Research - Chocolate / Cocoa
Cardioprotection by Cocoa Polyphenols and ω-3 Fatty Acids: A Disease-Prevention Perspective on Aging-Associated Cardiovascular Risk
Sergio Davinelli, Graziamaria Corbi, Stefano Righetti, Barry Sears, Hector Hugo Olarte, Davide Grassi, and Giovanni Scapagnini
Cardiovascular disease (CVD) remains the leading cause of death today. Many of the biochemical alterations associated with the pathophysiology of CVD can be modified by adequate intakes of bioactive nutrients through a correct diet or supplementation. Recently, there has been growing public and clinical interest in cocoa polyphenols (CPs) and omega-3 (ω-3) fatty acids. A plethora of nutritional intervention trials and experimental studies demonstrates that consumption of these bioactive food compounds is beneficial to promote cardiovascular health. The purpose of this review is to summarize the major cardioprotective effects of CPs and ω-3 fatty acids, providing a scientific rationale for incorporating the combination of these molecules as a nutritional intervention in the prevention of CVD. Although several studies have shown the individual cardioprotective nature of these compounds, a combination treatment with CPs and ω-3 fatty acids may be a promising approach to enhance the preventive value of these molecules and reduce cardiovascular risk factors associated with aging. Therefore, this article also reviews some of the key studies on the interaction between CPs and the metabolism of ω-3 fatty acids.
Nutritional strategies for enhancing cardioprotection and reducing CVD risk will continue to be an important area of research. For instance, the ongoing Cocoa Supplement and Multivitamin Outcomes Study (COSMOS), which aims to determine the efficacy of a flavanol-rich cocoa using a 5-year randomized trial among 18,000 healthy men and women, may provide definitive evidence on the health benefits of cocoa on cardiovascular outcomes.104 Based on the existing literature discussed here, it is evident that CPs and LC ω-3 PUFAs play crucial roles in the prevention of CVD. Many studies have shown the individual cardioprotective nature of these compounds, however, more efforts should be directed to understand whether a synergistic combination of CPs and LC ω-3 PUFAs is more beneficial for CVD prevention. Despite the paucity of studies assessing the synergistic benefits of CPs and LC ω-3 PUFAs on CVD, there is a growing body of evidence that can serve as a translational platform to design future human studies and address questions behind the fascinating outcomes of a combined approach using CPs and LC ω-3 fatty acids.105–110 There are interesting preliminary results in rodent studies that encourage further work in this field and which hold promise for utilizing a combined use of CPs and LC ω-3 fatty acids as a preventive tool in CVD. Although clinical/translational evidence already supports nutraceutical compounds for healthy aging, alternative strategies with combined actions of food bioactive compounds have the potential to enhance cardioprotection and cardiovascular health in older adults for whom a single compound may be not enough. Clearly, more work is needed to provide novel insights into the mechanisms by which CPs and LC ω-3 fatty acids synergize to prevent and/or reduce cardiovascular risk factors. However, the co-administration of these agents may be a possible nutraceutical strategy for a number of disorders that affect the heart or blood vessels.
Source : Journal of Medicinal Food
Link to Full Article
Cocoa Flavanol Consumption Improves Facial Wrinkles and Skin Elasticity in Women with Photo-aged Facial Skin
Yoon H-S, Kim JR, Park GY, et al. Cocoa flavanol supplementation influences skin conditions of photo-aged women: a 24-week double-blind, randomized, controlled trial. J Nutr. 2016;146(1):46-50.
Cocoa products, derived from the dried, fermented fatty seeds of the cocoa (Theobroma cacao, Malvaceae) tree, reportedly have many health benefits. They are rich in polyphenolic antioxidants and flavanols such as epicatechin, catechin, and procyanidins. Clinical trials conducted for 12 weeks that investigated the effects of consuming high-flavanol cocoa products on skin photo-aging have shown conflicting results. Since finding an adequate daily dose and duration of cocoa flavanol supplementation might provide significant antioxidant photoprotection, these authors conducted a 24-week, double-blind, randomized, clinical trial to investigate whether high-flavanol cocoa supplementation would improve the moderately photo-aged facial skin of female subjects.
The subjects were healthy females aged between 40 and 86 years (mean age, 61.7 ± 13.1 years) with visible wrinkles. The study was conducted between February 2014 and March 2015 at Seoul National University Hospital in Seoul, Korea. Sixty-four subjects were randomly assigned to either the cocoa group or placebo group, with 32 subjects in each group. Of those subjects, 1 from each group did not follow the protocol and did not complete the study.
The beverage consumed daily by the cocoa group contained 4 g fat-reduced cocoa powder (Barry Callebaut Belgium N.V.; Lebbeke-Wieze, Belgium) that was processed in a manner to preserve a high amount (320 mg) of cacao bean flavanols. A nutrient-matched cocoa-flavored beverage that did not contain cocoa flavanols was consumed by the placebo group. The beverage powders were dissolved in 150-200 mL hot water.
Wrinkles were measured in the crow's feet area on the outer corner of the eye by using a Skin-Visiometer® SV 600 (Courage+Khazaka electronic GmbH; Cologne, Germany) to assess the following 5 roughness variables: skin roughness, maximum roughness, average roughness, smoothness depth, and arithmetic average roughness. As wrinkles diminish in depth, those values decrease. A Cutometer® MPA580 (Courage+Khazaka electronic GmbH) was used to measure skin elasticity on the cheek in terms of gross elasticity, net elasticity, and biological elasticity. The closer the value is to 1 on the cutometer, the more elastic the skin. Using a Corneometer® and a Tewameter® (both, Courage+Khazaka electronic GmbH), the authors evaluated skin hydration on each subject's cheek.
The facial skin of each subject was evaluated at baseline and during the study at 12 and 24 weeks. Ten subjects in each group agreed to undergo ultraviolet (UV)-B irradiation. The minimal erythema dose (MED), or the minimal UV dose causing erythema on all edges of an irradiated square of skin on the buttock, was assessed at baseline and at 24 weeks in those subjects.
Adverse effects were evaluated at 12 and 24 weeks. Blood samples were drawn at baseline and at 24 weeks to measure aspartate aminotransferase, alanine transaminase, glucose, blood urea nitrogen, creatinine, and hemoglobin and hematocrit concentrations.
The authors report no significant between-group differences in visiometer measurements after 12 weeks of supplementation. After 24 weeks, however, the mean percentage changes in average roughness (P=0.023) and maximum roughness (P=0.030) were significantly lower in the cocoa group than in the placebo group. "Because visiometer values decrease as wrinkle diminish, these results suggest that the cocoa group showed improvement in wrinkle severity compared with the placebo group." Changes in the other visiometer variables were not significant at 24 weeks.
The only significant between-group difference in skin elasticity after 12 weeks was in the mean percentage change in gross elasticity of the skin, which was significantly greater in the cocoa group than in the placebo group (P=0.020). After 24 weeks, significant between-group differences were observed in gross elasticity (P=0.027), net elasticity (P=0.027), and biological elasticity (P=0.032), which were all greater for the cocoa group than for the placebo group. No significant between-group differences were seen in epidermal hydration variables after 12 or 24 weeks of supplementation.
No adverse effects were reported, and no abnormal laboratory values were observed. Body weight changes were minimal; the placebo group gained more than the cocoa group after 24 weeks (P=0.021). Although cocoa flavanols have been reported to have beneficial effects on obesity, in this study, the subjects' diet and physical activity were not controlled, so this finding "can only be interpreted as indirect evidence and was an unintended outcome," write the authors.
Overall adherence rates were 97.6% at 12 weeks and 98.4% at 24 weeks.
The MED of those in the placebo group undergoing UV irradiation did not change significantly during the study. In the cocoa group, however, a significantly increased MED was observed at 24 weeks (P=0.022). Changes in MED at 24 weeks were significantly higher in the cocoa group than in the placebo group (P=0.035).
Although this study showed that cocoa flavanols can improve facial wrinkles and elasticity, the effects were not as great as those reported for direct curative therapies such as topical tretinoin, laser resurfacing, and chemical peeling. "Therefore, the main effect of cocoa flavanols on photo-aging might be preventive rather than curative," the authors state.
The authors note that their findings of changes in wrinkle severity and skin elasticity are consistent with those of previous trials.1,2 Conflicting results remain regarding changes in MED after cocoa flavanol consumption, possibly because of the variations in age, skin phototype, and race of subjects used in the trials.
The authors conclude that "in moderately photo-aged women, regular cocoa flavanol consumption had positive effects on facial wrinkles and elasticity," and that "regular cocoa flavanol consumption may be a good strategy for prevention of the progression of skin photo-aging."
Source : American Botanical Council - HerbClip
Link to Source
Epicatechin and Quercetin Affects Some Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial1,2James I Dower3,4, Johanna M Geleijnse3,4, Lieke Gijsbers3,4,Casper Schalkwijk3,5, Daan Kromhout4, and Peter C Hollman3,4,*
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 randomized, 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 random 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 thez 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.
Source : Journal Nutrition
Link to Abstract
Research Review Supports Cardioprotective Role of Cocoa
Berends LM, van der Velpen V, Cassidy A. Flavan-3-ols, theobromine, and the effects of cocoa and chocolate on cardiometabolic risk factors. Curr Opin Lipidol. 2015;26(1):10-19.
Potential cardiovascular health benefits are attributed to cocoa (Theobroma cacao, Malvaceae) and chocolate through their bioactive constituents, including polyphenols, stearic acid, and methylxanthines. This review summarizes the recent research on the cardiometabolic effects of cocoa and chocolate and focuses on two key bioactive constituents: flavan-3-ols and theobromine. The main flavan-3-ols in chocolate are (–)-epicatechin, (+)-catechin, and some of their oligomers, known as procyanidins. Theobromine is another bioactive constituent of chocolate with potential beneficial health effects. The role of chocolate in cardiovascular disease (CVD) has been studied in both observational studies for cardiovascular endpoints and in randomized, controlled trials (RCTs) for cardiometabolic markers.
In a meta-analysis of six cohort studies and one cross-sectional study, a higher chocolate intake was associated with a reduced risk for cardiometabolic disorders.1 The greatest reductions were seen for CVD (37%) and stroke (29%) in three studies. In one study, a reduction in diabetes was observed; no effects of chocolate intake on heart failure were observed. A meta-analysis of observational data showed an overall relative risk reduction of 19% for stroke when comparing the highest and lowest categories of chocolate intake.2 Two other meta-analyses supported the association between chocolate intake and reduced risk for CVD.
Three meta-analyses of RCTs reviewed the impact of cocoa and chocolate consumption on cardiometabolic health from short-duration studies (≤18 weeks). One reported a 2.77 mmHg decrease in systolic blood pressure (SBP) and a 2.20 mmHg decrease in diastolic blood pressure (DBP) after cocoa intake.3 Two of the meta-analyses reported improved levels of both high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with cocoa consumption. In another study, daily cocoa intake significantly improved HDL-C, glucose, and several inflammatory biomarkers, but did not affect blood pressure, LDL-C, or triglyceride concentrations.4
The authors conclude that data from available RCTs on cardiometabolic markers "largely support the findings on CVD outcomes in observational studies; the short duration studies support potentially clinically relevant effects of cocoa and chocolate on vascular function and insulin resistance." Additional longer-term trials are needed.
According to the authors, the most recent prospective cohort studies on flavan-3-ol intake and cardiovascular health report no association with coronary heart disease (CHD) mortality, CHD incidence, or stroke risk. One study of 98,469 men and women over seven years, however, reported that higher flavan-3-ol intake was associated with a 17% decrease in CVD mortality.5 Another study of 1,063 women over five years reported a 66% decrease for atherosclerotic vascular disease mortality associated with flavanol intake.6 A third study of 7,172 subjects followed for more than four years reported a 60% decrease in CVD events and mortality.7
Three systematic reviews sought to determine the effective dose of flavan-3-ols. In one, a nonlinear dose-response effect with a maximal effect was observed at a total polyphenol intake of 500 mg. In another, intakes of epicatechin > 50 mg resulted in greater effects on SBP and DBP; flow-mediated dilatation (FMD) improved at all levels of epicatechin intake.
The authors conclude that "flavan-3-ols may mediate the beneficial effects of cocoa and chocolate. However, in addition to elucidating the effective doses, it remains to be established whether the flavan-3-ol monomers, their phase-II-conjugated metabolites, the procyanidins or their gut metabolites are driving any cardiometabolic effects."
Theobromine may be responsible for mediating the observed beneficial effects of cocoa and chocolate on lipoprotein levels, suggests a short-term RCT in which daily consumption of theobromine (850 mg) for four weeks significantly increased HDL-C concentrations.8 In another RCT, with a lower daily consumption of theobromine (476 mg daily for four weeks), no changes were reported in HDL-C levels.9 In some studies, high-dose theobromine consumption was associated with gastrointestinal complaints, and acute stimulatory effects on heart rate were observed following consumption of 500-1000 mg theobromine.
The authors suggest further studies should investigate how theobromine affects HDL-C functionality and cardiovascular health, along with the effects at dietary-relevant levels, and its potential synergistic effects with other bioactive compounds in chocolate.
The authors conclude, "Evidence for a cardioprotective role of chocolate consumption is apparent from the population-based studies and short-term RCTs, and currently provides greater support for the flavan-3-ol content rather than theobromine. However, interpretation of findings is difficult because of considerable variability between studies and it is unclear whether they work individually or in synergy."
Source : American Botanical Council
Link to Source
Dark Chocolate Consumption for One Month Improves Vascular Function in Young, Healthy Subjects
Pereira T, Maldonado J, Laranjeiro M, et al. Central arterial hemodynamic effects of dark chocolate ingestion in young healthy people: a randomized and controlled trial. Cardiol Res Pract. 2014;2014:945951. doi: 10.1155/2014/945951.
Ischaemic heart disease and stroke are the most important causes of mortality worldwide. Studies have shown that the severity of endothelial dysfunction relates to the risk for an initial or recurrent cardiovascular event.1Endothelial dysfunction plays a critical role in the development of atherosclerosis, leading to decreased arterial compliance. Nutrition is thought to affect endothelial function. Foods rich in flavanols have been investigated for their role in preventing cardiovascular disease. Cocoa (Theobroma cacao, Malvaceae) and chocolate products have a high flavanol concentration and antioxidant capacity. The authors conducted a randomized, controlled trial to determine whether daily ingestion of a small amount of cocoa-rich chocolate (>70%) improves the vascular function in young, healthy subjects.
Between November 2012 and February 2013, 60 clinically healthy subjects (20 men and 40 women), all undergraduate students at the Superior Polytechnic Institute of Coimbra, Portugal, were enrolled in the study. They were randomly allocated to the control group (CG) or the intervention group (IG). The 30 subjects in the CG were aged between 18 and 24 years; those in the IG, between 18 and 23 years.
The first study evaluation was done at baseline, after which the subjects in the IG ingested 10 g daily of dark chocolate with more than 75% cocoa for 1 month. [Note: Source of chocolate and other information regarding chocolate contents were not provided.] The CG had no intervention. A second evaluation was conducted 1 week after the end of the 1-month intervention period.
Among the clinical evaluations conducted were aortic pulse wave velocity (PWV), central pulse wave analysis (PWA), brachial artery flow-mediated dilation (FMD), augmentation index (AiX), distensibility index (ASI), blood pressure (BP), heart rate (HR), and clinical observation.
Baseline group characteristics were similar. The authors report no significant changes during the trial in body mass index, HR, or brachial BP in either group, although a consistent trend for reduced BP was seen in the IG.
Statistically significant decreases in PWV (P=0.02) and ASI (P<0.01) were seen in the IG, but not in the CG. A similar finding was also observed for the AiX, an indirect measure of arterial stiffness. At baseline, no significant differences in FMD were noted between the 2 groups; however, the FMD improved considerably after 1 month in the IG (P<0.001), with no significant changes in the CG. When pooling the mean within-group individual differences for each group, the authors reported a reduction in all variables after the 1-month intervention in the IG, with statistically significant effects for ASI (P<0.001) and PWV (P=0.010). Brachial and central BP levels also decreased in the IG.
To summarize, vascular function significantly improved in young, healthy subjects who consumed 10 g dark chocolate for 1 month.
The probable mechanism for improved PWV, ASI, and AiX after cocoa consumption may be the parietal relaxation of the large arteries, as well as a dilation of small- and medium-sized peripheral arteries and arterioles, say the authors. The "finding of improved FMD strongly suggests endothelium-dependent vascular relaxation as the motive for the vasomotor benefit found," leading to lower PWV, ASI, and AiX, and a trend toward reduced BP, write the authors.
"We can suggest flavanol-containing cocoa as a promising and powerful option for cardiovascular primary prevention."
Source : American Botanical Council - HerbClip
Link to Source
Dark Chocolate Intake Improves Walking Distance and Walking Time in Patients with Peripheral Artery Disease
Loffredo L, Perri L, Catasca E, et al. Dark chocolate acutely improves walking autonomy in patients with peripheral artery disease. J Am Heart Assoc. July 2014;3(4). pii: e001072. doi: 10.1161/JAHA.114.001072.
More than a fifth of adults older than 70 years are affected by peripheral arterial disease (PAD) in Western countries.1 A major symptom of the disease is intermittent claudication (IC), pain caused by impaired blood flow to the limbs during physical exercise. Reduced blood flow in patients with PAD is the result of endothelial dysfunction, reduced glucose oxidation, accumulation of toxic metabolites, impaired nitric oxide (NO) generation, and/or oxidative stress. In an earlier study,2 oxidative stress resulted in impaired walking distance autonomy (WDA), while inhibiting oxidative stress led to improved maximal walking distance (MWD). Polyphenol-rich cocoa (Theobroma cacao) has been associated with artery dilatation by reducing oxidative stress and increasing NO generation.3,4 In particular, dark chocolate enhances artery dilatation by lowering the activation of NOX2, a subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which has been shown to exert vasoconstrictor activity in both animals and humans. These authors conducted an interventional, crossover, single-blinded study to measure the acute effect of dark chocolate on WDA, artery dilatation, and NOX2-mediated oxidative stress in patients affected by moderate-to-severe PAD.
Specifically, the trial investigated the acute effect of 40 g chocolate (dark vs. milk) on MWD, maximal walking time (MWT), ankle brachial index (ABI) at rest and postexercise, flow-mediated dilatation (FMD), oxidative stress, and NO generation. Oxidative stress was assessed through blood levels of NOX-2 derivative peptide (sNOX2-dp; a marker of NOX2 activation) and isoprostanes. Serum levels of nitrite-nitrate (NOx) were used to evaluate NO generation.
The study, conducted between January 2012 and September 2013, included 20 patients with PAD with IC. At baseline, all patients underwent a full medical history and physical examination and answered a questionnaire about their fruit and vegetable intake. They were randomly assigned to receive either 40 g dark chocolate (≥85% cocoa) or milk chocolate (≤35% cocoa) in a crossover design, with at least 1 week separating the 2 intervention phases. The modified Folin-Ciocalteu colorimetric method used to determine the polyphenol content of the chocolate revealed a significantly higher total and single polyphenol content in the dark compared with the milk chocolate (P<0.001).
On study visit days, fasting blood samples were collected, followed by the first ABI and FMD at rest. The patients then completed the first treadmill test, after which MWD and MWT were measured and postexercise ABI was performed. The patients consumed 40 g of dark or milk chocolate. Two hours later, blood samples were again collected to analyze oxidative stress markers and epicatechin levels, and a second ABI and FMD evaluation was conducted. After 20 minutes, each patient completed a second treadmill test to determine MWD and MWT, followed by another postexercise ABI.
Compared with baseline, no difference was observed 2 hours after milk chocolate consumption in serum epicatechin, its metabolite EC-3-O-methylether, or epigallocatechin-3-gallate (EGCG) levels; however, the levels of serum catechin increased significantly. Two hours after dark chocolate intake, serum levels of epicatechin and its metabolite EC-3-O-methylether, catechin, and EGCG increased compared with baseline values.
Compared with baseline, MWD and MWT increased after dark chocolate intake (P<0.001 for both) but not after milk chocolate intake. This is a novel finding, according to the authors, noting that it supports the hypothesis that polyphenol content may be responsible for this effect, as dark chocolate is richer in polyphenols than milk chocolate.5
In a within-group analysis, no significant effect on ABI at rest or after exercise was observed after dark or milk chocolate intake. The analysis of variance performed on the study data revealed a significant difference for treatments in FMD (P=0.003); sNOX2-dp release (P=0.04); serum 8-iso-prostaglandin F2α-III, an indicator of lipid peroxidation (P=0.018); MWD (P=0.01); MWT (P=0.006); and postexercise ABI (P=0.04).
Pairwise comparisons showed that sNOX2-dp (P<0.001) and serum isoprostanes (P=0.01) significantly decreased after dark chocolate consumption but not after milk chocolate intake. FMD (P<0.001) and NOx(P=0.001) increased after dark chocolate intake, but no changes were observed after milk chocolate intake.
Performing a multiple linear regression analysis using a forward selection, the authors report "that Δ of MWD was independently associated with Δ of MWT (P<0.001) and Δ of NOx (P=0.018)."
The authors conducted an accompanying in vitro study in which human umbilical vein endothelial cells (HUVECs) were cultured to analyze the effect of scalar doses of single polyphenols such as epicatechin, catechin, or EGCG or a mixture of those on HUVEC activation. They found that HUVECs incubated with a mixture of polyphenols significantly increased NO (P<0.001). Significant decreases were seen in levels of E-selectin (P<0.001) and soluble vascular adhesion molecule-1 (P<0.001) (both associated with cardiovascular disease risk).
The vasodilating effect of dark chocolate could be due to the antioxidant effect of its polyphenols, which has been documented in humans through reduction of oxidative stress markers and an increase in its plasma antioxidant property. In this study, the patients who consumed dark chocolate experienced short-term changes in oxidative stress elicited by reduced serum isoprotanes, reduced NOX2 activity, and enhanced generation of NO. "These data may lead to speculation that the enhanced NO generation could be responsible for artery dilatation and eventually improve WDA," write the authors.
Referring to the study's limitations, the authors suggest that although the study is useful in understanding the mechanism of disease related to IC, the results are not transferable to clinical practice because of the small sample size and study design (single-blinded with no placebo group). Also, they say, only indirect evidence suggests that vasodilation is the mechanism behind the increase in walking autonomy; a direct analysis of peripheral circulation was not done.
"The results of this study suggest that short-term administration of dark chocolate improves walking autonomy with a mechanism involving its high content of polyphenols and perhaps mediated by an oxidative stress mechanism, which ultimately leads to enhanced NO generation." A longer duration of dark chocolate intake should be studied to assess whether it could be used to treat IC in patients with PAD.
Source : American Botanical Council
Link to Full Article + References
Cocoa Improves Cognitive Functioning in Older Adults with Neurovascular Compromise
Sorond FA, Hurwitz S, Salat DH, Greve DN, Fisher NDL.
Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people. Neurology. 2013;81(10):904-909.
Neurovascular coupling is the relationship between neuronal activity and cerebral blood flow; an increase in neuronal activity increases the demand for glucose and oxygen, so cerebral blood flow increases. The relationship between neurovascular coupling and cognition and aging is unknown. Cocoa (Theobroma cacao), which is rich in flavanols, may improve endothelial and cognitive function. The purpose of this randomized, double-blind, placebo-controlled study was to determine whether neurovascular coupling is associated with lower cognitive function, whether impaired coupling is associated with cerebral white matter disease, and whether cocoa can modify coupling.
Subjects (n = 60, aged > 65 years) were recruited from local advertisements near Boston, Massachusetts. Included subjects had hypertension (systolic blood pressure [SBP] > 140 mmHg or diastolic blood pressure [DBP] > 90 mmHg on repeated occasions, or treatment with antihypertensive medication) and/or well-controlled type 2 diabetes mellitus. Excluded subjects had absent temporal acoustic windows; intracranial stenosis; history of stroke, chest pain, or heart attack in the last 6 months; stage 2 high blood pressure not controlled by medication (> 160/100 mmHg); serum creatinine > 2 mg/dL; or diagnosis of dementia. Subjects received cocoa powder (Mars, Inc.; McLean, Virginia) in packets to be mixed with water and were instructed to consume 2 cups of cocoa daily either as flavanol-rich cocoa (609 mg flavanols/serving) or flavanol-poor cocoa (13 mg flavanols/serving) for 30 days.
Subjects continued with regular medications and were instructed to eliminate 100 kcal from the diet to prevent weight gain or worsening of diabetes. They were told to refrain from eating chocolate and not to consume caffeine on the study days. Cerebral blood flow velocity was measured at the middle cerebral artery via transcranial Doppler ultrasonography at baseline and after 30 days of treatment at rest, in response to cognitive tasks (N-back tasks), and before and after cocoa consumption. Magnetic resonance imaging (MRI) was conducted on 24 subjects to determine volumes of normal and abnormal brain white matter.
Subjects with intact neurovascular coupling had significantly better scores on the Trails B Cognitive test (P = 0.002) and the 2-Back Task (P = 0.02). There was no significant association between neurovascular coupling and the mini-mental state examination score. On MRI, abnormal white matter appears as hyperintensities, and tissue microstructure is measured with fractional anisotropy and mean diffusivity. As would be expected, greater neurovascular coupling occurred in subjects with less white matter macro- and microstructure damage (smaller volume of hyperintensities and higher fractional anisotropy, P = 0.02).
After both 24 hours and 30 days of cocoa consumption, cerebral blood flow and blood pressure did not significantly differ between high- and low-flavanol treatment groups, so both groups were combined for analysis. Blood pressure significantly decreased after 1 day of cocoa compared with baseline (SBP: 3.2 ± 13.4 mmHg, P = 0.07; DBP: 3.0 ± 9.6 mmHg, P = 0.02); however, at 30 days there was no significant effect on blood pressure. At rest, there was no significant difference between treatment groups for neurovascular coupling. During cognitive testing, 89% of subjects with impaired coupling at baseline had a significant improvement in coupling after 30 days of cocoa compared with 36% of those with intact baseline coupling (P = 0.0002). In those subjects with impaired baseline coupling, cocoa consumption was associated with 10.6% (P = 0.0001) and 8.3% (P < 0.0001) increases in coupling at 24 hours and 30 days, respectively. Cocoa resulted in very little change in coupling in subjects with intact coupling at baseline. Also, Trails B performance significantly improved in response to 30 days of cocoa consumption in those with impaired coupling at baseline (P < 0.007).
The authors conclude that neurovascular coupling is related to cognitive performance and cerebral white matter structural integrity in elderly subjects with vascular risk factors. In addition, they conclude that neurovascular coupling can be modified by cocoa. Cocoa had an effect irrespective of the amount of flavanols, indicating that there is something else in cocoa that is producing the benefit or that coupling is so sensitive to flavanols that even the small amount in the flavanol-poor group was enough to produce a benefit. It should be noted that this study population had vascular disease, so the effect of cocoa on healthy populations may be different. The authors do not discuss other forms of cocoa, for example, a chocolate bar, which may be preferable to drinking daily hot cocoa especially in warmer months.
—Heather S. Oliff, PhD
Source : ABC
Link to Source
Chocolate in History: Food, Medicine, Medi-Food
Donatella Lippi Department of Experimental and Clinical Medicine, Section of Health Services, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
Throughout history, chocolate has been used to treat a wide variety of ailments, and in recent years, multiple studies have found that chocolate can have positive health effects, providing evidence to a centuries-long established use; this acknowledgement, however, did not have a straight course, having been involved in religious, medical and cultural controversies. Christian Europe, in fact, feared the exhilarating effects of new drinks, such as chocolate, coffee and tea. Therefore, these beverages would have been banished, had not doctors and scientists explained that they were good for the body. The scientific debate, which reached its peak in Florence in the 18th century, regarded the therapeutic effectiveness of the various chocolate components: it was necessary to know their properties first, in order to prepare the best cacao concoction for every patient. When Dietetics separated from Medicine, however, chocolate acquired the role of vehicle for easing the administration of bitter medicines, being associated to different health problems. The recent rediscovery of the beneficial use of cacao and chocolate focuses upon its value as supplemental nutrition. Building a bridge to the past may be helpful to detect the areas where the potential health benefits of chocolate are likely to be further explored.
Source : Nutrients
Download Full Article
Prospective Study and Meta-Analysis of Chocolate and Reduction of Stroke Risk
by Risa N. Schulman, PhD
Reviewed: Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke: a prospective cohort of men and meta-analysis. Neurology. 2012;79(12):1223-1229.
Much evidence has accumulated to show that cocoa (Theobroma cacao, Sterculiaceae) and chocolate may have benefits for cardiovascular health through antioxidant, antiplatelet, anti-inflammatory, and blood pressure-lowering effects. In this paper, effects on stroke have been examined in four studies, with two having statistically significant results. However, none of these studies examined exclusively male populations, and only one made its evaluation based on stroke type. The prospective study assessed the association between chocolate consumption and risk of stroke and stroke subtypes in a cohort of Swedish men. In addition, the authors conducted a meta-analysis of prospective studies involving chocolate and stroke risk.
The study used data from the 1997 Cohort of Swedish Men (aged 45 to 79 years). Questionnaires with 350 items on diet and lifestyle were gathered from 48,850 men who were a good representation of the general population with respect to age distribution, relative body weight, and education level, compared with representative data from the Official Statistics of Sweden. After excluding questionnaires that were not completely filled in, and patients who had died or had a history of cancer, cardiovascular disease, diabetes, or an implausible total energy intake, 37,103 men remained.
Consumption of chocolate was assessed using a self-administered food-frequency questionnaire that included 96 foods and beverages. Consumption in grams was computed by multiplying the frequency of chocolate consumption by four age-specific portion sizes (43-54 years, 42 g; 55-63 years, 34 g; 64-71 years, 27 g; 72-77 years, 26 g), which were obtained from the authors’ validation study in Swedish men. Approximately 90 percent of chocolate consumption during the time frame of the study was in the form of milk chocolate.
Incidence of stroke was identified via the Swedish Hospital Discharge Registry and was classified as cerebral infarction (ICD-10 [International Statistical Classification of Diseases and Related Health Problems 10th Revision] code I63), intracerebral hemorrhage (I61), subarachnoid hemorrhage (I60), and unspecified stroke (I64).
In 10.2 years of follow-up, 1,995 cases of first-time stroke were identified, including 1,511 cerebral infarctions, 321 hemorrhagic strokes (254 intracerebral hemorrhages and 67 subarachnoid hemorrhages), and 163 unspecified strokes.
Patients in the highest quartile of chocolate consumption (62.9 g/week) had a statistically significantly lower risk of total stroke by 17 percent (95% confidence interval [CI]: 1-30) after adjustment for age and stroke risk factors, including blood pressure. This association was similar across stroke types. There was an inverse relationship between chocolate consumption and risk of total stroke observed in men without hypertension (relative risk [RR]: 0.76; 95% CI: 0.62-0.93), but not in men with a history of hypertension (RR: 1.04; 95% CI: 0.77-1.41; P for interaction = 0.04). The age-standardized incidence rates of stroke were 85 per 100,000 person-years among men in the lowest quartile of chocolate consumption and 73 per 100,000 person-years among men in the highest quartile.
For the meta-analysis, the databases PubMed and EMBASE were searched up to January 13, 2012, with no restrictions imposed. Four prospective studies examining the association between chocolate consumption and stroke were identified, plus the current study, making a total of five. These studies included a total of 4,260 stroke cases over a range of eight to 16 years of follow-up. Highest and lowest consumption of chocolate were compared, and dose response also was analyzed.
The RR of stroke in the highest compared to the lowest quartiles of chocolate consumption was 0.81 (95% CI: 0.73-0.90), with no heterogeneity. Dose response could be assessed in four out of five of the studies; for a 50 g increment per week, the RR was 0.86 (95% CI: 0.76-0.97), with no heterogeneity among studies (P=0.21; I2=34.1%).
The highest levels of chocolate consumption were associated with a decreased risk of stroke in men, and this was confirmed by the meta-analysis. The results can be extrapolated to men in general because of the wide representation of men present in the sample population. Though the exact mechanism of action for the stroke benefit has not been elucidated, it is likely due to the pleiotropic (producing multiple effects from one gene) cardiovascular benefits of chocolate, including the lowering of blood pressure. The strengths of the study are its large population and its nearly complete data regarding stroke incidence. Its limitations include a lack of differentiation between types of chocolate consumed, self-reporting of consumption, and evidence of small study effects in the meta-analysis. The authors caution that chocolate should be consumed in moderation because of its high fat and sugar content.
Source : American Botanical Council
Link to Full Article
Dark Chocolate and Red Wine The Food of Love and Health
If you want to keep your true love's heart beating strong, Susan Ofria, clinical nutrition manager at Gottlieb Memorial Hospital, said the real food of love is dark chocolate and red wine. In moderation, red wine and dark chocolate are good health choices not just on Valentine’s Day, but for any occasion. "You are not even choosing between the lesser of two evils, red wine and dark chocolate have positive components that are actually good for your heart," said Ofria, a registered dietitian at the Loyola University Health System's Melrose Park campus.
Red wine and dark chocolate with a cocoa content of 70 percent or higher contain resveratrol, which has been found to lower blood sugar. Red wine is also a source of catechins, which could help improve "good" HDL cholesterol.
Ofria, who is also a nutrition educator, recommends the following list of heart-healthy ingredients for February, which is national heart month, and for good heart health all year.
Eight Ways to Say "I Love You" From Loyola Dietitian
Red Wine - "Pinots, shirahs, merlots -- all red wines are a good source of catechins and resveratrol to aid 'good' cholesterol."
Dark chocolate, 70 percent or higher cocoa content -- "Truffles, soufflés and even hot chocolate can be a good source of resveratrol and cocoa phenols (flavonoids) as long as dark chocolate with a high content of cocoa is used."
Salmon/tuna -- "Especially white, or albacore, tuna and salmon are excellent sources of omega-3 fatty acids, and canned salmon contains soft bones that give an added boost of calcium intake."
Flaxseeds -- "Choose either brown or golden yellow, and have them ground for a good source of omega-3 fatty acids, fiber, phytoestrogens."
Oatmeal -- "Cooked for a breakfast porridge or used in breads or desserts, oatmeal is a good source of soluble fiber, niacin, folate and potassium."
Black or kidney beans -- Good source of niacin, folate, magnesium, omega-3 fatty acids, calcium, soluble fiber.
Walnuts and almonds -- "Both walnuts and almonds contain omega-3 fatty acids, vitamin E, magnesium, fiber and heart-favorable mono- and polyunsaturated fats."
Blueberries/cranberries/raspberries/strawberries -- "Berries are a good source of beta carotene and lutein, anthocyanin, ellagic acid (a polyphenol), vitamin C, folate, potassium and fiber."
Source : Newswise
Link to Source
Nonlinear Meta-analysis of Cocoa Effects on Blood Pressure Finds It Provides a Dose-dependent Benefit
Ellinger S, Reusch A, Stehle P, Helfrich HP.
Epicatechin ingested via cocoa products reduces blood pressure in humans: a nonlinear regression model with a Bayesian approach. Am J Clin Nutr. 2012;95(6):1365-1377.
Four separate meta-analyses have been performed on the effects of cocoa (Theobroma cacao) on blood pressure (BP), all showing that it provides a benefit. It is thought that these effects are due to the dose of epicatechin; if so, this may explain the differences in results in the studies used in the meta-analyses. This paper reports on the novel use of an alternate meta-analysis using a nonlinear regression model with a Bayesian approach and which includes a Markov chain Monte Carlo method that takes full account of the nonlinearity of the regression model. The authors hoped to thereby understand whether the dose of epicatechin is related to the magnitude of its BP-lowering effect and if this can explain between-study differences in effects.
Medline was searched until July 2011 for randomized, controlled trials (RCTs), which were included if they met the following criteria: (1) control substances were of low-flavanol composition; (2) BP was measured after an overnight fast; (3) mean or median systolic BP (SBP) or diastolic BP (DBP), standard deviations (SDs), standard error of the mean (SEM), 95% credible intervals (CIs), or P-values for changes were given; and (4) data on epicatechin intake were recorded.
Twenty-six RCTs were identified, of which 13 met the inclusion criteria. An additional study was obtained from an author; and 1 study had 3 arms, each of which was considered separately. This yielded a total of 16 studies for consideration (16 on SBP and 15 on DBP).
The regression curve showed that reductions in SBP and DBP were dependent on the dose of epicatechin. The estimated asymptotic value K of the treatment effect was -4.6 mmHg (95% CI: -5.4, -3.9 mmHg) for SBP and -2.1 mmHg (95% CI: -2.7, -1.6 mmHg) for DBP (Figure 3). The coefficient c reflecting the initial slope of the curve was -2.5 mmHg/mg for SBP (95% CI: -8.4, -0.6 mmHg/mg). For DBP, the mean value for c was -4.3 mmHg/mg (95% CI: -9.6, -0.2 mmHg/mg).
From this curve, a mean reduction for a dose of 25 mg of epicatechin for SBP could be estimated to be -4.1 mmHg (95% CI: -4.6, -3.6 mmHg) and for DBP, a mean reduction of -2.0 mmHg (95% CI: -2.4, -1.5 mmHg) could be estimated.
Because the 95% CIs are narrower in the nonlinear regression model than in the regular meta-analyses, the authors conclude that the dose of epicatechin is responsible for the heterogeneity of the studies, and that their model estimates the treatment effects more precisely than the linear regression model. They argue that the likelihood of confounding effects was low and that the merging of data from both ambulatory and 24-hour BP readings should not affect the results since they are very similar in magnitude. Limitations include the inability to understand the effects of low doses of epicatechin (because of lack of data for such doses) and the fact that the data cannot be readily extrapolated to normotensive subjects, since only 25% of the studies examined that population.
The authors conclude that a dose of 25-30 g of high-flavanol cocoa should lower SBP by -4.1 mmHg and DBP by -2.0 mmHg. The cocoa should be consumed in a form that will not lead to unwanted weight gain.
--Risa Schulman, PhD
Source : American Botanical Council
Link to Source
Chocolate: A Sweet Method for Stroke Prevention in Men?
Eating a moderate amount of chocolate each week may be associated with a lower risk of stroke in men, according to a new study published in the August 29, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“While other studies have looked at how chocolate may help cardiovascular health, this is the first of its kind study to find that chocolate, may be beneficial for reducing stroke in men,” said study author Susanna C. Larsson, PhD, with the Karolinska Institute in Stockholm, Sweden. For the study, 37,103 Swedish men ages 49 to 75 were given a food questionnaire that assessed how often they consumed various foods and drinks and were asked how often they had chocolate. Researchers then identified stroke cases through a hospital discharge registry. Over 10 years, there were 1,995 cases of first stroke.
Men in the study who ate the largest amount of chocolate, about one-third of a cup of chocolate chips (63 grams) per week, had a lower risk of stroke compared to those who did not consume any chocolate. Those eating the highest amount of chocolate had a 17-percent lower risk of stroke, or 12 fewer strokes per 100,000 person-years compared to those who ate no chocolate. Person-years is the total number of years that each participant was under observation.
In a larger analysis of five studies that included 4,260 stroke cases, the risk of stroke for individuals in the highest category of chocolate consumption was 19 percent lower compared to non-chocolate consumers. For every increase in chocolate consumption of 50 grams per week, or about a quarter cup of chocolate chips, the risk of stroke decreased by about 14 percent.
“The beneficial effect of chocolate consumption on stroke may be related to the flavonoids in chocolate. Flavonoids appear to be protective against cardiovascular disease through antioxidant, anti-clotting and anti-inflammatory properties. It’s also possible that flavonoids in chocolate may decrease blood concentrations of bad cholesterol and reduce blood pressure,” said Larsson.
“Interestingly, dark chocolate has previously been associated with heart health benefits, but about 90 percent of the chocolate intake in Sweden, including what was consumed during our study, is milk chocolate,” Larsson added.
Source : Newswise
Link to Source
Dark Chocolate Increases Nitric Oxide Levels and Decreases Blood Pressure in Prehypertensive Subjects
Sudarma V, Sukmaniah S, Siregar P. Effect of dark chocolate on nitric oxide serum levels and blood pressure in prehypertension subjects. Acta Med Indones. October 2011;43(4):224-228.
Prehypertension, a risk factor for coronary heart disease and stroke, is defined as a systolic blood pressure between 120 and 139 mm Hg or diastolic blood pressure between 80 and 89 mm Hg.1, 2 According to these authors from the University of Indonesia, the mean blood pressure in Indonesians aged 25 to 34 years is 124.7/79.9 mm Hg. Risk factors for hypertension are obesity, age, high intake of energy and sodium, a low level of physical activity, and alcohol intake. Vascular disorders in prehypertensive patients are influenced by, among other factors, a decrease in synthesis and bioavailability of nitric oxide (NO) leading to endothelial dysfunction.3 Flavanols reportedly can activate endothelial nitric oxide synthase, which increases synthesis and bioavailability of NO and in turn restores endothelial function. Dark chocolate (Theobroma cacao) is a major source of flavanols. These authors conducted a parallel, randomized clinical trial to investigate the effects of dark chocolate on NOx serum levels and blood pressure in individuals with prehypertension. NOx serum levels are the sum of nitrite and nitrate levels as the metabolite of NO. Investigators estimate NO production by measuring NOx levels.
Thirty-two male and female employees of a dental faculty and a private company were recruited and divided into 2 groups of 16 each. Exclusion criteria included those with a history of hypertension; smokers; those who consumed red wine or alcohol; pregnant or breast feeding women; menopausal women; those who used antihypertension drugs; and those who took vitamin C, vitamin E, or other antioxidant supplements. Data are reported on 30 of the subjects (14 in the treatment group and 16 in the control group). The treatment group received 30 grams of dark chocolate daily (containing 70% cocoa; no other data on the source given) and dietary counseling. Those in the placebo group received 25 grams of white chocolate daily (no data on the source given) and dietary counseling. The study lasted 15 days.
The subjects were aged 25 to 44 years, prehypertensive, and had a body mass index (BMI) of 18.5 to 24.9 kg/m2. The characteristics of the members of the 2 groups were similar, except that the treatment group was more physically active than the placebo group.
Food intake data were obtained to determine energy, sodium, and polyphenol intake. The subjects were asked to fast overnight for 10 to 12 hours before having blood samples drawn to measure NOx serum levels.
At baseline, on treatment day 8, and after treatment, blood pressure was measured for all subjects. Mean intakes of energy and sodium were not significantly different between the 2 groups. The polyphenol intake of the treatment group during weeks 1 and 2 were significantly higher than those of the placebo group. After 15 days, the NOx serum levels in the treatment group increased significantly compared to baseline (P=0.001), while the same levels in the placebo group decreased significantly compared to baseline (P=0.001). The intergroup difference was also significant (P<0.001), with the treatment group being 4-fold higher than the control after 15 days. After 15 days, the systolic blood pressure decreased by an average of 8 mm Hg compared to baseline (significant, but P value not fully reported). The difference in systolic blood pressure between the groups was significant (P=0.001), while the difference in diastolic blood pressure was not significant.
The authors report a strong negative correlation between the changes in NOx serum levels and the changes in systolic blood pressure, while there was a significantly moderate negative correlation for the changes in diastolic blood pressure. The authors cite a study4 confirming that increased NOx serum levels increase vasodilation, which in turn decreases blood pressure.
According to the authors, this study was limited by the difficulty in blinding between the dark and white chocolate, although they claim that it was minimized by placing the chocolates in boxes of the same shape and color.
The authors conclude that in prehypertensive subjects, the consumption of 30 grams of dark chocolate with 70% cocoa daily for 15 days increased NOx serum levels. Systolic blood pressure was significantly decreased in those who consumed the dark chocolate; however, the decrease in diastolic blood pressure was not significant. There were a number of limitations to the study, including insufficient blinding and use of a food database lacking in many of the locally eaten foods. The reporting in this paper was also of poor quality with errors in data interpretation, omissions of critical information about the study design, and misreporting of statistics. The authors mention the importance of flavanols, but yet no testing was done on the dark chocolate to evaluate the flavanol level. The use of a list of polyphenol content is not enough.
1Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. 2003;289(19):2560-2572.
2Lim S. Recent update in the management of hypertension. Acta Med Indones. 2007;39(4):186-191.
3Foëx P, Sear JW. Hypertension: pathophysiology and treatment. Continuing Education in Anaesthesia, Critical Care & Pain. 2004;4(3):71-75.
4Hall WL, Formanuik NL, Harnpanich D, et al. A meal enriched with soy isoflavones increases nitric oxide-mediated vasodilation in healthy postmenopausal women. J Nutr. 2008;138(7):1288-1292.
Source : American Botanical Council
Link to Source
Prevention: Evidence of Heart Benefits From Chocolate
An analysis of studies including more than 100,000 subjects has found that high levels of chocolate consumption are associated with a significant reduction in the risk of certain cardiovascular disorders.
The seven studies looked at the consumption of a variety of chocolate — candies and candy bars, chocolate drinks, cookies, desserts and nutritional supplements. By many measures, consumption of chocolate was linked to lower rates of stroke, coronary heart disease, blood pressure and other cardiovascular conditions.
But there was no beneficial effect on the risk for heart failure or diabetes.
Over all, the report, published Monday in the British medical journal BMJ, showed that those in the group that consumed the most chocolate had decreases of 37 percent in the risk of any cardiovascular disorder and 29 percent in the risk for stroke.
Still, the lead author, Dr. Oscar H. Franco, a lecturer in public health at the University of Cambridge, warned that this finding was not a license to indulge and noted that none of the studies reviewed involved randomized controlled trials.
“Chocolate may be beneficial, but it should be eaten in a moderate way, not in large quantities and not in binges,” he said. “If it is consumed in large quantities, any beneficial effect is going to disappear."
Source + Link : New York Times (Aug 2011)
Link to Study - BMJ - Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis