Effect of Equol Supplementation on Arterial Stiffness and Cognition in Healthy Volunteers

Description

The ACE trial is an early-stage multi-center randomized controlled trial (RCT) designed to test the effect of a 24-month intervention of 10 mg/day equol supplementation on arterial stiffness, white matter lesions (WMLs) in the brain and cognitive decline among 400 individuals aged 65 and 85 without dementia. Recent studies in Japan reported that a diet high in soy and soy isoflavones is inversely associated with incident cognitive impairment and dementia. The Women’s Isoflavone Soy Health (WISH) in the US, an RCT of soy isoflavones, however, showed no significant effect on cognition. We posit that the discrepant result is due to the difference in equol-producing capability. Equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most bioactive among all soy isoflavones and their metabolites. 50-70% of Japanese convert daidzein to equol in contrast to 20-30% of Americans. Arterial stiffness, a significant predictor of cognitive decline, is significantly improved in a short-duration RCT of 10 mg/day equol supplementation in middle-aged subjects. WMLs are a risk factor for age-related cognitive decline and dementia. We reported a longitudinal association of equol-producing status with WML% (WML volume normalized to total brain volume) in cognitively normal elderly in Japan. The subgroup analysis of WISH showed that equol producers had better cognition than the control group, suggesting that equol may slow cognitive decline. No previous study has tested the effect of equol supplementation on arterial stiffness, WMLs or cognitive decline in older adults.