Relevance of Vascular Function Markers: Study on the Effects of Quercetin and Epicatechin on Blood Pressure and Vascular Function in (Pre)Hypertensive Subjects

Decreased vascular function and increased blood pressure are both risk factors
for cardiovascular disease. Nutrition and lifestyle can significantly influence
both vascular function and blood pressure. The right choice of foods, rich in
certain nutrients, can help lower the risk of myocardial infarction or stroke.

Foods with a high flavonoid content (such as tea, cocoa, red wine, apples and
onions) have already been shown to have a blood pressure-lowering effect. These
effects are often thought to be due to the high flavonoid content, however,
because these foods contain many different types of flavonoids, it is difficult
to say which flavonoid in particular may have a beneficial role.

During the FLAVO-studie, we aim to investigate if (and how) certain pure
flavonoids can beneficially effect vascular function. This will be done by
providing participants with capsules containing two different types of
flavonoids. Participants will be asked to consume these flavonoid capsules for
4 weeks. Measurements will be taken be and after the 4-week intervention
period.

The FLAVO-studie is a scientific study aimed at investgating if (and how)
certain pure flavonoids can beneficially influence vascular function.

The study will commmence with a run-in week. During the run-in week,
participants will receive dietary advice asking them to refrain from consuming
food products known to have a high flavonoid content (such as tea, cocoa,
apples, red wine and onions).

Following the run-in week, participants will be asked to follow three
intervention periods of 4 weeks. Each intervention period will be separated by
a washout period. During the washout period, participants will not have to
consume any capsules and will only be asked to follow the dietary advice.

During an intervention period, participants will be asked to consume capsules
containing either a flavonoid supplement or a placebo capsule (two capsules per
day). Participants will be asked to consume one capsule at lunch and one at
dinner - with a glass of water.

Every four weeks, participants will be asked to visit the university following
an overnight fast. During these visits, various measurements of vascular
function will be taken. On the last day of each intervention period, a number
of measurements (including a blood sample) will be taken twice - once in the
morning and again two hours after consumption of a final supplement. Every two
weeks additional blood samples will be taken.

During an intervention period, participants will be asked to consume capsules
containing either flavonoid supplements or placebo capsules (two capsules per
day). Participants will be asked to consume one capsules during lunch and one
during dinner - with a glass of water.

The flavonoid supplements which will be used are epicatechin (100mg/day) and
quercetin-3-glucoside (160mg/day). The dosage of the supplements corresponds to
3 times the 90th percentile of habitual intake in the Netherlands.

Risks for the subjects are considered low. Only healthy subjects with a
systolic blood pressure between 125 and 159mmHg will be included in the study.
To determine if subjects are healthy, they will be screened on several safety
parameters including liver and renal function.

The dosage of flavonoids provided (160mg for quercetine-3-glucoside and 100mg
for epicatechin) are equal to three times the 90th percentile of habitual
intake in the Netherlands. This means that the dosage provided is equivalent to
what could be consumed following a flavonoid-rich diet. A safety report of both
supplements to be used has been provided to the METC.

There is a chance of bruising as a result of venepuncture and some subjects may
feel light-headed or experience a slight headache as a result of nitroglycerine
administration. In such cases, subjects will be advised to remain seated until
the effects have subsided and to avoid physical activity immediately following
administration.

Parameters of liver and renal function as well as whole blood cell count will
be taken and analysed every two weeks in order to monitor the health status of
the subjects during the study period.

In contrast, it is hypothesized that the consumption of flavonoid supplements
will decrease blood and improve vascular function.