Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different levels of cocoa powder. Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults. Estimated dietary intake and major food sources of polyphenols in the Polish arm of the HAPIEE study☆ High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome Supplementation of the Pure Flavonoids Epicatechin and Quercetin Affects Some Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial. Total polyphenol intake, polyphenol subtypes and incidence of cardiovascular disease: The SUN cohort study. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascular disease. Chocolate and Prevention of Cardiovascular Disease: A Systematic Review Chronic Consumption of Flavanol-rich Cocoa Improves Endothelial Function and Decreases Vascular Cell Adhesion Molecule in Hypercholesterolemic Postmenopausal Women Flavonoid rich dark cocoa may improve fatigue in people with multiple sclerosis, yet has no effect on glycaemic response: An exploratory trial. Flavonoid-Rich Dark Chocolate Improves Endothelial Function and Increases Plasma Epicatechin Concentrations in Healthy Adults Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Realistic intake of a flavanol-rich soluble cocoa product increases HDL-cholesterol without inducing anthropometric changes in healthy and moderately hypercholesterolemic subjects. Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals Effects on Peripheral and Central Blood Pressure of Cocoa With Natural or High-Dose Theobromine: A Randomized, Double-Blind Crossover Trial
BACKGROUND Flavonoids are polyphenolic compounds of plant origin with antioxidant effects . Flavonoids inhibit LDL oxidation and reduce thrombotic tendency in vitro . Little is known about how cocoa powder and dark chocolate , rich sources of polyphenols , affect these cardiovascular disease risk factors . OBJECTIVE We evaluated the effects of a diet high in cocoa powder and dark chocolate ( CP-DC diet ) on LDL oxidative susceptibility , serum total antioxidant capacity , and urinary prostagl and in concentrations . DESIGN We conducted a r and omized , 2-period , crossover study in 23 healthy subjects fed 2 diets : an average American diet ( AAD ) controlled for fiber , caffeine , and theobromine and an AAD supplemented with 22 g cocoa powder and 16 g dark chocolate ( CP-DC diet ) , providing approximately 466 mg procyanidins/d . RESULTS LDL oxidation lag time was approximately 8 % greater ( P = 0.01 ) after the CP-DC diet than after the AAD .  Serum total antioxidant capacity measured by oxygen radical absorbance capacity was approximately 4 % greater ( P = 0.04 ) after the CP-DC diet than after the AAD and was positively correlated with LDL oxidation lag time ( r = 0.32 , P = 0.03 ) . HDL cholesterol was 4 % greater after the CP-DC diet ( P = 0.02 ) than after the AAD ; however , LDL-HDL ratios were not significantly different . Twenty-four-hour urinary excretion of thromboxane B(2 ) and 6-keto-prostagl and in F(1)(alpha ) and the ratio of the 2 compounds were not significantly different between the 2 diets . CONCLUSION Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility , increasing serum total antioxidant capacity and HDL-cholesterol concentrations , and not adversely affecting prostagl and ins Background Consumption of flavonoid-rich beverages , including tea and red wine , has been associated with a reduction in coronary events , but the physiological mechanism remains obscure . Cocoa can contain extraordinary concentrations of flavanols , a flavonoid subclass shown to activate nitric oxide synthase in vitro . Objective To test the hypothesis that flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in humans . Design The study prospect ively assessed the effects of Flavanol-rich cocoa , using both time and beverage controls . Participants were blinded to intervention ; the endpoint was objective and blinded . Methods Pulse wave amplitude was measured on the finger in 27 healthy people with a volume-sensitive vali date d calibrated plethysmograph , before and after 5 days of consumption of Flavanol-rich cocoa [ 821 mg of flavanols/day , quantitated as (−)-epicatechin , (+)-catechin , and related procyanidin oligomers ] . The specific nitric oxide synthase inhibitor , NG-nitro-l-arginine methyl ester ( l-NAME ) was infused intravenously on day 1 , before cocoa , and on day 5 , after an acute ingestion of cocoa . Results Four days of flavanol-rich cocoa induced consistent and striking peripheral vasodilation ( P = 0.009 ) . On day 5 , pulse wave amplitude exhibited a large additional acute response to cocoa ( P = 0.01 ) . l-NAME completely reversed this vasodilation ( P = 0.004 ) . In addition , intake of flavanol-rich cocoa augmented the vasodilator response to ischemia . Flavanol-poor cocoa induced much smaller responses ( P = 0.005 ) , and none was induced in the time-control study . Flavanol-rich cocoa also amplified the systemic pressor effects of l-NAME ( P = 0.005 ) . Conclusion In healthy humans , flavanol-rich cocoa induced vasodilation via activation of the nitric oxide system , providing a plausible mechanism for the protection that flavanol-rich foods induce against coronary events Cocoa powder is rich in polyphenols , such as catechins and procyanidins , and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis . Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder ( 13 , 19.5 , and 26 g/d ) in normocholesterolemic and mildly hypercholesterolemic humans . In this comparative , double-blind study , we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds ( placebo-cocoa group ) or 3 levels of cocoa powder containing high-polyphenolic compounds ( 13 , 19.5 , and 26 g/d for low- , middle- , and high-cocoa groups , respectively ) for 4 wk . The test powders were consumed as a beverage after the addition of hot water , twice each day . Blood sample s were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids . Plasma oxidized LDL concentrations decreased in the low- , middle- , and high-cocoa groups compared with baseline . A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of > or = 3.23 mmol/L at baseline . In these subjects , plasma LDL cholesterol , oxidized LDL , and apo B concentrations decreased , and the plasma HDL cholesterol concentration increased , relative to baseline in the low- , middle- , and high-cocoa groups . The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol , an elevation in HDL cholesterol , and the suppression of oxidized LDL 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 CONTEXT Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies . Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure ( BP ) due to the action of the cocoa polyphenols , but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear . OBJECTIVE To determine effects of low doses of polyphenol-rich dark chocolate on BP . DESIGN , SETTING , AND PARTICIPANTS R and omized , controlled , investigator-blinded , parallel-group trial involving 44 adults aged 56 through 73 years ( 24 women , 20 men ) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors . The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006 . INTERVENTION Participants were r and omly assigned to receive for 18 weeks either 6.3 g ( 30 kcal ) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate . MAIN OUTCOME MEASURES Primary outcome measure was the change in BP after 18 weeks . Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide ( S-nitrosoglutathione ) and oxidative stress ( 8-isoprostane ) , and bioavailability of cocoa polyphenols . RESULTS From baseline to 18 weeks , dark chocolate intake reduced mean ( SD ) systolic BP by -2.9 ( 1.6 ) mm Hg ( P < .001 ) and diastolic BP by -1.9 ( 1.0 ) mm Hg ( P < .001 ) without changes in body weight , plasma levels of lipids , glucose , and 8-isoprostane . Hypertension prevalence declined from 86 % to 68 % . The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 ( 0.12 ) nmol/L ( P < .001 ) , and a dark chocolate dose result ed in the appearance of cocoa phenols in plasma . White chocolate intake caused no changes in BP or plasma biomarkers . CONCLUSIONS Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00421499 An inverse relation exists between intake of flavonoid-rich foods , such as cocoa , and cardiovascular-related mortality . Favorable effects of flavonoids on the endothelium may underlie these associations . We performed a r and omized , double-blind , placebo-controlled study to test the hypothesis that acute cocoa ingestion dose dependently increases endothelium-dependent vasodilation , as measured by an increase in brachial artery flow-mediated dilation ( FMD ) , in healthy older adults . Measurements were obtained before ( preingestion ) and after ( 1- and 2-h postingestion ) ingestion of 0 ( placebo ) , 2 , 5 , 13 , and 26 g of cocoa in 23 adults ( 63 ± 2 yr old , mean ± SE ) . Changes in brachial artery FMD 1- and 2-h postingestion compared with preingestion were used to determine the effects of cocoa . FMD was unchanged 1 ( Δ-0.3 ± 0.2%)- and 2-h ( Δ0.1 ± 0.1 % ) after placebo ( 0 g cocoa ) . In contrast , FMD increased both 1-h postingestion ( 2 g cocoa Δ0.0 ± 0.2 % , 5 g cocoa Δ0.8 ± 0.3 % , 13 g cocoa Δ1.0 ± 0.3 % , and 26 g cocoa Δ1.6 ± 0.3 % : P < 0.05 compared with placebo for 5 , 13 , and 26 g cocoa ) and 2-h postingestion ( 2 g cocoa Δ0.5 ± 0.3 % , 5 g cocoa Δ1.0 ± 0.3 % , 13 g cocoa Δ1.4 ± 0.2 % , and 26 g cocoa Δ2.5 ± 0.4 % : P < 0.05 compared with placebo for 5 , 13 , and 26 g cocoa ) on the other study days . A serum marker of cocoa ingestion ( total epicatechin ) correlated with increased FMD 1- and 2-h postingestion ( r = 0.44 - 0.48 ; both P < 0.05 ) . Collectively , these results indicate that acute cocoa ingestion dose dependently increases brachial artery FMD in healthy older humans . These responses may help to explain associations between flavonoid intake and cardiovascular-related mortality in humans Objective The aim of this study was to estimate the intake of known individual polyphenols and their major dietary sources in the Polish arm of the HAPIEE ( Health , Alcohol and Psychosocial factors In Eastern Europe ) study . Methods A total of 10,477 r and om sample ( 45–69 y ) of urban population of Krakow , Pol and , completed a vali date d 148-item food frequency question naire .  Polyphenol intake  was calculated by matching food consumption data with the recently developed Phenol-Explorer data base . Results The mean intake of polyphenols  was 1756.5 ± 695.8 mg/d ( median = 1662.5 mg/d ) . The main polyphenol groups were flavonoids ( 897 mg/d ) and phenolic acids ( 800 mg/d ) . A total of 347 polyphenols from 19 polyphenol subclasses were found . The individual compounds with the highest intakes were isomers of chlorogenic acid ( i.e. , 5-caffeoylquinic acid and 4-caffeoylquinic acid ) among hydroxycinnamic acids ( average intake 150 mg/d ) , that largely originated from coffee , and compounds belonging to the catechin chemical family ( i.e. , [+]-gallocatechin , [-]-epigallocatechin 3-O-gallate , and [-]-epicatechin ) among flavanols ( average intake 50 mg/d ) , that mostly originated from tea and cocoa products . Conclusions The current study provides the most up date d data for  individual polyphenols  intake in the diet of a well-established nutritional cohort . These findings will be useful to assess potential beneficial role on health of specific foods with high polyphenol content and characterize the effects of individual phenolic compounds Background Chocolate is rich in flavonoids that have been shown to be of benefit in disparate conditions including cardiovascular disease and cancer . The effect of polyphenol rich chocolate in subjects with chronic fatigue syndrome ( CFS ) has not been studied previously . Methods We conducted a double blinded , r and omised , clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate ( HCL/PR ) in comparison to simulated iso-calorific chocolate ( cocoa liquor free/low polyphenols(CLF/LP ) ) on fatigue and residual function in subjects with chronic fatigue syndrome . Subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled . Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP , with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate . Results Ten subjects were enrolled in the study . The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [ median ( range ) Exact Sig . ( 2-tailed ) ] [ 33 ( 25 - 38 ) vs. 21.5 ( 6 - 35 ) 0.01 ] , but that deteriorated significantly when subjects were given simulated iso-calorific chocolate ( CLF/CP ) [ 28.5 ( 17 - 20 ) vs. 34.5 ( 13 - 26 ) 0.03 ] . The residual function , as assessed by the London H and icap scale , also improved significantly after the HCL/PR arm [ 0.49 ( 0.33 - 0.62 ) vs. 0.64 ( 0.44 - 0.83 ) 0.01 ] and deteriorated after iso-calorific chocolate [ 00.44 ( 0.43 - 0.68 ) vs. 0.36 ( 0.33 - 0.62)0.03 ] . Likewise the Hospital Anxiety and Depression score also improved after the HCL/PR arm , but deteriorated after CLF/CP . Mean weight remained unchanged throughout the trial . Conclusion This study suggests that HCL/PR chocolate may improve symptoms in subjects with chronic fatigue syndrome BACKGROUND Consumption of flavonoid-rich foods such as cocoa and tea may reduce cardiovascular disease risk . The flavonoids epicatechin ( in cocoa and tea ) and quercetin ( in tea ) probably play a role by reducing endothelial dysfunction and inflammation , 2 main determinants of atherosclerosis . OBJECTIVE We studied the effects of supplementation of pure epicatechin and quercetin on biomarkers of endothelial dysfunction and inflammation . METHODS Thirty-seven apparently healthy (pre)hypertensive men and women ( 40 - 80 y ) participated in a r and omized , double-blind , placebo-controlled crossover trial . Participants ingested (-)-epicatechin ( 100 mg/d ) , quercetin-3-glucoside ( 160 mg/d ) , or placebo capsules for a period of 4 wk , in r and om order . Plasma biomarkers of endothelial dysfunction and inflammation were measured at the start and end of each 4-wk intervention period . The differences in changes over time between the intervention and placebo periods ( Δintervention - Δplacebo ) were calculated and tested with a linear mixed model for repeated measures . RESULTS Epicatechin  changed Δepicatechin - Δplacebo for soluble endothelial selectin ( sE-selectin ) by -7.7 ng/mL ( 95 % CI : -14.5 , -0.83 ; P = 0.03 ) but did not significantly change this difference ( -0.30 ; 95 % CI : -0.61 , 0.01 ; P = 0.06 ) for the z score for endothelial dysfunction . Quercetin changed Δquercetin - Δplacebo for sE-selectin by -7.4 ng/mL ( 95 % CI : -14.3 , -0.56 ; P = 0.03 ) , that for IL-1β by -0.23 pg/mL ( 95 % CI : -0.40 , -0.06 ; P = 0.009 ) , and that for the z score for inflammation by -0.33 ( 95 % CI : -0.60 , -0.05 ; P = 0.02 ) . CONCLUSIONS In (pre)hypertensive men and women , epicatechin may contribute to the cardioprotective effects of cocoa and tea through improvements in endothelial function . Quercetin may contribute to the cardioprotective effects of tea possibly by improving endothelial function and reducing inflammation . This trial was registered at clinical trials.gov as NCT01691404 BACKGROUND AND AIMS Polyphenol-rich diets have been associated with reduced risk of cardiovascular disease ( CVD ) . However , few prospect i ve epidemiological studies have examined the relationship between classes of ingested polyphenols and risk of CVD . Our aim was to evaluate the association between polyphenol intake and risk of major cardiovascular events in a prospect i ve Spanish cohort . METHODS AND RESULTS We included 17,065 university graduates ( 60.7 % women , mean age : 37.2 years , age range : 20 - 89 ) followed-up for a mean of 10.1 years .  Polyphenol intake was assessed at baseline using a vali date d semi-quantitative 136-item food frequency question naire and matching food consumption data with the Phenol-Explorer data base . Cox proportional hazards models were used to estimate the adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) for incident cardiovascular events ( myocardial infa rct ion , stroke or cardiovascular death ) . Cherries , chocolate , coffee , apples , and olives were the major sources of variability in polyphenol intake . Participants with higher flavonoids intake ( fifth quintile ) had a 47 % lower incidence of cardiovascular events compared to those in the lowest quintile ( HR : 0.53 , 95 % CI : 0.29 - 0.98 ; P for trend = 0.09 ) after adjusting for potential confounders . The results were non-significant for other polyphenol types . CONCLUSION The intake of flavonoids showed an inverse association with risk of cardiovascular events in a prospect i ve cohort of Spanish middle-aged adult university graduates . REGISTRATION NUMBER FOR CLINICAL TRIALS NCT02669602 in Clinical Trials BACKGROUND Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis . OBJECTIVE We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects . DESIGN Twenty-five subjects were r and omly assigned to ingest either 12 g sugar/d ( control group ) or 26 g cocoa powder and 12 g sugar/d ( cocoa group ) for 12 wk . Blood sample s were collected before the study and 12 wk after intake of the test drinks . Plasma lipids , LDL oxidative susceptibility , and urinary oxidative stress markers were measured . RESULTS At 12 wk , we measured a 9 % prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group . This prolongation in the cocoa group was significantly greater than the reduction measured in the control group ( -13 % ) . A significantly greater increase in plasma HDL cholesterol ( 24 % ) was observed in the cocoa group than in the control group ( 5 % ) . A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL . At 12 wk , there was a 24 % reduction in dityrosine from baseline concentrations in the cocoa group . This reduction in the cocoa group was significantly greater than the reduction in the control group ( -1 % ) . CONCLUSION It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol OBJECTIVES This study was design ed to assess the effect of flavanol-rich food on the circulating pool of bioactive nitric oxide ( NO ) and endothelial dysfunction in smokers . BACKGROUND Studies suggest that smoking-related vascular disease is caused by impaired NO synthesis and that diets rich in flavanols can increase bioactive NO in plasma . METHODS In smokers ( n = 11 ) , the effects of flavanol-rich cocoa on circulating NO species in plasma ( RXNO ) measured by reductive gas-phase chemiluminescence and endothelial function as assessed by flow-mediated dilation ( FMD ) were characterized in a dose-finding study orally administering cocoa containing 88 to 370 mg flavanols and in a r and omized double-blind crossover study using 100 ml cocoa drink with high ( 176 to 185 mg ) or low ( < 11 mg ) flavanol content on two separate days . In addition to cocoa drink , ascorbic acid and NO-synthase inhibitor L-NMMA ( n = 4 ) were applied . RESULTS There were significant increases in RXNO ( 21 + /- 3 nmol/l to 29 + /- 5 nmol/l ) and FMD ( 4.5 + /- 0.8 % to 6.9 + /- 0.9 % , each p < 0.05 ) at 2 h after ingestion of 176 to 185 mg flavanols , a dose potentially exerting maximal effects . These changes correlated with increases in flavanol metabolites . Cocoa-associated increases in RXNO and FMD were reversed by L-NMMA . Ascorbic acid had no effect . CONCLUSIONS The circulating pool of bioactive NO and endothelium-dependent vasodilation is acutely increased in smokers following the oral ingestion of a flavanol-rich cocoa drink . The increase in circulating NO pool may contribute to beneficial vascular health effects of flavanol-rich food Rationale There has recently been increasing interest in the potential of flavanols , plant-derived compounds found in foods such as fruit and vegetables , to ameliorate  age-related cognitive decline .  Research suggests that cocoa flavanols improve memory and learning , possibly as a result of their anti-inflammatory and neuroprotective effects . These effects may be mediated by increased cerebral blood flow ( CBF ) , thus , stimulating neuronal function . Objectives The present study employed arterial spin labelling functional magnetic resonance imaging to explore the effect of a single acute dose of cocoa flavanols on regional CBF . Methods CBF was measured pre- and post-consumption of low ( 23 mg ) or high ( 494 mg ) 330 ml equicaloric flavanol drinks matched for caffeine , theobromine , taste and appearance according to a r and omized counterbalanced crossover double-blind design in eight males and ten females , aged 50–65 years .  Changes in perfusion from pre- to post-consumption were calculated as a function of each drink . Results Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink , particularly in the anterior cingulate cortex and the central opercular cortex of the parietal lobe . Conclusions Consumption of cocoa flavanol improves regional cerebral perfusion in older adults . This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance OBJECTIVES Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients . BACKGROUND Even in fully medicated diabetic patients , overall prognosis is unfavorable due to deteriorated cardiovascular function . Based on epidemiological data , diets rich in flavanols are associated with a reduced cardiovascular risk . METHODS In a feasibility study with 10 diabetic patients , we assessed vascular function as flow-mediated dilation ( FMD ) of the brachial artery , plasma levels of flavanol metabolites , and tolerability after an acute , single-dose ingestion of cocoa , containing increasing concentrations of flavanols ( 75 , 371 , and 963 mg ) . In a subsequent efficacy study , changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day , thrice-daily dietary intervention with either flavanol-rich cocoa ( 321 mg flavanols per dose ) or a nutrient-matched control ( 25 mg flavanols per dose ) . Both studies were undertaken in a r and omized , double-masked fashion . Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites , respectively . RESULTS A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD ( at 2 h : from 3.7 + /- 0.2 % to 5.5 + /- 0.4 % , p < 0.001 ) . A 30-day , thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30 % ( p < 0.0001 ) , while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study . Treatment was well tolerated without evidence of tachyphylaxia . Endothelium-independent responses , blood pressure , heart rate , and glycemic control were unaffected . CONCLUSIONS Diets rich in flavanols reverse vascular dysfunction in diabetes , highlighting therapeutic potentials in cardiovascular disease BACKGROUND AND AIMS Epidemiological studies suggest that regular consumption of cocoa-containing products may confer cardiovascular protection , reducing the risk of coronary heart disease ( CHD ) . However , studies on the effects of cocoa on different cardiovascular risk factors are still scarce . The aim of this study was too evaluate the effects of chronic cocoa consumption on lipid profile , oxidized low-density lipoprotein ( oxLDL ) particles and plasma antioxidant vitamin concentrations in high-risk patients . METHODS AND RESULTS Forty-two high-risk volunteers ( 19 men and 23 women , mean age 69.7 ± 11.5 years ) were included in a r and omized , crossover feeding trial . All received 40 g of cocoa powder with 500 mL of skimmed milk/day(C + M ) or only 500 mL/day of skimmed milk ( M ) for 4 weeks in a r and om order . Before and after each intervention period , plasma lipids , oxLDL and antioxidant vitamin concentrations were measured , as well as urinary cocoa polyphenols metabolites derived from phase II and microbial metabolisms . Compared to M , C + M intervention increases HDLc [ 2.67 mg/dL ( 95 % confidence intervals , CI , 0.58 - 4.73 ; P = 0.008 ) ] and decreases oxLDL levels [ -12.3 U/L ( CI,-19.3 to -5.2;P = 0.001 ) ] . No changes between intervention groups were observed in vitamins B1 , B6 , B12 , C and E , or folic acid concentrations . In addition , subjects who showed higher increments in urinary cocoa polyphenol metabolites exhibited significant increases in HDLc and significant decreases in oxLDL levels ( P < 0.05 ; all ) . CONCLUSIONS Consumption of cocoa power with milk modulates the lipid profile  in high-risk subjects for CHD . In addition , the relationship observed between the urinary excretion of cocoa polyphenol metabolites and plasma HDLc and oxLDL levels suggests a beneficial role for cocoa polyphenols in lipid metabolism Background Consumption of chocolate has been often hypothesized to reduce the risk of cardiovascular disease ( CVD ) due to chocolate 's high levels of stearic acid and antioxidant flavonoids . However , debate still lingers regarding the true long term beneficial cardiovascular effects of chocolate overall . Methods We review ed English- language MEDLINE publications from 1966 through January 2005 for experimental , observational , and clinical studies of relations between cocoa , cacao , chocolate , stearic acid , flavonoids ( including flavonols , flavanols , catechins , epicatechins , and procynadins ) and the risk of cardiovascular disease ( coronary heart disease ( CHD ) , stroke ) . A total of 136 publications were selected based on relevance , and quality of design and methods . An up date d meta- analysis of flavonoid intake and CHD mortality was also conducted . Results The body of short-term r and omized feeding trials suggests cocoa and chocolate may exert beneficial effects on cardiovascular risk via effects on lowering blood pressure , anti-inflammation , anti-platelet function , higher HDL , decreased LDL oxidation . Additionally , a large body of trials of stearic acid suggests it is indeed cholesterol-neutral . However , epidemiologic studies of serum and dietary stearic acid are inconclusive due to many method ologic limitations . Meanwhile , the large body of prospect i ve studies of flavonoids suggests the flavonoid content of chocolate may reduce risk of cardiovascular mortality . Our up date d meta- analysis indicates that intake of flavonoids may lower risk of CHD mortality , RR = 0.81 ( 95 % CI : 0.71–0.92 ) comparing highest and lowest tertiles . Conclusion Multiple lines of evidence from laboratory experiments and r and omized trials suggest stearic acid may be neutral , while flavonoids are likely protective against CHD mortality . The highest priority now is to conduct larger r and omized trials to definitively investigate the impact of chocolate consumption on long-term cardiovascular outcomes Endothelial dysfunction characterizes many disease states including sub clinical atherosclerosis . The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal , healthy individuals when administered either acutely or over a period of several days , or weeks . Women experience increased risk for cardiovascular disease after menopause , which can be associated with endothelial dysfunction . Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known . The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women . Thirty-two postmenopausal hypercholesterolemic women were r and omly assigned to consume a high-flavanol cocoa beverage ( high cocoa flavanols (CF)—446 mg of total flavanols ) , or a low-flavanol cocoa beverage ( low CF—43 mg of total flavanols ) for 6 weeks in a double-blind study ( n=16 per group ) . Endothelial function was determined by brachial artery-reactive hyperemia . Plasma was analyzed for lipids ( total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol ) , hormones ( follicle-stimulating hormone ) , total nitrate/nitrite , activation of cellular adhesion markers ( vascular cell adhesion molecule 1 , intercellular adhesion molecule 1 , E-Selectin , P-Selectin ) , and platelet function and reactivity . Changes in these plasma markers were then correlated to brachial reactivity . Brachial artery hyperemic blood flow increased significantly by 76 % ( P<0.05 vs. baseline ) after the 6-week cocoa intervention in the high CF group , compared with 32 % in the low CF cocoa group ( P = ns vs. baseline ) . The 2.4-fold increase in hyperemic blood flow with high CF cocoa closely correlated ( r2=0.8 ) with a significant decrease ( 11 % ) in plasma levels of soluble vascular cell adhesion molecule-1 . Similar responses were not observed after chronic use of low CF . There were no significant differences between high and low CF in other biochemical markers and parameters measured . This study is the first to identify beneficial vascular effects of flavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women . In addition , our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved vascular reactivity CONTEXT Current research suggests that dark cocoa may reduce fatigue ; however , the effect on fatigue in people with MS ( pwMS ) has never been established . The objective of this feasibility study was to explore the acute effect of high flavonoid cocoa on measures of fatigue and glycaemic response . METHODS This was a r and omised crossover participant blind exploratory study in 12 participants ( 2 male and 10 female ) with MS-related fatigue ( > 4 on the Fatigue Severity Scale ; FSS ) . After fasting overnight , participants consumed the high flavonoid cocoa drink ( 350 mg gallic acid equivalents {GAE}/g ) or a low flavonoid cocoa control ( 120 mg GAE/g ) , consuming the alternative drink on the next visit . Fatigue was self-reported on a 100 mm visual analogue scale at 30-min time intervals for 2 h post cocoa consumption and every 2 h for the rest of the day . Fatigability was monitored using a 6 min walk test ( 6MWT ) at the end of the visit ( 2 h ) , and activity monitors worn for 24 h commencing at 12 noon on the day of testing . The feasibility of performing the trial including outcome measures was documented . RESULTS A moderate effect was found in self-reported fatigue throughout the day in favour of the high flavonoid group ( Cohen 's d 0.32 , 95 % non- central t CI -0.57 to 1.20 ) . Fatigability measures did not change . Participants consumed and enjoyed the cocoa , all participants completed the study and outcome measures were accepted . CONCLUSION The results of this study support further trials to investigate the feasibility and efficacy of pure cocoa as a dietary supplement for fatigue in pwMS Background : Dark chocolate derived from the plant ( Theobroma cacao ) is a rich source of flavonoids . Cardioprotective effects including antioxidant properties , inhibition of platelet activity , and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids . Objective : To investigate the effects of flavonoid-rich dark chocolate on endothelial function , measures of oxidative stress , blood lipids , and blood pressure in healthy adult subjects . Design : The study was a r and omized , double-blind , placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects . Subjects were r and omly assigned to daily intake of high-flavonoid ( 213 mg procyanidins , 46 mg epicatechin ) or low-flavonoid dark chocolate bars ( 46 g , 1.6 oz ) . Results : High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation ( FMD ) of the brachial artery ( mean change = 1.3 ± 0.7 % ) as compared to low-flavonoid chocolate consumption ( mean change = −0.96 ± 0.5 % ) ( p = 0.024 ) . No significant differences were noted in the resistance to LDL oxidation , total antioxidant capacity , 8-isoprostanes , blood pressure , lipid parameters , body weight or body mass index ( BMI ) between the two groups . Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group ( 204.4 ± 18.5 nmol/L , p ≤ 0.001 ) but not in the low-flavonoid group ( 17.5 ± 9 nmol/L , p = 0.99 ) . Conclusion : Flavonoid-rich dark chocolate  improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults . No changes in oxidative stress measures , lipid profiles , blood pressure , body weight or BMI were seen BACKGROUND Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease . Because atherosclerosis is considered a low- grade inflammatory disease , some feeding trials have analyzed the effects of cocoa ( an important source of flavonoids ) on inflammatory biomarkers , but the results have been controversial . OBJECTIVE The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients . DESIGN Forty-two high-risk volunteers ( 19 men and 23 women ; mean + /- SD age : 69.7 + /- 11.5 y ) were included in a r and omized crossover feeding trial . All subjects received 40 g cocoa powder with 500 mL skim milk/d ( C+M ) or only 500 mL skim milk/d ( M ) for 4 wk . Before and after each intervention period , cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated . RESULTS Adherence to the dietary protocol was excellent . No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups . However , in monocytes , the expression of VLA-4 , CD40 , and CD36 was significantly lower ( P = 0.005 , 0.028 , and 0.001 , respectively ) after C+M intake than after M intake . In addition , serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower ( both P = 0.007 ) after C+M intake than after M intake . CONCLUSIONS These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease . These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis . This trial was registered in the Current Controlled Trials at London , International St and ard R and omized Controlled Trial Number , at controlled-trials.com as IS RCT N75176807 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 Background : Sleep deprivation is a risk factor for cardiovascular disease . Cocoa flavonoids exert cardiovascular benefits and neuroprotection . Whether chocolate consumption may mitigate detrimental effects of sleep loss on cognitive performance and cardiovascular parameters has never been studied . Aim : We investigated the effects of flavanol-rich chocolate consumption on cognitive skills and cardiovascular parameters after sleep deprivation . Methods : Thirty-two healthy participants underwent two baseline sessions after one night of undisturbed sleep and two experimental sessions after one night of total sleep deprivation . Two hours before each testing session , participants were r and omly assigned to consume high or poor flavanol chocolate bars . During the tests were evaluated , the Psychomotor Vigilance Task and a working memory task , office SBP and DBP , flow-mediated dilation and pulse-wave velocity . Results : Sleep deprivation increased SBP/DBP . SBP/DBP and pulse pressure were lower after flavanol-rich treatment respect to flavanol-poor treatment ( SBP : 116.9 ± 1.6 vs. 120.8 ± 1.9 mmHg , respectively , P = 0.00005 ; DBP : 70.5 ± 1.2 vs. 72.3 ± 1.2 mmHg , respectively , P = 0.01 ; pulse pressure : 46.4 ± 1.3 vs. 48.4 ± 1.5 mmHg , P = 0.004 ) . Sleep deprivation impaired flow-mediated dilation ( 5.5 ± 0.5 vs. 6.5 ± 0.6 % , P = 0.02 ) , flavanol-rich , but not flavanol-poor chocolate counteracted this alteration ( flavanol-rich/flavanol-poor chocolate : 7.0 ± 0.6 vs. 5.0 ± 0.4 % , P = 0.000001 ) . Flavanol-rich chocolate mitigated the pulse-wave velocity increase ( P = 0.001 ) . Flavanol-rich chocolate preserved working memory accuracy in women after sleep deprivation . Flow-mediated dilation correlated with working memory performance accuracy in the sleep condition ( P = 0.04 ) . Conclusion : Flavanol-rich chocolate counteracted vascular impairment after sleep deprivation and restored working memory performance . Improvement in cognitive performance could be because of the effects of cocoa flavonoids on blood pressure and peripheral and central blood flow Flavanol-rich cocoa products have been reported to lower  blood pressure .  It has been suggested that theobromine is partially responsible for this effect . We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure . In a double-blind , placebo-controlled 3-period crossover trial we assigned 42 healthy individuals ( age 62±4.5 years ; 32 men ) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg and low added cardiovascular risk to a r and om treatment sequence of dairy drinks containing placebo , flavanol-rich cocoa with natural dose consisting of 106 mg of theobromine , or theobromine-enriched flavanol-rich cocoa with 979 mg of theobromine . Treatment duration was 3 weeks with a 2-week washout . The primary outcome was the difference in 24-hour ambulatory systolic blood pressure between placebo and active treatment after 3 weeks . The difference in central systolic blood pressure between placebo and active treatment was a secondary outcome . Treatment with theobromine-enriched cocoa result ed in a mean±SE of 3.2±1.1 mm Hg higher 24-hour ambulatory systolic blood pressure compared with placebo ( P<0.01 ) . In contrast , 2 hours after theobromine-enriched cocoa , laboratory peripheral systolic blood pressure was not different from placebo , whereas central systolic blood pressure was 4.3±1.4 mm Hg lower ( P=0.001 ) . Natural dose theobromine cocoa did not significantly change either 24-hour ambulatory or central systolic blood pressure compared with placebo . In conclusion , theobromine-enriched cocoa significantly increased 24-hour ambulatory systolic blood pressure while lowering central systolic blood pressure
FRC consumption significantly improves blood pressure , insulin resistance , lipid profiles , and FMD .
A growing body of evidence suggests that the consumption of foods rich in polyphenolic compounds , particularly cocoa , may have cardioprotective effects .
No review , however , has yet examined the effect of flavonoid-rich cocoa ( FRC ) on all major cardiovascular risk factors or has examined potential dose-response relationships for these effects .