The effects of oligomeric procyanidins (OPCs) on vascular function, biomarkers of oxidative stress and inflammation in smokers: a pilot study

Atherosclerosis and the associated complications of coronary artery disease and
myocardial infarction (MI) account for the majority of the morbidity and
mortality associated with cardiovascular disease (CVD). Smoking has been
identified as a key risk factor for the development of CVD. It was found that a
persistent increase in levels of oxidative stress and a prolonged inflammatory
state play a pivotal role in the pathogenesis of smoking associated CVD.
Oligomeric proanthocyanidins (OPC) are widely known for their anti-oxidant and
anti-inflammatory effects, in vitro and in vivo. However, there are hardly any
studies available that systematically investigated their acute and long-term
effects on macro- and microvascular function as well as on established
biomarkers of oxidative stress and inflammation in an *at risk* population such
as smokers.

To evaluate the potential attenuating effects of an eight-week supplementation
with 200 mg OPCs per day on macro- and microvascular function as well as on
systemic biomarkers of inflammation and oxidative stress in healthy smoking
subjects.

Double blind, randomised, placebo-controlled study with two parallel test
groups.

Subjects will be allocated randomly to one of the 2 test groups under
accounting for their smoking habits. Subjects are asked to take either 2
capsules of the verum each containing 100 mg of the standardized OPC extract
(MASQUELLIER*S® Original OPCs) or 2 capsules of the appropriate placebo product
every morning over the 8 weeks intervention period.

Subjects have to take 2 capsules of either the verum or the placebo every
morning during an 8 week period. They will participate in 6 visits (including
the screening visit) at the investigational site. Two visits will take
approximately 30 min, three visits will last ca. 2.5 h and the screening visit
will take approximately 45 min.
Since individual acute benefits of the verum supplementation can hardly be
predicted, and all subjects will undergo the same procedures, there is no real
advantage or dissadvantage of the allocation to one or the other test group.

In general, the risks associated with the participation are addressed and
judged as follows:
1) Intake of investigational products
The intake of the OPCs is generally well-tolerated and not associated with any
side effects. Moreover, both the placebo and the verum product will be
delivered in pharmaceutical quality.
2) Blood collection
As a consequence of the intra-venous punctures local haematomas can occur.
However, most of the times this is a transient local reaction which does not
require any medical care.
The risks being associated with the collected amount of 132 mL venous blood
(screening visit ca. 12 mL and 3 study visits in 4 week intervals samplings of
40 mL per visit) are negligible.
3) LDF with iontophoresis of ACh, L-NMMA and SNP
This is a slightly invasive, pain- and harmless technique to assess capillary
blood flow. The vasoreactive substances ACh, L-NMMA and SNP will be delivered
locally in quite low doses by means of a very low current. The compounds remain
in the skin and do not become systemically available. Side effects are very
seldom and can include allergic reactions. The laser used on the skin for the
blood flow assessments does not elicit any side effects.
4) FMD measurements
FMD is a non-invasive, pain- and harmless method to assess endothelium function
of conduit arteries. 5 min. inflation of the forearm cuff may possibly cause
transient ischemia of the subject*s arm which is generally not associated with
any symptoms except of a potential slightly tingly sensation. This sensation
dissappears within a few minutes as soon as the cuff is released.