Controversies on meanings of OPC, polyphenol & tannin
There is not a generally acceptable definition of “oligomer” based on the number of monomers in chemistry & biology. Some leading researchers and manufacturers in France suggested a clear definition that OPCs contain dimmers to pentamers. OPCs do not include monomers and polymeric proanthocyanidins (PPCs or high molecular weight tannins). We wish to explain here why this clear definition of OPCs based on molecular sizes is justified in this particular field of nutraceutical chemistry.
There are basically two proanthocyanidin monomers - catechin and epicatechin. Each monomer binds at either the alpha or beta position on their molecular structures to form dimers, trimers, etc. Catechin and epicatechin can further form esters from gallic acid and yield catechin or epicatechin gallate. OPCs are a complex mixture, very different from a single nutrient compound such as vitamin C (ascorbic acid) or vitamin E (d-alpha tocopherol). Typical natural OPC extracts such as grape seed and pine bark extracts contains significant amount of monomers up to 20-30%, which also have health benefits at lower potency. OPC manufacturers don’t make effort to separate the monomers from OPC. The best OPC natural extract ingredients may contain truly OPCs up to 70-80%. A label of “95% OPC” or “OPC 95%” means the label maker either does not know what “OPC” really means, or wants to play tricks to sell.
“Poly” in “polyphenol” does not mean polymers here, but 2 or more aromatic hydroxyl groups in a molecule. Polyphenols include monomers (catechin and epicatechin), OPCs, polymeric proanthocyanidins (high molecular weight tannins), and a variety of other phytochemicals such as anthocyanins (flavonoids), quercetin, myricetin, resveratrol, etc.
A label of “95% polyphenols” does not necessarily mean a high quality unless you know the content of oligomeric distribution, as most OPC ingredients contain significant amount of polymeric proanthocyanidins that cannot be absorbed by cells and hence by human bodies. A label of “95% proanthocynidins” does not either have a clear meaning, but is surely a mistake. Proanthocyanidins include not only OPCs, but also high molecular weight tannins / polymeric proanthocyanidins (not bio-available). The content of total proanthocyanidins of even the best OPC extracts is less than 80%, plus 20-30% monomers.
In chemistry, oligomers can contain as many as a dozen of connected monomers such oligonucleotide, oligopepetides, etc. In this particular sector of nutraceutical industry with OPCs as a nutritional ingredient, the extensive studies were conducted and demonstrated that OPC dimmers to tetramers have the best bio-availability and can be easily absorbed by cells and human bodies. The famous OPC Professor in France claimed that only 3 oligomers: dimmers, trimmers and tetramers, have the listed health benefits. His claim was on the basis of scientific investigations and is a piece of scientific truth. The bioavailability of OPC pentamers starts to decrease, and that of hexamers diminishes almost completely. That is, tannins bigger than hexamers cannot be absorbed as nutrients, as they cannot cross the plasma membrane. This is not surprising if we consider some knowledge in the closely related field of medicinal chemistry. Every medicinal chemist knows the famous Lipinski Rules of Five (from Pfizer) of pharmacokinetic properties of a compound. One of the Rules of Five says that molecular weight of a drug like molecule should be less than 500. The Lipinski rules are very useful in small molecule drug discovery despite of occasional exceptions. Bioavailability of nutritional compounds essentially follows the same Lipinski rule on the molecular weight.
Controversies on tannins
There is lack of a clear and consistent definition of “tannins”, too. It says in the on-line Wikipedia, “tannins have molecular weight of 500-3000.” One may or may not agree with this statement. But tannins are indeed outside the molecular weight range defined by the Lipinski rule, distinguishing from OPCs. That is, the Lipinski rule predicts that tannins or polymeric proanthocyanidins have poor bioavailability.
It would be appropriate and clear to draw a line between tannins and OPCs. If we say that OPCs are nutritional ingredients, OPCs have to be absorbable by human bodies, and hence have to be dimmers to pentamers. It is reasonable to define “OPCs” as dimmers to pentamers, and “tannins” as molecules bigger than pentamers. “Proanthocyanidins” include OPCs and tannins.
Vitaflavan ® grape seed extract and Oligopin ® French maritime pine bark extract are specially refined OPC ingredients, using a proprietary technology that can efficiently remove high molecular weight tannins. Vitaflavan ® & Oligopin ® are the only OPC ingredients in the market that have been demonstrated to be free from tannins or polymeric proanthocyanidins, using several methods of strict characterization such as LC-MS and HPLC in several laboratories.
Most other OPC consumer products are made of ingredients, which are not separated well from the high molecular weight tannins and from other complex natural components of no health benefits. The OPC ingredient prices have huge differences, as do the OPC qualities. Only the traceable scientific data from analytical chemistry lab can tell the differences of the real qualities.
One of the consistent views is that high molecular weight tannins are not bio-available because they cannot across the plasma membrane as OPCs can. This point can be easily verified in a biological lab. The animal model studies indicate that tannins / polymeric proanthocyandins do not have the health benefit as OPCs have. There have been further arguments that tannins can exert antioxidant health benefits more than OPCs when passing through intestines despite of not being absorbed. This is just an arbitrary assumption without any scientific basis, in favor of low grade OPC ingredient manufacturers. The antioxidant activity of tannins can be neglected as soon as they cannot be absorbed by cells. Further, large doses of tannins from low quality OPC ingredients could be bad to human bodies as the tannins shrink extracellular functional proteins in stomach and intestines, and inhibit or destroy their biological functions. Tannins or polymeric proanthocyanidines are also strong metal chelators, and can prevent the mineral absorption by the human body. The intake of polymeric proanthocyanidins with OPC products in the long term may be harmful. A daily intake up to 300 mg OPCs of high quality proves to be safe and very beneficial.
Proanthocyanidin oligomers are the real target of extraction
The modern nutritional science distinguishes itself from traditional herbal medicines from many cultures such as China, India, and Egypt. In the modern nutritional science, nutritional scientists and natural product chemists identify particular chemical entities (such as OPCs) that have nutritional benefits to human bodies. The scientists do not make unfounded claims without scientific evidence on the basis of chemical and biological mechanisms at the molecular level. Further, the scientific evidence is independent of testimonials, while testimonials are the sole foundations in many cultures and religions.
We don’t gain the health benefits of OPC nutrients by simply eating the grape seeds, because the OPC nutrients in the raw grape seeds cannot be absorbed. OPCs are a class of chemical entities of natural products, identified in the content of science, to be effective antioxidants for living systems. The quality of OPC ingredients solely relies on the extracting and refining technologies to enrich and retain diverse OPCs and other health beneficial small molecules such as anthocyanins, catechin, epicatechin, resveratrol, etc. This goal to increase the OPC antioxidant potency by removing the un-absorbable or non-beneficial components have been pursued for more than 60 years since the discovery of pycnogenol pine bark extract OPCs by 1950 by Professor Jacques Masquelier (1922-2009). In 1970, the same OPC Professor also discovered proanthocyanidins as an OPC extract from grape seeds. The compounds found in grape seeds and grape plant were also referred to as pycnogenol, as they are chemically the same thing as pine bark extract with only slight differences.
There is so far lack of scientific basis for claims that impurities and other unknown minor components in the OPC extracts contribute to significant nutritional values of an OPC product. In fact, studies have shown that lack of a particular minor component such as anthocyanin or resveratrol in an OPC extract antioxidant does not significantly impact on the health benefits. For example, Dipak Das from the University Of Connecticut School Of Medicine, collaborating with researchers from the University of Milan and several other research institutes in Italy, published in the Journal of Agricultural and Food Chemistry (doi: 10.1021/jf061048k), that both skin and flesh have cardioprotective potential despite vastly differing polyphenol content. "The results indicate for the first time that the flesh of grapes is equally cardioprotective as skin, and the antioxidant potential of skin and flesh of grapes are comparable with each other despite of the fact that flesh does not possess any anthocyanin activities," wrote the authors.
The content and richness of diverse OPCs are the predominant factor of the nutritional strength of OPC consumer products, plus the benefits from known small molecules such as catechin, epicatechin, taxifolin, anthocyanins, quercetin, myricetin, resveratrol, etc.
Credible specifications of raw OPC ingredients as the quality indicator
As the OPC inventor, Dr. Masquelier passed away at age 87 after life-time contributions to the nutritional natural product chemistry. The OPC invention by Dr. Masquelier is a treasure of all the human kind, and provides a basis of OPC commercial competitions. Severe competition benefits OPC consumers, only if the competition is on a fair basis. The advances of modern science and technologies would provide many opportunities for the OPC ingredients to be improved. On the other hand, any credible claim of an OPC extract must be accompanied by clear, detailed and reproducible scientific data.
OPCs as pine bark extract, grape seed extract, and red wine extract all exhibit similar health benefits. OPCs of pine bark extract and grape seed extract are both demonstrated to reduce and balance high blood pressure in small human clinical trials, although they cannot be sold for treatment/prevention of any diseases based on the strict scientific criteria set by the US FDA.
In our scientific opinions, OPCs of different sources have close and analogous health benefits, while slight differences may be possible. Again, the strength of health benefits almost solely relies on the extracting technologies that can maximally retain the OPC nutrients and remove non-beneficial or harmful components.
The specification sheet accompanying an OPC ingredient from its manufacturer is a document that OPC consumers should look at, if the OPC ingredient manufacturer is credible company.
Disclosure of the detailed specifications of an OPC ingredient is the only way that consumers trust the quality of an isotonic OPC antioxidant. FrenchGlory ® isotonic OPC products make the history by fully declaring the specifications of the major OPC ingredients for the first time to isotonic OPC consumers. The OPC consumers can find by themselves the real product quality, not relying on marketing tricks from many OPC sellers.
OPC is regulated as dietary supplement, not a drug
Dietary Supplement Health and Education Act was first enacted in 1994. This regulatory system has been evolving to include currently the following 5 key elements.
1. Prior to its marketing, the manufacturer of a dietary supplement is responsible for ensuring that the supplement is safe;
2. Manufacturers are only permitted to make certain types of claims, and may not make false or misleading claims of any kind;
3. Manufacturers must abide by current Good Manufacturing Practices (cGMPs);
4. Manufacturers must submit to FDA all reports that they receive of serious adverse events associated with a product that they manufacture; and
5. A manufacturer must submit a notification to FDA before it markets a dietary supplement containing a “New Dietary Ingredient.”
FDA permits some health claims that are not authorized by regulation but are supported by credible evidence and accompanied by a non-misleading disclaimer. Such claims are referred to as “qualified health claims.”
Human beings do not take enough antioxidants such as OPC from regular diet. Nutritional deficiency due to imbalanced diet is a widely recognized health problem in both developed and undeveloped countries. In-sufficient intake of diverse antioxidants may cause accelerated ageing and many nutrition-deficient health problems, such as heart and vein problems. OPC antioxidants have been demonstrated a variety of nutritional benefits by scientific studies. An OPC antioxidant supplement is intended to supplement the diet and provide the OPC nutrient that is otherwise not consumed in sufficient quantity in a regular diet.
OPCs are far more than antioxidant
OPC consumer products are widely marketed as antioxidants, as consumers know antioxidants very well. The health benefits of OPCs are actually far more than those derived from OPCs’ antioxidant property. OPC do have the superior ability to quench free radicals in a test tube. But in the body, scientific studies have shown that many functional enzymes are regulated by OPC. The 3 easy examples of OPC properties other than those of antioxidants are properties of anti-inflammation, changing gene expression, and boosting the levels of compounds to relax blood vessels. The diverse properties more than antioxidant make OPCs more much useful, both in the maintenance of optimal health and in reducing the risk of chronic diseases, even though OPCs are not legally approved drugs. We wish always to emphase that none of clinical studies on OPCs for treatment of any diseases have been officially recognized by the US FDA based on the strict scientific criteria. It is illegal for any one or any seller to claim/testify that OPC can reduce blood pressure, relieve diabetes, etc.
OPC trademark issues and the related law
A legal professional advised us that it would be foolish for us to use “OPC-90”, “OPC-110” and “OPC-150” for trademarks of our 3 isotonic OPC products, which have the OPC extract content in 90, 110, and 150 mg each serving, respectively.
The term “OPC” is simply a chemical name or a common scientific term. In the trademark laws, “OPC” is a generic term, not qualified for protection as a trademark. “OPC + number” is essentially a generic term, too, and should not be lawful for trademark protection.
Under U.S. Trademark Law, not-distinctive words, elements and functional elements of a product cannot serve as trademarks (see TMEP 1202.02(a)). Indistinctive words or descriptive words don’t stand out as belonging to one source. Not-Distinctive words or elements or Not-Distinctive designs can only attain trademark rights through secondary meaning (otherwise known as acquired distinctiveness). Functional elements of a product or service cannot be lawfully protected as trademarks even if they acquire distinctiveness. A merely descriptive mark is not-distinctive under Trademark Act Section 2(e)(1), 15 U.S.C. §1052(e)(1), if the word or phase describe an ingredient, quality, characteristic, function, feature, purpose or use of the relevant goods.
The combination of “OPC” and “number” has many direct meanings for the underlying product, which every commercial company is entitled for description or specification of their own product of the same kind. If I have a product with the OPC extract content of 300 mg each serving, the specification term “OPC-300 mg” or “OPC-300” belongs to any one who wants to use it as the description, even though I was the first one to use this term OPC-300. OPC-300 is not a lawful trademark for a product of oligomeric proanthocyanidins.
Can a combination of “OPC” and “number” acquire secondary meaning or distinctiveness? Let’s see the following terms that are found in Google search:
“OPC 300 grams”, “OPC 3-bottle pack”, “OPC 3-months supply”, “OPC $39.95”, “serving size of isotonic OPC: ¾ teaspoon…..”, “major ingredients of isotonic OPC: 3 extracts from pine……”, ……
These terms are used by a variety of OPC marketing companies, indicating that the symbol (or mark) of “3 following OPC” does not have any distinctiveness for a single company, and therefore, cannot acquire a secondary meaning by any means.
Many lawfully unprotectable marks do go through the registration process for 3 possible reasons. 1) A term or a phrase is the first time to be used in commerce (but not necessarily protectable as a trademark; 2) trademark examination lawyers have limited knowledge in a particular (especially scientific) field; 3) some lawyers don’t care and/or there are also bad lawyers.
It is absolutely not a good thing for an OPC trademark owner if an unprotectable mark goes through the registration successfully, with troubles down the road. An unprotectable mark even after the registration for many years is subject to cancellation any time. There have been endless lawsuits year-by-year on the trademark cancellations. Any one/organization with commercial interest in a particular trademark can initiate a trademark cancellation petition by paying a fee of $300.00 at Trademark Trial and Appeal Board (TTAB) of the United States Patent and Trademark Office USPTO. It is terrible thing that a company advertises a brand name (a term of a phrase) of no distinctiveness.
These are just our personal opinions. The reason for us to write this section is to suggest the people in the same commercial field including our competitors do not use the simple combination of “OPC and a number” as your brand name. It is neither good to yourself, nor to others. A good and strong trademark is a unique word or term that other people don’t use for the direct product description and specification. FrenchGlory is a distinctive mark for our isotonic OPC antioxidants.
The Original Strength of French OPC Science & Technologies
Natural OPC extracts are among the best selling dietary supplement products in the market. The 3 richest OPC sources – grape seed extract, pine bark extract and red wine extract were all originated from France as “3 co-incidences”. The OPC “3-co-incidences” started more than 60 years ago, and have brought scientific and technological strengths for French companies to extract and refine the best OPC ingredients from 3 different sources. The leading French OPC manufacturers emphasize the content of 3-4 OLIGOMERs that are fully bio-available. The best OPC ingredients from France contain the 3-4 proanthocyanidin oligomers in 65-80%. Most other OPC extract manufacturers across the world have not been able to address the purity for the 3-4 procyanidin oligomers in clear numbers.
OPC science history of 60 years in 3 periods in France
The history of OPC science can be roughly divided in 3 periods. Period 1, the early effort was focused on how to make better isolation of OPC from 3 different sources, and OPC was first isolated from peanut skins and then pine bark; About 2 decades later as the period 2, grape seed extract OPC got more popular in France; Period 3, OPC has been very popular in nutritional products world-wide after another 3 decades. OPC ingredients have been so far used for more than 3,000 different OPC consumer products world-wide. The best selling OPC products are those of combinations of 3 different OPC ingredients - pine bark extract, grape seed extract and red wine extract.
OPC science has 3 research areas
OPC science in 3 areas includes: 1, OPC extraction and purification; 2, OPC tested for biological activities; 3, OPC tested in human clinical trials.
1. OPC extraction and purification: The OPC purity has been optimized by at least 3 French OPC ingredient manufacturers, while most other OPC extract manufacturers across the world lag behind. The 3 French companies demonstrated that the best OPC extract contains the 3-4 major oligomers of proanthocyanidins in 65-80%, while the monomer content of catechin and epicatechin co-exist in about 20-30%. Other minor components such as phenolic acids and gallic acid esters in grape seed extract and pine park extract may make 5% or less. Red wine extract contains more diverse polyphenols than OPC, such as anthocyanins, quercetin, myricetin, resveratrol, etc. It is really unlikely or unnecessary to further purify the oligomers by removing the monomers and other minor components, which also have nutritional values.
However, majority of other OPC ingredients across the world contain low levels of the 3 or 4 major oligomers in 10-40%, with high content of polymeric proanthocyanidins, regardless their OPC specifications. At least 3 world-prominent OPC experts argued that large intakes of polymeric proanthocyanidins from low quality OPC ingredients could harm human health in 3 different ways. The proanthocyanidin polymers in low quality OPC extracts have 3 problems: 1) un-absorbable; 2) interfering with mineral absorption by human body as strong metal chelators; 3) strong in binding extracellular functional proteins and deactivating them.
2. OPC tested for biological activities: there have been more 3,000 publications and patents related to the OPC biological activity claims. The OPC biological research has been conducted quite extensively based on molecular biology and animal models, mainly related to 3 human health problems – heart health (including hypertension & vein health), diabetes, and bone diseases. The OPC biological studies also established for the next 3 heath benefits for weight management, inflammation, and anti-aging. It is beyond any doubt by the results of biological studies that OPC also has a wide range of other health benefits as dietary supplement. There are also a variety of undergoing scientific investigations for the OPC 3 extracts to be used in possible treatment/prevention of diseases.
The biological studies of OPC have 3 trends. 1) To extend the examination of OPC benefits for some rare health problems. 2) To study the detailed mechanisms of the nutritional benefits - how the OPC molecules interact with biological macro-molecules. 3) OPC extract can be used as a probe or a tool in the studies of fundamental biological issues, and answer some general scientific inquiries that cannot be otherwise answered. These research efforts are fundamentally very important for clues how human can fight diseases in better ways, while OPC may or may not be the best choice.
3. The OPC Research Area 3 is human clinical trials. This is the most challenging task facing OPC scientists. The human clinical trials for the therapeutic activities of OPC extracts are still in the early stage, and much more work needs to be done in the future.
OPC is studied as both a dietary supplement and a possible drug
OPCs are not only regulated as dietary supplement as mentioned above. OPCs are also studied in science as both a dietary supplement and a possible drug. An OPC dietary supplement is intended to supplement the diet and provide additional OPC nutrient, which is otherwise not consumed in sufficient quantity from the diet alone. As a dietary nutrient, OPC antioxidant has been demonstrated to have a variety of nutritional benefits for optimal health of the human body. OPC scientific research is to study the nutritional benefits and fundamental biological mechanisms.
An OPC dietary supplement is different from an approved drug in several ways. An approved drug must go through 4 phases of vigorous human clinical trials and must be demonstrated the significance of efficacy by statistics, as well as the safety and bioavailability. On the other hand, many approved drugs have some side effects, which may or may not have been defined. A dietary supplement as being natural from plants such as OPC is generally safe and has little side effects for human consumption in long-terms. The long–term benefits for maintenance of optimal health are often the real miracles that may or may not be quantifiable in the limited length period of clinical trials. Therefore, FDAs in many countries allow the commercial use of dietary supplement without proof of the clinical efficacy data, but proofs of biological studies, human safety data, and human bioavailability studies. Our FrenchGlory ® isotonic OPC antioxidants are dietary supplements of a variety of health benefits, - the best products on the market of America to fight nutrition-deficient health problems due to imbalanced diet. The FrenchGlory ® isotonic OPC antioxidants are not intended to diagnose, treat, care or prevent diseases. And this web site is a comprehensive OPC antioxidant review and is dedicated to convey the OPC research information to OPC consumers.