***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: Evidence suggests that flavonoid-containing diets reduce cardiovascular risk , but the mechanisms responsible are unclear . In the present study , we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD ( coronary artery disease ) . Forty subjects ( 61+/-8 years ; 30 male ) with CAD were recruited to a 6-week r and omized double-blind placebo-controlled study . Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily ( total flavanols , 444 mg/day ) or matching isocaloric placebos daily ( total flavanols , 19.6 mg/day ) for 6 weeks . Brachial artery FMD ( flow-mediated dilation ) and SAC ( systemic arterial compliance ) were assessed at baseline , 90 min following the first beverage and after 3 and 6 weeks of daily consumption . Soluble cellular adhesion molecules and FBF ( forearm blood flow ) responses to ACh ( acetylcholine chloride ; 3 - 30 microg/min ) and SNP ( sodium nitroprusside ; 0.3 - 3 microg/min ) infusions , forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks . FMD , SAC and FBF responses did not differ between groups at baseline . No acute or chronic changes in FMD or SAC were seen in either group . No difference in soluble cellular adhesion molecules , FBF responses to ischaemia , exercise , SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks . These data suggest that over a 6-week period , flavanol-rich cocoa does not modify vascular function in patients with established CAD AIMS Flavanol-rich chocolate ( FRC ) is beneficial for vascular and platelet function by increasing nitric oxide bioavailability and decreasing oxidative stress . Congestive heart failure ( CHF ) is characterized by impaired endothelial and increased platelet reactivity . As statins are ineffective in CHF , alternative therapies are a clinical need . We therefore investigated whether FRC might improve cardiovascular function in patients with CHF . METHODS AND RESULTS Twenty patients with CHF were enrolled in a double-blind , r and omized placebo-controlled trial , comparing the effect of commercially available FRC with cocoa-liquor-free control chocolate ( CC ) on endothelial and platelet function in the short term ( 2 h after ingestion of a chocolate bar ) and long term ( 4 weeks , two chocolate bars/day ) . Endothelial function was assessed non-invasively by flow-mediated vasodilatation of the brachial artery . Flow-mediated vasodilatation significantly improved from 4.98 ± 1.95 to 5.98 ± 2.32 % ( P = 0.045 and 0.02 for between-group changes ) 2h after intake of FRC to 6.86 ± 1.76 % after 4 weeks of daily intake ( P = 0.03 and 0.004 for between groups ) . No effect on endothelial-independent vasodilatation was observed . Platelet adhesion significantly decreased from 3.9 ± 1.3 to 3.0 ± 1.3 % ( P = 0.03 and 0.05 for between groups ) 2 h after FRC , an effect that was not sustained at 2 and 4 weeks . Cocoa-liquor-free CC had no effect , either on endothelial function or on platelet function . Blood pressure and heart rate did not change in either group . CONCLUSION Flavanol-rich chocolate acutely improves vascular function in patients with CHF . A sustained effect was seen after daily consumption over a 4-week period , even after 12 h abstinence . These beneficial effects were paralleled by an inhibition of platelet function in the presence of FRC only The consumption of cocoa and dark chocolate is associated with a lower risk of CVD , and improvements in endothelial function may mediate this relationship . Less is known about the effects of cocoa/chocolate on the augmentation index ( AI ) , a measure of vascular stiffness and vascular tone in the peripheral arterioles . We enrolled thirty middle-aged , overweight adults in a r and omised , placebo-controlled , 4-week , cross-over study . During the active treatment ( cocoa ) period , the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage ( total cocoa = 22 g/d , total flavanols ( TF ) = 814 mg/d ) . Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar ( TF = 3 mg/d ) . Treatments were matched for total fat , saturated fat , carbohydrates and protein . The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6 % ( + 2 mm ) and basal blood flow volume by 22 % . Substantial decreases in the AI , a measure of arterial stiffness , were observed in only women . Flow-mediated dilation and the reactive hyperaemia index remained unchanged . The consumption of cocoa had no effect on fasting blood measures , while the control treatment increased fasting insulin concentration and insulin resistance ( P= 0·01 ) . Fasting blood pressure ( BP ) remained unchanged , although the acute consumption of cocoa  increased resting BP by 4 mmHg . In summary , the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women Cocoa flavanol ( CF ) intake improves endothelial function in patients with cardiovascular risk factors and disease . We investigated the effects of CF on surrogate markers of cardiovascular health in low risk , healthy , middle-aged individuals without history , signs or symptoms of CVD . In a 1-month , open-label , one-armed pilot study , bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function ( measured as flow-mediated vasodilation ( FMD ) ) that plateaued after 2 weeks . Subsequently , in a r and omised , controlled , double-masked , parallel-group dietary intervention trial ( Clinical trials.gov : NCT01799005 ) , 100 healthy , middle-aged ( 35–60 years ) men and women consumed either the CF-containing drink ( 450 mg ) or a nutrient-matched CF-free control bi-daily for 1 month . The primary end point was FMD . Secondary end points included plasma lipids and blood pressure , thus enabling the calculation of Framingham Risk Scores and pulse wave velocity . At 1 month , CF increased FMD over control by 1·2 % ( 95 % CI 1·0 , 1·4 % ) . CF decreased systolic and diastolic blood pressure by 4·4 mmHg ( 95 % CI 7·9 , 0·9 mmHg ) and 3·9 mmHg ( 95 % CI 6·7 , 0·9 mmHg ) , pulse wave velocity by 0·4 m/s ( 95 % CI 0·8 , 0·04 m/s ) , total cholesterol by 0·20 mmol/l ( 95 % CI 0·39 , 0·01 mmol/l ) and LDL-cholesterol by 0·17 mmol/l ( 95 % CI 0·32 , 0·02 mmol/l ) , whereas HDL-cholesterol increased by 0·10 mmol/l ( 95 % CI 0·04 , 0·17 mmol/l ) . By applying the Framingham Risk Score  , CF predicted a significant lowering of 10-year risk for CHD , myocardial infa rct ion , CVD , death from CHD and CVD . In healthy individuals , regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk , demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects Consumption of flavanol-rich dark chocolate ( DC ) has been shown to decrease blood pressure ( BP ) and insulin resistance in healthy subjects , suggesting similar benefits in patients with essential hypertension ( EH ) . Therefore , we tested the effect of DC on 24-hour ambulatory BP , flow-mediated dilation ( FMD ) , and oral glucose tolerance tests ( OGTTs ) in patients with EH . After a 7-day chocolate-free run-in phase , 20 never-treated , grade I patients with EH ( 10 males ; 43.7±7.8 years ) were r and omized to receive either 100 g per day DC ( containing 88 mg flavanols ) or 90 g per day flavanol-free white chocolate ( WC ) in an isocaloric manner for 15 days . After a second 7-day chocolate-free period , patients were crossed over to the other  treatment . Noninvasive 24-hour ambulatory BP , FMD , OGTT , serum cholesterol , and markers of vascular inflammation were evaluated at the end of each treatment . The homeostasis model assessment of insulin resistance ( HOMA-IR ) , quantitative insulin sensitivity check index ( QUICKI ) , and insulin sensitivity index ( ISI ) were calculated from OGTT values . Ambulatory BP decreased  after DC ( 24-hour systolic BP −11.9±7.7 mm Hg , P<0.0001 ; 24-hour diastolic BP −8.5±5.0 mm Hg , P<0.0001 ) but not WC . DC but not WC decreased HOMA-IR ( P<0.0001 ) , but it improved QUICKI , ISI , and FMD . DC also decreased serum LDL cholesterol ( from 3.4±0.5 to 3.0±0.6 mmol/L ; P<0.05 ) . In  summary , DC  decreased BP and serum LDL cholesterol , improved FMD , and ameliorated insulin sensitivity in hypertensives . These results suggest that , while balancing total calorie intake , flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH To assess whether antioxidant , anti-inflammatory and other cardio-protective effects attributed to cocoa are achieved when regularly consuming moderate amounts of a flavanol-rich soluble cocoa product , a non-r and omized , controlled , crossover , free-living study was carried out in healthy ( n = 24 ; 25.9 ± 5.6 years ) and moderately hypercholesterolemic ( 200 - 240 mg dL(-1 ) ; n = 20 ; 30.0 ± 10.3 years ) volunteers . Participants consumed two servings per day ( 7.5 g per serving ) of a soluble cocoa product ( providing 45.3 mg flavanols per day ) in milk , which was compared with consuming only milk during a 4 week period . The effects on systolic and diastolic blood pressure and heart rate were determined , as well as on serum lipid and lipoprotein profiles , interleukins (IL)-1β , IL-6 , IL-8 , IL-10 , tumor necrosis factor-α ( TNF-α ) , monocyte chemoattractant protein-1 ( MCP-1 ) , vascular ( VCAM-1 ) and intercellular cell adhesion molecules ( ICAM-1 ) , serum malondialdehyde ( MDA ) , carbonyl groups ( CG ) , ferric reducing/antioxidant power ( FRAP ) , oxygen radical absorbance capacity ( ORAC ) , and free radical scavenging capacity ( ABTS ) . During the study , the volunteers ' diets and physical activity were also evaluated , as well as any changes in weight , skin folds , circumferences and related anthropometric parameters . Cocoa and certain polyphenol-rich fruits and vegetables and their derivatives were restricted . After consuming the cocoa product positive effects were observed such as an increase in serum HDL-C ( p < 0.001 ) and dietary fiber intake ( p = 0.050 ) , whereas IL-10 decreased ( p = 0.022 ) . Other cardiovascular-related biomarkers and anthropometric parameters were unaffected . We have therefore concluded that regular consumption of this cocoa product in a Spanish-Mediterranean diet may protect against cardiovascular disease in healthy and hypercholesterolemic subjects without producing any weight gain or other anthropometric changes Increased vascular stiffness , endothelial dysfunction , and isolated systolic hypertension are hallmarks of vascular aging . Regular cocoa flavanol ( CF ) intake can improve vascular function in healthy young and elderly at-risk individuals . However , the mechanisms underlying CF bioactivity remain largely unknown . We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history , signs , or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging . In a r and omized , controlled , double-masked , parallel-group dietary intervention trial , 22 young ( < 35 years ) and 20 elderly ( 50–80 year ) healthy , male non-smokers consumed either a CF-cont 
    Output:
    
The control group received either a flavanol-free product ( n = 26 treatment comparisons ) or a low-flavanol-containing cocoa powder ( range 6.4 to 88 mg flavanols ( mean = 55 mg , 13 treatment comparisons ; 259 mg , 1 trial).Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration ( mean nine weeks):Mean difference systolic blood pressure ( SBP ) ( 95 % confidence interval ( CI ) : -1.76 ( -3.09 to -0.43 ) mmHg , P = 0.009 , n = 40 treatment comparisons , 1804 participants ; Mean difference diastolic blood pressure ( DBP ) ( 95 % CI ) : -1.76 ( -2.57 to -0.94 ) mmHg , P < 0.001 , n = 39 treatment comparisons , 1772 participants .Baseline blood pressure may play a role in the effect of cocoa on blood pressure .
While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people ( n = 9 treatment comparisons , 401 participants ) , and tended to be lowered in prehypertensive people ( n= 8 treatment comparisons , 340 participants ) , there was no significant difference in normotensive people ( n = 23 treatment comparisons , 1063 participants ) ; however , the test for subgroup differences was of borderline significance ( P = 0.08 ; I2 = 60 % ) , requiring further research to confirm the findings .Subgroup meta- analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials , albeit statistically not significant .
Subgroup analysis by type of control ( flavanol-free versus low-flavanol control ) did not reveal a significant difference .
This review provides moderate- quality evidence that flavanol-rich chocolate and cocoa products cause a small ( 2 mmHg ) blood pressure-lowering effect in mainly healthy adults in the short term .
These findings are limited by the heterogeneity between trials , which could not be explained by prespecified subgroup analyses , including blinding , flavanol content of the control groups , age of participants , or study duration .