pycnogenol benefits & side effects
updated on May 1, 200      Zhion@zhion.com
HEALTH BENEFITS OF PYCNOGENOL, RESEARCH
FINDS

ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE ACTIVITIES
Korean 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]

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.

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]

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].

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 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. [11]

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.

VENOUS THROMBOSIS, THROMBOPHLEBITIS, PLATELET
AGGREGATION
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 200 mg pycnogenol 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 (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]

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 (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]

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].

CHOLESTEROL
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 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]

DIABETIC
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 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]

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]

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]

WOUND HEALING AND SCAR FORMATION
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]

DYSMENORRHEA
Kohama T et al, Keiju Medical Center, Japan, treated 47 patients with
menstrual pain, aged 21-45 years, with Pycnogenol at 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]

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]

PYCNOGENOL SIDE EFFECTS
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. [39]

                                               
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ALL RIGHTS RESERVED 2006 zhion. AUTHOR DOES NOT GUARANTEE THE
ACCURACY OF THE INFORMAITION. THIS ARTICLE IS FOR YOUR REFERENCE
ONLY. IF YOU HAVE ANY QUESTION, PLEASE, CONSULT YOUR DOCTOR. PLEASE,
NOTE THAT THE STUDIES HERE ARE LIMITED FOR EACH CONDITION. DOSAGE
DESIGN AND PURITY OF PYCONOGENOL OF COMMERCIAL PRODUCTSMAY BE
DIFFERENT FROM THOSE USED IN THE EXPERIMENTS.  Pyconogenol is a strong
anti-oxidant; it is expecteded to have benefits on other conditions such as
thrombosis, platelet aggregation and  retinopathy.

[1] Cho KJ et al,Toxicol Appl Pharmacol. 2000 Oct 1;168(1):64-71 [2] Packer L et
alFree Radic Biol Med. 1999 Sep;27(5-6):704-24 [3] Nelson AB et al, Loma Linda
University, Drug Dev Ind Pharm. 1998 Feb;24(2):139-44] [4] Zhang D et al
Academia Sinica, Beijing, Toxicol Ind Health. 2002 Jun;18(5):215-24] [5] Ni Z et
al,  China,Phytother Res. 2002 Sep;16(6):567-71.] 6] Kimbrough C et al, Loma
Linda University, CA, Phytomedicine. 2002 Jul;9(5):410-3][7] Stefanescu M et al,
Cantacuzino Institute, Romania, found thatPhytother Res. 2001
Dec;15(8):698-704. [8] Hosseini S et al, The University of Arizona, AZJ Med Food.
2001 Winter;4(4):201-209]. [9] Lau BH et al, Loma Linda University, CAJ Asthma.
2004;41(8):825-32.  [10] Sime S and Reeve VE., University of Sydney, Australia,
Photochem Photobiol. 2004 Feb;79(2):193-8. [[11] Huynh HT and Teel RW, Loma
Linda University, CAAnticancer Res. 2000 Jul-Aug;20(4):2417-20 [12] Feng WH et
al, Beijing, Phytomedicine. 2002 Jul;9(5):414-8] [13] Peng Q et al, Loma Linda
University, California,Cell Mol Life Sci. 2000 May;57(5):834-41 [14] Belcaro G et al,
L'Aquila University, Italy, Clin Appl Thromb Hemost. 2004 Oct;10(4):373-7] [15]
Koch R, Wolfsschlucht 6a, 34117 Kassel, Germany , Phytother Res. 2002 Mar;16
Suppl 1:S1-5. [15] Petrassi C et al, Universita degli Studi di L'Aquila, Italy,
Phytomedicine. 2000 Oct;7(5):383-8. [16] Putter M et al, Westfalische
Wilhelms-Universitat Munster, Germany Thromb Res. 1999 Aug 15;95(4):155-61
[17] [Araghi-Niknam et al, University of Arizona, AZ, Integr. Med.. 2000 Mar
21;2(2):73-77].[19] Phytother Res. 2001 May;15(3):219-23].[18]  [Int
Ophthalmol. 2001;24(3):161-71] [[20] [Brain Res Mol Brain Res. 2002 Jul
15;104(1):55-65] [21] Biol Pharm Bull. 2000 Jun;23(6):735-7][21] Free Radic
Res. 2000 Feb;32(2):115-24] [22] Lipids. 2002 Oct;37(10):931-4] [23] Phytother
Res. 2002 Mar;16 Suppl 1:S1-5][24] Phytother Res. 2000 Sep;14(6):472-3][25]
Devaraj S et al, University of California, Davis,Lipids. 2002 Oct;37(10):931-4] [26]
Maritim A et al, J Biochem Mol Toxicol. 2003;17(3):193-9][27]  [J Biochem Mol
Toxicol. 2003;17(3):193-9, Details in Section of Antioxidant Activity].[28]Life Sci.
2004 Oct 8;75(21):2505-13] [29] J Sex Marital Ther. 2003 May-Jun;29(3):207-13]
[30]  [J Reprod Med. 2002 Oct;47(10):821-4][31] [Phytother Res. 2004
Jul;18(7):579-81][32] J Reprod Med. 2004 Oct;49(10):828-32] [33] [Growth Horm
IGF Res. 2002 Feb;12(1):34-40] [34][Treatment of erectile dysfunction with
pycnogenol and L-arginine, J Sex Marital Ther. 2003 May-Jun;29(3):207-13]. [35]
[Pycnogenol in chronic venous insufficiency. Phytomedicine. 2000
oct;7(5):383-8.][36] [Pycnogenol for diabetic retinopathy. A review. Int
Ophthalmol. 2001;24(3):161-71] [37] [Phytother Res. 2002 Sep;
16(6):567-71.][39] Pycnogenol, French maritime pine bark extract, improves
endothelial function of hypertensive patients. Life Sci. 2004 Jan 2; 74(7):855-62].
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 supplements.
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 Apr;40(4):158-68].
VASCULAR
DISORDERS
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 molecule-1

(VCAM-1)
and
intercellular adhesion
molecule-1
(ICAM-1).
The heightened
expression of these
adhesion molecules is
known to be important
in atherosclerosis,
inflammation, ischemic
vascular disorders,
diabetes, and cancer
metastasis.
WHAT ARE THE HEALTH BENEFITS OF PYCNOGENOL? 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.
30 minutes walking is
already a good exercise.
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