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Grape Seed Extract
Potent Antioxidant

by Max Costello

     It seems that nearly every week a new fad, health product or diet comes to our attention. Maybe we have become disillusioned by the proliferation of articles and claims being made. Do we label everything as fake and how can we sort the wood from the vines? You will get that later! Hopefully my information will blend the scientific with the natural aspects in a product that covers both areas. Much of science started in nature. Would you be surprised if your doctor prescribed 12 grams of dried grape seed three times daily? Would it be more understandable if he said 100mg Oligomeric Proanthocyanidin Complex three times daily, or sound more like medicine? Was it nature’s grand ironic design that the symbol of affluent lifestyles, grapes and wine, had the antidote to decadence at its very heart, in the discarded pip?
     Sixty years ago a scientist won a Nobel prize for work on vitamin C, the substance used by Capt. Cook 200 years ago to stop scurvy. Cook knew that fresh fruit was important to diet but it took a while for his anecdotal evidence to be accepted. Now we hear of a substance science tells us is an antioxidant 20 times more powerful than vitamin C and 50 times more powerful an antioxidant than vitamin E. Dr Clark Hansen N.D., claims it is the most significant discovered this century! We will also see that 400 years ago this antioxidant was used by the North American Indians, but the actual properties were only identified by the scientific community 40 years ago. Now this natural antioxidant, used extensively for years in France where it is registered as a medication, and becoming popular in other western countries, is gaining popularity here.
     Is this information important? To decide we have to understand what an antioxidant (against oxidation) is. Rust is an iron oxide (oxidation). Hardening/drying of paint is a process of oxidation. Eventually aged paint becomes chalky with oxidation. The brown on the cut piece of an apple is “oxidised apple”. Citrus juice is an antioxidant, rub some lemon juice on the cut apple and it slows down the oxidation (browning). Magic? Ageing (collagen deterioration) is a form of bodily oxidation. Free radicals found widely in our environment, water, air, food, smoke, smog, sunlight, chemicals, detergents, etc. are the nasty “unstable” oxygen molecules which are responsible for attacking (oxidising) our bodies. As they are unstable, they are looking to attack, and in our bodies they attack and destroy cell membranes, collagen and other connective tissue, disrupt physiological processes and create mutations in the DNA cells. Free radicals are blamed for many problems from ageing spots (oxidised fat in the skin) to cancer.   Nutritionist and chemist Dr Jeffrey Bland Ph.D. claims the destructive effect of free radicals are responsible for more than 60 diseases including Allergies, Arthritis, Attention Deficit Disorder, Cataracts, Cold fingers and toes from circulatory problems, Diabetes, Edemas, Hardening or Narrowing of the Arteries and High Blood Pressure (Oxidation of Cholesterol causing plaque in the vessel walls), Heart Disease, Inflammation, Kidney and Liver disorders, Parkinson’s Disease, Prostate Enlargement, Rheumatism, Stroke, Ulcers, Varicose Veins and Wrinkles. Oxidation is very important in the chain to break down waste minerals, dead plants and dead animals and for regeneration. Antioxidants stop it starting before we actually die. Now back to where this antioxidant all started for us. . . .
     In the 1530s French explorer Jacques Cartier was leading an expedition up the Saint Lawrence River in North America. When the crew were trapped in the ice they were limited to eating rationed biscuits and salted meat and it wasn’t long before scurvy (a lack of vitamin C) became rife. However, native Indians introduced them to a tea made from the bark and needles of the pine tree. They recovered and the story was recorded but the healing event, how and why, did not progress scientifically until 400 years later when Professor Jacques Masquelier of the University of Bordeaux, France, read about it and formed the conclusion that the tree contained Vitamin C. Later he isolated and identified the substance as proanthocyanidins and called his product Pycnogenol. His method of extraction from the pine tree was patented in the early 1951, and further research showed the substance present in many plants such as, lemon tree bark, peanuts, hazel nuts, cranberries, blue berries, cherries, citrus peel, purple, red and white grape skins and seed purple grape seeds being the most concentrated source. This substance, a bioflavonoid, is now usually referred to as OPCs (Oligomeric Proanthocyanidin Complexes) or less frequently PCO (Proanthocyanidolic oligomers).
     Bioflavonoids, of which there are approximately 4000, are some of the most important and interesting biological compounds. As shown they are present in a wide variety of edible plants, fruit and vegetables with a typical Western diet providing about 1g of them per day. They were originally identified as the flavin (yellowish colouring) in plants. Remember carrots and seeing in the dark or doctors suggesting drinking a glass of wine daily for health? Bioflavonoids have a low molecular weight and occur naturally as aglycons, glycosides and methylated derivatives.¹
     In the early 1980s bioflavonoids were reviewed for a wide range of biological activities focusing on their potential therapeutic use as anti-inflammatory, anti-allergenic, antiviral, anticancer and immunostimulant drugs.^2,3
     Since 1984, in an attempt to give an account for bioflavonoids wide pharmacological potential many papers have been published dealing with the interaction between flavonoids and such key enzymes as cyclo-oxygenase, lipoxygenase, phospholipase A2, cyclic nucleotide phosphodiesterases, protein-kinase C, hyaluronidase, reverse transcriptase, mitochondrial succinoxidase, NADH-oxidase and glutathione reductase. This led to the big question of how do bioflavonoids work?
     In the light of Middleton’s³ hypothesis it appeared the key steps in producing the biological effect could be the interaction with the protein phosphorylation as well as its antioxidant activity. This combined with the increasing evidence that toxic oxygen species were involved in a number of pathological conditions, including inflammatory processes, ageing and cancer.^4,5,6
     Leucoanthocyanins (proanthocyanidins or OPCs, pycnogenols) are natural polyphenols belonging to the class of bioflavonoids.^7,8 The Leucoanthocyanins are constituted by a variable number of flavin units and they yield an anthrocide after heating in acid medium. From grape seeds an oligomeric fraction partially esterified with gallic acid and containing only little amounts of momomeric polyphenols (catechin and epicatechin) has been isolated.⁹
     Leucoanthocyanins have been reported to improve biological properties of blood vessels¹⁰ leading to their use in the therapy of such different types of vascular disorders as capillary fragility, peripheral chronic venous insufficiency and micro-angiopathy of the retina.^11-15
     Until recently pharmacological properties of Leucoanthocyanins were attributed to their ability to increase tonicity and the resistance to the degradative action of elastase and collagenase.^16,17 More recently increasing evidence supports the hypothesis of the anti-oxidant properties and possible chemoprevention on free radicals already mentioned in association with cancer, ageing etc. 

Antioxidant Effect
     The antioxidant effect of Leucoanthocyanins has been studied “in vitro” in phosphatidylcholine liposomes using 1/ Iron-promoted lipid peroxidation and 2/ Ultrasound-induced lipid peroxidation. Both showed Leucoanthocyanins markedly more effective than alpha-tocopherol.

Anti-enzyme Effect
     In vitro activity of Leucoanthocyanins was tested by conventional techniques on several enzymes such as Xanthine oxidase [2.4], Elastase [4.2], Collagenase [38.0], Hyaluronidase [80.0] (-Glucuronidase [1.1]. Note the individual results in brackets [IC50 (mol/l)].
     The anti-oxidant and anti-enzyme effect provide a strong molecular basis for the capillary protective action of Leucoantho- cyanins, demonstrated in several “in vitro” experimental models of altered capillary permeability.^10,18,19 This protective effect of Leucoanthocyanins is therefore a pluricentric mechanism based on radical scavenging and antioxidant effects and the inhibitions of some key enzymes. The integrated action hypothesis is also supported by data which clearly indicate a marked tropism of Leucoanthocyanins for vessel walls, skin and other tissues, characterised by the elevated presence of glycosaminoglycans.^20-26

Antimutagenic Effect
     Saccharomyces cerevisiae strain S288C were tested
     1 Mitochondrial Antimutagenesis tested the production of respiratory deficient mutants as phenotypic manifestation of mitochondrial mutation.²⁷
     2 Nuclear Antimutagenesis activity was studied and the effect established using the forward mutation system from L-canavanine sensitivity to L-canavanine resistance.^28,29
     The results clearly suggest a possibility to employ natural antioxidant/antimutagen principles such as Leucoanthocyanins in a preventative diet-based strategy against major pathologies. In fact we are now proving scientifically what many believed for a long time, the assumption of antioxidant/antimutagenic substances contained in food is correlated with a lower incidence of some types of cancer and cardiovascular disease.^30-32

Tolerability
     The prime factor for management of long term preventative treatments is safety.
     Leucoanthocyanins are practically devoid of oral toxicity (LD50>4000 mg/kg in rats and mice) and any other toxic effects even at high dosages, in oral chronic toxicity tests (60 mg/kg/day for 12 months in dogs and 6 months in rats). Note: That equates to a 100 kg man taking 60 capsules 100mg strength daily. Leucoanthocyanins are also devoid of any mutagenic and teratogenic effects and are safe as far as fertility, peri- and post-natal toxicity are concerned.

Efficacy
     Leucoanthocyanins have been investigated in the treatment of venous-lymphatic insufficiency, and post-surgical lympho-oedema of the breast, at a dosage of 150mg twice daily.
The table above summarises a double blind placebo study in which Leucoanthocyanins were administered 30mg daily for 3 months to patients suffering from venous-lymphatic disease.¹²
    In a double blind test for peripheral disease of lower limbs improvement was seen in 87% of the cases using Leucoantho- cyanins compared with 45% with the placebo.

Clinical Sight Indications
     1 Controlled double blind testing was carried out on resistance to night glare and night vision by means of Comberg’s nyctometer and ergovision on 100 subjects treated for 5 weeks with twice daily doses of 100mg of Leucoanthocyanins.³³ Results showed a marked improvement in visual performance compared to the control group. This was attributed to a faster regeneration of the retinal structures from Leucoanthocyanins.
     2 A study on 75 patients suffering from ocular stress caused by their working at a computer screen were treated with Leucoanthocyanins (300 mg/day) for 2 months. Graphs of the results show considerable improvement.³⁴
     3 Two further tests on 200 patients with myopic chorioretinosis were conducted for two months with Leucoanthocyanins (150 mg daily). Computerised examination at the start and end of the trials demonstrated a marked global increase on visual functions.^35,36

Grape Seed and Pine Bark
     There are some important differences.
     1 Antioxidant advantage. In the words of Professor Masquelier, developer and patentee of both OPC products announced: . . . “I underline that in 1986 I discovered that grape seed has an intense free radical scavenging effect (FRSE) on radical oxygen species. These discoveries were laid down in my U.S. Patent (no 4,698,360) of Oct. 6 1987, ‘Radical Scavenging Effect of Proanthocyanidins’ . . . The tests showed that in this respect OPC from Grape seed has an advantage over OPC from Pine bark. OPC from grape seed contains the gallic esters of proanthocyanidins (in particular: Proanthocyanidin      B2-3’-O-gallate). These proanthocyanidins – esters have been recently described as the most active substances in the battle against free radicals.” October 1991 Martiliac, France (Procyanidines de France).
     Independent research by Dr Ricardo Da Silva showed “Proanthocyanidin B2-3’-O-gallate” available only in grape seed was found the most effective compound in trapping free radicals.³⁸
     2 Strength. Pycnogenol (Pine tree) has an OPC strength ranging from 80-85% compared with Grapeseed normally marketed at 90-95%. Be careful that the Grapeseed is 95%. A slight difference in favour of grapeseed. Research points toward the fact that proanthocyanidin 100% purity is non-mutagenic.³⁷ Thus the range 90-95% for maximum benefit.
     3 Price. Both are sold in capsule form. You will find that whilst both products are not cheap, per milligramme of OPCs as Pycnogenol cost 6-8 times OPCs in grape seed extract.

Breast Cancer
     Dr Jacques Masquelier, points out breast cancer is caused for a large part by the destruction of our DNA by free radicals. By protecting our DNA with OPCs we are also protecting ourselves indirectly against this risk.
     Note: Readers interested in more detailed and/or scientific information please send a stamped self addressed A4 envelope to Max Costello, c/o P.O. Box 18, Abbots Langley, Herts WD5 OSY.

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