Comparison of Pure Epicatechin and Cocoa on Markers of Vascular Function (FLAVO2)

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.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction; Bioavailability
• Intervention / Treatment: Dietary supplement: Pure Epicatechin; Dietary supplement: High flavan-3-ol cocoa; Dietary supplement: Placebo

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:

1. High flavan-3-ol chocolate (70g) plus placebo capsule;
2. White chocolate (70g) plus 100mg of epicatechin in capsule form;
3. 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Wageningen, Netherlands, 6703 HD
    • Wageningen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Top Institute Food and Nutrition
• Investigators: Principal Investigator: Peter Hollman, Dr, Wageningen University

Publications and helpful links

Helpful Links

• Website for the study (in dutch)

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: August 19, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 20, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 14, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Bioavailability; Endothelial function; Cocoa; Chocolate; Flavan-3-ol; Flavonoids; Epicatechin
• Other Study ID Numbers: FLAVO2