human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction There is a growing interest in nutraceuticals improving cardiovascular risk factor levels and related organ damage . Methods This double-blind , placebo-controlled r and omized clinical trial aims to compare the effect of a combined nutraceutical containing red yeast rice ( 10 mg ) , phytosterols ( 800 mg ) , and l-tyrosol ( 5 mg ) on lipid profile , blood pressure , endothelial function , and arterial stiffness in a group of 60 patients with polygenic hypercholesterolemia resistant to Mediterranean diet . Results After 8 weeks of treatment , when compared to the placebo group , the active treated patients experienced a more favorable percentage change in total cholesterol ( −16.3 % vs 9.9 % , P < 0.001 always ) , LDL-C ( −23.4 % vs −13.2 % , P < 0.001 always ) , and hepatic steatosis index ( −2.8 % , P < 0.01 vs −1.8 % , P < 0.05 ) . Moreover , ALT ( −27.7 % , P < 0.001 ) , AST ( −13.8 % , P = 0.004 ) , and serum uric acid ( −12.3 % , P = 0.005 ) were reduced by the tested nutraceutical compound both compared to r and omization and to placebo , which did not affect these parameters ( P < 0.01 for all ) . Regarding the hemodynamic parameters , there was a decrease of systolic blood pressure ( −5.6 % ) with the active treatment not observed with placebo ( P < 0.05 vs baseline and placebo ) and endothelial reactivity improved , too ( −13.2 % , P < 0.001 vs baseline ) . Consequently , the estimated 10-year cardiovascular risk score improved by 1.19 % ( SE 0.4 % ) ( P = 0.01 ) in the nutraceutical-treated patients . Conclusion The tested nutraceutical association is able to improve the positive effects of a Mediterranean diet on a large number of CV risk factors and consequently of the estimated CV risk . Trial registration Clinical Trials.gov identifier NCT02492464 . Funding IBSA Farmaceutici BACKGROUND Although modifiable cardiovascular disease risk factors are common , some patients eschew conventional drug treatments in favor of natural alternatives . Pine bark extract , a dietary supplement source of antioxidant oligomeric proanthocyanidin complexes , has multiple putative cardiovascular benefits . Studies published to date about the supplement have notable method ological limitations . METHODS We r and omized 130 individuals with increased cardiovascular disease risk to take 200 mg of a water-based extract of pine bark  ( n = 64 ; Toyo-FVG , Toyo Bio-Pharma , Torrance , California ; Shinyaku Co , Ltd , Saga , Japan ; also marketed as Flavagenol in Japan ) or placebo ( n = 66 ) once per day . Blood pressure , our primary outcome , and other cardiovascular disease risk factors were measured at baseline and at 6 and 12 weeks . Statistical analyses were conducted using regression models . RESULTS Baseline characteristics did not differ between the study groups . Over the 12-week intervention , the sum of systolic and diastolic blood pressures decreased by 1.0 mm Hg ( 95 % confidence interval , -4.2 to 2.1 mm Hg ) in the pine bark extract-treated group and by 1.9 mm Hg ( -5.5 to 1.7 mm Hg ) in the placebo group ( P = .87 ) . Other outcomes were likewise not significantly different , including body mass index , lipid panel measures , liver transaminase test results , lipoprotein cholesterol particle size , and levels of insulin , lipoprotein(a ) , fasting glucose , and high-sensitivity C-reactive protein . There were no subgroups for whom intake of pine bark extract affected cardiovascular disease risk factors . CONCLUSIONS This pine bark extract ( at a dosage of 200 mg/d ) was safe but was not associated with improvement in cardiovascular disease risk factors . Although variations among participants , dosages , and chemical preparations could contribute to different findings compared with past studies , our results are consistent with a general failure of antioxidants to demonstrate cardiovascular benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00425945 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 ® , 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 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 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 
    Output:
    
agent
Therefore , the present meta- analysis does not suggest any significant effect of pycnogenol  on BP
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction There is a growing interest in nutraceuticals improving cardiovascular risk factor levels and related organ damage . Methods This double-blind , placebo-controlled r and omized clinical trial aims to compare the effect of a combined nutraceutical containing red yeast rice ( 10 mg ) , phytosterols ( 800 mg ) , and l-tyrosol ( 5 mg ) on lipid profile , blood pressure , endothelial function , and arterial stiffness in a group of 60 patients with polygenic hypercholesterolemia resistant to Mediterranean diet . Results After 8 weeks of treatment , when compared to the placebo group , the active treated patients experienced a more favorable percentage change in total cholesterol ( −16.3 % vs 9.9 % , P < 0.001 always ) , LDL-C ( −23.4 % vs −13.2 % , P < 0.001 always ) , and hepatic steatosis index ( −2.8 % , P < 0.01 vs −1.8 % , P < 0.05 ) . Moreover , ALT ( −27.7 % , P < 0.001 ) , AST ( −13.8 % , P = 0.004 ) , and serum uric acid ( −12.3 % , P = 0.005 ) were reduced by the tested nutraceutical compound both compared to r and omization and to placebo , which did not affect these parameters ( P < 0.01 for all ) . Regarding the hemodynamic parameters , there was a decrease of systolic blood pressure ( −5.6 % ) with the active treatment not observed with placebo ( P < 0.05 vs baseline and placebo ) and endothelial reactivity improved , too ( −13.2 % , P < 0.001 vs baseline ) . Consequently , the estimated 10-year cardiovascular risk score improved by 1.19 % ( SE 0.4 % ) ( P = 0.01 ) in the nutraceutical-treated patients . Conclusion The tested nutraceutical association is able to improve the positive effects of a Mediterranean diet on a large number of CV risk factors and consequently of the estimated CV risk . Trial registration Clinical Trials.gov identifier NCT02492464 . Funding IBSA Farmaceutici BACKGROUND Although modifiable cardiovascular disease risk factors are common , some patients eschew conventional drug treatments in favor of natural alternatives . Pine bark extract , a dietary supplement source of antioxidant oligomeric proanthocyanidin complexes , has multiple putative cardiovascular benefits . Studies published to date about the supplement have notable method ological limitations . METHODS We r and omized 130 individuals with increased cardiovascular disease risk to take 200 mg of a water-based extract of pine bark  ( n = 64 ; Toyo-FVG , Toyo Bio-Pharma , Torrance , California ; Shinyaku Co , Ltd , Saga , Japan ; also marketed as Flavagenol in Japan ) or placebo ( n = 66 ) once per day . Blood pressure , our primary outcome , and other cardiovascular disease risk factors were measured at baseline and at 6 and 12 weeks . Statistical analyses were conducted using regression models . RESULTS Baseline characteristics did not differ between the study groups . Over the 12-week intervention , the sum of systolic and diastolic blood pressures decreased by 1.0 mm Hg ( 95 % confidence interval , -4.2 to 2.1 mm Hg ) in the pine bark extract-treated group and by 1.9 mm Hg ( -5.5 to 1.7 mm Hg ) in the placebo group ( P = .87 ) . Other outcomes were likewise not significantly different , including body mass index , lipid panel measures , liver transaminase test results , lipoprotein cholesterol particle size , and levels of insulin , lipoprotein(a ) , fasting glucose , and high-sensitivity C-reactive protein . There were no subgroups for whom intake of pine bark extract affected cardiovascular disease risk factors . CONCLUSIONS This pine bark extract ( at a dosage of 200 mg/d ) was safe but was not associated with improvement in cardiovascular disease risk factors . Although variations among participants , dosages , and chemical preparations could contribute to different findings compared with past studies , our results are consistent with a general failure of antioxidants to demonstrate cardiovascular benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00425945 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 ® , 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 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 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 
    Output:
    