Pycnogenol® French maritime pine bark extract in randomized, double-blind, placebo-controlled human clinical studies.

Pycnogenol® French maritime pine bark extract is a well-known and thoroughly studied patented extract from the bark of Pinus pinaster Ait. ssp. Atlantica. In 39 randomized double-blind, placebo-controlled (RDP) human clinical trials including 2,009 subjects, Pycnogenol® French maritime pine bark extract supplementation for two weeks to six months has been shown to beneficially affect cardiovascular health, chronic venous insufficiency, cognition, joint health, skin health, eye health, women's health, respiratory health and allergies, oral health and sports performance. The mechanisms of action that can explain the respective effects on different conditions in the human body are discussed as well. As investigated in several in vitro, in vivo and in clinical studies, Pycnogenol® French maritime pine bark extract showed antioxidative effects, anti-inflammatory abilities, beneficial effects on endothelial function and reinforcing effects on the extracellular matrix. The present review aims to give a comprehensive overview of currently available "gold standard" RDP trials of Pycnogenol®'s benefits across various health domains compared to placebo. In addition, some of the processes on which the presented effects of Pycnogenol® French maritime pine bark extract are based will be elucidated and discussed. This broad overview of RDP studies on Pycnogenol® in different health domains can be used as a basis for further research on applications and mechanisms of this unique French maritime pine bark extract.

Restless legs syndrome: prevention with Pycnogenol® and improvement of the venoarteriolar response.

BACKGROUND: The aim of this registry study was to evaluate the preventive efficacy of Pycnogenol® (French maritime pine bark, standardized extract), an anti-inflammatory and antioxidant supplement, previously used for muscular pain and cramps, in otherwise healthy subjects with restless legs syndrome (RLS). METHODS: Two management groups were formed: one using the standard management (SM) and one using SM and Pycnogenol® 150 mg/day for 4 weeks. RESULTS: Forty-five subjects were included in the study, 21 took Pycnogenol® and 24 were in the SM group. After 4 weeks no side effects or tolerability problems were observed. Compliance was optimal. The two groups were comparable at baseline. Limb sensations were assessed with a Visual Analogue Scale Line (0 to 4). There was a statistically non-significant improvement with SM in all subjects. Improvement with Pycnogenol® supplementation was significant (P<0.05) for all assessed parameters with important clinical meanings as 19 out of 21 supplemented subjects reported a clear benefit from supplementation. Resting flux - slightly elevated at inclusion - was normalized in the supplemented group (P<0.05) as seen by a decrease in flux. The venoarteriolar response - affected at inclusion in all subjects with RLS - was improved with the supplement, indicating a better axon-axon reflex response and a lower level of subclinical neural alteration. The need for pain managements was significantly reduced (P<0.05) with supplementation after 4 weeks, as only 4/21 supplemented subjects vs. 16/24 in the SM-only group had to use analgesics. Thermography of the leg did not reveal any significant asymmetry of perfusion. Oxidative stress as plasma free radicals (PFR) was significantly improved (reduced) (P<0.05) in subjects using Pycnogenol®. Likewise, minimal edema, measured with the edema tester, was significantly decreased with Pycnogenol®. CONCLUSIONS: Pycnogenol® prevents or relieves symptoms associated with restless leg syndrome and positively affects the venoarteriolar response. Future studies in this condition, including more complex subjects may indicate the role of Pycnogenol® in this common and still obscure syndrome and in subclinical muscular and neurological alterations.

Projected supportive effects of PycnogenolⓇ in patients suffering from multi-dimensional health impairments after a SARS-CoV2 infection.

Corona virus disease 2019 (COVID-19) is triggered by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV2) and has rapidly developed into a worldwide pandemic. Unlike other SARS viruses, SARS-CoV2 does not solely impact the respiratory system, but additionally leads to inflammation of endothelial cells, microvascular injuries and coagulopathies, thereby affecting multiple organs. Recent reports of patients who were infected with SARS-CoV2 suggest persistent health problems even months after the initial infection. The French maritime pine bark extract PycnogenolⓇ has demonstrated anti-inflammatory, vascular and endothelium-protective effects in over 90 human clinical studies. It is proposed that PycnogenolⓇ may be beneficial in supporting recovery and mitigating symptoms and long-term consequences resulting from a SARS-CoV2 infection in COVID-19 patients.

Pleiotropic Effects of French Maritime Pine Bark Extract to Promote Healthy Aging.

Extension of the healthy life span is of primary importance for the aging society. Among exercise, healthy nutrition, and mental training, food supplements are widely used as preventive measures to postpone the diverse symptoms of aging. The extract from the bark of the French maritime pine, Pycnogenol, rich on flavonoids, has anti-inflammatory and antioxidative property, proven in in vivo studies. The extract reduces oxidative stress and improves endothelial health. Its antithrombotic properties are based on inhibition of platelet aggregation. In double-blind, placebo-controlled clinical studies, Pycnogenol shows diverse positive effects. With respect to cardiovascular symptoms, the extract has an antihypertensive effect, slows down the progression of atherosclerosis, and prevents venous thrombosis. As reported in studies in China and the United States, type 2 diabetes and diabetic retinopathy is improved with Pycnogenol. The extract restores mobility of seniors in case of patients suffering from osteoarthritis, Pycnogenol reduces pain and stiffness and use of analgesics. Furthermore, cognitive functions of elderly people, especially spatial memory, are significantly ameliorated. Climacteric symptoms are significantly alleviated by the pine bark extract. Urinary symptoms of benign prostatic hyperplasia are reduced by Pycnogenol. In combination with L-arginine, Pycnogenol restores erectile function in men with erectile dysfunction. The sum of these positive effects on relevant symptoms of aging suggests using Pycnogenol for a more extended period of healthy aging.

Robuvit®: improvement of fatigue in medical convalescence.

BACKGROUND: The aim of this registry study was the evaluation of symptoms of fatigue following supplementation with an oak wood extract (Robuvit®) after disappearance of acute symptoms. Robuvit®, with established antioxidant-antifatigue activity, has been successfully used in hepatic failure and in chronic fatigue syndrome: these conditions are characterized by weakness and fatigue and are broadly comparable to convalescence that is associated to increased oxidative stress. METHODS: The registry study lasted 3 weeks. After a period (7-10 days) of flu, during the post-disease period (3 days without disease) subjects were included into the study. One group of subjects was supplemented with Robuvit® (300 mg/day) in addition to a standard management (SM) plan, another group of patients was treated with the standard management only. RESULTS: The SM and the supplement group were comparable in all convalescence parameters at inclusion. Weakness and heart rate were significantly reduced with Robuvit® in comparison with the controls (P<0.05) at 10 days and at 3 weeks; Attention and sleep patterns improved significantly at 3 weeks with Robuvit® (P<0.05) in comparison to controls. Recovery after efforts was normalized at 10 days in the supplement group, significantly better versus controls (P<0.05). O2 saturation increased significantly with Robuvit® at 10 days in comparison to controls (P<0.05). The alterations in working/concentration capacity were better improved with the supplement (P<0.05). Oxidative stress was significantly decreased (P<0.05) in comparison to controls. The improvement of health according to the Karrnofsky Scale was significantly more pronounced in the Robuvit® group (P<0.05). The supplement was well tolerated. CONCLUSIONS: The causative relations between Robuvit® supplementation, oxidative stress, vigor and fatigue in convalescence need more specific evaluations in a larger number of subjects. This preliminary study may indicate a possible supplementation in convalescence.

Review on Sustained Relief of Osteoarthritis Symptoms with a Proprietary Extract from Pine Bark, Pycnogenol.

This review summarizes the effects of the standardized proprietary bark extract of the French maritime pine (Pycnogenol®) in mild osteoarthritis (OA), stage 1 and 2. The extract exerts antioxidative, anti-inflammatory, and chondroprotective effects in vitro and in vivo. Its phenolic acids as well as catechin and taxifolin are quickly absorbed. Active metabolites, produced by gut microbiota in the intestinal tract from oligomeric procyanidins, appear in blood 6 h following ingestion and remain for at least 14 h, providing a long-lasting flow of anti-inflammatory substances for relief of OA symptoms. These constituents of Pycnogenol could be detected in serum, blood cells, and synovial fluid of OA patients. The resulting inhibition of cartilage-destructing proteases and pain-producing cyclo-oxygenases provides the basis for relief from pain, improvement of stiffness, enhanced mobility, and well-being in three clinical studies with the pine bark extract as an adjunct supplement. Sparing the use of nonsteroidal anti-inflammatory drugs, supplementation with the pine bark extract reduced gastric complications and hospital admissions of OA patients. Because of its favorable safety profile and sustained anti-inflammatory action, Pycnogenol represents an option as an add-on supplement for OA patients.

Improvement of seminal quality and sexual function of men with oligoasthenoteratozoospermia syndrome following supplementation with L-arginine and Pycnogenol®.

We evaluated the effectiveness of antioxidant co-supplementation therapy using Larginine and Pycnogenol(®) in Japanese men with oligoasthenozoospermia and mild erectile dysfunction (ED). A total of forty-seven adult males with oligoasthenoteratozoospermia syndrome (OAT) were eligible for enrollment. The effectiveness of supplementation with a combination of L-arginine 690 mg and French maritime pine bark extract (Pycnogenol(®)) 60mg for OAT and ED was investigated. The sperm concentration was enhanced significantly after treatment 2 and 4 months (11.79 ± 9.86 to 21.22 ± 28.17 and 20.15 ± 23.99 × 106/ml). Significant improvements in the International Index of Erectile Function (IIEF) were observed in the total score of IIEF (57.69 ± 11.04 to 59.43 ± 12.57) and domain of Orgasmic Function (9.01 ± 1.92 to 9.34 ± 1.66) after 4 months of treatment. L-arginine acts to increase the production of nitric oxide and Pycnogenol(®) activates the endothelial nitric oxide synthase and it is a potent antioxidant and inhibitor of inducible nitric oxide synthase. This study suggests that the combination of Pycnogenol(®) and L-arginine (Edicare(®)) is helpful for infertile men to ameliorate simultaneously quality of sperms as well as erectile functions.

An Effect of Oak-Wood Extract (Robuvit®) on Energy State of Healthy Adults-A Pilot Study.

The purpose of our study was to examine the psychological benefits of the treatment with Robuvit® (Horphag Research Ltd.) - polyphenolic extract obtained from the wood of oak Quercus robur - on the healthy elderly individuals using energy subscale scores of the Activation - Deactivation Adjective Check List. Analysis was focused on the comparison of pre-post treatment effect of Robuvit on symptoms of fatigue. In the total group of volunteers, significant increase of average question scores was found in three of four subscales of feelings (energy, tiredness, and tension) after 4 weeks of Robuvit administration. Effects of extract were observed mainly after stratification of total group of volunteers according to the level of feeling at the pre-treatment questionnaire. Our results demonstrate positive effect of Robuvit on mental and energy level in healthy human without any unwanted side effects.

Effect of the French oak wood extract Robuvit on markers of oxidative stress and activity of antioxidant enzymes in healthy volunteers: a pilot study.

We examined in vitro antioxidant capacity of polyphenolic extract obtained from the wood of oak Quercus robur (QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found an in vitro antioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasma in vivo.

Pycnogenol treatment of acute hemorrhoidal episodes.

We investigated the efficacy of orally and topically applied Pycnogenol for the management of acute hemorrhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days' treatment and again seven days following treatment cessation. The decrease in scores was significantly more pronounced in the Pycnogenol-treated groups than in the control group given placebo (p < 0.05), showing the efficacy of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol in addition to oral Pycnogenol the improvement in symptoms set in significantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol eases the management of acute hemorrhoidal attacks and help avoid bleedings.

Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation.

Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease (CVD). We investigated the clinical effectiveness of Pycnogenol, a flavonoid-rich dietary supplement, in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes. Forty-eight individuals were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors. Subjects were randomly assigned to receive either Pycnogenol pill (125 mg daily) or matched placebo for 12 weeks. According to the values of blood pressure (BP) measured at 2-week intervals, the pretrial ACE inhibitor dosage was left unchanged, reduced by 50%, or brought back to the pretrial dosage until a stable BP was obtained. Fasting plasma glucose, low-density lipoprotein (LDL) cholesterol, glycosylated hemoglobin (HbA1c), serum endothelin-1, and urinary albumin were evaluated monthly. Pycnogenol treatment achieved BP control in 58.3% of subjects at the end of the 12 weeks with 50% reduction in individual pretrial dose of ACE-inhibitors (P <.05). Plasma endothelin-1 decreased by 3.9 pg/mL in Pycnogenol-treated group vs 0.5 pg/mL increase in control group (P < .001). Mean HbA1c dropped by 0.8% in Pycnogenol-treated group (P < .05), whereas it decreased by 0.1% in control group. Fasting plasma glucose declined by 23.7 mg/dL in Pycnogenol-treated group vs 5.7 mg/dL in control group (P < .0001). Low-density lipoprotein cholesterol improved significantly in Pycnogenol-treated group, declining by 12.7 mg/dL (P < .001). A significant decrease in urinary albumin level was observed at week 8 compared with the control group (P < .05). However, this reduction was not significant at 12th week. After 12 weeks of supplementation, Pycnogenol resulted in improved diabetes control, lowered CVD risk factors, and reduced antihypertensive medicine use vs controls.

Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis.

OBJECTIVE: The safe and efficacious use of Pycnogenol (French maritime pine bark extract) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis (OA). The aim of the study was to evaluate whether Pycnogenol reduces the symptoms of OA in a double-blind, placebo-controlled, randomly allocated trial with patients suffering from knee osteoarthritis stages I and II. METHODS: 100 patients were treated for 3 months either by 150 mg Pycnogenol per day at meals or by placebo. Patients had to report any change of use of previously prescribed antiinflammatory medication during the study period. Patients filled the Western Ontario and Mc Masters University (WOMAC) questionnaire for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain intensity. RESULTS: Following treatment with Pycnogenol patients reported an improvement of WOMAC index (p < 0.05), and a significant alleviation of pain by visual analogue scale (p < 0.04), the placebo had no effect. The use of analgesics diminished in the verum group but increased under the placebo. Treatment with Pycnogenol was well tolerated. CONCLUSION: Results show that Pycnogenol in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs.

In vitro inhibition of Helicobacter pylori growth and adherence to gastric mucosal cells by Pycnogenol.

The emergence of antibiotic resistant H. pylori strains has necessitated the identification of alternative additive therapies for the treatment of this infection. The study tested whether a specific pine bark extract (Pycnogenol is effective in inhibiting the growth and adherence of H. pylori in vitro. Inhibition of H. pylori growth by Pycnogenol was tested in liquid medium as well as in an in vitro model by using sessile bacteria attached to AGS cells. Adherence was determined by co-incubation of gastric cells with Pycnogenol and H. pylori in vitro. Pycnogenol inhibited H. pylori growth in suspension with an MIC(50) of 12.5 microg/mL. Growth of H. pylori in infected cells was reduced to 10% of the control value by 125 microg/mL Pycnogenol. Adherence of H. pylori to gastric cells was reduced by 70% after 3 h incubation with 125 microg/mL Pycnogenol. The results show a significant, yet limited inhibition of growth and adherence of H. pylori to gastric cells by Pycnogenol. In vivo studies have to demonstrate the clinical relevance of these findings.

Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (pycnogenol).

Our study tested the hypothesis that treatment with a potent polyphenol complex not only reduces hyperactivity of children, but also catecholamine excretion and oxidative stress. Urine catecholamine concentrations were measured in attention deficit hyperactivity disorder (ADHD) children and healthy controls. ADHD children received either placebo (PL) or Pycnogenol (Pyc), a bioflavonoid extract from the pine bark, for one month. The study was performed in a randomized, double-blind, PL controlled design. Concentrations of catecholamines were higher in urine of ADHD patients compared to those of healthy children. Moreover, noradrenaline (NA) concentrations positively correlated with degree of hyperactivity of ADHD children. In ADHD patients, adrenaline (A) and NA concentrations positively correlated with plasma levels of oxidized glutathione. The treatment of ADHD children with Pyc caused decrease of dopamine (D) and trend of A and NA decrase and increased GSH/GSSG ratio. In conclusion, the data provide further evidence for the overactivity of the noradrenergic system in ADHD and demonstrate that A release may be increased, as well. Treatment of ADHD children with Pyc normalized catecholamine concentrations, leading to less hyperactivity, and, consequently, to reduced oxidative stress.

Impact of Pycnogenol on cardiac extracellular matrix remodeling induced by L-NAME administration to old mice.

Cardiac remodeling is a determinant of the clinical progression of heart failure and now slowing or reversing remodeling is considered as a potential therapeutic target in heart failure. Pycnogenol has been reported to mediate a number of beneficial effects in the cardiovascular system but its effects on hemodynamic and functional cardiovascular changes following cardiac remodeling have not been elucidated. Therefore, we investigated the influence of Pycnogenol supplementation (30 mg/kg) on left ventricular function and myocardial extracellular matrix composition in old C57BL/6N mice following induction of cardiac remodeling by chronic nitric oxide synthase blockade by NG-nitro-L-arginine methyl ester (L-NAME) administration. L-NAME-treated mice demonstrated dilated cardiomyopathy at compensated state, associated with a significant increase of pro-matrix metalloproteinase (MMP)-9 gene expression and activity, a marked decrease in pro-collagen IIIalpha1 gene expression, and a subsequent reduction in cardiac total and cross-linked collagen content. Upon supplementation with Pycnogenol in L-NAME-exposed mice, cardiac gene expression patterns for pro-MMP-2, -9, and -13, and MMP-9 activity were significantly decreased, associated with a significant increase in cardiac tissue inhibitor of metalloproteinase (TIMP)-4 expression. These findings were coincided with a marked increase in myocardial total and cross-linked collagen content, compared with L-NAME-only-treated mice. Moreover, Pycnogenol treatment was associated with reversal of L-NAME-induced alternations in hemodynamic parameters. These data indicate that Pycnogenol can prevent adverse myocardial remodeling induced by L-NAME, through modulating TIMP and MMPs gene expression, MMPs activity, and further reduction in myocardial collagen degradation rate.

A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol on the climacteric syndrome in peri-menopausal women.

BACKGROUND: French maritime pine bark extract (Pycnogenol) was found to alleviate menstrual pain and reduce hyperactivity in clinical studies. These results suggest the possibility to observe positive effects in treating climacteric syndrome. OBJECTIVE: Clinical investigation of the effect of Pycnogenol, French maritime pine bark extract, on the climacteric syndrome. METHODS: Some 200 peri-menopausal women were enrolled in a double-blind, placebo-controlled study, and treated with Pycnogenol (200mg) daily. Climacteric symptoms were evaluated by the Women's Health Questionnaire (WHQ), patients were checked for antioxidative status and routine chemistry. A total of 155 women completed the study. RESULTS: All climacteric symptoms improved, antioxidative status increased and LDL/HDL ratio was favourably altered by Pycnogenol. No side effects were reported. CONCLUSION: Pycnogenol may offer an alternative method to reducing climacteric symptoms without unwanted effects.

Treatment of ADHD with French maritime pine bark extract, Pycnogenol.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric disorder in children. Pycnogenol, an extract from the bark of the French maritime pine, consisting of phenolic acids, catechin, taxifolin and procyanidins, has shown improvement of ADHD in case reports and in an open study. Aim of the present study was to evaluate the effect of Pycnogenol on ADHD symptoms. Sixty-one children were supplemented with 1 mg/kg/day Pycnogenol or placebo over a period of 4 weeks in a randomised, placebo-controlled, doubleblind study. Patients were examined at start of trial, 1 month after treatment and 1 month after end of treatment period by standard questionnaires: CAP (Child Attention Problems) teacher rating scale, Conner's Teacher Rating Scale (CTRS), the Conner's Parent Rating Scale (CPRS) and a modified Wechsler Intelligence Scale for children. Results show that 1-month Pycnogenol administration caused a significant reduction of hyperactivity, improves attention and visual-motoric coordination and concentration of children with ADHD. In the placebo group no positive effects were found. One month after termination of Pycnogenol administration a relapse of symptoms was noted. Our results point to an option to use Pycnogenol as a natural supplement to relieve ADHD symptoms of children.

Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II.

A double-blind, placebo-controlled, randomized, multi-center study was performed with 77 diabetes type II patients to investigate anti-diabetic effects of the French maritime pine bark extract, Pynogenol. Supplementation with 100 mg Pycnogenol for 12 weeks, during which a standard anti-diabetic treatment was continued, significantly lowered plasma glucose levels as compared to placebo. HbA1(c) was also lowered; however, the difference as compared to placebo was statistically significant only for the first month. In the Pycnogenol-group endothelin-1 was significantly decreased, while 6-ketoprostaglandin F(1a) in plasma was elevated compared to placebo. Nitric oxide levels in plasma increased during treatment in both groups, but, differences did not reach statistical significance. Pycnogenol was well-tolerated with ECG, electrolytes, creatinine and blood urea nitrogen remaining unchanged in both groups. Mild and transient unwanted effects were reported for both groups without significant differences. Supplementation of Pycnogenol to conventional diabetes treatment lowers glucose levels and improves endothelial function.

Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients.

A placebo-controlled, double-blind, parallel group study was performed with 58 patients to investigate effects of French maritime pine bark extract, Pycnogenol, on patients with hypertension. Supplementation of the patients with 100 mg Pycnogenol over a period of 12 weeks helped to reduce the dose of the calcium antagonist nifedipine in a statistically significant manner. The intake of Pycnogenol decreased endothelin-1 concentrations significantly compared to placebo while concentrations of 6-keto prostaglandin F1a in plasma were significantly higher compared to placebo. Values for nitric oxide (NO) in plasma increased in both groups, but the differences were not significant. Angiotensin II concentrations in plasma were lowered in the placebo group to a larger extent than in the Pycnogenol group. Heart rate, electrolytes and blood urea nitrogen were not changed during treatment in both groups of patients. Unwanted effects observed in both groups were of mild and transient nature, such as gastrointestinal problems, vertigo, headache and nausea. Differences in rate of side effects were not statistically significant between the two groups. Study results support a supplementation with Pycnogenol for mildly hypertensive patients.