Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Treatment of vascular retinopathies with Pycnogenol. Normalization of cardiovascular risk factors in peri-menopausal women with Pycnogenol®. Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. PYCNOGENOL in chronic venous insufficiency. A Controlled Trial of the Effect of Folate Supplements on Homocysteine, Lipids and Hemorheology in End-Stage Renal Disease The effect of garlic tablet on plasma lipids and platelet aggregation in nulliparous pregnants at high risk of preeclampsia. Effects on blood lipid and androgen levels of two triphasic oral contraceptives. The effects of thiazide diuretics upon plasma lipoproteins. The Effect of Atorvastatin on Serum Lipids, Lipoprotein(a) and Plasma Fibrinogen Levels in Primary Dyslipidaemia – A Pilot Study Involving Serial Sampling Pycnogenol may alleviate adverse effects in oncologic treatment. Pycnogenol in chronic venous insufficiency.
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 r and omized , 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 r and omly 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 result ed in improved diabetes control , lowered CVD risk factors , and reduced antihypertensive medicine use vs controls 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 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 prostagl and in 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 AIMS Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine . Pycnogenol is a proprietary bark extract of the French maritime pine tree ( Pinus pinaster ssp . atlantica ) that exerts antioxidative , anti-inflammatory , and anti-platelet effects . However , the effects of Pycnogenol on endothelial dysfunction , a precursor of atherosclerosis and cardiovascular events , remain still elusive . METHODS AND RESULTS Twenty-three patients with coronary artery disease ( CAD ) completed this r and omized , double-blind , placebo-controlled cross-over study . Patients received Pycnogenol ( 200 mg/day ) for 8 weeks followed by placebo or vice versa on top of st and ard cardiovascular therapy . Between the two treatment periods , a 2-week washout period was scheduled . At baseline and after each treatment period , endothelial function , non-invasively assessed by flow-mediated dilatation ( FMD ) of the brachial artery using high-resolution ultrasound , biomarkers of oxidative stress and inflammation , platelet adhesion , and 24 h blood pressure monitoring were evaluated . In CAD  patients , Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 ( P < 0.0001 ) , while no change was observed with placebo ( 5.4 ± 2.4 to 4.7 ± 2.0 ; P = 0.051 ) . This difference between study groups was significant [ estimated treatment effect 2.75 ; 95 % confidence interval ( CI ) : 1.75 , 3.75 , P < 0.0001 ] . 15-F(2t)-Isoprostane , an index of oxidative stress , significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment , while no change was observed in the placebo group ( mean difference 0.06 pg/mL with an associated 95 % CI ( 0.01 , 0.11 ) , P = 0.012 ] . Inflammation markers , platelet adhesion , and blood pressure did not change after treatment with Pycnogenol or placebo . CONCLUSION This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress Pycnogenol ® ( PYC ) , an extract of French maritime pine bark ( Pinus pinaster ) , is a potent antioxidant with potential health benefits . Its bioavailabilty has previously been shown by urinary excretion studies of constituents and metabolites of PYC . The aim of this study was to test the effect of PYC supplementation on measures of oxidative stress and the lipid profile in humans . Twenty-five healthy subjects received  PYC  ( 150 mg/d ) for 6 wk . Fasting blood was collected at baseline , after 3 and 6 wk of supplementation , and again after a 4-wk washout period . After 6 wk of supplementation with PYC , a significant increase in plasma polyphenol levels was detectable , which was reversed after the 4-wk washout phase . The antioxidant effect of PYC was demonstrated by a significant increase in oxygen radical absorbance capacity ( ORAC ) in plasma throughout the supplementation period ( P<0.05 ) . The ORAC value returned to baseline after the 4-wk washout period . Moreover , in addition to its antioxidant effects  , PYC significantly reduced LDL-cholesterol levels and increased HDL-cholesterol levels in plasma of two-thirds of the subjects . While the LDL changes reversed during washout , the HDL increase did not . There was no significant difference in LDL oxidizability or plasma lipid peroxides following PYC supplementation . Hence , following oral supplementation in humans  , PYC significantly increases antioxidant capacity of plasma , as determined by ORAC , and exerts favorable effects on the lipid profile The aim of this study was to compare the efficacy of Venostasin ( horse chestnut seed extract ) and Pycnogenol ( French maritime pine bark extract ) in the treatment of chronic venous insufficiency ( CVI ) . In an open , controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks . The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment : circumference of the lower legs and rating of subjective symptoms ( scores ) of pain , cramps , night-time swelling , feeling of " heaviness " , and reddening of the skin . In addition , blood levels of cholesterol LDL and HDL were determined before and at the end of treatment . Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms . Furthermore , Pycnogenol significantly decreased cholesterol and LDL values in the blood , whereas HDL remained unaffected . Venostasin only moderately but not significantly , reduced the circumference of the lower limbs and marginally improved symptoms .  Venostasin had no influence on the determined lipid values . Both medications were equally well tolerated . In conclusion , Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI 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 r and omly 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 BACKGROUND The aim of the study was the evaluation of the efficacy of Pycnogenol ® in peri-menopausal women in controlling homocysteine and C-reactive protein ( CRP ) levels , borderline cardiovascular risk factors , oxidative stress ( OS ) and symptoms associated to menopausal transition ( MT ) . METHODS Pycnogenol ® , 100mg/day , was used as a supplement for 8 weeks by a group of 35 women . A comparable group of 35 women with identical cardiovascular risk factors was included as the control group . All women were instructed to participate in a best management plan of menopause . RESULTS The two groups were comparable . All women completed the eight weeks study . Only minor deviations from the best management plan were observed . At inclusion , both groups were similar in respect to risk factors . Supplementation with Pycnogenol ® decreased the slightly elevated cholesterol and triglycerides after 8 weeks ( P<0.05 ) . Also the fasting glucose levels were normalized ( P<0.05 ) . The borderline increased blood pressure was reduced to normal values at 8 weeks ( P<0.05 ) . Plasma free radicals dropped significantly by 22 % ( P<0.05 ) . Homocysteine and CRP levels decreased sharply by 43 % and 60 % , respectively ( P<0.05 ) . No significant changes of these risk factors were noted in the control group . Almost all menopausal symptoms , scored by The Menopausal Symptoms Question naire 34 , improved significantly following supplementation with Pycnogenol ® . The supplementation was well tolerated . CONCLUSIONS The supplementation with Pycnogenol ® improved the quality of life of perimenopausal women and normalized a series of cardiovascular risk factors , especially factors connected to cardiovascular events , as homocysteine and CRP A double-blind , placebo-controlled , r and omized , 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 st and ard 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-ketoprostagl and in 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 The aim of out study was to investigate the efficacy of Pycnogenol - a French maritime pine bark extract - in the treatment of chronic venous insufficiency ( CVI ) . The study consisted of a double-blind phase - in which 20 patients were recruited and r and omly treated with placebo or Pycnogenol ( 100 mg 2 3/day for 2 months ) - and an open phase - in which other 20 patients were treated with Pycnogenol at the same dose schedule . In total , 40 patients were enrolled ; 30 of them were treated with Pycnogenol and 10 with placebo . Pycnogenol significantly improved the legs ' heaviness and subcutaneous edema ; the venous pressure was also significantly reduced by the Pycnogenol treatment , thus adding further clinical evidence to its therapeutic efficacy in patients with CVI .  Pycnogenol was effective , probably by either stabilizing the collagenous subendothelial basal membrane or scavenging the free radicals , or by a combination of these activities . Clinical ly , capillary leakage , perivascular inflammation and subcutaneous edema were all reduced . The safety of use of Pycnogenol is demonstrated by the lack of side effects or changes in blood biochemistry and hematologic parameters .  Pycnogenol can be therefore recommended both for prevention and treatment of CVI and related veno-capillary disturbances Elevated plasma homocysteine ( Hcy ) , dyslipidemia and hemorheological abnormalities all occur commonly in end-stage renal disease ( ESRD ) and are recognized risk factors for arteriosclerosis . To study the effect of folate supplementation on these factors we conducted a r and omized controlled trial . Thirteen hemodialysis ( HD ) and 8 continuous ambulatory peritoneal dialysis ( CAPD ) patients received either 5 mg folic acid daily or placebo for 3 months . After 1 and 3 months , fasting blood sample s were taken for Hcy , lipid profile , blood and plasma viscosity , red blood cell ( RBC ) osmotic fragility , plasma fibrinogen concentration and in vivo platelet aggregability . At baseline , the CAPD patients had a higher mean plasma fibrinogen concentration than the HD patients and they also tended to have higher mean plasma viscosity .  Folate-treated patients showed marked increases in RBC folate and an average decrease in plasma Hcy concentration of 33 % . Mean total cholesterol , LDL cholesterol and triglyceride concentrations decreased significantly in the CAPD patients who took folate . Folate had no significant effect on hemorheology . In conclusion , folate supplements in ESRD reduce plasma Hcy concentrations and may improve lipid profiles . In our patients , hemorheological abnormalities were more marked in patients on CAPD than in those on HD and were not improved by folate supplementation OBJECTIVE This study was design ed to determine the effect of garlic tablet ( Garlet ) on plasma lipids , and platelet aggregation and the efficacy of this treatment in the prevention of preeclampsia . STUDY DESIGN In a r and omized , single-blind , placebo-controlled study , 100 primigravidas with positive roll-over test were treated with daily doses of 800 mg Garlet/day ( n=50 ) or 800mg/day placebo ( n=50 ) during the third trimester of pregnancy . Serum total cholesterol , LDL- and HDL-cholesterol , triglyceride , and platelet aggregation were measured before and after the treatment . Blood pressure , weight , and edema were also examined during the entire study period . RESULTS In the case group , there was no significant difference in the means of total cholesterol , HDL , LDL , and triglyceride before and after the experiment . Furthermore , the inhibition of platelet aggregation did not show any significant difference before and after the treatment . There were not any significant difference in the means of HDL , LDL , triglyceride , inhibition of platelet aggregation , the means of systolic and diastolic blood pressure and the mean arterial blood pressure ( MAP ) , between the two groups , but there was a significant difference in the means of total cholesterol ( P=0.038 ) and hypertension alone ( P=0.043 ) . CONCLUSION The administration of 800mg/day of Garlet during the third trimester of pregnancy was effective in reducing the occurrence of hypertension alone , but it was no effective in preventing of preeclampsia At Hospital Saint-Louis in Paris France physicians compared data on 34 women using a levonorgestrel triphasic oral contraceptive ( OC ) with data on 32 women using a norgestimate triphasic OC  to examine the triphasic OCs effects on blood lipids and and rogen levels . They also compared post-OC blood lipids and and rogen levels with baseline blood lipids and and rogen levels . 47 % of all subjects smoked . After 6 cycles neither triphasic OC caused a significant difference in low density lipoprotein ( LDL ) cholesterol levels or in triglyceride levels . High density lipoprotein ( HDL ) levels in women using the norgestimate OC were significantly higher than in those using the levonorgestrel OC ( p = .001 ) . Accordingly the OCs had a significant effect on the LDL/HDL ratio . Levels of HDL subfractions ( HDL-2 and HDL-3 ) were also significantly higher in the norgestimate OC group than in the levonorgestrel OC group ( p < .01 ) . Women using the norgestimate OC had a significant increase in apolipoproteins A-1 and 1 - 2 after 6 cycles ( 12.7 % and 15.8 % respectively ; p = .001 and .0001 respectively ) . Neither triphasic OC affected a greater increase in sex hormone binding globulin ( SHBG ) levels than did the levonorgestrel OC ( 163 % vs. 72 % ; p = .0005 ) . It reduced the free testosterone level by 40 % . The levonorgestrel OC reduced it by 30 % but neither change was significant . Neither OC had an effect on body weight or blood pressure . These findings showed a trend toward lower and rogenicity with the norgestimate OC . The norgestimate OC may be beneficial since it was linked with significant increases in all HDL subfractions and SHBG In a double-blind , placebo-controlled , crossover study in 16 hypertensives , 4 weeks of 50 mg  hydrochlorothiazide twice daily , caused significant elevations in total plasma cholesterol , high density lipoprotein (HDL)-cholesterol , low density lipoprotein (LDL)-cholesterol , very low density lipoprotein (VLDL)-cholesterol and triglycerides . Significant elevations in fasting plasma glucose and in plasma insulin were observed , but no correlation between individual lipid elevations and either glucose or insulin elevations was apparent . The metabolic effects developed within 2 weeks , and dissipated within 4 weeks . Changes induced within 4 weeks of treatment with hydrochlorothiazide were unaltered at 6 months . Hydrochlorothiazide induces elevation of all lipoprotein cholesterol fractions and VLDL-triglyceride . However , as the important ratio between LDL- and HDL-cholesterol is unchanged , coronary risk may be unchanged Summary We conducted an open-label study to test the effects of atorvastatin on serum lipids , lipoprotein(a ) [ Lp(a ) ] and plasma fibrinogen levels .  A total of 90 dyslipidaemic , nonsmoking patients ( 45 patients with primary hypercholesterolaemia and 45 patients with primary mixed hyperlipidaemia ) aged 48 ± 11 years were studied . The patients were treated with 20 mg of atorvastatin for 24 weeks , in a single nocturnal dose . At baseline and every eight weeks , the fasting lipid profile , together with serum Lp(a ) and plasma fibrinogen levels ( Clauss method ) , were measured . Atorvastatin was highly effective in normalising the serum lipid profile . No significant change in median serum Lp(a ) levels was observed in the whole group of patients ( 0.14 g/l before , vs. 0.16 g/l after , treatment ) as well as in patients with raised ( > 0.30 g/l ) baseline levels ( n = 32 ) . A small non-significant increase of plasma fibrinogen was found ( 3.04 g/l vs. 3.14 g/l ) after 24 weeks of atorvastatin administration . The effects of atorvastatin on both these variables did not differ in patients with hypercholesterolaemia or mixed hyperlipidaemia . In conclusion , our findings suggest that the effect of atorvastatin  on plasma fibrinogen levels in dyslipidaemic patients without evident vascular disease is not clinical ly relevant . Furthermore , any rise in fibrinogen levels that may occur is likely to be transient in nature . Further studies are necessary to clarify this issue . There was no evidence that atorvastatin  influences serum Lp(a ) levels AIM A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology . Specific medications exist to target individual side effects . The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient 's quality of life . METHODS Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition , both physically and psychologically , were recruited for this study and divided into two groups . These patients received their first cycle of radiotherapy or chemotherapy , which lasted from 10 days up to 1 month . Then one group of patients received 150 mg Pycnogenol , the control group comparable placebo in a single-blinded fashion . The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy , respectively . RESULTS Twenty five radiotherapy patients receiving Pycnogenol  showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo  , though in many categories the difference was limited . The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes . A decreased incidence of nausea /vomiting , diarrhoea , edema and weakness was noticed , which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group . Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group ( 2.9 % vs 10 % ) . Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30 patients were in the control group . For all patients this was the first chemotherapy treatment period . The Pycnogenol group presented with a lowered incidence of all investigated side effects as compared to the control group , though in many cases to a limited extent . The most prominent improvements were found for nausea , vomiting , diarrhoea and weight loss . Semi-quantitative evaluation showed that here again symptom severity was half or less pronounced than in the control group . Various further symptoms improved such as cognitive impairment and also cardiotoxicity and neutropenia . Effects on anemia could not be investigated as several patients received erythrocyte transfusion . In the Pycnogenol group one case of superficial vein thrombosis was indentified while 3 cases of superficial vein thromboses and one deep vein thrombosis were detected in the control group ( 4 % vs 19 % ) . In both chemotherapy and radiotherapy patients Pycnogenol lowered the requirement for medication to address side effects . This was reflected by less days of hospitalisation the patients required . The authors did not investigate a possible interference with the anti-neoplastic efficacy of chemo- and radiotherapy . This possibility requires attention in future studies with Pycnogenol . From their previous clinical experience the authors suggest that alleviation of side effects described in this study results from Pycnogenol activities related to endothelial protection , and anti-inflammatory anti-edema activities . CONCLUSION The results of this pilot trial warrant further prospect i ve studies with larger number of patients to vali date benefits more specifically with regard to type of malignancy and treatment regimen Forty patients with chronic venous insufficiency ( CVI ) and varices of the legs were selected and double-blindly r and omly assigned to a treatment with Pycnogenol ( French maritime pine bark extract ) , 100 mg x 3/day or a placebo for 2 months , according to a double-blind experimental design . The effects of the treatment were evaluated by scoring the symptomatology with a semi-quantitative scale , and the venous blood flow by means of a h and -held Doppler ultrasound . The tolerability was evaluated by recording the adverse effects and by means of hematology and blood chemistry parameters , before and at the end of the treatment . Pycnogenol treatment induced a significant reduction in subcutaneous edema as well as heaviness and pain in the legs , on both after 30 and 60 days , the evaluation time periods . Approximately 60 % of patients treated with Pycnogenol(R ) experienced a complete disappearance of edema ( the most rapidly disappearing symptom ) and pain at the end of the treatment , while almost all the patients reported a reduction in leg heaviness which disappeared in approximately 33 % of patients . These changes were statistically significant . No effect was observed in the placebo-treated subjects . No effect on the venous blood flow was observed in either of the experimental groups
The results indicate that pycnogenol supplementation improves levels of HDL-C ; however , the changes in TC , TAG , and LDL-C were not clinical ly relevant .
Since there are few phytochemicals that have a significant increasing effect on HDL-C levels  , pycnogenol may have important role in prevention of cardiovascular diseases
The effects of pycnogenol on plasma lipids are controversial .
A systematic review and meta- analysis of clinical trials were conducted to obtain a conclusive result in humans .