Metabolism of Anthocyanins and Heart Health

Study Overview
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Brief Summary
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This study aims to find out if consuming a single dose of blueberries, rich in anthocyanins, within an energy dense meal, improves blood vessel function and biomarkers of heart health. The study specifically aims to confirm if differences in how individuals process the bioactive compounds in blueberries, called anthocyanins, has an influence on heart health. The investigators will assess the effects of eating one portion of blueberries on vascular health over a 48hour period, and will track the breakdown compounds within blood and urine, to see if health effects are related to metabolism.

Detailed Description
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The primary aim of this cross-over designed, placebo controlled, acute dietary intervention study, is to prospectively recruit participants on the basis of anthocyanin metabolism profiles (based on profiles confirmed in our previous studies) following a 'blueberry challenge'. Acute cardio and metabolic function responses will be assessed (by metaboliser profile), following an energy dense test meal with/without the addition of blueberries. Participants will be healthy, but overweight and obese (BMI inclusion: ≥ 25kg/m2) men and women (aged 50 y to 80 y), who will initially undertake a 'blueberry challenge' by consuming a single dose of freeze dried blueberries. Anthocyanin metaboliser type will be profiled from the analysis of metabolites within urine, collected for 48h following the 'challenge'. A total of 70 participants will complete the intervention (n=35 FAST and n=35 SLOW metabolisers) which consists of two, test meal periods (separated by at least 7d and allocated in random order); 1) energy dense test meal plus freeze dried blueberries, 2) energy dense test meal plus an isocaloric matched placebo material. Urine samples and ambulatory blood pressure measures will be collected for 24h prior to, and then over the 48h period which follows the test meal intake. Further assessment of vascular and metabolic function will be made at pre-defined times over the 48h postprandial period. Dietary restrictions to abstain from blueberries and reduce the anthocyanin intake level, will be applied for 5d before each test meal intake. In addition, all food and drink will be provided for a 4d period (2d before and during the 48h following the energy dense test meal) to further control the intake of flavonoids and to standardise the influence of background diet on metabolism profile.

Official Title
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The Effects of Blueberry Anthocyanin Metabolism on Acute Cardiometabolic Health

Conditions
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Healthy

Intervention / Treatment
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* Other: Freeze dried blueberry powder
* Other: Anthocyanin free, sugar-matched placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI >= 25 kg/m2 Adults aged 50 - 80 years old Successful biochemical, haematological, and urinalysis assessment at screening Exclusion Criteria: Current smokers, or ex-smokers ceasing < 6 months ago existing or significant past medical history of vascular disease or medical conditions likely to affect the study measures Fructose or lactose intolerant subjects or known allergies to intervention treatments Those unprepared to adhere to dietary instructions Parallel participation in another research project involving dietary intervention and/or sampling of biological fluids/material Those on therapeutic diets or having experienced substantial weight loss within 2 months of screening. Those taking flavonoid, nitrate / nitrite containing or fish oil containing supplements (and unwilling to cease intake during, and 1 month preceding the trial) or unwilling to maintain existing intake of other supplements. Prescribed hypoglycaemic, anti-hypertensive, vasodilator or hormone replacement therapy (HRT) medication. Unsatisfactory biochemical, haematological or urinary results or measurements considered to be counter indicative for the study Undiagnosed hypertension (elicited at screening; i.e. ≥ 180 / 110mmHg) at a level requiring immediate referral back to general practitioner for follow-up

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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
Interventional Model Description: Our research design involves screening individuals and then prospectively recruiting on the basis of two distinct blueberry metabolism profiles based on our previous research findings (in a population with metabolic syndrome). Our study will assess whether individuals with SLOW and FAST anthocyanin metabolism profiles respond differently and will test if the difference in processing may influence cardio metabolic responses. Our study involves feeding a single energy-dense meal which we anticipate will have a transient deleterious effect on acute markers of health. We will test whether adding blueberries to the energy dense meal improves acute responses compared against when adding the equivalent isocaloric amount of placebo. Participants will experience the blueberry and placebo treatments in random order
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLOW anthocyanin metabolisers<br>Participants will be prospectively recruited to the SLOW anthocyanin metaboliser group, following a pre-intervention screen (blueberry challenge). Participants in this arm will consume (in random order) blueberry and placebo interventions (both consumed with an energy dense meal) in a cross-over manner. At least 7 days washout will be observed between the two treatments. | Other: Freeze dried blueberry powder<br>* 36 g of freeze-dried blueberry powder to be mixed with milk and served together with an energy-dense meal.<br>Other: Anthocyanin free, sugar-matched placebo<br>* 36 g of isocaloric placebo, matched for sugars to be mixed with milk and served together with an energy-dense meal.<br>|
| Experimental: FAST anthocyanin metabolisers<br>Participants will be prospectively recruited to the FAST anthocyanin metaboliser group, following a pre-intervention screen (blueberry challenge). Participants in this arm will consume (in random order) blueberry and placebo interventions (both consumed with an energy dense meal) in a cross-over manner. At least 7 days washout will be observed between the two treatments. | Other: Freeze dried blueberry powder<br>* 36 g of freeze-dried blueberry powder to be mixed with milk and served together with an energy-dense meal.<br>Other: Anthocyanin free, sugar-matched placebo<br>* 36 g of isocaloric placebo, matched for sugars to be mixed with milk and served together with an energy-dense meal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial artery endothelial function | percentage maximum dilatation assessed via flow mediated dilation (%FMD): (diametermax-diameterbaseline) / diameterbaseline×100. | assessed at 0, 1.5, 3, 6, 24, 48 hours after intervention intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Office blood pressure | Measurements of blood pressure | Assessed at 0, 3, 6, 24, 48 hours after intervention intake. | 
| Bioavailability - serum | Assessment of flavonoid and metabolite levels in blood samples | Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake. | 
| Postprandial Insulin response | Assessment of postprandial insulin control | Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake. | 
| Total cholesterol | Assessment of blood cholesterol | Measured prior to, and then at +20, +40, +60, +90, +120, +180, +270 and +360 minutes, +24 hours and +48 hours following the energy dense meal intake. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blueberry, Metabolism, Anthocyanins, Inter-individual variation, Cardiometabolic health