Cocoa: a flavanol powerhouse

Debra L Miller, PhD, traces the storied past of one of the world?s most favoured foods: chocolate. Now, thanks to modern analytical methods, scientists are finding there is truth to cocoa?s long-touted health benefits, thanks to its impressive polyphenol content, which is one of the highest of all plant-based foods

There is much news today about the potential health benefits of chocolate, but these benefits are certainly not new. Chocolate is a food as rich in history as it is in taste. Packed with polyphenols, cocoa has been used by indigenous peoples to improve health for thousands of years.

Ancient societies revered the cocoa bean for its sustaining and health-affirming qualities.1 In all, more than 100 medicinal uses of cacao are listed in ancient codex.1 Specific benefits were noted in these documents including alleviating ?faint of heart,? reducing angina, generating blood, relieving heart palpitations and even prolonging life.1 After chocolate?s journey from Central America to Europe, much of its connection to health was lost when Europeans created a more indulgent chocolate treat by adding milk and sugar.

The Kuna Indians (or Amerinds) provide a modern day example of this ancient effect. The Kuna live off the coast of Panama on the San Blas Islands. Their traditional diet is high in sodium yet they show little to no rise in blood pressure with age.2 When they migrate to other areas, however, their blood pressure rises with age similar to other populations. When in their indigenous villages, the Kuna drink an average of five cups of a cocoa-based beverage per day. This phenomena intrigued researchers.

With the advent of modern analytical methods, numerous bioactive compounds in foods — especially plants — have been detected. Cocoa, it turns out, contains several bioactive compounds including polyphenols, theobromine, phenylethylamine, anadamide, phenylalanine and tyrosine. Still many others may exist in the bean as well.

The compounds receiving the most attention are the polyphenols — a large class of molecules that includes numerous sub-categories. One sub-category, flavonoids, can be further divided into 13 sub-classes, including the flavanols (or more precisely flavan-3-ols) found in cocoa. A few plant-based foods including apples, onions, soybeans, blueberries, cranberries, teas (green and black) and red wines are distinguished by their high polyphenolic content. Interestingly, gram for gram, cocoa ranks among the highest in flavanol concentration compared to other plant-based foods.3

Further, data from the USDA and independent research sponsored by The Hershey Co indicates that most cocoa-containing products have flavanols. Generally, the higher the concentration of cocoa, the more flavanols in the product.4 Natural cocoa has the highest concentration and flavanol content, followed by baking chocolates, dark chocolate and milk chocolate.4

The structure of flavanols suggests these chemicals have a strong antioxidant capacity. Bioavailability studies indicate plasma levels of the two main flavanols — epicatechin and catechin — are elevated one hour after consumption of chocolate or cocoa and are dissipated after six hours.5

The heart of chocolate
One characteristic of cardiovascular disease is atherosclerosis. Hardening of the arteries results from inflammation due to chronic injury to the endothelium. There are many causes of this injury such as smoking, infections, and high blood levels of homocysteine and free radicals.6 Free radicals are thought to contribute to atherosclerosis through toxic action on the endothelium and by oxidizing ?bad? low-density lipoprotein cholesterol. When LDL cholesterol is oxidized, its potential to cause arterial damage is greatly increased.7

Following such damage, the endothelium attempts to heal itself by attracting monocytes and other inflammatory molecules and cells. This promotes the formation of the hallmark of cardiovascular disease: atherosclerotic plaque. The endothelium tends to constrict in the regions where plaque forms, which can lead to blood clots.6

A large number of studies have shown that several biomarkers of cardiovascular risk are influenced by flavonoid-rich foods.8 The flavonoids subclass has been the subject of much research due to their antioxidant activity. Flavanols, the flavonoids abundan in cocoa, however, are unique in that while they can act as antioxidants, they also have other important properties.

Cocoa in the test tube
Numerous in vitro studies indicate cocoa flavanols may mitigate cardiovascular risk factors. The addition of dark chocolate to blood samples inhibited LDL oxidation even at low concentrations in the blood.9,10,11 Purified cocoa flavanols reduced platelet activation and aggregation in the presence of an activating agent.12 Cocoa flavanols also led to a decrease in blood clotting and inflammation, not only through direct effects on platelet activation and aggregation, but by moderating the production of eicosanoids.13

Cocoa in the body
The strong in vitro evidence of dark chocolate, cocoa and cocoa components in improving cardiovascular disease risk led to a number of clinical trials with humans. Risk factors of interest include: blood cholesterol, platelet activity and eiscosanoid production, high blood pressure and endothelial function/nitric oxide production.

Cholesterol: One factor of concern during clinical studies was whether ingestion of dark chocolate, which contains saturated fat, would lead to negative effects on serum cholesterol. However, the fat from cocoa butter is mainly comprised of stearic acid. A number of studies have shown that stearic acid (and cocoa butter) does not elevate blood cholesterol.14,15,16

Both cocoa and dark chocolate have shown promising results on cholesterol levels. Consumption of cocoa-based beverages for two to four weeks have increased the lag time for oxidation of LDL cholesterol.11,17,18,19. In a four-week study combining cocoa and dark chocolate, significant improvements were found for blood levels of ?good? HDL cholesterol and oxidized LDL cholesterol.11 Another recent study found improvements in total cholesterol and LDL cholesterol levels following the consumption of 100g of dark chocolate.20

Platelet activity: Platelets carry blood-clotting factors and are important for wound healing, but in the arterial endothelium, they can aggregate and cause plaque. A decrease in platelet activity is thus favourable to overall cardiovascular health.

In one study, after drinking cocoa high in polyphenols, a reduction in platelet surface markers (PAC-1) was found, indicating decreased platelet activation.21 A separate study showed cocoa consumption decreased the formation of platelet microparticles — which correlates positively with thrombotic disorders.21

?Aspirin-like? effects: Low-dose aspirin therapy is often prescribed for cardiovascular disease patients because it reduces the production of prostaglandins involved in inflammation. An experiment was thus designed to compare cocoa and low-dose aspirin administration. Measures of platelet functions were measured for low dose (baby) aspirin, 300ml (~10oz) of cocoa beverage and a combination of the two. The cocoa treatment demonstrated an inhibitory effect on platelet activation and function.22 The effect from the cocoa beverage was slightly less than the baby aspirin treatment, while the combination produced slightly better results, especially related to microparticle formation.22

This indicates that cocoa is associated with a transitory reduction in platelet reactivity, which may reduce the risk for formation of clots. Consumption of dark chocolate has been noted to decrease leukotriene formation.13 A high level of leukotrienes is associated with an increased risk of some disorders such as asthma, ischemia and shock.

High blood pressure: The observation of the Kuna Indians sparked interest in a potential cocoa/blood pressure relationship. Two studies have tested cocoa or dark chocolate consumption in people with high blood pressure. In one, both systolic and diastolic blood pressures were reduced following ingestion of flavanol-rich cocoa for 10 days.23 The other found similar results after 15 days of eating 100g of dark chocolate.24

Two studies have reported blood pressure values for individuals with normal blood pressure fed cocoa or chocolate. One found that dark chocolate, but not white chocolate, reduced blood pressure, yet still in the normal range.20 However, the other study noted no change in blood pressure in their healthy study population after ingestion of flavanol-rich cocoa.25

Endothelial function/nitric oxide: Endothelial dysfunction correlates strongly with cardiovascular disease, and high-antioxidant dietary compounds have been shown to improve endothelial function.26 Given the high levels of flavanol antioxidants in cocoa and dark chocolate, investigations were conducted.

Two studies testing dark chocolate or cocoa found significant improvement in overall function of the endothelium in healthy volunteers.27,28 Another study investigated this effect in participants with high blood pressure and found 100g of dark chocolate fed for 15 days produced significant improvements in endothelial function as well as other markers related to insulin resistance and blood pressure.24

Perhaps the most interesting and meaningful aspect of endothelial function tests is the underlying physiological mechanism influenced by cocoa flavanols. Nitric oxide is a gas produced in the endothelium that acts as a signalling molecule for arteries to properly dilate when necessary. The discovery of this effect was awarded the 1998 Nobel Prize for Medicine and is the basic mechanistic premise for pharmaceuticals that treat vascular problems.

Fisher and colleagues were able to determine, via the use of nitric oxide inhibitors, that the endothelial improvements associated with cocoa flavanols were mediated via the production of nitric oxide.25 Enhanced blood flow, via increases in nitric oxide, has been linked to improved cognitive, cardiovascular and reproductive health.25

Everything in moderation
Consumption of cocoa may convey the protective effects in healthy people and those with risk factors for cardiovascular disease. At this time, long-term effects of cardiovascular protection have not been determined and deserve further investigation.

Of course, cocoa and chocolate products can provide fat and calories and need to be consumed in moderation and as part of a balanced diet, but now science agrees with history — chocolate and cocoa are not only good to eat, they may also be good for you.

Debra L Miller, PhD, is senior staff scientist of nutrition at The Hershey Co in Hershey, Pa. Founded in 1893, Hershey?s was the first North American company to develop a milk chocolate formula and is today the continent?s largest manufacturer of chocolate products, with exports to 90 countries.
Respond: [email protected]

ORAC value of high flavanol-containing foods

ORAC units/svg

Dark chocolate




Cocoa (natural)














Milk chocolate


Grapes (red)






Chocolate data from Gu et al. FASEB J 2005;20:598. Other foods from Wu et al. J Ag Food Chem 2004;52:4026-37.

Food of the gods
The Olmecs pronounced it kakaw. The Aztecs called it zocolatl (zho?-co-la-tl). The Mayans used cacahuatl (ca-ca-what?-tl). Whatever its name, however, for the ancients chocolate was a mixture of ground cocoa beans, cornmeal, spices (such as chilis) and water, which was boiled and poured into a frothy hot drink.1

Cocoa, the base material from which all chocolate products are made, comes from the beans of the cocoa plant — tropical trees with large pods that grow directly from the trunk and the main stems. Cocoa beans are actually seeds contained within the pods. The scientific name for the cocoa plant is Theobroma cacao, which translates to ?food of the gods.?1

European chocolate products declare the ?per cent cacao? on products and similar statements are now appearing on US premium chocolate products to denote the amount of natural ingredients from the cocoa bean.

1 Dillinger TL, et al. Food of the gods: cure for humanity? A cultural history of the medicinal and ritual use of chocolate. J. Nutr 2000; 130:2057S-2072S.
2 Hollenberg NK, et al. Aging, acculturation, salt intake, and hypertension in the Kuna of Panama. Hypertension 1997; 29:171-6.
3 Lazarus SA, et al. Chocolate contains additional flavonoids not found in tea. Lancet 1999; 354:1825.
4 Hurst WJ, et al. The determination of polyphenols and the correlation to cocoa content in selected US confectionery products. 2005, Functional foods, bioactive compounds and human health conference, Ithaca, NY (abstract).
5 Baba S, et al. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic 2000; Res 33:635-641.
6 Hannum SM, et al. Chocolate: a heart healthy food? Show me the science. Nutr Today 2002; 37:103-9.
7 Ginter R. Effect of free radicals and antioxidants on the vascular wall. Vnitr Lek 2000; 46:354-9.
8 Manach C, et al. Polyphenols and prevention of cardiovascular diseases. Curr Opin Lipidol. 2005; 16:77-84.
9 Pearson DA, et al. Inhibition of in vitro low-density lipoprotein oxidation by oligomeric procyanidins present in chocolate and cocoas. Methods Enzymol 2001; 335:350-60.
10 Vinson JA, et al. Phenol antioxidant quantity and quality in foods : cocoa, dark chocolate, and milk chocolate. J Agric Food Chem 1999; 47:4821-4.
11 Wan Y, et al. Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Am J Clin Nutr 2001; 74:596-602.
12 Kris-Etherton PM, Keen CL. Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr Op in Lipid 2002; 13:41-9.
13 Schramm DD, et al. Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. Am J Clin Nutr. 2001; 73:36-40.
14 Weisburger JH. Chemopreventive effects of cocoa polyphenols on chronic diseases. Exp Biol Med 2001 226:891-7.
15 Kris-Etherton PM, Mustad VA. Chocolate feeding studies: a novel approach for evaluation of the plasma lipid effects of stearic acid. Am J Clin Nutr 1994; 60:1029S-36S.
16 Yu S, et al. Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic. Am J Clin Nutr 1995; 61:1129-39.
17 Kondo K, et al. Inhibition of LDL oxidation by cocoa. Lancet 1996 34:1514.
18 Osakabe N, et al. Daily cocoa intake reduces the susceptibility of low-density lipoprotein to oxidation as demonstrated in healthy volunteers. Free Radic Res 2001; 34:93-9.
19 Osakabe N, et al. Catechins and their oligomers linked by C4 C8 bonds are major cacao polyphenols and protect low-density lipoprotein from oxidation in vitro. Exp Biol Med 2002; 227:51-6.
20 Grassi D, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 2005; 46: 1-8.
21 Rein D et al. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000; 72 :30-5.
22 Pearson DA et al. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb Res 2002; 106:191-7.
23 Taubert D, et al. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 2003; 290:1029-30.
24 Grassi D, et al. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 2005; 81:611-4.
25 Fisher ND, et al. Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J Hypertens 2003; 21:2281-6.
26 Vita JA. Polyphenols and cardiovascular disease: effects on endothelial and platelet function. Am J Clin Nutr 2005; 81:292S-7S.
27 Engler MB, et al. Flavonoid-rich cocoa improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 2004; 23:197-204.
28 Heiss C, et al. Vascular effects of cocoa rich in flavan-3-ols. JAMA 2003; 290:1030-1.

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