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PYCNOGENOL & THE BIOFLAVONOIDS
AN APPLE A DAY DOES KEEP THE DOCTOR AWAY
OVERVIEW: Pycnogenol and related bioflavonoids have potent anti-oxidant, free-radical quenching, and vitamin C sparing properties, and in addition combat the effects of the inflammatory prostaglandins. Additional anti-histamine, anti-allergy, and pro-collagen effects make pycnogenol one of our most versatile naturally occurring health promoting substances. Free of toxicity, low in cost, and now widely available over the counter, pycnogenol and the other bioflavonoids have been shown to be of value as a non-drug treatment of problems ranging from stomach ulcers to atherosclerosis to PMS.
HISTORY, BIOCHEMISTRY, & NOMENCLATURE: Pycnogenol was “discovered” in 1583, when our first North American nutritional doctor, an American Indian, applied a pycnogenol rich pine bark poultice to the bleeding wounds of Jacques Cartier’s sailors, curing them of scurvy. Dr. Albert Szent-Gyorgyi, the Nobel Prize winning scientist who first isolated Vitamin C, described a substance which he labeled as Vitamin P, which potentiated the action of the newly isolated, physiologically important Vitamin C. His Vitamin P substance could cure scurvy and increase survival in guinea pigs, even if their dietary intake of Vitamin C remained restricted. In the 1960’s, Professor Jacques Masquelier, Dean Emeritus of the faculty of Materia Medica at the University of Bordeaux, and fortunately for us somewhat of a history buff, set out to discover just what component of pine bark, not known to be a particularly rich source of Vitamin C, had cured the sailors’ scurvy, a disease caused by Vitamin C deficiency. In 1966, he isolated the “anti-scurvy” principle, and found that it wasn’t one element but a family of compounds that he named pycnogenol (which means “substances which deliver condensation products”). Dr. Masquilier patented the process for extracting pycnogenol from pine bark, grape seeds, and other natural sources, and obtained a U.S. “use” patent in 1987. Bioflavonoids, the blue and red pigments of plants, fall under the category of Phytochemicals (phyto meaning plant sourced). These substances, such as the naturally occurring hormone precursor diosgenin, derived from the Mexican Wild Yam Dioscorea, the cancer inhibiting phytochemicals isolated from cruciferous vegetables, and the biologically active Acemannan component of the Aloe Vera plant, are considered to be adaptogens. While not absolutely necessary for life, and hence not considered to be true vitamins, adaptogens function to help prevent and fight off disease states, and are the “other good things” that we get from fruits and vegetables, besides the anti-oxidant vitamins that we are already familiar with. Modern day processing techniques remove most of the bioflavonoid and other adaptogens from our food supply, and given our preference for processed as opposed to whole, naturally grown foods, modern Americans are as adaptogen deficient as we are vitamin malnourished-this is why we begin to fall apart at age 50! Pycnogenol is 85% composed of proanthocyanidins, representatives of the bioflavanol subfamily of the bioflavonoids. The basic unit of the proanthocyanidins is the compound catechin. The biological activity of catechin is enhanced when individual molecules of catechin are linked together, and commercially available pycnogenol or proanthocyanidin preparations actually contain a mixture of catechin monomers (one molecule) and the more biologically potent oligomeres (several molecules of catechin linked together).
NATURE’S STRONGEST BIOLOGICAL ANTI-OXIDANT: Free radicals are killing us! A free radical is a molecule with one, as opposed to the normal two, electrons in its outer orbital shell. They are unstable and highly reactive, and will snatch an electron from an adjacent molecule, quenching its thirst for an electron, but in the process creating a new free radical. The new free radical will steal an electron from the next molecule in the line, creating yet another free radical, and a chain reaction will follow, with thousands of free radicals being formed, damaging the structures within our cells. If our genetic blueprint, the cellular DNA, is affected, then the cell can turn cancerous. If the cell membrane is damaged, the cell will have trouble taking in nutrients and clearing its wastes, compromising its function. The range of physiologic impairments caused by free radical attack is endless. We are learning that free radical attack produces much if not all of the damage done to our cells and internal organs by non-infectious diseases, the wear and tear or “premature aging” diseases that are maiming and killing an ever increasing number of Americans. These are maladies ranging from hayfever to arthritis to dementia to cancer. As a cardiac patient(or someone that never wants to become a cardiac patient) it is critical that you understand that circulating, non-lipoprotein(a) bound LDL cholesterol cannot be incorporated into the atherosclerotic plaque that narrows your blood vessels until it has been damaged , or “oxidized”, by free radical attack. Potent free radicals, most notably superoxide, hydroxyl, and peroxyl anions, are created in our cells, as a byproduct of the trillions of oxygen reactions that took place within your body as you read this line. In addition, our modern environment pummels us with damaging free radicals in the form of cigarette smoke, metabolic toxins added to our food, ionizing radiation from the sun, and countless other sources. Mother nature has provided us with anti-oxidant defenses such as vitamins C, E, and beta-carotene, and the anti-oxidant minerals selenium, manganese, zinc, and others, but modern day food processing techniques and our current preference for processed foods has rendered our entire society vitamin malnourished, leaving us with weakened defenses against free-radical attack. As our children consume the same, nutritionally deficient diet, it is no wonder that cancer and heart disease are occurring at a younger and younger age in our country. Fortunately, we can make up for our dietary indiscretions and bolster our anti-disease defenses by taking anti-oxidant vitamin and mineral supplements. It is no longer a matter of contention that these nutritional supplements prevent LDL oxidation, and by this mechanism serve as a powerful means of preventing the initiation and progression of coronary disease and atherosclerotic narrowing of our other vessels, both before and after bypass surgery. It is critical that we as preventative physicians use vitamins as vitamins and not as drugs. It is not a matter of choosing the most potent vitamin and taking it in high doses, but of provided complete anti-oxidant protection-we need each and every one of the anti-oxidant vitamins. This is why studies using only one vitamin often fail to show a benefit, leading to the mistaken impression in American medicine that “vitamins don’t work”, or that vitamins “only produce expensive urine”. All of the vitamins need to be provided; if we had a three drug combination therapy that could effectively eradicate a given cancer, would we as physicians administer only one of the drugs to our patient and expect it to be effective? Circulating vitamin C protects and replenishes intracellular vitamin E, which in turn protects beta carotene, which protects the cell-the benefits of an anti-oxidant program is superior to the sum of its parts. Pycnogenol fits well into our cellular protection (and therefore disease prevention) program. Pycnogenol is not only an extremely effective anti-oxidant in its own right, but it also serves as the “protector” of vitamin C, and possesses an anti-platelet stickiness property- a cardiology “triple play”. As an isolated anti-oxidant, pycnogenol’s ability to neutralize free radicals, such as the potentially plaque producing superoxide, hydroxyl, and peroxyl radicals produced as a by-product of our own metabolism, pycnogenol’s potency is 50 times that of vitamin E and 20 times that of vitamin C working alone. Citrus fruits contain bioflavonoids in the bitter tasting rinds, surrounding the vitamin C rich, sweeter tasting pulp. Mother Nature knew what she was doing here, combining vitamin C with bioflavonoids, as the bioflavonoids’ and pycnogenol’s most important contribution to coronary health derive from their function as vitamin C “helpers”. Pycnogenol inhibits the enzymes that degrade ingested vitamin C, thereby potentiating and prolonging its anti-oxidant, pro-collagen, anti-inflammatory, and vascular wall protecting effects. In addition, some research suggests that pycnogenol actually enhances vitamin C absorption and helps transport it into the tissues to its site of action. Pycnogenol effects the blood platelets in a manner similar to aspirin, making them less likely to stick to a damaged vascular surface, there initiating blood clotting and potentially producing a heart attack. Given these multiple artery protecting properties, you will not be surprised to learn that the bioflavonoids have been shown to help prevent coronary disease in humans. As early as 1957, it was shown that red wine protected laboratory animals on a high cholesterol diet. Studies in the ‘70s and ‘80s demonstrated that pycnogenol was effective in preventing experimental atherosclerosis in laboratory animals. In 1990, we learned that pycnogenol could inhibit atherogenic test tube LDL oxidation, just like vitamins E, C, and beta-carotene. The “French Paradox”, the fact that coronary rates are low in France, despite intake of saturated fats and cholesterol similar to that in the U.K. and U.S., was explained in 1993 on the basis of the high intake of red wine in France. Red, but not white wine contains-you guessed it- relatively high concentrations of bioflavonoids. Data from the European Seven Countries Study, published in February of 1995, showed that dietary bioflavonoid intake was second only to saturated fat intake in explaining differences in coronary death rates between 16 population groups in Europe. The Zutphen study, published in 1993, described a similar, extremely important protective effect of dietary bioflavonoid intake on subsequent five year coronary mortality. The average bioflavonoid intake amongst the Dutchmen studied was 26 mg/day. Those in the upper 20% of bioflavonoid intake, taking in 30 mg. or more of bioflavonoids each day, enjoyed a 58% decrease in coronary death risk in comparison to the men in the lowest 20% of bioflavonoid intake, who took in less than 19mg/day. The relative risk reduction associated with bioflavonoid intake became even greater after the investigators adjusted the data to take into account differences in cholesterol, smoking, anti-oxidant intake, and the other usual risk factors, between the groups. Foods found to be particularly good sources of bioflavonoids, containing >50 mg/kg include onion, kale, broccoli ,celery, endive, and cranberry. Red wine, tea, apple, strawberry, lettuce, tomato, grape, tomato juice, and red pepper contain <50 but >10 mg/kg or mg/liter of bioflavonoids, while white wine, coffee, pea, spinach, carrot, mushroom, and orange juice serve as less important sources, providing <10 mg/kg or ml/kg. These are ideal world values, but sadly, just as with the anti-oxidant vitamins, our “pick before ripening” and food processing practices rob these foodstuffs of most of their beneficial bioflavonoid content well before they get to your plate. While an apple a day may have kept your grandmother out of the cardiologist’s office, the prematurely picked, alar coated, chemically ripened apple that spent some time in a warehouse before it was trucked up I-75 to your grocery store isn’t going to provide you with the same benefit. Given the benefits of bioflavonoids and their relative absence from our fruit and vegetable lean diets, adding pycnogenol or another bioflavonoid containing preparation to your risk factor reduction program makes sense.
BLOCKER OF ALLERGIC, INFLAMMATORY, AND HISTAMINE REACTIONS: Allergic, asthmatic, and auto-immune diseases( lupus, rheumatoid arthritis, thyroiditis, etc.) are brought on by confusion within our immune system. Our immune system, or “natural defense” is charged with recognizing our normally functioning cells as “self”, and leaving them alone, while at the same time recognizing invading infectious agents and damaged or malignantly transformed cells as “non-self”, and then eliminating them. Immune T cells and B cells orchestrate this defense system, but much of the actual cell killing is carried out by free radicals, and by histamine and the leukotrienes, potent mediators of inflammation that kill all in their path. In allergic diseases, an environmental agent fools or “sensitizes” the immune system into inappropriately attacking our own cells. In hay fever, ragweed sensitizes the immune system to release histamine within our sinuses and nasal passages; in asthma the lungs are affected, producing inflammation and wheezing. In the auto-immune diseases, a chronic, tissue damaging inflammatory reaction occurs. A good example would be the progressive joint dysfunction and damage seen in rheumatoid arthritis. The bioflavonoids cannot prevent the immune system confusion that sets up asthma and these other problems, but as effective blockers of histamine and leukotriene release, the “business end” of the immune system, they can significantly reduce the symptoms and cellular damage that would otherwise occur. Pycnogenol blocks histamine release, and is used in Europe as a recognized treatment for hayfever. Vitamin C also lowers histamine levels, and when combined with pycnogenol will enhance its anti-allergic, anti-histamine effect. Bioflavonoids and vitamin C have been shown to favorably effect the capillary fragility characteristic of rheumatoid arthritis. Leukotrienes, potent mediators of inflammatory tissue damage, and immune system generated free radicals, are also favorably affected by pycnogenol. Why put yourself asleep with Benadryl; why not try pycnogenol and vitamin C the next time your sinuses flare up?
Emotional and medical stress can produce ulceration and bleeding of the stomach, small intestine, and esophagus. This inflammatory response is mediated by histamine, and we commonly treat this condition with “histamine blockers”, drugs such as Zantac, Tagamet, and Pepcid. These drugs lessen gastric inflammation by blocking the action of histamine on the lining of the digestive organs, while pycnogenol, as a nutritional supplement, can get the job done by blocking the release of histamine in the first place (Using drugs instead of nutrition and prevention in this manner is kind of like proceeding with the $40,000 bypass that you need following a heart attack, when you could have prevented the coronary narrowing and the heart attack in the first place with nutrition and risk factor reduction).
PROTECTING THE CIRCULATION: Our circulatory system consists of an intricate and extensive network of arteries, veins, and capillaries (Extensive is right; a piece of skin the size of a quarter contains over one yard of blood vessels). The circulatory system has only one job, the exchange of nutrients for waste products. Disease oriented medicine (how we doctors make our living) focuses on the arteries and veins, the conduits that transport nutrition to, and waste products away from, our five trillion cells. Preventative cardiology certainly does not ignore the arteries, but in discussing the benefits of bioflavonoids we will focus more on the thin walled capillaries, the “functional end” of the circulation, where the exchange of nutrients for wastes actually takes place. The arteries carry nutrients and oxygenated blood, under pressure, away from the heart and to our vital organs. To handle this load, the wall of the artery is thickened by layers of muscular and connective tissue cells; sugar and oxygen cannot pass from blood to our cells directly through an artery’s thick wall. The major arteries divide into smaller arterial vessels, known as arterioles, which then subdivide into billions of thin walled capillaries. The capillary is composed of a single layer of a specific type of cell known as a vascular wall or endothelial cell. The endothelial cells are supported and “glued together” by a matrix composed of collagen and to a lesser extent elastin fibers, which in turn are critically dependent on vitamin C for their production and maintenance. Dysfunction of the endothelial cell, due to vitamin malnutrition and undefended free radical attack, or disruption of the collagen support matrix, due to vitamin C deficiency or the damaging actions of histamine, the inflammatory prostaglandins, or leukotrienes, will produce a “leak” in the capillary barrier. Fluids then begin to ooze out from the bloodstream, producing the tissue swelling medically termed as edema. This edema fluid is now sequestered out of the circulation; the heart no longer has the opportunity to pump it to the kidneys for elimination. The fluid just sits there, producing discomfort, discoloration, inflammation, and further tissue damage that leads to even more edema( What does chronic edema do to the appearance of your skin?). Pycnogenol can mount a four pronged attack to “plug” capillary leaking and break the inflammatory edema cycle. First, as a protector of vitamin C, pycnogenol enhances collagen production, leading to a stronger capillary surface. Second, as a potent anti-oxidant, pycnogenol helps ward off free radical attack on the endothelial cell. Third, by preventing the release of histamine and the formation of the inflammatory prostaglandins, pycnogenol helps prevent inflammation at the site of capillary leakage (“it gets the red out”). Unique among the bioflavonoids, pycnogenol has the ability to crosslink collagen fibers; this helps strengthen and protect the fibers from inflammatory attack, further strengthening and improving the capillary membrane. While new to the U.S., the benefits of bioflavonoid nutrition have long been appreciated overseas. Six million tablets of pycnogenol are consumed in Europe every day, and its use in the treatment of capillary leak edema is fully covered by medical insurance . The European medical literature is fully supportive of its use. 77% of varicose vein patients experienced a clear improvement in their symptoms while on daily treatment with 90 mgs. of pycnogenol; 93 % reported that pycnogenol helped prevent nightly leg cramps. In a controlled study of edema patients taking 300 mgs. of pycnogenol per day, swelling disappeared in 26% after 30 days, and in 63% following 60 days of treatment. Leg pain resolved in 38% at 30 days and in 67% by 60 days. Pycnogenol is also used in Europe in the treatment of diabetic retinopathy, bleeding behind the eye due to the fragile retinal capillaries of the diabetic patient. In our patients, ankle swelling may occur as a consequence of congestive heart failure, where edema fluid within the vasculature builds up behind a poorly functioning heart. A diuretic agent such as lasix is then prescribed to help mobilize this fluid. Much more frequently, we see ankle swelling as the consequence of abnormal capillary permeability, venous insufficiency, or as a side effect of an otherwise necessary medication. Lasix will mobilize this fluid, but only by first producing volume depletion within your vascular space, stressing your kidneys, and exposing you to really unnecessary side effects, such as diuretic related elevations in cholesterol, blood sugar, and uric acid (the cause of gout). A program of periodic leg elevation, pycnogenol, preferably supported by vitamin C and the other anti-oxidants, and if needed, support stockings, makes much more sense in this situation (And does anyone really like having to get up at night when the lasix is doing its work?).
SKIN PROTECTION AND REJUVENATION: The appearance and barrier function of your skin depends upon the integrity and function of the dermal collagen and elastin fibers that support it. Just as with the vasculature, free radicals, histamine, and other inflammatory enzymes such as collagenase and elastase can disrupt these fibers, damaging your skin. Just think how easy it is for you to identify a long term smoker or over zealous sun worshipper. Years of undefended free radical attack produces the dry, inelastic, wrinkled appearance of their skin. Fortunately, free radical skin damage can be prevented, and in some cases improved and reversed, and pycnogenol can help. As an anti-oxidant, pycnogenol can neutralize the attacking free radicals before they have a chance to do damage. Unique among the bioflavonoids and other anti-oxidants, pycnogenol can bind to collagen and elastin fibers, protecting them from the damaging effects of inflammatory enzymes, while at the same time realigning the fibers, to give the skin a more functional and youthful appearance. It is little wonder that pycnogenol is a component in many oral and topical skin protection and rejuvenation products; it also works well as a sunscreen and helps prevent easy bruising in some individuals.
OTHER REPORTED BENEFITS: Given its ability to quench free radicals, block the release of histamine, and neutralize the inflammatory prostaglandins, you won’t be surprised to learn that many other benefits have been associated with the use of pycnogenol and the other bioflavonoids as nutritional supplements. This isn’t “snake oil”; rather it is the intelligent application of cellular biochemistry to improve your health. If pycnogenol can help one cell, why shouldn’t it help all of your cells? Bioflavonoids with vitamin C, just like dioscorea, help reduce the hot flashes and other symptoms that some women experience with menopause. In a double blind study comparing 1200 mgs. per day each of vitamin C and a bioflavonoid mixture to “conventional” therapy, the anti-oxidants won out, producing complete relief of symptoms in 67%, while a standard estrogen preparation produced complete relief in only 36% of the women. While interpreting this information, keep in mind that estrogen treatment does increase your risk of developing endometrial cancer. Anti-oxidants are felt to have a protective effect against malignancy, and bioflavonoids, including components of pycnogenol, have been shown to help prevent experimental cancer in laboratory animals. Given their anti-inflammatory and radical quenching abilities, many researchers feel that the bioflavonoids and the other anti-oxidant vitamins will have similar effects in humans. Excessive menstrual blood flow has been shown to respond to the combination of vitamin C and bioflavonoids. Sports injuries occur less frequently and heal more rapidly in athletes who take vitamin C and bioflavonoids, as shown in studies involving the Los Angeles Dodgers baseball team and the Louisiana State University football squad. Vitamin C with bioflavonoids decreased the incidence of bleeding complication from anti-coagulation therapy with coumadin in one study. Capillary fragility in rheumatoid arthritis patients improved in response to this combination. Anecdotal reports describe an improvement in arthritic symptoms overnight following a large bedtime dose of pycnogenol. One report described a significant improvement in the functional status of AIDS patients.
DOSAGE AND SAFETY CONSIDERATIONS: Like vitamin C, pycnogenol is water soluble and is therefore not stored to an appreciable extent in our bodies. Most authorities recommend that supplementation be initiated with a loading or “saturation” dose of 150 mgs/day for one week, followed by an ongoing or “maintenance” dose of 50 mgs. each day. Individuals bearing an increased free radical burden, such as smokers and individuals with active, inflammatory medical problems, might benefit from a higher maintenance dose of 100 mgs/day. The dose that makes you feel your best is the best dose for you, as there are essentially no safety considerations with pycnogenol. While new to the U.S., pycnogenol supplements have been taken in Europe for over 20 years.
The books and literature that I reviewed did not describe any adverse reactions or side-effects associated with the use of pycnogenol as a nutritional supplement. This really shouldn’t surprise you. Unlike chemically synthesized pharmacological agents, which alter cellular physiology to achieve the desired therapeutic effect, pycnogenol and related bioflavonoids are naturally occurring substances, extracted from naturally grown plant sources, that simply help your cells do what they want to do-to fight off free radical attack, ward off the effects of inflammatory enzymes, histamine, and prostaglandins, and to go on functioning in the normal, optimum fashion that nature intended. We don’t expect side-effects from Mother Nature and we don’t get them. Pycnogenol has been tested for mutagenic (DNA altering), teratogenic (birth defect), carcinogenic (cancer causing), and antigenic (allergy provoking) characteristics and none have been found. Extrapolating from studies in animals, humans would not begin to experience significant toxicity from pycnogenol until 35,000 mgs. had been taken on a daily basis for 6 months. Acute toxicity would not be expected until 336,000 mgs. had been taken in.
HOW TO OBTAIN PYCNOGENOL: The name Pycnogenol is trademarked to Horphag Research Ltd., and refers to a mixture of proanthocyanidins and other organic acids of pine bark origin. The same group of compounds can be extracted from grape seeds and other natural sources; the original research by Dr. Masquilier was actually carried out with pycnogenol derived from grape seeds. My reading turned up no evidence that pycnogenol preparations derived from grape or mixed sources are better than pycnogenol of pine bark origin, or visa versa. Claims to the contrary are, in my opinion, only for marketing purposes. Preparations containing the proanthocyanidin catechin molecules bound together in repeating units (called oligomeres), do possess more potent free radical fighting strength and are worth paying a slight (and only slight) premium for. Pycnogenol is naturally occurring and cannot be patented, and as such will never be distributed as a prescription drug. Fortunately for us, Pycnogenol and preparations containing Pycnogenol and other bioflavonoids are relatively low in cost and are readily available. Pycnogenol can be obtained from health food stores and nutritional mail order concerns; many pharmacies are beginning to carry Pycnogenol in their non-prescription supplement sections.
Health care in America has until now focused primarily on “sick care”, high tech (and highly reimbursing) intervention that begins only after you become ill. The cost of this disease oriented approach is rising rapidly, especially in cardiology, and threatens to bankrupt our entire health care delivery system. The only solution is for Americans to learn how to promote their own good health, and then to take the responsibility to put these measures into action. We hope that the information contained in this monograph and in our other patient information materials will help you to put yourself on the road to good health.
James C. Roberts MD FACC