There has been growing interest in the potential cardiovascular benefits associated with cocoa consumption. As a result of accurate analytical methodologies, there is evidence to support that the flavanols in cocoa can be absorbed, are bioactive, and may be responsible for the cardiovascular benefits associated with regular cocoa consumption. The flavanols in cocoa exist in a multitude of different stereochemical configurations, thus giving rise to a unique and complex mixture of compounds. Given this complexity, the quantitative analysis of cocoa flavanols in foods can be challenging. While there are published methods suitable for the analysis of these compounds, these methods require sophisticated instrumentation and can be challenging to set up. As such, simpler techniques that measure such things as total phenolic content or antioxidant potential have been used as indicators of flavanol content. However, as these simpler assays are prone to interferences and are not specific for flavanols, these methods are not appropriate for use in studies that aim to examine the physiological effects of cocoa flavanols. It is only through the use of methods that can accurately quantify these flavanols that it will be possible to make meaningful dietary recommendations regarding the consumption of cocoa flavanol containing foods.
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Epidemiologic investigations support the hypothesis that regular consumption of flavonoid-containing foods can reduce the risk of cardiovascular diseases (CVD). While flavonoids are ubiquitous in plants, cocoa can be particularly rich in a sub-class of flavonoids known as flavanols. A number of human dietary intervention trials with flavanol-containing cocoa products have demonstrated improvements in endothelial and platelet function, as well as blood pressure. These studies provide direct evidence for the potential cardiovascular benefits of flavanol-containing foods and help to substantiate the epidemiological data. In this review, results from selective published trials with cocoa and chocolate focused on risk for CVD will be discussed along with a study we recently completed evaluating the effects of the daily consumption of flavanol-containing dark chocolate (CocoaVia?) with and without plant sterol esters on CVD markers in a normotensive population with mild hypercholesterolemia. In this study, the daily consumption of flavanol-containing dark chocolate was associated with a significant mean reduction of 5.8 mmHg in systolic blood pressure. Together the results of these human dietary intervention trials provide scientific evidence of the vascular effects of cocoa flavanols and suggest that the regular consumption of cocoa products containing flavanols may reduce risk of CVD.
Signs of chronic or acute inflammation have been demonstrated in most cardiovascular diseases of multifactorial pathogenesis, including atherosclerosis and chronic heart failure. The triggers and mechanisms leading to inflammation may vary between clinical conditions but they share many common mediators, including specific patterns of eicosanoid and cytokine production. Certain cocoa-based products can be rich in a subclass of flavonoids known as flavanols, some of which have been found in model systems to possess potential anti-inflammatory activity relevant to cardiovascular health. Indeed, experimental evidence demonstrates that some cocoa-derived flavanols can reduce the production and effect of pro-inflammatory mediators either directly or by acting on signaling pathways. However, it should be noted that the evidence for any beneficial effects of cocoa flavanols in providing a meaningful anti-inflammatory action has been gathered predominantly from in vitro experiments. Therefore, additional research in well-designed human clinical experiments, using cocoa properly characterized in terms of flavanol content, would be a welcome addition to the evidence base to determine unambiguously if this benefit does indeed exist. If so, then flavanol-rich cocoa could be a potential candidate for the treatment, or possibly prevention, of the broad array of chronic diseases that are linked to dysfunctional inflammatory responses.
Flavanols and their related oligomeric compounds, the procyanidins, have received increased attention during the past decade due to their reported health benefits. On the basis of compelling data published during the past decade demonstrating that the consumption of certain flavanol-rich foods can improve markers of cardiovascular health, additional clinical, and epidemiological research is clearly warranted to establish appropriate public health recommendations. However, recommendations on the consumption of these foods appropriate for use by health professionals can only be made on the basis of clinical investigations that accurately identify and quantify--through proper analytical measurement systems--the flavanols in the foods used in these investigations. This manuscript provides an overview of the strengths, weaknesses, and limitations of commonly used analytical methods to characterize the content of flavanols in foods. Two nonspecific measurements widely used by investigators, the Folin-Ciocalteu assay and the Oxygen Radical Absorbance Capacity (ORAC) measurement, are discussed in this context, as is the use of various high-performance liquid chromatography methods that provide more specific data related to the content of flavanols in foods. A comparison of the data obtained from these analytical methods to those of the more rigorous high-performance liquid chromatography analyses demonstrates that these nonspecific methods are ill-suited for providing unequivocal data necessary to evaluate the importance of dietary flavanols in the context of improving cardiovascular health. Meaningful dietary recommendations for the consumption of flavanol-rich foods will only be made possible by additional well-designed clinical and epidemiological studies enabled by detailed compositional data obtained through use of appropriate analytical methods.
Atherosclerosis is the major cause for chronic vascular diseases. The key event in the pathogenesis of atherosclerosis is believed to be dysfunction of the endothelium and disruption of endothelial homeostasis, leading to vasoconstriction, inflammation, leukocyte adhesion, thrombosis, and proliferation of vascular smooth muscle cells. Endothelium-derived nitric oxide (NO) plays a major role in vascular homeostasis and a decrease in NO-bioavailability accelerates the development of atherosclerosis. Given that endothelial dysfunction is at least in part reversible, the characterization of endothelial function and therapeutical approaches have gained much attention over the past years. Recent studies demonstrated that especially the consumption of plant-derived foods rich in certain flavonoids can improve endothelial function in both compromised and healthy humans. Furthermore, various physiologic and biochemical measures have been used previously as biomarkers for the assessment of the proposed beneficial effects of flavonoids in this context. More recently, the analysis of plasma nitros(yl)ated species (RXNOs), referred to as the circulating NO pool, has gained recognition, especially as a marker for endothelial function. This review is aimed at evaluating the suitability of quantifying this NO pool as a biomarker for cardiovascular function in humans, in particular during dietary interventions with flavonoid-rich foods.
Epidemiology studies suggest that the consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular disease. Plant-derived foods and beverages, such as red wine, tea, grape and grape juice, cocoa and chocolate, can be rich in 1 particular class of flavonoid, the flavan-3-ols. There is now an increasing body of research that suggests that consuming flavanol-rich foods can positively affect hemostasis, through mechanisms that either directly affect platelet function or increase certain endothelium-derived factors that maintain platelet acquiescence or increase fibrinolysis. In this paper, we will review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent hemostasis. In addition, we will briefly review the body of literature with regard to other flavanol-rich foods and beverages, and possible mechanisms of action.
Endothelial dysfunction is the pathophysiologic principle involved in the initiation and progression of arteriosclerosis, thus endothelial function serves as a "barometer" for cardiovascular health that can be used for the evaluation of new therapeutic strategies. This review provides an introduction to the concept of endothelial dysfunction, and it explores the importance of this prognostic marker in the context of clinical, dietary interventions in humans. Moreover, we summarize and evaluate the findings of various clinical trials that demonstrated an improvement of endothelial dysfunction in subjects with cardiovascular risk factors after the acute and chronic consumption of flavanol-rich foods, including cocoa products, red wine, and tea.
Cardiovascular benefits for cocoa are being claimed in the scientific literature with growing intensity. To date, excitement over the potential health benefits of flavonoids has been driven mostly by epidemiological studies of tea and red wine, but raw cocoa contains specific flavonoids in concentrations far exceeding those from most other sources. Early evidence supports cocoa's enhancement of endothelial function via improvement of nitric oxide synthesis. However, many new studies have brought more confusion than clarity to the enterprise. This review provides guidelines for legitimate research in this promising field. TOPICS OF DISCUSSION: Evidence generated from epidemiological studies, linking an increase in flavonoid ingestion to a reduction in cardiovascular events, is less convincing than data from controlled clinical trials. Whereas a few trials have shown evidence for an enhancement of endothelial function, inhibition of platelet adhesion and low-density lipoprotein oxidation, many studies have ignored scientific principles. Tremendous variability in cocoa processing, flavonoid content, measurement and dosing threatens the field. Valid research depends upon the precise identification and measurement of compounds of interest, which are probably the flavanols catechin and epicatechin, their oligomers and metabolites. These measures depend upon reliable methods of separation and quantification. Whether the monomers, dimers or larger flavanol oligomers, or their metabolites, are responsible for biological efficacy remains to be determined. Final questions surround bioavailability and dosing frequency. CONCLUSIONS: Evidence is mounting to support cardiovascular health benefits from the consumption of flavanol-rich cocoa. This review hopes to illuminate sound scientific principles by which future research in the field can be guided.
Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP) IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg) aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.
Fruits and vegetables have historically been considered rich sources of essential dietary micronutrients, soluble fiber, and antioxidants. More recently they are have been recognized as important sources for a wide array of phytochemicals that individually, or in combination, may benefit vascular health. Flavonoids are the largest, and most widely distributed class of phytochemicals, and can be further subdivided into several different sub-classes. Several epidemiology studies have observed an inverse association between flavonoid intake and risk of cardiovascular mortality. One sub-class of flavonoids, the flavanols, is found in foods such as grapes, red wine, tea, cocoa and chocolate; however, it is important to note that common food processing practices can significantly reduce the levels of these compounds found in finished food products. Recent studies have examined the potential of flavanol-rich cocoa and chocolates to influence vascular health. In this review, we discuss evidence for the hypothesis that the consumption of flavanol-rich cocoa can reduce the risk for cardiovascular disease through a multiplicity of mechanisms, including changes in oxidant defense mechanisms, vascular reactivity, cytokine production, and platelet function.
There has been a long-standing interest in the relation between what we eat and cardiovascular risk. Over the years, attention has been given to calories, total fat, saturated fat, cholesterol, omega-3 polyunsaturated fatty acids, trans fatty acids, folic acid, antioxidants and, most recently, flavanols. Flavanol concentrations can be moderately high in a number of foods that have been associated with a reduction in cardiovascular risk including red wine, and black and green tea. Some cocoa and chocolate products are extraordinarily rich in flavanols but, as with other flavanol-containing foods, certain post-harvesting and processing procedures can have a striking influence on the flavanol content of chocolate and cocoa. Endothelial dysfunction with a consequent reduction in nitric oxide production has achieved a central conceptual role in the pathogenesis of atherosclerosis and coronary artery disease, diabetes mellitus and hypertension. Recent evidence that flavanol-rich cocoa activates vascular nitric oxide synthesis in the intact human raises an interesting possibility of a therapeutic potential.
This paper offers a review of current scientific research regarding the potential cardiovascular health benefits of flavonoids found in cocoa and chocolate. Recent reports indicate that the main flavonoids found in cocoa, flavan-3-ols and their oligomeric derivatives, procyanidins, have a variety of beneficial actions, including antioxidant protection and modulation of vascular homeostasis. These findings are supported by similar research on other flavonoid-rich foods. Other constituents in cocoa and chocolate that may also influence cardiovascular health are briefly reviewed. The lipid content of chocolate is relatively high; however, one third of the lipid in cocoa butter is composed of the fat stearic acid, which exerts a neutral cholesterolemic response in humans. Cocoa and chocolate contribute to trace mineral intake, which is necessary for optimum functioning of all biologic systems and for vascular tone. Thus, multiple components in chocolate, particularly flavonoids, can contribute to the complex interplay of nutrition and health. Applications of this knowledge include recommendations by health professionals to encourage individuals to consume a wide range of phytochemical-rich foods, which can include dark chocolate in moderate amounts.
Cocoa and chocolate foods produced by appropriate methods can contribute significant amounts of heart-healthy flavanols to the diet. These flavanols may enhance cardiovascular health by delaying blood clotting, improving vascular endothelial function, and helping to moderate inflammation. The benefits of chocolate can be enjoyed without guilt as part of a healthful balanced diet.
Fruits and vegetables have historically been considered rich sources of essential dietary micronutrients, soluble fiber, and antioxidants. More recently they are have been recognized as important sources for a wide array of phytochemicals that individually, or in combination, may benefit vascular health. Flavonoids are the largest, and most widely distributed class of phytochemicals, and can be further subdivided into several different sub-classes. Several epidemiology studies have observed an inverse association between flavonoid intake and risk of cardiovascular mortality. One sub-class of flavonoids, the flavanols, is found in foods such as grapes, red wine, tea, cocoa and chocolate; however, it is important to note that common food processing practices can significantly reduce the levels of these compounds found in finished food products. Recent studies have examined the potential of flavanol-rich cocoa and chocolates to influence vascular health. In this review, we discuss evidence for the hypothesis that the consumption of flavanol-rich cocoa can reduce the risk for cardiovascular disease through a multiplicity of mechanisms, including changes in oxidant defense mechanisms, vascular reactivity, cytokine production, and platelet function.
Epidemiologic studies suggest an inverse association of tea consumption with cardiovascular disease. The antioxidant effects of flavonoids in tea (including preventing oxidative damage to LDL) are among the potential mechanisms that could underlie the protective effects. Other possible mechanisms include attenuating the inflammatory process in atherosclerosis, reducing thrombosis, promoting normal endothelial function, and blocking expression of cellular adhesion molecules. Cocoa and chocolate can also be rich sources of flavonoids. Flavanols and procyanidins isolated from cocoa exhibit strong antioxidant properties in-vitro. In acute feeding studies, flavanol-rich cocoa and chocolate increased plasma antioxidant capacity and reduced platelet reactivity. Based on limited data, approximately 150 mg of flavonoids is needed to trigger a rapid antioxidant effect and changes in prostacyclin. Some dose-response evidence demonstrates an antioxidant effect with approximately 500 mg flavonoids. Brewed tea typically contains approximately 172 mg total flavonoids per 235 ml (brewed for 2 min); hence, consumption of 1 and 3.5 cups of tea would be expected to elicit acute and chronic physiologic effects, respectively. Chocolate is more variable with some products containing essentially no flavonoids (0.09 mg procyanidin/g), whereas others are high in flavonoids (4 mg procyanidin/g). Thus, approximate estimates of flavonoid rich chocolate needed to exert acute and chronic effects are 38 and 125 g, respectively. Collectively, the antioxidant effects of flavonoid-rich foods may reduce cardiovascular disease risk.
Chocolate and cocoa are extensively used in many cultures. Although their composition has been studied, the functional significance of the components has not been as well defined. There are indications that cocoa constituents exert beneficial effects on human health, and therefore cocoa and chocolate may be considered functional foods. The use of functional foods to modulate human health has gained greater significance in recent years, and chocolate is widely consumed throughout society. We performed an extensive review of literature in both animal and human systems with respect to composition, bioavailability, comparative analysis with other food products and, especially, implications for cardiovascular disease and the human immune system. Although chocolate contains a high amount of saturated fats, the two major fatty acids are palmitic and stearic acid, which appear to have fewer implications for progression of coronary artery disease than other saturated fatty acids. In addition, the implications of flavonoids and other polyphenols in chocolate as antioxidants are significant, and their ability to modulate the immune system may also be applicable to infection and neoplasia. In this review, we attempt to place these issues in perspective and to provide the reader with an extensive summary of the literature on chocolate and cocoa and their potential mechanisms of action with respect to human health.
Nutrients exert measurable effects on biological processes and are among many factors that optimize health by helping to prevent, cure, treat or slow the progression of chronic diseases. Certain plant components (i.e., phytochemicals) may not be considered essential by traditional measures, but are increasingly recognized for their beneficial health effects. In particular, dietary flavonoids may make an important contribution to cardiovascular health. Epidemiological studies have shown that intake of flavonoids may be inversely associated with long-term mortality from coronary heart disease in epidemiological studies. Research with flavonoid-rich foods such as red wine, tea, blueberries and chocolate has demonstrated their antioxidant capacity. However, different flavonoids appear to have varying degrees of effect (e.g., inhibiting the oxidation of low-density lipoprotein cholesterol) and most of the flavonoid research has been limited to a few simple flavonoids, rather than a comprehensive investigation of all flavonoids present in the diet or a particular foodstuff. Well-controlled clinical studies are needed to determine whether flavonoids offer true benefits to cardiovascular health and to understand other potential mechanisms, in addition to antioxidant activity, which may be responsible for their protective action.
