Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure (FLAVO)

This study has been completed.
Sponsor:
Collaborator:
Top Institute Food and Nutrition
Information provided by (Responsible Party):
Wageningen University
ClinicalTrials.gov Identifier:
NCT01691404
First received: September 12, 2012
Last updated: April 22, 2013
Last verified: November 2012
  Purpose

Flavonoid-rich foods such as tea and cocoa have been identified as having a blood pressure-lowering effect. Part of this effect is thought to be due to the flavonoid content of these foods although it is currently unknown which flavonoids play a role. Epicatechin is one the major flavonoids in cocoa while quercetin is largely found in tea.

During this study the investigators plan to investigate the effects of pure epicatechin and quercetin supplementation on vascular function and blood pressure in untreated (prehypertensive) subjects by way of a three-armed double-blind crossover intervention. Participants will sequentially consume supplements containing quercetin, epicatechin or placebo for a period of 4 weeks. Before and after this 4 week period, measurements of vascular function and blood pressure will be taken.

The investigators hypothesize that the supplementation of epicatechin and quercetin will improve vascular function and blood pressure.


Condition Intervention
Hypertension
Endothelial Dysfunction
Dietary Supplement: Epicatechin
Dietary Supplement: Quercetin
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure in Untreated (Pre)Hypertensive Subjects

Resource links provided by NLM:


Further study details as provided by Wageningen University:

Primary Outcome Measures:
  • Change in Endothelium-dependent flow-mediated dilation as a result of epicatechin and quercetin-3-glucoside supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    Change in arterial diameter as a result of 5 minute arterial occlusion (200mmHg). Arterial diameter will be measured by means of ultrasonography.


Secondary Outcome Measures:
  • Change in blood pressure as a result of epicatechin and quercetin-3-glucoside supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    Office BP (Dinamap, 4 consecutive measurements with 2-min intervals)and 24-hour ABPM (Spacelab; 1x24h)

  • Change in pulse wave velocity as a result of epicatechin and quercetin supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    Measured using a SphygmoCor device at baseline and the end of each intervention

  • Change in vasomotion as a result of epicatechin and quercetin supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    Measured using a PeriFlux 5001 device at baseline and the end of each intervention.

  • Changes in biomarkers of endothelial function as a result of epicatechin and quercetin supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    Plasma analysis of endothelin-1, ADMA, MCP-1, sVCAM-1, sICAM-1, sE-selectin, sTM, CRP, SAA, IL-6, IL-8, TNF-α, vWF, nitric oxide

  • Changes in peripheral blood mononuclear cell gene expression of markers of inflammation as a result of epicatechin and quercetin supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    PBMC gene expression of markers of inflammation

  • Change in cardiovascular parameters in plasma as a result of epicatechin and quercetin supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose

  • Changes in pulse wave analysis as a result of epicatechin and quercetin supplementation [ Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20) ] [ Designated as safety issue: No ]
    Measured using a SphygmoCor device at baseline and the end of each intervention

  • Adverse events [ Time Frame: Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20) ] [ Designated as safety issue: Yes ]
    During the study subjects will be asked to maintain a diary in which they can report any adverse events they may have a result of the supplements. Diaries will be checked every 2 weeks. Study subjects will also be asked to contact the research team if they experience repeated adverse events.


Enrollment: 38
Study Start Date: September 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Epicatechin
Subjects will be asked to consume supplements containing 100mg of epicatechin daily
Dietary Supplement: Epicatechin
Subjects will be asked to consume supplements containing 100mg of epicatechin daily
Active Comparator: Quercetin
Subjects will be asked to consume supplements containing 160mg of quercetin-3-glucoside daily
Dietary Supplement: Quercetin
Subjects will be asked to consume 160mg of quercetin-3-glucoside daily
Placebo Comparator: Placebo
Subjects will be asked to consume capsules containing a placebo (cellulose) daily
Dietary Supplement: Placebo
Subjects will be asked to consume capsules containing placebo (cellulose) daily

Detailed Description:

By means of a three-armed double-blind crossover intervention, the effects of pure flavonoid supplementation will be investigated. The products under investigation will be epicatechin and quercetin-3-glucoside. Subjects will be asked to consume either 160mg of quercetin-3-glucoside, 100mg of epicatechin or a placebo capsule for a period of 4 weeks. Measurements of vascular function and blood pressure will be taken before and after each 4-week intervention period. A 4-week washout period will be planned between each intervention.

Measurements of vascular function will include flow-mediated dilation, pulse wave analysis, pulse wave velocity and vasomotion as well as biomarkers of inflammation and vascular function.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Systolic Blood Pressure between 125 and 160 mmHg
  • Age between 30 and 80 years
  • BMI > 20 and ≤ 40
  • 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 diabetes mellitus
  • Fasting laboratory parameters within normal range: complete blood count (RBC, WBC, PLT, HB, HT), renal function (serum creatinine, urea), liver function (ALAT, ASAT, ɣ-GT), and serum glucose.

Exclusion Criteria:

  • Body mass index > 40 and ≤20
  • Secondary hypertension
  • Weight loss or weight gain of 5 kg or more during the last 2 months
  • Usage of non-steroidal anti-inflammatory drugs (acetylsalicylic acid, ibuprofen, naproxen) and not able or willing to stop taking them from at least 4 weeks prior to the study
  • Usage of cholesterol-lowering medication
  • Daily usage of corticosteroids
  • Medical treatment that may affect blood pressure and not able (or willing) to stop
  • Taking nutritional supplements and unwilling to discontinue
  • Lactating, pregnant or intention to become pregnant during study
  • Reported dietary habits, medically prescribed diet, slimming diet
  • Reported average alcohol consumption > 2 glasses/d (men) or >1 glass/d (women)
  • Problems with consuming the supplements or following the study guidelines
  • Unwilling to undergo home or office blood pressure measurements
  • Recent blood donation i.e. 1 month (male subjects) or 2 months (female subjects) prior to the study and planned donation during the study period
  • Reported intense sporting activities > 10 h/w
  • 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
  • Clinical disorders that could interfere with the intervention
  • Unable to comply with the study procedure (e.g. holidays, urine collection, blood sampling)
  • Smokers
  • Difficulty imaging brachial artery by ultrasonography
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691404

Locations
Netherlands
Wageningen University
Wageningen, Netherlands, 6703 HD
Sponsors and Collaborators
Wageningen University
Top Institute Food and Nutrition
Investigators
Principal Investigator: Peter Hollman, PhD Wageningen University
  More Information

Additional Information:
No publications provided

Responsible Party: Wageningen University
ClinicalTrials.gov Identifier: NCT01691404     History of Changes
Other Study ID Numbers: NL4077208112
Study First Received: September 12, 2012
Last Updated: April 22, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Wageningen University:
Flavonoids
Quercetin
Epicatechin
Vascular function
Blood pressure
Endothelial function

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Quercetin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2014