Home Ingredients Equol (S-Equol)
Menopause SupportBone HealthHair, Skin & Nails

Equol (S-Equol)

Evidence Level
Limited
8 Clinical Trials
6 Documented Benefits
2/5 Evidence Score

Equol is a compound that some people's gut bacteria make from daidzein, an isoflavone in soy; only about 30 to 50 percent of people carry those bacteria. S-equol supplements supply it directly and are made by fermenting soy germ isoflavones with an equol-producing bacterium. Most human trials are small Japanese studies in women after menopause who do not make equol, usually at 10 mg a day. In the largest placebo-controlled trial (160 women), hot flashes fell more than on placebo, and smaller pilot trials reported lower bone breakdown markers and smaller crow's-feet wrinkles. Other studies found no effect, including a single-dose arterial stiffness test, and several trials had authors or supplies from companies that make or sell S-equol. The North American Menopause Society does not recommend equol for hot flashes. It is a separate ingredient from daidzein and soy isoflavones.

Studied Dose 10 mg a day in most trials, for 12 weeks to 12 months. Other arms used 2 or 6 mg (bone pilot), 10 mg three times a day (mood trial), 20 or 40 mg (comparison with soy isoflavones) and 30 mg (skin trial).
Active Compound S-equol (S-(-)-equol), the gut-bacteria metabolite of the soy isoflavone daidzein, made for the SE5-OH ingredient used in most trials by fermenting soy germ isoflavones with Lactococcus garvieae.

Benefits

Hot flash frequency in women who do not make equol

In a 12-week multicenter trial in 160 postmenopausal Japanese women who did not make equol, 10 mg a day of S-equol cut daily hot flashes by 58.7%, versus 34.5% on placebo; severity and neck or shoulder stiffness also improved more. 126 women finished. The North American Menopause Society does not recommend equol for hot flashes.

Supported by Trial 1, Trial 2

Mood scores in midlife women

In a 12-week placebo-controlled trial in 134 Japanese women aged 40 to 59, 10 mg of S-equol three times a day lowered depression scores and tension, depression and fatigue ratings on a mood questionnaire, and raised vigor, compared with placebo. Other symptom gains were changes from baseline within one subgroup, not comparisons with placebo.

Supported by Trial 2, Trial 6

Hot flashes compared with soy isoflavones

In an 8-week trial of 102 postmenopausal women with at least 5 hot flashes a day, 10, 20 or 40 mg of S-equol and a soy isoflavone supplement gave similar drops in hot flash frequency at week 8; over the whole 8 weeks, 40 mg did better than isoflavones. There was no placebo group, and the lead author worked for Pharmavite, which sells an S-equol supplement.

Supported by Trial 3

Bone resorption marker after menopause

In a 1-year placebo-controlled pilot in 93 postmenopausal Japanese women who did not make equol, 10 mg a day of S-equol lowered urinary deoxypyridinoline, a bone breakdown marker, by 23.9% versus 2.9% on placebo, and the authors report it prevented a fall in whole-body bone density. Fractures were not studied.

Supported by Trial 4

Crow's-feet wrinkle area after menopause

In a 12-week placebo-controlled pilot in 101 postmenopausal Japanese women who did not make equol, 10 and 30 mg a day of S-equol reduced crow's-feet wrinkle area more than placebo, and 30 mg reduced wrinkle depth. Skin hydration, water loss and elasticity did not differ. The lead author worked at Otsuka Pharmaceutical, which makes the S-equol ingredient.

Supported by Trial 5

Arterial stiffness and blood sugar markers in overweight adults

In a 12-week crossover trial with no washout in 54 overweight Japanese adults, 10 mg a day of S-equol lowered HbA1c, LDL cholesterol and an arterial stiffness index versus placebo, most clearly in women who did not make equol. In 14 men who did not make equol, a single 40 mg dose did not change arterial stiffness, blood pressure or blood vessel function.

Supported by Trial 6, Trial 7

Mechanism of action

1

Selective binding to estrogen receptor beta

S-equol binds preferentially to estrogen receptor beta, and it has been reported to block the action of the male hormone dihydrotestosterone in vivo. These properties come from experimental research; they explain why it was tested around menopause but do not show a benefit on their own.

2

Supplies equol without relying on gut bacteria

Only some people carry gut bacteria that turn daidzein from soy into S-equol: 25% to 34% of the women in two of the studies cited here, and about 30% in Western populations by one estimate. The SE5-OH ingredient used in most of these trials is made by fermenting soy germ isoflavones with the equol-making bacterium Lactococcus garvieae, so it delivers S-equol directly.

3

Well absorbed with a half-life of about 8 hours

In 12 healthy postmenopausal women, single 10 and 30 mg doses were rapidly absorbed, with a plasma half-life of about 8 hours, and about 82% of each dose was recovered in urine. Absorption did not differ by whether women made equol themselves, though only 3 of the 12 did.

Clinical trials

1
S-Equol 10 mg for Hot Flashes in Equol Non-Producers: Multicenter Placebo-Controlled RCT
PubMed

Multicenter, double-blind, placebo-controlled randomized trial of a natural S-equol supplement for 12 weeks, with follow-up at week 18. (Aso et al. 2012, J Womens Health (Larchmt))

160 postmenopausal Japanese women who did not produce equol and had at least 1 hot flash a day (77 S-equol 10 mg/day, 83 placebo); 126 completed.

Daily hot flash frequency fell by 1.9 a day (58.7%) with S-equol versus 1.0 a day (34.5%) with placebo (p = 0.009). Hot flash severity and neck or shoulder muscle stiffness also fell more with S-equol. No changes in clinical lab values or serious adverse effects were reported. About one in five women did not finish.

2
S-Equol 10 or 30 mg Daily and Menopause Symptoms and Mood: Placebo-Controlled RCT
PubMed

Randomized, double-blind, placebo-controlled 12-week trial of a new S-equol supplement at 10 mg once daily or 10 mg three times daily, with habitual isoflavone intake limited to 20 mg a day. (Ishiwata et al. 2009, Menopause)

134 Japanese women aged 40 to 59 (44 placebo, 44 at 10 mg/day, 46 at 30 mg/day); 127 completed; 34.3% were equol producers.

Compared with placebo, the 30 mg/day group had lower depression scores and lower tension-anxiety, depression-dejection and fatigue scores, with higher vigor, on the Profile of Mood States. Perimenopausal and postmenopausal non-producers on 30 mg/day improved from baseline on all menopause symptom scores except depression, a within-group change. The abstract does not report a placebo comparison for the 10 mg/day arm. One woman on 30 mg/day developed a systemic rash.

3
S-Equol (SE5-OH) vs Soy Isoflavones for Hot Flashes: 8-Week Pilot (no placebo)
PubMed

8-week randomized, double-blind, active-comparator pilot of the natural S-equol supplement SE5-OH at three doses versus soy isoflavones; lead author employed by Pharmavite LLC. (Jenks et al. 2012, J Womens Health (Larchmt))

102 postmenopausal women aged 45 to 65 with at least 5 hot flashes a day (S-equol 10, 20 or 40 mg/day, or soy isoflavones).

Hot flash frequency at week 8 fell by similar amounts in all four groups. Across the whole 8 weeks, 40 mg/day S-equol reduced frequency more than isoflavones (p = 0.021); in a subgroup with more than 8 hot flashes a day, 20 and 40 mg/day did better than isoflavones. 10 and 20 mg/day improved muscle and joint pain scores versus isoflavones. With no placebo arm, the trial cannot show how much any group beat no treatment.

4
Natural S-Equol and Bone Resorption in Non-Producers: 1-Year Placebo-Controlled Pilot
PubMed

1-year double-blind, randomized, placebo-controlled pilot trial of natural S-equol supplements at 2, 6 or 10 mg a day. (Tousen et al. 2011, Menopause)

93 postmenopausal Japanese women who did not produce equol, split into placebo, 2, 6 and 10 mg/day groups.

At 12 months, urinary deoxypyridinoline fell 23.94% with 10 mg/day versus 2.87% with placebo (P = 0.020), and the authors report that 10 mg/day prevented a decrease in whole-body bone mineral density. Equol in blood and urine rose with dose. Sex and thyroid hormone levels did not differ among groups. A small pilot of bone markers and density; fractures were not measured.

5
Natural S-Equol and Crow's-Feet Wrinkles: 12-Week Placebo-Controlled Pilot (Otsuka authors)
PubMed

Randomized, double-blind, placebo-controlled 12-week pilot of a natural S-equol supplement on skin aging; lead author from Otsuka Pharmaceutical's nutraceuticals research institute. (Oyama et al. 2012, Menopause)

101 postmenopausal Japanese women who did not produce equol (34 placebo, 34 at 10 mg/day, 33 at 30 mg/day).

Both S-equol groups had a significantly larger reduction in crow's-feet wrinkle area than placebo (P < 0.05), and wrinkle depth differed from placebo at 30 mg/day only. Hydration, transepidermal water loss and elasticity did not differ in any group. Hormone tests, vaginal cytology, endometrial thickness and mammography showed no abnormal results.

6
Natural S-Equol in Overweight Adults: 12-Week Crossover (no washout)
PubMed

Randomized, double-blind, placebo-controlled crossover trial with no washout period of natural S-equol tablets, 10 mg a day for 12 weeks. (Usui et al. 2013, Clin Endocrinol (Oxf))

54 overweight or obese Japanese outpatients (BMI 25 or higher); 67.9% were equol non-producers.

Compared with placebo, S-equol lowered HbA1c, LDL cholesterol and the cardio-ankle vascular index (CAVI), a measure of arterial stiffness, with larger effects in women who did not produce equol. A small crossover without a washout period; outcomes were lab markers, not health events.

7
Single Dose of S-Equol and Arterial Stiffness in Men: No Effect in Non-Producers
PubMed

Double-blind, placebo-controlled crossover study of soy isoflavones by equol-producer status, plus a separate single 40 mg dose of commercially produced S-equol (SE5-OH, donated by Otsuka Pharmaceutical) in non-producers; funded by the UK Biotechnology and Biological Sciences Research Council. (Hazim et al. 2016, Am J Clin Nutr)

28 men at moderate cardiovascular risk (14 equol producers, 14 non-producers); the S-equol test was in the 14 non-producers.

A single 40 mg dose of S-equol did not improve carotid-femoral pulse wave velocity, blood pressure, endothelial function or nitric oxide 2 hours later in non-producers, even though plasma equol reached 3.2 micromol/L. Soy isoflavones improved pulse wave velocity at 24 hours only in men who made equol themselves. This tested one dose, not daily use.

8
Equol Supplement for 3 Months After Menopause: Open RCT with No-Supplement Control
PubMed

Single-center randomized trial (alternate assignment, no placebo) of an equol supplement (10 mg S-equol, FlavoCel EQ-5, Daicel Corporation, taken with lactobionic acid) versus no supplement; funded by Advanced Medical Care Co. Ltd. (Yoshikata et al. 2021, PLoS One)

57 postmenopausal Japanese women (mean age 56); 27 received the supplement.

More women improved on a climacteric symptom questionnaire with the supplement than without it (81% vs 53%, p = 0.045). There was no benefit on the main metabolic and aging biomarkers overall; skin advanced glycation end products and visceral fat improved only in some subgroups, mainly equol producers. With no placebo, the symptom result may include an expectation effect.

Side effects and drug interactions

Common Potential side effects

Generally well tolerated in trials of 8 weeks to 12 months at 10 to 40 mg a day. In one trial, a woman taking 30 mg a day developed a body-wide rash.
In a 12-month trial, sex and thyroid hormone levels did not differ from placebo, and a 12-week trial found no abnormal hormone, vaginal cell, endometrial thickness or mammography results. The longest trials lasted 12 months.
S-equol acts on estrogen receptors. If you have a personal history of hormone-sensitive cancer, endometriosis or fibroids, talk to your doctor before using it.
Supplements are made from fermented soy germ, so people with a soy allergy should check with the maker before use.
In rat studies, the SE5-OH ingredient showed no adverse effects at the highest dose tested (2,000 mg/kg a day for 91 days) and was not genotoxic in standard lab tests.
The trials enrolled adults, mostly women around or after menopause; use in pregnancy, breastfeeding and children was not studied.

Important Drug interactions

Anastrozole, letrozole, exemestane and tamoxifen: in 24 healthy postmenopausal women, 10 mg a day of an S-equol supplement for a week did not change blood levels of these drugs. The study did not test whether S-equol changes how well they work, so ask your oncologist before using it.
Estrogen or other menopausal hormone therapy: S-equol acts on estrogen receptors, and combined use was not studied in the trials cited here; discuss it with your doctor.
Levothyroxine (thyroid hormone): thyroid hormone levels did not change over 12 months in one trial, but interactions with thyroid medicine were not tested.

More Menopause Support Ingredients

Menopause Support
Black Cohosh (Actaea racemosa)
Black cohosh is a plant in the buttercup family that grows in North America. Native Americ…
Menopause Support
EstroG-100® (Three-Herb Menopause Extract — Naturalendo Tech)
EstroG-100® is a standardized blend of root extracts from three herbs used in Korean tradi…
Menopause Support
Shatavari (Asparagus racemosus / Xeya®)
Shatavari is the root of Asparagus racemosus, an herb used in Ayurveda for women's health.…
Menopause Support
FenuSmart® (Standardized Fenugreek Extract for Menopause — Akay Bioactives)
FenuSmart (also written FenuSMART) is Akay's standardized fenugreek (Trigonella foenum-gra…

Explore Other Ingredients

Metabolic Health
Berberine
Berberine is a yellow compound from plants such as barberry, goldenseal and Chinese goldth…
Metabolic Health
GlucoVantage® (Dihydroberberine)
GlucoVantage® is NNB Nutrition's branded dihydroberberine (DHB), a reduced form of berberi…
Metabolic Health
Inositol (Myo-Inositol)
Inositol is a sugar-like compound that the body makes from glucose and that takes part in…

Related articles from our blog

📝 Article
Red Clover for Hot Flashes: What a New 2026 Meta-Analysis Found
Red clover, the pink-purple wildflower most people walk past without a second look, has been sold for menopausal hot fla…
July 18, 2026

Frequently asked questions about Equol (S-Equol)

How is equol different from daidzein and soy isoflavones?

Daidzein is one of the isoflavones in soy. In some people, gut bacteria convert it into S-equol, which binds more selectively to estrogen receptor beta. People who lack those bacteria get little or no equol from soy, so S-equol supplements supply it ready-made. The trials cited here tested S-equol itself, not soy or daidzein, and most enrolled women who could not make equol.

Does S-equol help with hot flashes?

The evidence is small. In one 12-week trial of 160 Japanese women who did not make equol, 10 mg a day reduced hot flashes more than placebo. A pooled analysis of five trials, which also counted soy isoflavone trials in women who make equol, favored equol, but two of the five found no significant benefit. The North American Menopause Society does not recommend equol for hot flashes, and a 118-woman US trial of an S-equol product finished in 2020 has no results posted.

How much S-equol was used in studies?

Most trials used 10 mg a day for 12 weeks to 12 months. Other arms tested 2, 6, 20, 30 and 40 mg a day; in one trial the 30 mg dose was taken as 10 mg three times a day. Follow the product label.

Do I need to know whether I make equol?

Most S-equol trials enrolled only women who did not make equol, identified by measuring equol after soy intake. Whether people who already make equol gain anything from a supplement has been studied far less. In a study of absorption, S-equol from a supplement was absorbed the same way in producers and non-producers.

Is S-equol being studied for arteries or memory?

A single 40 mg dose did not change arterial stiffness in men who did not make equol, while a small 12-week crossover in overweight adults reported a lower arterial stiffness index. A 2-year placebo-controlled trial of 10 mg a day in 369 adults aged 65 to 85, measuring arterial stiffness and memory and thinking, has enrolled but not yet reported results.

What is Equol?

Equol is a compound that some people's gut bacteria make from daidzein, an isoflavone in soy; only about 30 to 50 percent of people carry those bacteria. S-equol supplements supply it directly and are made by fermenting soy germ isoflavones with an equol-producing bacterium.

What is Equol used for?

Equol is researched primarily for Menopause Support, Bone Health, and Hair, Skin & Nails. In a 12-week multicenter trial in 160 postmenopausal Japanese women who did not make equol, 10 mg a day of S-equol cut daily hot flashes by 58.7%, versus 34.5% on placebo; severity and neck or shoulder stiffness also improved more.

What is the recommended dosage of Equol?

The clinically studied dose is 10 mg a day in most trials, for 12 weeks to 12 months. Other arms used 2 or 6 mg (bone pilot), 10 mg three times a day (mood trial), 20 or 40 mg (comparison with soy isoflavones) and 30 mg (skin trial). Always follow the product label and check with a healthcare provider for personal advice.

Is Equol safe, and does it have side effects?

Side effects and cautions reported for Equol include: Generally well tolerated in trials of 8 weeks to 12 months at 10 to 40 mg a day. In one trial, a woman taking 30 mg a day developed a body-wide rash. It may also interact with some medications. Equol is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Equol interact with any medications?

Possible interactions include: Anastrozole, letrozole, exemestane and tamoxifen: in 24 healthy postmenopausal women, 10 mg a day of an S-equol supplement for a week did not change blood levels of these drugs. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Equol?

NutraSmarts rates the evidence for Equol as Limited (2 out of 5). It is backed by 8 clinical trials and 15 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(15 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Aso T, Uchiyama S, Matsumura Y, Taguchi M, Nozaki M, Takamatsu K, Ishizuka B, Kubota T, Mizunuma H, Ohta H. A natural S-equol supplement alleviates hot flushes and other menopausal symptoms in equol nonproducing postmenopausal Japanese women. J Womens Health (Larchmt). 2012;21(1):92-100. doi: 10.1089/jwh.2011.2753.PubMedUsed to support: Multicenter double-blind trial in 160 postmenopausal Japanese women who did not produce equol: 10 mg a day of S-equol for 12 weeks reduced daily hot flash frequency by 58.7% versus 34.5% with placebo (p = 0.009) and reduced hot flash severity and neck or shoulder muscle stiffness more than placebo. 126 women completed. No serious adverse effects.
  2. Ishiwata N, Melby MK, Mizuno S, Watanabe S. New equol supplement for relieving menopausal symptoms: randomized, placebo-controlled trial of Japanese women. Menopause. 2009;16(1):141-8. doi: 10.1097/gme.0b013e31818379fa.PubMedUsed to support: 12-week placebo-controlled trial in 134 Japanese women aged 40 to 59: S-equol 10 mg three times a day lowered depression scores and improved tension-anxiety, depression-dejection, fatigue and vigor mood scores versus placebo. Other menopause symptom improvements were within-group changes in non-producers. 34.3% of participants were equol producers. One systemic rash on the higher dose.
  3. Jenks BH, Iwashita S, Nakagawa Y, Ragland K, Lee J, Carson WH, Ueno T, Uchiyama S. A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt). 2012;21(6):674-82. doi: 10.1089/jwh.2011.3153.PubMedUsed to support: 8-week double-blind pilot in 102 postmenopausal women comparing the S-equol supplement SE5-OH (10, 20 or 40 mg a day) with soy isoflavones, without a placebo: week-8 hot flash reductions were similar in all groups, while 40 mg did better than isoflavones over the full 8 weeks. The lead author was employed by Pharmavite LLC.
  4. Tousen Y, Ezaki J, Fujii Y, Ueno T, Nishimuta M, Ishimi Y. Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: a pilot randomized, placebo-controlled trial. Menopause. 2011;18(5):563-74. doi: 10.1097/gme.0b013e3181f85aa7.PubMedUsed to support: 1-year placebo-controlled pilot in 93 postmenopausal Japanese women who did not produce equol: 10 mg a day of natural S-equol lowered urinary deoxypyridinoline by 23.94% versus 2.87% with placebo (P = 0.020) and was reported to prevent a decrease in whole-body bone density. Sex and thyroid hormone levels did not differ among groups.
  5. Oyama A, Ueno T, Uchiyama S, Aihara T, Miyake A, Kondo S, Matsunaga K. The effects of natural S-equol supplementation on skin aging in postmenopausal women: a pilot randomized placebo-controlled trial. Menopause. 2012;19(2):202-10. doi: 10.1097/gme.0b013e318227427b.PubMedUsed to support: 12-week placebo-controlled pilot in 101 postmenopausal Japanese women who did not produce equol: 10 and 30 mg a day of natural S-equol reduced crow's-feet wrinkle area versus placebo, and 30 mg reduced wrinkle depth; other skin measures did not differ, and gynecological and hormone checks were normal. The lead author was from Otsuka Pharmaceutical.
  6. Usui T, Tochiya M, Sasaki Y, Muranaka K, Yamakage H, Himeno A, Shimatsu A, Inaguma A, Ueno T, Uchiyama S, Satoh-Asahara N. Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin Endocrinol (Oxf). 2013;78(3):365-72. doi: 10.1111/j.1365-2265.2012.04400.x.PubMedUsed to support: 12-week placebo-controlled crossover with no washout in 54 overweight or obese Japanese outpatients: 10 mg a day of natural S-equol lowered HbA1c, LDL cholesterol and the cardio-ankle vascular index versus placebo, more clearly in female non-producers. 67.9% of participants did not produce equol.
  7. Hazim S, Curtis PJ, Schär MY, Ostertag LM, Kay CD, Minihane AM, Cassidy A. Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial. Am J Clin Nutr. 2016;103(3):694-702. doi: 10.3945/ajcn.115.125690.PubMedUsed to support: Crossover study in 28 men at moderate cardiovascular risk: soy isoflavones improved arterial stiffness at 24 hours only in equol producers, and a single 40 mg dose of commercially produced S-equol (SE5-OH, donated by Otsuka Pharmaceutical) gave no vascular benefit in 14 non-producers. Equol is produced after soy intake in about 30% of Western populations.
  8. Yoshikata R, Myint KZY, Ohta H, Ishigaki Y. Effects of an equol-containing supplement on advanced glycation end products, visceral fat and climacteric symptoms in postmenopausal women: A randomized controlled trial. PLoS One. 2021;16(9):e0257332. doi: 10.1371/journal.pone.0257332.PubMedUsed to support: 3-month randomized trial in 57 postmenopausal Japanese women comparing a 10 mg S-equol supplement with no supplement (no placebo): climacteric symptoms improved in more women on equol (81% vs 53%, p = 0.045), but metabolic and aging biomarkers did not improve overall. Funded by Advanced Medical Care Co. Ltd.
  9. Daily JW, Ko BS, Ryuk J, Liu M, Zhang W, Park S. Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2019;22(2):127-139. doi: 10.1089/jmf.2018.4265.PubMedUsed to support: Systematic review of 6 randomized trials (779 women), 5 pooled (728 women), of equol supplements or soy isoflavones in equol producers: two of the pooled studies found no significant benefit and three did, and the pooled result favored equol for hot flash scores. The first author was affiliated with the R&D department of Daily Manufacturing, Inc.
  10. North American Menopause Society; advisory panel: Shufelt CL, Brown V, Carpenter JS, Chism LA, Faubion SS, Joffe H, Kling JM, Soares CN, Thurston RC. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause. 2023;30(6):573-590. doi: 10.1097/GME.0000000000002200.PubMedUsed to support: Position statement on nonhormone options for menopausal vasomotor symptoms: soy foods, soy extracts and the soy metabolite equol are listed as not recommended (Level II, limited or inconsistent evidence).
  11. Setchell KD, Zhao X, Shoaf SE, Ragland K. The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausal women. J Nutr. 2009;139(11):2037-43. doi: 10.3945/jn.109.110874.PubMedUsed to support: Crossover study in 12 healthy postmenopausal women: SE5-OH, made by incubating the equol-producing bacterium Lactococcus garvieae with soy germ isoflavones, delivered S-equol that was rapidly absorbed, with an 8-hour half-life and 82% of the dose recovered in urine at 10 and 30 mg; producer status did not change absorption. S-equol has selective affinity for estrogen receptor beta and antagonizes dihydrotestosterone in vivo.
  12. Sambe T, Imamura CK, Hida N, Yamazaki T, Mizukami T, Ryu K, Fukunaga K, Mushiroda T, Miyakawa H, Uchiyama S, Uchida N, Kobayashi S. Lack of effects of S-equol-containing supplement on the pharmacokinetics of oral hormone therapy drugs for breast cancer. Cancer Chemother Pharmacol. 2025;95(1):123. doi: 10.1007/s00280-025-04852-y.PubMedUsed to support: Open-label crossover in 24 healthy postmenopausal women: 10 mg a day of an S-equol supplement for 7 days did not significantly change blood exposure to anastrozole, letrozole, exemestane or tamoxifen. Two authors were Otsuka Pharmaceutical employees, and two others reported honoraria or research funding from Otsuka.
  13. Yee S, Burdock GA, Kurata Y, Enomoto Y, Narumi K, Hamada S, Itoh T, Shimomura Y, Ueno T. Acute and subchronic toxicity and genotoxicity of SE5-OH, an equol-rich product produced by Lactococcus garvieae. Food Chem Toxicol. 2008;46(8):2713-20. doi: 10.1016/j.fct.2008.04.026.PubMedUsed to support: Rat and lab safety study of the SE5-OH ingredient: oral LD50 above 4,000 mg/kg, no adverse effects at the highest dose tested in a 91-day study (2,000 mg/kg a day), and negative results in bacterial mutation, chromosome aberration and micronucleus tests. Animal and lab data, not human safety data.
  14. Sekikawa A, Wharton W, Murray-Krezan C, Wu M, Chang Y, Snitz BE, Coccari M, Yang S, Love ML, Cusick D, Wang R, Li M, Park C, Li J, DeConne TM, Smith C, Verble DD, Lancet MQ, Foroud T, Kim T, Nadkarni NK, Mettenburg JM, Zamora E, Lopez OL, Hughes TM. ACE trial design: Equol targeting estrogen receptor-β in vascular and cognitive aging. Alzheimers Dement (N Y). 2025;11(3):e70144. doi: 10.1002/trc2.70144.PubMedUsed to support: Design paper for the ACE trial: 369 adults aged 65 to 85 without dementia were randomized to 10 mg a day of equol or placebo for 24 months, with arterial stiffness (carotid-femoral pulse wave velocity) as the primary outcome and brain white matter lesions and cognition as secondary outcomes. No outcome results are reported yet.
  15. Pharmavite LLC (ClinicalTrials.gov record NCT04516304). A Double-Blind, Randomized, Placebo-Controlled Study to Assess a Nutritional Supplement on Vasomotor Symptoms In Perimenopausal and Menopausal Women ClinicalTrials.gov. 2026;NCT04516304 (record last updated April 2024; accessed 2026).SourceUsed to support: Not PubMed-indexed: registry record of a Pharmavite-sponsored placebo-controlled trial of Equelle (10 mg S-equol a day) for vasomotor symptoms in 118 perimenopausal and menopausal women, completed in May 2020. No results are posted on the registry.