S-equol (AUS-131) / Ausio Pharma - LARVOL DELTA

Lack of effects of S-equol-containing supplement on the pharmacokinetics of oral hormone therapy drugs for breast cancer. (PubMed, Cancer Chemother Pharmacol) - "S-equol-containing supplement has no clinically significant effects on the exposure of oral hormone therapy drugs for breast cancer. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: jRCTs031200084, August 13th, 2020."

Journal • PK/PD data • Breast Cancer • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Pain • Solid Tumor

Mechanisms Underlying S-Equol–Mediated Suppression of Neuronal Hyperexcitability (AES 2025) - "These findings suggest that S-equol's suppressive effects on neuronal hyperexcitability are not mediated through ESRβ or BK channels in this model but instead involve GPR30/GPER1 signaling. Our results highlight a previously unrecognized mechanism of S-equol's neuroprotective action in TMEV-induced seizures and underscore the complexity of its molecular targets, warranting further investigation."

CNS Disorders • Epilepsy • Infectious Disease • GPER1

S-Equol: A Novel Therapeutic For HIV-1-Associated Gastrointestinal Dysbiosis. (PubMed, bioRxiv) - "Prevotella_UCG_001 was significantly associated with lever presses for drug, suggesting an effect on motivation for cocaine. Alloprevotella was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease

S-equol status modulates skin response to soy isoflavones in postmenopausal women: results from a randomized placebo-controlled pilot trial. (PubMed, Front Nutr) - P=N/A | "Findings suggest region-specific, time-sensitive effects dependent on S-equol levels. https://clinicaltrials.gov/study/NCT06047145, NCT06047145."

Journal

In Vivo and In Vitro Mechanisms of Equol Synthesis and Key Influencing Factors: A Critical Review. (PubMed, Nutrients) - "Background: Equol exists in two enantiomers of S-equol and R-equol... This review suggests that breakthroughs based on synthetic biology and gene editing technology will support the efficient in vitro synthesis of equol. This review serves as a valuable reference for future research."

Journal • Preclinical • Review • Cardiovascular

Maresin-1 and S-Equol as Emerging Metabolic Biomarkers in Gestational Diabetes-Associated Inflammation. (PubMed, Diagnostics (Basel)) - " The observed reductions in MaR-1 and S-Equol levels among GDM patients suggest a potential role for these anti-inflammatory mediators in the inflammatory processes associated with GDM. That is, these findings imply that the advantages of using these MaR-1 and S-Equol could be predictive for GDM."

Biomarker • Journal • Diabetes • Gestational Diabetes • Inflammation • Metabolic Disorders • CRP

Acute Equol Supplementation and Vascular Function in Women With and Without CKD (clinicaltrials.gov) - P2 | N=38 | Recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Mar 2025 ➔ Dec 2026 | Trial primary completion date: Mar 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease

Gut derived (S)-Equol mitigates influenza viral pneumonia by modulating macrophage polarization via Nrf2 mediated AKT/ERK/NF-κB signaling pathways. (PubMed, Free Radic Biol Med) - "Moreover, serum (S)-Equol level was lower in influenza patients at progressed phase and was negatively correlated with serum levels of IL-6, IL-1β, and TNF-α. Collectively, our data highlighted gut derived (S)-Equol a promising postbiotic for alleviating influenza pneumonia."

Journal • Infectious Disease • Inflammation • Influenza • Pneumonia • Respiratory Diseases • IL1B • IL6 • TNFA

Menopausal hormone therapy shows superior efficacy to complementary and alternative medicine in treating symptomatic hand osteoarthritis in Japanese women during perimenopause. (PubMed, Womens Health (Lond)) - "Compared with complementary and alternative medicine, menopausal hormone therapy showed superior efficacy in improving hand pain and dysfunction associated with symptomatic hand osteoarthritis in perimenopausal Japanese women."

Journal • Observational data • Retrospective data • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

Receptor interacting protein kinase 2 (RIPK2) regulated gut microbiota promotes acute radiation syndrome. (IMMUNOLOGY 2025) - "Treatment with S-Equol resulted in significant protection from radiation exposure compared to WT controls. In conclusion, our study reveals an important role for Ripk2-associated gut bacteria in influencing radiation-induced morbidity and mortality."

Gut Microbiota • RIPK2

Microbiota-derived S-equol ameliolates inflammatory pathway in metabolic dysfunction-associated fatty liver disease (EASL 2025) - "This study demonstrates the significant liver-protective effects of S-equol in a MASLD model. S- equol is a representative metabolite produced by gut microbiota during the metabolism of daidzein that offering potential for microbiome-targeted therapies for MASLD and related liver disorders."

Hepatology • Inflammation • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • IL6 • PPARG • TGFB1 • TNFA

Evaluating serum S-Equol, indoxyl sulfate, and TMAO in predicting urinary stones in children: a prospective study. (PubMed, Urolithiasis) - "There were also no significant correlations between serum metabolite levels and age in either group. Children with urinary stone disease had significantly lower serum S-equol and TMAO levels than healthy control subjects, suggesting a possible link between these metabolites and stone formation."

Biomarker • Journal • Nephrology • Pediatrics • Renal Calculi • Urolithiasis

Fermented soybean powder containing S-equol alleviates the postmenopausal signs of ovariectomized rats. (PubMed, Food Sci Biotechnol) - "In conclusion, SE5-OH may alleviate postmenopausal symptoms, including hot flashes, lipid metabolism changes, and osteoporosis. The online version contains supplementary material available at 10.1007/s10068-024-01768-w."

Journal • Preclinical • Metabolic Disorders • Osteoporosis • Rheumatology • ER

Dietary supplements and prevention of preeclampsia. (PubMed, Hypertens Res) - "We also reviewed other dietary supplements, including vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins), minerals (magnesium, zinc, and iron), amino acids (l-arginine and l-carnitine), anti-oxidants (lycopene, resveratrol, and astaxanthin), and other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol). In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE."

Journal • Review • Cardiovascular • Gynecology • Hypertension • Renal Disease

Mechanism of dsDNA binding, enzyme inhibition, antioxidant activities, and molecular docking studies of taxifolin, daidzein, and S-equol. (PubMed, Int J Biol Macromol) - "As a result, the studied compounds were found to prefer minor groove binding. This research analyzed the contribution of the structure-activities of natural flavones in terms of their biological properties, which is important for their future application against diseases."

Journal • Pain

Suppression of HIV-induced neurotoxicity and synaptodendritic injury by the selective estrogen receptor ?; agonist S-Equol (Neuroscience 2024) - "Further, HIV-Tg animals treated with vehicle exhibited alterations in spine morphology consistent with previously described effects of the HIV-Tg transgene. Taken together, these data suggest the beneficial effects of S-Equol in cognitive performance previously reported may be attributed to its ability to enhance neuroregeneration."

CNS Disorders • Cognitive Disorders • RHOA

Cardioprotective effects of S-equol, a soybean metabolite with estrogen activity, and role of the PI3K/Akt pathway in a male rat model of ischemic reperfusion. (PubMed, Steroids) - "S-equol exerts a protective effect against myocardial ischemia-reperfusion injury, possibly by activating PI3K/Akt signaling."

Journal • Preclinical • Cardiovascular • Myocardial Ischemia • Reperfusion Injury

ACE: Effect of Equol Supplementation on Arterial Stiffness and Cognition in Healthy Volunteers (clinicaltrials.gov) - P2 | N=400 | Active, not recruiting | Sponsor: Akira Sekikawa | Recruiting ➔ Active, not recruiting

Enrollment closed • CRP • GFAP

S-equol supplement (SE5-OH) affects exercise training-induced improvement in arterial compliance in Japanese postmenopausal women (NAMS 2024) - "Aerobic exercise with S-equol improved arterial compliance and stiffness more than that of exercise alone, especially in menopausal women after 5 years when the hormone fluctuation was stable. The improvement of oxidative stress status may be implicated in this effect."

Clinical • Compliance • Cardiovascular • Infectious Disease • Metabolic Disorders

ACE: Effect of Equol Supplementation on Arterial Stiffness and Cognition in Healthy Volunteers (clinicaltrials.gov) - P2 | N=400 | Recruiting | Sponsor: Akira Sekikawa | Trial completion date: Apr 2026 ➔ Jan 2027 | Trial primary completion date: Apr 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • CRP • GFAP

S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation. (PubMed, Nutrients) - "Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation."

Journal • Preclinical • Immunology • Osteoarthritis • Osteoporosis • Pain • Rheumatology • COL1A2 • MMP1 • MMP13 • MMP3

High Pretreatment DHEA Is Associated with Inferior Immunotherapy Response in Metastatic Non-Small Cell Lung Cancer. (PubMed, Cancers (Basel)) - "Six sex hormone levels [pyrazole triol, 17 β-estradiol, 5-androstenediol, 3β-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS)...A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89-23.35); p < 0.0001]. High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs."

Journal • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The effect of soy isoflavones in brain development: the emerging role of multiple signaling pathways and future perspectives. (PubMed, Endocr J) - "As a conclusion, the soy product consumption during the pre-and post-natal periods under proper range of dose showed beneficial effects in neurobehavior development, including improvement of anxiety, aggression, hyperactive behavior, and cognition, whereas their adverse effect by taking higher doses cannot be excluded. We also present novel research lines to further assess the effect of soy isoflavone administration during brain development."

Journal • Mood Disorders • Psychiatry • GPER1

Acute Equol Supplementation and Vascular Function in Women With and Without CKD (clinicaltrials.gov) - P2 | N=38 | Recruiting | Sponsor: University of Colorado, Denver

New P2 trial • Chronic Kidney Disease • Nephrology • Renal Disease

Anti-neuroinflammatory Effects of Active Compound SPA1413 via Suppression of the MAPK and JAK/STAT Signaling Pathways. (PubMed, Biol Pharm Bull) - "Recently, the active compound SPA1413 (dehydroequol) derived from S-equol, an isoflavone-derived metabolite produced by human intestinal bacteria, was identified as a potent anti-amyloidogenic and neuroinflammatory candidate against Alzheimer's disease...In addition, SPA1413 inhibited neuronal cell death by reducing LPS-activated microglia in neuronal N2a cells. Our findings suggest that SPA1413 may act as a strong anti-neuroinflammatory candidate by suppressing the MAPK and JAK/STAT signaling pathways."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Oncology • IL6 • MAPK8 • TNFA