Equol is a soy isoflavone metabolite produced by specific gut bacteria and has attracted growing attention as a promising ingredient for women’s health and healthy aging. As a phytoestrogen with estrogen-like and antioxidant activities, equol has been studied for its potential role in supporting menopausal symptoms, bone health, cardiovascular health, central nervous system function, and skin aging. Because only around 20–60% of people can naturally produce equol, supplementation may provide an alternative source for non-producers. This article reviews the origin, biosynthesis, biological properties, and potential health benefits of equol, while highlighting current scientific evidence and the need for careful interpretation of health-related findings.
As the global population continues to age, women’s health has received increasing attention, particularly the health challenges faced by women during and after menopause. Conditions and symptoms such as osteoporosis, cardiovascular disease, hot flashes, and mood fluctuations have become important areas of research in medicine and nutrition. Against this background, equol, a naturally occurring phytoestrogen, has gradually emerged as an ingredient of interest for women’s healthy aging due to its reported biological activities and potential health benefits, including support for bone health, cardiovascular health, and healthy skin aging.
Equol is a metabolite produced by specific intestinal microorganisms from the soy isoflavone daidzein. However, not everyone has the ability to naturally produce equol. Approximately 20–60% of individuals are considered “equol producers,” depending on factors such as gut microbiota composition, dietary habits, and genetic background. This individual difference has contributed to growing interest in equol as a dietary supplement ingredient. For people who do not naturally produce equol, supplementation may provide a direct source of this compound. Research has investigated its potential role in supporting menopausal symptoms, bone health, cardiovascular health, central nervous system health, and skin aging. Nevertheless, as with other bioactive ingredients, the available evidence should be interpreted carefully, particularly when translating findings from experimental studies into human health applications.
The Origin of Equol
In 1932, researchers first isolated a new phenolic compound from the urine of pregnant mares and named the compound equol in recognition of its source. For several decades, relatively little attention was paid to equol. However, in 1982, researchers unexpectedly discovered that equol was present in trace amounts in the urine of many adults. It was also the first isoflavone-derived compound detected in human urine and blood.
Following a series of studies, researchers identified a close relationship between equol and soy. The introduction of soy protein was found to substantially increase the amount of equol excreted in urine. Researchers subsequently isolated daidzein from soy isoflavones and demonstrated that it is a precursor of equol. The discovery of relatively high concentrations of equol in the urine of adults consuming soy foods led researchers to hypothesize that this non-steroidal estrogen may provide benefits in the prevention of several hormone-dependent diseases. As a result, interest in equol increased rapidly.
From a chemical perspective, equol [7-hydroxy-3-(4′-hydroxyphenyl)-chroman] is an isoflavan. It is a degradation product of soy isoflavones produced by specific intestinal microorganisms in the human gastrointestinal tract. Because it contains a chiral carbon at the C-3 position of its heterocyclic ring, equol exists as two isomers: R-equol and S-equol. However, the metabolism of soy isoflavones by intestinal microorganisms produces only S-equol.
Equol belongs to the group of phytoestrogens and has biological activities similar to those of human estrogen. Only approximately 20–60% of the population, known as “equol producers,” can convert soy isoflavones into equol through their gut microbiota. This ability is closely associated with individual differences in gut microbiota composition, dietary habits, and genetic factors.
The conversion of soy isoflavones into equol is a complex process that requires the participation of intestinal microorganisms and the specific enzymes they produce. Soy isoflavones are first metabolized in the intestine into dihydrodaidzein (DHD) and tetrahydrodaidzein (THD), and are ultimately converted into S-equol and O-desmethylangolensin (O-DMA).
Reference [2]: Schematic illustration of equol biosynthesis.
For individuals who do not naturally produce equol, equol supplements may serve as a source of equol. However, it is worth noting that supplementation may cause some mild side effects, such as constipation and bloating.
Potential Health Benefits of Equol
A large body of epidemiological data suggests that regular consumption of soy isoflavones may be associated with a lower incidence of estrogen-dependent and aging-related conditions, including menopausal symptoms in women, osteoporosis, and cardiovascular disease. Equol is produced from soy isoflavones and is considered one of the isoflavone metabolites with strong estrogenic and antioxidant activities. Compared with its precursor molecule, soy isoflavones, equol is more stable, more readily absorbed, and has a lower clearance rate. It also demonstrates stronger estrogenic activity than other isoflavones or isoflavone-derived metabolites [3]. Therefore, equol has been considered a compound with potentially beneficial effects on human health, particularly in menopausal women.
Support for Menopausal Symptoms
Equol may help reduce menopausal symptoms by exerting estrogen-like activity. Studies have reported reductions in the frequency of hot flashes and night sweats among menopausal women.
Compared with placebo, supplementation with S(-)-equol at 10–30 mg per day for 8–12 weeks has been reported to provide benefits for major menopausal symptoms, including hot flashes and arterial stiffness. Another analysis showed that among both equol-producing and non-equol-producing menopausal women, equol supplementation significantly reduced hot flash scores, including their incidence and/or severity. Equol may therefore have potential as a complementary intervention for women experiencing vasomotor symptoms.
Support for Bone Health
Osteoporosis is a major health concern for women during and after menopause. Equol may help maintain bone health by promoting bone formation and inhibiting bone resorption, potentially helping maintain bone mineral density and reduce the risk of osteoporosis and fractures.
Research has found that equol reduced the expression of genes associated with inhibition of bone formation, osteoclasts and immature osteoblasts, as well as cartilage degradation in mice. In a human trial, postmenopausal women receiving 10 mg/day of equol for one year were protected against a decline in total-body bone mineral density.
The same trial also showed that equol supplementation significantly inhibited bone resorption, as demonstrated by a reduction in urinary deoxypyridinoline excretion.
Cardiovascular Health
Equol may influence lipid metabolism, potentially reducing low-density lipoprotein (LDL) levels while increasing high-density lipoprotein (HDL) levels, which may help reduce the risk of atherosclerosis.
Research has found that menopausal women who supplemented with equol experienced reductions in hot flash scores, including incidence and/or severity. Compared with placebo, supplementation with S(-)-equol at 10–30 mg per day for 8–12 weeks was associated with benefits for major menopausal symptoms, particularly hot flashes, as well as arterial stiffness.
In a natural equol intervention study involving overweight Japanese men and women, equol was found to potentially help prevent cardiovascular disease by reducing low-density lipoprotein cholesterol (LDL-C) levels and improving the cardio-ankle vascular index (CAVI), an arterial stiffness index independent of blood pressure.
Central Nervous System Protection
Research has found that in lipopolysaccharide (LPS)-activated mouse microglial cells, equol inhibited LPS-induced TLR4 activation, MAPK activation, NF-κB-mediated transcription of inflammatory mediators, nitric oxide (NO) production, prostaglandin E2 (PGE-2) release, and the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).
In addition, equol protected neurons against neuroinflammatory damage mediated by LPS-activated microglia by reducing neuronal apoptosis, increasing neurite outgrowth in N2a cells, and promoting the production of neurotrophic factors such as nerve growth factor (NGF) by astrocytes. These findings suggest that equol has potential neuroprotective properties.
Equol may also have potential in supporting the prevention of cognitive impairment and dementia.
Healthy Aging and Skin Health
Healthy aging has long been an important concern for women. Topical equol interventions have indicated potential anti-aging effects on the skin of postmenopausal women, including reductions in wrinkle area and depth [4].
Equol has also been associated with improvements in skin roughness, texture, and smoothness, as well as changes in certain epigenetic molecular markers in skin cells, including LINE-1 methylation and telomere length.
In recent years, equol compounds have attracted considerable attention from the cosmetics industry.
References
[1] Kenneth D. R. Setchell, Carlo Clerici. Equol: History, Chemistry, and Formation. PMCID: PMC2884333. PMID: 20519412.
[2] Jing Lv, Shengkai Jin, Yuwei Zhang, Yuhua Zhou, Menglu Li, Ninghan Feng. Equol: a metabolite of gut microbiota with potential antitumor effects. Gut Pathogens. 2024;16:35.
[3] Baltasar Mayo, Lucía Vázquez, Ana Belén Flórez. Equol: A Bacterial Metabolite from The Daidzein Isoflavone and Its Presumed Beneficial Health Effects. Nutrients. 2019;11(9):2231. doi:10.3390/nu11092231. PMCID: PMC6770660. PMID: 31527435.
[4] Nutrients. 2019 Sep 16;11(9):2231. doi:10.3390/nu11092231. PMCID: PMC6770660. PMID: 31527435.