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

Not Applicable
Completed
Conditions
Hypertension
Endothelial Dysfunction
Interventions
Dietary Supplement: Epicatechin
Dietary Supplement: Quercetin
Dietary Supplement: Placebo
Registration Number
NCT01691404
Lead Sponsor
Wageningen University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
38
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
EpicatechinEpicatechinSubjects will be asked to consume supplements containing 100mg of epicatechin daily
QuercetinQuercetinSubjects will be asked to consume supplements containing 160mg of quercetin-3-glucoside daily
PlaceboPlaceboSubjects will be asked to consume capsules containing a placebo (cellulose) daily
Primary Outcome Measures
NameTimeMethod
Change in Endothelium-dependent flow-mediated dilation as a result of epicatechin and quercetin-3-glucoside supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

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
NameTimeMethod
Change in blood pressure as a result of epicatechin and quercetin-3-glucoside supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

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 supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

Measured using a SphygmoCor device at baseline and the end of each intervention

Change in vasomotion as a result of epicatechin and quercetin supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

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 supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

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 supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

PBMC gene expression of markers of inflammation

Change in cardiovascular parameters in plasma as a result of epicatechin and quercetin supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose

Changes in pulse wave analysis as a result of epicatechin and quercetin supplementationBaseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)

Measured using a SphygmoCor device at baseline and the end of each intervention

Adverse eventsBaseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)

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.

Trial Locations

Locations (1)

Wageningen University

🇳🇱

Wageningen, Netherlands

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