Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia

• Type of Material: Article
• Authors: Akira Sekikawa, University of Pittsburgh; Whitney Wharton, Emory University; Brittany Butts, Emory University; Cole V Veliky, University of Pittsburgh; Joshua Garfein, University of Pittsburgh; Jiatong Li, University of Pittsburgh; Shatabdi Goon, University of Pittsburgh; Annamaria Fort, University of Pittsburgh; Mengyi Li, University of Pittsburgh; Timothy M Hughes, Wake Forest School of Medicine
• Language: English
• Date: 2022-10-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijms231911921
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: 23
• Issue: 19
• Grant/Funding Information: This study is supported by the National Institute on Aging of the National Institutes of Health (R01 AG074971).
• Keywords: Chemistry; Biochemistry & Molecular Biology; HYPERCHOLESTEROLEMIC ADULTS; ANTIOXIDANT ACTIVITY; OXIDATIVE STRESS; MENOPAUSAL SYMPTOMS; Chemistry, Multidisciplinary; Physical Sciences; vascular contributions to cognitive impairment and dementia; ARTERIAL STIFFNESS; Alzheimer's disease and related dementias; DIETARY PATTERNS; PULSE-WAVE VELOCITY; HEALTHY POSTMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR-BETA; estrogen receptor-beta agonist; arterial stiffness; ALZHEIMERS-DISEASE; Life Sciences & Biomedicine; white matter lesions; S-equol; Science & Technology
• Research Categories: Health Sciences, Nursing; Health Sciences, Epidemiology

Abstract

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-β. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40–70% of East Asians produce S-equol, whereas 20–30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood–brain barrier than soy isoflavones, although their affinity to estrogen receptor-β is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.