Investigating the Acute Effects of Flavonoids in Blueberries on Cognitive Function.

Study Overview
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Brief Summary
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This study was a controlled, cross-over, acute flavonoid intervention trial with younger and older adults. Subjects consumed a blueberry beverage during one visit and a control beverage on another. Cognitive function pre drink was assessed, blood and urine samples were taken as well as blood pressure and a measure of vascular reactivity. These outcome measures were taken at 2 and 5 hours post drink. It was predicted that the flavonoids in the blueberry drink would lead to improved performance on the cognitive tests and vascular reactivity measure compared to following the control drink. It was thought this could be due to increased vaso-dilation and improving blood flow to the brain which was investigated in an extension to the project where a sample of individuals underwent brain imaging in an MRI scanner pre and post a blueberry and a control drink.

Detailed Description
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The control drink was matched to the blueberry drink for other bioactive compounds which may have affected cognition, specifically sugars and vitamin C. Volunteers were healthy, not on any medication, without high blood pressure, high cholesterol, high BMI, diabetes or other medical conditions. Older adults were aged 61-75 years and younger adults 18-26 years. Blood and urine samples will be analysed for flavonoid levels and Brain Derived Neurotrophic Factor, a biomarker of memory and learning, flavonoids may lead to increased BDNF production through the ERK-CREB-BDNF pathway. Flavonoids may also increase nitric oxide production and improve the flexibility of the blood vessels hence the measure of vascular reactivity using the Digital Volume Pulse machine. This can lead to increased vaso-dilation and blood flow to the brain, therefore an fMRI study was carried out the investigate this using arterial spin labeling following acute blueberry supplementation compared to a control drink.

Official Title
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A Controlled, Cross-over, Acute Intervention Study Investigating the Cognitive and Neuronal Effects of Flavonoids in Blueberries.

Conditions
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Healthy Adults.

Intervention / Treatment
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* Dietary Supplement: Flavonoids
* Dietary Supplement: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No medical conditions Not taking any medication or supplements (or willing to stop taking supplements for duration of study) Not lactose intolerant Willing to give blood and urine samples Not partaking in frequent vigorous exercise Not suffering from or history of depression Exclusion Criteria: On blood pressure medication, taking Aspirin or other blood thinning medication BMI > 30 Cholesterol > 6 Diabetes or other serious medical condition Lactose intolerant Any learning difficulty e.g. dyslexia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Blueberry drink<br>30g of blueberry powder (equivalent to 200g fresh blueberries) and 300ml of semi-skimmed milk | Dietary Supplement: Flavonoids<br>* 475g of anthocyanidins in 300ml of blueberry drink.<br>* Other names: Anthocyanidins, flavanols, flavonols.;|
| Placebo Comparator: Control drink<br>29g of powder consisting of sugars and vitamin C, values of which were matched to that of the blueberry drink, with 1 g of citric acid to match for taste. | Dietary Supplement: Control<br>* 29g powder: sugars (glucose, sucrose, fructose), vitamin C and citric acid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function | Extensive cognitive test battery including tasks measuring executive function such as updating, and memory tests such as free recall. | pre drink, 2 hours and 5 hours post drink | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailability and pharmacology | Flavonoid and BDNF levels in plasma and urine samples. | Pre drink and 1 hour post drink | 
| Vascular Reactivity | Measurements taken using Digital volume pulse equipment. Blood pressure also recorded. | Pre and 1 hour post drink | 
| Neuronal effects | Using fMRI to determine whether flavonoid supplementation leads to greater activation in brain regions associated with the cognitive abilities tested and to calculate cerebral blood flow before and after the blueberry compared to the control drink. | Pre and 1 hours post drink |