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: 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 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 CONTEXT A prior national survey documented the high prevalence and costs of  alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS  Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient There is evidence from several studies that supplementation with French maritime pine bark extract ( Pycnogenol ) improves inflammatory symptoms in vivo . However , the molecular pharmacological basis for the observed effects has not been fully uncovered yet . Direct inhibitory effects of plant extracts or components upon cyclooxygenase ( COX ) activity have been repeatedly reported , but the question remained whether sufficiently high in vivo concentrations of bioactive compounds could be achieved in humans . The purpose of the present study was to determine a possible inhibition of the enzymatic activity of COX-1 and COX-2 by serum sample s of human volunteers after intake of French maritime pine bark extract .  This methodology considered that the serum sample s would contain any bioavailable active principle . Therefore , we obtained blood sample s before and after 5 days administration of 200 mg  Pycnogenol to five healthy humans . The plasma moderately inhibited both COX-1 and COX-2 activities ex vivo . In a second approach , 10 volunteers received a single dose of 300 mg Pycnogenol . Only 30 min after ingestion of the pine bark extract the serum sample s induced a statistically significant increase in the inhibition of both COX-1 ( P < 0.02 ) and COX-2 ( P < 0.002 ) . This suggests a strikingly rapid bioavailability of bioeffective compounds after oral intake of the extract . Thus , we provide evidence that Pycnogenol exerts effects by inhibition of eicosanoid generating enzymes which is consistent with reported clinical anti-inflammatory and platelet inhibitory effects in vivo . The next challenge is to identify the active principle(s ) that are rapidly bioavailable in human plasma 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 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 8 
    Output:
    
agent
Present systematic review and meta- analysis suggested Pycnogenol consumption can decrease the level of CRP and have anti-inflammatory effect .
***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: 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 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 CONTEXT A prior national survey documented the high prevalence and costs of  alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS  Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient There is evidence from several studies that supplementation with French maritime pine bark extract ( Pycnogenol ) improves inflammatory symptoms in vivo . However , the molecular pharmacological basis for the observed effects has not been fully uncovered yet . Direct inhibitory effects of plant extracts or components upon cyclooxygenase ( COX ) activity have been repeatedly reported , but the question remained whether sufficiently high in vivo concentrations of bioactive compounds could be achieved in humans . The purpose of the present study was to determine a possible inhibition of the enzymatic activity of COX-1 and COX-2 by serum sample s of human volunteers after intake of French maritime pine bark extract .  This methodology considered that the serum sample s would contain any bioavailable active principle . Therefore , we obtained blood sample s before and after 5 days administration of 200 mg  Pycnogenol to five healthy humans . The plasma moderately inhibited both COX-1 and COX-2 activities ex vivo . In a second approach , 10 volunteers received a single dose of 300 mg Pycnogenol . Only 30 min after ingestion of the pine bark extract the serum sample s induced a statistically significant increase in the inhibition of both COX-1 ( P < 0.02 ) and COX-2 ( P < 0.002 ) . This suggests a strikingly rapid bioavailability of bioeffective compounds after oral intake of the extract . Thus , we provide evidence that Pycnogenol exerts effects by inhibition of eicosanoid generating enzymes which is consistent with reported clinical anti-inflammatory and platelet inhibitory effects in vivo . The next challenge is to identify the active principle(s ) that are rapidly bioavailable in human plasma 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 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 8 
    Output:
    