, is secreted mostly in the testes of men. As the major male sex hormone, testosterone helps in the development and maintenance of male reproductive tissues including the prostate. After testosterone secretion, an enzyme converts the hormone into dihydrotestosterone (DHT) which is a potent androgen and required for sex development. The conversion to DHT occurs in the prostate gland, testes, hair follicles and adrenal glands. DHT is responsible for the formation of primary male sex characteristics and most secondary male sex characteristics during puberty, such as muscular growth, facial and body hair growth, and deepening of the voice.

Six of the placebo group, five of the 10 mg SE5-OH group and eight of the 30 mg SE5-OH group were documented as equol producers, based on their equol levels after a soymilk challenge. This standard test for equol production in humans includes a three-day soy milk challenge followed by measures of urinary equol concentration on day four of the test. The two treatment groups did not differ by average age, body mass index or smoking status. To enroll in the study, the men were required to be antibiotic free.

How SE5-OH is made

SE5-OH for the study was created under current Good Manufacturing Practices using the equol-producing lactic acid bacterial strain Lactococcus 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.

EB Presentation

Sunday, April 25, 2010, Poster # A76
Belinda Jenks, Ph.D. , (Scientific Affairs, Pharmavite LLC in Northridge, CA); and Soh Iwashita, Ph.D., and Shigeto Uchiyama, M.S.,(Otsuka Pharmaceutical Co, LTD,
Nutraceuticals Research Institute in Saga, Japan);


About the Experimental Biology 2010 meeting

The six sponsoring societies for Experimental Biology 2010 are: the American Association of Anatomists (AAA), The American Physiological Society (APS), American Society for Biochemistry and Molecular Biology (ASBMB), American Society for Investigative Pathology (ASIP), American Society for Nutrition (ASN) and American Society for Pharmacology and Experimental Therapeutics (ASPET).

About Pharmavite LLC: For almost 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 comprises 153 companies and employs approximately 36,000 people in 23 countries and regions worldwide. Otsuka and its consolidated subsidiaries earned ¥955.9 billion (approx. US $9.7 billion*) in annual revenues in fiscal 2008. * Exchange rate as of March 31, 2009.

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