Lamm_editQ8_Layout 1 27/08/2009 17:07 Page 71
Prelox
®
for Improvement of Erectile Quality
release neuronal NO from neuronal NOS (nNOS). Within the smooth- plethysmography, in response to infusion of increasing amounts
muscle cells of arteries the NO activates guanylate cyclase, which of acetylcholine. Corresponding controls employing administration of
catalyses the breakdown of guanosine triphosphate (GTP) into 3’5’- NG–monomethyl–L-arginine, an eNOS inhibitor, completely abolished
cyclic guanosine monophosphate (cGMP). the Pycnogenol-induced augmented forearm blood flow response to
acetylcholine. These investigations in healthy volunteers conform
cGMP plays a key role as second messenger for releasing smooth- to earlier studies carried out in isolated arteries ex vivo.
12
The exact
muscle constriction and increasing arterial blood flow to engorge the molecular effects of Pycnogenol and its metabolites on eNOS are the
penis. This is facilitated by activation of protein kinase G for subject of extensive investigation. In theory, antioxidants may extend
phosphorylation of potassium channels, causing K
+
outflow and, the half-life of NO by preventing the oxidation of NO to inactive nitrite
subsequently, decreased intracellular Ca
2+
. Physiologically, intracellular and nitrate.
13
This possibility was ruled out in experiments with isolated
Ca
2+
regulates cavernous capillary smooth-muscle constriction to aortic rings ex vivo, where the presence of superoxide dismutase
maintain flaccidity. The depletion of smooth-muscle Ca
2+
lowers significantly altered Pycnogenol-induced vasorelaxation.
12
The acute
actin–myosin interaction (relaxation) and, consequently, leads to release of aortic constriction, induced by adrenaline or noradrenaline
vasodilatation. This process is counteracted by the enzyme (epinephrine or norepinephrine), within 10 minutes after Pycnogenol
phosphodiesterase (PDE), which breaks down cGMP into inactive presence suggests a catalytic activity on eNOS for enhanced NO
5’ guanosine monophosphate (5-GMP). There are several PDE isoforms synthesis. However, current in vitro investigations of possible
present in the corpus cavernosum, with PDE5 being the most mechanisms of Pycnogenol effects point to an upregulation of NOS
abundant.
4
While the impaired ability of the endothelium to generate expression (Petra Högger, University of Würzburg, Germany; personal
sufficient quantities of NO represents the pathophysiological reason for communication). Detailed investigations of the molecular interactions
men’s declining erectile quality, the temporary inhibition of PDE5 of Pycnogenol–L-arginine combinations related to synergetic activities
represents the pharmacological leverage for its compensation. An for NO synthesis are currently ongoing.
attempt to reinstate healthy endothelial function would help restore
natural erectile function. Synergistic effects of the enzyme substrate L-arginine and Pycnogenol
catalytic activity for eNOS are indeed expected to significantly elevate
Prelox
®
NO synthesis. While the detail of what happens on a cellular level
Pharmacology and Rationale should be revealed in the near future, exploratory human studies have
Prelox
®
is a registered trademark of Horphag Research Ltd for a demonstrated a synergistic effect of Pycnogenol and L-arginine
patented proprietary blend of French maritime pine extract aspartate for increased eNOS activity in sperm lysate.
14
Sperm
Pycnogenol
®
and L-arginine aspartate (US patent 6,565,851 B2). Prelox specimens were collected from men with moderate ED participating in
was developed to improve NO synthesis and, consequently, erectile a clinical trial before and after treatment with Prelox. Spermatozoa bear
quality in men. An erection vitally depends on the availability of both an NOS isoform whose activity can be measured subsequent to lysation
neuronal and endothelial NO; the nutritional components provided with by quantification of L-citrulline.
15
After Prelox consumption, sperm
Prelox facilitate the physiological processes involved. lysates synthesised almost twice as much citrulline as sperm lysates
from the same men before they took Prelox. The limitation of this
The amino acid L-arginine plays a key role in vasculature dynamics experiment is that it offered only circumstantial evidence for increased
because it represents the substrate for all NOS isoforms. Arginine NO synthesis, as it was demonstrated in other tissue.
supplementation is able to increase NO production despite
physiological concentrations exceeding saturation levels of NOS, a History of Development
phenomenon known as the ‘arginine paradox’.
5
In patients with A pilot trial investigated the effect of Pycnogenol in 21 subjects
diagnosed ED, dietary supplementation with L-arginine alone appears presenting with moderately high total cholesterol (average 5.41mmol/l)
to be effective for improving the condition, provided the dosage and and mild to moderate ED as judged by the erectile domain of the
intake duration are sufficient. One group in a double-blind, placebo- International Index of Erectile Function (IIEF-5).
16
The daily consumption
controlled trial found significant improvements with 5g L-arginine per of 120mg Pycnogenol steadily increased men’s IIEF-5 score from one
day over a period of six weeks.
6
Another group found in a double-blind, month to another. Starting from a baseline of 12.6/25, the values
placebo-controlled, cross-over study that 1.5g L-arginine a day for reached 13.8, 14.6 and 16.8 following one, two and three months of
17 days was ineffective.
7
Experiments with isolated human corpus treatment, respectively.
17
Erectile function values improved from
cavernosum leave little doubt that L-arginine evokes detectable ‘moderate’ to ’mild’ ED after three months, and at this time reached
corpus cavernosum relaxation proportional to concentration and time.
8
statistical significance compared with a placebo-treated group. After
discontinuation for one month the IIEF score decreased again to 14.5.
Pycnogenol consists of phenolic substances chemically classified as This study showed that Pycnogenol alone may improve erectile quality,
flavonoids: phenolic acids resembling benzoic acid and cinnamic acid most likely due to improved endothelial function, provided the
derivatives, taxifolin and procyanidins, condensed catechin and treatment duration is sufficient.
epicatechin moieties of variable chain length (n=2–12).
9
Pycnogenol is
standardized to contain 65±5% procyanidins, as detailed in the United The validation of the concept of Prelox displaying synergistic effects of
States Pharmacopoeia.
10
Human pharmacological studies have Pycnogenol and L-arginine aspartate was shown by testing the
demonstrated that Pycnogenol stimulates endothelium-dependant components individually and then acting in concert
18
in a group of 40
vasodilatation in a double-blind, randomised, placebo- and active-drug- men with confirmed functional ED to the extent that they were unable
controlled study.
11
Healthy students consuming Pycnogenol over a to achieve adequate erections sufficient for vaginal penetration or
period of two weeks showed a faster and more pronounced relaxation completion of successful intercourse. For a period of one month, they
of forearm arteries, measured by forearm blood flow by means of were given a daily dosage of 3g L-arginine aspartate, which corresponds
EUROPEAN ENDOCRINOLOGY 71
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87