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OPC- Antioxidant Superstar

By Yousry Naguib, Ph.D.

Vitamin Retailer magazine (February 2001)

Almost half a century ago, Dr. Masquelier in France discovered OPC. He became intrigued with the story of the French explorer Jacques Carier who along with his crew suffered scurvy, during the winter of 1534, and survived after drinking a tea made from Pine bark. Dr. Masquelier began working on Pine bark and extracted a group of chemicals known as oilgomeric proanthocyanidins, OPC, and he named it Pycnogenol (pronounced pik-nah-ja-nol), a term which became a trade name for OPC derived from French maritime bark.

In 1970, Dr. Masquelier patented an extraction method to obtain OPC from another natural source, namely grape seeds [1], which has become the preferential source of OPC. Proanthocyanidins are also found in green tea, other fruits (such as grapes, cranberry, bilberry), vegetables, seeds, and nuts. These substances are responsible for providing the pigments that color plants.

OPC belongs to a group of compounds known as flavonoids. Flavonoids are polyphenolic compounds that are widely distributed in fruits and vegetables and are components of the human diet. It is estimated that the human intake of all flavonoids is a few hundreds milligrams per day. To date, more than 4000 different flavonoids have been isolated and identified.

The flavonoids family members include flavones, isoflavones, flavonols, and flavonones. Flavonones undergo a series of biochemical transformations in plants which give rise to other family members of flavonoids, including anthocyanins and their aglycones anthocyanidins, catechins, and epicatechins. OPC consists of two or more repeating units of monomeric flavan-3-ol molecules (mostly catechin and epicatechin). The term OPC covers many different and complex molecules (various oligomers of proanthocyanidins).

Some flavonoids have been shown to elicit anti-lipoperoxidant, anti-tumor, anti-platelet, anti-ischemic, anti-allergic, and anti-inflammatory activities. Certain flavonoids also possess potent inhibitory activity against a wide array of enzymes such as protein kinase C, protein tyrosine kinases, and phospholipase A2.

Anti-Oxidant Activity

A number of studies have indicated that the antioxidant activity of flavonoids accounts for their potential health benefits, because oxidative stress leads to a variety of pathophysiological events.

A single-blinded randomized, placebo-controlled study involving 20 young volunteers, given two capsules of 300mg grape seed procyanidin extracts (Leucoselect-Phytosome) or placebo daily for five days, showed that the extract had no effect on serum vitamins C and E levels but increased serum total antioxidant activity [2].

In a recent study, Dr. Bagchi and coworkers at Creighton University found that a novel grape seed proanthocyanidin extract (IH636, marketed as Activin) is highly bioavailable and provides greater protection against free radical-induced lipid peroxidation, and DNA damage than vitamins C, E, and beta-carotene [3].

A Japanese study found that plasma obtained from rats fed proanthocyanidins at 25mg/kg of body weight was significantly more resistant against oxidation, induced by copper ions or the free radical initiator AAPH, than that from control rats. The study suggested that intake of proanthocyanidins may contribute to physiological functions through their antioxidant ability [4].

A standardized extract obtained from the French maritime pine bark (Pycongenol) was found in a number of studies to be a potent antioxidant against oxygen and nitrogen free radical, and to participate in the cellular antioxidant network as indicated by its ability to regenerate ascorbic acid and to protect endogenous vitamin E and glutathione (an essential antioxidant in cellular systems) from oxidative stress [5]. In an in vitro study, Dr. Packer at the University of California found that the French maritime pine bark extract provided protection of endothelial cells from reactive nitrogen free radicals induced glutathione depletion [6].

Cardiovascular System

Cardiovascular diseases remain the major cause of mortality and morbidity in Western countries. The lower incidence of heart diseases in French and Mediterranean people, despite a diet rich in saturated fat, referred to as the “French paradox”, has been ascribed to high consumption of red wine. Red wine contains flavonoids (approximately 750mg/Litre), which can provide their beneficial effects by inhibiting oxidation of lipoproteins LDL, and by decreasing platelet aggregation, a condition which occurs when blood cells stick together and forms clots in the blood.

An alcohol free wine extract containing 50% proanthocyanidins (monomers and oligomers) was shown to protect low density-lipoprotein (LDL) from oxidation induced by either copper ion or free radical initiator AAPH [7]. Prevention of LDL oxidation is sought to reduce the risk of atherosclerosis, the main cause of coronary artery disease.

In an animal study, Activin was shown to provide significant protection against myocardial ischemia-reperfusion injury. Rats were given Activin, 100mg/kg/day, for three weeks and then sacrificed. Their hearts were subjected to ischemic- reperfusion; those fed Activin showed improvement in ventricular heart function, a reduction in the extent of myocardial infarction, and reduction in tissue damage caused by ischemic-reperfusion injury as compared to the control group [8]. The cardioprotective effect of Activin was ascribed, at least in part, to its potent antioxidant activity and ability to scavenge oxygen free radicals, which are generated in the heart during ischemic and reperfusion.

Fitzpatrick and colleagues at University of South Florida conducted a series of experiments, mostly on Pycnogenol, to understand the mechanism of cardioprotective effects of OPC. In an in vitro study, Fitzpatrick subjected Pycnogenol to fractionation, and isolated a fraction, which was shown to stimulate nitric oxide synthase enzyme to produce nitric oxide molecule (also called endothelium-relaxing factor), thus enhancing vasodilation and reducing high blood pressure. Nitric oxide also protects the vessel wall by inhibiting the stickiness of platelets (which forms blood clots), and by inhibiting oxidation of LDL. The latter effect is thought to be important in preventing plaque formation during development of atherosclerosis [9].

Earlier test tube studies also showed that aqueous grape skin extracts, as well as red wine, grape juices, and extracts of grape seeds produce endothelium dependent relaxing activity in arteries. Grape skin extracts and wines inhibited contractions induced by the vasoconstrictor norepinephrine [10].

In another test tube study, Activin exhibited a synergestic effect with vitamins C and E in inhibiting LDL oxidation by cupric ions. This study also reported that hamsters fed Activin, at 50mg/kg, in conjunction with a hyper-cholesterolemic diet of 0.2% cholesterol and 10% coconut oil showed 50% reduction in foam cells, which cover the aorta in atheroscelerosis [11], indicating the beneficial effect of Activin in ameliorating the incidence of atheroscelerosis.

Circulatory System

Healthy blood vessels including arteries, veins and capillaries are necessary for the blood to transport nutrients and oxygen to all tissues in our body, and to carry waste away. If blood vessels become weak, fragile, or brittle, blood can’t circulate properly and a host of vascular-related disorders, such as venous insufficiency (varicose veins) and retinopathy develop.

OPC (from grape seeds and pine bark) has been proven to strengthen blood vessels, to improve blood flow, and to reduce capillary fragility and permeability. Because of these therapeutic values, OPC has become quite popular in Europe for treatment of varicose veins and various vascular disorders. Indeed, OPC is the active ingredient in a proprietary pharmaceutical product (Endotelon) sold in France that is used for microcirculatory disorders [12].

In a double-blind study, 92 patients with venous insufficiency received 300mg OPC from grape seed (Endotelon) daily. After four weeks, a significant reduction in symptoms (pain, swelling, tingling, cramps) was observed in 75 percent of the OPC treated patients compared to 41 percent of the patients given a placebo [13].

In another double-blind study, OPC (Endotelon), 150mg/day, was compared with the commonly prescribed pharmaceutical drug Diosmine on 50 patients with symptoms of chronic venous insufficiency. Both therapies were effective and all symptoms improved within thirty days, but OPC worked more rapidly and its action lasted longer [14].

Anti-Tumor

Topical application of grape seed extract was found to possess high anti-tumor promoting activity in mouse skin, employing a model system that involves initiation with dimethylbenzanthracene and promotion with a derivative of phorbol (a well-known inducer of free radicals and tumor promotion in living organisms). Fractionation of the grape seed extract resulted in a fraction containing mainly procyanidin B5-3- gallate that showed the most potent antioxidant activity in an epidermal lipid peroxidation assay [15].

Activin demonstrated significant cytotoxicity towards human breast, lung, and gastric cancer cells, and enhanced the growth and viability of normal cells [16]. A study on mice revealed that Activin is bioavailable and provides better protection against TPA (12-O-tetradecanoylphorbol-13-acetate) induced free radical production in the peritoneal macrophages (white blood), lipid peroxidation, and DNA damage in the brain and liver tissues as compared to vitamins C and E, beta-carotene, and a combination of vitamins C and E [17].

Anti-Ulcer Activity

A recent Japanese study demonstrated that grape seed extract at 200mg/kg of body weight inhibited the stomach mucosal damage, induced by an alcohol (EtOH) containing hydrochloric acid (HCl). This protective effect was dependent on the number of catechin and epicatechin units in the proanthocyanidin oligomers. Oligomers with four or more units showed a strong protective effect. The study proposed that procyanidins protect the stomach surface by scavenging free radicals produced by EtOH/HCl treatment [18].

Other Benefits

OPC has also been shown to relieve eye stress and improve visual performance after glare, which is important for night driving. A French controlled clinical trial on 100 subjects, with no major retinal or ophthalmological pathology, found OPC (Endotelon) supplementation, at 200mg per day for five weeks, resulted in a dramatic increase in the recovery of visual acuity after being subjected to bright lights [19]. In another study, nearsighted people with ocular stress caused by working at a computer display unit were treated with OPC (300mg/day for 60 days). Contrast sensitivity was significantly improved by OPC as compared to the placebo [20]. Other studies have found that OPC was successful in treating retinopathy that causes deteriorating eyesight, particularly in diabetics [21].

Activin was also shown to protect liver and kidney in mice from acetaminophen (AAP) induced toxicity, this action is presumed to be due to the antioxidant activity of Activin or, in part, due to the ability of Activin to inhibit the drug metabolizing enzymes [22].

The efficacy of OPC (Endotelon) in alleviating premenstrual syndrome (PMS) was demonstrated in a multi-center study on 165 women. Women supplemented with OPC for 4 months experienced a 78 percent reduction in duration and intensity of PMS symptoms, abdominal swelling, pelvic pain, venous problems of the legs [23].

Safety and Dosage

OPC has been tested in laboratory animals. It was well tolerated with no toxic, mutagenic effects [24]. The recommended dosage of OPC is between 150-300 mg per day for treatment of medical disorders, and between 50-100mg as a preventive regimen.

Summary

OPCs possess quite broad therapeutic applications, due mostly to their potent antioxidant activity. OPC has been proven to be a good medicine for varicose veins. OPC can block free radical-induced damage to cells lining arteries (endothelial cells), to inhibit oxidation of low-density lipoprotein, and the aggregation of platelets, and therefore may provide cardiovascular protection. OPC has also been shown to enhance adaptation of the eye to bright light and to ameliorate diabetic retinopathy.

References

[1] Bert Schwitters and Prof. Jack Masquelier. OPC in Practice. Alfa Omega Editrice, Publishers, 1993.

[2] Nuttal SL et al. An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. J Clin Pharm Ther 1998;23:385

[3] Bagchi D et al. Free radicals and grape seed proanthocyanidin : importance in human health and disease prevention. Toxicology 2000;148:187

[4] Koga T et. Al. Increase of antioxidative potential of rat plasma by proanthocyanidin extract from grape seeds. L Agric Food Chem 1999;47:1892

[5] Packer L et al. Antioxidant activity and biological properties of a procyanidin extract from pine bark, Pycnogenol. Free Radic Biol Med 1999;27:704

[6] Packer L et al. Effect of procyanidins from Pinus maritime on glutathione levels in endothelial cell. Redox Rep 1999;4:171

[7] Fremont L. Antioxidant activity of resveratrol and alcohol free wine on LDL oxidation and polyunsaturated fatty acids. Life Sci 1999;64:2511

[8] Sato M et al. Cardioprotective effects of grape seed proanthocyanidin against ischemic reperfusion injury. J Mol Cell Cardiol 1999;31:1289

[9] Fitzpatrick D et al. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmcol 1998;32:509

[10] Fitzpatrick D et al. Vasorelaxation, endothelium, wine. BioFactors 1997;6:455

[11] Vinson JA et al. Beneficial effects of a novel grape seed extract in atherosclerosis models. Free Radic Biol Med 1999;S45 (Suppl):Abstract 99

[12] HerbalGram No.39, p.20

[13] Thebaut JF et al. Study of Endotelon in functional manifestation of peripheral venous insufficiency. Gaz Med France 1985;92:96

[14] Delacrois P. Double-blind study of Endotelon in chronic venous insufficiency. La Revue De Med 1981;27:28

[15] Zhao J et al. Anti-tumor promoting activity of a polyphenolic fraction from grape seeds in mouse skin. Carcinogensis 1999;20:1737

[16] Ye X et al. Cytotoxic effects of a novel IH636 grape seed extract in cultured human cancer cells. Mol Cellular Biochem 1999;196:99

[17] Bagchi D et al. Protective effects of grape seed proanthocyanidins and selected antioxidans against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation in mice. Gen Pharmacol 1998;30:771

[18] SaitoM et al. Antiulcer activity of grape seed extract. J Agric Food Chem 1998;46:1460

[19] Corbe C et al. Light vision and chorioretinal circulation. Study of the effects of procyanidolic oligomers (Endotelon). J Fr Ophthalmol 1988;11:453

[20] Jean Carper. Miracle Cures. Harper Collin Publishers 1998

[21] Verin MP et al. Therapeutic assay. Retinopathy and OPC. Bord Med 1978;11:1467

[22] Ray SD etal. A novel proanthocyanidin IH636 grape seed extract in creases in vivo Bc1-XL expression and prevents acetaminophen induced programmed cell death in mouse liver. Archives Biochem Biophys 1999;369:42

[23] Amsellen M et al. Endotelon in treatment of venolymphatic problems in premenstrual syndrome. Tempo Medical 1987;282

[24] Bombardelli E et al. Vitis vinifera. Fitoterapia 1995;v. LXVI, No. 4, 291

 

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