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 Interviews with Nutritional Experts: Pycnogenol -- Safe and Effective  
 
Interview with Professor Peter Rohdewald
   as interviewed by Richard A. Passwater PhD

Professor Peter Rohdewald, Ph.D. specializes in pharmaceutical research, but he has a special interest in natural compounds that serve as both nutrients and therapeuticals. Dr. Rohdewald is a professor and the former commissarial director of the Institute for Pharmaceutical Chemistry at the University of Muenster in Germany. Professor Rohdewald is co-author of two textbooks on pharmaceutical analytical investigations and has published dozens of scientific articles on pharmacokinetics, bioavailability and efficacy of pharmaceuticals. His research includes examinations of pharmaceutical suspensions and plant extracts, as well as pharmacokinetic and pharmacodynamic investigations on analgesics, antihistaminics, glucocorticoids, cytostatic drugs and antibiotics. In addition to his research, Professor Rohdewald teaches pharmacy majors clinical chemistry, physical chemistry and molecular pharmacology.

As I mentioned in my last column, after my earlier column on Pycnogenol(R), and especially after my booklet on the nutrient, I received many letters from readers wishing to know more about this amazing nutrient. So I set about visiting several researchers around the world to learn more about Pycnogenol(R) and the latest research on its health benefits. First on my list was Professor Peter Rohdewald of the Institute of Pharmaceutical Chemistry at the University of Muenster to observe the latest research on the safety and effectiveness of Pycnogenol(R).

Passwater: Professor Rohdewald, as a pharmacist you have studied many interesting drugs. What attracted you to research Pycnogenol?

Rohdewald: I am intrigued by the pharmacology of plant extracts and I was curious if all of the benefits attributed to Pycnogenol were due to bioflavonoids or other substances in the extract.

Passwater: How long has Pycnogenol(R) been studied and how long have you been studying it?

Rohdewald: Pycnogenol(R) has been studied since 1953, and I have been studying it since 1982.

Passwater: As a pharmacist, you also have extensive training in toxicology. I have read several independent toxicological studies on Pycnogenol(R) in which you served as the "Study Monitor." What can you tell us about the safety of Pycnogenol(R)?

Rohdewald: Yes, as a pharmacist, I am involved with toxicity studies. The composition of Pycnogenol(R) tells us a lot about its safety. We have completely identified and characterized more than 85% of the ingredients in Pycnogenol(R) and all of these substances but taxifolin are found in other plants that have been used in human nutrition over the centuries. As you know, the main constituents are natural antioxidants called proanthocyanidins which are also contained in foods such as sorghum, avocado, strawberries, bananas, and others.

Furthermore, catechin and taxifolin are minor constituents, and both are effective free radical scavengers. In addition, catechin has anti-ulcer activity and taxifolin is known to inhibit the activity of oxygen-radical producing enzymes. Catechin is also found in hops and berries.

There are small quantities of other nutrients in the extract such as caffeic acid, cinnamic acid, fumaric acid, gallic acid, vanillic acid, ferulic acid and related substances. You can tell from the names of these nutrients that they are found in other plants. Caffeic acid and ferulic acid are found in parsley and spinach. Caffeic acid is also found in onions, ferulic acid is also found in rhubarb and grapes, fumaric acid in chives and beetroot, and gallic acid in aubergine (eggplant) and radish. Also present are vanillic acid and protocatechuic acid which are proven antioxidants and anti-inflammatory substances.

Caffeic acid helps protect the liver against toxic substances and both caffeic acid and ferulic acid stimulate transport of bile from the liver cells to the gall bladder. Both are excellent free-radical scavengers and they prevent the formation of nitroso compounds of amino acids. Nitroso compounds are carcinogens which can be produced within the gastrointestinal tract. Also, both compounds are potent inhibitors of allergic reactions and edema. Caffeic acid is a fast-acting and selective blocker of leukotriene biosynthesis, inhibiting the key enzyme, arachidonate-5-lipoxygenase. Leukotrienes are involved in allergic reactions. Thus, these "minor" organic acids add a significant positive contribution to the beneficial effects of Pycnogenol(R).

Even though these nutrients are available in other vegetables, fruits, spices and beverages, Pycnogenol(R) has the advantage of providing these valuable nutrients in a concentrated form. However, because there is a greater potency due to this concentration, it is extremely important the extract be tested for adverse effects. Just because it is a natural plant extract, doesn't mean that a concentration of these natural compounds could not have adverse effects. Therefore intensive investigations using laboratory mice, rats, guinea pigs, dogs and even minipigs have been performed to see if Pycnogenol(R) does any harm. There have also been studies to determine if Pycnogenol(R) has any mutagenic, carcinogenic or adverse effects in pregnant animals. The outcome of these many studies is that Pycnogenol(R) has been shown by accepted toxicological protocols to not be mutagenic, carcinogenic, teratogenic or toxic. It is safe, as could be expected from its composition.

Passwater: The studies that I have read, and the unpublished ones that you have allowed me to review during my visit are quite reassuring. However, most people aren't familiar with all of the nutrients in foods, and many of the constituents of Pycnogenol(R) are new to them. Even the term "bioflavonoids" is new to the general public, who have only recently learned terms such as "antioxidants" and "carotenoids." Pycnogenol(R) is primarily a mixture of bioflavonoids of the proanthocyanidin family. In last month's interview with Dr. Kandaswami, we discussed the term "proanthocyanidin" and that it identified those compounds which formed a reddish pigment called anthocyanidin when hydrolyzed (Bate-Smith reaction). Pycnogenol contains several monomers, dimers and oligomers. Which compounds in Pycnogenol are proanthocyanidins, and how would you describe the rest?

Rohdewald: The extract from the maritime pine consists not only of proanthocyanidins, but also contains other water-soluble nutrients. These nutrients are building blocks for the biosynthesis of proanthocyanidins in the living plant and are extracted together with the proanthocyanidins from the pine bark. Catechin and even taxifolin are called monomers of proanthocyanidins, although they do not produce the red color on hydrolysis (Bate - SMith reaction). The proanthocyanidins themselves are a family of compounds differing in structure and chain length, but all composed of catechin or epicatechin units. The other substances are organic acids.

Passwater: You sent one of your graduate students, Mr. Robert Sibbel, for a while to study the latest techniques in measuring antioxidant profiles with Dr. Barry Halliwell at the University of London. Earlier studies that focused on one measure of antioxidant activity called the "TBARS" test indicated that Pycnogenol(R) was a very potent antioxidant possessing many times the antioxidant activity of both vitamins C and E in this TBARS test. What have you found?

Rohdewald: My co-worker, Robert Sibbel, has determined in experiments using a rather stable free radical, that Pycnogenol(R) could inactivate this radical better than vitamin E. In another study using the superoxide radical, Pycnogenol(R) was a better radical scavenger than vitamin C. Therefore, Pycnogenol(R) can act as a really powerful antioxidant in aqueous solution in the way that vitamin C acts, and in a non-aqueous medium, it catches radicals, too, as vitamin E does, but, better!

Passwater
: Therefore, Pycnogenol(R) can offer wide antioxidant protection in both watery and fatty environments. However, this great versatility still does not tell us everything we want to know about how Pycnogenol(R) acts against all radicals and oxidative species.

Rohdewald: True. That's why we are still studying the antioxidant profile of Pycnogenol(R). I also want to point out that this versatility still doesn't mean that we don't need to be well-nourished with vitamins C and E. These vitamins are still required and they have their own functions. Pycnogenol(R) should be considered a helper -- a very powerful helper -- for both of these vitamins. Pycnogenol(R) is an important adjunct to other antioxidants such as vitamins C and E and the carotenoids. Pycnogenol(R) does not replace these other nutrients, but it sure does increase our protection against free radicals.

Passwater: You mentioned that one of the properties that sets Pycnogenol(R) apart from other bioflavonoids was its cellular bioavailability. Some of the earlier studies of the bioavailability of Pycnogenol(R) indicated that it was rapidly absorbed and transported in the blood, but it was later discovered that these earlier test may have been inadvertently flawed by overlooking a pat of fruit jam eaten by the study participants as part of their breakfast. Would you tell us about the new findings that show the superior Pycnogenol(R) bioavailability?

Rohdewald: We have demonstrated bioavailability by placing students on a diet free from fruits, coffee, wine and beer -- a difficult task for German students -- and then analyzing their urine for Pycnogenol(R) components and metabolites. We could detect -- but not identify as yet -- metabolites that appear on the days when Pycnogenol(R) is taken, but not on days when a placebo is taken. Therefore, we have demonstrated that some Pycnogenol(R) is absorbed from the gastrointestinal tract.

In addition, and even more convincing, is that we have demonstrated increased capillary resistance following the intake of Pycnogenol(R). By applying a vacuum to the skin of elderly patients, you can easily produce microbleedings within the skin. Following the intake of one single dose of 100 milligrams of Pycnogenol(R), you must markedly increase the strength of the vacuum to produce skin microbleedings. Pycnogenol(R) strengthens the capillary vessels so that they don't "leak" or bleed as easily. Obviously, to produce such an objective effect, Pycnogenol(R) must be absorbed from the gastrointestinal tract.

Passwater: Yes, that shows that Pycnogenol(R) is bioavailable, but it also demonstrates that it is effective in strengthening vascular walls and maintaining capillary health. Pycnogenol(R) is also known for its effectiveness in reducing inflammation and edema. Have you studied this effect in your laboratory?

Rohdewald: It is widely known that during inflammation, oxygen radicals are produced. The scavenging of these radicals reduces the degree of inflammation. We have not made studies here, but perhaps the World's leading researcher in the role of Pycnogenol(R) on both capillary permeability and inflammation is Professor Miklos Gabor of Szent-Gyorgyi University in Hungary. Professor Gabor has found Pycnogenol(R) very effective in maintaining capillary permeability and reducing inflammation.

His most recent studies examine the relationship between free radicals and the inflammation process, and the role of Pycnogenol(R). There is good correlation between the free-radical scavenging and the anti-inflammatory activity of Pycnogenol(R). Professor Gabor has found that Pycnogenol(R) scavenges very well for the superoxide and hydroxyl radicals involved in inflammation. The inflammatory process involves a series of events, and Professor Gabor has evidence that suggests Pycnogenol(R) also acts by inhibiting various oxygenase enzymes such as lipoxygenase and cyclooxygenase.

Passwater: Thank you for the referral. I will visit with him in a few days. In your opinion, what differentiates Pycnogenol(R) from other antioxidants?

Rohdewald: I think that the high affinity of Pycnogenol(R) to collagen and elastin, the main tissue constituents, is an advantage over other antioxidants, because Pycnogenol(R) will be fixed in the areas where we need it, in the tissues. Another advantage of Pycnogenol(R) is that it stabilizes red blood cell membranes. This also aids in distributing Pycnogenol(R) throughout the body.

Passwater: The affinity of Pycnogenol(R) to the skin proteins, collagen and elastin, has been reported to improve the skin elasticity, restoring characteristics of younger skin. Is this because Pycnogenol(R) improves the beneficial cross-linkages between the fibers?

Rohdewald: In vitro experiments pointed to this type of stabilization, and experiments in rabbits demonstrated that Pycnogenol(R) maintained normal capillary function even when the skin was irritated by solvents. However, we have no direct evidence for a cross-linking introduced by Pycnogenol(R).

Passwater: The free-radical scavenging property of Pycnogenol(R) should also protect skin against the aging effects of excessive sunlight. Have you studied this protective effect?

Rohdewald: Yes, we have studied the protective effect of Pycnogenol(R) encapsulated in liposomes, and I also noticed a protective effect in real life in Florida, I realized that Pycnogenol(R) lessened sun damage to my own skin.

The protective effect of Pycnogenol(R) on fibroblasts (skin cells) against damage from sunlight -- particularly the UV-B

band of sunlight -- has been studied by Professor Antti Arstila at the University of Jyvaeskylae in Finland.

Passwater: That sounds interesting, so I will make Professor Arstila's laboratory my next stop. I have one last question before I leave the beautiful University Town of Muenster and its 1200th anniversary celebration. Where will your research lead you from here?

Rohdewald: We will continue to research Pycnogenol(R) seeking to demonstrate more beneficial and protective effects, in cell cultures, in animals, in man, and we are still characterizing the trace components. Our main goal is to follow the positive effects of its antioxidant property on human health.

Passwater Thank you Professor Rohdewald for discussing your research with this very powerful adjunct nutrient. It should be part of everyone's antioxidant team.

All rights, including electronic and print media, to this article are copyrighted by © Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).

   
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 About The Author
Richard A. Passwater, Ph.D. has been a research biochemist since 1959. His first areas of research was in the development of pharmaceuticals and analytical chemistry. His laboratory research led to his discovery of......moreRichard Passwater PhD
 
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