The Blueberry Study

Study Overview
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Brief Summary
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This is a research study about the effects of blueberries on the health of children who do not eat much fruits and vegetables. By doing this study, we hope to find out what nutrients from blueberries appear in the blood and urine of the child

Detailed Description
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This is a double blinded randomized control trial aiming to characterize the profile of polyphenol-derived metabolites in plasma and urine for children ages 11-12 years supplemented short term with wild blueberry powder. The study will assess if a short-term supplementation (5 days) with wild blueberry powder impacts immune responses as well as markers for cardiovascular and bone health. Up to 44 children will be recruited. The participants will attend three visits at Arkansas Children's Nutrition Center.

Official Title
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Plasma and Urine Profiles of Blueberry Derived Polyphenols After a Short Term Intervention With Blueberry in Children With Typical Low Fruit and Vegetable Consumption.

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Wild blueberry containing foods
* Dietary Supplement: Placebo containing foods


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eats <1.5 cup of fruit and <2.0 cup of vegetables per day Boys or girls All ethnicities All BMIs Exclusion Criteria: Known allergy to blueberries Epilepsy Asthma Chronic kidney disease Hormonal disease Autoimmune disease Bleeding disorders Chronic infections Type 2 and Type 1 diabetes mellitus Attention deficit hyperactivity disorder Opposition defiant disorder Autistic spectrum disorder Pre-existing medical conditions or medications as determined by the investigators to affect the outcomes of interest If the participants/parents perceive barriers with adhering to low-polyphenol meals Parent or child refusal to stop nutritional supplements Parent or child refusal to have blood drawn

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 12 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Wild Blueberry Supplement<br>30 grams of wild blueberry powder per day in foods items provided to them | Dietary Supplement: Wild blueberry containing foods<br>* Foods that contain wild blueberry supplement to deliver up to 30 grams of blueberry powder<br>|
| Placebo Comparator: Placebo supplement<br>Food items will be provided to them without the wild blueberry power. | Dietary Supplement: Placebo containing foods<br>* Foods that do not contain the blueberry powder but a placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma and urine levels of blueberry derived polyphenols and their metabolites | Blood will be collected twice following an overnight fast. Twelve-hour urine will be collected twice by participants at home. Plasma and urine samples will be analyzed using mass spectrometry to identify blueberry-derived polyphenols and their levels | up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of lymphocytes cluster of differentiation 4 (CD4), lymphocytes cluster of differentiation 8 (CD8) and natural killer (NK) cells | Mitogen stimulated blood will be stained with combinations of fluorochrome-labeled antibodies and analyzed by flow cytometry. Absolute and relative number of CD4, lymphocytes CD8 and natural killer (NK) will be compared between groups. | up to 2 weeks | 
| T-lymphocyte responsiveness to immune stressors | Blood will be collected following an overnight fast after 5 days on the intervention. Whole blood will be cultured and cells stressed with E. coli lipopolysaccharide (LPS) to induce cytokine release from immune cells. Cytokines will be assayed using electrochemiluminescence based detection platform with multiplexed immunoassays, and their levels compared between study groups. | up to 2 weeks | 
| Endothelial function by brachial artery flow mediated dilation | Endothelial-dependent flow-mediated vasodilation of the brachial artery will be measured using high resolution ultrasound at enrollment and after 5 days on the intervention. This technology uses sound waves (ultrasound) to visualize the diameter of the brachial artery. A baseline image of the brachial artery will be recorded at rest. A blood pressure cuff will be placed around the lower arm and the cuff will be inflated to 50 mmHg above systolic pressure for 5 minutes, followed by rapid deflation of the cuff. The diameter of the brachial artery will be measured from ultrasound images captured throughout the 8 minute recording protocol. The percent change in the brachial artery will be compared between and within groups. | up to 2 weeks |