Clinical trial NCT01691404: Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure (FLAVO)
Official title: Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure in Untreated (Pre)Hypertensive Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Endothelial Dysfunction
Keywords: Flavonoids
Quercetin
Epicatechin
Vascular function
Blood pressure
Endothelial function
Lead sponsor: Wageningen University
Sponsor class: OTHER
Collaborators: name: Top Institute Food and Nutrition
First posted: 2012-09-24
Enrollment: 38
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: Change in Endothelium-dependent flow-mediated dilation as a result of epicatechin and quercetin-3-glucoside supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Secondary outcomes:
measure: Change in blood pressure as a result of epicatechin and quercetin-3-glucoside supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
measure: Change in pulse wave velocity as a result of epicatechin and quercetin supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
measure: Change in vasomotion as a result of epicatechin and quercetin supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
measure: Changes in biomarkers of endothelial function as a result of epicatechin and quercetin supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
measure: Changes in peripheral blood mononuclear cell gene expression of markers of inflammation as a result of epicatechin and quercetin supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
measure: Change in cardiovascular parameters in plasma as a result of epicatechin and quercetin supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
measure: Changes in pulse wave analysis as a result of epicatechin and quercetin supplementation
timeFrame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
measure: Adverse events
timeFrame: Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)
Other outcomes:
Locations:
city: Wageningen
country: Netherlands
facility: Wageningen University
Study officials:
affiliation: Wageningen University
name: Peter Hollman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van den Eynde MDG, Geleijnse JM, Scheijen JLJM, Hanssen NMJ, Dower JI, Afman LA, Stehouwer CDA, Hollman PCH, Schalkwijk CG. Quercetin, but Not Epicatechin, Decreases Plasma Concentrations of Methylglyoxal in Adults in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial with Pure Flavonoids. J Nutr. 2018 Dec 1;148(12):1911-1916. doi: 10.1093/jn/nxy236.
citation: Dower JI, Geleijnse JM, Gijsbers L, Schalkwijk C, Kromhout D, Hollman PC. Supplementation of the Pure Flavonoids Epicatechin and Quercetin Affects Some Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial. J Nutr. 2015 Jul;145(7):1459-63. doi: 10.3945/jn.115.211888. Epub 2015 May 13.
citation: Dower JI, Geleijnse JM, Gijsbers L, Zock PL, Kromhout D, Hollman PC. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial. Am J Clin Nutr. 2015 May;101(5):914-21. doi: 10.3945/ajcn.114.098590. Epub 2015 Feb 25.