Public Release: 

Larger percentage of bioactive forms of S-equol appear to play role in managing menopausal symptoms


Northridge, CALIF (October 1, 2015) - A study of how the body processes a nutritional supplement containing S-equol, a novel soy germ-based ingredient, shows that metabolism yields two forms that are biologically active. The new study, which builds on previously published peer-reviewed studies showing that daily 10 milligram (mg) doses of S-equol help relieve certain menopause symptoms, was reported in a peer-reviewed poster at the 2015 North American Menopause Society (NAMS) annual scientific meeting.

"The study documented that approximately 43 percent of the S-equol in the plasma of women, following their ingestion of the supplement, is in two bioactive forms, as free S-equol and as a sulfated conjugate. This large concentration may be the reason that S-equol can contribute to the relief of certain menopause symptoms, as documented in other controlled clinical trials," 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. The new study is part of an ongoing scientific research effort to document the benefits associated with S-equol.

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 a supplement containing S-equol 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.

S-Equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is produced via natural metabolism of daidzein, an isoflavone found in whole soybeans, in the intestine. 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 S-equol. Preliminary evidence from observational studies suggests that women who are S-equol producers may experience fewer menopausal symptoms compared to non-producers.

S-equol-containing Supplements Metabolized to Two Active Types

In the study, 11 healthy postmenopausal Japanese women (ages 43 to 62 years) each ingested one dose of the supplement containing 10 milligrams of S-equol. Blood plasma samples showed the presence of S-equol, both as free and sulfate conjugate forms. The study identified three sulfate conjugates: equol 7-sulfate, equol 4'-sulfate, and equol 4',7-disulfate. Both the free and sulfate conjugate forms of S-equol have biological activity, but until this study, their respective processing within the body (bioavailability and pharmacokinetics) had not been examined.

Metabolism in the liver of the S-equol-containing supplement yielded both forms. The time to reach the maximum plasma concentrations of the free and sulfate conjugates forms and total S-equol were each about one hour. The maximum plasma concentrations, the sum of the free and sulfate conjugates forms, was 0.85 μmol/L and in total S-equol were 2.38μmol/L. A determination of the available plasma concentrations during the first 24 hours after dosing, called an Area Under the Curve (AUC) calculation, revealed that, together, the free and sulfate conjugated forms tallied 43.4 percent of the total S-equol present.

S-equol is excreted almost exclusively in urine. Elimination times for half of the concentrations of both free and sulfate conjugates forms were six to nine hours. Within 48 hours, 76 percent of the S-equol was excreted in the urine.

This was a single-center, randomized, open label study whereby the participants ingested a single tablet containing 10 mg of S-equol. Of the women, six were natural equol producers and five were non-producers. Investigators collected blood samples before and 0.5, one, two, four, six, eight, 12, 16, 24, 36 and 48 hours after the women ingested the supplement and urine samples during the same 48 hours. All pharmacokinetics measures of S-equol did not differ when examined by the women's equol producing status. The data will be submitted for peer-review publication.


About S-equol

Standard animal testing has evaluated the safety of the supplement containing S-equol, including a laboratory 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 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. Pharmavite LLC, a subsidiary of Otsuka, is studying the supplement containing S-equol for the management of menopausal symptoms.

More information about the supplement containing S-equol, including results of studies, is at

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 daidzein to S-equol. The supplement containing S-equol is created under current Good Manufacturing Practices. Following fermentation, the bacteria undergo heat denaturation and are deactivated. The process is designed to produce an S-equol rich product, or nutraceutical ingredient. The ingredient has self-affirmed GRAS (Generally Recognized As Safe) status.

NAMS Poster # P-37

Thursday, October 1, 2015 6:00 pm
Pharmacokinetics of S-equol After Administration of a Fermented Soy Germ in Equol Producing and Non-Producing Postmenopausal Women
Shigeto Uchiyama, Soh Iwashita, Tomomi Ueno, Noriyuki Koyama, and Tohru Uesugi of Otsuka Pharmaceutical Co., Ltd. and Belinda H. Jenks and James Brooks of Pharmavite LLC, Northridge, CA

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 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

About Otsuka Pharmaceutical Co., Ltd.:

Otsuka Pharmaceutical and its affiliates, which employ approximately 30,000 people worldwide, are wholly owned subsidiaries of Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group that is headquartered in Tokyo, Japan. The Otsuka Group has business operations in 27 countries and regions around the world, with consolidated sales of approximately USD 10.2 billion in fiscal year 2014, a nine-month period (4/1/2014-12/31/2014) due to the company's change to a calendar year reporting cycle. Otsuka Pharmaceutical welcomes you to visit its global website at

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