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Maritime Pine

Scientific Name(s): Pinus pinaster Aiton., Pinus radiata
Common Name(s): Enzogenol, Maritime pine extract, Monterey pine extract, Pine bark extract, Pycnogenol

Clinical Overview

Use

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.

Dosing

Doses of pine bark extract have been studied in clinical trials, most commonly at 150 mg per day in 3 divided doses.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Pine bark extract is generally well tolerated, with occasional minor gastric discomfort, dizziness, nausea, and headache.

Toxicology

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.

Botany

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

History

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

Chemistry

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

Asthma

Animal data

Animal data regarding the use of pine bark extract in asthma are lacking.

Clinical data

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

CNS

Animal data

Animal data regarding the use of pine bark extract in diseases of the CNS are lacking.

Clinical data

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

Cardiovascular effects

Animal data

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

Clinical data

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

Cancer

Animal data

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

Clinical data

There are no clinical data regarding the use of pine bark extract in cancer.

Diabetes

Animal data

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

Clinical data

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.

Erectile dysfunction

Animal data

Animal data regarding the use of pine bark extract in erectile dysfunction are lacking.

Clinical data

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

Inflammation

Animal studies

Animal and in vitro studies suggest that pine bark extract exerts an anti-inflammatory effect possibly via proinflammatory mediators.37, 38, 39, 40

Clinical studies

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

Other uses

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

Dosing

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

Interactions

None well documented. Older studies suggest decreased platelet aggregation43, 44, 45; however, case reports of interactions are lacking.

Adverse Reactions

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

Toxicology

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

References

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. 2012;50(12):4316-4324.22982471
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. 2012;4:CD008294.22513958
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. 2003;103(1):67-72.12525796
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. 2004;41(8):825-832.15641632
11. Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R, Watson RR. Pycnogenolin the management of asthma. J Med Food. 2001;4(4):201-209.12639402
12. Pipingas A, Silberstein RB, Vitetta L, et al. Improved cognitive performance after dietary supplementation with a Pinus radiata bark extract formulation. Phytother Res. 2008;22(9):1168-1174.18683195
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. 2013;20(8):1135-1144.23384428
14. Trebatická J, Kopasová S, Hradecná Z, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry. 2006;15(6):329-335.16699814
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. 2011;19:216-227.21827936
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. 2010;55(6):1373-1380.20421515
17. Klimas J, Kmecova J, Jankyova S, et al. Pycnogenol improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats. Phytother Res. 2010;24(7):969-974.19957251
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. 2010;170(17):1541-1547.20876405
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. 2012;33(13):1589-1597.22240497
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. 2006;40(1):85-94.16298763
21. Nishioka K, Hidaka T, Nakamura S, et al. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res. 2007;30(9):775-780.18037769
22. Huynh HT, Teel RW. Selective induction of apoptosis in human mammary cancer cells (MCF-7) by Pycnogenol. Anticancer Res. 2000;20(4):2417-2430.10953304
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. 2005;29(6):685-692.15863210
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. 2002;9(5):414-418.12222661
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. 2006;20(8):676-679.
26. Sime S, Reeve VE. Protection from inflammation, immunosuppression and carcinogenesis induced by UV radiation in mice by topical Pycnogenol. Photochem Photobiol. 2004;79(2):193-198.15068032
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. 2010;24(10):1549-1553.20878709
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. 2010;58(11):7088-7095.20465310
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. 2012;26(3):403-411.21796705
30. Hasegawa N. Inhibition of lipogenesis by Pycnogenol. Phytother Res. 2000;14(6):472-473.10960907
31. Lee HH, Kim KJ, Lee OH, Lee BY. Effect of Pycnogenol on glucose transport in mature 3T3-L1 adipocytes. Phytother Res. 2010;24(8):1242-1249.20658573
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. 2004;18(6):345-352.15674846
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. 2014;66(6):875-885.24611864
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. 2003;23(9):1189-1198.
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. 2012;26(2):204-207.21618639
37. Sharma SC, Sharma S, Gulati OP. Pycnogenol inhibits the release of histamine from mast cells. Phytother Res. 2003;17(1):66-69.12557250
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. 2000;168(1):64-71.11000101
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. 2001;928:141-156.11795505
40. Mochizuki M, Hasegawa N. Therapeutic efficacy of Pycnogenol in experimental inflammatory bowel diseases. Phytother Res. 2004;18(12):1027-1028.15742344
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. 2006;6:4.16887024
42. Kohama T, Inoue M. Pycnogenol alleviates pain associated with pregnancy. Phytother Res. 2006;20(3):232-234.16521117
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. 1999;7:19-25.
44. Pütter M, Grotemeyer KH, Würthwein G, et al. Inhibition of smoking-induced platelet aggregation by aspirin and Pycnogenol. Thromb Res. 1999;95(4):155-161.10498385
45. Araghi-Niknam M, Hosseini S, Larson D, Rohdewald P, Watson RR. Pine bark extract reduces platelet aggregation. Integr Med. 2000;2(2):73-77.10882879
46. Sahebkar A. A systematic review and meta-analysis of the effects of pycnogenol on plasma lipids. J Cardiovasc Pharmacol Ther. 2014;19(3):244-255.24346156

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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