OPCs – Oligomeric and Monomeric Flavanols ?

When judged purely from the core of their structure, OPCs are classified as flavonoids. Flavonoids, or bioflavonoids, is the name of a group of plant compounds distinguished by an identical structure in the molecule’s center: the flavan nucleus. Flavus means yellow, and the “flav-” term came into use because the early research concerned yellow pigments. Later, many non-yellow substances were found to have a flavan nucleus. Yet the term bioflavonoids remained in use, confusing generations of scientists because the admission of one chemical similarity does not overcome the many essential differences between flavonoids and OPCs. A subclass of the flavonoids is the flavanols. OPCs are in the flavanols subclass.

Not only are many bioflavonoids not yellow, but a classification on the basis of core chemical structure is of no great help in the field of health and nutrition because the range of this group of bioflavonoid plant compounds is extremely broad. From a biological, nutritional, and medicinal viewpoint, the various individual bioflavonoids may present substantially different properties, such as with respect to their absorption and their biological effects. This is why, in the course of his research, Masquelier became increasingly convinced that the flavanols should no longer be regarded as a subcategory of flavonoids but rather as a separate, independent class that is equivalent to flavonoids.

Clusters of Flavanols

The group of flavanol compounds comprises single flavanols as well as clusters of two, three, or more flavanol units. In nature, some flavanol units are destined to remain single. These “bachelor” flavanols are called catechins. Catechins remain single for the duration of their existence. The catechin has a mirror-image flavanol called epicatechin. The difference between them is like the difference between your left hand and your right hand. Both the catechin and epicatechin are single flavanols. Both forms of catechin remain bachelors.

How is it then that clusters of two, three, four, or more “bachelors” come into being? To understand, this we must take one step back in the process of the formation of flavanols in plants. Before there is catechin, there is an “almost catechin” called carbocation. On the road from carbocation to catechin, there is a fork with a sign that points in the direction of proanthocyanidins. Once the decision to go left or right has been made, there is no way back. A carbocation that “goes catechin” ends up as irreversibly single. A carbocation that “goes proanthocyanidin” ends up as irreversibly “married catechins.” Interestingly, coupled catechins (proanthocyanidins) behave differently from the way they behave as singles. Coupled, they behave as proanthocyanidins. Catechins differ sufficiently from proanthocyanidins to warrant a different name. There remains an intriguing question. On the way to marriage, is there a single “monomeric” proanthocyanidin, a flavanol monomer that does not behave as a catechin but as a procyanidin?

The Proanthocyanidins

Does nature know single proanthocyanidins? It does, but its existence is somewhat theoretical in that it is hard to isolate a single proanthocyanidin. Theoretically, a single proanthocyanidin is a flavanol, and its structure is similar but not identical to that of the single flavanols named catechin and epicatechin. Like the multiple proanthocyanidins, the singles behave as true proanthocyanidins. The primary and most visible difference is that the proanthocyanidins are unlike the catechins in that a catechin does not produce red anthocyanin under the Bate-Smith reaction, while all the proanthocyanidins do. You can heat catechins in an acid solution for days, and they will not turn red. There has been confusion about this issue up to the present day because the proanthocyanidins so abundantly found in nature are clusters (pairs, triples, quadruples, etc.) of catechins and epicatechins.

Single proanthocyanidins are hardly found in nature because once they exist, they find another single proanthocyanidin to marry. Once married, they find another proanthocyanidin to be married, and so the proanthocyanidins form bigger and bigger proanthocyanidolic clusters. Paradoxically, these clusters consist of catechins, but these catechins don’t speak for themselves as individuals. They can express themselves only as proanthocyanidins, in complete bondage, so to speak. The bonding is the process described by Masquelier in 1948 as he observed how chromogen evolved into tannins. Many years later, Masquelier realized that he had been observing the formation of proanthocyanidins.

Single and Oligomeric Flavanols

What process in nature decides whether the carbocation, the precursor that catechins and proanthocyanidins have in common, “goes single” and becomes a catechin or turns into a single proanthocyanidin to marry another proanthocyanidin to form clusters of oligomers (just a few units) and polymers (many units)? Masquelier and his colleagues have tried to unravel this secret because they wanted to see if they could synthesize OPCs in the laboratory. Many attempts were made, but they found that proanthocyanidins cannot be stably produced in the laboratory, which means that OPCs cannot be synthetically produced. OPCs can only be isolated from plant materials. This is an important aspect of OPCs because many of the phyto- and micronutrients present in today’s foods and food supplements have been synthetically produced. Practically all commercially available vitamins are synthetic. Even substances such as CoQ10 are not extracted but fermented. In contrast, OPCs are truly phyto because they are always isolated from plant materials.

Whether a carbocation becomes a single “starter proanthocyanidin” depends on the presence of a certain enzyme. If a plant that contains catechins also contains this enzyme, it presents a marked propensity to condensation of flavanols and produces OPCs and thicker “polymerized” clusters of catechins, the tannins. So far, nature alone has decided on the plant’s enzymatic composition. Recent studies indicate that influencing the plant’s propensity to form procyanidins by way of “engineering” enzymes into plants that lack OPCs and tannins seems to be a possibility. The reason for this research will probably not be of interest to most readers because it primarily concerns the inhibiting of “pasture bloating” in cattle. According to these genetic engineers, tannins increase the amount of protein that leaves the animal, thus diminishing the bloating caused by proteins. This kind of research touches on another very important distinction we must make: that between OPCs and tannins.

OPCs and Tannins

The final step that we must make in distinguishing OPCs is to determine at what point the process of thickening turns the proanthocyanidins from valuable phytonutrients (OPCs) into useless, anti-nutritional tannins. To make that final distinction, I must take you a few steps further into the process of condensation or polymerization. The Latin word merus or ancient Greek meros means part. When identical parts form pairs, triples, quadruples, major clusters, or even chains, this process is referred to as polymerization, with poly standing for many. Plastics are a common household example of such polymers in that plastics are the result of polymerization. Smaller groups consisting only of several identical parts are called oligomers; in ancient Greek oligo means few. The single part is called a monomer, mono meaning single or one.

We can now distinguish the various proanthocyanidolic compounds by way of the words polymers, oligomers, and monomers. The single proanthocyanidin (the starter unit) is a monomeric proanthocyanidin. Two bonded flavan-3- ol parts constitute a “dimer.” Three bonded flavan-3-ol parts are referred to as “trimers,” four constitute a “tetramer,” and five, a “pentamer.” All proanthocyanidins consisting of two, three, four, and five units are the oligomeric proanthocyanidins. To simplify this complicated terminology, Masquelier and his team began referring to the oligomers of proanthocyanidins as OPCs during the 1960s.

According to Masquelier, clusters of six and more units belong to the polymers or tannins. One could call them PPCs. As is explained in this book, only the OPCs and the catechins have nutritional value. Only OPCs and catechins are phytonutrients. Compared with catechins, OPCs are by far the superior phytonutrient. PPCs or tannins are considered to be anti-nutritional because they interfere with the digestion and absorption of proteins. Researchers and members of industry have had heated discussions about whether the term oligo really stops at five units or may be conveniently stretched to the level of 10-unit compounds (decamers) to extend the merits of OPCs to worthless products. Because these discussions are often fought on commercial rather than on scientific grounds, The American Heritage Dictionary of the English Language is probably the best authority to resolve this discussion. Its Third Edition defines an oligomer as “a polymer that consists of two, three, or four monomers.” According to the authors of this authoritative dictionary, who are even stricter than OPCs’ discoverer, the procyanidolic pentamers (five units) and higher polymers are not OPCs but PPCs or tannins.

Catechins, OPCs and Tannins

Masquelier always explained this chemistry by way of a simple comparison representing catechins as the bricks used to build a house. In their catechin state, these bricks remain loose elements, with which one cannot construct a house. The bricklayer needs mortar to bond the bricks. The enzymes that can influence the formation of single starter proanthocyanidins are like the bricklayers who put mortar between the bricks. Once they have created a starter unit, the bricklaying proceeds almost automatically because the units cluster spontaneously. Without the enzymes (bricklayers) we find nothing but catechin-bricks that remain loose elements that cannot be used to build OPCs (the house). In plants that lack these “bricklaying” enzymes, we may find catechins, but we will not find OPCs. In plants that have these enzymes, we find catechins and OPCs. This is why Masquelier’s OPCs products always contain a certain amount of the loose catechins (bricks), which naturally “come” with the OPCs during the manufacturing process.

In this procyanidolic context, there exists a widespread, persistent, but incorrect use of the term “monomer.” By definition, a monomer is a molecule that can combine with other identical molecules to form a polymer. A catechin is not a monomer because a catechin lacks the capacity to combine with other catechins to form oligomers of proanthocyanidins. The true monomer of proanthocyanidins is the single starter proanthocyanidin, which is made from the carbocation under the influence of enzymes. Monomers of proanthocyanidins are so rare that it is safe to say that no product contains them. In the context of products containing proanthocyanidins, it is a mistake to speak of monomers. I know because I have made the mistake myself, thinking that catechins are the monomers of proanthocyanidins. There are catechins and epicatechins. There are oligomeric (OPCs) and polymeric (tannins) proanthocyanidins. The monomers exist in theory only. You won’t find them in any commercially available product. Product labels that mention “monomers” are incorrect.

Throughout the many years of Masquelier’s research, he and his colleagues developed an ever-clearer understanding of all these substances. Yet the problem remained that the scientific community never fully resolved the confusion caused by the fact that flavanols were wrongly classified as members of the large family of bioflavonoids, although they definitely deserved to be classified as a separate family because of the wide differences between the two groups. Until this very day, the confusion haunts scientific articles as well as the labels of many herbal medicines and dietary supplements.