Sekikawa Akira, Wharton Whitney, Murray-Krezan Cristina, Wu Minjie, Chang Yuefang, Snitz Beth E, Coccari Mindy, Yang Shaolin, Love Monica L, Cusick Deborah, Wang Rongrong, Li Mengyi, Park Chloe, Li Jiatong, DeConne Theodore M, Smith Carrie, Verble Danielle D, Lancet Michelle Quallich, Foroud Tatiana, Kim Tae, Nadkarni Neelesh K, Mettenburg Joseph M, Zamora Ezequiel, Lopez Oscar L, Hughes Timothy M
Department of Epidemiology School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA.
Nell Hodgson Woodruff School of Nursing Emory University Atlanta Georgia USA.
Alzheimers Dement (N Y). 2025 Aug 18;11(3):e70144. doi: 10.1002/trc2.70144. eCollection 2025 Jul-Sep.
Equol, a gut microbiome-derived metabolite of soy isoflavone daidzein, functions as a selective estrogen receptor beta (ERβ) agonist. In preclinical studies, it has demonstrated vascular protective and antioxidant effects, with emerging evidence suggesting potential neuroprotective properties. However, its role in preventing vascular aging and cognitive decline in humans remains unexplored. The Arterial Stiffness, Cognition, and Equol (ACE) trial investigates whether daily equol supplementation can slow the progression of arterial stiffness, brain white matter lesions, and cognitive decline in older adults without dementia.
ACE is a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted at the University of Pittsburgh, Wake Forest University, and Emory University. Community-dwelling adults aged 65 to 85 years without dementia were enrolled and randomized 1:1 to receive either 10 mg/day of equol or placebo for 24 months. The primary outcome is arterial stiffness assessed by carotid-femoral pulse wave velocity. Secondary outcomes include white matter lesions detected on the brain magnetic resonance imaging and cognitive function as assessed by the Preclinical Alzheimer Cognitive Composite. Power calculations were based on a planned sample size of 400 participants, accounting for an anticipated 20% attrition rate.
A total of 1783 individuals were pre-screened, and 764 underwent in-person eligibility assessment. Of these, 369 participants were randomized into two groups: Arm A ( = 185) and Arm B ( = 184). The randomized sample self-reported as 52% women and 22% Black/African American participants. Baseline demographic and clinical characteristics were well balanced between the two arms, indicating successful randomization.
ACE successfully enrolled a racially diverse population of older adults and achieved near-target recruitment. ACE is the first large-scale trial to evaluate whether equol, a selective ERβ agonist, can impact vascular and cognitive aging, paving the way for precision nutrition strategies in dementia prevention.
We detail the first randomized controlled trial of equol, an estrogen receptor beta (ERβ) agonist, for vascular and cognitive aging.The study tested equol's effects on arterial stiffness, white matter lesions, and cognition.The multisite trial enrolled 369 self-reported White and Black older adults aged 65 to 85 years.The trial investigated a novel dietary metabolite targeting ERβ pathways.
雌马酚是大豆异黄酮黄豆苷元经肠道微生物代谢产生的一种代谢产物，具有选择性雌激素受体β（ERβ）激动剂的作用。在临床前研究中，它已显示出血管保护和抗氧化作用，且越来越多的证据表明其具有潜在的神经保护特性。然而，其在预防人类血管衰老和认知衰退方面的作用仍未得到探索。动脉僵硬度、认知与雌马酚（ACE）试验旨在研究每日补充雌马酚是否能减缓无痴呆症老年人的动脉僵硬度、脑白质病变和认知衰退的进展。
ACE是一项在匹兹堡大学、维克森林大学和埃默里大学进行的多中心、随机、双盲、安慰剂对照临床试验。纳入年龄在65至85岁之间、无痴呆症的社区居住成年人，并按1:1随机分为两组，分别接受每日10毫克雌马酚或安慰剂治疗，为期24个月。主要结局是通过颈股脉搏波速度评估的动脉僵硬度。次要结局包括脑磁共振成像检测到的白质病变以及由临床前阿尔茨海默病认知综合量表评估的认知功能。样本量计算基于计划招募400名参与者，并考虑到预期20%的损耗率。
共有1783人进行了预筛查，764人接受了现场资格评估。其中，369名参与者被随机分为两组：A组（=185）和B组（=184）。随机样本中自我报告为女性的占52%，黑人/非裔美国人参与者占22%。两组的基线人口统计学和临床特征平衡良好，表明随机分组成功。
ACE成功招募了种族多样化的老年人群体，并接近目标招募人数。ACE是第一项评估选择性ERβ激动剂雌马酚是否会影响血管和认知衰老的大规模试验，为痴呆症预防中的精准营养策略铺平了道路。
我们详细介绍了第一项关于雌激素受体β（ERβ）激动剂雌马酚对血管和认知衰老影响的随机对照试验。该研究测试了雌马酚对动脉僵硬度、白质病变和认知的影响。这项多中心试验招募了369名自我报告为65至85岁的白人和黑人老年人。该试验研究了一种针对ERβ途径的新型饮食代谢产物。
