Blueberry Study Aimed at Improving Cognition and Peripheral Blood Flow

Metabolic Mechanisms Underlying the Responsiveness to Blueberry Interventions Aimed at Improving Cognition and Peripheral Blood Flow

Blueberries are rich in the content of a variety of biologically active chemicals that contribute to their health properties. The consumption of blueberries has beneficial effects on vascular function and brain health and function. Blueberries are present in human diet in a number of forms, but the investigator do not know which form is best for health and why people respond differently to eating blueberries.

The aim of the present study is to assess the effects of 1 week's supplementation of whole blueberries or freeze-dried blueberry powder or encapsulated blueberry components on vascular function and brain health and function. Investigators will then categorise participants as those who have large effects of the intervention (responders) and those that don't show much effect at all (non-responders). Then the investigators will look into the role that genes play in this response and determine if metabolism is similar in these groups of participants. Any changes in participants' brain health and vascular function will be linked to these metabolic and genomic pathways, and this will help the investigators to further understand how blueberry consumption can benefit human health.

Study design: The present study will supply either 160 g of fresh whole blueberry (4 handful portion) or 20 g of freeze-dried blueberry powder (measured with tablespoon provided; equivalent to 160 g of whole fresh blueberry), or placebo capsule with only microcrystalline cellulose (approx. 10 g, they will be blinded that this is encapsulated blueberry extract components) to 80 subjects on separate occasions with age range of 18-60 years old for 1 week with 1 week of washout period. Fresh blueberries will be purchased from local supermarkets; freeze-dried blueberry powder will be purchased from Lio-Licious freeze-dried fruits range; the microcrystalline cellulose will be purchased from Blackburn Distributions. There is no outside interest that could constitute commercial conflict of interest.

Methodology and sampling strategy: a randomised crossover design will be implemented. The study is a quantitative experiment and participants will be recruited through opportunity sampling.

Data collection: On each visit, cognition data will be obtained from computerised testing system COMPASS. Blood pressure will be obtained using fully automatic oscillometric device. On visits 2-7, PWV value is obtained by SphygmoCor; untargeted metabolomics and genomic data will be obtained from blood and urine sample collection.

For data analysis: The identification of responders to the treatments will be done by the calculation of response level first: response level = (change from baseline score/baseline score) x 100%. The calculated percentage will be used to characterise subjects from lowest response to highest response level. The association among -omics biomarkers and cognitive tests/endothelial parameters, lipid status under each treatment will be analysed using linear regression models after adjusting for confounding factors like age. Pathway analysis will be used to identify metabolic pathways that characterise responders and non-responders. Pathways will be identified using discriminatory metabolites from metabolomics and SNP analysis.

Inclusion Criteria:

• Interested in taking part in the study
• Healthy
• Aged 18-60 years (inclusive)

Exclusion Criteria:

• Smoking
• Aged under 18 or over 60
• Blood Pressure ≥ 145/100 mmHg and are taking medication
• Have vascular disease, or other cardiac abnormalities
• Have previously suffered any head injuries, history of seizures or other neurological disorders
• Have any metabolic disorders, malabsorption syndromes or gastrointestinal complications
• Current use of above disease relevant prescription medications (excluding contraception)
• Irregular bowel function (less than 1 bowel movement per day)
• Regularly consume blueberries/blueberry-contained products more than twice per week
• Have regularly used nutritional supplements or medications within the previous 3 months (defined as more than 3 consecutive days or 4 days in total)
• Learning difficulties and dyslexia
• Visual impairment that cannot be corrected with glasses or contact lenses including colour blindness
• Currently suffer from migraines (> 1 per month)
• Body mass index (BMI) under 18.5 or over 30
• Pregnancy, seeking to become pregnant, or current lactation
• Inability to complete all of the study assessments
• Current participation in other clinical or nutrition intervention studies
• Not proficient in English equivalent to IELTS band 6 or above
• Have any known active infections