Steven Lamm, M.D., is convinced that Pycnogenol is one of the most powerful antioxidants ever discovered. Although some researchers might dispute the New York City physician’s claim, Lamm may just be onto something.

Pycnogenol, derived from the bark of the French maritime pine tree (Pinus maritima), is a complex of more than 40 antioxidant compounds. Many of these compounds, described by chemists as flavonoids and polyphenolic organic acids, are found in fruits and vegetables – but not in the potency or specific ratio achieved through supplements.

“Pycnogenol is one of those substances that is synergistic with other antioxidants, such as vitamins C and E,” says Lamm, who devoted a full chapter to the subject in his book, Younger at Last (Simon & Schuster, 1997). “It’s part of my medical armamentarium to tip the balance in favor of a patient’s body.”

Flavonoids, such as those found in Pycnogenol, are a big part of the reason why fruits and vegetables are good for people and reduce the risk of disease. More than 5,000 have been identified in plants, though only a few hundred probably show up in even the best diets. Yet studies have shown than only 9 percent of Americans regularly eat fruits and vegetables – the richest source of flavonoids – and so most people are likely deficient in these important nutrients.


Every plant contains a unique combination of flavonoids, which is why different herbs, all rich in these substances, have very different effects on the body. Pycnogenol contains large amounts of a particular group of flavonoids called proanthocyanidins, and its distinctive chemical “fingerprint” accounts for its properties, according to Peter Rohdewald, D.Sc., Ph.D., of Westfälische Wilhelms University, Germany.

The first flavonoids were identified in 1936 by Albert Szent-Györgyi, M.D., Ph.D., who was awarded the Nobel prize for his discovery of vitamin C. One characteristic of nearly all flavonoids is that they enhance the ability of vitamin C to form strong but flexible blood vessel walls. When blood vessel walls are permeable, or leaky, fluid between cells increases and leads to swelling (edema) and inflammation.

Blood vessel permeability is associated with many conditions, and Lamm finds Pycnogenol a useful adjunct in treating patients with such diverse conditions as varicose veins and impotence. “Sixty percent of erectile dysfunction is related to poor circulation,” he says. “Whatever improves circulation will improve erectile dysfunction.” Indeed, Chinese researchers recently reported that ferulic acid, one of the antioxidants found in Pycnogenol, increased fertility in both normal and infertile men.

Pycnogenol, often considered the premium flavonoid supplements, may also be helpful in some cases of attention deficit disorder (ADD) and attention deficit hyperactive disorder (ADHD). Steven Tenenbaum, Ph.D., and Julie Paull, Ph.D., of St. Louis, are clinical psychologists who suffer from these disorders. They have found that Pycnogenol supplements ease their symptoms. Although they don’t prescribe Pycnogenol, some of their patients have taken it on their own and have also reported fewer ADD and ADHD symptoms.

It’s not clear why Pycnogenol would help in ADD and ADHD. But Lester Packer, Ph.D., of the University of California, Berkeley, speculates that it may help neutralize dangerous molecules called free radicals and improve communication among brain cells. In experiments, Packer has found that Pycnogenol quenches three specific types of free radicals – superoxide, hydroxyl, and nitric oxide. The interaction between nitric oxide and antioxidants does play a role in cardiovascular cell behavior, and so it may also effect the behavior of other cells.

Proanthocyanidins are also credited as the nutritional factor that makes red wine good for the heart. Numerous studies have found that red wine reduces the stickiness of blood platelet cells, making them less likely to cause unwanted clots. In experiments, Ana Maria Campos, M.D., of the University of Santiago, Chile, found red wines to have 6 to 16 times more antioxidants than did white wine. In studies of both people and monkeys, John D. Folts, Ph.D., head of the cardiology laboratory at the University of Wisconsin, Madison, reported that drinking three glasses of purple grape juice had virtually the same clot-preventing benefit as aspirin, but without the hazards.

Other combinations of proanthocyanidins can be found in blueberries, bilberries, the herbs feverfew and ginkgo, and grape seed extract. While each is a powerful antioxidant, these plants have different physiological effects. Bilberry is a traditional remedy for eye disorders, such as macular degeneration. Feverfew is well documented for its ability to reduce the incidence and severity of migraine headaches, and ginkgo has been shown to increase blood circulation in the brain and to improve memory.

The proanthocyanidin extract of grape seeds, recovered from the pulpy waste of the wine industry, also has cardiovascular benefits. One recent study by researchers at Creighton University, Omaha, Neb., confirmed the antioxidant properties of grape seed extract. In another experiment, Italian scientists found that grape seed extract could prevent ischemia-reperfusion injury, a type of free radical damage to the hearts of rabbits.

Citrus Flavonoids

The flavonoids found in citrus fruit – oranges, grapefruit, lemons, and limes – are also rich in flavonoids and related antioxidant polyphenols. They have a long history of use in preventing capillary fragility and bruising, but some of the most recent research has focused on their anticancer benefits.

Many of the citrus flavonoids have a kaleidoscopic nature – they are very similar in chemical structure, but slight variations yield different biological effects. For example, rutin is the same as quercetin except for having a sugar molecule; hesperidin is very similar to rutin, and diosmin is almost identical to hesperidin. Most of these flavonoids are found together in citrus, though their ratios vary in different types of fruit.

In a recent issue of Cancer Research, Japanese scientists described an animal experiment in which diosmin and hesperidin, alone or in combination, reduced the incidence of oral cancers by as much as 75 percent. Another study, led by Theodore Fotsis, Ph.D., of the University of Ioannina, Greece, found that many common citrus flavonoids inhibited angiogenesis, the growth of blood vessels in tumors. Fotsis wrote in the July 15, 1997, Cancer Research that flavonoids could play a role in “chemoprevention,” the use of natural substances to prevent cancer.

One citrus flavonoid in particular, quercetin, has attracted considerable interest for its possible role in preventing heart disease and cancer. Several years ago, Edith J. M. Feskins, Ph.D., of the National Institute of Public Health and the Environment, Netherlands, reported that high intake of quercetin (found in citrus, onions, and apples) reduced the risk of coronary heart disease. A more recent analysis of the data, reported in the March 8, 1997 Lancet, confirmed the apparent benefits of quercetin. High intake of this flavonoid was associated with a 53 percent lower risk of coronary heart disease and a 38 percent lower risk of death from all causes.

Green Tea Flavonoids

Green tea and, to a lesser extent, black tea are rich sources of still another group of flavonoids called catechins. These catehins – including the closely related epigallocatechin-3 gallate (EGCG), epigallocatechin (EGC), and epicatechin-3 gallate (ECG) – form about 30 percent of the dry weight of tea leaves.

Literally dozens of studies by Japanese researchers – avid drinkers of green tea – have shown that catechins can prevent free radical damage to cholesterol and lower the risk of heart disease and cancer. Population-based studies have shown that tea drinkers have a lower than average risk of heart disease, stroke, and several cancers including esophageal, stomach, and lung cancers.

A study, published in the June 5, 1997, Nature, described one of the ways green tea prevents cancer. Cancer cells use the enzyme urokinase to invade cells and metastasize. According to Jerzy Jankun, Ph.D., of the Medical College of Ohio, Toledo, the EGCG in green tea is a potent inhibitor of urokinase activity. A single cup of green tea contains enough EGCG to temporarily inhibit urokinase activity – and is safer than synthetic drugs that block urokinase activity.


Over the past three years, more than 1,000 scientific studies have been published on soy flavonoids, technically known as isoflavones. These isoflavones function as antioxidants, and they seem to possess properties that distinguish them from other types of flavonoids. (For more on isoflavones see Let’s Live, October 1997.)

The principal soy isoflavones are genistein, daidzein, and glycitein. They have very mild estrogenic effects without being true estrogen hormones and, as such, play paradoxical but beneficial roles. Several human studies have found that soy isoflavones mimic estrogen and promote bone density, likely reducing the risk of osteoporosis in post-menopausal women. But the isoflavones also seem to prevent estrogen from attaching to and stimulating cells. It’s for this reason, researchers believe, that soy isoflavones ease the intensity of menopausal hot flashes and may lower the long-term risk of breast cancer.

Laboratory experiments also indicate that isoflavones can block the activity of tyrosine kinase, an enzyme that promotes cancer growth. According to Stephen Barnes, Ph.D., of University of Alabama at Birmingham, genistein may also block angiogenesis and trigger the destruction of cancer cells.

What’s on the Horizon?

The flavonoids are part of a larger group of antioxidant compounds called polyphenols. These substances include resveratrol, ellagic acid, curcumin, and various cinnamic acids.

Resveratrol occurs widely in foods, though only in trace amounts. In laboratory experiments, it has been found to be a powerful antioxidant inhibitor of cancer cell growth. The best food sources for resveratrol are wine and peanuts.

Ellagic acid, found in strawberries and raspberries, prevent toxins from mutating genes and setting the stage for cancer cells.

Curcumin, a spice common in Asian Indian foods, is another polyphenolic antioxidant. A recent study published in Cancer Letters reported that it blocked the action of a known cancer-causing chemical.

Cinnamic acids, which include caffeic and ferulic acids, are also powerful antioxidants. Experiments have found that these compounds can stop the growth of cancer cells.

You’ll find the most diverse selection of flavonoids in a diet with many different kinds of fruits, vegetables, and spices. Flavonoid supplements don’t contain such wide assortment of antioxidants, but they do concentrate the most important ones.

If you have a known risk factor for heart disease or cancer, eating fruits and vegetables is important but may not be sufficient for optimal health. It’s also likely, points out Lamm, that you may need more than just vitamins C and E. In such cases, it might be best to supplement a good diet with a specific flavonoid supplement. There are certainly plenty to choose from.

  • 1 Interview with Steven Lamm, M.D., July 15, 1997.
  • 2 Presentation by Peter Rohdewald, D.Sc., Ph.D., Biarritz, France, may 5, 1997.
  • 3 Zheng R-L and Zhang H, “Effects of ferulic acid on fertile and asthenozoospermic infertile human sperm motility, viability, lipid peroxidation and cyclic nucleotides,” Free Radical Biology & Medicine, 1997;22:581-586.
  • 4 Presentation by Steven Tenenbaum, Ph.D., and Julie Paul, Ph.D., Natural Foods Expo West, Anaheim, Calif., March 6, 1997.
  • 5 Presentation by Fabio Virgili, Ph.D., at the meeting of the Oxygen Club of California, Santa Barbara, February 26-March 1, 1997.
  • 6 Campos AM, et al., “Total antioxidant potential of Chilean wines, Nutrition Research, 1996;16:385-389.
  • 7 Mann D, “Grape juice and beer may prevent heart disease,” Medical Tribune News Service, March 18, 1997.
  • 8 Bagchi D, et al., “Oxygen free radical scavening abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro,” Molecular Pathology and Pharmacology, 1997;95:179-189.
  • 9 Facino RM, et al., “Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusuon injury: antioxidant intervention and/or iron and copper sequestering ability,” Planta Medica, 1996;62:495-502.
  • 10 Tanaka T, et al., “Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination,” Cancer Research, 1997; 57:246-252.
  • 11 Fotsis T, et al., “Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis,” Cancer Research, 1997;57:2916-2921.
  • 12 Hertog MGL, et al., “Antioxidant flavonols and coronary heart disease risk,” Lancet, 1997;349:699.
  • 13 Weisburger JH, Tea and health: a historical perspective,” Cancer Letters, 1997;114:315-317.
  • 14 Jankun J, et al., “Why drinking green tea could prevent cancer, Nature, 1997;387:561.
  • 15 Barnes S, et al., “Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer,” Journal of Cellular Biochemistry, 1996;22S:181-187.

This article originally appeared in Let’s Live magazine.