Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Kidney Flow and Function in Hypertension: Protective Effects of Pycnogenol in Hypertensive Participants—A Controlled Study Normalization of cardiovascular risk factors in peri-menopausal women with Pycnogenol®. l-Arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. PYCNOGENOL in chronic venous insufficiency. 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, Augments Endothelium-Dependent Vasodilation in Humans Potassium supplementation in blacks with mild to moderate essential hypertension. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. EFFECT OF CALCIUM SUPPLEMENTATION ON DIASTOLIC BLOOD PRESSURE IN YOUNG PEOPLE WITH MILD HYPERTENSION Crossover design to test antihypertensive drugs with self-recorded blood pressure. Effect of oral calcium supplementation on blood pressure in patients with previously untreated hypertension: a randomised, double-blind, placebo-controlled, crossover study. Effect of calcium supplementation in an older population with mildly increased blood pressure.
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 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 This study evaluated the effects of Pycnogenol as an adjunct to angiotensin-converting enzyme (ACE)-inhibitor ramipril treatment of hypertensive patients presenting with early signs of renal function problems . One group of 26 patients was medicated with 10 mg ramipril per day only ; a second group of 29 patients  took Pycnogenol in addition to the ACE inhibitor over a period of 6 months . At trial end , a lowered systolic and diastolic blood pressure was found in both groups , with a significant further reduction of diastolic pressure in the group given Pycnogenol in addition to ramipril . The major aim of this study was the investigation of kidney-protective effects of Pycnogenol . Urinary albumin decreased from 87 ± 23 to 64 ± 16 mg/d with ramipril only . Additional Pycnogenol  lowered albumin significantly better from 91 ± 25 to 39 ± 13 mg/day ( P < .05 ) . In both groups , serum creatinine was lowered ; however , only in the combination treatment group did the effect reached statistical significance . In both groups , CRP levels decreased from 2.1 to 1.8 with ramipril and from 2.2 to 1.1 with the ramipril — Pycnogenol combination ; the latter reached statistical significance . Kidney cortical flow velocity was investigated by Doppler color duplex ultrasonography . Both systolic and diastolic flow velocities increased significantly after 6 months medication with ramipril . The addition of Pycnogenol to the regimen statistically significantly further enhanced kidney cortical flow velocities , by 8 % for diastolic flow and 12 % for systolic flow , relative to values found for the group taking ramipril only . The protective effects of Pycnogenol for initial kidney damage found in this study warrant further research with a larger number of patients and over a longer period of time 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 Objective . To evaluate l-arginine ( l-Arg ) supplementation in pregnant women with chronic hypertension and its effects on blood pressure ( BP ) and maternal and neonatal complications . Methods . We enrolled 80 women affected by mild chronic hypertension referred to the High Risk Clinic of the Mother – Infant Department of the University of Modena and Reggio Emilia . Each woman after obtaining oral consent was r and omized to receive oral l-Arg versus placebo and thereafter su bmi tted to 24-h ambulatory BP monitoring . The primary outcome was BP change after 10–12 weeks of treatment . Secondary outcomes were as follows : percentage of women on antihypertensive treatment at delivery , maternal , and fetal outcome . Results . The BP changes after 10–12 weeks of treatment did not differ between groups . A lower percentage of women received antihypertensive drugs in the l-Arg group than the placebo group . The incidence of superimposed preeclampsia indicated delivery before the 34th weeks and certain neonatal complications tended to be higher in the placebo group . Conclusions . l-Arg supplementation in pregnant women with mild chronic hypertension does not significantly affect overall BP but is associated with less need for antihypertensive medications and a trend toward fewer maternal and neonatal complications . The results of the study were limited by the small sample size and by the exclusion of women with severe chronic hypertension . In our policy , these patients needed many hypertensive drugs and were normally managed by the cardiologist . Nevertheless , considering the promising results on maternal and fetal outcome , we believe that further studies should be performed to confirm such data and to clarify the role of l-Arg as a protective supplement in high-risk pregnancy 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 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 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 Pycnogenol ® , an extract of bark from the French maritime pine , Pinus pinaster Ait . , consists of a concentrate of water-soluble polyphenols . Pycnogenol ® contains the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids . Antioxidants , such as bioflavonoids , enhance endothelial nitric oxide ( NO ) synthase expression and subsequent NO release from endothelial cells . The purpose of this study was to determine Pycnogenol ® 's effects on endothelium-dependent vasodilation in humans . This was a double-blind , r and omized , placebo and active drug study . We evaluated forearm blood flow ( FBF ) responses to acetylcholine ( ACh ) , an endothelium-dependent vasodilator , and to sodium nitroprusside ( SNP ) , an endothelium-independent vasodilator , in healthy young men before and after 2 weeks of daily oral administration of Pycnogenol ® ( 180 mg/day ) ( n=8 ) or placebo ( n=8 ) . FBF was measured by using strain-gauge plethysmography . Neither the placebo nor Pycnogenol ® altered forearm or systemic hemodynamics  . Pycnogenol ® , but not placebo , augmented FBF response to ACh , from 13.1±7.0 to 18.5±4.0 mL/min per 100 mL tissue ( p<0.05 ) . SNP-stimulated vasodilation was similar before and after 2 weeks of treatment in the control and Pycnogenol ® groups . The administration of NG-monomethyl-L-arginine , an NO synthase inhibitor , completely abolished Pycnogenol ® -induced augmentation of the FBF response to ACh . These findings suggest that Pycnogenol ® augments endothelium-dependent vasodilation by increasing in NO production  . Pycnogenol ® would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction Potassium chloride ( KCl ) salt ( 65 mmol ) daily reduced BP from 153/104 to 146/101 mmHg in 32 hypertensive black females during a 6-week placebo controlled crossover study . The fall in BP was independent of the order of r and omization and was significant for systolic ( SBP ; P less than 0.01 ) and diastolic ( DBP ; P less than 0.05 ) pressure after 4 weeks . Analysis of the 95 % confidence intervals in this and in five other studies , two of which were reported as showing no beneficial effect , suggests that potassium supplementation does lower BP , but that the change is small and within the confidence levels of all six trials . Thus , apparent discrepancies in the literature are not genuine statistically OBJECTIVE To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure . DESIGN R and omized control multicenter trials . SETTING Volunteers recruited from the community , treated and followed up at special clinics . PARTICIPANTS Of 16,821 screenees , 2182 men and women , aged 30 through 54 years , with diastolic blood pressure from 80 through 89 mm Hg were selected . Of these , 50 did not return for follow-up blood pressure measurements . INTERVENTIONS Three life-style change groups ( weight reduction , sodium reduction , and stress management ) were each compared with unmasked nonintervention controls over 18 months . Four nutritional supplement groups ( calcium , magnesium , potassium , and fish oil ) were each compared singly , in double-blind fashion , with placebo controls over 6 months . MAIN OUTCOME MEASURES Primary : change in diastolic blood pressure from baseline to final follow-up , measured by blinded observers . Secondary : changes in systolic blood pressure and intervention compliance measures . RESULTS Weight reduction intervention produced weight loss of 3.9 kg ( P less than .01 ) , diastolic blood pressure change of -2.3 mm Hg ( P less than .01 ) , and systolic blood pressure change of -2.9 mm Hg ( P less than .01 ) . Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h ( P less than .01 ) , diastolic blood pressure by 0.9 mm Hg ( P less than .05 ) , and systolic blood pressure by 1.7 mm Hg ( P less than .01 ) . Despite good compliance , neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly ( P greater than .05 ) . CONCLUSIONS Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons . Sodium reduction is also effective . The long-term effects of weight reduction and sodium reduction , alone and in combination , require further evaluation 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 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 In a double-blind trial 90 mildly hypertensive subjects aged 16 - 29 years were r and omly assigned to 1 g calcium per day or placebo . Calcium supplementation did not affect systolic blood pressure , but at six and twelve weeks diastolic blood pressure had fallen by 3.1 ( p = 0.04 ) and 2.4 ( p = 0.11 ) mm Hg , respectively , more in the calcium group than it had in the placebo group . Subjects with a baseline plasma parathyroid hormone ( PTH ) higher than the median showed a 6.1 mm Hg ( p = 0.01 ) greater fall in diastolic blood pressure after six weeks and 5.4 mm Hg ( p = 0.01 ) after twelve than in the placebo group . The fall in diastolic blood pressure was greater in the calcium group than in the placebo group in subjects with a lower than median serum total calcium and in those with a large bodyweight . Calcium supplementation may lower blood pressure in young people with mildly raised blood pressure , particularly in those with high plasma PTH and /or low serum total calcium In a double-blind , within-patient study , blood pressure was measured at regular intervals at the clinic by the physician and each day at home by the patient . Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone ( 25 mg ) and triamterene ( 50 mg ) and the beta-blocker oxprenolol ( 160 mg ) and the greater efficacy of the combination of the two therapies . During placebo , as well as during active treatment , blood pressure values were higher at the clinic than at home , except when the patients were taking the beta-blocker , which minimized the arousal response during blood pressure measurements in the clinic . With 2-week treatment periods , separated by 2 weeks of placebo administration , blood pressure returned toward its initial level after each of the three treatments and none of the carryover effects was significant at the 5 % level . This methodology was intended to make it possible to demonstrate in 27 patients at the clinic and in 20 patients with measurements made at home , at the usual statistical risks ( alpha = 5 % , beta = 10 % ) , a fall of 5 mm Hg in diastolic blood pressure in comparison with a placebo . Moreover , at the end of this 3-month follow-up , each patient could continue to receive the treatment that was the most effective and the best tolerated . In conclusion , the use of a within-patient trial design , with a 15-day washout period between active treatments and careful recording of blood pressure values , can minimize the number of patients included in hypertension trials and offer to each patient the possibility of individualization of treatment It has been cl aim ed that calcium lowers BP . The present r and omised , double-blind , placebo-controlled crossover study is the first to investigate the effect on BP of a high oral dose of calcium given for a long period to patients with previously untreated hypertension .  Elemental calcium ( 2 g ) was administered for 12 weeks interchanging with a period of 12 weeks of placebo .  Twenty patients completed the protocol . There was no significant difference in change of BP during the period of additional calcium intake when compared with placebo ( P = 0.33 ) . The risk of not detecting a real BP-lowering effect of calcium of at least 3 mmHg was < 5 % . No evidence for the existence of a subgroup of ' responders ' was found . It is concluded that a high daily dose of calcium supplementation given for 12 weeks does not decrease BP in previously untreated patients with mild to moderate hypertension This study was undertaken to determine if calcium carbonate supplementation could reduce blood pressure in an older population that had mildly increased pressure and if blood pressure reduction could be maintained over the course of 1 year with continued supplementation . Volunteers 50 to 80 years of age were included if their systolic blood pressure ( when not taking antihypertensive medication ) was consistently greater than or equal to 140 mm Hg or if diastolic blood pressure was greater than or equal to 90 mm Hg during a 4-week baseline period . Each subject then received placebo tablets for 4 weeks followed by 1 g calcium carbonate tablets for 12 weeks in a single-blinded fashion . If either systolic or diastolic blood pressure was reduced by at least 5 mm Hg with calcium supplementation as compared to placebo , calcium supplementation was continued for 36 weeks . A 25 % sub sample of subjects completed a 12-week placebo run-out . Supine and st and ing systolic and diastolic blood pressure did not change significantly with 12 weeks of calcium carbonate as compared to placebo ( P = NS ) . In 42 of 103 subjects with at least a 5 mm Hg initial decrease in blood pressure who were continued on calcium supplementation , blood pressure did not change significantly through 36 weeks . In the 12 subjects who completed the placebo run-out period , systolic pressures increased significantly ( P less than .05 ) and did not differ from baseline ( P = NS ) . There is no evidence in this study for general use of calcium supplementation to reduce blood pressure in an older population . ( ABSTRACT TRUNCATED AT 250 WORDS
Therefore , the present meta- analysis does not suggest any significant effect of pycnogenol  on BP
Results of previous clinical trials evaluating the effect of pycnogenol supplementation on  blood pressure ( BP )  are controversial .