Scientific Name(s): Pinus pinaster Aiton. Family: Pinaceae (Pine)
Common Name(s): Maritime 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 chronic venous insufficiency, cardiovascular conditions, and erectile dysfunction. However, many clinical studies have been limited in size, with nonrandomized or open-label designs conducted by a limited pool of researchers.
Doses of pine bark extract have been studied in clinical trials, most commonly at 150 mg of Pycnogenol per day.
Contraindications have not been identified.
Information regarding safety and efficacy during pregnancy and lactation is lacking.
None well documented.
Pine bark extract is generally well tolerated, with minor gastric discomfort, dizziness, nausea, and headache occasionally noted. Clinical studies using Pycnogenol report no clinically important adverse events.
Pine bark extract is generally recognized as safe (GRAS), based on data from clinical trials. Limited toxicological data are available.
P. pinaster Aiton (previously termed P. maritima Mill.) is a medium-sized pine growing up to 30 m tall with bright red-brown, deeply fissured bark. It has stout needles occurring in pairs, and the plant produces oval cones 10 to 20 cm long. The 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. Pycnogenol is a term used to describe a class of flavonoids and is derived from the Greek puknos (condensed) and genos (class, family). The name Pycnogenol is a trademark of the British company Horphag Research, Ltd. for a complex proprietary mixture of water-soluble proanthocyanidins derived from the bark of the European coastal pine, P. pinaster , which grows along the coast of southwest France in Gascogne.
Pine bark extract is available without a prescription in the United States in health food stores and pharmacies. Product literature indicates that the dietary supplement is a free radical scavenger, and claims for its effects include improving circulation, reducing inflammation, and protecting collagen from natural degradation. 2 , 3
Pycnogenol 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%). Using a patented process, 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, Pycnogenol -related compounds are designated procyanidiol oligomers (PCOs). The oligomers range from monomers to dodecamers. The phenolic acids are derivatives of benzoic and cinnamic acids. Tablets and capsules must contain a minimum of 20 mg of Pycnogenol for the right to use the Pycnogenol trademark on the label or as a product name. Confusion previously arose when grape seed extract was marketed as containing Pycnogenol . Maritime pine extract is monographed in the United States Pharmacopeia . 2 , 3 , 4 , 5
Uses and Pharmacology
Antioxidant properties of Pycnogenol have been well described in laboratory studies and are considered to be responsible for the majority of clinical effects of the extract. 2 , 3 However, clinical studies evaluating changes in antioxidant status after Pycnogenol administration in humans have produced equivocal results. 6 , 7 , 8 Many published clinical studies have been limited in size, with nonrandomized or open-label designs conducted by a small pool of researchers. 2 , 3Cardiovascular effects
Studies in spontaneously hypertensive rats suggest a protective effect on microvasculature by Pycnogenol , thought to be due to antioxidant effects. Small decreases in systolic blood pressure were also observed. 9 , 10 Cardiomyopathy in diabetic rats was reduced by Pycnogenol , also considered to be due to antioxidant activity, but theoretically also due to improved cardiac energy metabolism via observed lowered plasma glucose. 11 Inhibition of angiotensin-converting enzyme (ACE) in vitro by Pycnogenol was linked to a hypertensive effect seen in rats. 12Clinical data
Chronic venous insufficiency
Reviews of clinical trials evaluating pine bark extract in chronic venous insufficiency (CVI) have been published. 2 , 3 Positive effects, including reductions in edema, pain, capillary leakage and perivascular inflammation, and improved venous ulcer healing rates, have been demonstrated in several studies. 13 , 14 , 15 , 16 , 17 Head-to-head studies of Pycnogenol versus comparator must be interpreted carefully, because in at least 1 study the dose of the comparator was too low to be effective. 2 , 16 In another clinical study evaluating the efficacy of Pycnogenol versus stockings in CVI, 150 mg of Pycnogenol daily provided an additive positive effect on ambulatory venous pressure and clinical symptom scores over stockings alone. 18Heart failure
A 12-week, single-blind study evaluated the efficacy of Pycnogenol in combination with coenzyme Q 10 as adjunctive therapy in cardiac failure. Patients receiving the combination adjunctive therapy improved New York Heart Association class through decreased systolic and diastolic blood pressure, heart and respiratory rate, and improved heart ejection fraction and walking distances. 19Hypertension
A 16-week study in a small cohort of mildly hypertensive patients found a statistically insignificant reduction of diastolic blood pressure with 200 mg/day of Pycnogenol . 20 Another small pilot study (N = 55) found improvements in systolic and diastolic renal cortical flow velocity with Pycnogenol as an adjunct to ACE inhibitors in hypertensive patients with decreased renal function. Improved renal function was also observed; however, the study did not use randomization or blinding methodology. 21 A small, nonrandomized clinical study evaluated the effect of 150 mg of Pycnogenol daily in metabolic syndrome as an adjunct to ramipril over 6 months. Decreases were observed in blood pressure, serum creatinine, urinary albumin, and fasting blood sugar. 22Platelet function
The effect of Pycnogenol on the platelet function of smoking and nonsmoking patients with coronary artery disease was evaluated in 3 studies, 23 , 24 , 25 with Pycnogenol decreasing platelet aggregation ex vivo in all 3 studies. In the nonsmoker study, platelet activating factor (PAF)–stimulated aggregation was not affected, eliminating a role for PAF in the mechanism. 26 A 16-week study in a small cohort of mildly hypertensive patients found a statistically insignificant reduction of diastolic blood pressure and a statistically significant drop in serum thromboxane with 200 mg/day of Pycnogenol . 20Erectile dysfunction
Research reveals no animal data regarding the use of pine bark extract in erectile dysfunction.Clinical data
Limited clinical trials have evaluated the efficacy of pine bark extract in combination with L-arginine in mild/moderate erectile dysfunction. Indices of erectile function were improved with 60 to 80 mg of pine bark extract and 700 mg of L-arginine daily. Measurements of salivary and plasma testosterone levels showed slight increases. 27 , 28 , 29Diabetes
In vitro studies suggest pine bark extract exhibits a number of relevant effects, including inhibition of lipid accumulation in adipocytes, 30 , 31 stimulation of lipolysis, 32 , 33 and increased glucose uptake. 34Animal data
In a diabetic rat model, antioxidant effects of Pycnogenol in combination with beta-carotene and alpha-lipoic acid were studied. Each antioxidant appeared to act by a different route, and no combination effect was noted. 35 Antioxidant effects have also been observed in other experiments in diabetic rats. 2 , 36Clinical data
A small, nonrandomized clinical study evaluated the effect of 150 mg of Pycnogenol daily in metabolic syndrome as an adjunct to ramipril over 6 months. Decreases were observed in blood pressure, serum creatinine, urinary albumin, and fasting blood sugar. 22 Another trial found lowered plasma glucose in type 2 diabetic patients with Pycnogenol administration. 37Inflammation
Pycnogenol appears capable of inhibiting inflammatory mediators. Histamine release from rat mast cells was induced by either a calcium ionophore (A-23187) or a compound 48/80, and Pycnogenol reversed the action of these 2 secretogogues. 38 Pycnogenol reduced the production of the proinflammatory cytokine interleukin-1 in 2 macrophage cell lines, blocked activation of nuclear factor kappa beta (NF-kappa-B) and activator protein (AP)–1, and abolished lipopolysaccharide-stimulated (LPS)–induced IkB destruction. 39 , 40Animal studies
Dietary Pycnogenol decreased edema in mouse ears treated with croton oil. Similarly, rat hind paw edema due to compound 48/80 was decreased. Topical administration of Pycnogenol blocked ultraviolet damage to capillaries 41 and had a protective effect in a rat model of inflammatory bowel disease. 42Clinical studies
Similarly, human volunteers administered Pycnogenol demonstrated fewer incidents of erythema and NF-kappa-B expression in keratinocytes than did controls. 43 Inhibition of NF-kappa-B activation and matrix metalloproteinase (MMP)-9 secretion was found in human plasma after 5 days of oral Pycnogenol administration. 44 In a small clinical study, allergic rhinitis symptoms were reduced with administration of 100 mg/day of Pycnogenol for at least 5 weeks. 45 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 Pycnogenol 100 mg daily. 2Other effects
Pycnogenol 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 a clinical study and in rats. 2 , 46 , 47 , 48 , 49 , 50Diabetic retinopathy
A small clinical trial (N = 84) evaluated the effect of oral and topical Pycnogenol on pain and bleeding, and found improvements with 300 mg daily for 4 days and then 150 mg daily for a further 3 days. The cream was used at 0.5%. 53Tinnitus
A small pilot study (N = 50) found increased systolic and diastolic cochlear artery flow with administration of 100 and 150 mg of Pycnogenol daily for 2 weeks. 54Other
Pycnogenol has been tested in clinical trials of varying quality for other indications, including attention deficit hyperactivity disorder, hyperpigmentation in melasma, motion sickness, and traveler's thrombosis, as well as for the control of inflammation in lupus patients, as an adjunct for childhood asthma, and in a chewing gum for gingival bleeding and plaque. 55 , 56 , 57 , 58 , 59 , 60 , 61
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. 62 Doses of 60 to 300 mg daily of Pycnogenol have been studied in clinical trials, most commonly at 150 mg/day. 2 , 3
Information regarding safety and efficacy during pregnancy and lactation is lacking. Pycnogenol has been studied for pain in the third trimester of pregnancy at a dose of 30 mg/day. 63
None well documented, although a risk of interaction with antiplatelet therapy is possible. 24
Pine bark extract is generally well tolerated, with minor gastric discomfort, dizziness, nausea, and headache occasionally noted. Clinical studies using Pycnogenol report no clinically important adverse events at doses of 150 mg of Pycnogenol daily. 2 , 16 , 21 , 54
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