TABLE 1.
Summary of RDP human clinical studies on Pycnogenol® sorted by applications and by year of publication.
| References | Title | Study details | Main findings |
| Cardiovascular health and endothelial health | |||
| Trebaticky et al. (29) | Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction | 53 male subjects, 120 mg Pycnogenol® per day or placebo for 3 months | Total and LDL-cholesterol levels were reduced in subjects taking Pycnogenol®. In diabetes type 2 patients, plasma glucose levels were decreased after Pycnogenol® intake. Erectile function was improved after Pycnogenol® supplementation. Placebo showed no significant effects. |
| Enseleit et al. (9) | Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study | 23 subjects, 200 mg Pycnogenol® per day or placebo for 8 weeks | FMD was significantly improved by 32% in the Pycnogenol® group compared to baseline and by 49% compared to placebo. Lipid peroxidation was decreased by 7% with Pycnogenol®. |
| Zibadi et al. (22) | Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation | 48 subjects, 100 mg Pycnogenol® per day or placebo for 3 months | Serum endothelin 1-levels were lowered by 20% after Pycnogenol® intake compared to placebo. LDL cholesterol was reduced by 12% with Pycnogenol® (vs. +3% with placebo). Pycnogenol® was shown to lower glycated hemoglobin by 10% in the Pycnogenol® group, a significant effect compared to placebo. Fasting plasma glucose was lowered by 18.4% in type 2 diabetes subjects, taking Pycnogenol® compared to placebo-controlled subjects. |
| Nishioka et al. (21) | Pycnogenol®, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans | 16 subjects, 180 mg Pycnogenol® per day or placebo for 2 weeks | Forearm blood flow in response to acetylcholine significantly increased by up to 41% after Pycnogenol® intake, while placebo had no effect. Forearm blood flow in response to an endothelium independent vasodilator was not influenced by Pycnogenol® intake showing the effect of Pycnogenol® is mediated by the endothelium. |
| Yang et al. (12) | A randomized, double-blind, placebo-controlled trial on the effect of Pycnogenol® on the climacteric syndrome in peri-menopausal women | 155 female subjects, 200 mg Pycnogenol® per day or placebo for 6 months | LDL-cholesterol was significantly lowered, and HDL-cholesterol was significantly increased after Pycnogenol® intake compared to placebo. Systolic and diastolic blood pressure were significantly reduced after Pycnogenol® supplementation, compared to placebo. All climacteric symptoms improved with Pycnogenol® compared to placebo. |
| Liu et al. (20) | Pycnogenol®, French maritime pine bark extract, improves endothelial function of hypertensive patients | 58 subjects, 100 mg Pycnogenol® per day or placebo for 3 months | Endothelin 1-levels were significantly lowered by 16% after Pycnogenol® intake compared to placebo. 6-keto prostaglandin F1a-levels were increased after Pycnogenol®. 57% of the Pycnogenol® subjects and 13% of the placebo subjects could cut their individual anti-hypertensive drug medication by half. |
| Liu et al. (30) | Antidiabetic effect of Pycnogenol® French maritime pine bark extract in patients with diabetes type II | 77 subjects, 100 mg Pycnogenol® per day or placebo for 12 weeks | Plasma glucose levels of diabetes type 2 patients decreased significantly with Pycnogenol®, compared to placebo. Glycosylated hemoglobin and vasoconstrictive endothelin-1 in the blood were reduced and vaso-relaxant 6-keto prostaglandin f1 alpha was increased with Pycnogenol® but not in placebo. |
| D̆uračková et al. (11) | Lipid metabolism and erectile function improvement by Pycnogenol®, extract from the bark of Pinus pinaster in patients suffering from erectile dysfunction-a pilot study | 21 male subjects, 120 mg Pycnogenol® per day or placebo for 3 months | Total and LDL-cholesterol were significantly reduced while HDL-cholesterol was slightly increased after Pycnogenol® intake. |
| Hosseini et al. (28) | A randomized, double-blind, placebo-controlled, prospective, 16-week crossover study to determine the role of Pycnogenol in modifying blood pressure in mildly hypertensive patients. | 11 subjects, 200 mg Pycnogenol® per day or placebo for 8 weeks | Systolic blood pressure was significantly lowered after Pycnogenol® supplementation by 5% compared to placebo. In subjects with the highest systolic blood pressure, the reduction was greater (−11% compared to baseline). |
| Wang et al. (31) | The effect of Pycnogenol® on the microcirculation, platelet function and ischemic myocardium in patients with coronary artery diseases | 60 subjects, 150 mg Pycnogenol® per day or placebo for 4 weeks | The percentage of patients with improvement of the microcirculation at the fingertips was higher and platelet aggregation of the blood was reduced after Pycnogenol® intake compared to placebo. |
| Chronic venous insufficiency | |||
| Arcangeli (32) | Pycnogenol® in chronic venous insufficiency | 40 subjects, 300 mg Pycnogenol® per day or placebo for 2 months | Pycnogenol® supplementation reduced symptoms of CVI. |
| Petrassi et al. (33) | Pycnogenol® in chronic venous insufficiency | 20 subjects, 300 mg Pycnogenol® per day or placebo for 2 months | Leg heaviness, swelling and evening edema were relieved in CVI patients after Pycnogenol® intake, compared to placebo. Venous pressure was significantly decreased with Pycnogenol® not with placebo. |
| Cognitive function | |||
| Weyns et al. (37) | Clinical investigation of French maritime pine bark extract on attention-deficit hyperactivity disorder as compared to methylphenidate and placebo: Part 1: efficacy in a randomized trial | 88 children, 20 or 40 mg Pycnogenol® /day if < or ≥ 30 kg or 20 or 30 mg MPH /day if < or ≥ 30 kg or placebo for 10 weeks | Hyperactivity and impulsivity were significantly improved with both Pycnogenol® (by 34%) and MPH (by 36%) and deteriorated with placebo, according to teacher’s rating. Inattention (according to teachers) was improved with Pycnogenol® and significantly improved with MPH. The rate of adverse events was statistically significant with MPH (39%) and not with Pycnogenol® (8%) and placebo (9%). |
| Weyns et al. (38) | Clinical investigation of French maritime pine bark extract on attention-deficit hyperactivity disorder as compared to methylphenidate and placebo: Part 2: oxidative stress and immunological modulation | 88 children, 20 or 40 mg Pycnogenol® /day if < or ≥ 30 kg or 20 or 30 mg MPH /day if < or ≥ 30 kg or placebo for 10 weeks | MPH intake led to loss of appetite and a significant weight loss. After Pycnogenol® supplementation, children had physiologically appropriate weight gain. The orexigenic peptide, NPY was significantly reduced after MPH and insignificantly increased after Pycnogenol® intake. |
| Donovan et al. (39) | A placebo-controlled, pseudo-randomized, crossover trial of botanical agents for gulf war illness: curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French maritime pine bark (Pinus pinaster) | 20 subjects, 400 mg Pycnogenol® per day or placebo for 4 weeks | The symptoms of gulf war illness after intake of Pycnogenol® were significantly reduced compared to placebo. |
| Ryan et al. (13) | An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population | 101 subjects, 150 mg Pycnogenol® per day or placebo for 3 months | Spatial working memory and numeric quality of working memory were significantly improved with Pycnogenol® compared with placebo. Lipid peroxidation products (plasma F2 isoprostane) were reduced after Pycnogenol® intake compared to placebo. |
| Dvorakova et al. (36) | Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (Pycnogenol®) | 61 children, 1 mg Pycnogenol®/kg/day or placebo for 4 weeks | The levels of catecholamines (like adrenaline, noradrenaline and dopamine) in the urine were reduced after Pycnogenol® supplementation. |
| Chovanova et al. (14) | Effect of polyphenolic extract, Pycnogenol®, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder | 61 children, 1 mg Pycnogenol®/kg/day or placebo for 4 weeks | The increased levels of 8-oxoG, as a measure of oxidized DNA in ADHD children were reduced after Pycnogenol® intake compared to baseline and placebo. |
| Dvorakova et al. (35) | The effect of polyphenolic extract from pine bark, Pycnogenol® on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD) | 61 children, 1 mg Pycnogenol®/kg/day or placebo for 4 weeks | The levels of oxidized glutathione (GSSG) were significantly decreased by 22% after Pycnogenol® intake, while reduced glutathione (GSH) was significantly increased by 26.8%. Placebo had no significant effect on GSSH and GSH. |
| Trebaticka et al. (34) | Treatment of ADHD with French maritime pine bark extract, Pycnogenol® | 61 children, 1 mg Pycnogenol®/kg/day or placebo for 4 weeks | As rated by parents and teachers, hyperactivity was reduced and attention was increased after Pycnogenol® intake compared to placebo. |
| Joint health | |||
| Belcaro et al. (42) | Treatment of osteoarthritis with Pycnogenol®. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects | 156 subjects, 100 mg Pycnogenol® per day or placebo for 3 months | The joint discomfort scores were reduced after Pycnogenol® intake. Walking distance on a treadmill increased significantly more with Pycnogenol® supplementation compared to placebo. |
| Cisar et al. (41) | Effect of pine bark extract (Pycnogenol®) on symptoms of knee osteoarthritis | 100 subjects, 150 mg Pycnogenol® per day or placebo for 3 months | Joint discomfort, stiffness and analgesics consumption were lowered, and physical function increased after Pycnogenol® intake compared to placebo. |
| Farid et al. (40) | Pycnogenol supplementation reduces pain and stiffness and improves physical function in adults with knee osteoarthritis | 37 subjects, 150 mg Pycnogenol® per day or placebo for 3 months | Reduced joint discomfort, stiffness and need for NSAIDs with Pycnogenol® supplementation compared to placebo. |
| Skin health | |||
| Cai et al. (44) | An oral French maritime pine bark extract improves hair density in menopausal women: a randomized, placebo-controlled, double-blind intervention study | 76 female subjects, 150 mg Pycnogenol® per day or placebo for 6 months | Hair density of menopausal women was significantly increased after Pycnogenol® supplementation compared to baseline. Scalp water loss was reduced with Pycnogenol® intake compared to placebo. Resting flux of the scalp skin was improved with Pycnogenol® compared to baseline. |
| Zhao et al. (43) | Oral Pycnogenol® intake benefits the skin in urban Chinese outdoor workers: a randomized, placebo-controlled, double-blind, and crossover intervention study | 78 subjects, 100 mg Pycnogenol® per day or placebo for 3 months | Skin water loss was decreased while skin elasticity and skin tone regularity increased after Pycnogenol® supplementation, compared to baseline and placebo. |
| Eye health | |||
| Steigerwalt et al. (46) | Pycnogenol® improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy | 46 subjects, 150 mg Pycnogenol® per day or placebo for 3 months | Retinal edema score and retinal thickness were reduced, and visual acuity was significantly improved after Pycnogenol® intake compared to baseline and placebo. |
| Spadea and Balestrazzi (45) | Treatment of vascular retinopathies with Pycnogenol® | 20 subjects, 150 mg Pycnogenol® per day or placebo for 2 months | Vascular permeability of the eyes and retinal vascularization decreased, and visual acuity increased after Pycnogenol® supplementation, compared to placebo. |
| Women’s health | |||
| Kohama and Negami (47) | Effect of low-dose French maritime pine bark extract on climacteric syndrome in 170 perimenopausal women | 170 female subjects, 60 mg Pycnogenol® per day or placebo for 3 months | Total menopause symptom score was significantly reduced with Pycnogenol® compared to placebo. Vasomotor symptoms, sleep problems and fatigue were improved with Pycnogenol®. Hormone levels were not changed after Pycnogenol® intake, compared to baseline or placebo. |
| Suzuki et al. (48) | French Maritime Pine Bark Extract significantly lowers requirement of analgesic medication in dysmenorrhea–a multi-center, randomized, double-blind, placebo-controlled study | 116 female subjects, 60 mg Pycnogenol® per day or placebo for 2 menstrual cycles | The need for analgesic medication and the number of days on which analgesics were required was significantly reduced with Pycnogenol® supplementation compared to placebo. |
| Yang et al. (12) | A randomized, double-blind, placebo-controlled trial on the effect of Pycnogenol® on the climacteric syndrome in peri-menopausal women | 155 female subjects, 200 mg Pycnogenol® per day or placebo for 6 months | Menopause symptoms according to the Women’s health questionnaire were improved after Pycnogenol® intake, significantly more than with placebo. The cholesterol profiles were significantly improved after Pycnogenol® intake compared to placebo. Systolic and diastolic blood pressure were significantly reduced after Pycnogenol® intake. |
| Respiratory health and allergies | |||
| Wilson et al. (51) | A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of Pycnogenol® for improving allergic rhinitis symptoms | 39 subjects, 100 mg Pycnogenol® per day or placebo for 5 to 8 weeks | Allergic rhinitis symptoms from pollen allergy, such as nasal and eye symptoms were reduced in subjects, taking Pycnogenol® at least 5 weeks before pollen season. The number of subjects, requiring rescue antihistamines was reduced with Pycnogenol®. |
| Lau et al. (50) | Pycnogenol® as an adjunct in the management of childhood asthma | 60 children, 2 mg Pycnogenol® per kg per day or placebo for 3 months | Asthma symptoms and FEV1 improved after Pycnogenol® intake. Leukotriene levels were significantly reduced in the Pycnogenol® group. The need for albuterol rescue inhalers was reduced with Pycnogenol®. |
| Hosseini et al. (49) | Pycnogenol® in the management of asthma | 22 subjects, 2 mg Pycnogenol® per kg per day or placebo for 4 weeks | The FEV1 was increased after Pycnogenol® intake, compared to baseline and placebo. Subjective asthma symptom rating and the level of plasma leukotrienes reduced after Pycnogenol® intake compared to placebo and baseline. |
| Oral health | |||
| Watanabe et al. (52) | Effects of French Pine Bark Extract Chewing Gum on Oral Malodor and Salivary Bacteria | 21 subjects, 30 mg Pycnogenol® per day in a gum or placebo gum for 4 weeks | The levels of volatile sulfur compounds in the mouth, the tongue-coating score and hydrogen sulfide-producing bacteria in saliva were reduced with a Pycnogenol® gum compared to a placebo gum. |
| Sports | |||
| Ackermann et al. (55) | The effect of an acute antioxidant supplementation compared with placebo on performance and hormonal response during a high-volume resistance training session | 15 subjects, 2 ml per kg body weight of a sports drink, containing 4.8 mg Pycnogenol® per 2 ml or placebo drink, single dose, 4 h before training | Muscle contractile performance and accumulated power output during lower limb hypertrophic resistance training was improved after Pycnogenol® supplementation compared to placebo. |
| Bentley et al. (54) | Acute antioxidant supplementation improves endurance performance in trained athletes | 9 subjects, 360 mg Pycnogenol® in a drink or placebo drink, single dose 4 h before training | Cycling time before exhaustion was increased by 80 s after Pycnogenol® drink consumption, compared to placebo subjects. |
| Mach et al. (56) | The effect of antioxidant supplementation on fatigue during exercise: potential role for NAD+(H) | 13 subjects, 360 mg Pycnogenol® in a drink or placebo drink, single dose, 3 h before training | The physical work capacity until fatigue during cycling training was increased with Pycnogenol® compared to placebo and baseline. Serum NAD+ levels were increased significantly with Pycnogenol® compared to placebo. |
| Pavlovic (53) | Improved endurance by use of antioxidants | 24 subjects, 200 mg Pycnogenol® per day or placebo for 30 days | Performance time on a treadmill was increased with Pycnogenol® supplementation compared to placebo. |
FMD, Flow-mediated dilation; LDL, Low density lipoprotein; HDL, high density lipoprotein; CVI, chronic venous insufficiency; MPH, methylphenidate hydrochloride; NPY, neuropeptide Y; 8-oxo-G, 8-oxo-7,8-dihydroguanine; ADHD, attention deficit and hyperactivity disorder; NSAIDs, nonsteroidal anti-inflammatory drugs; FEV1, forced expiration volume in 1 s; NAD+, nicotinamide adenine dinucleotide.