Comparison of Pure Epicatechin and Cocoa on Markers of Vascular Function

Study Overview
=================
Brief Summary
-----------------
Intervention studies support a protective effect of flavonoid-rich foods such as chocolate and tea on cardiovascular disease risk. In a previous study we found that pure epicatechin improves markers of vascular function and insulin resistance although the results were less pronounced than the majority of chocolate intervention studies. The food matrix of chocolate or other compounds present in chocolate could play a role in the bioavailability of flavonoids, resulting in these heightened improvements in vascular function. In this study we aim to compare the acute effects of pure epicatechin and high-flavonoid chocolate on markers of vascular function.

Detailed Description
-----------------
Twenty male participants between the ages of 40 and 80 will visit the university on three days, separated by a 2-week washout. During each visit the participants will, in random order, be allocated to one of the three interventions: High flavan-3-ol chocolate (70g) plus placebo capsule; White chocolate (70g) plus 100mg of epicatechin in capsule form; White chocolate (70g) plus placebo capsule; Measurements of vascular function will be taken before, and 2 hours after consumption of the supplements. In order to determine flavonoid bioavailability, 24-hour urine samples will be collected and 7 blood samples will be taken over a period of 8 hours. The primary study parameter is the percentage change in Flow-Mediated Dilation (FMD) as a result of a high-flavonoid cocoa or epicatechin challenge. Additional study parameters include plasma flavonoid and nitric oxide concentrations as well as pulse wave analysis parameters.

Official Title
-----------------
Comparison of Pure Epicatechin and Cocoa on Markers of Vascular Function

Conditions
-----------------
Endothelial Dysfunction, Bioavailability

Intervention / Treatment
-----------------
* Dietary Supplement: Pure Epicatechin
* Dietary Supplement: High flavan-3-ol cocoa
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 40 and 80 years, BMI between > 20 and ≤ 30 No reported current or previous metabolic diseases, No history of cardiovascular diseases, No history of renal, liver or thyroid diseases, No history of gastrointestinal diseases, No diagnosed diabetes mellitus, Fasting laboratory parameters within normal range as judged by the study physician: renal function (serum creatinine, ureum), liver function (ALAT, ASAT, GGT), serum glucose and HDL, LDL and total cholesterol. Exclusion Criteria: Body mass index >30 or ≤20 kg/m2 Usage of CVD medication (e.g. anti-hypertensive and/or lipid-modifying medication, non-steroidal anti-inflammatory drugs, acetylsalicylic acid), antibiotics, corticosteroids or opioids and not able or willing to stop taking them from at least 4 weeks prior to the study Taking nutritional supplements and unwilling to discontinue Reported dietary habits: medically prescribed diet, slimming diet Reported average alcohol consumption greater than or equal to 3 glasses/d Reported intense sporting activities > 10 h/w Weight loss or weight gain of 5 kg or more during the last 2 months Smokers Vegetarians Problems with consuming the supplements or following the study guidelines Recent blood donation (i.e. 1 month) prior to the study and/or planned donation during and shortly after the study period Not agreeing to be informed about unexpected and medically relevant personal test-results, or not agreeing that their general practitioner will be informed about these results Participation in another biomedical trial less than 2 months before the start of the study or at the same time No signed informed consent form Unable to comply with the study procedure (e.g. holidays, urine collection, blood sampling)

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pure Epicatechin<br>Participants will consume 100mg of epicatechin (capsule) + 70g white chocolate | Dietary Supplement: Pure Epicatechin<br>* Participants will consume 100mg of epicatechin (capsule) + 70g white chocolate<br>|
| Active Comparator: High flavan-3-ol cocoa<br>Participants will consume 70g high flavan-3-ol cocoa (100mg epicatechin) + placebo capsule | Dietary Supplement: High flavan-3-ol cocoa<br>* Participants will consume 70g high flavan-3-ol cocoa (100mg epicatechin) + placebo capsule<br>|
| Placebo Comparator: Placebo<br>Participants will consume 70g white chocolate + placebo capsules | Dietary Supplement: Placebo<br>* Participants will consume 70g white chocolate + placebo capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endothelium-dependent flow-mediated dilation as a result of high flavan-3-ol cocoa or pure epicatechin consumption. | Change in arterial diameter as a result of 5 minute arterial occlusion (200mmHg). Arterial diameter will be measured by means of ultrasonography. | Baseline and 2 hours after consumption | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nitric oxide as a result of high flavan-3-ol cocoa or pure epicatechin consumption | Plasma analysis of nitric oxide | Baseline and 1 hr, 2hr, 3hr, 4hr, 6hr and 8hr after consumption | 
| Changes in arterial augmentation index as measured by Pulse Wave Analysis | Measured in triplicate using a SphygmoCor device at baseline and 2 hours after consumption | Baseline and 2 hours after consumption | 
| Bioavailability of plasma epicatechin metabolites | Plasma analysis of epicatechin metabolites will be measured up to 8 hours after consumption of high flavan-3-ol cocoa or pure epicatechin | Baseline and 1hr, 2hr, 3hr, 4hr, 6hr and 8hr after consumption | 
| Bioavailability of urine epicatechin metabolites | Urinary epicatechin metabolites will be measured in 24-hour urine samples | 24 hour urine samples | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Flavan-3-ol, Flavonoids, Epicatechin, Cocoa, Chocolate, Endothelial function, Bioavailability