Blueberry Enhances Activity and Cognition Through Increased Vascular Efficiency

Study Overview
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Brief Summary
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Recent evidence suggests that increased berry intake results in a variety of health benefits, across multiple health domains. This 3-month randomized, double-blind, placebo-controlled trial assess the effects of combining daily blueberry intake with weekly exercise (BB-EX) on cardiovascular function, as well as physical activity and cognitive function, in sedentary older adults (>60 years). We will compare these effects to the same outcomes with a control group consuming a blueberry placebo (P-EX) at 0, 4, 8 and 12 weeks.

Detailed Description
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A 12-week randomized, double-blind, placebo-controlled physical activity intervention will be administered in sedentary older (>60 years) women and men randomized to either lyophilized blueberry powder, rehydrated and consumed as a beverage twice daily with meals (BB-EX; n = 25), or an indistinguishable placebo powder, taken in the same manner (placebo control; P-EX; n = 25). Vascular function (primary outcome), 24-hr ambulatory blood pressure, cognitive performance, and related secondary measures will be assessed at 0 and 12 weeks; berry and nutrient intake and function are assessed every 4 weeks; and physical activity as step counts will be continuously monitored using a mobile device (Garmin). Blood, urine (24-hr), and stool samples will be collected at 0 and 12 weeks and archived for later analysis. The 12-week study duration is based upon the timing of vascular responses seen in other trials, as well as the minimal time needed to expect a change in cognitive performance in an older adult population. The blueberry dose of 36 grams per day in a split dose consumed with meals is based on (1) a 33% increase in dose over that previously used in a longer (6-month) trial; (2) delivering the most effective dose of blueberry bioactives; and (3) reduced likelihood of any gastrointestinal symptoms.

Official Title
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Effects of Blueberry Consumption on Vascular Function, Physical Activity, and Cognition in Sedentary Older Adults

Conditions
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Sedentary Lifestyle, Blood Pressure, Arterial Stiffness, Overweight and Obesity

Intervention / Treatment
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* Dietary Supplement: Blueberry Plus Exercise (BB-EX)
* Dietary Supplement: Blueberry Placebo Plus Exercise (P-EX)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60 and older Overweight (BMI ≥25 to 35 kg/m2) Well-controlled blood pressure (< 150/90 mmHg) Able to speak and understand spoken and written English Cognitively normal (Mini-Cog score 3-5) Able to walk independently Social security number (required for compensation) Own a smartphone or other mobile device capable of downloading the Garmin Connect app Exclusion Criteria: Exercise > 150 minutes/week Unwillingness or inability to be randomized to any one of two intervention groups without knowing which (double-blind), submit to all study testing, or continuously participate in a randomly assigned diet and exercise intervention for six months. Unwilling to restrict consumption of anthocyanin-rich foods Unwillingness to abstain from mood altering drugs (including marijuana but excluding CBDs) for 7 days prior to baseline and endpoint testing. Self-reported vegetarian or vegan. Inability to complete written recording forms including journals of eating and exercise behaviors. Inability to complete written and computerized cognitive tasks (presented in English). Allergy or intolerance to blueberry or placebo powder ingredients Placebo ingredients include: maltodextrin, fructose, artificial blueberry flavor, natural blueberry flavor, artificial purple color (water, FD&C Red #40, FD&C Blue #1, malic acid, sodium benzoate) citric acid, and artificial red color (water, FD&C Red #40, malic acid, sodium benzoate, silica dioxide). Gastrointestinal disorders that influence digestion and absorption of food, e.g., IBD History of frequent urinary tract or Clostridium difficile infections Presence of unstable, acutely symptomatic, or life-limiting illness. Regular use of medication that interferes with the measurement of study outcomes as determined by the study physician. Unstable use of medications, other than statins, for conditions associated with metabolic syndrome (hypertension, diabetes, dyslipidemia) during the prior 6 months or during the study. Antibiotic use in the last 3 months. Cigarette smoking, chewing, or use of nicotine replacement products in the past 3 months or during the course of the study. Colonoscopy in last 2 months. History of stomach or bowel resection (other than appendectomy), gastric bypass or other bariatric weight loss procedure effecting absorption. History of significant weight instability (defined as > 10 pounds weight gain or loss over one month prior to study participation). History of cancer treatment (other than melanoma skin cancer) and not cancer-free for at least 1 year. History of anti-hormonal therapy (eg., for breast or prostate cancer) within the last 6 months.

Ages Eligible for Study
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Minimum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blueberry Plus Exercise (BB-EX)<br>BB-Ex participants will consume lyophilized blueberry powder, mixed with water (18 grams, equivalent to 3/4ths cup of blueberries) with 2 daily meals (36 g/d blueberry powder total; approx. 1.5 servings/d) | Dietary Supplement: Blueberry Plus Exercise (BB-EX)<br>* Pre-packaged blueberry powders are from U.S. Highbush Blueberry Council and are packaged in sealed single-serving packets (18 g/packet) to prevent exposure to light and moisture. All supplement packets are stored under refrigeration until distribution to study participants. Participants will be asked to increase physical activity through a weekly supervised exercise class and increasing baseline daily step counts gradually over the course of the intervention.<br>* Other names: Lyophilized Blueberry Powder;|
| Placebo Comparator: Blueberry Placebo Plus Exercise (P-EX)<br>Participants randomized to P-EX treatment will consume an indistinguishable placebo powder, matched for color, flavor, consistency, and caloric content, in the same manner. | Dietary Supplement: Blueberry Placebo Plus Exercise (P-EX)<br>* Pre-packaged placebo powders are from U.S. Highbush Blueberry Council and are packaged in sealed single-serving packets (18 g/packet) to prevent exposure to light and moisture. All supplement packets are stored under refrigeration until distribution to study participants. Participants will be asked to increase physical activity through a weekly supervised exercise class and increasing baseline daily step counts gradually over the course of the intervention.<br>* Other names: Placebo Blueberry Powder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pulse wave velocity at 12 weeks | Change in carotid-femoral pulse wave velocity will be assessed using applanation tonometry, (SphygmoCor Pulse Wave Velocity System) | 0 to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in cognitive flexibility at 12 weeks | Change in cognitive performance will be assessed using a computerized task-switching test in which participants predictably alternate between two discrimination tasks. | 0 to 12 weeks | 
| Change from baseline in physical activity at 12 weeks | Change in physical activity will be measured using a commercial activity monitor, which will be worn 24 hr/d to capture total daily steps as the measure of physical activity. | 0 to 12 weeks | 
| Change from baseline in ambulatory blood Pressure at 12 weeks | Change in ambulatory blood pressure will be measured using an Ambulatory BP Monitor, with readings taken every 30 min. during the day and 60 min. at night, over a 24-hour period. | 0 to 12 weeks | 
| Change from baseline in total calories at 4, 8 and 12 weeks | Total calories will be measured using 3-day food records (participants record everything they eat and drink for three days) | 0 to 12 weeks (0, 4, 8 and 12 weeks) | 
| Change from baseline in macronutrient intake at 4, 8 and 12 weeks | Total calories will be measured using 3-day food records (participants record everything they eat and drink for three days) | 0 to 12 weeks (0, 4, 8 and 12 weeks) | 
| Change from baseline in micronutrient intake at 4, 8 and 12 weeks | Total calories will be measured using 3-day food records (participants record everything they eat and drink for three days) | 0 to 12 weeks (0, 4, 8 and 12 weeks) | 
| Change from baseline aerobic endurance at 4, 8, and 12 weeks | Change in aerobic endurance will be determined by a 6-minute walk where subjects walk as many laps as possible in 6 minutes between cones placed 100 feet apart. | 0 to 12 weeks (0, 4, 8 and 12 weeks) | 
| Change from baseline hand grip strength at 4, 8 and 12 weeks | Change in maximal upper body strength will be determined using hydraulic isometric hand dynamometer. | 0 to 12 weeks (0, 4, 8 and 12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blueberries, Pulse Wave Velocity, Aging, Exercise, Cognition