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.
Among the most recent candidates that have drawn important attention are the flavonoids - polyphenolic compounds found in a variety of foods of vegetable origin, including tea, cocoa, chocolate, red wine, purple grapes, apples, onions and cranberries. In particular, a specific subclass of flavonoids - known as flavanols - has attracted increasing interest as a result of recent epidemiological, mechanistic and human intervention studies. Among the wide variety of dietary flavanol sources, some cocoas and chocolates can be extraordinarily rich in certain flavanols.
A possible confounder in epidemiological studies is a contribution from sources of flavonoids that were not part of the analysis. One striking example in this area is cocoa and chocolate, which can contain flavonoid, specifically flavanol, profiles and concentrations very different from those of other sources. Equally important is the fact that foods recognized as being flavonoid-rich vary in their flavonoid content substantially, largely due to common techniques used during post-harvest handling of raw materials and processing during food production.
The biological effects of plant flavonoids are wide-ranging and sometimes substantial. In vitro, flavanols found in cocoas and chocolates have shown specific activities related to vascular health and, in particular, mechanisms associated with endothelial function, endothelium-derived nitric oxide synthesis, platelet function, and cellular processes modified by reactive oxygen and nitrogen species.
Epidemiological evidence linking flavonoid consumption to heart disease or mortality in humans is impressive but has often been conflicting. For example, there has been enormous interest in the 'French paradox' reflecting the interesting finding that the French do not have a myocardial infarction rate to match their fat intake. Attempts have been made to implicate red wine as a contributor via its flavonoid content. Regarding flavanols consumed as cocoa and chocolate and their potential influence on cardiovascular risk in epidemiological studies, there is a paucity of data. Such studies examining the potential health effects of foods rich in flavonoids have, at times, shown a very large influence on cardiovascular risk. For example, researchers reported the findings in a prospective study on the determinants of mortality after acute MI. Patients who consumed an average of 14 or more cups per week of black tea showed a 39% reduction in mortality during a median follow-up of 3.8 years. Perhaps more striking was the fact that the moderate tea drinkers who averaged only two cups of tea per week showed a 31% reduction. Adjustment for the usual risk factors did not alter this association. Why should the results of studies be in conflict given such a robust influence? There are several reasons: indeed, they provide the rationale for this review focusing on the potential cardiovascular health benefits of flavanols in cocoas and chocolates. Sometimes identifying the responsible mechanism(s) can have a substantial influence on the attempt to resolve such issues.
The clinical processes of interest are characterised by endothelial dysfunction. Studies in vitro, in animal models, and in intact humans have provided growing evidence for an action of this class of natural products on endothelial dysfunction. The final common pathway appears to be activation of nitric oxide synthesis. This story has at least one of its beginnings a long way from the issue of phytochemicals in foods. The Kuna Indians in Panama, living in their indigenous island home in the Caribbean, do not show the typical rise in blood pressure with age, and hypertension is very rare. In a study that began with the search for protective genes, the observation that migration to Panama City led to a loss of the protection against hypertension made it clear that an environmental factor was involved. Examination of their diet uncovered the fact that they drank large volumes of a flavanol-rich cocoa. Subsequent in vitro studies suggesting that cocoa extracts can induce endothelium-dependent relaxation led to studies in healthy volunteers, and in patients with vascular risk or disease. In one study researchers found that ingestion of flavanol-rich cocoa led to an increase in flow-mediated vasodilation of the brachial artery following five minutes of ischaemia, a response that correlated with biochemical evidence of increased nitric oxide bioavailability. In the normal volunteers studied flavanol-rich cocoa induced striking dilatation of the vessels of the finger, which was reversed completely by an arginine analogue that blocks nitric oxide synthesis.
