Pine Bark Extract

Health Care Professional Information

Scientific Name
Pinus maritima
Common Name

French Marine Pine Bark Extract, Pine Bark, Procyanidin Oligomers, Procyanodolic Oligomers, PCO, PCOs

Brand Name

Pycnogenol®

Clinical Summary

Obtained from the bark of the French maritime pine tree, Pinus maritima, pine bark extract consists of proanthocyanidins and is marketed under the tradename Pycnogenol®. In vitro and animal studies indicate that pine bark extract has antioxidant, anti-inflammatory (6), immunostimulant (1), and neuroprotective (31) effects. Pine bark extract may also have antiviral and antimicrobial activities. It inhibits HIV attachment and replication (15), suppresses encephalomyocarditis virus (EMV) replication (16), and represses Helicobacter pylori growth and adherence to gastric cells (17).

Pine bark extract has been studied in humans for various conditions. Preliminary research suggests that it reduces menopausal symptoms in peri-menopausal women (8), relieves symptoms of dysmenorrhea (27), and improves osteoarthritic symptoms (9) (10). It is also used to treat skin disorders such as hyperpigmentation (11), erythema (12), endometriosis (13), and systemic lupus erythematosus (14).
Pine bark extract can improve endothelial dysfunction (2) (33) and chronic venous insufficiency (5). Chewing gum containing pine bark extract may reduce gingival bleeding and plaque accumulation (19). When used in conjunction with L-arginine, Pycnogenol is effective in improving symptoms of erectile dysfunction (18) (29). Pycnogenol supplementation also enhanced memory in elderly participants (7). Studies of attention deficit hyperactivity disorder in adults and in children yielded mixed results (3) (4).
However, a systematic review concluded that large scale studies are needed to establish the value of Pycnogenol in the treatment of chronic disorders (34).

In vitro studies show antimetastatic effects of pine bark extract (32). Pycnogenol may also protect against cardiotoxicity caused by doxorubicin without antagonizing its cytotoxic activity (20). Preliminary findings from a study involving cancer patients suggest usefulness of pycnogenol is reducing adverse effects associated with radiotherapy and chemotherapy (30). Further research is needed.

Adverse effects may include irritability and decreased energy especially when used for ADHD.
Pine bark extract may interact with certain chemotherapeutic drugs, anticoagulant/antiplatelet drugs, and immunosuppressants.

Purported Uses
  • Attention deficit hyperactivity disorder
  • Cancer prevention
  • Chronic venous insufficiency
  • Erectile dysfunction
  • Hypertension
  • Inflammation
Constituents
  • Procyanidins
  • Phenolic acids such as ferulic, caffeic, protocatechic, p-hydroxybenzoic and vanillic acid
    (35)
Mechanism of Action

Pine bark extract acts as an antioxidant by scavenging reactive oxygen and nitrogen species and suppressing production of peroxides (21). It increases the activities of antioxidant enzymes by increasing the intracellular glutathione levels (22). In addition to increasing NO production which induces vasodilation (2), pine bark extract also blocks the NF-kB activation stimulated by tumor necrosis factor-alpha (TNF-alpha) and inhibits production of adhesion proteins that cause inflammation and atherosclerosis (22). An in vitro study suggests that Pycnogenol induces apoptosis in human breast cancer cells and not in normal breast cells although the mechanism is not clear (23). Other in vitro studies have also shown that it reduces neuronal apoptosis, an important feature of Alzheimer's disease, by decreasing free radical generation (24). In animal studies, pine bark extract exhibits a protective effect on cardiotoxicity caused by antitumor drugs, such as doxorubicin, due to its ability to act as a free-radical scavenger (20).

Pharmacokinetics

Many pine bark extracts on the market are not standardized and the concentration of active components and bioactivities are hard to determine. Since pycnogenol is a complex mixture of different compounds, the bioavailability and metabolic pathways that most of them follow are still unknown. However, one of the components in pycnogenol, ferulic acid, was shown to be excreted in the urine as glucuronide and sulfate within 18-24 hours after oral administration (25).

Warnings

Pine bark extract has potent antioxidant effects. It may interfere with the action of certain chemotherapeutic drugs and radiation therapy.

Contraindications
  • Hypersensitivity to pine bark (26)
Adverse Reactions
  • May cause irritability and lower energy levels especially when used for ADHD. (26)
Herb-Drug Interactions
  • Chemotherapeutic Agents: Pine bark extract has potent antioxidant effect and may interfere with the action of anthracyclines, platinum compounds, and alkylating agents.
  • Immunosuppressants: Pine bark extract has immunostimulant effect and may antagonize the effects of immunosuppressants, such as cyclosporine and tacrolimus.
  • Anticoagulant and/or Antiplatelet drugs: Pine bark extract can inhibit platelet aggregation and may increase risk of bleeding when used with these drugs (28).
Literature Summary and Critique

Yang HM, Liao MF, Zhu SY, Liao MN, Rohdewald P. A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol on the climacteric syndrome in peri-menopausal women. Acta Obstet Gynecol Scand. 2007;86(8):978-985.
A randomized, double-blind, placebo-controlled study of 200 peri-menopausal Taiwanese women analyzed the effect of pine bark extract (Pycnogenol®, 200 mg daily) on menopausal symptoms. After 6 months, the participants completed the Women's Health Questionnaire, which demonstrated the climacteric symptom-relieving characteristics of Pycnogenol as compared to the placebo group. The authors concluded that because Taiwanese women report differing peri-menopausal symptoms compared to European women, this study should be expanded to other populations of women.

Nishioka K, et al. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res 2007;30(9):775-780.
The effect of Pycnogenol on forearm blood flow in response to endothelial-dependent (acetylcholine, Ach) and independent (sodium nitroprusside, SNP) vasodilators was assessed in this small, double-blind, randomized, placebo-controlled study of 16 healthy men. Participants either received placebo or Pycnogenol (180 mg daily) for 2 weeks before forearm blood flow was measured. Although Pycnogenol alone did not affect forearm blood flow, Ach-dependent forearm blood flow was increased in the Pycnogenol-treated group, an effect that was reversed upon administration of a NO synthase inhibitor. Pycnogenol did not influence vasodilation mediated by SNP, indicating that Pycnogenol influences endothelial-dependent vasodilation most likely through enhancing NO synthesis. Further studies with larger numbers of participants are required to determine if Pycnogenol is beneficial in subjects with oxidative stress-related diseases.

Ryan J, et al. An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. J Psychopharmacol 2008;22(5):553-562.
In a double-blind, placebo-controlled, matched-paired study, the effect of Pycnogenol on cognitive function and serum lipid profiles was assessed in 101 elderly participants. After 3 months, working memory was enhanced in the participants receiving Pycnogenol (150 mg/day) as compared to the placebo group. The authors surmise that this enhancement may be due to the anti-oxidant activity of Pycnogenol. Larger, long term studies are necessary to full determine the clinical benefits of Pycnogenol supplementation on memory.

Dosage (Inside MSKCC Only)
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References
  1. Liu, F.J. et al. Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated mice. Cell Mol Life Sci. 1998;54(10):1168-72
  2. Nishioka K, Hidaka T, Nakamura S, et al. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res. Sep 2007;30(9):775-780.
  3. Tenenbaum, S. et al. An experimental comparison of pycnogenol and methylphenidate in adults with Attention-deficit-hyperactivity disorder (ADHD). J Atten Disord 2002;6(2):49-60
  4. Trebaticka J, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry 2006.
  5. Arcangeli, P. Pycnogenol in chronic venous insufficiency. Fitoterapia 2000;71(3):236-44
  6. Cho, K.J et al.Inhibition mechanisms of bioflavonoids extracted from the bark of Pinus maritima on the expression of proinflammatory cytokines. Ann N Y Acad Sci. 2001;928:141-56
  7. Ryan J, Croft K, Mori T, et al. An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. J Psychopharmacol. Jul 2008;22(5):553-562.
  8. Yang HM, Liao MF, Zhu SY, Liao MN, Rohdewald P. A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol on the climacteric syndrome in peri-menopausal women. Acta Obstet Gynecol Scand. 2007;86(8):978-985.
  9. Belcaro G, Cesarone MR, Errichi S, et al. Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects. Phytother Res. Apr 2008;22(4):518-523.
  10. Cisar P, Jany R, Waczulikova I, et al. Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis. Phytother Res. Aug 2008;22(8):1087-1092.
  11. Ni, Z. et al. Treatment of melasma with pycnogenol. Phytother Res 2002;16(6):567-71
  12. Saliou, C. et al. Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med 2002;30(2):154-60
  13. Kohama T, Herai K, Inoue M. Effect of French maritime pine bark extract on endometriois as compared with leuprorelin acetate. J Reprod Med 2007;52(8):703-8.
  14. Stefanescu, M. et al. Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients. Phytother Res. 2002;15(8):698-704
  15. Feng WY, Tanaka R, Inagaki Y, et al. Pycnogenol, a procyanidin-rich extract from French maritime pine, inhibits intracellular replication of HIV-1 as well as its binding to host cells. Jpn J Infect Dis. Jul 2008;61(4):279-285.
  16. Matsumori A, Higuchi H, Shimada M. French maritime pine bark extract inhibits viral replication and prevents development of viral myocarditis. J Card Fail. Nov 2007;13(9):785-791.
  17. Rohdewald P, Beil W. In vitro inhibition of Helicobacter pylori growth and adherence to gastric mucosal cells by Pycnogenol. Phytother Res. May 2008;22(5):685-688.
  18. Stanislavov, R and Nikolova, V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003;29(3):207-13
  19. Kimbrough, C. et al. Pycnogenol chewing gum minimizes gingival bleeding and plaque formation. Phytomedicine 2002;9(5):410-13
  20. Feng, W. et al. Effect of Pycnogenol on the toxicity of heart, bone marrow and immune organs as induced by antitumor drugs. Phytomedicine 2002;9(5):414-18
  21. Packer, L et al. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radic Biol Med 1999;27:704-24
  22. Peng, Q. et al. Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cell Mol LifeSci. 2000;57(5):834-41
  23. Huynh, H.T. and Teel, R. W. Selective induction of apoptosis in human mammary cancer cells (MCF-7) by pycnogenol. Anticancer Res 2000;20(4):2417-20
  24. Peng, Q. et al. Pycnogenol protects neurons from amyloid-beta peptide induced apoptosis. Brain Res Mol Brain Res 2002;104(1):55-65
  25. Virgili, F et al. Ferulic acid excretion as a marker of consumption of a french maritime pine (Pinus maritima) bark extract. Free Radic Biol Med 2000;28(8):1249-56
  26. MICROMEDEX(R) Healthcare Series. 120. 2004. Thomson MICROMEDEX.
  27. Suzuki N, Uebaba K, Kohama T, et al. French maritime pine bark extract significantly lowers the requirement for analgesic medication in dysmenorrhea: a multicenter, randomized, double-blind, placebo-controlled study. J Reprod Med. 2008 May;53(5):338-46.
  28. Pütter M, Grotemeyer KH, Würthwein G, et al. Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol. Thromb Res. 1999 Aug 15;95(4):155-61.
  29. Ledda A, Belcaro G, Cesarone MR, Dugall M, Schönlau F. Investigation of a complex plant extract for mild to moderate erectile dysfunction in a randomized, double-blind, placebo-controlled, parallel-arm study. BJU Int. 2010;106(7):1030-3.
  30. Belcaro G, Cesarone MR, Genovesi D, et al. Pycnogenol may alleviate adverse effects in oncologic treatment. Panminerva Med. 2008 Sep;50(3):227-34.
  31. Ansari MA, Keller JN, Scheff SW. Protective effect of Pycnogenol in human neuroblastoma SH-SY5Y cells following acrolein-induced cytotoxicity. Free Radic Biol Med. 2008 Dec 1;45(11):1510-9.
  32. Wu DC, Li S, Yang DQ, Cui YY. Effects of Pinus massoniana bark extract on the adhesion and migration capabilities of HeLa cells. Fitoterapia. 2011 Dec;82(8):1202-5.
  33. Enseleit F, Sudano I, Périat D, Winnik S, et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012 Jul;33(13):1589-97.
  34. Schoonees A, Visser J, Musekiwa A, Volmink J. Pycnogenol (extract of French maritime pine bark) for the treatment of chronic disorders. Cochrane Database Syst Rev. 2012 Apr 18;4:CD008294.
  35. Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68.

Consumer Information

How It Works

Bottom Line: Pine bark extract has not been shown to treat or prevent cancer.

Pycnogenol is derived from the bark of the French maritime pine tree. Studies have shown that it is effective in treating many inflammatory conditions, skin disorders, and chronic venous insufficiency (poor blood circulation) because of its antioxidant and antiinflammatory properties. It was also shown to be effective in treating erectile dysfunction when used in combination with L-arginine. Animal studies indicate that pycnogenol exhibits protective effect against cardiac toxicity caused by doxorubicin (a chemo drug). But human data is lacking.

Purported Uses
  • Chronic venous insufficiency
    Several clinical trials support this use.
  • Attention deficit hyperactivity disorder (ADHD)
    One study found pycnogenol is not effective in treating ADHD in adults.
  • Cancer prevention
    This use has not been proven by clinical studies.
  • Inflammation
    A preliminary study supports this use. More clinical trials are needed.
  • Hypertension
    There are limited clinical data showing pine bark extract can be used together with standard blood pressure medication.
  • Erectile dysfunction
    Limited studies have been conducted and more trials are needed to establish this use.
Research Evidence

Treatment of attention deficit hyperactivity disorder (ADHD)In a recent clinical trial, 24 patients with ADHD were given pycnogenol, Ritalin or placebo for 3 weeks. After a 1-week no-treatment period, patients were switched to another treatment for 3 more weeks. Researchers found no difference between the treatments and researchers concluded that neither pycnogenol nor Ritalin was effective in comparison to placebo in treating ADHD.

Treatment of chronic venous insufficiency (CVI)
In a recent study, 40 patients with CVI were given either 360 mg of pycnogenol or 600 mg of Venostasin (horse chestnut seed extract) daily for 4 weeks. Researchers found that pycnogenol effectively improved the symptoms associated with CVI such as increased circumference of lower limbs, pain, and night-time swelling in comparison to Venostasin. It also lowered the low-density lipoprotein (LDL) cholesterol values.

Treatment of hypertensionThis clinical trial involved 58 patients with hypertension. Patients were given a combination of 5mg nifedipine and placebo or 5mg nifedipine and 100mg pyncogenol daily for 12 weeks. All patients were given 20mg of nifedipine before the study began. The dosage of nifedipine was adjusted (increased or lowered by 5 mg) according to measured blood pressure values every two weeks. Researchers found that most patients had normal blood pressure after the 12 week period with 10mg nifedipine and pycnogenol. They concluded that pycnogenol is effective in treating mild hypertension.

Do Not Take If
  • You have hypersensitivity to pine bark
  • You are taking chemotherapeutic agents (Pine bark extract has potent antioxidant effect and may interfere with the action of anthracyclines, platinum compounds, and alkylating agents)
  • You are using Anticoagulant and/or Antiplatelet drugs: (Pine bark extract can inhibit platelet aggregation and may increase risk of bleeding when used with these drugs)
  • You are taking immunosuppressants (Pine bark extract has immunostimulant effect and may antagonize the effects of immunosuppressants, such as cyclosporine and tacrolimus).
Side Effects
  • Irritability
  • Lowered energy levels
Special Point

Many pine bark extracts on the market are not standardized and the concentration of active components and bioactivities are hard to determine.

E-mail your questions and comments to aboutherbs@mskcc.org.