PYCNOGENOL

Pycnogenol (trade name) describes "an entire class of bioflavanoids that are composed of polyphenols, or Proanthocyanidin complexes." The bioflavanoids may be extracted from pine bark, lemon tree bark, grape seeds, grape skins, or cranberries. (Hansen)

"To confuse matters more, use of the term `pycnogenol,' first coined in 1979 by J.A. Masquelier, as a generic term to describe proanthocyanidins has been trademarked by different corporate entities in different countries, leading to confusion. In the American market Pycnogenol is a registered trademark of a pine bark product derived from Pinus pinaster Ait. (usually referred by the obsolete name Pinus maritima Mill.)." (Tyler)

"However, pycnogenol has also been assigned to a group of flavonoids termed the flavan-3-ol derivatives. Numerous plants have been found to be sources for the class of compounds generally termed the flavonoids, and the chemical condensation of flavonoid precursors results in the formation of compounds known as condensed tannins. The broader term, bioflavonoid, has been used to designate those flavonoids with biologic activity." (Anonymous)

"Pycnogenol is absorbed into the bloodstream in about 20 minutes. Once absorbed, the maximum protective effect lasts about 72 hours. The protective effect begins to fall as it is excreted in the urine." (Passwater)

Pycnogenol has a recommended dosage of "20 mg [milligrams] per every 20 pounds of body weight, or approximately 150-200 mg [milligrams] per day." (Hansen)

History
"Pycnogenol was used in 1979 by Jacques Masquelier of the University of Bordeaux." (Hansen)

The extract from grape pips was patented in 1970. (Hansen)

Proponent / Advocate Claims 
"A US patent for this material describes a mixture of proanthocyanidins that are effective in combating the deleterious effects of free radicals. The compound is said ... to reduce tumor promotion..." (Anonymous)

"Anthocyanin and other flavonoids extracted from grape seeds are highly effective `scavengers' of harmful free radicals. The antioxidant components of grape seed extract seem particularly helpful in curbing free-radical damage (from peroxidation) which can alter fats and lipids (low-density lipoproteins) circulating in the bloodstream and embedded in cell membranes." (Diamond)

"Pycnogenol, as an antioxidant, has been shown to be 20 times more powerful than vitamin C and 50 times more powerful than vitamin E." (Pycnogenol/OPC) (Nutrition)

Pycnogenol is claimed to treat 60 free radical-related disorders including Alzheimer's, A105, cancer, hemorrhoids, and senility. (BC Cancer Agency)

"Pycnogenol has the capability to bond collagen fibers" and reverse tissue damage and injury. (Pycnogenol/OPC)

Proponents claim that Pycnogenol causes no adverse effects and can assist vitamin C to enter cells. (Passwater)

Toxicity / Risks

Proponents believe that Pycnogenol is non-mutagenic, non-carcinogenic and non-toxic. (Pycnogenol/OPC)

Research on proanthocyanidins has been ongoing in Europe for the past 20 years. The results of this research are very exciting, but unfortunately have gained little interest in the U.S. Recently, publicity for the results of the European research on plant extracts including those obtained from pine bark and grape seeds has increased in this country. For example, Morton Walker has published articles on pycnogenol in both Raum & Zeit¹ and the Townsend Newsletter for Doctors². Furthermore, during the past two years certain of these plant extracts have been imported and incorporated into several very effective products. The purpose of this article is to provide greater details on both the laboratory and clinical research findings, particularly for the class of bioflavonoids termed the pycnogenols by Jack Masquelier³, the primary researcher of these materials. The pycnogenols include the catechins, oligomeric proanthocyanidins, and condensed tannins.

The term pycnogenol itself has become somewhat confusing for historical and legal reasons. An European company has trademarked the name pycnogenol in the U.S. (currently being contested) as it particularly relates to the extract of pine bark. However, historically the research literature has used terms such as leucocyanidins, pycnogenols, procyanidins, oligomeric proanthocyanidins, and others to refer to the plant materials which are extracted by a process patented⁴ by Jack Masquelier about 20 years ago and which has a unique signature when subjected to a test developed by Bate-Smith⁵. Furthermore, as refined and more sophisticated research tools have become available, some of the older findings have been surpassed; but it is left to the reader to unravel and understand the confusion. I shall try to make it clear in this article how it all fits together.

2.0 BACKGROUND

Before delving deeply into the research findings, I will provide a little background on the structure of bioflavonoids. One way of looking at the bioflavonoids is that they are two benzene rings connected by a three carbon chain. Figure 1 shows the general structure of bioflavonoids. The main classes which are distinguished by the types of molecules found at the different numbered positions are FLAVONOL (yellow), ISOFLAVONOL, FLAVONE (yellow), FLAVONONE (colorless), ISOFLAVONONE, ISOFLAVONE (colorless), ANTHOCYANDIN (red, blue, violet), CHALCHONE, and CATECHIN (colorless). Those classes beginning with the "iso" prefix refer to the structures in which the "B" ring is flipped down from the 2 position to the 3 position. For the anthocyanidins and the catechins the "C" ring is considered to be open which accounts for their greater water solubility. The catechins which are in the class termed flavon-3 ols have an "OH" molecule at the 3, 5, and 7 positions. Depending upon the orientation of the "OH" molecule in the 3 position the material is called catechin (C) or epicatechin (E). In the diagrams these are distinguished by arrows and dashed lines.

The catechins (referring to both catechins and epicatechins) have the peculiar property of forming polymers with themselves. Jack Masquelier calls these polymers condensation products and coined the unique term pycnogenol for them, which according to Latin means "that which forms condensation products"⁶. When the number of connected catechins is 10 or less they are called oligomers and hence the term oligomeric proanthocyanidins. When the number of connected catechins is more than 10 the term condensed tannins is generally used. The term proanthocyanidins comes about because when these materials are subjected to 10% hydrochloric acid and heated to boiling (this is what is termed the Bate-Smith test⁵), they yield an anthocyanidin, with its intense red coloration, and a catechin.

Figure 2 shows a dimeric proanthocyanidin which consists of catechin on top and epicatechin on the bottom. Depending upon which molecule of the lower "A" ring attaches to the "4" position of the upper "C" ring, there are different series of these dimers. The one shown in the diagram fits into what is called the "B" series and is the one of most interest to us here. The dimeric "B" series itself has four members depending whether and where there are catechins and epicatechins, Eg., E-E, C-E, E-C, and C-C. Each of these have been synthesized and studied in the laboratory and have somewhat different chemical properties.

It has taken almost 20 years for the researchers to come to this understanding concerning the dimers. The situation with respect to trimers, tetramers, pentamers, etc. gets extremely complex and, therefore, much of the research has concentrated upon the dimers or upon materials in which the dimers are the main constituent. This background is sufficient for the reader to understand the bulk of the research results.

3.0 THE EXTRACTION PROCESS

In 1969 Jack Masquelier was granted U.S. Patent No. 3,436,407 regarding the process by which the oligomeric proanthocyanidins could be extracted from raw plant materials in general and pine bark in particular. A flow diagram of the process is shown in Figure 3. The steps of this process insure that the materials obtained are highly water soluble, do not contain condensed tannins, and are not contaminated with toxic substances such as heavy metals, pesticides, and residual solvents.

The proanthocyanidins content of the extracted material is quantitatively assessed by using their property of having a strong affinity for collagen -- no other component of the extract having a strong affinity for collagen. In this assessment, a solution of known titre of the extract is prepared and brought in contact with hide powder (collagen). The amount of proanthocyanidins fixed to the hide powder is determined by filtration and weighing, which gives a measure of the original content of the proanthocyanidins in the extract.

The material obtained from pine bark by this process is an astringent tasting light beige powder which can be kept indefinitely in a dry bottle at room temperature. When subjected to high pressure liquid chromatography (HPLC) the constituents shown in Table 1 are typically indentified.

• 1. GALIC ACID -- 3.2%
• 2. DIMERS (Catechin and Epicatechin) -- 40.9%
• 3. CATECHIN -- 18.9%
• 4. PIC X -- 12.8%
• 5. CAFEIC ACID -- 1.9%
• 6. EPICATECHIN -- 0.2%
• 7. COUMARIC ACID -- 0.2%
• 8. TAXIFOLIOL -- 2.1%
• 9. FERULIC ACID -- 0.5%
• 10. OTHER including Trimers, Tetramers -- ~19%

It can be seen from the analysis that the dimeric proanthocyanidins are by far the major component in pine bark pycnogenol with a significant amount of the catechin monomer and of other constituents identified to be mostly trimeric and tetrameric proanthocyanidins. Gallic acid, cafeic acid, and ferulic acid are known to have potent in vitro anti-bacterial and anti-viral properties⁷.

Research investigations^8,9,10 have discovered that pycnogenols may be found in a wide range of other plants materials including:

• CRAB APPLE
• APPLE
• MOUNTAIN CRANBERRY
• AVOCADO PEAR STONE
• UNRIPE COCOA BEAN
• HORSE CHESTNUT (seed shell)
• HAWTHORNE FRUIT
• GOAT WILLOW (catkin)
• UNRIPE STRAWBERRY (fruit, stem)
• UNRIPE RASPBERRY (fruit, stem)
• COLA NUTS
• PEANUT SKINS
• GRAPE PIPS/SEEDS
• RED WINE

Commercial production of pycnogenols/proanthocyanidins using grape pips/seeds is routinely practiced in Europe (and is now available in the U.S.) and the skins of peanuts have also been used. It has been known since the 1960s that red wine is especially high in proanthocyanidins and another European company is now preparing a red wine extract which takes advantage of this fact.

Recent comparisons of grape pip/seed and pine bark pycnogenols with regard to their polyphenol content are shown in Table 2.

Table 2 -- Comparion of Polyphenol Content of Grape Pip/Seed and Pine Bark Extracts

Source: Procyanidins de France - brochure available from Crossover Marketing 203-481-8863

4.0 BIOCHEMICAL PROPERTIES

4.1 U.S. Patent on Use of Proanthocyanidins

In 1987, Jack Masquelier was granted U.S. Patent No. 4,698,360 entitled "Plant Extract with a Proanthocyanidins Content as Therapeutic Agent Having Radical Scavenging Effect and Use Thereof". The abstract for this patent is given below:

"The invention provides a method for preventing and fighting the harmful biological effects of free radicals in the organism of warm blooded animals and more especially human beings, namely cerebral involution, hypoxia following atherosclerosis, cardiac or cerebral infarction, tumor promotion, inflammation, ischaemia, alterations of the synovial fluid, collagen degradation, among others. The method consists of administering ....... an amount, efficient against said effects, of a plant extract with a proanthocyanidins content which has a radical scavenger effect, the extract being in the form of a medicament and coming more especially from the bark of conifers"

Clearly, Masquelier is claiming a significant therapeutic effect for the proanthocyanidins by means of their potent free-radical scavenging ability. According to the abstract the proanthocyanidins can play a major role in the prevention and cure of a wide range of illnesses. The patent also specifies the dosages which need to be used in order to obtain the therapeutic effects claimed These are:

• Orally -- 1.5 to 3.0 mg daily per kilogram of body weight
• Intravenously -- 5 to 10 mg daily
• Topically -- application of 0.5% ointment one or more times daily

   

4.2 Bioavailability

One of the key issues relating to the use of any nutritional supplement or medication is the ability of the substance to get into the body and be utilized at the cellular level. In order to demonstate the bioavailability of the oligomeric proanthocyanidins (PCOs), Masquelier and his colleagues used an isotopic labelling technique¹¹. Grape vines were cultivated in an atmosphere containing ¹⁴CO₂ for 40 days, during which time each carbon of the flavan molecule became labelled. After extraction and purification the product had an activity of 0.5 µCi per mg. When the PCOs were administered orally to a rat or mouse they became rapidly absorbed into the intestinal mucous membrane. The results indicate that radioactivity in the blood was highest after 45 minutes with a half-life in the plasma of 5 hours. Passage into the bile occurs relatively early; within 11 hours almost 14% of the radioactivity was eliminated in this way.

Radioautographic techniques and measurement of the radioactivity in different organs were used to study the fixation and localization in tissues. The radioautographic cross-sections of the whole mouse showed the distribution of the radioactivity throughout the animal, with a preferential localization in tissues rich in glycosaminoglycans. Measurement of the radioactivity found in various organs confirms the results of the radioautographic measurements. Radioactivity observed in these experiments was associated with the PCOs and not their degradation products since the fixation takes place in a matter of minutes well before any ¹⁴C appears in the exhaled breath.

The results of this study showed that the PCOs are rapidly absorbed into virtually all of the tissue of mammals (including the brain), and that there is a concentration in tissues high in glycosaminoglycans, namely connective tissues in the skin and organ systems, basement membranes of blood vessels, and cartilage.

4.3 Oligomeric Proanthocyandins Effects on Collagen Fibers

Collagen is the most abundant protein found in the human body. It is the key ingredient in the "glue" that holds us together and consists of helical structures of polypeptides connected together into long chains. Each collagen molecule actually consists of 3 chains, each of which is coiled in a left-handed helix. The three chains are twisted around one another, as the strands of a rope, to form a superhelix. It has been found that Vitamin C is needed in every step of the body processes by which collagen is made. The stability of collagen depends mainly upon the crosslinks which exist between the polypeptide chains.

When collagen fibers are placed into hot water they undergo denaturation and contract rapidly. As the number of crosslinks increase, the contraction temperature increases. An important property of certain polyphenols is that they are able to attach onto collagen and create crosslinks. It is possible to measure the stabilizing effect of these polyphenols by observing the thermal contraction of the fibers onto which they become attached.

In his laboratory, Jack Masquelier conducted a comparison study of the flavonoids with the pycnogenols¹¹. In the study, reconstituted beef tendon collagen fibers were incubated for 24 hours in an aquous solution of various test substances at a concentration of 1 mg/ml. Each fiber was 10 cm long and supported a weight of 5 grams. When plunged into water at 75 °C the reference (untreated) fibers quickly shrank to 4 cm. Table 4 shows shows the contraction time of the various treated fibers, the calculated force of contraction, and the measured amount of the test substance that was actually attached to the collagen fibers.

The results show that the bioflavonoids have no effect as far as crosslinking and stabilizing collagen are concerned. Although catechin does indeed crosslink and stabilize collagen, the PCOs are over 4.5 times more effective than catechin. Furthermore, even though the collagen fixes 50% more of the condensed tannins than PCOs, the PCOs are three times as effective at stabilizing the collagen fibers. The conclusion is that the molecular configuration of the PCOs is optimal for the stabilization of collagen.

4.4 Free Radical Trapping Effect

The in-vitro free-radical trapping effect of the pycnogenols can be checked in several ways. The tetrazolium nitroblue (TNB) test¹² is particularly effective at evaluating the effect of inhibition of superoxide radicals O₂-. In this test oxygen radicals have the property of reducing TNB into formazan blue, the quantity of which can be colorimetrically determined at 560 nm. In the presence of antioxidants operating as O₂- scavengers, reduction of the TNB is inhibited, which is demonstrated quantatively by a reduction of absorption at 560 nm. Table 5 shows the amount of inhibition obtained with a variety of substances.

The results show that the dimeric proanthocyandins are nearly 20 times more effective than vitamin C at trapping oxygen radicals, and are greater than two times more effective than the bioflavonoids and the pycnogenol monomers.

Another similar study was reported by Masquelier^11A, in which the NBT test was used to compare the ability of various substances to inhibit superoxide radicals, and the results are shown in Table 5A below. One sees that the the oligomeric proanthocyanidins are about 20 times more effective at trapping oxygen radicals than some of the commonly used bioflavonoids.

Another more recent and complete test compared the free-radical scavenger activity of procyanidolic oligomers and anthocyanosides with respect to superoxide anion and lipid peroxidation^11B. In this study the NBT test was used for comparing superoxide activity. Lipid peroxididation induced by ascorbate and the Fe²⁺ - ADP complex was assessed in boiled rat liver microsomes. This system produces the hydroxyl radical OH-, which reacts with polyunsaturated fatty acids in microsomal membranes causing the uprooting of a H atom and the subsequent triggering of a cycle of fatty acid self-oxidation. The test is based upon the assay of malondialdehyde (MDA) released as a result of the degradation of lipoperoxides. The results of this study are summarized in Table 5B. This study shows the clear superiority of grape seed procyanidolic oligomers (pycnogenol) as free-radical trappers.

Source: M.T. Meunier, E. Duroux, P. Bastide, Plantes medicinales et phytotherapie, 1989, Tome XXIII, n.4, p.267-274.

Notes: PCO = oligomeric proanthocyanidins AC = anthocyanidins

* references are from the source article

Furthermore, using human umbilical cord and chicken embryo vascular tissue cultures the free-radical scavenging effect of pine bark pycnogenol was checked^12A. Under certain conditions, these tissue cultures degenerate rapidly and in particular show destruction of the membrane phospholipids caused by oxygen radicals. When pine bark extract was added to the medium, the tissues cultures were maintained in a normal histologic condition.

These results indicate that the pycnogenols in general and more specifically the PCOs have very potent free-radical scavenging effects.

4.5 In Vivo Tests of the Effect of Pine Bark Pycnogenol on Capillary Resistance

Most of the studies described above were done in vitro or on animals. We will now present the results of a clinical study carried out with a total of 45 patients including 8 controls¹³. The patients were suffering from skin diseases or phlebological illnesses (eczema, ulcerated varicose veins, etc.). Various bioflavonoids as well as pycnogenol were used to conduct this study. Capillary resistance was measured by means of a Parrot angiosterrometer which allows one to ascertain with precision the amount of suction which causes purpura (red spots from broken capillaries) to appear on the skin.

In the first part of the study, patients were given a single 100 mg dose of pine bark pycnogenol and the capillary resistance was periodically measured over a 120 hour time inteval. The results are provided in Table 6.

It is observed that the mean capillary resistance increases rapidly peaking initially after 6 hours, then decreases and finally increases to its maximum value and remains at this high level. The term "diphasic" has been applied to this increasing, then decreasing, and finally increasing effect on the capillary resistance.

The next part of the study looked at the effect on the capillary resistance of several other well-known bioflavonoids over a 120 hour period and compared the results with those obtained with pine bark pycnogenol. The results are displayed in Table 7.

It is clear from the results shown in Table 7 that the traditional bioflavonoids do increase the capillary resistance for a short period of time, but none of those tested show the secondary long-term increase that the pycnogenol does. Obviously there is an effect from the pycnogenol that is not inherent in the other traditional bioflavonoids.

Table 8 shows the average percentage increase in capillary resistance over the first 72 hours after administration of the tested substance. This result indicates the almost threefold factor of effectiveness for pycnogenol as compared to the other bioflavonoids.

Masquelier has concluded that the initial increase in capillary resistance shown with all of the bioflavonoids and pycnogenol is due to the effect that all of these substances have on inhibiting the enzyme Catecholamine O-Methyl Transferase (COMT) which is responsible for breaking down adrenaline in the body. The prolonged life of adrenaline caused by the flavonoids allows it to decrease capillary permeability (equivalent to increasing capillary resistance). The longer-term effect of increased capillary resistance shown only by pycnogenol in the experiments comes about from the effect that the oligomeric proanthocyandins in pycnogenol have upon Vitamin C. The PCOs, which are powerful reducing agents, work with glutathione to reduce dehydroascorbic acid back to ascorbic acid within the tissues, which in turn is responsible for the increased capillary resistance by allowing the body to build or rebuild the collagen in the basement membranes of the capillaries.

4.6 Effects of Pycnogenol on Histamine Formation

During the initial stages of inflammation, damaged tissues release several chemical substances that activate the inflammation process. These include enzymes that breakdown or decarboxylate histidine into histamine which then increases the permeability of blood vessels. Middleton has reported that a number of the bioflavonoids inhibit histamine release thereby blocking the process of inflammation¹⁴. A study was conducted by Dr. David White at the University of Nottingham in England investigating the effect that pycnogenol has on histidine decarboxylase^14B.

In the study, rat gastric mucosa were assayed in vitro for histidine decarboxylase (HDC) activity. HDC was measured by following the release of ¹⁴CO₂ from ¹⁴C-histamine using the method of Beaven et. al.¹⁵. The results showed that HDC activity was inhibited in a dose dependent manner by pycnogenol An in-vivo study was conducted by measururing HDC activity in the gastric mucosa of rats which had been given pycnogenol in their diet for 5 weeks at levels of 5 and 50 mg per kilogram of bodyweight. The HDC activity in pycnogenol animals treated at both high and low doses were reduced compared with controls, and, although this was not a very sensitive test, it does confirm the in-vitro results.

4.7 Effect of Pycnogenol on Collagenases and Elastases

Both in vivo and in vitro studies have provided evidence that the binding of pycnogenols to elastin affects its rate of degradation by elastases¹⁶. In these studies procyanidol oligomers (PCO) and (+) catechin bound to insoluble elastin markedly affected its rate of degradation by elastases. Insoluble elastin pretreated with PCO was resistant to the hydrolysis induced by both porcine pancreatic and human leukocyte elastases. (+) Catechin-insoluble elastin complexes were partially resistant to the degradation induced by human leukocyte elastase but were hydrolysed at the same rate as untreated samples by a constant amount of pancreatic elastase.

These studies emphasize the potential effect of these compounds in preventing degradation by elastases as occur in inflammatory processes.

In another study¹⁷ treatment of radioactively labeled guinea-pig skin collagen or calf collagen with the bioflavonoid (+) - catechin makes the collagen resistant to the action of mammalian collagenase but not to the action of bacterial collagenase.....Since incubation of the mammalian enzyme with (+) - catechin does not inhibit its activity, it is postulated that (+) - catechin binds tightly to collagen and modifies its structure sufficiently to make it resistant to enzyme degradation.

4.8 Effect of Pycnogenol on Blood Vessels

Figure 4 summarizes the ways in which the pycnogenols protect the blood vessels, especially the capillaries. Regulation of vessel resistance and permeability occur in three separate ways:

• The pycnogenols crosslink the collagen fibers in the vessel basement membranes which make them stronger and less permeable.

• The pycnogenols inhibit the production of histamine which prevents the histamine associated increase in permeability. In addition, pycnogenol allows adrenalin to function for an extended time period by blocking the COMT enzyme, thereby allowing for increased vessel resistance.

• By protecting and carrying vitamin C to the basement membranes, vitamin C is enabled to function more effectively in the production of the collagen needed to keep the vessels strong.

Because much of the cholesterol produced in the body is broken down by Vitamin C, the protective effect that the pycnogenols have on Vitamin C indirectly helps the body to reduce high levels of cholesterol which may adversely affect the vessels by plague buildup on the walls.

Some of the effects described above are properties of the common bioflavonoids, however, the pycnogenols have more potent as well as additional effects when compared to the common bioflavonoids. Based on the research, it can be expected that on an overall basis, pycnogenol will be many times more effective at protecting the blood vessels than the common bioflavonoids

Pycnogenol As Adjunctive Therapy

Helps Manage Autoimmune Disease in Lupus Patients

Hillside, New Jersey – January 8, 2002—A pilot study, published in the December 2001 issue of Phytotherapy Research, shows the anti-inflammatory agent Pycnogenol® may prevent immune cells from over-reacting when used as an adjunctive therapy to glucocorticoids and/or hydroxychloroquine to treat Lupus patients. In the study conducted through a collaboration between the Universities of Bucharest (Romania) and Munster (Germany), 11 patients with the autoimmune disease Lupus continued their normal medication (glucocorticoids and/or hydroxychloroquine), while 6 of them additionally received 120 mg Pycnogenol per day for 1 month, and 60 mg/day for the following month. The remaining five patients continued their normal medication and received a placebo, as control group.

The researchers took blood samples from the study patients and investigated the status of their immune cells. It was discovered that a particular subset of white blood cells (granulocytes) produced significantly less reactive oxygen species when patients had taken Pycnogenol. Immune cells produce reactive oxygen species as toxins to eliminate germs and other infections. In Lupus patients, these weapons are taking the body's own tissue under "friendly fire". Pycnogenol seems to calm down these over-reacting immune cells.

Lupus patients who took Pycnogenol experienced a normalizing of their immune cells suggesting that Pycnogenol may be helpful for patients diagnosed with Lupus. Specifically, in these patients, their immune cells attacked their own body tissue with less aggressiveness. Future studies will need to be conducted in order to show whether Pycnogenol may be beneficial for autoimmune diseases in general.

Another phenomenon typical in Lupus is the premature death of lymphocytes, the subset of immune cells responsible for orchestrating the body's immune response. It is believed that the failure of the immune system to distinguish between "body-own" and "foreign" is largely a consequence of the premature decay of lymphocytes. Pycnogenol significantly increased the lifetime of lymphocytes, which allows them to exert their influence to prevent the immune-system from over-reacting. This effect was significant in patients taking Pycnogenol but not in those receiving placebo.

Pycnogenol and Immunology Studies

These actions of Pycnogenol on immune cells are in agreement with various studies by Benjamin Lau (Loma Linda University) and Lester Packer (University of California, Berkeley), whose studies demonstrated that Pycnogenol is an anti-inflammatory and prevents immune cells from over-reacting. In one study Lester Packer has described a possible benefit of Pycnogenol for psoriasis, an inflammatory skin disorder. In another clinical study with human volunteers he demonstrates that Pycnogenol taken orally can prevent inflammation of the skin in response to UV-irradiation (sunburn).

Lupus Background

Lupus erythematosus represents a particular type of autoimmune disease, which often can be recognized by a butterfly-shaped rash over the cheeks. This gives people something of a wolf-like appearance, and this gave the disease its name (Lupus (Latin) = wolf). Lupus usually develops between the age of 15-35, and more than 90% of patients are women.

A commonality between Lupus and other autoimmune diseases is that the immune system mistakenly recognizes body components as foreign and attacks them, as if they were invading bacteria or viruses. The body develops antibodies against parts of its own body, and immune cells excrete toxic substances causing destruction of the body’s own organs and tissues.

In the case of Lupus, the result is a chronic inflammation of skin, blood vessels, joints, kidneys, and other tissues. The first symptoms resemble those of arthritis, with swollen and painful fingers and other joints. Typically there are periodic flare-ups followed by periods of remission. The severity of Lupus ranges from mild to life threatening forms. Currently, Lupus cannot be cured and medical treatment involves turning-down the immune system in general (e.g. with glucocorticoids) to prevent it from attacking its own tissue.

 

Pycnogenol® French Maritime Pine Bark Extract Reduced Systolic Pressure and/or Diastolic Pressure in Stage 1 Hypertensive Patients

TUSCON, AZ – November 1, 2001 –Lead investigator Ronald Watson, PhD, College of Public Health, and School of Medicine, Health Sciences Center, University of Arizona, in Tucson, AZ, conducted an 11 patient double-blind placebo controlled crossover study with Pycnogenol® and Stage 1 hypertensive patients resulting in significant reduction in blood pressure. In the study entitled, "A Randomized, Double-Blind, Placebo-Controlled, Prospective, 26 Week Study to Determine the Role of Pycnogenol in Modifying Blood Pressure in Mildly Hypertensive Patients," subjects were given 200 mg of Pycnogenol® French Maritime Pine Bark Extract per day for eight weeks. Pycnogenol® reduced systolic blood pressure to 134 mmHg, and reduced diastolic blood pressure to 94 mmHg in patients participating in the study.

The 11 patients had an average age of 50 years and mild hypertension defined as systolic blood pressure of 140-159 mmHg, and/or diastolic pressure of 90-99 mgHg. People with blood pressure within this range are considered to be Stage 1 Hypertensive and are not routinely treated with pharmaceutical drugs. The study participants refrained from using any medication.

"Hypertension affects nearly 50 million Americans, and is the number one cause of heart attacks and strokes, and 40,000 deaths a year," says Dr. Watson. "Our research here demonstrates Pycnogenol’s ability to elevate the production of nitric oxide in the vessel walls to reduce blood pressure which may help decrease hypertensive morbidity and mortality."

Muscles surrounding blood vessels control their diameter and blood flow and pressure. Stress hormones instruct muscles to constrict and reduce diameter while increasing blood pressure. Nitric oxide, on the other hand, relaxes muscles, expands blood vessels and improves blood flow, thus lowering blood pressure.

In addition to Pycnogenol reducing patients’ blood pressure, Dr. Watson found that the amount of thromboxane, and important blood parameter, was also reduced after treatment with Pycnogenol. Thromboxane is a hormone-like substance triggering increased constriction of blood vessels and simultaneously instructing blood platelets to become sticky and coagulate. Both of these processes may result in the formation of a dangerous blood clot that may clog a constricted blood vessel and cause a stroke.

STUDY SHOWS HERBAL SUPPLEMENT REDUCES PROGRESSION OF BLINDNESS CAUSED BY DIABETES, HYPERTENSION AND ATHEROSCLEROSIS

Pycnogenol® French Maritime Pine Bark Extract

Is Shown To Improve Visual Acuity and Suspend Deterioration of Retinal Function

Hillside, New Jersey, Natural Health Science, LLC -- May 30, 2001 -- A clinical study published earlier this month in the journal Phytotherapy Research demonstrates that Pycnogenol® improves visual acuity and suspends deterioration of retinal function in 30 patients experiencing a deterioration in vision due to complications of diabetes, atherosclerosis and other vascular diseases involving the retina. The goal of the study was to investigate the effects of Pycnogenol® on the progression of diabetic retinopathy and other vascular retinal disorders.

The study consisted of a double-blind phase in which 20 patients were recruited and randomly treated with placebo or Pycnogenol® at a dose of 50 milligrams three times a day for 2 months. In addition, the study conducted on open phase in which another 20 patients were treated with Pycnogenol® at the same dose schedule. In total, 40 patients with either diabetes, atherosclerosis or other vascular disease involving the retina were enrolled. In total, 30 patients were treated with Pycnogenol® and 10 were treated with a placebo.

The study results demonstrated that Pycnogenol® had a beneficial effect on the progression of retinopathy, and that the patients who received placebo experienced a progressively worsening retinopathy and a significant decrease in visual acuity.

"We are very excited about the study results because they show that Pycnogenol® is an effective and safe option for people to use to reduce the progression of retinopathy," says Victor Ferrari, Chief Executive Officer and Executive Vice President of Horphag Research. The company is represented by Natural Health Science in North America.

 

TEST METHODOLOGIES

Five highly regarded testing methodologies were used to determine the safety and efficacy of Pycnogenol® as well as its ability to slow down the progression of diabetic retinopathy and other vascular retinal disorders. The test included Visual Acuity, Opthalmoscopy, Fluorangiography, Electroretinogram and Visual Field.

The Visual Acuity test included results from the famous Snellen Chart (testing eyesight by reading a line of letters at 20 feet). The study found that Pycnogenol® slowed down the deterioration of Visual Acuity, and in some cases improved the recovery. The study also found that the Retinopathy progressively reduced the Visual Acuity in the placebo treated patients.

An Opthalmoscopy examination was then conducted on both Pycnogenol® and placebo treated patients. This examination looks at the retina to discover if there are any macular odema’s, hemorrhages or hard exudates visible. It was reported that there were improvements in retinas of patients treated with Pycnogenol® statistically significant in both the left and right eye; however, the placebo treated patients reported no changes.

A clinical procedure, Fluorangiography, was used to check the blood flow in the retina as well as the integrity of the blood. Patients taking Pycnogenol® reported reduced vascular permeability and improvement of the blood-retina barrier while the placebo treated patients reported no changes.

The Electroretinogram procedure was used to assess metabolic and physiological changes in the retina. The study showed a remarkable improvement in the retinas of Pycnogenol® treated patients, while the placebo treated patient’s retinas remained the same. The physicians in the study scored the Pycnogenol® patients retina results as "very good" in 53% of the cases, meanwhile the placebo treated patients only scored a "good" rating in 30% of the cases.

The Visual Field methodology examined the entire visual field of the patient’s retina as well as any retinopathy deterioration in any one part of the eye. The study found there was no statistical differences in either the Pycnogenol® or placebo treated patients.

 

PYCNOGENOL’s® MECHANISM OF ACTION:

Researchers in the study believe the clinical improvement in the Pycnogenol® controlled patients is a direct result of its free radical scavenging properties. Free radicals are harmful molecules that damage the body by attaching themselves to capillaries and cells that weaken cell walls. In Diabetic Retinopathy, free radicals adhere to the cells in the eye, weakening the eye and causing macular oedema’s, hemorrhages or hard exudates that ultimately fill the eye with blood and obstruct vision, causing blindness. Pycnogenol® helps to strengthen the vascular cells in the eye to avoid the progression of Retinopathies.

 

DIABETIC RETINOPATHY IN THE U.S.

Nearly 16 million Americans suffer from Diabetes in the United States, of which 12,000 to 24,000 people lose their vision as a result of the disease each year. Diabetic retinopathy, a common complication resulting from both Type I and Type II diabetes, is the leading cause of new cases of blindness in people age 20-74 years old in the United States.

The prevalence of retinopathy is strongly related to how long a diabetes sufferer has the disease. It is likely that most patients who have Type I Diabetes for 20 years will develop diabetic retinopathy. In addition, up to 21% of people diagnosed with Type II diabetes are generally diagnosed with retinopathy at the same time. Diabetic Retinopathy is a major concern considering it is responsible for 8% of legal blindness, making it the leading cause of new cases of blindness in the US.

 

Pycnogenol® Significantly Improves Asthma Symptoms

New Clinical Study in Journal of Medicinal Food Finds the Herbal Extract Pycnogenol® Significantly Improves Asthma Symptoms

TUCSON, AZ -December 28, 2001-In today's issue of the Journal of Medicinal Food, a new clinical study entitled "Pycnogenol® in the Management of Asthma," indicates that taking the nutraceutical Pycnogenol®, an herbal extract derived from the French maritime pine tree, can significantly improve asthma symptoms. In addition to the study conducted by Ronald Watson, Ph.D., College of Public Health and School of Medicine, University of Arizona in Tucson, there is a significant body of clinical evidence comprised over 30 years and over 70 studies that verify Pycnogenol's anti-inflammatory and antioxidant properties.

"Pycnogenol® may be a valuable new nutraceutical in the management of asthma. It was well-tolerated, only one patient experienced some initial stomach discomfort, and overall the patients generally noted an improvement of their breathing ability when they received Pycnogenol®, says Dr. Watson. "These favorable preliminary results suggest that additional research is warranted."

This random, double-blind, placebo-controlled, crossover study was comprised of 12 women and 10 men between the ages of 18 and 50 years, who had suffered from asthma for 1 to 16 years. Patients were randomly assigned to either the Pycnogenol® group, receiving 1mg/lb/day (without exceeding 200 mg/day), or to the group receiving placebo for four weeks. Thereafter, subjects were crossed over to the alternate group.

The airway function of the patients was assessed using a well-established method called "forced expiration volume in 1 second" (FEV1), by means of an instrument called a spirometer. For accurate measurement, the subject fills his lungs and then exhales as fast as he can for exactly 1 second, while the spirometer measures the volume of exhaled air. The exhaled volume is expressed relative to the total lung volume, so the FEV1 value represents the percentage of a specific patient's lung volume he can exhale in a second. Understandably, the percentage is lower in asthma patients as their airways are constricted, and breathing is aggravated. Dr. Watson showed that the percentage of the total lung volume which the asthma patients could exhale within one second rose considerably after treatment with Pycnogenol®, while placebo had no effect.

The improvement of airway function was paralleled by a reduction of mediators called leukotrienes in the blood. The leukotrienes cause the inflammatory condition and constriction of bronchi, processes which are largely responsible for the airway obstruction in asthma. Pycnogenol® significantly reduced the leukotriene values, as compared to both baseline as well as placebo medication. Taking placebo tablets had no significant influence on leukotriene levels in the blood.

The severity of asthma symptoms was rated on a 4-point scale, ranging in steps from a mild intermittent form up to a severe persistent form. Before treatment and while receiving placebos the mean symptom score of all patients was considered as being a "severe persistent" form. After treatment with Pycnogenol® the symptom severity score was significantly reduced to the "moderate persistent" form.

Asthma Backgrounder

Asthma Statistics
More than 17 million Americans are currently estimated to have asthma, and the prevalence of the disease has increased by 75% from 1980 to 1994. Annually in America, there are approximately 10.4 million physician office visits for the treatment of asthma. There were more than 1.9 million emergency room visits for asthma in 1995. There are more than 5,300 deaths from asthma each year. Direct health care costs for asthma in the U.S. total more than $9.8 billion annually.

What is Asthma?
Asthma is characterized by episodes of wheezy breathlessness with intervals of relative or complete freedom from symptoms. Asthma is believed to result from inflammatory processes of the bronchi causing them to constrict and swell, aggravating the airflow. In many patients, specific hypersensitivity reactions to inhaled antigenic substances (e.g. pollen, animal hair etc.) cause the episodic obstruction of the airways. Moreover, various unspecific irritants can trigger asthmatic episodes. Chemical irritants (e.g. tobacco smoke, dust, air pollution), certain medications, cold air and even exercise or psychological factors can cause a sudden over-reaction of the bronchial receptors, causing inflammation and subsequent narrowing of the air passages. Asthma is far more than a respiratory discomfort, and occasionally can take life-threatening forms. And the occurrence is considerable, affecting about 4-5% of the population
 

Pycnogenol® Outperforms Other Plant-Derived Antioxidant Products Tested


BACKGROUND: Fruits, vegetables, and herbal products contain complex mixes of naturally occurring antioxidants, including flavonoids (which function as pigments) and vitamins. All of these antioxidants protect against free radicals, which damage cells and contribute to the aging process and diseases. However, it is important to identify how much of their antioxidant activity is related to flavonoids and how much is related to vitamin C, which is easily and inexpensively obtained from other sources. It's also important to determine the effect of high temperatures on these products.

RESEARCH: Using a new and highly sophisticated analytical technique, researchers compared the antioxidant properties of several plant-derived antioxidant products after (1) being boiled in water for 10 minutes or (2) having their vitamin C removed. The products included Pycnogenol® (an antioxidant complex extracted from the bark of French maritime pine trees), Ginkgo biloba, tea and other flavonoid-containing products. Each product was tested by measuring how effectively it neutralized hydroxyl and superoxide free radicals.

RESULTS: Compared to the other products, Pycnogenol® was a powerful scavenger of both hydroxyl and superoxide radicals and the most resistant to heat damage. Pycnogenol® was by far the best scavenger of hydroxyl radicals after vitamin C was removed from the products. This is significant because hydroxyl radicals are the most damaging of all free radicals. Boiling destroyed more than 50 percent of the superoxide neutralizing ability of all the products except Pycnogenol®.

IMPLICATIONS: Free radicals are produced in inflammation and during the immune system's response to infection. Pycnogenol's® antioxidant properties likely protect cells against damage from these free radicals.

Noda Y, Anzai K, Mori A, et al., "Hydroxyl and superoxide anion radical scavenging activities of natural source antioxidants using the computerized JES-FR30 ESR spectrometer system," Biochemistry and Molecular Biological International, 1997;42:35-44.

Pycnogenol® Neutralizes Free Radicals In Heart Cellsnol® NeutCells

BACKGROUND: Hazardous molecules known as free radicals have been implicated as a cause of coronary heart disease. This knowledge has led to research on how antioxidants neutralize free radicals and might lower the risk of heart disease.

RESEARCH: In a study using endothelial heart cells from cows, researchers tested how Pycnogenol® quenched specific types of free radicals. Pycnogenol® is a naturally occurring mix of antioxidants derived from the bark of French maritime pine trees.

RESULTS: Pycnogenol® reduced cell levels of superoxide and hydrogen peroxide radicals. It also increased cell production of glutathione, superoxide dismutase, and catalase -- all powerful antioxidants made within cells.

IMPLICATIONS: Pycnogenol® protected against two types of free radicals and increased cellular production of important antioxidants. These changes would lower the risk of free radical damage to endothelial cells and coronary heart disease.

Wei ZH, Peng QL, Lau BHS, "Pycnogenol® enhances endothelial cell antioxidant defenses," Redox Report, 1997;3:219-224.

 

Pycnogenol® Reduces Free Radicals That Could Lead To Heart Disease

BACKGROUND: Pycnogenol®, an extract of the French maritime pine tree, is a rich source of antioxidant flavonoids. As a group, flavonoids are increasingly thought to play important roles in maintaining health and preventing disease.

RESEARCH: In laboratory experiments, researchers tested the ability of Pycnogenol® to (1) reduce the release of free radicals by white blood cells, (2) inhibit the oxidation of human low-density lipoprotein (LDL), and (3) prevent damage to deoxyribonucleic acid (DNA), the complex protein that forms genes.

RESULTS: These experiments demonstrated that Pycnogenol® has potent antioxidant properties. It reduced the release of free radicals by white blood cells and prevented the oxidation of LDL. Pycnogenol® also minimized damage to DNA.

IMPLICATIONS: Although these were laboratory studies, they demonstrated that Pycnogenol® has potentially useful roles in human health. By reducing the release of free radicals by white blood cells, Pycnogenol® could reduce inflammation. By inhibiting oxidation of LDL, it may slow the development of coronary heart disease. And by preventing DNA damage, Pycnogenol® may slow the development of a wide range of degenerative diseases and the aging process itself.

Nelson AB, Lau BHS, Ide N, et al., "Pycnogenol inhibits macrophage oxidative burst, lipoprotein oxidation, and hydroxyl radical-induced DNA damage," Drug Development and Industrial Pharmacy, 1998;24:139-144.

 

Pycnogenol® Potent Antioxidant, Anti-inflammatory

BACKGROUND: Flavonoids, a class of water-soluble antioxidants found in plants, have diverse and beneficial health effects. One group of flavonoids, called Pycnogenol®, is derived from the bark of French maritime pine trees.

RESEARCH: A review of published literature on Pycnogenol® showed it to be a potent antioxidant and to enhance the integrity of blood vessel walls. It is also exceptionally safe, with no reported side effects in 30 years of study.

RESULTS: Based on published studies, Pycnogenol® also acts as an anti-inflammatory, mild blood thinner, and immune enhancer.

IMPLICATIONS: Although flavonoids are common in fruits and vegetables, Pycnogenol® contains a distinctive group of flavonoids in a high concentration. It has also been better standardized - that is, more consistent in composition - than many other flavonoids and plant-based products.

Rohdewald P, "Flavonoids in Health and Disease", eds: Rice-Evans C and Packer L, New York: Marcel Dekker, 1998:405-419.

 

Pycnogenol® Reduces Blood Clotting, Cardiovascular Risks

BACKGROUND: Abnormal platelet aggregation increases the risk of blood clots, which in turn increase the risk of heart attacks and strokes. Cigarette smoking increases platelet aggregation, as does adrenaline (induced by stress).

RESEARCH: Researchers asked 39 healthy smokers to smoke three cigarettes in a controlled setting. Two hours later, the researchers drew blood from the subjects and determined that cigarette smoking had increased platelet aggregation. One week later, the same procedure was followed, but the subjects were also given either 500 mg of aspirin or 100 mg of Pycnogenol®, a natural complex of antioxidants obtained from the bark of French maritime pine trees.

RESULTS: Both Pycnogenol® and aspirin reduced platelet aggregation after the subjects smoked cigarettes. However, aspirin increased bleeding time by 41 percent, while Pycnogenol® did not. In a separate laboratory study, Pycnogenol® was also found to inhibit adrenaline-induced platelet aggregation.

IMPLICATIONS: Pycnogenol®, a natural source of antioxidant flavonoids, can reduce platelet aggregation and likely reduce the risk of cardiovascular disease. Unlike aspirin, it does not promote abnormal bleeding.

Watson RR, Araghi-Niknam M, Putter M, et al., "Pycnogenol® inhibits platelet aggregation in vivo," presented at the American Society for Biochemistry and Molecular Biology annual meeting, Washington, D.C., May 20, 1998.

 

Pycnogenol Regulates Excess Levels Of Harmful Nitric Oxide Radicals

BACKGROUND: Nitric oxide (known also as nitrogen monoxide, or simply NO) has diverse roles in the body. Produced by the immune system, it helps the body destroy pathogenic bacteria. Excess NO, however, is associated with arthritis, diabetes, stroke, inflammation, heart disease, and other diseases.

RESEARCH: In a cell-culture study, researchers activated white blood cells by exposing them to interferon (an immune compound) and substances found in bacterial walls. The researchers also tested what effect Pycnogenol® would have on the activated white blood cells.

RESULTS: When activated, the white blood cells produced large amounts of nitric oxide synthase, the enzyme that generates NO. However, when white blood cells were first exposed to Pycnogenol® and then activated, NO production was significantly decreased. Pycnogenol® scavenged NO radicals and inhibited the activation of nitric oxide synthase and the gene that codes for nitric oxide synthase.

IMPLICATIONS: Although NO plays important and necessary roles in health, excess levels are associated with various diseases. Pycnogenol, a natural antioxidant complex derived from the bark of French maritime pine trees, can reduce NO production and levels.

Virgili F, Kobuchi H, and Packer L, "Procyanidins extracted from Pinus maritima (Pycnogenol® ): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine raw 264.7 macrophages," Free Radical Biology & Medicine, 1998;24:1120-1129.

 

Pycnogenol® Helps Maintain Vitamin C Levels


BACKGROUND: Antioxidants are often considered synergistic substances, working together to limit free radical (oxidative) damage. For example, vitamin C helps the body recycle vitamin E - essentially extending the useful life of vitamin E in the body.

RESEARCH: Scientists used a new analytical technology to determine whether Pycnogenol® French maritime pine bark extract, Ginkgo biloba extract, green tea, and various other antioxidants would extend the lifetime of vitamin C.

RESULTS: Pycnogenol® extended the lifetime of the vitamin C radical longer than did any of the other antioxidants. In doing so, Pycnogenol® delayed the further breakdown of vitamin C and helped "refresh" it. Pycnogenol® extended the lifetime of vitamin C by four times over initial values.

IMPLICATIONS: This study demonstrates that Pycnogenol® helps maintain vitamin C levels, at least experimentally. According to previous research, vitamin C, in turn, helps recycle and maintain vitamin E levels. Thus, Pycnogenol® can interact with and directly help preserve levels of vitamins C and E in the body.

Cossins E, Lee R, Packer L, "ESR studies of vitamin C regeneration, order of reactivity of natural source phytochemical preparations," Biochemistry and Molecular Biology International, 1998;45:583-597.

 

Vitamin E and Pycnogenol® Work Together, May Reduce Heart Disease Risk


BACKGROUND: Antioxidant nutrients, such as vitamins C and E, are "used up" in the process of quenching hazardous molecules known as free radicals. However, antioxidants routinely recycle (and regenerate) each other, thereby extending their useful life span in the body. Of the antioxidants, vitamin E is particularly important because it is the body's principal fat-soluble antioxidant and may reduce the risk of coronary heart disease.

RESEARCH: In cell culture experiments, researchers confirmed that activated white blood cells (that is, those stimulated by bacterial proteins) increased free radical levels and decreased vitamin E levels in endothelial cells. These free radicals can damage endothelial cells, which are crucial to normal heart and blood vessel function. So researchers added Pycnogenol®, a natural antioxidant complex extracted from French maritime pine trees, to a cell culture of endothelial cells before exposing them to activated white blood cells.

RESULTS: Pycnogenol® protected vitamin E levels in endothelial cells and, in fact, increased vitamin E levels by about 15 percent. The experiments demonstrated that Pycnogenol® could help recycle vitamin E.

IMPLICATIONS: Pycnogenol® can enter into complex biochemical reactions and enhance vitamin E levels in endothelial cells.

 

Pycnogenol® Prevents Platelet Aggregation, A Leading Cause of Heart Attacks and Strokes




Washington, D.C., May 19, 1998 - Pycnogenol® may provide protection from heart attacks or strokes, especially for smokers or those with a family history of heart disease, according to a breakthrough study presented here during the American Society for Biochemistry and Molecular Biology annual meeting.

In the new study, Pycnogenol® French maritime pine bark extract significantly reduced platelet aggregation, a condition that occurs when the smallest blood cells stick together and form clumps in the blood. A clump of cells in a narrowed artery feeding a region of the brain can produce a stroke, while aggregated platelets in restricted blood vessels feeding the heart can lead to heart attacks. The cycle begins when the body experiences stress, whether it's from daily activities, smoking or even exercising. When stress results, large amounts of adrenaline are released. Adrenaline, a stress hormone, causes platelets to aggregate and this can lead to a heart attack or stroke. Pycnogenol® may benefit the entire cardiovascular system by preventing excessive platelet aggregation brought on by smoking and stress.

"Pycnogenol® serves as a natural shield, helping to prevent cell aggregation which would restrict the blood supply struggling to move through narrow arteries," said the study's author Ronald Watson, Ph.D., Professor, University of Arizona Medical School at Tucson. "Here's a completely natural substance with remarkable activity, producing effects within minutes. It may have enormous health implications for an aging population," Dr. Watson said.

A U.S. patent (#5,720,956) was recently granted based on the compelling research findings of Dr. Watson and the patent's inventor, Peter Rohdewald, Ph.D., of the University of Münster, Germany. The new patent shows, for the first time, that Pycnogenol® can inhibit platelet aggregation.

The study was conducted with a group of 38 healthy smokers at the University of Münster in Germany, and at the University of Arizona in Tucson. Volunteers were given a single dose of 100-120 mg of Pycnogenol® or 500 mg of aspirin®. Then they smoked to increase platelet aggregation and blood clumping during the two hours prior to having their blood drawn. Within 2 hours after smoking, participants were evaluated to measure the effects of Pycnogenol® or aspirin in reducing smoking-induced platelet aggregation. The study focused on smokers because it is easier to measure their dramatically increased clumping of platelets. The results showed that both the Pycnogenol® and the aspirin reduced platelet aggregation significantly. A single, smaller dose of the natural nutrient Pycnogenol® was as effective as a five times larger amount of the drug aspirin.

This is good news for the substantial portion of the population that cannot tolerate long-term aspirin use with its side effects, including increased bleeding and stomach problems. Pycnogenol® did not increase bleeding while aspirin did. Studies are now underway to assess the long-term effects of Pycnogenol® supplementation in non-smokers and smokers.

"While aspirin is currently recommended by cardiologists to prevent platelet aggregation, this research suggests that Pycnogenol® is efficacious and safer for people needing reduction in platelet aggregation," Dr. Watson said.

Dr. Watson's study is expected to be published in a peer-reviewed journal within a few months.

Pycnogenol® (Pik-NAH-je-nol) is a trademarked natural extract made only from the bark of French maritime pine trees. Pycnogenol® is an extract of water-soluble flavonoids containing a distinctive complex of more than 40 compounds. Years of research support its antioxidant properties and its ability to enhance the body's circulation.

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