pycnogenol benefits & side effects
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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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[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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