Oligomeric proanthocyanidins - OPCs - Monograph

Alternative Medicine Review,  Nov, 2003  

• E-mail
• Print
• Link

Introduction

Oligomeric proanthocyanidins (OPCs) are some of the most abundant polyphenolic substances in the plant kingdom. Proanthocyanidins are an integral part of the human diet, found in high concentrations in fruits such as apple, pear, and grapes, and in chocolate, wine, and tea. OPCs in nutritional supplements are generally extracted from grape seeds or pine bark. Due to potent antioxidant activity, OPCs have been the subject of recent research, demonstrating anticarcinogenic, anti-inflammatory, antimicrobial, and vasodilatory properties, making them a potentially valuable therapeutic tool for the treatment of a variety of conditions.

Synonyms for oligomeric proanthocyanidins include procyanidins, procyanidolic oligomers (PCOs), leucoanthocyanins, condensed tannins, and pycnogenols, although the latter term is no longer used. Pycnogenol[R] is the trade name for an OPC extract from the bark of the French maritime pine tree.

Jacques Masquelier of the University of Bordeaux, France, first studied OPCs in depth after reading of explorer Jacques Cartier's 1534 expedition up the St. Lawrence River, in which Cartier's crew, trapped in ice flows and dying of scurvy, survived after Native Americans gave them a tea brewed from the bark and needles of the native pine. Masquelier later postulated the pine constituents contained vitamin C and flavonoids that aided in the crew's recovery. Today, dietary intake of OPCs varies from tens to hundreds of milligrams per day, depending on geographical and seasonal dietary differences. (1)

Biochemistry

Proanthocyanidins are high-molecular weight oligomers or polymers of a basic flavan-3-ol unit, with an average degree of polymerization between 4 and 11. Proanthocyanidin mixtures from grapes are a combination of dimers, trimers, tetramers, oligomers, and polymers. The reducing capacity of OPCs is thought to be proportional to weight concentration rather than the degree of polymerization. (2,3) The polymeric nature of proanthocyanidins is unique among polyphenols; they complex and precipitate proteins and inhibit enzymes involved in vascular tissue degradation. The ability of OPCs to complex proteins is referred to as astringency and is responsible for the "puckery" sensation when tea or red wine comes in contact with saliva and buccal tissue. (4)

Pharmacokinetics

Human studies of polyphenol absorption are limited and results have varied depending on the structure and solubility of the phenolic compound. Available research has demonstrated the acidic environment of the human stomach does not readily degrade proanthocyanidins; therefore, absorption rates in the upper gastrointestinal tract are not high. It appears, however, that even the low amounts observed in urine after an oral dose (usually <25 percent of original dose) are enough to significantly increase plasma/ serum antioxidant capacity. (5-7) OPCs reaching the colon undergo extensive degradation by the colonic flora. The metabolites and biological properties of this process have not yet been explored, but it has been suggested they may also have direct antioxidant and protective effects on colonic tissue. (3,8)

Mechanisms of Action

OPCs possess antioxidant, antimutagenic, anticarcinogenic, anti-inflammatory, and antiviral properties.

Antioxidant

The potent antioxidative properties of OPCs account for their therapeutic benefit in disease states characterized by oxidative stress. OPCs also demonstrate potent, concentration-dependent, free radical scavenging ability. (9) Studies in mice show OPCs inhibit chemically-induced lipid peroxidation, DNA fragmentation, and subsequent apoptosis (indicators of oxidative tissue damage) in a dose-dependent manner in hepatic and brain tissue. (10) Human studies also demonstrate an antioxidative mechanism as evidenced by decreased lipid peroxidation of LDL cholesterol (11,12) and increased free-radical trapping capacity after consumption of red wine containing OPCs. (7)

OPCs appear to have an affinity for vascular tissue and strongly inhibit several enzymes involved in degradation of collagen, elastin, and hyaluronic acid, the main structural components of the extravascular matrix. (13) These effects are perhaps attributable to trapping reactive oxygen species and preventing oxidative injury to vascular endothelium. In vitro studies have also found OPCs increase resistance of cell membranes to injury and degradation. (14,15)

Proanthocyanidins possess endothelium-dependent relaxing (EDR) activity in blood vessels by increasing nitric oxide production, (16) and stimulate vascular endothelial growth factor, a signaling factor involved in initiation of wound healing. OPCs may also protect the microvasculature of the retina and increase visual acuity, possibly by increasing the rate of rhodopsin regeneration. (17-19) In a rabbit model of ischemia/ reperfusion, OPCs' beneficial effects were attributed to binding of copper and iron liberated from myocardial tissue, thereby reducing their oxidative effects. (20) The positive effects of OPCs on microcirculation are also attributed to their inhibition of LDL oxidation. (11,12,21) and decreased incidence of foam cells, markers of early stage atherosclerosis. (22) Grape seed proanthocyanidins may have a vitamin E-sparing effect. (23) A clinical study of 10 healthy volunteers examining the effect of OPC supplementation on markers of oxidative stress showed significantly increased levels of alpha-tocopherol in red cell membranes. (24)