- Title
- The role of resveratrol in promoting healthy ageing in women
- Creator
- Thaung Zaw, Jay Jay
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2021
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Ageing and menopause are associated with decreased endothelium-dependent vasodilator function, contributing to initiation and/or progression of many chronic conditions such as coronary heart disease and dementia, which are the major causes of morbidity and mortality in elderly Australian women. This suggests that vascular dysfunction underlies various chronic diseases and maintenance of endothelial function with suitable interventions may have a potential role in reducing disability and improving the quality of life of elderly women. Hormone therapy was widely prescribed for prevention of chronic diseases in many peri- and postmenopausal women until the concerns of increased risks over benefits arose after the initial publications from the first large-scale randomized controlled trial with hormone therapy – Women’s Health Initiative study, leaving many symptomatic women seeking other viable alternatives for menopause management. Phytoestrogens such as resveratrol have weak estrogenic properties and prominent vasodilator benefits in both systemic and cerebral endothelium. Promising pilot evidence showed that a 14-week resveratrol supplementation improved cognitive performance and menopause-related quality of life in elderly postmenopausal women, where the improvements were associated with enhanced circulatory function. It suggests that vascular benefits of resveratrol may in turn improve overall functionality of target organs and clinical endpoints, which could be the potential holistic approach to assist healthy ageing in older women who experience ageing and menopause simultaneously. The effects of long-term resveratrol supplementation in multiple age- and menopause-related health conditions in postmenopausal women has not been evaluated in a comprehensive study. This thesis aims to evaluate the effects of 12-month resveratrol supplementation on cognitive performance, cerebrovascular function, cardiometabolic markers, bone mineral density and general wellbeing in community dwelling postmenopausal women. The Resveratrol for Healthy Ageing in Women (RESHAW) was a 2 × 12-month randomized, double-blind, placebo-controlled crossover study to evaluate the benefits of low-dose resveratrol (75mg twice daily) on multiple health outcomes, which determine the quality of ageing in postmenopausal women. Cognitive function was examined by using a comprehensive battery of neuropsychological tests to assess overall cognitive performance (primary outcome) and domains of processing speed, language, verbal memory, episodic memory, working memory and cognitive flexibility. Cerebrovascular function, including cerebrovascular responsiveness (CVR), which serve as a surrogate marker of endothelial function, was assessed by transcranial Doppler ultrasound in the middle cerebral arteries in response to hypercapnic and cognitive stimuli. Blood biomarkers, bone mineral density and general wellbeing were also assessed by standardised measures. A parallel comparison between placebo and resveratrol arms of differences in outcome measures following the first 12-month supplementation phase from baseline was undertaken using one-way ANOVA (Analysis of Variance). At the end of 24-month supplementation, within-individual treatment effects at the end of placebo and resveratrol supplementation period were compared using repeated measures ANOVA. The Benjamini-Hochberg procedure was applied for secondary outcomes to control false discovery rate. The primary outcome of the study, overall cognitive performance was significantly improved following resveratrol, which was even evident in a parallel analysis undertook after the first 12 months of supplementation (Chapter 4). Participants in resveratrol group performed significantly better on the domains of processing speed and cognitive flexibility compared to placebo group. These improvements were accompanied by improved basal cerebral blood flow, cerebral arterial stiffness and attenuation of decline in CVR assessments, representing the enhancement of cerebral endothelial function. Crossover analysis at the end of 24-month supplementation period confirmed the sustained cognitive benefits of resveratrol, where the improvements were correlated with resveratrol-induced CVR improvements. These findings suggest that resveratrol supplementation may help to counteract the accelerated cognitive decline associated with ageing and menopause, partly mediated by enhancements in cerebral endothelial function. The effects of long-term resveratrol were also observed in secondary outcomes including improved insulin sensitivity (Chapter 4), attenuation of decline in bone mineral density (Chapter 5) and improved aspects of general wellbeing (Chapter 6) which altogether indicated the enhanced quality of life of elderly postmenopausal women. These improvements were attributed, at least in part, to attenuation of a postmenopausal decline in circulatory function by long-term resveratrol supplementation. In summary, the research presented in this thesis provides novel evidence for the effective use of resveratrol supplementation for attenuating multiple menopause-related health conditions to uplift the quality of ageing in postmenopausal women. Benefits of resveratrol observed were associated with improvements in circulatory function; suggesting that other vasoactive nutrients or lifestyle interventions that can improve vascular function may also have a role in assisting healthy ageing. Findings from this study have direct translational capacity to the community-dwelling, health-conscious, Australian elderly women who are seeking non-pharmacological interventions to improve mental acuity, vitality and overall wellbeing for prolonged independent living. This research also provides first time evidence on the long-term safety and tolerability of the low-dose resveratrol, which can be easily incorporated into habitual diet by simple daily consumption. The work presented in this thesis adds significant evidence to the existing literature on the fields of non-pharmacological interventions and chronic disease prevention that resveratrol is a viable intervention for attenuating age and menopause-related health conditions in community dwelling postmenopausal women. This thesis is organized into seven chapters: introduction and literature review sections, methodology, six peer-reviewed papers in scientific journals and a general discussion with conclusions.
- Subject
- resveratrol; healthy ageing; thesis by publication; menopause; cognitive decline; cerebrovascular function; cardiometabolic function; bone mineral density; wellbeing; phytoestrogen; women's health
- Identifier
- http://hdl.handle.net/1959.13/1440233
- Identifier
- uon:41107
- Rights
- Copyright 2021 Jay Jay Thaung Zaw
- Language
- eng
- Full Text
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