title: Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile No beneficial effects of pine bark extract on cardiovascular disease risk factors. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Normalization of cardiovascular risk factors in peri-menopausal women with Pycnogenol®. Kidney Flow and Function in Hypertension: Protective Effects of Pycnogenol in Hypertensive Participants—A Controlled Study
abstract: 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 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
target: Present systematic review and meta- analysis suggested Pycnogenol consumption can decrease the level of CRP and have anti-inflammatory effect .
background: Pycnogenol is a st and ardized extract from the bark of the French maritime pine .
  The aim of the present systematic review and meta- analysis was to clarify the effect of Pycnogenol supplementation on C-reactive protein ( CRP ) concentration .