New scientific review suggests some women may benefit from considering use of S-equol to ease menopause symptoms

The investigational S-equol nutritional supplement may be a viable agent to alleviate certain menopause symptoms, such as hot flashes, according to a new peer-reviewed article in the March Journal of Women’s Health (1).

“Current data suggest that women may have benefits with S-equol for menopausal vasomotor symptoms and possibly additional benefits, such as skin health. Given the studies supporting safety of S-equol, physicians and health care professionals may consider the use of S-equol as a future first round option for menopause symptoms, especially for women not wanting to use pharmaceuticals,” said coauthor Wulf H. Utian, M.D., Ph.D., D.Sc., Founder of the North American Menopause Society (NAMS) and Director Emeritus of the Department of Obstetrics and Gynecology, University Hospitals of Cleveland.

Menopause may be associated with vasomotor symptoms (VMS) related to diminished production of estrogen. While VMS such as hot flashes and night sweats are well known as several of the key symptoms during this time period in the woman’s life, the estrogen loss during menopause contributes to other key changes including bone loss, atrophy of the reproductive and urinary tissues, vaginal dryness, painful intercourse, sexual dysfunction, decreased libido, urinary tract infections and incontinence, increased cardiovascular risk and loss of skin elasticity. Although estrogen replacement therapy can help manage these menopause-related symptoms, some women may prefer not use such hormone-based therapy.

The FDA has approved some pharmaceuticals for women to manage their menopause-related VMS. For some women, if they react with side effects or decide that they do not want to use these, S-equol may offer another approach to manage their menopause-related VMS. “Many women are confused about the controversies surrounding estrogen replacement therapies for menopause. S-equol offers women an alternative for symptom relief without the potential harmful effects of estrogen,” said coauthor Michelle Jones, M.D., FAAFP, a family practice physician at Wilmington Health Associates, North Carolina.

Estrogen-like Properties of S-equol

S-equol, made from fermented soy germ, is chemically and has physiological properties different from soybean isoflavones and estrogen. The estrogen-like properties of S-equol have been investigated for more than four decades. S-equol [7-hydroxy-3-(4’-hydroxyphenyl)-chroman] 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.

“S-equol is a natural metabolite of soy isoflavones that has unique SERM-like (selective estrogen receptor modulators) properties , thus offering the ‘beneficial effects’ of estrogen while not having the negative effects associated with estrogen. It has potential for many hormone-dependent conditions associated with menopause,” said coauthor Kenneth D. R. Setchell, Ph.D., Professor in the Department of Pediatrics and Director of Clinical Mass Spectrometry at the University of Cincinnati College of Medicine.

New scientific review suggests some women may benefit from considering use of S-equol to ease menopause symptoms S-equol is found in very few foods and only in trace amounts. S-equol is produced in the intestine after consuming soy via the natural metabolism of daidzein, an isoflavone found in whole soybeans. Not everyone can produce S-equol, as the production depends on the types of bacteria present in the large intestine. About 50 percent of Asians and 25 percent of non-Asians, who in general consume less soy than Asians, have the ability to produce S-equol.

S-equol Efficacy

Daily doses of the S-equol supplement have relieved hot flash frequency and muscle and joint pain in controlled clinical trials in both U.S. and Japanese postmenopausal women. Additional clinical trials in Japanese individuals have documented beneficial effects of S-equol on cardiovascular disease as well as bone and skin health. Studies of how the body processes S-equol have documented that twice-daily dosing of the supplement, rather than once-daily, is optimal for maximum efficacy.

A 12-week randomized placebo controlled study to evaluate the effects of S-equol on hot flashes in non-equol producing Japanese women documented a significant 58.7 percent decrease of hot flash frequency in the S-equol group, compared to 34.5 percent in the placebo group, (P=0.009). Moreover, significant decreases occurred in the severity of hot flashes (P=0.015) and neck or shoulder muscle stiffness (P=0.015) in the S-equol group. A U.S. trial evaluated S-equol in Caucasian and African American women and found that for those who had more than eight hot flashes daily, S-equol significantly reduced hot flash frequency and muscle and joint pain, more so than taking 50 mg/day soy isoflavones.

Additional clinical trials in Japanese individuals have documented significant beneficial effects of S-equol on cardiovascular disease markers, including lower hemoglobin A1c (P < 0.05), serum low-density-lipoprotein (LDL) cholesterol (P < 0.01) and cardio-ankle vascular index scores (P < 0.01 ), which is an indicator of arterial stiffness.

A 12-month bone study of Japanese postmenopausal women documented that S-equol significantly inhibited bone break down (P=0.020) as well as prevented a decrease in whole body bone mineral density (P=0.027). Additionally, a skin aging study documented consuming S-equol significantly decreased (P < 0.05) the crow's-feet wrinkle area in postmenopausal Japanese women who did not naturally make S-equol after eating soy.

S-equol Safety

Two clinical studies found no evidence for S-equol having a proliferative effect on the uterus, particularly endometrial thickness. Additionally, clinical studies examining the degree of abnormal vaginal cells found, after 12 weeks of S-equol supplement use, all of the women remained classified as either having no abnormal cells or cells that showed no evidence of malignancy. Standard animal testing also 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.

Further studies are needed before definitive conclusions of S-equol effectiveness for VMS can be made, but it is worth noting that population-based studies of soy isoflavones lend indirect support for the safety of S-equol, since 25 to 30 percent of Westerners and 50 to 60 percent of Asians or Western vegetarians naturally produce S-equol when consuming soy foods.

The article's authors are members of the Menopausal Health Advisory Board of Pharmavite, LLC. Setchell also holds intellectual property in the form of inventorship on several patents related to S-equol that are licensed by Cincinnati Children's Hospital Medical Center.

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.

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 developed by 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 an S-equol rich product, or nutraceutical ingredient. The ingredient has self-affirmed GRAS (Generally Recognized As Safe) status.


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

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.)

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