Oligomeric Proanthocyanidins (OPCs) are the Heart of the French Paradox

Oligomeric Proanthocyanidins (OPCs) are the Heart of the French Paradox

In the USA, the right to mention antioxidant properties on the packaging of products intended for internal use is set to be governed by an official regulation. As of 1997, the FDA plans to restrict such labeling of foodstuffs to products containing vitamin C, vitamin E or beta carotene.( 1) Any consumer buying a product presented as being antioxidative will therefore be entitled to demand that the product contain at least one of these three vitamins.

Undeniably, there is considerable confusion at present in the field of dietetics and nutritional supplements with regard to the actual antioxidant effects of the plethora of formulas currently on offer to the public. It is not exceptional to see a dozen or more substances claimed to fill this function on one and the same package, and the profusion of ingredients hangs question marks over the efficacy of each of them. The FDA points out that molecules whose antioxidant power in vivo has been irrefutably proven in humans are rare, hence its very narrow selection of the three aforementioned vitamins.

I believe, however, that this reductive stance ought to be moderated, and it should be admitted that the FDA's choice is not the only possible choice with regard to beneficial effects, particularly when an idea that originated in the United States has been so enthusiastically received by the American people. I refer to the French Paradox. Widely disseminated in the press, the idea has proven to be of far greater consequence than a mere media rage. It attributes the low death rate of the French from heart disease to their regular consumption of red wine together with a Mediterranean type of diet. In fact, the French Paradox reveals to the public and proclaims to the world at large, ideas that have long been known by a small circle of scientists.( 2)

For example, as early as 1957, in the USA, Fay Morgan( 3) noted that laboratory animals given wine retain significantly less cholesterol than those given water or diluted alcohol. I, myself, announced the ability of wine to break down cholesterol at the international medical conference held in Bordeaux in 1961.( 4) I attributed this phenomenon to tannins, and particularly to OPCs (proanthocyanidolic oligomers) which I had discovered shortly before in wine.( 5)

Due to their protective effect on the blood vessels( 6) these OPCs later found their way into medicine: the active ingredient in the drug Endotelon, manufactured by Sanofi Winthrop, is derived from grape seeds. When St Leger published his famous article in The Lancet in 1979 on the protective effect of wine in relation to death from heart disease,( 7) an entire body of previous literature, which already held the answer to the problem he had just raised, was mysteriously left unmentioned.

Nowadays, more is known about the pathogenics of atheroma. We know that the fatty deposit of the lesion is the result of peroxidation of LDL fraction transporting the cholesterol. Oxygenic free radicals are involved in this reaction. We can deduce from this that the benefit derived by the French from their way of life is based on the fact that their diet is rich in natural antioxidants, red wine being the main source of these. Although wine is devoid of vitamin C, vitamin E, or beta-carotene, its OPC content is superior to all the other food sources: it is not unusual to find a gram in a litre of red wine.

In 1985, I patented the anti-radical effects of OPCs and their use in medicine, food products and cosmetics( 8) in the USA. Two years later, the Japanese biologist Uchida confirmed this anti-radical effect of OPC, which he found to be 50 times superior to that of vitamin E.( 9) In 1993, Frankel( 10) showed that the antioxidants in wine inhibit the peroxidation of human LDL. Finally, in 1995, Renaud,( 11) working in my laboratory on OPC extracted from grapes, attributed to them the capacity to prevent thrombocytic clotting and the rebound phenomenon characteristic of alcohol.

A decade of recent research has thus furnished proof that the cardiovascular protection of the French Paradox is largely based on the antioxidant properties of OPCs. Ignoring this evidence opens the way to the American Paradox, where we see the FDA turning its back on one of the most significant contributions made towards human biology.

Obviously, all new products for use in dietetics and medicine should be screened extremely rigorously, but let's face it, OPC is not the result of some recent synthesis. People have been eating them since they started eating fruits and vegetables. Even before the arrival of humans on earth, OPC was exercising its antioxidative powers in the tissues of vegetation which would otherwise have succumbed to the aggressions of free radicals. Why does one find OPC in such large amounts, as in grape seeds for example? Simply because they protect the fragile oil of these seeds from the degenerative effects of oxidation. Our increased need of antioxidants is due to the current sophistication of our food. We resort to red wine because botanic selection and cooking habits have depleted our dietary sources of OPCs.

The fact that the FDA is uninterested in a vegetable product designed to protect the most fragile structures in the living cell would appear proof of its indifference towards the problem of aging. The American people, on the other hand, are not mistaken in their increasing consumption of OPC in the form of nutritional supplements.

Allow me to draw your attention to one more interesting aspect of the FDA's proposal. This concerns the fact that under certain circumstances antioxidants can turn into pro-oxidants. The matter was brought to the forefront of public attention by an article from Barry Halliwell, an English scientist, who is specialized in the field of antioxidants.( 12) Halliwell warns against the adverse effects of vitamin C when it comes in contact with iron or copper ions in the body. He writes: "A mixture of ascorbate and copper rapidly inactivates the H( 2)O( 2) -- degrading enzyme catalase."

Catalase is the enzyme that deactivates hydrogen peroxide (H( 2)O( 2)), a highly toxic oxygen free radical. According to Halliwell, in healthy humans the antioxidant effect of vitamin C "probably predominates." This is because the healthy body has minute control systems to keep the iron and copper always in a captured (chelated) state. But some people suffer from an excess of free iron or copper in their tissues. This is called hemochromatoxin. When taking ascorbic acid these patients may incur a certain risk, because free iron and copper can make the antioxidative vitamin C into a pro-oxidant. Also, at the time of an injury, iron and copper may "leak" from the body's chelating system and may turn vitamin C into a pro-oxidant.

Already in 1951, I showed how proanthocyanidins (OPCs) protect vitamin C against the oxidative action of free form copper molecules (Cu(++) ions). In an additional study, I demonstrated that OPC also inhibits the enzyme that oxidizes ascorbic acid (ascorbic acid oxidase). This protective and inhibiting property only concerns hydroxyflavans (OPC), while ordinary bioflavonoids prove inactive or even pro-oxidant.

In brief, I give you the results I obtained with testing OPC, rutin and aesculin in vitro. Rutin is the widest known bioflavonoid. Aesculin is a standardized chestnut extract, also a Bioflavonoid. At the time, we still obtained the OPC from peanut skins. We brought ascorbic acid in contact with elemental copper and then we checked the protective influence of OPC, rutin and aesculin. As a reference we had one solution to which nothing was added (Column 4).

After 30 minutes 73% of all the ascorbic acid was oxidized in the reference solution. To our surprise we found that aesculin has a pre-oxidative effect, because 80% of the ascorbic acid was oxidized. An increase of 7%. Rutin did not have a protective effect worthy of mentioning (3%). But OPC protected 23% of the vitamin C from oxidation.

1.
2.
3.

4 Protective

OPC/Proantho- Rutin Aesculin Control substances

cyanidins Oxidized

* 50%
* 70%
* 80%
* 73% ascorbic acid after 30 mins Protected

* 23%
* 3% accelerated
* 0 ascorbic acid

oxidation

Again, I must repeat it, this brings to our attention that we must make differences between the various bioflavonoids and especially between bioflavonoids and OPC. All my life I have struggled against people who equate flavonoids with OPC. They are wrong, as this 1951 study shows.

In our experiment we first used equal weights of OPC, rutin and aesculin. In other tests, we increased the concentration of rutin and aesculin, while that of vitamin C remained constant. However, the protecting activity of rutin remained very weak. And, aesculin always accelerated oxidation, though somewhat less at these higher dosages. It demonstrates the superiority of OPC over these flavonoids.

We repeated the experiment to see how OPC and these two flavonoids would inhibit the ascorbic acid oxidase enzyme. We found practically the same results: Inhibiting

OPC/Proantho- Rutin Aesculin Control substances

cyanidins Oxidized

* 70%
* 95% 95%
* 95% ascorbic acid after 30 mins Inhibition in %
* 25%
* 0
* 0
* 0 ascorbic acid

In this in vitro experiment, we found that aesculin and rutin did not show any oxidase inhibiting effect. The OPC, however, opposes the action of the enzyme and this inhibition preserves 25% of the initial ascorbic acid. Technically speaking, the results are logical to me because in comparison with ordinary bioflavonoids, OPC has the maximum degree of reduction of the heterocycle, which actually prevents them from playing a pro-oxidative role. They therefore take off a highly individual character in their antiradical and antioxidant effect: not only does their chelate-forming capacity vis-a-vis iron prevent them from provoking a Fenton reaction, but their affinity for proteins (absent in bioflavonoids) also allows them to inhibit numerous enzymes (hyaluronidase, collagenase, proteases, etc.), and ascorbic acid oxidase in particular.

Let us hope that the F.D.A. will add proanthocyanidins/OPC to the trilogy of the vitamins C, E, and beta-carotene, confirming their prior choice by countless users throughout the world.

Correspondence:

Professor Jack Masquelier

c/o Primary Services International

P.O. Box 1099

Southport, Connecticut 06490 USA 203-256-1188

Fax 203-255-9402
References

(1.) Food and Drug Administration, Federal Register, Vol. 60. No. 249, December 28, 1995.

(2.) OPC in Practice, Bert Schwitters and Jack Masquelier, Alfa Omega Editrice, Rome, Italy, 1995.

(3.) Fay-Morgan, A., Brinner, L., Plaa, C.B., Stone, M.M., Am. J of Phys, 1957, 189, 290-292.

(4.) Masquelier, J., C.R. Congres Medic. Intern., Wine and Grape Cnference, Bordeaux, 1956.

(5.) Masquelier, J. Point, G. Bull. Soc. Phie. Bordeaux 1956, 95, 6-11.

(6.) Masquelier, J., These Doct. Sciences, Bordeaux 1948.

(7.) St. Leger A.S., Cochrane, A. L., Moore (F.), The Lancet, 12 May 1979, 1017-1020.

(8.) Masquelier, J., U.S. patent no. 4698360.

(9.) Uchida, S., Edamatsu, R., Hiramatsu, M., Med. Sci. Res.

(10.) Frankel, E.N., Kanner, J., German, J.B., The Lancet, 20 February 1993, 454-457.

(11.) Ruf, J.C., Berger, J.L., Renaud, S., Arter. Thromb. Vasc. Biol., 1995, 15, 140-144.

(12.) Halliwell.

(13.) Masquelier, J., Bulletin de la Societe de Chimie biologique, Extract from volume XXXIII, nos. 3-4, 1951, p. 302-303

(14.) Masquelier, J., Bulletin de la Societe de Chimie biologique, Extract from volume XXXIII, nos. 3-4, 1951, p. 304-305

The Basic Chemical Structure of Proanthocyanidins (OPC)

- Oligomeric proanthocyanidins (OPC) is a flavan-3-ol molecule compound. "OPC" is found throughout plant life, however, grape seed and pine bark are proven to yield high levels of OPC and therefore have been the most commercially viable sources. The flavan-3-ol molecule is unique by virtue of its natural tendency toward condensation, i.e. its ability to form new configurations made up of two, three, four or five flavan-3-ol molecules bonded to each other. These multiple molecule structures are frequently referred to as "oligomers" because "oligo" means "some."

- A single flavan-3-ol molecule (a monomer) is called a "catechin (+)." The monomers are known as the "precursors" to OPC. When the flavan-3-ol molecule is joined together in pairs and triples (known as "dimers" and "trimers"), then you have OPC or "oligomeric proanthocyanidins." When the molecule joins together in quadruples and higher compositions, then the structure is called "tannins" or "polymeric proanthocyanidins" ("poly" meaning many. The whole group is called "flavanols."

Although the OPC flavan-3-ol molecule compound is found throughout plant life, grape seed and pine bark yield the highest, most commercially viable levels. While other active compounds can be extracted from these plant sources, the OPC flavanol molecule compound remains the only reason to utilize a pine bark or grape seed extract.

In 1952, when the totality of vegetable polyphenols was first described with the flavan carbon skeleton as flavonoids, these flavonic pigments formed a homogenous chemical class. The term described generally all the compounds that consist of two benzene rings bound together by a chain of 3 atoms -- which includes literally over a thousand botanical molecular compounds.

Later, when the biological effects of these particular molecular compounds was recognized as more important than their basic chemical considerations, the flavan-3-ol molecule and its pharmacological properties were studied in depth. For Dr. Jack Masquelier, who had been spending his professional life studying OPC, it was no longer possible to consider the catechin/OPC molecule as simply part of the larger bioflavanoid group. The separation of the flavanol molecule compound from the flavanoids, based upon its proven superior effects of OPC on human health, is what Dr. Jack Masquelier brought to light.

As much as 20-25% of an OPC extract consists of monomeric precursors, the building blocks of OPC. In OPC extracted from grape seed, there are catechin (+) as well as epicatechin (-) monomers, which are mirror complements to each other; in OPC extracted from pine bark, catechin and taxifolin are the monomers This is part of the subtle distinction between OPC from grape seed and OPC from pine bark.

On their own, these monomers are inactive and short-lived. But when catalyzed by the presence of OPC (the dimers and trimers), the monomers become stable and active and unleash their own unique biological benefits. This is why they are considered part of the total "proanthocyanidin/OPC" percentage of active ingredient.

The word "polyphenols" is the broadest, most generic term which defines the entire category of molecule compounds represented in both the flavanoid and flavanol groups. In other words, "polyphenols" represents over a thousand molecule compounds, of which some are effective and some are not. While some are bioavailable to the body, most are not. Some even have toxic properties. Some may display antioxidant activity, although most of those are not bioavailable, meaning they can be therapeutically ineffective.

For these reasons, it is misleading and virtually meaningless to sell a product based on the substance being "high in polyphenols." OPC stands alone in its bioavailability and efficacy as an antioxidant, superiority as a cardiovascular protector, and capability as a formidable collagen cross-linking regulator. If you are buying or selling OPC, it is important to speak of a "proanthocyanidins (OPC)" content in a standardized percentage. OPC is the only reason to have a grape seed or pine bark extract.

When a consumer buys grape seed or pine bark extract, the specific active ingredient should be expressed on the label as a percentage, not simply as "polyphenols," or other dubious marketing terms. Thus, if a consumer is looking for the antioxidant grape seed or pine bark extracts, specify Masquelier's OPC-85(TM). This is the only way to guarantee that active antioxidants are what they are buying.

Townsend Letter for Doctors & Patients.

~~~~~~~~

By Jack Masquelier

Share this with your friends