Scientific Name(s): Pinus pinaster Aiton., Pinus radiata
Common Name(s): Enzogenol, Maritime pine extract, Monterey pine extract, Pine bark extract, Pycnogenol
Pine bark extract demonstrates antioxidant and anti-inflammatory actions and has been studied for a wide range of clinical conditions, including asthma, attention deficit hyperactivity disorder (ADHD), chronic venous insufficiency, cardiovascular conditions, diabetes, and erectile dysfunction. However, the publication of many methodologically weak clinical trials makes it difficult to provide unequivocal support for the use of pine bark extract for any condition.
Doses of pine bark extract have been studied in clinical trials, most commonly at 150 mg per day in 3 divided doses.
Contraindications have not yet been identified.
Information regarding safety and efficacy during pregnancy and lactation is lacking.
None well documented.
Pine bark extract is generally well tolerated, with occasional minor gastric discomfort, dizziness, nausea, and headache.
Pine bark extract is generally recognized as safe (GRAS) based on data from animal studies and clinical trials; however, few studies evaluate safety as a primary outcome.
P. pinaster Aiton (previously termed Prunus maritima Mill.) and P. radiata are medium-sized pines growing up to 30 m tall with bright red-brown, deeply fissured bark. They have stout needles occurring in clusters and produce oval cones 10 to 20 cm long. The pine tree is native to the western and southwestern Mediterranean regions but has rapidly naturalized to other countries, including the United States, England, South Africa, and Australia. The largest man-made forest in the world, the 900,000 hectare Les Landes on the Atlantic coast of southwestern France, is populated almost entirely by P. pinaster.1, 2
In 1535, a French explorer is reputed to have used tea made from the bark of the maritime pine to treat scurvy among his sailors when his ship became icebound. The extract has been used for anemia, inflammation, and cardiovascular conditions. Pine bark has been used as a food source in emergencies. Pine bark extract is available without a prescription in the US health food stores and pharmacies, as well as from online sources.2, 3, 4, 5
Pine bark extract is composed of 80% to 85% proanthocyanidins, the monomers catechin and taxifolin (5%), and phenolic acids, including derivatives of benzoic and cinnamic acids (2% to 4%). Depending on the extraction process and the source Pinus species used (P. radiata or P. pinaster), the exact composition will vary. Geographical and seasonal variation is also expected. Pine bark is boiled with saturated sodium chloride, cooled, and extracted with ethyl acetate. After concentration, the solution is precipitated with chloroform. This process is repeated several times to remove condensed tannins. In some studies, the extracted compounds are designated procyanidiol oligomers. The phenolic acids are derivatives of benzoic and cinnamic acids. Confusion previously arose when grape seed extract was marketed as containing "pycnogenol." Maritime pine extract is included in the United States Pharmacopeia.2, 3, 4, 5
Uses and Pharmacology
The quality of many published clinical studies has been limited by small sample sizes or the use of nonrandomized or open-label designs. Many of the studies have been conducted by a small pool of researchers, some being industry-sponsored. Insufficient evidence exists supporting the use of pine bark extracts for any long-term condition. The findings from ongoing clinical trials are anticipated.2, 3, 6
Antioxidant properties of pine bark extracts have been well described in laboratory studies and are considered to be responsible for the majority of clinical effects.2, 3, 4 However, clinical studies evaluating changes in antioxidant status after pine bark extract administration in humans have produced equivocal results.7, 8, 9
Animal data regarding the use of pine bark extract in asthma are lacking.
Limited small studies have been conducted in children and adults.6 Reductions in the mean use of asthma inhaler puffs and improved peak flow measures were reported.10, 11
Animal data regarding the use of pine bark extract in diseases of the CNS are lacking.
Limited small clinical studies with positive findings have been conducted in cognition, ADHD, and brain injury.12, 13, 14 These studies also report no serious adverse effects; more clinical studies are needed. Results from a systematic review of ADHD in children and adults found results to be equivocal.15
Studies in spontaneously hypertensive rats suggest a protective effect on microvasculature by pine bark extract thought to be due to antioxidant effects. Small decreases in systolic blood pressure were also observed.16 Cardiomyopathy in diabetic rats was reduced by pine bark extract, also considered to be due to antioxidant activity, but possibly due to improved cardiac energy metabolism via observed lowered plasma glucose.17
Multiple trials conducted in various cardiovascular conditions, including chronic venous insufficiency and hypertension, report positive findings. The majority of these studies are methodologically weak or subject to bias,2, 6 and at least 1 clinical study has been published that found no impact of supplemental pine bark extract on cardiovascular disease risk factors.18 Changes in markers of oxidative stress in cardiovascular disease have been demonstrated in small clinical trials.6, 19, 20, 21
Lipid parameters (ie, total cholesterol, high-density lipoprotein, triglycerides), excluding low-density lipoprotein (LDL), were not found to be affected by supplementation of the standardized maritime pine extract Pycnogenol in a meta-analysis of 5 controlled studies (N = 442) published between 2003 to 2012. A significant dose-effect association was, however, found for LDL (slope −0.007; P = 0.01). Studies included healthy volunteers as well as patients with hypertension, stable coronary artery disease, type 2 diabetes and hypertension, erectile dysfunction, elderly patients, and perimenopausal women; Pycnogenol was dosed at 120 to 200 mg/day for a duration of 2 to 24 weeks. Limitations of the analysis included observed effect sizes too small to be clinically relevant, lack of data on concomitant lipid-lowering drugs, and uncontrolled dietary measures.46
Pine bark extracts induced apoptosis in MCF-7 breast cancer cells and in HL-60 leukemia cells and reduced the adverse effects of chemotherapy and radiation therapy in rats.22, 23, 24, 25, 26, 27, 28
There are no clinical data regarding the use of pine bark extract in cancer.
In vitro studies suggest pine bark extract exhibits a number of beneficial effects, including inhibition of lipid accumulation in adipocytes, stimulation of lipolysis, and increased glucose uptake.29, 30, 31
In rodent studies, pine bark extract showed antioxidant effects and improved insulin resistance and hyperglycemia.32, 33
Limited, methodically weak clinical trials have been conducted in type 2 diabetes.6 Doses of pine bark extract 150 mg daily have been used in these studies with no apparent serious adverse effects; more robust clinical studies are needed.
Animal data regarding the use of pine bark extract in erectile dysfunction are lacking.
One small clinical trial showed improved symptom scores for erectile dysfunction. Markers of oxidative stress remained unchanged.6, 34 Other limited clinical trials have evaluated the efficacy of pine bark extract in combination with L-arginine.35, 36
Animal and in vitro studies suggest that pine bark extract exerts an anti-inflammatory effect possibly via proinflammatory mediators.37, 38, 39, 40
Limited clinical studies suggest a role in the management of osteoarthritis with improved Western Ontario and McMaster Universities Osteoarthritis Index scores after 3 months of pine bark extracts 100 mg per day; however, methodological weaknesses limit the impact of these trials.2, 6
Pine bark extract has been studied for multiple conditions including diabetic retinopathy and ulceration, tinnitus, hemorrhoids, hyperpigmentation in melasma, menopausal symptoms, motion sickness, traveler's thrombosis, control of inflammation in lupus patients, as an adjunct for childhood asthma, and in a chewing gum for gingival bleeding and plaque. The majority of these clinical studies are methodologically weak or subject to bias.2, 6
Doses of pine bark extract 60 to 300 mg daily have been studied in clinical trials, most commonly at 150 mg/day in 3 divided doses.2, 3, 5 The pharmacokinetics of maritime pine bark extract constituents have been studied in human volunteers. A total of 15 compounds were found to be rapidly absorbed and metabolized by phase 2 enzymes.41
Pregnancy / Lactation
Information regarding safety and efficacy during pregnancy and lactation is lacking. Pine bark extract has been studied in a small clinical trial for pain in the third trimester of pregnancy at a dose of 30 mg/day; however, this should not be regarded as evidence of safety.42
None well documented. Older studies suggest decreased platelet aggregation43, 44, 45; however, case reports of interactions are lacking.
Pine bark extract is generally well tolerated, with occassional minor gastric discomfort, dizziness, nausea, and headache. Clinical studies using pine bark extracts report no clinically important adverse events at doses of 150 mg daily; however, few studies evaluate safety as a primary outcome.2, 6 Studies in dogs report emesis and production of soft feces.4
Pine bark extract is GRAS, based on data from animal studies and clinical trials; however, few studies evaluate safety as a primary outcome.2, 3, 4, 9 P. radiata extract was nonmutagenic in the Ames test.4 Consumption of pine needles is associated with abortion in cattle.44
1. Pinus Pinaster
Aiton, Pinus radicata
D. Don. USDA, NRCS. 2014. The PLANTS Database (http://plants.usda.gov
, July 2014). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed November 6, 2014.
2. Maimoona A, Naeem I, Saddiqe Z, Jameel K. A review on biological, nutraceutical and clinical aspects of French maritime pine bark extract. J Ethnopharmacol
. 2011;133(2):261-277. 21044675
3. D'Andrea G. Pycnogenol
: a blend of procyanidins with multifaceted therapeutic applications? Fitoterapia
. 2010;81(7):724-736. 20598812
4. Frevel MA, Pipingas A, Grigsby WJ, Frampton CM, Gilchrist NL. Production, composition and toxicology studies of EnzogenolPinus radiata
bark extract. Food Chem Toxicol
5. Duke J, Bogenschutz-Godwin M, duCellier J, Duke P. Handbook of medicinal herbs
. 2nd ed. ed. Boca Raton, FL: CRC Press; 2002.
6. 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
7. Devaraj S, Vega-López S, Kaul N, Schönlau 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. 12530550
8. Silliman K, Parry J, Kirk LL, Prior RL. Pycnogenol
does not impact the antioxidant or vitamin C status of healthy young adults. J Am Diet Assoc
9. Dvořáková M, Paduchová Z, Muchová J, Duračková Z, Collins AR. How does Pycnogenol
influence oxidative damage to DNA and its repair ability in elderly people? Prague Med Rep
. 2010;111(4):263-271. 21189165
10. Lau BH, Riesen SK, Truong KP, Lau EW, Rohdewald P, Barreta RA. Pycnogenol
as an adjunct in the management of childhood asthma. J Asthma
11. Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R, Watson RR. Pycnogenolin the management of asthma. J Med Food
12. Pipingas A, Silberstein RB, Vitetta L, et al. Improved cognitive performance after dietary supplementation with a Pinus radiata
bark extract formulation. Phytother Res
13. Theadom A, Mahon S, Barker-Collo S, et al. Enzogenol
for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT. Eur J Neurol
14. Trebatická J, Kopasová S, Hradecná Z, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol
. Eur Child Adolesc Psychiatry
15. Sarris J, Kean J, Schweitzer I, Lake J. Complementary medicines (herbal and nutritional products) in the treatment of attention deficit hyperactivity disorder (ADHD): a systematic review of the evidence. Complement Ther Med
16. Rezzani R, Porteri E, De Ciuceis C, et al. Effects of melatonin and Pycnogenol
on small artery structure and function in spontaneously hypertensive rats. Hypertension
17. Klimas J, Kmecova J, Jankyova S, et al. Pycnogenol
improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats. Phytother Res
18. Drieling RL, Gardner CD, Ma J, Ahn DK, Stafford RS. No beneficial effects of pine bark extract on cardiovascular disease risk factors. Arch Intern Med
19. Enseleit F, Sudano I, Periat D, 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
20. Young JM, Shand BI, McGregor PM, Scott RS, Frampton CM. Comparative effects of enzogenol and vitamin C supplementation versus vitamin C alone on endothelial function and biochemical markers of oxidative stress and inflammation in chronic smokers. Free Radic Res
21. Nishioka K, Hidaka T, Nakamura S, et al. Pycnogenol
, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res
22. Huynh HT, Teel RW. Selective induction of apoptosis in human mammary cancer cells (MCF-7) by Pycnogenol
. Anticancer Res
23. Huang WW, Yang JS, Lin CF, Ho WJ, Lee MR. Pycnogenol
induces differentiation and apoptosis in human promyeloid leukemia HL-60 cells. Leuk Res
24. 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
25. de Moraes Ramos FM, Schönlau F, Novaes PD, Manzi FR, Bóscolo FN, de Almeida SM. Pycnogenol protects against ionizing radiation as shown in the intestinal mucosa of rats exposed to x-rays. Phytother Res
26. Sime S, Reeve VE. Protection from inflammation, immunosuppression and carcinogenesis induced by UV radiation in mice by topical Pycnogenol
. Photochem Photobiol
27. Schmidt AJ, Krieg JC, Hemmeter UM, et al. Impact of plant extracts tested in attention-deficit/hyperactivity disorder treatment on cell survival and energy metabolism in human neuroblastoma SH-SY5Y cells. Phytother Res
28. Kim DS, Kim MS, Kang SW, Sung HY, Kang YH. Pine bark extract enzogenol attenuated tumor necrosis factor-alpha-induced endothelial cell adhesion and monocyte transmigration. J Agric Food Chem
29. Lee OH, Seo MJ, Choi HS, Lee BY. Pycnogenol inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses. Phytother Res
30. Hasegawa N. Inhibition of lipogenesis by Pycnogenol
. Phytother Res
31. Lee HH, Kim KJ, Lee OH, Lee BY. Effect of Pycnogenol
on glucose transport in mature 3T3-L1 adipocytes. Phytother Res
32. Berryman AM, Maritim AC, Sanders RA, Watkins JB III. Influence of treatment of diabetic rats with combinations of Pycnogenol
, beta-carotene, and alpha-lipoic acid on parameters of oxidative stress. J Biochem Mol Toxicol
33. Bang CY, Choung SY. Enzogenol
improves diabetes-related metabolic change in C57BL/KsJ-db/db mice, a model of type 2 diabetes mellitus. J Pharm Pharmacol
34. Durackova Z, Trebaticky B, Novotny V, Zitnanova I, Breza J. Lipid metabolism and erectile function improvement by Pycnogenol
, extract from the bark of Pinus pinaster
in patients suffering from erectile dysfunction-a pilot study. Nutr Res
35. 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):1030-1033. 20184576
36. Aoki H, Nagao J, Ueda T, et al. Clinical assessment of a supplement of Pycnogenol
and L-arginine in Japanese patients with mild to moderate erectile dysfunction. Phytother Res
37. Sharma SC, Sharma S, Gulati OP. Pycnogenol inhibits the release of histamine from mast cells. Phytother Res
38. Cho KJ, Yun CH, Yoon DY, et al. Effect of bioflavonoids extracted from the bark of Pinus maritima
on proinflammatory cytokine interleukin-1 production in lipopolysaccharide-stimulated RAW 264.7. Toxicol Appl Pharmacol
39. Cho KJ, Yun CH, Packer L, Chung AS. Inhibition mechanisms of bioflavonoids extracted from the bark of Pinus maritima
on the expression of proinflammatory cytokines. Ann N Y Acad Sci
40. Mochizuki M, Hasegawa N. Therapeutic efficacy of Pycnogenol
in experimental inflammatory bowel diseases. Phytother Res
41. Grimm T, Skrabala R, Chovanová Z, et al. Single and multiple dose pharmacokinetics of maritime pine bark extract (Pycnogenol
) after oral administration to healthy volunteers. BMC Clin Pharmacol
42. Kohama T, Inoue M. Pycnogenol
alleviates pain associated with pregnancy. Phytother Res
43. Wang S, Tan D, Zhao Y, Guankai G, Gao X, Hu L. The effect of Pycnogenol
on the microcirculation, platelet function and ischemic mycardium in patients with coronary artery diseases. Eur Bull Drug Res
44. Pütter M, Grotemeyer KH, Würthwein G, et al. Inhibition of smoking-induced platelet aggregation by aspirin and Pycnogenol
. Thromb Res
45. Araghi-Niknam M, Hosseini S, Larson D, Rohdewald P, Watson RR. Pine bark extract reduces platelet aggregation. Integr Med
46. Sahebkar A. A systematic review and meta-analysis of the effects of pycnogenol on plasma lipids. J Cardiovasc Pharmacol Ther
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