pycnogenol side effects, pycnogenol benefits              September 4, 2011
pycnogenol reviews, dosage
pycnogenol benefits

scientists found that  pycnogenol had anti-inflammatory and immunosuppressive activities, as pycnogenol
showed inhibitory effects on the expression of the proinflammatory cytokine IL-1 by regulating redox-sensitive
transcription factors. [1]

Pycnogenol benefits - of ANTI-OXIDATIVE ACTIVITIES Pycnogenol was found to have strong free
radical-scavenging activities against reactive oxygen and nitrogen species.  [2] In a study,  pycnogenol
prevented vascular endothelial cells from injury induced by an organic oxidant t-butyl hydroperoxide and
inhibited macrophage oxidative burst, plasma low density lipoprotein (LDL) oxidation, and hydroxyl
radical-induced plasmid DNA damage. [3] When, pycnogenol was added to cigarette filters and free radicals
were found to be depleted in a dose dependent manner. [4]A significant increase in oxygen radical
absorbance capacity (ORAC) was observed in plasma throughout a pycnogenol supplementation period. The
average melasma area of 30 patients was found decreased by 25.86 +/- 20.39 mm and the average
pigmentary intensity decreased by 0.47 +/- 0.51 unit after pycnogenol supplementation (25 mg, 3 times a
day) for 30 days. The general effective rate was 80%. [5]  Pycnogenol chewing gums significantly reduced
gingival bleeding and led to no increases in plaque accumulation in a double-blinded study. [6] Actually, most
of pycnogenol benefits found are related to its anti-inflammatory and anti-oxidant activities.

Pycnogenol benefits - on SYSTEMIC LUPUS ERYTHEMATOSUS Pycnogenol treatment reduced the
reactive oxygen species production, apoptosis, p56(lck) specific activity and erythrocyte sedimentation rate
and improved SLE disease activity index in systemic lupus erythematosus (SLS). [7]

Pycnogenol benefits - on ASTHMA Asthma is considered as a chronic inflammatory process. Because of
pycnogenol's anti-oxidant and anti-inflammatory activities, it may have benefits on asthma.

In a study, patients were assigned to receive either 1 mg/lb/day (maximum 200 mg/day) Pycnogenol or
placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks.
All 22 patients responded favorably to Pycnogenol in contrast to placebo. Pycnogenol also significantly
reduced serum leukotrienes. [8]

In an another study, pycnogenol significantly improved pulmonary functions and asthma symptoms in 60
subjects aged 6-18 years old, suffered from mild-to-moderate asthma. The subjects were able to reduce or
discontinue their use of rescue inhalers more often than the placebo group. There was also a significant
reduction of urinary leukotrienes in the Pycnogenol group [9].

Pycnogenol benefits - on CANCER / TUMOR Concentrations of Pycnogenol of 0.05-0.2% was applied to
the irradiated dorsal skin of kh:hr hairless mice immediately after exposure resulted in dose-dependent
reduction of the inflammatory sunburn reaction. Pycnogenol lotions applied postirradiation also reduced this
immunosuppression . Chronic exposure to UV on 5 days/week for 10 weeks induced skin tumors from 11
weeks in both control mice and in mice receiving daily applications of 0.05% Pycnogenol, but tumor
appearance was significantly delayed until 20 weeks in mice receiving 0.2% Pycnogenol. Consequently, they
concluded that topical Pycnogenol offered significant and dose-dependent protection from UV-induced acute
inflammation, immunosuppression and carcinogenesis, when applied to the skin after daily irradiation.[10]

A research group compared the response of human breast
cancer cells (MCF-7) and normal human
mammary cells (MCF-10) to apoptosis in the presence of pycnogenol. They plated out MCF-7 and MCF-10
cells in culture dishes and grown in medium containing
pycnogenol dosages of 0, 40, or 80 micrograms
pycnogenol/ml culture medium. They detected the apoptosis by morphology, chromatin condensation, nuclear
DNA fragmentation, DNA strand breakage or apoptotic bodies. They found that DNA fragmentation was
significantly higher in MCF-7 cells treated with pycnogenol than the untreated cells while pycnogenol did not
significantly alter the number of apoptotic cells in MCF-10 samples. In conclusion, pycnogenol selectively
induced death in human mammary cancer cells (MCF-7) and not in normal human mammary MCF-10 cells.

In a mice study, found that pycnogenol was found to have no antagonizing effect on the anticancer activity of
doxorubicin and cyclophosphamide. Pycnogenol possesses a protective effect on the cardiotoxicity of
doxorubicin and the inhibition of thymus DNA synthesis induced by cyclophosphamide in mice.  [12]

Pyconogenol is a strong anti-oxidant; it may also benefit on  conditions such as thrombosis, platelet
aggregation and  retinopathy.

In a study,  pycnogenol inhibited NF-kappa B activation, VCAM-1 and ICAM-1 expression. Thus, pycnogenol
might play an important role in halting or preventing the atherogenic process. [13]

In another study, 211 subjects at moderate to high-risk of deep venous thrombosis was given with
pycnogenol dosage of 200 mg 2-3 hours before a long-haul flight and another 200 mg pycnogenol 6 hours
later. Five thrombotic events happened in the control group but not in pycnogenol group. [14]

Forty patients with diagnosed CVI were treated  with 360 mg pycnogenol per day over 4 weeks. A significantly
reduction of the circumference of the lower limbs and significantly improved subjective symptoms (e.g. pain,
cramps, night-time swelling, feeling of "heaviness", and reddening of the skin) and a significant decrease in
cholesterol and LDL values in the blood were observed, whereas HDL remained unaffected. [15]

In a double-blind study involving 20 patients randomly treated with placebo or pycnogenol (
dosage of 100
mg 2 3/day for 2 months) and another open study, in which 20 patients treated with pycnogenol, pycnogenol
significantly improved the legs' heaviness and subcutaneous edema. Pycnogenol also reduced the venous
pressure. Pycnogenol may be a preventive measure for CVI or related veno-capillary disturbances. [15]

In another study, researchers found that cigarette smoking increased heart rate and blood pressure and this
increases could not be prevented by pycnogenol or aspirin consumption just before smoking. However,  
increased platelet reactivity yielding aggregation 2 hours after smoking could be prevented by 500 mg aspirin
or 100 mg pycnogenol from a study of 22 German heavy smokers. Similar findings was also obtained from
another group of 16 American smokers. [16]  While, another group showed that a single dose of pycnogenol
reduced platelet aggregation in cigarette smokers in a dose-response fashion. [17]

Pycnogenol benefits - on RETINOPATHY
Schonlau F and Rohdewald P., Westfalische Wilhelms Universitat, Germany, consider that diabetic
retinopathy represents a serious health threat to a rapidly growing number of patients with diabetes mellitus.
The retinopathy is characterized with vascular lesions with exudate deposits and haemorrhages. And, the
patients may have vision loss. They also consider that pycnogenol is known to increase capillary resistance.
They reviewed couples of old study reports in French and German and found that Pycnogenol retains
progression of retinopathy and partly recovers visual acuity. Pycnogenol was shown to improve capillary
resistance and reduce leakages into the retina. [18]

Spadea L and Balestrazzi E., Cattedra di Clinica Oculistica, Italy, recruited 20 patients in a double-blind study
randomly treated with placebo or Pycnogenol (
dosage 50 mg x 3/day for 2 months) and another 20 patients
in a open study treated with Pycnogenol at the same dose schedule. They found a beneficial effect of
Pycnogenol on the progression of retinopathy. With placebo, the retinopathy progressively worsened and the
visual acuity significantly decreased. With pycnogenol-treatment, the retinal function stopped to deteriorate
and visual acuity significantly recovered. They both thought that the mechanism might be related to its free
radical (FR) scavenging, anti-inflammatory and capillary protective activities. They considered that
pycnogenol might bind to the blood vessel wall proteins and mucopolysaccharides and produce a capillary
'sealing' effect, leading to a reduced capillary permeability and oedema formation. [19]

Peng QL et al, Loma Linda University, CA, investigated the effect of pycnogenol on Abeta(25-35)-induced
apoptosis and ROS generation using a rat pheochromocytoma (PC12) cell line. They demonstrated
Abeta(25-35)-induced apoptosis in PC12 cells by: (1) a dose-dependent loss of cell viability; (2) a time- and
dose-dependent increase in the apoptotic cells; (3) an induction of DNA fragmentation; and (4) an increase in
caspase-3 activity and cleavage of poly (ADP-ribose) polymerase (PARP). They found a (1) significant
increase in ROS formation preceded apoptotic events after exposuring PC12 cells to Abeta(25-35)and (2)
PYC not only suppressed the generation of ROS but also attenuated caspase-3 activation, DNA
fragmentation, PARP cleavage, and eventually protected against Abeta-induced apoptosis. They also
demonstrated that Vitamin E also suppressed cell death and caspase-3 activation induced by Abeta(25-35).
Consequently, they concluded that (1) ROS might be involved in Abeta-induced apoptosis in PC12 cells and
(2) pycnogenol reduced apoptosis, possibly by decreasing free radical generation in PC12 cells [20]

Pycnogenol benefits - on ALZHEIMER'S DISEASE
Alzheimer's disease (AD) is characterized with senile plaques, cerebrovascular beta-amyloidosis,
neurofibrillary tangles, and selective neuronal loss. Beta-amyloid (Abeta) is believed to cause vascular
damage mediated by generation of reactive oxygen species and this damage is considered an early event in
the development of AD.

Liu F et al, Loma Linda University, CA, exposed pulmonary artery endothelial cells (PAEC) to Abeta for 24 h.
They assessed the cell injury by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by
determining the release of intracellular lactate dehydrogenase (LDH). They exposed PAEC to Abeta resulted
in a decrease in cell viability, an increase of LDH release. However, they pre-incubated PAEC with
pycnogenol, they prevented these changes significantly. The data suggest that pycnogenol may be useful for
the prevention and/or treatment of vascular or neurodegenerative diseases associated with Abeta toxicity. [20]

Kobayashi et al, University of California, Berkeley , have shown  that antioxidant therapy was beneficial to
neurological disorders including Alzheimer's disease and cerebral ischemia. Glutamate-induced cytotoxicity in
HT-4 neuronal cells was due to oxidative stress caused by depletion of cellular glutathione (GSH).  
Consequently, they demonstrated that a wide variety of antioxidants inhibit glutamate-induced cytotoxicity in
HT-4 neuronal cells. They found that low concentrations of alpha-tocopherol and its analogs were highly
effective in protecting neuronal cells against cytotoxicity. Purified flavonoids and herbal extracts of Gingko
biloba and pycnogenol were also effective. [21].

Pycnogenol benefits - ON CHOLESTEROL PROFILE
Devaraj S et al, University of California, Davis, tested the effect of Pycnogenol supplementation on measures
of oxidative stress and the lipid profile in humans. And, they found that a significant increase in oxygen radical
absorbance capacity (ORAC) in plasma throughout the supplementation period and the ORAC value returned
to baseline after the 4-wk washout period. They also found that Pycnogenol significantly reduced
LDL-cholesterol levels and increased HDL-
cholesterol levels in plasma of two-thirds of the subjects. [22].

Koch R, Wolfsschlucht 6a, 34117 Kassel, Germany , conducted an open, controlled comparative study 40
patients with diagnosed CVI were treated with a
dosage of 360 mg pycnogenol per day over a period of 4
weeks. He found a significantly reduction of the circumference of the lower limbs and significantly improved
subjective symptoms (e.g. pain, cramps, night-time swelling, feeling of "heaviness", and reddening of the skin)
and a significant decrease in cholesterol and LDL values in the blood, whereas HDL remained unaffected. [23]

Hasegawa N, Nagoya Bunri College, Japan, found that pycnogenol inhibited the expression of
glycerophosphate dehydrogenase. Consequently, he considered pycnogenol inhibits the accumulation of lipid
droplets in adipose tissue. [24]

Pycnogenol also significantly reduced LDL-cholesterol levels and increased HDL-cholesterol levels in plasma
of two-thirds of the human subjects. [25]

pycnogenol benefits - ON DIABETES
Researchers in Kenya found that pycnogenol treatment significantly reduced blood glucose concentrations in
diabetic rats. Elevated hepatic catalase activity in
diabetic rats was restored to normal levels after pycnogenol
treatment [26]

Maritim A et al, Moi University Faculty of Health Sciences, Kenya demonstrated pycnogenol treatment
significantly reduced blood glucose concentrations in diabetic rats. [27]

Liu X et al, Guang An Men Hospital of Chinese Medical Science Research Institute, Beijing, PR China
conducted a double-blind, placebo-controlled, randomized, multi-center study was performed with 77 diabetes
type II patients to investigate anti-diabetic effects of the French maritime pine bark extract, Pynogenol. They
found that supplementation with
dosage of 100 mg Pycnogenol for 12 weeks, during which a standard
anti-diabetic treatment was continued, significantly lowered plasma glucose levels as compared to placebo.
And, it also improved endothelial function. [28]

Pycnogenol benefits - on ERECTILE DYSFUNCTION
Relaxation of the cavernous smooth muscle is required for penile erection, while nitric oxide triggers such
relaxation. Stanislavov R and Nikolova V. Seminological Laboratory SBALAG, Bulgaria, investigated the
possibility of overcoming
erectile dysfunction (ED) by increasing the amounts of endogenous NO.

Pyconogenol is known to increase production of NO by nitric oxide syntase together with L-arginine as
substrate for this enzyme. They orally administered 40 men, aged 25-45 years, with pycnogenol and
L-arginine. They found that treatment with a combination of L-arginine and Pycnogenol for the following
month increased the number of men with restored sexual ability to 80%. And, 92.5% of the men experienced a
normal erection, after the third month of treatment. They concluded that oral administration of L-arginine in
combination with Pycnogenol causes a significant improvement in sexual function in men with ED. [29]

Pycnogenol benefits - on SPERM QUALITY AND FUNCTION
Roseff SJ, West Essex Center for Advanced Reproductive Endocrinology, NJ, found that the mean sperm
morphology following Ham's F-10 capacitation increased by 38% following a pycnogenol treatment (
200 mg daily for 90 days) to 19 subfertile men, and the mannose receptor binding assay scores improved by
19%. [30]

Blazso G et al, University of Szeged, Hungary, applied pycnogenol to experimental wounds inflicted on healthy
rats by means of a branding iron. They found that 1% Pycnogenol significantly shortened the wound healing
time as well as the diameter of the scars. And, the wound healing time was found to be dose-dependent. [31]

Pycnogenol benefits - on DYSMENORRHEA
Kohama T et al, Keiju Medical Center, Japan, treated 47 patients with menstrual pain, aged 21-45 years, with
Pycnogenol at
dosage of 30 mg (2 capsules) orally twice a dysmenorrl day. The administration of
Pycnogenol began on the eighth day of the first menstrual cycle and continued until the seventh day of the
third menstrual cycle. They found that treatment with Pycnogenol lowered the pain scores for abdominal pain
significantly (p < 0.05) as compared to pretreatment values and continuation of treatment during the second
cycle produced significant pain relief (p < 0.01). [32]

Pycnogenol benefits - on AGING
Buz'Zard AR et al, Loma Linda University, CA, established an in vitro model using genetically-engineered
keratinocytes to screen natural compounds for the ability to stimulate HGH secretion. They found that a
combination of equal amounts of L-arginine and L-lysine, aged garlic extract (Kyolic), S-allyl cysteine and
Pycnogenol significantly increased secretion of HGH in this in vitro model. [33]

Probably, pycnogenol is safe with limited or no side effect. Studies reported no side effects of pycnogenol
include [1] using pycnogenol for 40 men suffered from erectile dysfunction for 3 months [34] [2] using
pycnogenol for patients patients suffered from chronic venous insufficiency. [35] [3] using pycnogenol for 30
women suffered from melasma. [37]

In a study of using pycnogenol for patients with diabetic retinopathy, the side effect was found to be mild and
it was confined to gastric discomfort. [36] While in another study of 58 patients suffered from hypertension
(hight blood pressure),  the
side effects included gastrointestinal problems, vertigo, headache and nausea.
Pycnogenol is getting popular in the last year. Research scientists consider pyconogenol as a strong
anti-oxidant  It may also provide  benefits for various conditions . Consult with your doctor, before using any
Pycnogenol is primarily
composed of procyanidins
and phenolic acids.
Procyanidins are
biopolymers of catechin and
epicatechin while the
phenolic acids are
derivatives of benzoic and
cinnamic acids.
[Int J Clin
Pharmacol Ther. 2002
The transcriptional regulatory
protein nuclear factor kappa B

(NF-kappa B)
participates in the
control of gene expression of
many modulators of inflammatory
and immune responses,
including vascular cell adhesion
(VCAM-1) and
intercellular adhesion molecule-1

The heightened
expression of these adhesion
molecules is known to be
important in atherosclerosis,
inflammation, ischemic vascular
disorders, diabetes, and cancer
Pcynogenol Reviews - health benefits and side effects Pycnogenol is an extract from the bark of French Maritime Pine trees
that grow in the Landes Forest of southwestern France. Pycnogenol contains concentrated levels of unique flavonoid compounds.
Studies have shown that these compounds may have benefits on  inflammation, asthma, cancer (tumor), vascular disorders,
retinopathy, Alzheimer's disease, diabetes, cholesterol, erectile dysfunction, sperm quality, wound healing, dymenorrhea and aging.
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