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Life Extension Magazine August 2012


Treatment of vascular retinopathies with Pycnogenol. 

The aim of our study was to investigate the effects of Pycnogenol on the progression of diabetic retinopathy and other vascular retinal disorders. The study consisted of a double-blind phase in which 20 patients were recruited and randomly treated with placebo or Pycnogenol (50 mg x 3/day for 2 months) and an open phase in which another 20 patients were treated with Pycnogenol at the same dose schedule. In total, 40 patients with diabetes, atherosclerosis and other vascular diseases involving the retina were enrolled; 30 of them were treated with Pycnogenol and 10 with placebo. The results demonstrated a beneficial effect of Pycnogenol on the progression of retinopathy. Without any treatment (placebo) the retinopathy progressively worsened during the trial and the visual acuity significantly decreased; on the contrary, the Pycnogenol-treated patients showed no deterioration of retinal function and a significant recovery of visual acuity was also obtained. The fluorangiography showed an improvement of retinal vascularization and a reduced endothelial permeability and leakage in the Pycnogenol, but not in the placebo-treated, patients. The ophthalmoscopy and the electroretinogram (ERG) also confirmed the beneficial effects of Pycnogenol. The mechanism of action of Pycnogenol may be related to its free radical (FR) scavenging, anti-inflammatory and capillary protective activities. It has been suggested that Pycnogenol may bind to the blood vessel wall proteins and mucopolysaccharides and produce a capillary 'sealing' effect, leading to a reduced capillary permeability and oedema formation.

Phytother Res. 2001 May;15(3):219-23

Improvement of diabetic microangiopathy with Pycnogenol: A prospective, controlled study.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, United Kingdom) in patients with diabetic microangiopathy. Patients without a history of diabetic ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily for 4 weeks). A group of 30 patients was included (severe microangiopathy); 30 comparable patients were observed as controls (no treatment during the observation period). All patients (age, 59 years; range, 55-68 years; male:female = 18:12) included in the treatment group completed the 4-week study. Also, all controls completed the follow-up period. There were no drop-outs. All included subjects had signs and symptoms of diabetic microangiopathy. The duration of diabetes-from the first signs/symptoms--was on average 7.5 years (SD = 3). After 4 weeks, microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot (indicating an improvement in the level of microangiopathy), a significant decrease in capillary filtration, and a significant improvement in the venoarteriolar response in all treated subjects. There were no visible effects in controls except a slight reduction in skin flux at rest in the foot. Treatment was well tolerated in both groups. In conclusion, this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy. The study indicates the clinical role of Pycnogenol in the management, treatment, and control of this common clinical problem. The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy.

Angiology. 2006 Aug-Sep;57(4):431-6

Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury.

The neuropathological hallmarks of Alzheimer's disease (AD) are senile plaques, cerebrovascular beta-amyloidosis, neurofibrillary tangles, and selective neuronal loss. Beta-amyloid (Abeta) has been shown to cause vascular damage mediated by generation of reactive oxygen species and this damage is considered an early event in the development of AD. In this study, we determined the effect of pyenogenol, a potent antioxidant phytochemical, on Abeta-induced cellular injury. Pulmonary artery endothelial cells (PAEC) were exposed to Abeta for 24 h. Cell injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were determined by measuring thiobarbituric acid-reactive substances (TBARS). Exposure of PAEC to Abeta resulted in a decrease in cell viability, an increase of LDH release indicating membrane damage, and an elevated level of TBARS. Preincubation of PAEC with pycnogenol significantly minimized these changes. This study demonstrated that pycnogenol can protect vascular endothelial cells from Abeta-induced injury. The data suggest that pycnogenol may be useful for the prevention and/or treatment of vascular or neurodegenerative diseases associated with Abeta toxicity.

Biol Pharm Bull. 2000 Jun;23(6):735-7

Pycnogenol protects neurons from amyloid-beta peptide-induced apoptosis.

Neuronal apoptosis is one of the pathological features of Alzheimer's disease (AD). Morphological pathology reveals that neuronal apoptosis is associated with senile plaques containing amyloid-beta peptide (Abeta) in AD brains. Reactive oxygen species (ROS) has been proposed to be involved in the apoptotic mechanism of Abeta-mediated neurotoxicity. In the present study, using a rat pheochromocytoma (PC12) cell line, we investigated the effect of Pycnogenol (PYC), a potent antioxidant and ROS scavenger, on Abeta(25-35)-induced apoptosis and ROS generation. We used vitamin E, a known antioxidant agent, to verify the effect of PYC. Abeta(25-35)-induced apoptosis in PC12 cells was demonstrated by: (1) a dose-dependent loss of cell viability; (2) a time- and dose-dependent increase in the apoptotic cells; (3) an induction of DNA fragmentation; and (4) an increase in caspase-3 activity and cleavage of poly (ADP-ribose) polymerase (PARP). Our data showed that a significant increase in ROS formation preceded apoptotic events after PC12 cells were exposed to Abeta(25-35). We further found that PYC not only suppressed the generation of ROS but also attenuated caspase-3 activation, DNA fragmentation, PARP cleavage, and eventually protected against Abeta-induced apoptosis. Vitamin E also suppressed cell death and caspase-3 activation induced by Abeta(25-35). Taken together, these results suggest that ROS may be involved in Abeta-induced apoptosis in PC12 cells. They further suggest that PYC can reduce apoptosis, possibly by decreasing free radical generation in PC12 cells.

Brain Res Mol Brain Res. 2002 Jul 15;104(1):55-65

An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.

The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.

J Psychopharmacol. 2008 Jul;22(5):553-62

Pycnogenol attenuates the inflammatory and nitrosative stress on joint inflammation induced by urate crystals.

Acute gouty arthritis results from monosodium urate (MSU) crystal deposition in joint tissues. Deposited MSU crystals induce an acute inflammatory response which leads to damage of joint tissue. Pycnogenol (PYC), an extract from the bark of Pinus maritime, has documented antiinflammatory and antioxidant properties. The present study aimed to investigate whether PYC had protective effects on MSU-induced inflammatory and nitrosative stress in joint tissues both in vitro and in vivo. MSU crystals upregulated cyclooxygenase 2 (COX-2), interleukin 8 (IL-8) and inducible nitric oxide synthase (iNOS) gene expression in human articular chondrocytes, but only COX-2 and IL-8 in synovial fibroblasts. PYC inhibited the up-regulation of COX-2, and IL-8 in both articular chondrocytes and synovial fibroblasts. PYC attenuated MSU crystal induced iNOS gene expression and NO production in chondrocytes. Activation of NF-κB and SAPK/JNK, ERK1/2 and p38 MAP kinases by MSU crystals in articular chondrocytes and synovial fibroblasts in vitro was attenuated by treatment with PYC. The acute inflammatory cell infiltration and increased expression of COX-2 and iNOS in synovial tissue and articular cartilage following intra-articular injection of MSU crystals in a rat model was inhibited by coadministration of PYC. Collectively, this study demonstrates that PYC may be of value in treatment of MSU crystal-induced arthritis through its anti-inflammatory and anti-nitrosative activities.

Free Radic Biol Med. 2012 Feb 15;52(4):765-74

Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol.

In a previous, double-blind, placebo-controlled study we evaluated the efficacy of a 3-month treatment with Pycnogenol for 156 patients with osteoarthritis of the knee. Pycnogenol significantly decreased joint pain and improved joint function as evaluated using the WOMAC score and walking performance of patients on a treadmill. In this study, we further investigated the anti-inflammatory and antioxidant activity of Pycnogenol in a subset of the osteoarthritis patients presenting with elevated C-reactive protein (CRP) and plasma-free radicals. Elevated CRP levels have been suggested to be associated with disease progression in osteoarthritis. In our study, 29 subjects of the Pycnogenol group and 26 patients in the placebo group showed CRP levels higher than 3 mg/l at baseline. Comparison of blood specimens drawn at baseline and after 3-month treatment showed that Pycnogenol significantly decreased plasma free radicals to 70.1% of baseline values. Plasma CRP levels decreased from baseline 3.9 mg/l to 1.1 mg/l in the Pycnogenol group whereas the control group had initial values of 3.9 mg/l which decreased to 3.6 mg/l. The CRP decrease in the Pycnogenol was statistical significant as compared to the control group (P < 0.05). Fibrinogen levels were found to be lowered to 62.8% of initial values (P < 0.05) in response to Pycnogenol. No significant changes for plasma free radicals, CRP and fibrinogen were found in the placebo-treated group. The decrease of systemic inflammatory markers suggests that Pycnogenol may exert anti-inflammatory activity in osteoarthritic joints and patients did not present with other ailments or infections. The nature of the anti-inflammatory effects of Pycnogenol with regard to CRP warrants further investigation.

Redox Rep. 2008;13(6):271-6

Treatment of melasma with Pycnogenol.

Melasma (or chloasma) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women. The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects. Pycnogenol is a standardized extract of the bark of the French maritime pine (Pinus pinaster), a well-known, potent antioxidant. Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition, it recycles vitamin C, regenerates vitamin E and increases the endogenous antioxidant enzyme system. Pycnogenol protects against ultraviolet (UV) radiation. Therefore its efficacy in the treatment of melasma was investigated. Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily, i.e. 75 mg Pycnogenol per day. These patients were evaluated clinically by parameters such as the melasma area index, pigmentary intensity index and by routine blood and urine tests. After a 30-day treatment, the average melasma area of the patients decreased by 25.86 +/- 20.39 mm(2) (p < 0.001) and the average pigmentary intensity decreased by 0.47 +/- 0.51 unit (p < 0.001). The general effective rate was 80%. No side effect was observed. The results of the blood and urine test parameters at baseline and at day 30 were within the normal range. Moreover, several other associated symptoms such as fatigue, constipation, pains in the body and anxiety were also improved. To conclude, Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma.

Phytother Res. 2002 Sep;16(6):567-71

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.

Nutr Res. 2008 May;28(5):315-20

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with Pycnogenol.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

Clin Appl Thromb Hemost. 2004 Oct;10(4):373-7