Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial

Abstract

We tested whether chronic supplementation with resveratrol (a phytoestrogen) could improve cerebrovascular function, cognition and mood in post-menopausal women. Eighty post-menopausal women aged 45–85 years were randomised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance, cerebral blood flow velocity and pulsatility index (a measure of arterial stiffness) in the middle cerebral artery (using transcranial Doppler ultrasound), and cerebrovascular responsiveness (CVR) to both cognitive testing and hypercapnia were assessed. Mood questionnaires were also administered. Compared to placebo, resveratrol elicited 17% increases in CVR to both hypercapnic (p = 0.010) and cognitive stimuli (p = 0.002). Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020), which correlated with the increase in CVR (r = 0.327; p = 0.048). Mood tended to improve in multiple measures, although not significantly. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

Does phytoestrogen supplementation improve cognition in humans? A systematic review

“…Most of the isoflavone studies were conducted in postmenopausal women, whereas resveratrol studies were evaluated in young and older adults of both genders, except for the study by Evans et al. , which was conducted in postmenopausal women only. Four studies showed that early postmenopausal women (less than 11 years since onset of menopause) gained cognitive benefits following soy isoflavone supplementation .…”

“…Eight of the 23 studies in this review evaluated the effects of resveratrol or grape formulation on cognition with mixed outcomes . Kennedy et al .…”

“…The 75 mg dose also enhanced neurovascular coupling capacity and performance index to a complex multitasking test ( d = 0.21) in type 2 diabetes older adults . As such, the authors used 75 mg of resveratrol twice daily in their follow‐up chronic study in 72 postmenopausal women, where they observed improvements in verbal memory and overall performance to the cognitive test battery, with a small effect size of 0.35 and 0.48, respectively, following 14 weeks of supplementation . This was the first study to evaluate the phytoestrogenic effects of resveratrol in postmenopausal women.…”

“…hypothesized that resveratrol can enhance CVR, which in turn can influence cognitive function in humans . Since then, most of the resveratrol studies included in this review have tried to link the postulated mechanistic actions of resveratrol on vascular responsiveness with cognition . Kennedy et al .…”

Reduction of Cognitive Decline in Patients with or at High Risk for Diabetes

“…In humans, conflicting results [57, 58] and the lack of confirmation of several mechanisms involved in its activity in ‘preclinical’ models [52] preclude its current pharmacological use in patients with or at high risk of diabetes, or at high risk for development of cognitive impairment. However, recent clinical trials support the notion that resveratrol is capable of increasing cerebral blood flow during task performance [59, 49, 60] and enhancing oxygen extraction [49], reducing glycated hemoglobin A1c, preserving hippocampus volume, and improving hippocampus resting state functional connectivity in at-risk patients for dementia [61]. A randomized, double-blind clinical trial phase 1 (NCT02502253) will evaluate the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), a combination of two nutraceutical preparations (grape seed polyphenolic extract, and resveratrol) in mood and cognition of patients with MCI and prediabetes or type 2 diabetes.…”