title: Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study. Cocoa Reduces Blood Pressure and Insulin Resistance and Improves Endothelium-Dependent Vasodilation in Hypertensives Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk factors in a normotensive population with elevated cholesterol. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults. Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Flavonoid-Rich Dark Chocolate Improves Endothelial Function and Increases Plasma Epicatechin Concentrations in Healthy Adults Stress and blood pressure in Kuna Amerinds. Dark chocolate or tomato extract for prehypertension: a randomised controlled trial Regular Consumption of a Flavanol-rich Chocolate can Improve Oxidant Stress in Young Soccer Players Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. Eating chocolate can significantly protect the skin from UV light. Chronic Consumption of Flavanol-rich Cocoa Improves Endothelial Function and Decreases Vascular Cell Adhesion Molecule in Hypercholesterolemic Postmenopausal Women Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. Cocoa flavanol-enriched snack bars containing phytosterols effectively lower total and low-density lipoprotein cholesterol levels. Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease. Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults.
abstract: 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 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 Previous studies with plant sterols ( PS ) and cocoa flavanols ( CF ) provide support for their dietary use in maintaining cardiovascular health . This double-blind , placebo-controlled , cross-over study evaluated the efficacy of daily consumption of a cocoa flavanol-containing dark chocolate bar with added PS on serum lipids , blood pressure , and other circulating cardiovascular health markers in a population with elevated serum cholesterol . We recruited 49 adults ( 32 women , 17 men ) with serum total cholesterol concentrations of 5.20 - 7.28 mmol/L and blood pressure of < or = 159/99 mm Hg . Following a 2-wk lead-in utilizing the AHA style diet , participants were r and omized into 2 groups and instructed to consume 2 cocoa flavanol-containing dark chocolate bars per day with ( 1.1 g sterol esters per bar ) or without PS . Each 419-kJ bar was nutrient-matched and contained approximately 180 mg CF . Participants consumed 1 bar 2 times per day for 4 wk then switched to the other bar for an additional 4 wk . Serum lipids and other cardiovascular markers were measured at baseline and after 4 and 8 wk . Blood pressure was measured every 2 wk . Regular consumption of the PS-containing chocolate bar result ed in reductions of 2.0 and 5.3 % in serum total and LDL cholesterol ( P < 0.05 ) , respectively . Consumption of CF also reduced systolic blood pressure at 8 wk ( -5.8 mm Hg ; P < 0.05 ) . Results indicate that regular consumption of chocolate bars containing PS and CF as part of a low-fat diet may support cardiovascular health by lowering cholesterol and improving blood pressure BACKGROUND Numerous studies indicate that flavanols may exert significant vascular protection because of their antioxidant properties and increased nitric oxide bioavailability . In turn , nitric oxide bioavailability deeply influences insulin-stimulated glucose uptake and vascular tone . Thus , flavanols may also exert positive metabolic and pressor effects . OBJECTIVE The objective was to compare the effects of either dark or white chocolate bars on blood pressure and glucose and insulin responses to an oral-glucose-tolerance test in healthy subjects . DESIGN After a 7-d cocoa-free run-in phase , 15 healthy subjects were r and omly assigned to receive for 15 d either 100 g dark chocolate bars , which contained approximately 500 mg polyphenols , or 90 g white chocolate bars , which presumably contained no polyphenols . Successively , subjects entered a further cocoa-free washout phase of 7 d and then were crossed over to the other condition . Oral-glucose-tolerance tests were performed at the end of each period to calculate the homeostasis model assessment of insulin resistance ( HOMA-IR ) and the quantitative insulin sensitivity check index ( QUICKI ) ; blood pressure was measured daily . RESULTS HOMA-IR was significantly lower after dark than after white chocolate ingestion ( 0.94 + /- 0.42 compared with 1.72 + /- 0.62 ; P < 0.001 ) , and QUICKI was significantly higher after dark than after white chocolate ingestion ( 0.398 + /- 0.039 compared with 0356 + /- 0.023 ; P = 0.001 ) . Although within normal values , systolic blood pressure was lower after dark than after white chocolate ingestion ( 107.5 + /- 8.6 compared with 113.9 + /- 8.4 mm Hg ; P < 0.05 ) . CONCLUSION Dark , but not white , chocolate decreases blood pressure and improves insulin sensitivity in healthy persons Flavanols from chocolate appear to increase nitric oxide bioavailability , protect vascular endothelium , and decrease cardiovascular disease ( CVD ) risk factors . We sought to test the effect of flavanol-rich dark chocolate ( FRDC ) on endothelial function , insulin sensitivity , beta-cell function , and blood pressure ( BP ) in hypertensive patients with impaired glucose tolerance ( IGT ) . After a run-in phase , 19 hypertensives with IGT ( 11 males , 8 females ; 44.8 + /- 8.0 y ) were r and omized to receive isocalorically either FRDC or flavanol-free white chocolate ( FFWC ) at 100 g/d for 15 d. After a wash-out period , patients were switched to the other treatment . Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry , respectively , flow-mediated dilation ( FMD ) , oral glucose tolerance test , serum cholesterol and C-reactive protein , and plasma homocysteine were evaluated after each treatment phase . FRDC but not FFWC ingestion decreased insulin resistance ( homeostasis model assessment of insulin resistance ; P < 0.0001 ) and increased insulin sensitivity ( quantitative insulin sensitivity check index , insulin sensitivity index ( ISI ) , ISI(0 ) ; P < 0.05 ) and beta-cell function ( corrected insulin response CIR(120 ) ; P = 0.035 ) . Systolic ( S ) and diastolic ( D ) BP decreased ( P < 0.0001 ) after FRDC ( SBP , -3.82 + /- 2.40 mm Hg ; DBP , -3.92 + /- 1.98 mm Hg ; 24-h SBP , -4.52 + /- 3.94 mm Hg ; 24-h DBP , -4.17 + /- 3.29 mm Hg ) but not after FFWC . Further , FRDC increased FMD ( P < 0.0001 ) and decreased total cholesterol ( -6.5 % ; P < 0.0001 ) , and LDL cholesterol ( -7.5 % ; P < 0.0001 ) . Changes in insulin sensitivity ( Delta ISI - Delta FMD : r = 0.510 , P = 0.001 ; Delta QUICKI - Delta FMD : r = 0.502 , P = 0.001 ) and beta-cell function ( Delta CIR(120 ) - Delta FMD : r = 0.400 , P = 0.012 ) were directly correlated with increases in FMD and inversely correlated with decreases in BP ( Delta ISI - Delta 24-h SBP : r = -0.368 , P = 0.022 ; Delta ISI - Delta 24-h DBP r = -0.384 , P = 0.017 ) . Thus , FRDC ameliorated insulin sensitivity and beta-cell function , decreased BP , and increased FMD in IGT hypertensive patients . These findings suggest flavanol-rich , low-energy cocoa food products may have a positive impact on CVD risk factors BACKGROUND In recent years , there has been increased interest in the potential health-related benefits of antioxidant- and phytochemical-rich dark chocolate and cocoa . OBJECTIVE The objective of the study was to examine the short-term ( 6 wk ) effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health in healthy older adults . DESIGN A double-blind , placebo-controlled , fixed-dose , parallel-group clinical trial was used . Participants ( n = 101 ) were r and omly assigned to receive a 37-g dark chocolate bar and 8 ounces ( 237 mL ) of an artificially sweetened cocoa beverage or similar placebo products each day for 6 wk . RESULTS No significant group ( dark chocolate and cocoa or placebo)-by-trial ( baseline , midpoint , and end-of-treatment assessment s ) interactions were found for the neuropsychological , hematological , or blood pressure variables examined . In contrast , the midpoint and end-of-treatment mean pulse rate assessment s in the dark chocolate and cocoa group were significantly higher than those at baseline and significantly higher than the midpoint and end-of-treatment rates in the control group . Results of a follow-up question naire item on the treatment products that participants believed they had consumed during the trial showed that more than half of the participants in both groups correctly identified the products that they had ingested during the experiment . CONCLUSIONS This investigation failed to support the predicted beneficial effects of short-term dark chocolate and cocoa consumption on any of the neuropsychological or cardiovascular health-related variables included in this research . Consumption of dark chocolate and cocoa was , however , associated with significantly higher pulse rates at 3- and 6-wk treatment assessment 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 Flavonoids may be partly responsible for some health benefits , including antiinflammatory action and a decreased tendency for the blood to clot . An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits platelet activation and function over 6 h in humans . OBJECTIVE This study sought to evaluate whether 28 d of supplementation with cocoa flavanols and related procyanidin oligomers would modulate human platelet reactivity and primary hemostasis and reduce oxidative markers in vivo . DESIGN Thirty-two healthy subjects were assigned to consume active ( 234 mg cocoa flavanols and procyanidins/d ) or placebo ( < or = 6 mg cocoa flavanols and procyanidins/d ) tablets in a blinded parallel- design ed study . Platelet function was determined by measuring platelet aggregation , ATP release , and expression of activation-dependent platelet antigens by using flow cytometry . Plasma was analyzed for oxidation markers and antioxidant status . RESULTS Plasma concentrations of epicatechin and catechin in the active group increased by 81 % and 28 % , respectively , during the intervention period . The active group had significantly lower P selectin expression and significantly lower ADP-induced aggregation and collagen-induced aggregation than did the placebo group . Plasma ascorbic acid concentrations were significantly higher in the active than in the placebo group ( P < 0.05 ) , whereas plasma oxidation markers and antioxidant status did not change in either group . CONCLUSIONS Cocoa flavanol and procyanidin supplementation for 28 d significantly increased plasma epicatechin and catechin concentrations and significantly decreased platelet function . These data support the results of acute studies that used higher doses of cocoa flavanols and procyanidins 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 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 Is migration from isolated indigenous isl and communities to Panama City associated with an increase in stress ? Individuals were r and omly sample d from two Kuna communities : 325 individuals in Panama City and 133 on a Caribbean isl and . Stress was assessed through the Milcom question naire , which explores physical symptoms and symptoms relevant to mood and emotional state , and Cantril 's ladder , which examines life satisfaction . Physical symptoms were more common in the urban community ( p < 0.001 ) , and complaints reflecting mood were also significantly higher on the mainl and ( p < 0.001 ) ; the two measures were highly correlated . While systolic and diastolic blood pressure was higher in the mainl and community ( p < 0.001 ) , there was no relation between blood pressure level and any index of stress . Despite unambiguous evidence of an increase in stress in migrants to the city , there was no indication that the stress contributed to the rise in blood pressure level . Migration to an urban setting is associated with an increase in physical symptoms and symptoms reflecting depressed mood , suggesting increased stress level . Life satisfaction is less influenced , possibly providing a measure of the degree of stress Background Flavanol-rich chocolate and lycopene-rich tomato extract have attracted interest as potential alternative treatment options for hypertension , a known risk factor for cardiovascular morbidity and mortality . Treatment of prehypertension ( SBP 120–139/DBP 80–89 mmHg ) may forestall progression to hypertension . However , there has been only limited research into non-pharmacological treatment options for prehypertension . We investigated the effect of dark chocolate or tomato extract on blood pressure , and their acceptability as an ongoing treatment option in a prehypertensive population . Methods Our trial consisted of two phases : a r and omised controlled three-group-parallel trial over 12 weeks ( phase 1 ) followed by a crossover of the two active treatment arms over an additional 12-week period ( phase 2 ) . Group 1 received a 50 g daily dose of dark chocolate with 70 % cocoa containing 750 mg polyphenols , group 2 were allocated one tomato extract capsule containing 15 mg lycopene per day , and group 3 received one placebo capsule daily over 8 weeks followed by a 4-week washout period . In phase 2 the active treatment groups were crossed over to receive the alternative treatment . Median blood pressure , weight , and abdominal circumference were measured 4-weekly , and other characteristics including physical activity , general health , energy , mood , and acceptability of treatment were assessed by question naire at 0 , 8 and 20 weeks . We analysed changes over time using a linear mixed model , and one time point differences using Kruskal-Wallis , Fisher's-Exact , or t-tests . Results Thirty-six prehypertensive healthy adult volunteers completed the 6-month trial . Blood pressure changes over time within groups and between groups were not significant and independent of treatment . Weight and other characteristics did not change significantly during the trial . However , a marked difference in acceptability between the two treatment forms ( chocolate or capsule ) was revealed ( p < 0.0001 ) . Half of the participants allocated to the chocolate treatment found it hard to eat 50 g of dark chocolate every day and 20 % considered it an unacceptable long-term treatment option , whereas all participants found it easy and acceptable to take a capsule each day for blood pressure . Conclusion Our study did not find a blood pressure lowering effect of dark chocolate or tomato extract in a prehypertensive population . Practicability of chocolate as a long-term treatment option may be limited . Trial registration http://www.anzctr.org.au Identifier : The consumption of a diet rich in certain flavonoids , including the flavanol sub-class , has been associated with a reduced risk for vascular disease . We evaluated the effects of the regular consumption ( 14 d ) of a flavanol-containing milk chocolate ( FCMC ) or cocoa butter chocolate ( CBC ) on variables related to vascular disease risk , oxidative stress and physical activity . Twenty-eight free-living , young ( 18–20 years old ) male soccer players consumed daily 105 g of FCMC ( 168 mg of flavanols ) or CBC ( < 5 mg of flavanols ) , as part of their normal diet . The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure ( -5 mm Hg ) , mean blood pressure ( -5 mm Hg ) , plasma cholesterol ( -11 % ) , LDL-cholesterol ( -15 % ) , malondialdehyde ( -12 % ) , urate ( -11 % ) and lactate dehydrogenase ( LDH ) activity ( -11 % ) , and an increase in vitamin E/cholesterol ( + 12 % ) . No relevant changes in these variables were associated with CBC consumption . No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood sample s. In conclusion , FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress . The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results BACKGROUND Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance . Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium . OBJECTIVE The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure , improve endothelial dysfunction , and ameliorate insulin resistance in subjects with essential hypertension . DESIGN We conducted a r and omized , placebo-controlled , double-blind , crossover trial of a flavanol-rich cocoa drink ( 150 mL twice a day , approximately 900 mg flavanols/d ) in individuals with essential hypertension ( n = 20 ) . Antihypertensive medications were discontinued before study enrollment . After a 7-d cocoa-free run-in period , cocoa or flavanol-poor placebo ( approximately 28 mg flavanols/d ) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm . Blood pressure was measured thrice weekly . At baseline and after each treatment period , we assessed insulin sensitivity ( hyperinsulinemic-isoglycemic glucose clamp ) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment ( Doppler ultrasound with or without microbubble contrast ) . RESULTS Cocoa treatment for 2 wk increased insulin-stimulated changes in brachial artery diameter when compared with placebo [ median percentage increase from baseline ( 25th-75th percentile ) : 8.3 ( 4.2 - 11.3 ) compared with 5.9 ( -0.3 to 9.6 ) ; P < 0.04 ] . Nevertheless , cocoa treatment did not significantly reduce blood pressure or improve insulin resistance and had no significant effects on skeletal muscle capillary recruitment , circulating plasma concentrations of adipocytokines , or endothelial adhesion molecules . CONCLUSIONS Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension . This trial was registered at clinical trials.gov as NCT00099476 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 BACKGROUND Cocoa beans fresh from the tree are exceptionally rich in flavanols . Unfortunately , during conventional chocolate making , this high antioxidant capacity is greatly reduced due to manufacturing processes . AIM To evaluate the photoprotective potential of chocolate consumption , comparing a conventional dark chocolate to a specially produced chocolate with preserved high flavanol ( HF ) levels . METHODS A double-blind in vivo study in 30 healthy subjects was conducted . Fifteen subjects each were r and omly assigned to either a HF or low flavanol ( LF ) chocolate group and consumed a 20 g portion of their allocated chocolate daily . The minimal erythema dose ( MED ) was assessed at baseline and after 12 weeks under st and ardized conditions . RESULTS In the HF chocolate group the mean MED more than doubled after 12 weeks of chocolate consumption , while in the LF chocolate group , the MED remained without significant change . CONCLUSIONS Our study demonstrated that regular consumption of a chocolate rich in flavanols confers significant photoprotection and can thus be effective at protecting human skin from harmful UV effects . Conventional chocolate has no such effect 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 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 Dietary intervention studies incorporating phytosterol-enriched margarine spreads have reported significant decreases in total and low-density lipoprotein ( LDL ) cholesterol in population s with both normal lipid levels and those with hypercholesterolemia . There is emerging support for more diverse and lower-fat phytosterol-enriched matrixes . Controversy exists , however , over whether phytosterol-enriched foods affect serum fat-soluble vitamins . OBJECTIVE We investigated whether a flavanol-rich cocoa snack food containing phytosterols would decrease total and LDL cholesterol levels in subjects with hypercholesterolemia and significantly affect serum fat-soluble vitamins and carotenoids . DESIGN A r and omized , double-blind parallel arm study design was used . Subjects were r and omized to one of two dietary treatments : a cocoa flavanol-enriched snack bar containing 1.5 g phytosterol ( n=32 ) , or a control product containing no phytosterols ( n=35 ) . Subjects consumed two servings per day . RESULTS Consumption of the phytosterol-enriched snack bars but not control bars for 6 weeks was associated with significant reductions in plasma total ( 4.7 % ; P<0.01 ) and LDL cholesterol ( 6 % ; P<0.01 ) , and the ratio of total to high-density lipoprotein cholesterol ( 7.4 % ; P<0.001 ) . There were no changes in high-density lipoprotein cholesterol , triglycerides , or lipid-adjusted lycopene , beta-cryptoxanthin , lutein/zeaxanthin , alpha-carotene levels , or levels of serum vitamins A or E. A significant reduction in lipid-adjusted serum beta-carotene was observed in the phytosterol but not the no-phytosterol-added group ( P<0.05 ) . CONCLUSIONS This study supports the use of a novel phytosterol-enriched snack bar to effectively reduce plasma total and LDL cholesterol levels in a population with hypercholesterolemia . The data suggest that the incorporation of this snack food into a balanced diet represents a practical dietary strategy in the management of serum cholesterol levels OBJECTIVES In patients with coronary artery disease ( CAD ) medically managed according to currently accepted guidelines , we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells ( CACs ) . BACKGROUND Dietary flavanols can improve endothelial dysfunction . The CACs , also termed endothelial progenitor cells , are critical for vascular repair and maintenance of endothelial function . METHODS In a r and omized , controlled , double-masked , cross-over trial , 16 CAD patients ( 64+/-3 years of age ) received a dietary high-flavanol intervention ( HiFI [ 375 mg ] ) and a macronutrient- and micronutrient-matched low-flavanol intervention ( LoFI [ 9 mg ] ) twice daily in r and om order over 30 days . RESULTS Endothelium-dependent vasomotor function , as measured by flow-mediated vasodilation of the brachial artery , improved by 47 % in the HiFI period compared with the LoFI period . After HiFI , the number of CD34+/KDR+-CACs , as measured by flow cytometry , increased 2.2-fold as compared with after LoFI . The CAC functions , as measured by the capacity to survive , differentiate , proliferate , and to migrate were not different between the groups . The HiFI led to a decrease in systolic blood pressure ( mean change over LoFI : -4.2+/-2.7 mm Hg ) , and increase in plasma nitrite level ( mean change over LoFI : 74+/-32 nM ) . Applying a mixed-effects linear regression model , the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs . CONCLUSIONS Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs . ( Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients : Interaction Between Endothelial Progenitor Cells , Reactivity of Micro- and Macrocirculation ; NCT00553774 ) BACKGROUND Studies of cocoa suggest an array of cardiovascular benefits ; however , the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function ( EF ) have yet to be established . METHODS 44 adults ( BMI 25 - 35 kg/m2 ) participated in a r and omized , controlled , crossover trial . Participants were r and omly assigned to a treatment sequence : sugar-free cocoa beverage , sugar-sweetened cocoa beverage , and sugar-sweetened cocoa-free placebo . Treatments were administered daily for 6 weeks , with a 4-week washout period . RESULTS Cocoa ingestion improved EF measured as flow-mediated dilation ( FMD ) compared to placebo ( sugar-free cocoa : change , 2.4 % [ 95 % CI , 1.5 to 3.2 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 3.2 % [ 95 % CI , 1.8 to 4.6 ] ; p<0.001 and sugar-sweetened cocoa : change , 1.5 % [ 95 % CI , 0.6 to 2.4 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 2.3 % [ 95 % CI , 0.9 to 3.7 ] ; p=0.002 ) . The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater , but not significantly . Other biomarkers of cardiac risk did not change appreciably from baseline . BMI remained stable throughout the study . CONCLUSIONS Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk , and does not cause weight gain . Sugar-free preparations may further augment endothelial function
target: FRC consumption significantly improves blood pressure , insulin resistance , lipid profiles , and FMD .
background: 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 .