Pycnogenol for Cardiovascular Health

Cardiovascular Health

L O O K , F E E L A N D L I V E B E T T E R

2I Horphag Research-Geneva, Switzerland I Horphag Research Asia-Shanghai, China I Natural Health Science-Hoboken NJ, USA I www.pycnogenol.com I ©HORPHAG I

Pycnogenol® restores healthy endothelial functionThe common denominator of most cardiovascular risk

factors is the inability of a blood vessel to generate the

most important vascular mediator: nitric oxide (NO).

Nitric oxide is continuously synthesized by cells lining

blood vessel walls (endothelial cells). The NO mole-

cules diffuse out of the blood vessel and interact with

a specific receptor on arterial smooth muscle causing

relaxation and consequently an increased vessel diam-

eter. This then facilitates better blood perfusion and

normalizes blood pressure. Nitric oxide also acts on

blood cells. A specific interaction with platelets causes

these to be less activated, less “sticky” and thus low-

ers platelet aggregation.

In hypertension, atherosclerosis, diabetes and also

gradually with increasing age, the synthesis of nitric

oxide from the endothelium declines. This results in

blood vessel constriction which impairs blood flow

and increased “stickiness” of platelets which elevates

the risk for thrombosis.

Pycnogenol® acts as a catalyst on the enzymes in

the endothelium which synthesizes nitric oxide. In

presence of Pycnogenol® the endothelial nitric oxide

synthase more efficiently generates nitric oxide from

the precursor amino acid L-arginine [Fitzpatrick et al.,

1998].

The increased generation of nitric oxide with

Pycnogenol® translates into a broad range of cardio-

vascular health benefits [Watson 2003].

Pycnogenol® improves blood fl ow Microscopical evaluation of capillaries at the root of

the finger nails showed that consumption of 60 mg

Pycnogenol® per day for 4 weeks significantly di-

lates these vessels and improves the micro-circulation

[Kohama, 2004]. After discontinuation of Pycnogenol®

the improved micro-circulation persists for up to 4

weeks. When Pycnogenol® tablets were chewed an

increased blood micro-circulation was noticeable in

78% of the subjects already after 15 minutes.

The majority of ailments involve insufficient vascular functions in one way or the other. The delivery of oxygen and nutrients to every part of the body is vital and just minor impairment can strain energy, metabolism and may result in flawed concentration and well-being. Vascular functions typically decline slowly and silently as we age. Blood pressure, blood glucose and atherosclerosis develop largely unnoticed and during the time until diagnosis cause irreversible damage to the vascular system.

A healthy life style involving more physical activity and dietary interventions can significantly defy cardio-vascular risk factors. A plethora of clinical research demonstrates that Pycnogenol® is highly effective for keeping blood vessels in good shape and keeping cardiovascular health problems at bay.

Pycnogenol® for Cardiovascular Health


Investigation of Pycnogenol® on endothelium depen-

dent vaso-relaxation and blood flow was investigated

in 16 young healthy volunteers in a double blind,

placebo controlled study [Nishioka et al., 2007]. En-

dothelium mediated vaso-relaxation was initiated by

intra-venous infusion of increasing amounts of acetyl-

choline, a neurotransmitter which stimulates enhanced

synthesis of nitric oxide. The resulting forearm blood

flow was monitored by means of a plethysmograph.

After 2 weeks supplementation with Pycnogenol® the

acetylcholine-triggered vasorelaxation yielded an up

to 46% higher forearm blood flow than at baseline.

This effect was significant as compared to ineffective

placebo. When subjects were given an NO-synthase

inhibitor (NG-monomethyl-L-arginine) Pycnogenol®

had no effect, which demonstrates that Pycnogenol®

acts as catalyst for endothelial nitric oxide synthase

yielding elevated NO synthesis.

In certain pathologies such as diabetes an impaired

blood flow can cause significant health problems. In-

sufficient blood-microcirculation such as in diabetic

microangiopathy may cause tissue necrosis and open

wounds which very slow heaking process. Supple-

mentation with Pycnogenol® was shown to improve

blood circulation in diabetes and also improve the

healing of diabetic ulcers. For detailed information on

Pycnogenol® in diabetes please refer to “Pycnogenol®

for Diabetes”.

Pycnogenol® relieves high blood pressure Pycnogenol® acting as catalyst on endothelial nitric

oxide synthase results in arterial relaxation and conse-

quently helps to normalize elevated blood pressure.

Pycnogenol® was investigated in a double-blind, pla-

cebo-controlled, cross-over study with patients with

borderline hypertension, who were not yet receiving

anti-hypertensive medication. Pycnogenol® supple-

mentation over a period of 8 weeks significantly low-

ered blood systolic blood pressure as compared to

placebo. Diastolic pressure was found to be lowered

as well [Hosseini et al, 2001].

Pycnogenol® has further been tested in hypertensive

patients receiving treatment with calcium channel

blocker nifedipin (20 mg per day). One group of pa-

tients received Pycnogenol® in addition to nifedipine,

whereas the control group was administered placebo

in addition to the nifedipine regimen. Every two weeks

the individual nifedipine dosage was adjusted so that

a blood pressure below 130 mmHg was achieved. Al-

most 60% of the patients who supplemented with

Pycnogenol® were able to cut their prescribed medi-

cation dosage by half to keep their blood pressure in

a healthy range [Liu et al, 2004].

Moreover, Pycnogenol® was shown to significantly

improve impaired endothelial function in these indi-


withoutPycnogenol®

Increased i.v. infusion of acetylcholine

Forearm blood flow relative to baseline

+38%

+30%

+46%

Pycnogenol® stimulates endothelium-mediated vaso-relaxation

Pycnogenol®Placebo

baseline

systolic blood pressure

diastolic blood pressure

139.9

93.8 93.7

138.9

132.7

92.0

Pycnogenol® relieves high blood pressure (1)


viduals. Vaso-constrictory endothelin-1 was signifi-

cantly lowered, whereas vaso-dilatory NO and pros-

tacyclin were increased.

Pycnogenol® normalizes blood platelet activityWhereas hypertension, atherosclerosis and diabetes

contribute to progressive damage of blood vessel

walls, the acute problems occurring during thrombo-

sis and heart attack result from aggregating blood

platelets. The damage to blood vessel walls also man-

ifests in lowered nitric oxide synthesis. The absence of

nitric oxide favors activation of platelets which then

tend to form aggregates.

When platelets recognize a pathologically altered ves-

sel wall as injured the development of a clot is trig-

gered. The resulting thrombus may cause clogging of

blood vessels (embolism) and subsequently interrupt

the blood flow to certain areas of the body. This may

be life-threatening when a blood clot obstructs arter-

ies of the lung, disabling vital oxygen uptake (pul-

monary embolism). When arteries supporting heart

muscle (coronaries) are affected, oxygen supply is in-

terrupted causing myocardial infarction.

By virtue of increasing the production of endothelial

nitric oxide, Pycnogenol® significantly lowers the ac-

tivity of blood platelets. NO is the natural body-own

messenger molecule to release increased platelet ac-

tivity.

Pycnogenol® was shown to dose-dependently lower

platelet activity in individuals typically presenting with

increased platelet activity: cigarette smokers. Blood

was drawn before and 2 hours after administration of

a single Pycnogenol® dose. The results clearly showed

a dose-dependent reduction of platelet activity. Al-

ready the lowest dose of 25 mg significantly lowered

blood platelet “stickiness” [Pütter et al., 1999].

Pycnogenol® was shown to be as effective for con-

trolling platelet activity as aspirin in these experi-

ments [Pütter et al., 1998]. Moreover, Pycnogenol®

was found not to increase bleeding time, an ef-

fect which is well known in case of aspirin, which

significantly prolongs bleeding. The application of

Pycnogenol® for regulation of platelet function is pat-

ented (US 5,720,956).

Pycnogenol® was tested in a group of 200 high-risk

individuals for developing thrombosis [Belcaro et al.,

2004]. Subjects were remaining in sedentary position

for prolonged time during long-haul travel exceeding

8 hours. These conditions are known to cause pool-

ing of venous blood in the legs which contributes to

the development of thrombosis. The result showed 5

incidents of thrombosis in the 97 subjects (5.15 %)


Continued initial nifedipine dosage

Lowered nifedipinedosage to 3 tablets

Require only half theinitial nifedipine doses

21%

22%

57%

Pycnogenol® relieves high blood pressure (2)

Baseline 25mg150mg

50mg 100mg200mg

Pycnogenol®:

elevated plateletactivity

Single Pycnogenol® dose

healthy plateletactivity

Pycnogenol® inhibits platelet aggregation


in the placebo group. In contrast, none of the 101

high-risk subjects in the Pycnogenol®-treated group

developed thrombosis during the long-haul flight.

Placebo Pycnogenol®

Number of passengers 97 101

Superficial vein thrombosis 1 0

Deep vein thrombosis 4 0

Thrombosis frequency 5.51% 0%

Pycnogenol® improves blood lipid profi lePycnogenol® was found in three clinical trials to lower

LDL cholesterol and increase HDL. A significantly im-

proved blood lipid profile was initially discovered in

young healthy subjects [Devaraj et al, 2002].

Supplementation with Pycnogenol® for 6 weeks sig-

nificantly increased HDL and lowered LDL cholesterol.

A follow-up measurement 4 weeks after discontinu-

ation of Pycnogenol® showed that LDL returned to

baseline values whereas HDL largely remained un-

changed. No effect on total triglycerides was found.

In men with mild hypercholesterolemia supplementa-

tion with Pycnogenol® over a period of three months

statistical significantly lowered both total cholesterol

and LDL by 9.4% and 16%, respectively [Durackova

et al., 2003].

A large scale double-blind, placebo-controlled clini-

cal trial with 200 peri-menopausal women showed

a significant decrease of LDL as compared to base-

line as well as ineffective placebo by 9.9% [Liao et

al., 2007]. HDL cholesterol increased significantly by

4.6% during the 6 months treatment period. No ef-

fect on total triglycerides was found.


HDLLDL

baseline Pycnogenol®(3 months)

Pycnogenol®(6 months)

blood lipidprofile

111 mg/dL

44.7 mg/dL

46.8 mg/dL

+4.6%45.3 mg/dL

100 mg/dL

-5.5% -9.9%

105 mg/dL

Pycnogenol® improves blood lipid profile (2)

HDLLDL

baseline Pycnogenol®(6 weeks)

discontinued(4 weeks)

blood lipidprofile 104 mg/dL

48 mg/dL

54 mg/dL

53 mg/dL

104 mg/dL

-7%

+10%

97 mg/dL

Pycnogenol® improves blood lipid profile (1)


Thus, Pycnogenol® significantly improves the athero-

sclerotic index and thus helps prevent the onset of

cholesterol deposits in arteries.

Pycnogenol® strengthens capillary wallsPycnogenol® stabilizes capillary walls by interaction

with the collagen scaffolding [Rohdewald, 2002].

This renders blood vessels more resistant to mechani-

cal rupture and significantly decreases capillary filtra-

tion. The decreased capillary wall permeability was

shown to be highly effective for edema. Several clini-

cal trials have demonstrated that Pycnogenol® po-

tently improves chronic venous insufficiency by de-

creasing edema and alleviating associated symptoms

[Cesarone et al., 2006]. For detailed information

please refer to “Pycnogenol® for venous problems”.

Pycnogenol® was shown to help against retinal bleed-

ings in diabetic retinopathy. In five clinical trials with

in total more than 1200 patients Pycnogenol® was

found to stop progression of retinopathy [Schönlau

et al., 2002]. For more information please refer to

“Pycnogenol® for eye health”.

Pycnogenol® offers a safe nutritional approach to address all major cardio-vascular risk factors simultaneously.

Pycnogenol® improves the blood lipid profile with lowering of LDL cholesterol, lowers blood glucose in hyperglyce-

mia, normalizes elevated blood pressure and helps prevent thrombosis.

ReferencesBelcaro G, Cesarone MR, Ricci A, Ippolito E, et al. Prevention of venous thrombosis in long-haul flights with Pycnogenol®. Clin

Appl Thromb Hemost 10: 373-377, 2004.

Cesarone MR, Belcaro G, Rohdewald P, et al. Comparison of Pycnogenol® and Daflon in treating chronic venous insufficiency: a

prospective, controlled study. Clin Appl Thromb Hemost 12: 205-212, 2006.

Devaraj S, Vega-López S, Kaul N, et al. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxi-

dant capacity and alters the plasma lipoprotein profile. Lipids 37: 931-934, 2002.

Durackova Z, Trebaticky B, Novotny V, et al. Lipid metabolism and erectile function improvement by Pycnogenol®, extract from

the bark of Pinus pinaster in patients suffering from erectile dysfunction – a pilot study. Nutr Res 23: 1189-1198, 2003.

Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol®. J Cardiovas Pharmacol 32: 509-

515, 1998.


Hosseini S, Lee J, Sepulveda RT, Fagan T, et al. A Randomized, double blind, placebo controlled, prospective, 16 week cross-

over study to determine the role of Pycnogenol® in modifying blood pressure in mildly hypertensive patients. Nutr Res 21(9):

67-76, 2001.

Kohama T. Clinical applications of Pycnogenol® in Japan. Prog Med 24: 1503-1510, 2004.

Liao M-F, Yang H-M, Liao M-N, et al. A randomized, double-blind, placebo-controlled trial on the effect of Pycnogenol® on

the climacteric syndrome in peri-menopausal women. Acta Obstetricia Gynecologica Scandinavica, in print 2007.

Liu X, Wei J, Tan F, et al. Pycnogenol®, French maritime pine bark extract, improves endothelial function of hypertensive

patients. Life Sciences 74: 855-862, 2004.

Nishioka K, Hidaka T, Takemoto H, et al. Pycnogenol®, French maritime pine bark extract, augments endothelium-dependent

vasodilation in humans. Hypertension Research, in print 2007.

Pütter M, Grotemeyer KHM, Würthwein G, et al. Inhibition of smoking-induced platelet aggregation by Aspirin and

Pycnogenol®. Thromb Res 95: 155-161, 1999.

Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol®), a herbal medication with a diverse pharma-

cology. Int J Clin Pharmacol Ther 40(4): 158-168, 2002.

Schönlau F, Rohdewald P. Pycnogenol® for diabetic retinopathy. A review. Int Ophthal 24: 161-171, 2002.

Watson RR. Pycnogenol® and cardiovascular health. Review. Evidence Based Integr Med 1: 27-32, 2003.


Pycnogenol for Cardiovascular Health

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