Fernández-Murga L, Tarín JJ, García-Perez MA, Cano A.The impact of chocolate on cardiovascular health.  Maturitas. 2011 Aug;69(4):312-321.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in women.  After menopause, the loss of ovarian function increases the risk of CVD. Since the disappointing evidence regarding hormone replacement therapy (HRT) came to light, there has been an increasing interest in functional foods to help mitigate this risk. Cocoa (Theobroma cacao) and chocolate have been shown to have multiple beneficial effects for the cardiovascular system. This review article provides an in-depth summary of the experimental and clinical research of the last two decades on the protective effects of cocoa and chocolate.

Ancient use of chocolate, or 'xocolatl,' was reported by the Spanish conqueror Hernán Cortés, who noted its energizing effects. Epidemiological studies with the Kuna Indians, a native population of the islands off of Panama, showed that the use of cocoa as their predominant beverage correlated with a very low incidence of hypertension; this changed when they migrated and reduced cocoa consumption. Other large epidemiological studies showed an inverse correlation with prevalent coronary heart disease and coronary artery calcification. Three prospective cohort studies in elderly men, postmenopausal women, and mammography patients (a total of over 66,000 of the latter two subjects) showed reduced risk of cardiovascular mortality.

The pure extract of cocoa beans is called cocoa liquor, which contains about 55% cocoa butter (the fat component). When the cocoa butter is removed, the remainder is called cocoa. Chocolate is a combination of cocoa liquor, cocoa butter, sugar, and milk. The health compounds of interest are flavanols (also called flavan-3-ols or catechins), which are a subset of flavonoids, and in turn polyphenols. The specific flavanols in cocoa are the monomers (-)-epicatechin and (+)-catechin, which together form oligomers and polymers called procyanidins. Processing cocoa reduces the flavanol concentration. Dark chocolate contains 120-150 mg polyphenols/10 g, whereas cocoa has five times that amount, and milk chocolate provides very little. Cocoa also contains small amounts of plant sterols, fiber, the minerals potassium, calcium, magnesium, and copper, while cocoa butter lipid is one-third stearic acid, which has a neutral effect on serum cholesterol.

Cocoa flavanols are absorbed quickly from the intestine and reach peak serum levels two hours post-consumption. Epicatechin is the best absorbed; serum catechin levels are only 10% those of epicatechin. Procyanidins are absorbed very poorly. Conjugation and gut flora metabolism also play a role in bioavailability and metabolite impact.

Atherosclerosis is a key factor in the development of vascular disease. Its progression is a complex web of effects that at its worst leads to a heart attack or stroke. Any mitigating effect on any of the progressive steps helps to lessen cardiovascular risk. Following is a review of such areas with the current experimental and clinical evidence for the mitigating effects of cocoa and chocolate.

Oxidative stress facilitates atherosclerosis by promoting the oxidation of low-density lipoprotein cholesterol (LDL-c), one of the first steps in atherosclerotic plaque formation. There is in vitro evidence that cocoa has a greater antioxidant capacity than other flavanol-rich foods and that cocoa flavanols protect LDL-c from being oxidized. However, the lack of data from human intervention studies, as well as the low serum concentrations of flavanols relative to the total serum antioxidant pool, has raised serious doubts as to the extent of antioxidant activity of flavanols in the body.

Inflammation is also a primary factor in CVD. In in vitro studies, depending on the degree of polymerization, cocoa flavanols have been shown to inhibit several facilitators of inflammation, including matrix metalloproteinase (MMP), nuclear factor-kappa B (NF-Κβ), and the cytokines interleukin-1 beta (IL-1β), IL-4, IL-5, and tumor necrosis factor-alpha (TNF-α). Two randomized, human studies showed a decrease in monocyte inflammatory markers or in plasma leukotrienes after cocoa or chocolate consumption, respectively.

The health of the endothelial wall is another contributor to cardiovascular health. Certain cells from bone marrow (endothelial progenitor cells) are known to help repair damaged endothelium and were recently shown in a double-blind study to be elevated by 30 days of cocoa consumption. Nitric oxide (NO) is a compound produced by the body which helps maintain the health of the wall as well as supply the signal to vessels to expand when there is an increased demand for blood flow. Cocoa flavanols have been shown to increase levels of NO both in vitro and in humans, and in turn to improve vessel flexibility (as measured by flow-mediated dilation [FMD]) after both short- and long-term intake of cocoa in a number of areas of the macro- and micro-circulation. This was true for patients with particular cardiovascular risk, such as diabetics and obese persons. That this effect is not seen when an NO inhibitor is introduced has provided evidence that increased NO is the causal factor. Two studies in atherogenic rabbits fed cocoa powder or its polyphenols showed a reduction in aortic plaque area.

Based on the epidemiological observations with regard to hypertension, a number of randomized controlled trials have been performed. A meta-analysis of 13 studies up to 2009 showed a moderate effect on both systolic and diastolic blood pressure (-5.0 ± 3.0 mmHg [P=0.0009] and -2.7 ± 2.2 mmHg [P=0.01], respectively) in a subgroup analysis that demonstrated this was true for prehypertensive or hypertensive individuals only. More recent long-term trials have had mixed results. The mechanism of action has not been well studied, but there is some evidence of an angiotensin converting enzyme (ACE)-inhibitor effect.

The effect of cocoa and chocolate on cholesterol is limited to small studies, but a meta-analysis of 8 studies found a small decrease in total cholesterol (-5.82 mg/dL) and LDL-c (-5.87 mg/dL) in participants with cardiovascular risk, but no change in high-density lipoprotein cholesterol (HDL-c).

Platelets play a role in plaque formation and in the acute events that lead to stroke. Data from well-controlled human studies are strong in showing a platelet-inhibiting effect of cocoa; these data are backed up by similar results in ex vivo studies.

There is some investigation into effects on glucose tolerance, though human trials are limited and results ambiguous. It is also unclear whether any effects would be due to flavanols or other substances in cocoa such as magnesium.

The amount of research that has been generated on cocoa and chocolate in the last two decades is impressive. There are still gaps that need to be filled, such as bridging the epidemiological evidence with causality and with effects on cardiovascular events rather than just biomarkers. Additional issues include the lack of standardization of flavanol content due to processing effects, as well as the possibility that beneficial effects may be restricted to those with existing dysfunction. The promise of the existing data together with the remaining areas of inconsistency makes for a ripe area for continued work. In the meantime, recommending uncontrolled chocolate consumption for health purposes is not prudent, especially for those who are obese, due to its caloric content.