Circulatory and cognitive benefits of resveratrol: benefits for an aging population
A healthy circulation is essential for healthy aging, yet many risk factors that contribute to the increasing rates of disability in our aging society, such as smoking, obesity and other components of metabolic syndrome, do so by undermining circulatory function. This results in adverse effects extending well beyond cardiovascular disease. Apart from deleterious metabolic and inflammatory changes affecting muscles and joints, poor tissue perfusion in the brain has been implicated in the severity of cognitive decline with aging.
We have been examining the potential for certain vasoactive nutrients such as omega-3 fatty acids, cocoa flavanols and soy isoflavones to improve endothelial function and in turn counteract adverse effects of an unhealthy lifestyle on circulatory function. By conducting double-blind placebo controlled clinical trials in at-risk populations, we have shown that such vasoactive nutrients can boost vasodilator function in both systemic and cerebral arteries.
The most potent vasoactive that we have evaluated is resveratrol, an ingredient of grapes and berries that can act via numerous mechanisms to enhance endothelial nitric oxide production. We conducted the first dose-response evaluation in humans with DSM’s synthetic trans-resveratrol (resVida®) and found that as little as 30mg significantly enhanced flow mediated dilatation in the brachial artery1. We subsequently showed that this benefit was sustained by regular consumption (75mg/day for six weeks); moreover, performance of an executive function test was marginally improved2. This led us to hypothesise that resveratrol could improve cognitive performance by enhancing cerebral vasodilator responsiveness (CVR).
In an acute dose-response evaluation of resveratrol in volunteers with type 2 diabetes, we assessed CVR to both hypercapnic (breathing CO2) and cognitive challenges using transcranial Doppler ultrasound and found that 75mg optimally enhanced both CVR and the performance of a multi-tasking test 3,4. Diabetes is associated with premature cognitive decline and we had recently shown that CVR to selected cognitive tests is impaired in adults with type 2 diabetes5.
Women are also at heightened risk of premature cognitive decline post-menopause, due to loss of estrogen. Given that resveratrol is also a phytoestrogen, we undertook a 14-week supplementation trial with resveratrol (75mg twice daily) in healthy postmenopausal women, postulating that resveratrol could improve their cognitive performance by enhancing CVR. Their baseline data strengthened our hypothesis: we found that poor cerebrovascular function was predictive of cognitive deficits and therefore a very early biomarker of cognitive decline in these women6. The intervention data has now provided the first clinical evidence that regular consumption of trans-resveratrol leads to a sustained enhancement of CVR which is accompanied by improvements of cognitive performance, including verbal memory, compared to placebo treatment. Those taking resveratrol also reported less anxiety, pain and an improvement in overall well-being.
These landmark findings offer a novel approach to counteract cognitive decline in post-menopausal women. Moreover, our cohort had high cognitive function, evidenced by their 3MS scores and years of education, suggesting that the cognitive benefits elicited by resveratrol may be translated to the general population. We are now conducting a longer term (two year) crossover trial to further explore the effects of resveratrol on cerebrovascular function, mood and cognition and the underlying mechanisms.
The latest scientific findings on resveratol were presented at the Resveratrol2016 Conference in Taipei, 17-19 November 2016.
Globally, the population is aging rapidly. Between 2015 and 2050, the proportion of the world’s population over 60 years of age will nearly double, from 12% to 22%. Of these, approximately 15% will suffer from a mental disorder7. According to a recent study on consumer health concerns8, 37% of adults in Europe worry about mental health, whereas the main driver in mature adults is losing memory. Much can be done to support and improve the lives of people with cognitive decline, such as optimizing physical and psychological health and well-being, whereas nutrition is an important factor.
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1. Wong RHX, Howe PRC, Buckley JD, Coates AM, Kunz I, Berry NM. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutrition, Metabolism and Cardiovascular Diseases. 2011;21(11):851-856.
2. Wong RHX, Berry NM, Coates AM, et al. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. Journal of Hypertension. 2013;31(9):1819-1827.
3. Wong RHX, Nealon RS, Scholey A, Howe PRC. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. Nutrition, Metabolism and Cardiovascular Diseases. 2016;26(5):393-399.
4. Wong RH, Raederstorff D, Howe PR. Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus. Nutrients. 2016;8(7).
5. Nealon RS, Howe PRC, Jansen L, Garg M, Wong RHX. Impaired cerebrovascular responsiveness and cognitive performance in adults with type 2 diabetes. Journal of Diabetes and its Complications.
6. Wong RHX, Evans HM, Howe PRC. Poor cerebrovascular function is an early marker of cognitive decline in healthy postmenopausal women. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2016;2(3):162-168.
7. WHO Factsheet Mental Health and Older Adults, April 2016