The Effects of Flavonoid Supplementation on Cognition and Neural Mechanisms in Healthy Older Adults
- Conditions
- Mental Processes
- Interventions
- Dietary Supplement: Cocoa-Flavanol SupplementsDietary Supplement: Control Supplements
- Registration Number
- NCT03030053
- Lead Sponsor
- University of Reading
- Brief Summary
A double-blind, randomised, controlled, parallel arm chronic intervention trial with healthy older adults will be conducted to determine the effect of a flavonoid-rich supplement on cognitive function, peripheral arterial health and brain mechanisms. It is predicted that chronic flavonoid supplementation will result in cognitive benefits and that these may be due to beneficial effects of flavonoids on vascular and brain function.
- Detailed Description
There has recently been an increasing interest in the potential of flavonoids, plant derived compounds found in foods such as fruit and vegetables, to improve cognitive function. Research suggests that flavonoids improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects, for example by increasing cerebral blood flow (CBF), protecting vulnerable neurons, or by stimulating neuronal function and growth. The proposed research will involve a parallel design chronic dietary supplementation trial using a flavonoid-supplement and a matched control containing no flavonoids, to investigate long-term changes in cognitive performance. To understand the neural mechanisms behind potential changes in cognitive performance, resting cerebral blood flow (CBF), blood-oxygen level dependent (BOLD) response during two sensitive tests of cognitive performance, and structural brain changes will be measured in a group of healthy elderly adults (N=70, age range 60-75 years) using magnetic resonance imaging (MRI). Additionally, peripheral vascular health will be measured using flow mediated dilatation (FMD), and bioavailability of flavonoid monomers and metabolites will be determined through analysis of plasma and urine samples. Biomarkers in the blood associated with vascular health and neural functioning as well as markers of interest in relation to the possible mechanisms of action of flavonoids will also be measured. All endpoints will be acquired before and after a 24-week chronic supplementation of either a high flavonoid supplementation or a control product, consumed in addition to participants' normal diet. Measures will also be taken following a 12-week post-intervention washout period in order to investigate whether any beneficial effects are sustained following cessation of supplementation.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Active Cocoa-Flavanol Supplements Cocoa-Flavanol Supplements: 3 capsules per day each containing 300mg (total dose of 900mg daily) for 24 weeks Control Control Supplements Control Supplements: 0mg cocoa-flavanols per day for 24 weeks
- Primary Outcome Measures
Name Time Method Change in Cognitive Performance (0-24 weeks) Change from baseline (pre intervention) to week 24 (post intervention) Composite measure of global cognitive function (scores from different cognitive tasks will be standardised to allow an overall score of global cognitive function to be calculated)
Change in Cognitive Performance (0-36 weeks) Change from baseline (pre intervention) to week 36 (follow-up) Composite measure of global cognitive function (scores from different cognitive tasks will be standardised to allow an overall score of global cognitive function to be calculated)
- Secondary Outcome Measures
Name Time Method Change in cerebral blood flow (0-24 weeks) Change from baseline (pre intervention) to week 24 (post intervention) Use of arterial spin labelling to determine cerebral blood flow at rest
Change in Flow Mediated Dilatation (0-24 weeks) Change from baseline (pre intervention) to week 24 (post intervention) Technique to measure the flexibility of the endothelium in larger peripheral blood vessels
Change in flavanol monomer levels Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of epicatechin and catechin in plasma and urine samples
Change in brain activity (0-24 weeks) Change from baseline (pre intervention) to week 24 (post intervention) Use of functional MRI to determine BOLD response (indicative of brain activation) during cognitive activity
Change in levels of nitroso compounds Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of nitric oxide, nitrate and nitrite levels in plasma/serum \&/ urine
Change in levels of a marker of oxidative stress Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of uric acid in plasma/serum
Change in Flow Mediated Dilatation (0-36 weeks) Change from baseline (pre intervention) to week 36 (follow-up) Technique to measure the flexibility of the endothelium in larger peripheral blood vessels
Change in brain structure (0-24 weeks) Change from baseline (pre intervention) to week 24 (follow-up) Use of high resolution images to determine changes to brain structure such as grey and white matter
Change in brain activity (0-36 weeks) Change from baseline (pre intervention) to week 36 (post intervention) Use of functional MRI to determine BOLD response (indicative of brain activation) during cognitive activity
Change in procyanidin levels Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of procyanidin dimers through to decamers in plasma and urine samples
Change in cerebral blood flow (0-36 weeks) Change from baseline (pre intervention) to week 36 (post intervention) Use of arterial spin labelling to determine cerebral blood flow at rest
Change in brain structure (0-36 weeks) Change from baseline (pre intervention) to week 36 (follow-up) Use of high resolution images to determine changes to brain structure such as white and grey matter
Change in levels of flavanol monomer metabolites/derivatives Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of epicatechin and catechin metabolites/derivatives in plasma and urine samples
Change in levels of procyanidin metabolites/derivatives Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of procyanidin metabolites/derivatives in plasma and urine samples
Change in levels of markers of inflammation Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of pro and anti-inflammatory cytokines and C-reactive protein (CRP) levels in plasma/serum
Change in levels of markers of neuronal function Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of brain-derived neurotrophic factor (BDNF) and lactate in plasma/serum
Change in levels of markers of vascular function/cardiovascular disease (CVD) risk Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of glucose, insulin, cholesterol (total, high density lipoprotein \[HDL\], low density lipoprotein \[LDL\]), non-esterified fatty acids \[NEFA\], triglycerides \[TAG\] in plasma/serum
Change in levels of a marker of stress/anxiety Change from baseline (pre intervention) to week 24 (post intervention) Concentrations of cortisol in plasma/serum
Trial Locations
- Locations (1)
Hugh Sinclair Unit of Human Nutrition, University of Reading
🇬🇧Reading, Berkshire, United Kingdom