Latin name: Vitis vinifera L. [Vitaceae]
Plant part: Seed
The grape plant is a woody, perennial vine that produces fruit from
which juice, raisins, and wine are produced. Pigments and tannins in
grapes contribute to the color and taste of the fruit. The tannins are
polymers of the polyphenols catechin and epicatechin. Other names
for these polymers are procyanidins, leucoanthocyanins, procyanidolic
oligomers, and oligomeric proanthocyanidins (OPCs). The
strong antioxidant properties of the OPCs have sparked interest in
their therapeutic use. OPCs are concentrated in the skins of red grapes,
but are even more abundant in the seeds. A patented process has been
developed that produces a highly concentrated extract of polyphenols
from crushed grape seeds (Bombardelli and Morazzoni, 1995).
Most of the clinical studies on grape seed preparations have focused
on benefits to the circulatory system. The studies described in
this section explore the possible benefit of grape seed preparations in
treating venous insufficiency, capillary fragility, edema, and visual
contrast sensitivity due to glare, as well as antioxidant properties.
The procyanidins in grape seed extracts are thought to help maintain
normal blood capillary function through their antioxidant, freeradical
scavenging activity. In addition, the procyanidins inhibit the
enzymes involved in the degradation of collagen, elastin, and hyaluronic
acid, the main structural components of the matrix that surrounds
the capillaries. Capillaries are the small blood vessels that
allow for the exchange of fluid, nutrients, and blood cells between the
blood and surrounding tissues. An increase in the permeability of
the capillaries leads to an increase in fluid and blood cells in the tissues
surrounding the capillaries. This decrease in capillary resistance,
also called capillary fragility, can cause bleeding under the
skin (purpura) sometimes observed as pinpoint black and blue spots
(Dartenuc, Marache, and Choussat, 1980).
Chronic venous insufficiency is a term applied to a syndrome resulting
from insufficient circulation to the legs and feet. Symptoms
can include edema, bluish discoloration of the skin, and ultimately ulcers.
Treatment can include elastic support stockings, drugs, or surgery
(Schulz, Hänsel, and Tyler, 2001).
The circulatory system supports vision through the capillaries that
deliver blood to the retina of the eye. The effect of grape seed extracts
on recovery of vision after exposure to strong light or glare has been
tested in a few studies. The procyanidins are thought to assist in the
regeneration of rhodopsin, a visual pigment depleted by glare (Corbe,
Boissin, and Siou, 1988).
Chronic Venous Insufficiency
Three good-quality trials focused on the effect of Endotelon on venous
insufficiency in the legs. A large, placebo-controlled study, including
357 subjects with venous insufficiency in the legs, reported
improvement in a clinical symptom composite score consisting of
heaviness or fatigue, itching (paresthesia), nocturnal leg cramps, leg
agitation, and subjective edema. A benefit compared to placebo was
observed following administration of 300 mg per day for two months,
and increased benefit when treatment was extended for three months
(Henriet, 1988). A smaller study, with 50 participants, compared the
effects of 150 mg Endotelon to 450 mg Diosmine (a semisynthetic
bioflavonoid) for one month. Endotelon appeared to benefit patients
sooner (at day 9 compared to day 14) and to be more effective than
Diosmine (Delacroix, 1981). This study would have been strengthened
by the addition of a placebo group. A placebo-controlled trial,
also with 50 patients diagnosed with venous insufficiency, showed
significant benefit compared to placebo following treatment with 150
mg per day for 45 days. The trial used thermography (the use of heat
to assess circulation) and rheography (the use of electrical impedance
to measure blood volume) measurements as end points. Both measurements
indicated statistical improvements in arterial and venous
tone with treatment compared to placebo (Paitel, 1981).
Capillary Fragility
Three poorly described, small, placebo-controlled trials explored
the effect of Endotelon on vascular resistance. One trial included 25
subjects with either hypertension or diabetes, and used a dose of 150
mg per day for one to three months. It reported a trend toward increasing
capillary resistance (from 14.6 to 18.0 cmHg as measured using a
capillarodynamometer) with treatment and no change with placebo
(Lagrue, Olivier-Martin, and Grillot, 1981). Another trial included 37
subjects with capillary fragility who were given a dose of 100 mg
grape seed extract or placebo per day for 15 days. The Endotelon
group showed greater improvement than the placebo group, as measured
using an angiosterrometer. The fact that some subjects had normal
capillary resistance to begin with, along with other inadequacies
in the methodology, meant the possible benefit of treatment was not
determined by this study (Dartenuc, Marache, and Choussat, 1980).
The third trial included two sets of subjects: patients with venous insufficiency
and healthy subjects who took aspirin to experimentally
induce a reduction in capillary resistance. Both sets of participants
were given either 150 mg Endotelon per day or placebo for one
month. The authors reported improvement in both sets of participants
following treatment with Endotelon compared with placebo (Dubos,
Durst, and Hugonot, 1980). However, the number of subjects was
judged too small, 30 in total, by our reviewer, Dr. Mary Hardy, for
such a complex four-part design.
Postoperative Edema
A rather unique study explored the effect of Endotelon on postoperative
edema caused by face-lift operations. Treatment was 300
mg per day for five days before surgery and for five days after surgery.
The postoperative edema resolved more quickly in the treatment
group (11.4 days) compared with the placebo group (15.8
days), according to the subjective evaluation of the physician. The
volume of the edema did not differ in the two groups (Baruch, 1984).
Vision
A trial with 95 subjects without any major retinal or ophthalmological
pathology studied the effect of Endotelon on visual contrast
sensitivity. The trial was designed to imitate exposure to glare
from video display units or traffic headlights while driving. Subjects
received either 200 mg per day or nothing for five weeks. Visual recovery
from glare, both general retinal glare and night vision glare, as
a function of time, was significantly better in the treatment group
compared to the baseline and the control group (Corbe, Boissin, and
Siou, 1988).
Antioxidant Activity
A small, placebo-controlled trial including a total of 20 healthy
young students measured antioxidant activity in the plasma following
one dose of 300 mg of LeucoSelect-phytosome or placebo and again
after five days of treatment. After one dose of grape seed extract, the
antioxidant activity in the serum of subjects increased for a period of
30 minutes to three hours. No effectwas observed following administration
of placebo. Similar results were obtained following five days
of treatment (Nuttall et al., 1998).
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