Pinus pinaster

Maritime pine


In 1534, a French explorer, Jacques Cartier, led a winter expedition up the St Lawrence River in New York. The group soon found themselves trapped by ice and forced to survive on salted meat and hard biscuits. The crew began to show signs and symptoms of scurvy, long before anyone knew what caused it. Due to a chance meeting with a Native American, who showed them how to make a tea from the bark and needles of pine trees, the men survived.

Professor Jacques Masquelier, of the University of Bordeaux, France, read a book written by Cartier about his experiences and became intrigued with the story and postulated that the pine bark must contain vitamin C as well as flavonoids having ascorbate-like effects. This was the beginning of an exhaustive study of these compounds which Masquelier named pycnogenols, a term no longer used in the scientific community today except as a trademark for OPCs derived from French maritime pine bark. Today they are known as oligomeric proanthocyanidin complexes (OPCs). It was also Professor Masquelier who confirmed the structure, effects, and lack of toxicity of these proanthocyanidins. Masquelier went on to patent the method of extracting OPCs from pine bark in 1951, and from grape seeds in 1970.1

Pycnogenol® is the patented trade name for a water extract of the bark of the French maritime pine (Pinus pinaster ssp. atlantica), which is grown in coastal southwestern France. Pycnogenol® contains oligomeric proanthocyanidins (OPCs) as well as several other bioflavonoids: catechin, epicatechin, phenolic fruit acids (such as ferulic acid and caffeic acid), and taxifolin.


Maritime pine bark extract contains bioflavonoids including catechin, caffeic acid, ferulic acid, procyanidins, and taxifolin. Oligomeric proanthocyanidins (OPCs) are some of the most abundant polyphenolic substances in the plant kingdom. Proanthocyanidins are an integral part of the human diet, found in high concentrations in fruits such as apple, pear, and grapes, and in chocolate, wine, and tea. OPCs in nutritional supplements are generally extracted from grape seeds or pine bark. The ability of OPCs to complex proteins is referred to as astringency and is responsible for the 'puckery' sensation when tea, red wine or an OPC-rich extract comes in contact with saliva and buccal tissue.2

Therapeutic activities

Considerable recent research has explored therapeutic applications of oligomeric proanthocyanidin complexes (OPCs), naturally occurring plant metabolites widely available in fruits, vegetables, nuts, seeds, flowers, and bark. OPCs are primarily known for their antioxidant activity. However, these compounds have also been reported to demonstrate antibacterial, antiviral, anticarcinogenic, anti-inflammatory, anti-allergic, and vasodilatory actions. In addition, they have been found to inhibit lipid peroxidation, platelet aggregation, capillary permeability and fragility, and to affect enzyme systems including phospholipase A2, cyclooxygenase, and lipoxygenase. Based on these reported findings, OPCs may be a useful component in the treatment of a number of conditions.1

Pharmacodynamic studies

Antioxidant activity

An OPC extract has been shown to have antioxidant activity in several in vitro, in vivo and human studies. The extract reduces lipidperoxidation,3 oxidation of LDL,4 increase basal levels of alpha-tocopherol in endothelial cells and protects endothelium from oxidative stress induced by reactive nitrogen species,5, 6 and protect endothelial cells from activated macrophage-induced glutathione depletion7 In healthy human subjects, supplemented with a OPC-rich extract six weeks has been shown to improve the plasma oxygen radical absorbance capacity score (ORAC)8 and in children with attention deficit hyperactivity disorder (ADHD), supplementation with an An OPC extract was shown to improve the reduced (GSH) to oxidised (GSSG) glutathione ratio (an indication of improved antioxidant status) and improved total antioxidant status. In the pathogenesis of ADHD genetic and non-genetic factors play an important role. It is assumed that one of non-genetic factors is oxidative stress.9

Cardiovascular activity

One explanation for the 'French Paradox' - relatively low rates of cardiovascular disease in France despite a diet of rich foods - is that OPCs in red wine offer protection by reducing LDL oxidation, inhibiting cyclooxygenase and lipoxygenase in platelets and macrophages, and decreasing thrombotic events. Epidemiological studies support this theory, indicating red wine consumption reduces the incidence of coronary heart disease.2 Apart from drinking red wine, therapeutically, OPC-rich extracts of grape seed/skin or maritime pine bark extracts can be used. In vitro studies have shown that OPC from marine pine bark increase increase erythrocyte membrane fluidity10, reduce platelet aggredation11, and stimulate constitutive endothelial nitric oxide synthase (eNOS) activity to increase nitric oxide levels, which could counteract the vasoconstrictor effects of epinephrine and norepinephrine.12 A clinical study found that OPC from maritime pine bark reduced LDL-cholesterol and increased HDL-cholesterol.8

Antiallergic activity

An OPC extract has been shown to reduct the histamine release induced by compound 48/80 or the calcium ionophore A-23187 in isolated rat peritoneal mast cells.13

Anticancer activity

An OPC extract has been shown to selectively induce apoptosis (programmed cell death) in human mammary cancer cells (MCF-7) and not in normal human mammary MCF-10 cells.14 The extract has also been shown to induce differentiation and apoptosis in leukemia cells. It was shown to dose- and time-dependently inhibit cell proliferation in HL-60, U937, and K562 human leukemia cell lines and to induce apoptosis, or programmed cell death, in human breast cancer in vitro but not in normal human mammary cells.15 The OPC extract has also been shown to inhibit nitrosamine activation in lung microsomes in vitro and in vivo.16, 17 And incorporating an OPC-rich extract in to a cigarette filter has been shown to reduce toxicity and mutagenicity in rodents exposed to cigarette smoke.18

Anti-diabetic activity

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. In a in vivo study an OPC extract treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after treatment. Additionally, diabetic rats treated with an OPC extract had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that OPCs alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.19

Chronic diabetes is characterised by microvascular pathologies, especially in the kidney, peripheral nerve, and eye. Although hyperglycemia can be controlled with insulin and/or antihyperglycemic medications, diabetic retinopathy due to oxidative stress continues to be the leading cause of blindness. A study found that decreased retinal gamma-glutamyl transferase activity of diabetic rats was normalised by the administration of the OPC extract alone or in combination with beta-carotene. Treatment with an OPC-rich extract and alpha-lipoic acid alone or in combination decreased the activity of glutathione peroxidase. Elevated activity of superoxide dismutase in diabetic retina was normalised by treatment with OPCs and beta-carotene in combination. This study shows that antioxidants can access the retina and, once there, can alter antioxidant enzyme activities. In both normal and diabetic rats, combinations of antioxidants have different effects on retinal antioxidant enzyme activities than do individual antioxidants.20

Anti-inflammatory activity

OPCs from pine bark decrease symptoms of chronic inflammation. In vitro studies demonstrate anti-inflammatory effects may be due to inhibition of peroxide generation by macrophages. In addition, animal studies demonstrate OPCs from grape seed significantly inhibit formation of proinflammatory cytokines, interleukin 1-beta, and tumor necrosis factor-alpha.2, 21 OPCs also inhibit release of histamine from mastcells.13

Clinical studies

Clinical studies using maritime bark extract are all based on the maritime pine bark extract Pycnogenol®. These studies are summarised in the chart below.22

Condition Description
Asthma Two randomised, controlled clinical trials have been conducted in individuals with asthma, one in children and one in adults. Results from these studies suggest that OPCs may offer clinical benefit to these patients.
ADHD Studies in children suggest OPCs improves attention and various rating scales.
Chronic venous insufficiency OPCs may reduce oedema and pain.
Diabetes Preliminary human data suggests that supplementation of OPCs with conventional diabetes treatment may lower glucose levels and improve endothelial function.
Hypertension Use of may reduce the need for nifedipine and decrease systolic blood pressure in mildly hypertensive patients.
Platelet aggregation (smokers) Two human studies report reduced platelet aggregation in smokers with OPCs supplementation.
Prevention of blood clots during long airplane fights Preliminary human studies suggest that OPCs may be effective in decreasing the number of thrombotic events (deep vein thrombosis and superficial vein thrombosis) in moderate-to-high risk subjects, during long-haul flights. Oedema may also be reduced.
Retinopathy OPCs may be efficacious in the treatment and prevention of retinopathy, including slowing the progression of retinopathy in diabetics. Suggested mechanisms include improvement of capillary resistance and reduction of leakage into the retina. Improvement of visual acuity has also been reported.
Systemic lupus erythematosus (SLE) Preliminary human data suggests that OPCs may be useful as a second line therapy to reduce inflammatory features of systemic lupus erythematosus (SLE). Further research is needed before a recommendation can be made.
Venous leg ulcers Preliminary human data suggests that OPCs may be useful for reduction of leg ulcers.
Skin protection Oral supplementation of OPCs (1.10mg/kg body weight daily for four weeks followed by 1.66mg/kg body weight daily for the next four weeks), resulted in reduced erythema in the skin


Pharmacokinetic studies have shown that more than 15 metabolites of the OPCs in maritime pine bark extracts including catechin, caffeic acid, ferulic acid, taxifolin and metabolite M1 (δ-(3,4-dihydroxy-phenyl)-γ-valerolactone) are detectable in the serum after oral intake.23


Antioxidant, antimutagenic, anticarcinogenic, anti-inflammatory and antiviral.

Traditional usage

Decoction of pine needles and bark was used by early North American natives and settlers to prevent scurvy and teeth and gum disorders during the winter months.


  • Antioxidant therapy
  • Asthma
  • Cholesterol reduction
  • Chronic venous insufficiency
  • Diabetes
  • Hypertension
  • Gingival bleeding/plaque
  • Oedema
  • Retinopathy
  • Sunburn
  • To reduce the risk of thrombotic events from long-haul flights
  • Venous insufficiency and leg ulcers

Use in pregnancy

No specific information available. Likely to be safe.

Contraindications and cautions

Maritime pine bark extract is generally well tolerated. Low acute and chronic toxicity with mild unwanted effects, including vertigo, headache, and nausea have been reported has been reported to occur in a small percentage of patients following oral administration of the OPC-rich extract.24 Because of its astringent taste and occasional minor stomach discomfort, it may be best to take maritime pine bark extract with or after meals. To date, no serious adverse effects have been reported in the available scientific literature, although systematic study of safety is not available.

Drug interactions

An in vitro study has showed that an OPC extract may improve the efficacy of acetylsalicylic acid in the inhibition of platelet function. Whether this has any clinical relevance needs to be demonstrated.11 OPCs may reduce adverse effects of common chemotherapy drugs cyclophosphamide and doxorubicin. An animal study found that OPCs inhibit thymus DNA synthesis induced by cyclophosphamide.25 An in vitro study found that an OPCs may have a protective effect on the cardiotoxicity of doxorubicin.25, 26 In a clinical trial with an OPC-rich extract, it was shown to reduce the need for the Calcium channel blocker nifedipine in mildly hypertensive patients.27

A case report of a 10 year-old with attention deficit hyperactivity disorder (ADHD) suggests that the OPC-rich extract in addition Dexedrine (dextroamphetamine) may decrease hyperactive and impulsive behavior.28

Administration and Dosage

Daily dosage of OPCs: Tablets or capsules containing 100-200 mg OPCs-rich extract daily.
Liquid extract (1:2): 0.1ml daily take with or after meals.

Reference List

  1. Fine AM. Oligomeric proanthocyanidin complexes: history, structure, and phytopharmaceutical applications. Altern Med Rev 2000; 5(2):144-151.
  2. Thorne. Oligomeric proanthocyanidins (OPCs). Monograph. Altern Med Rev 2003; 8(4):442-450.
  3. Horakova L, Licht A, Sandig G, Jakstadt M, Durackova Z, Grune T. Standardized extracts of flavonoids increase the viability of PC12 cells treated with hydrogen peroxide: effects on oxidative injury. Arch Toxicol 2003; 77(1):22-29.
  4. Nelson AB, Lau BH, Ide N, Rong Y. Pycnogenol inhibits macrophage oxidative burst, lipoprotein oxidation, and hydroxyl radical-induced DNA damage. Drug Dev Ind Pharm 1998; 24(2):139-144.
  5. Virgili F, Kim D, Packer L. Procyanidins extracted from pine bark protect alpha-tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide and peroxynitrite. FEBS Lett 1998; 431(3):315-318.
  6. Virgili F, Kobuchi H, Packer L. Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine RAW 264.7 macrophages. Free Radic Biol Med 1998; 24(7-8):1120-1129.
  7. Rimbach G, Virgili F, Park YC, Packer L. Effect of procyanidins from Pinus maritima on glutathione levels in endothelial cells challenged by 3-morpholinosydnonimine or activated macrophages. Redox Rep 1999; 4(4):171-177.
  8. Devaraj S, Vega-Lopez S, Kaul N, Schonlau F, Rohdewald P, Jialal I. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids 2002; 37(10):931-934.
  9. Dvorakova M, Sivonova M, Trebaticka J, Skodacek I, Waczulikova I, Muchova J et al. The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD). Redox Rep 2006; 11(4):163-172.
  10. Sivonova M, Waczulikova I, Kilanczyk E, Hrnciarova M, Bryszewska M, Klajnert B et al. The effect of Pycnogenol on the erythrocyte membrane fluidity. Gen Physiol Biophys 2004; 23(1):39-51.
  11. Golanski J, Muchova J, Golanski R, Durackova Z, Markuszewski L, Watala C. Does pycnogenol intensify the efficacy of acetylsalicylic acid in the inhibition of platelet function? In vitro experience. Postepy Hig Med Dosw (Online ) 2006; 60:316-321.
  12. Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol 1998; 32(4):509-515.
  13. Sharma SC, Sharma S, Gulati OP. Pycnogenol inhibits the release of histamine from mast cells. Phytother Res 2003; 17(1):66-69.
  14. Huynh HT, Teel RW. Selective induction of apoptosis in human mammary cancer cells (MCF-7) by pycnogenol. Anticancer Res 2000; 20(4):2417-2420.
  15. Huang WW, Yang JS, Lin CF, Ho WJ, Lee MR. Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL-60 cells. Leuk Res 2005; 29(6):685-692.
  16. Huynh HT, Teel RW. Effects of pycnogenol on the microsomal metabolism of the tobacco-specific nitrosamine NNK as a function of age. Cancer Lett 1998; 132(1-2):135-139.
  17. Huynh HT, Teel RW. Effects of intragastrically administered Pycnogenol on NNK metabolism in F344 rats. Anticancer Res 1999; 19(3A):2095-2099.
  18. Zhang D, Tao Y, Gao J, Zhang C, Wan S, Chen Y et al. Pycnogenol in cigarette filters scavenges free radicals and reduces mutagenicity and toxicity of tobacco smoke in vivo. Toxicol Ind Health 2002; 18(5):215-224.
  19. Maritim A, Dene BA, Sanders RA, Watkins JB, III. Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats. J Biochem Mol Toxicol 2003; 17(3):193-199.
  20. Dene BA, Maritim AC, Sanders RA, Watkins JB, III. Effects of antioxidant treatment on normal and diabetic rat retinal enzyme activities. J Ocul Pharmacol Ther 2005; 21(1):28-35.
  21. Blazso G, Gabor M, Rohdewald P. Antiinflammatory activities of procyanidin-containing extracts from Pinus pinaster Ait. after oral and cutaneous application. Pharmazie 1997; 52(5):380-382.
  22. Conquer J. Pycnogenol (Pinus pinaster ssp. atlantica). 2008. Natural Standard. 13-2-2008. Ref Type: Electronic Citation
  23. Grimm T, Skrabala R, Chovanova Z, Muchova J, Sumegova K, Liptakova A et al. Single and multiple dose pharmacokinetics of maritime pine bark extract (pycnogenol) after oral administration to healthy volunteers. BMC Clin Pharmacol 2006; 6:4.
  24. Koch R. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res 2002; 16 Suppl 1:S1-S5.
  25. Feng WH, Wei HL, Liu GT. Effect of PYCNOGENOL on the toxicity of heart, bone marrow and immune organs as induced by antitumor drugs. Phytomedicine 2002; 9(5):414-418.
  26. Mojzisova G, Mirossay L, Kucerova D, Kyselovic J, Mirossay A, Mojzis J. Protective effect of selected flavonoids on in vitro daunorubicin-induced cardiotoxicity. Phytother Res 2006; 20(2):110-114.
  27. Liu X, Zhou HJ, Rohdewald P. French maritime pine bark extract Pycnogenol dose-dependently lowers glucose in type 2 diabetic patients. Diabetes Care 2004; 27(3):839.
  28. Heimann SW. Pycnogenol for ADHD? J Am Acad Child Adolesc Psychiatry 1999; 38(4):357-358.