© 2017 by OPC-DOC

I

Prof. Dr. Jack Masquelier's scientific speech


Baltimore, the 18 October 1996

Ladies and gentlemen, I'm very pleased to have the opportunity to speak here today in Baltimore, before such a select audience.  I hope I will be able to interest you in the story of the why, when and how, of my discovery of OPCs, the vegetable substances on which I have been working - I must admit - for nearly half a century. But working on these substances has its charm, and does not lack certain poetry either, because, as you see, I am beginning this lecture by showing you some beautiful flowers. [For illustration purposes Professor Masquelier showed colour slides of plants, chemical formula etc. which he occasionally refers to in the course of his lecture.]

The substances to which I have devoted 50 years of my life, as professor and researcher, belong to the vast group of polyphenols. They are vegetable substances, and as we all know, the plant world is at the origin of the animal world, and thus, at the origin of all life on earth. In order to create life, a considerable power of synthesis is needed, so much in fact that plants are exceptionally rich in chemical components and that, when we speak of pycnogenols or polyphenols, we are immediately confronted with lists of hundreds and hundreds of components. Obviously, unless we want to end up with a veritable chemical and physiological tower of Babel, we will have to create some sort of order in these countless components.

I would, therefore, like to give you a very short course in plant chemistry, in polyphenols to be precise. Polyphenols are colorful substances or at least the polyphenols that are plant pigments are colored. Let me give you an example. This flower is red because its petals contain, what is known as anthocyanin or anthocyanic pigments, from the Greek 'anthos', which means flower, and 'kyanos', which means blue. Now you will tell me that the name is rather badly chosen, because the flower is red and the name means blue flower. But this is because the first known anthocyanin was derived from the cornflower, which is, of course, blue. One of the characteristics of anthocyans, is that they are red in acid and blue in alkaline environments. So we have to remember that the enormous group of polyphenols contains a number of red and blue pigments, the anthocyanins.

Let's now look at another group of polyphenols, the yellow pigments. Yellow, in Latin, is 'flavus', hence the name 'flavonic pigments', of which there are myriad varieties. Ever since these substances have been used as drugs, the word flavonic has gradually acquired a very broad meaning in pharmacy and medicine, and it has become the custom to speak of flavanoids. Flavanoid is a very handy umbrella term, but it is not quite clear what it covers. The suffix - oid denotes 'form' or 'resemblance'. Humanoid, for example, means resembling a human being. But with flavanoids, we have the bad habit to introduce into the group large quantities of molecules that have nothing at all to do with yellow pigments. I tell you this to give you a general idea, to sort of warn you against inordinate use of the term flavanoid. One must always specify which flavanoid is meant.

In addition to the red pigments, the anthocyanins, and the yellow pigments, the flavons or flavonoids, there are a number of plants, that seem to be pigmented only by chlorophyll, the green pigment that enables leaves to perform organic synthesis. You see here before you some photographs of grape leaves. These leaves hide something truly special, namely procyanidins or proanthocyanidins, the substances on which I have been working for many years. They too, are polyphenols, but colorless ones. You see that the term polyphenol will fill a great big bag, a whole lumber-room full of substances and that it is absolutely necessary to be specific when talking about them. One must know whether a polyphenol is colored or not, whether it is a pigment, a blue, yellow, red pigment, etcetera, or whether it is not pigmented at all. At this very moment, Mother Nature is showing us that many green leaves turn red in autumn.  The reason for this is that they contain proanthocyanidins.

There is a very simple experiment to prove the presence of proanthocyanidins. It takes an investment of, say, 30 dollars in materials, no more. But the fact that the experiment is cheap does not make it invalid. It is also a very simple experiment to perform. You cut a grape leaf into small pieces, put these in an Erlenmeyer flask, add a diluted mineral acid, a 10-percent solution of hydrochloric acid, and heat it. While it is being heated, a red coloring will appear. After filtration, you can recover this coloring in a solution, and when you shake the solution with isoamyl alcohol, all of the red coloring will float to the top. This is how proanthocyanidins behave; or rather, how they behave in the laboratory. Whenever these proanthocyanidins are treated very intensively with a mineral acid, they transform into anthocyanins, into red pigments.

Once these proanthocyanidins have been isolated in their pure form, the experiment can be repeated in the laboratory, and each time we heat them in the presence of acid, they will be transformed into red pigment. An anthocyanin. And this is why these substances are called proanthocyanidins, because they are the precursors of anthocyanin.

It is very clear that in nature - and I regret that being inside prevents us from seeing the beautiful spectacle nature has put on outside, although you know very well what it looks like because it is taking place under your very - a red maple forest that takes on its typical autumn coloring. But what happens in these maple leaves when they are colored red in autumn? They also procure red anthocyanins. This transformation, however, did not happen because of the addition of muriatic acid. And it is also clear that we only have a simple transformation here, the transformation of  procyanidins into anthocyanins, and no synthesis, since the leaves are about to die. After this clarification we can now comprehend the problem precisely. Once can prove the existence of these molecules in two ways that I have studies extensively throughout my life. First in the laboratory: You take small plant fragment, heat it up in an acid environment and when it turns red, an anthocyanin production is present. The second argumentation consists in waiting patiently for autumn and observing if the leaves turn red. Then you know that the concerning plant secludes proanthocyanidins.

I do not want to annoy you with the chemical formulas of these substances, I just want to make you aware that these phenomena occur in plants that can synthesize catechins. Catechins are polyphenols; at the same time they are another member of the huge and highly complex and diverse group of polyphenols. Catechins are monomers and I will depict them here as a circle with the letter C. [Here, Masquelier referred to the depiction of a chemical formula.] Some plants only synthesize catechins. A very well-known example is tea. Green tea contains catechins and nothing else. These catechins might vary in their complexity, but all of them are monomers. Whereas the catechin monomer  in other plants, such as grapes, maple and others, is being synthesized  and then it connects itself to groups of two, three, four and sometimes even five, even though these are much rarer. These groups are known as oligomeric procyanidins or OPC. They are the center of my studies and I want to talk about them in depth today.

As you see, I have indicated catechins by the letter C. Once catechins, bonded by means of carbon-carbon bridges, have formed OPCs, they lose their identity as catechins and become procyanidolic units. For this reason I substituted the letter C by the letter U so as to show you that when OPCs are formed, each unit loses its identity as a catechin.

It is to show that we are dealing with something other than a condensed catechin. These catechins, bonded to each other in a U shape by means of a carbon-carbon bridge and another catechin like unit, are characterized by the fact that, when you break the carbon bridge, you do not get catechins but anthocyanins. This is the reaction I have shown you, the famous 30-dollar-experiment which may not look very serious, but which is very interesting despite its modest price, and here you see it. It demonstrates that dimmers, i.e. two catechins bonded together by means of a carbon bridge, completely lose their separate identities. It is as if Miss Durand and Mr. Dupont were getting married and that, once married, no trace was left of either Dupont or Durant, but that they had taken a new name. They are still two individuals, two human beings, but the marriage that unites them has made them lose their former identity.  It is important to remember that when dimmers, trimmers etc. are formed, i.e. when OPCs are formed, we end up with a completely different substance. In other words, when nature decides to let a plant, tea-leaves for example, produce nothing but catechins, it will ensure that these catechins are specific.  It is a mistake to talk of tannin in tea. Tea leaves contain nothing but catechins. They may be more or less varied, but they are nevertheless all catechins. In grape leaves and maple leaves nature has decided to transform the catechins into OPCs, and has in these conditions created new individuals. Both from a chemical and from a medical or physiological point of view we must not confuse catechins with OPCs.

I will give you an example I know very well, because I come, as you know, from a region in France where a lot of wine is produced. And very good wine too, if you'll excuse me saying so, almost as good as the Napa Valley wines. The synthesis that takes place in wine, or rather in the grape leaf, is particularly complex, because the grape leaf produces not only monomers, i.e. catechins, but also oligomers, which are, as we have seen, catechins bonded by a carbon-carbon bridge and transformed into OPCs. And then beyond these bonds of two, four, say five catechins to be generous, we get polymers. They are no longer OPCs but polymers, because beyond a certain condensation, these substances become tannings. And here, too, we must avoid possible confusion. You now see how complex the chemistry of natural substances is! The general impression is that what is natural is good, pure, simple and easily accessible. But the chemistry of natural substances is one of the most difficult kinds of chemistry to learn and remember. We should absolutely not confuse a catechin with  tannin, and that is easily done, because we speak of the tannin in tea, for example, which is a big mistake.  Tea contains catechins and that's it.  No tannin.

But we should also avoid thinking that there is no difference between OPCs and tannin. Tannin is an enormous molecule which, physiologically speaking, is no longer interesting. In my opinion, tannin has been used for the only valuable property it has, which has been known for a long time: its effectiveness against diarrhea. Tannins, however, are unable to cross the intestinal barrier and are therefore not bioavailable. So let's forget about tannins and concentrate on the real oligomers, small clusters of two, three, four, very rarely even five catechins bonded together by a carbon-carbon-bridge and causing an anthocyanin reaction. This means that they are transformed into red pigment under the conditions I described earlier.

In 1979, I coined the word Pycnogenol to create a little order in this highly complex chemistry. Because when we spoke of tannins, we never really knew what was what. From a chemical point of view, I coined the word Pycnogenol as a chemist. This word covers all these substances, because they are substances that can bond with each other under certain conditions. And the word Pycnogenol means in Greek: 'Having the tendency to condense with itself, to create clusters of increasing complexity'. Well, you now know almost as much about this subject as I do, and if I went on about it, things would soon get very complicated and your attention would probably flag.

I will now tell you something about the research I have done, about why I am an inventor and, in particular, why I invented OPCs for medicinal purposes. You know that an inventor does not create something out of nothing. If I were suddenly to create a white rabbit out of nothing, I would be a creator. We all know that the term creator is reserved for God, who is unbeatable in this field anyway, so it's no use trying to measure oneself with Him. The inventor is part of the universe created by God. And as we have known since Lavoisier, the great French chemist who is regarded as the father of modern chemistry, nothing in this world is created, nothing is lost, everything is transformed. So all an inventor does is transform what is already present in nature. This transformation often consists in the discovery of a new possibility of a known substance. In this sense, I was an inventor when I discovered the therapeutic qualities of OPCs which I will turn to now.

I started my research on peanuts. Why peanuts, you will ask? Because oil is extracted from peanut, and this was the case back in 1945. I was still a young student at the time, working on my PhD. The reason I was working on peanuts was that France had come out of the war rather badly. The United States had helped us get rid of our enemies, but the country had been bled white. We could not feed ourselves properly in France at that time. So the question was whether what remained of the peanut after its oil had been extracted, which so far had always been used to feed cattle, could not be used to feed the French? That is, provided it contained useful amino acids. So this was the problem I had been asked to tackle. In order to study the amino acids remaining in the peanut after the oil had been extracted, I had to apply an acid to reduce the proteins to amino acids. Each time I used an acid, a red color appeared. Without knowing it, I was causing cyanidolic reactions. I wanted to know what caused this red coloring, and I discovered that it was a colorless substance present in the peanut skin, a substance that was created in the peanut itself and that was afterwards concentrated in the skin.

In short my dissertation slowly took shape. This happened in 1948, to be precise, on the 12 of July in 1948. You can calculate yourself that I was pretty young at that time, since I've been born in Paris in 1922. And yet, this dissertation contained some new facts about polyphenols. At this time I actually framed the hypothesis that these monomeric substances connect with each other during the metabolism, with the help of a carbon-carbon-bridge, in order to form dimers.

This was one of my first discoveries at that time. The second one was the following: I worked with guinea pigs and measured their capillary resistance, after giving them the substance that I have isolated from the peanuts, which was OPC, a proanthocyanidin. I realized that this substance increases the capillary resistance of the animals. But I will come back later to the problem of capillary resistance.

For me, the important point was: I, of course, performed this research in a biochemical laboratory, and in fact one that was affiliated with a medical faculty. It's more or less certain, that I would have restricted myself  to examine the chemistry of these substances, if I would have worked in a laboratory which was affiliated with a scientific faculty. But since I was accidentally working in a medical faculty, I wanted to know if these substances had any physiologic meaning. In doing so, I was very fortunate, because I discovered that this substance has an effect on the vessel system, that they increased the capillary resistance. In fact it was so strong, that the first OPC based medicine was introduced to the French market in 1950, after I patented the method of extracting these substances. It is called ResivitTM and was based on proanthocyanidins that were obtained from peanut skins. If you would have come to France and asked for ResivitTM in a pharmacy, they would have loved to sell it to you. Of course, because the pharmacists earn their money with it, but this shows  that this vessel preservative ResivitTM is being sold in France since 1950 and it's still on the market. The peanuts that were used in order to create ResivitTM, were imported in their shells from Africa. Shortly after the launch of ResivitTM, the peanuts, however, arrived in Bordeaux without the shells. The Senegalese started to peel them with this easy device and since then they came to Bordeaux without their shell. This meant that our source of raw material for the medicine was dried up and I had to find another OPC source. Accidentally, I found it in the pine forest close to Bordeaux, which starts in the south of the city and goes all the way to the Spanish border. This area is called "Les Landes", and in the bark of the pine trees I found again proanthocyanidins, OPC. I researched them and discovered a method to extract it.  This extraction method was part of the patent that I registered in 1951. As you can see, this goes back a long, long time, and it clearly shows that the French were interested in the substance back then. At least in Bordeaux and in my laboratory.

This patent was the base for FlavanTM, a pharmaceutical that was based on OPC from pine bark. The OPC that is extracted from pine barks also has an effect on the vessel system. That's why FlavanTM is also a vessel preservative. It is still being sold in French pharmacies and prescribed by French doctors.

To proceed with the positive results of my research: Approximately ten years later, we had the idea in my laboratory, to analyze grape seeds. We discovered that the OPC, that can be found in the grape leaf, also goes into the seeds of the fruit and is being collected there. This way, the grape seed became a very interesting raw material for the extraction of OPC, especially because it was cheaply available and abundant, since it's a by-product of the manufacturing process of Bordeaux wine. After the grapes were picked and pressed, one could find veritable mountains of grape seeds. Grape seeds are sometimes used for oil extraction, because grape seed oil is excellent, delicious edible oil, rich in polyunsaturated fatty acids. But they cannot all be used for oil extraction, there are far too many, so the industry began to use them as as a new source of OPC. In a grape seed, the oil is on the inside; on the outside is a zone containing tannin and right on the surface of this tannic zone are the OPCs.

The tangible result of all this is the third drug. Endotelin, another vascular protector, based on grape seeds left over from the Bordeaux wine-making process.

As you see, it has been a continuous process through the decades, a process of development of three drugs based on natural substances all with the same therapeutic profile, i.e. protection of the vascular system. But how does one establish this protective effect on the vascular system? By measuring the resistance of the small capillary vessels. Capillary resistance is simple to measure. All you have to do is make a vacuum in this class vial with this little piece of equipment, and you can measure the depression that has been created with a manometer, in centimers of mercury. To perform the measurement, you apply the equipment to the skin and draw a vacuum until tiny little hemorrhages appear. The measurement that you see here has been performed at a depression lower than capillary resistance, but if you create a depression equivalent to 25 centimeters of mercury on the manometer, which is generally the required depression for a healthy human male, the first capillaries will start to burst, and you will have measured capillary resistance. This measurement can, of course, also be performed on guinea pigs or other animals. What happens under the skin during this measurement?  Quite simply: the capillaries burst. Here you see a picture of a burst capillary taken with an electron microscope. You see the red blood cells, the lymphocytes, the interior of the capillary, the cells surrounding it and something else that is worth noticing because it acts more or less like wrapping tissue around the cell wall: collagen fibers.

And with this, I have reached the most essential element of my new discoveries on OPCs at the time, their effect on collagen. One might say that since my publication of this encompassing table, proanthocyanidins, OPCs, can be considered as 'collagen vitamins', because they partake in the biosynthesis of collagen and prevent its destruction. Let's first of all take a look at the biosynthesis. As you know, the biosynthesis of collagen needs ascorbic acid, vitamin C, because the amino acids proline and lysin need to be hydroxylated before they can be incorporated as a physiological active collagen. The OPCs act as a cofactor of vitamin C, reinforce its effect and thus activate collagen production. You can compare this to repairing a broken ladder with only two rungs left. It must be repaired and given new rungs. Thanks to the OPCs, the collagen reinforces itself by means of cross-links, which renders it once again functional, physiological, and solid, as in the image of the repaired ladder.

But I need not tell you, ladies and gentlemen, that you cannot repair a ladder with any of piece of wood.  The pieces of wood must have the right size and must fit between the two uprights. If you use pieces of wood that are too long, your ladder will turn out all crooked and be useless. I use this image to make it clear that if you were to use tannin or, on the other hand, a cate-chin, you would be using pieces of wood that were too big or too small and would never fit between the uprights. The uprights of the ladder are collagen fibers and here, for example, you have a polyphenol that wants to fit into the two uprights of the ladder. These polyphenol substances need to have a certain molecular size in order to repair the collagen. Accidentally, OPC has the right size and fits exactly between the collagen fibers. One can measure that on the contraction of a collagen fiber that comes into contact with hot water. As soon as the hot water is opened, the collagen fiber contracts. We can see that very well in the fast contraction of control fibers. The same goes for fibers that, for the first time, come into contact with what I call the "ordinary" bioflavanoids. With catechin, the contraction is being delayed a little. That means that the collagen is slightly stronger. And even if tannins ensure a longer delay, you still get the longest contraction time with OPC. The longer the contraction time, the better the collagen was repaired. Here you can see again prove of the fact that you need molecules of a certain size, in order to perform the reparation. One cannot just repair destroyed collagen with anything.

My laboratory also did other experiments with guinea pigs in order to prove that OPC is the cofactor of vitamin C. We experimented with animals that were separated into four groups. The first group did not get any vitamin C. The guinea pigs lived for approximately five weeks until they died from scurvy. One control group was on a balanced died with a lot of vitamin C, and in the course of the experiment, they did not only survive, but they also gained weight. But we discovered something very interesting in the two other groups, where the guinea pigs got a little bit less vitamin C, but not as much as it is needed to survive. Here you can see the curve that you get, if you give the guinea pigs the same insufficient amount of vitamin C, but OPC as well: The animals survived. If you add OPC to ascorbic acid, their effect extends and strengthens. That's why one could say, that OPC is the cofactor of ascorbic acid. And there's no better way to prove the soothing effect of OPC on vitamin C. Here - I will deal with this subject very quickly - you can see the proof that OPC inhibits enzymes that destroy the collagen, like elastase, and inhibits general enzymes that attack proteins. Finally, when we return to the last table, we see that under these circumstances proanthocyanidins play a role in the construction of collagen and inhibits its destruction by enzymes that accelerate collagen destruction, such as collagenases. As you know, there are certain diseases, known as collagen diseases, that are characterized by hyperactivity of these destructive enzymes. These experiments proved the therapeutic effect of OPCs on the circulation. Given that the wall of a blood vessel, the endothelium, is full of collagen, which ensures the elasticity and resistance of the vessel, it follows that by protecting the collagen, by improving the quality of the collagen, you also improve the quality of the vessel itself.

We also had to prove the OPCs were bioavailable. And this was not at all self-evident, because polymerized OPCs begin to resemble tannins, and we knew that tannins were not bioavailable. Tannins taken orally do not cross the intestinal barrier. How would we prove that OPCs do cross this barrier? In other words, how to prove that OPCs taken orally, whether by an animal or human being, would end up more or less everywhere inside the body? To achieve this, we marked grape OPCs with radioactive carbon 14. Of course, we could not mark the pine trees of the Les Landes region, since we could not take them to our laboratory, so we grew 'mini-vines' instead.  These were kept in an atmosphere of carbonic acid for 45 days, using radioactive carbon 14. Photosynthesis continued for 45 days and in particular the OPCs synthesized with the radioactive carbon. After 45 days, when we picked the leaves from the vines and placed them on photographic paper in the dark, we obtained 'auto X-rays': the grape leaves were radioactive and photographed themselves. So, if you feed an animal proanthocyanidins, OPCs derived from grape seeds treated with radioactive carbon, their distribution inside the body becomes measureable by the radioactivity emitted by each of the animal's organs, as you see on this table. In this table, we have set the blood total at 1, and you see that the aorta is most radioactive at the same time. If the blood's total radioactivity is set at 1, that of the aorta is 7 or 8 times higher. This first of all means that OPCs spread throughout the body but have a particular affinity for the vascular system.

If you take a slice of the animal, this is a cross-section of a mouse frozen in liquid helium, and place it on radiographic film, all the patches that show up white are radioactive. Here is the cross-section of the aorta, for example, and the skin. In short, radioactivity is spread throughout the body, which proves that OPCs are bioavailable.  Here you have the radioactivity on a blow-up of the animal's heart, and you see how much the OPCs do indeed attach themselves to the collagen in the walls of the arteries that transport the blood to and from the animal's heart

It is far from self-evident that other polyphenols arc also bioavailable.  I have already indicated that tannins are not, and there is another polyphenol named rutin or rutoside that is widely sold as a food supplement. And I am sure it has some activity, I don't doubt it, but when we marked rutoside with carbon 14 as we had done for the grape seed OPC and fed it to an animal, the only radioactivity we could detect was in the digestive tract. Obviously, the rutoside had to be somewhere, but it had remained inside the intestine. We had to pencil in the outline of the animal's body, because only the intestine was radioactive, nothing else. This proves that this flavanoid is not bioavailable. It is still on sale as a medicine, which is of course very nice for those who sell it, but it has not been proven like OPCs.

I'm not coming to the final part of my lecture [...]. As you will remember, my first work was on peanuts.  Peanuts contain oil and, as if by chance, this oil is enveloped in a skin that contains OPCs. I subsequently worked on the pine tree from the Les landes region, which contains a resin that is very sensitive to oxidation, and, as if by chance, this resin is also protected by a sort of 'bark shell' very rich in OPCs. Thirdly, I turned to grape seeds. I have already told you that grape seeds contain oil that is very rich in polyethylenic fatty acids, and lo and behold, grape seeds, too, are surrounded by a zone rich in OPCs. In brief, plants take the precaution to surround themselves with OPCs if they have to protect themselves from oxidation. Why should we humans not do the same? We, too, have reason to fear the effects of oxygen. I asked myself this question, and in trying to answer it I discovered the particularly powerful protective effect of OPCs against the free radicals of oxygen.

This is a photo of a book. This book from my library is hundred years old and like all old books, it has turned yellow. Despite careful handling, oxygen has caused the paper to turn yellow, as everyone can see for themselves. Something else everyone can easily check themselves in the following. Take a page from a newspaper and put it outside in the mid-day sun on a fine summer's day, after first having placed an opaque plate in the center of the paper. Leave the paper exposed to the sun for three hours. After three hours, you will find that the paper has yellowed almost as much as the book has in a whole century. So what happened? The paper has clearly not turned yellow underneath the plate where it was protected from the sun. It means that oxygen reinforced by sunlight tends to transform into free radicals. In other words, molecular oxygen becomes the radical superoxide and woe to the molecules that stand in its way, because they stand a fair chance of being broken into pieces. The effect of all this on collagen is clear from this picture of an old peasant woman from the mountains of Peru. You don't need me to tell you that this is an example of seriously deteriorated collagen in someone who has passed more than sixty years at high altitude and has therefore been exposed not only to oxygen, but also to sunlight and free radicals.

All this is rather commonplace and very well known. But we might be led to believe that it only concerns the outside of our bodies. Well, it doesn't. Each cell in our body has to eliminate molecules, and cells generally use oxygen to eliminate molecules they have no use for, awkward molecules they do not want inside their cytoplasm. However, some of these molecules cannot be eliminated by the molecular oxygen we breathe. Our own bodies transform part of the oxygen into free radicals. Indeed, we have inside our bodies free radicals we produce ourselves in order to rid the interior of our cells from substances such as 'capital X' that cannot be oxidated by the normal oxygen we breathe. So you see that free radicals have a physiological role. Incidentally, 'X' could be alcohol. Alcohol is one of the substances that require free radicals to be removed from our cells. All this is hardly consoling, but we do have certain natural defenses. The way our body uses free radicals to detoxify its cells is a bit like killing a fly with a Kalashnikov.  Effective, certainly, but the damage to everything around the fly is substantial. So, to prevent this 'overkill' we have protective systems in the form of enzymes, such as super oxide dismutase, Glutathion peroxidase, catalase. They prevent the initial reaction by the super oxide molecule from turning into a chain reaction; they prevent the production of the super oxide from being followed by a whole host of free radicals. All this works very well, but... these enzymes are proteins, and with age our capacity to synthesize proteins decreases. Besides age, there are genetic defects that affect our capacity to synthesize proteins.

Now you will say: "But surely there are vitamins, vitamin E, vitamin C. They are antioxidants that play a role in our natural defense system." They do indeed, but only if we eat food that contains enough of them! And we cannot always check the doses of vitamin C and E we consume in a day. And then there is the extremely unhealthy modern practice of strict dieting that often causes a highly insufficient vitamin consumption. The result is that many people produce an excess of free radicals. We can thank our lucky stars for the existence of radical scavengers, substances that help us fight free radicals. These substances are OPCs. I will prove it to you. This is DPPH, diphenyl-picryl-hydrazyl, a free radical. If, little by little, you add OPCs, proanthocyanidins, for example, to the DPPH, radical activity will disappear. Here you see the DPPH without OPCs, with a little OPC and with sufficient OPCs to ensure complete suppression of radical activity.  All this can be observed with the naked eye. Here you have the free radicals, which is colored, and which slowly loses its color and disappears as we add more OPCs to the solution.

You may object that this is all very well, but that it only happens 'in vitro', that it is not real.  So the question is, does this really happen in our bodies? I have already demonstrated that OPCs are bioavailable and are absorbed into our tissue. So I carried out an experiment, using myself as guinea pig. I applied some dithranol, a substance that produces free radicals, on my arm. Forty-eight hours later, the skin of my arm showed characteristics of the action of free radicals, unless I applied a small quantity of a cream based on OPCs derived from grape seeds five minutes after applying the dithranol. You see here that the reaction to the radicals is much weaker. This proves that the antiradical action also occurs in living tissue.

All this has led to my registering this patent in 1987. A US patent that was granted to me for a 'plant extract with a proanthocyanidins content, as therapeutic agent having radical scavenger effect, and use of thereof.'  I must say that his patent has not been received with unbounded joy in some circles in this country. Some people wondered where I got the cheek to register a patent under their very noses, as it were. But that's how it was. If you have been doing research for 40 years, I'd say you have a right to register a few patents. And I have registered patents all over the world. Anyway, the US patent office in Washington has been so kind as to grant me this patent, and I am very proud to be holder of a United States patent for this discovery. This is to show you that the cosmetics industry, both here and in France, make use of antiradical substances. There is a brought variety of cosmetics in France that contains pycnogenols extracted from grape sees.

A few last words to the "French paradox". I promise to make it short. Here you can see the photo of a presentation I published in 1961. Here I argue that wine lowers cholesterol thanks to the "flavanoid derivatives". That's how we called proanthocyanidins at that time. The word proanthocyanidin was coined only in 1970, that's why we were still speaking of flavanoid derivatives. I gave that presentation on an international medical conference about the usage of wine and grape seeds. In the audience there was the dean of the medical faculty of the University of California in Los Angeles (UCLA), Milton Silvermann. When I was done, Mr. Silvermann stood up and said: "Dear Professor, please come to us and give that presentation at  UCLA, I'm sure it will be a great success. Nowadays, in the year 1961, there are two things that Americans fear the most: communism and cholesterol. "I will end this lecture by showing you that the "French paradox" was already a part of my work in 1961.

Professor Jack Masquelier

In 1948 the doctorand Jack Masquelier discovered a colorless substance in the red peanut skins in the university of Bordeaux that he identified as oligomeric proanthocyanidins (OPC).  They are stable connections of two, three, four, rarely five flavan-3-ol-molecules (gr.: oligo = some). A single flavan-3-ol-molecule is called monomer, two connected monomers are a dimer, three connected ones are trimers etc.

Dr. Jack Masquelier dedicated his life to the research of OPC. In 1956 he was appointed to the "Matière Médicale" chair in Bordeaux. In 1957 he became vice dean of the medical and pharmaceutical faculty, Professor of phytochemistry on the university of Laval in Quebec in 1963 and from 1970 until his  retirement in the year 1984, he was dean of the pharmaceutical faculty on the university of Bordeaux.