March 2006: 109 –118
Special Article
The Emerging Role of Flavonoid-Rich Cocoa and Chocolate
in Cardiovascular Health and Disease
Mary B. Engler, PhD, and Marguerite M. Engler, PhD
Cocoa and chocolate have recently been found to be rich
plant-derived sources of antioxidant flavonoids with ben-
eficial cardiovascular properties. These favorable phys-
iological effects include: antioxidant activity, vasodila-
tion and blood pressure reduction, inhibition of platelet
activity, and decreased inflammation. Increasing evi-
dence from experimental and clinical studies using co-
coa-derived products and chocolate suggest an impor-
tant role for these high-flavanol-containing foods in
heart and vascular protection.
Key words: cardiovascular, chocolate, cocoa, fla-
vonoid, flavanol
© 2006 International Life Sciences Institute
doi: 10.1301/nr.2006.mar.109 –118
INTRODUCTION
Evidence based on epidemiological studies suggests
that flavonoid-rich diets high in fruits and/or vegetables
reduce the risk of coronary heart disease.1-3 Recent
studies also report reduced cardiovascular risk and
events associated with the consumption of foods rich in
flavonoids.4,5 A meta-analysis of seven prospective co-
hort studies with 105,000 individuals indicates that high
dietary intake of flavonoids from a small number of fruits
and vegetables, tea, and red wine is inversely associated
with coronary heart disease risk6. Dietary flavonoids and
their potential role in the prevention of cardiovascular
disease have gained recent scientific and medical interest
due to their antioxidant properties: their ability to scav-
enge reactive oxygen species (ROS) and reactive nitro-
gen species.7,8
Oxidative stress due to excess production of free
Drs. Engler are with the Department of Physiological
Nursing, Laboratory of Cardiovascular Physiology, Uni-
versity of California, San Francisco, California, USA.
Please address all correspondence to: Dr. Mary B.
Engler, Professor, University of California, 2 Koret
Way, Suite N631, San Francisco, CA 94143-0610;
Phone: 415-476-0984; Fax: 415-476-8899; E-mail:
mary.engler@nursing.ucsf.edu.
Nutrition Reviews姞, Vol. 64, No. 3
radicals or ROS is associated with a number of cardio-
vascular risk factors such as hypertension, dyslipidemias,
diabetes, and smoking. Cellular DNA, proteins, and
lipids are susceptible to ROS attack, which can result in
damage to cell membranes and organelles. Mitogenicity
and apoptosis of vascular cells is enhanced, and in-
creased expression and activation of redox-sensitive
genes occurs. Tissue damage and pathophysiological
processes, including endothelial dysfunction and athero-
sclerosis, eventually ensue.9 Oxidative modification of
low-density lipoproteins (LDL) due to oxidative stress is
believed to be a major contributing factor in atheroscle-
rosis. The antioxidant properties of flavonoids represent
one of many diverse beneficial effects that these poly-
phenolic compounds may exert in cardiovascular dis-
ease. The direct antioxidant-quenching theory of fla-
vonoids is now being supplanted by other physiological
theories, including their effects on cellular redox regula-
tion, signal transduction, and modulation of other en-
zyme and genomic systems.
Flavonoids, a subclass of polyphenols, are ubiqui-
tous micronutrients derived from plants, primarily fruits
and vegetables. There are more than 5000 flavonoids and
six major flavonoid categories: flavanols, flavanones,
flavones, isoflavones, flavonols, and anthocyanidins.10
The various subclasses are listed below and include
typical foods or beverages with a substantial content of
flavonoids:
● Flavanols (catechin, epicatechin): chocolate, tea, red
wine, beans, apricot, cherry, grape, peach, black-
berry, apple;
● Flavanones (hesperetin, naringenin, eriodictyol): cit-
rus fruits and juices;
● Flavones: (apigenin, luteolin): parsley, celery;
● Isoflavones: (daidzein, genistein): soy products;
● Flavonols: (quercetin, kaempferol, myricetin): on-
ions, kale, broccoli, tomato, blueberry, apples, tea,
red wine; and
● Anthocyanidins (cyanidin, pelargonidin, peonidin,
delphinidin, malvidin): blueberry, black grape,
cherry, blackberry, black currant, rhubarb, straw-
berry, red wine, plum, red cabbage.11,12
109
 The antioxidant properties of flavonoids are related
to their structure, two aromatic rings (an A-ring and a
B-ring) on the ends bound by an oxygenated heterocycle
in the middle (C-ring), which promote free radical scav-
enging. Specifically, the presence of the catechol or
dihydroxylated B-ring allows rapid donation of hydrogen
(electron) for stabilization of radical species. This is
considered the most important structural feature defining
the “classical” antioxidant nature of flavonoids.13 Struc-
ture-activity studies also show that flavonoids inhibit key
enzymes such as NAD(P)H-oxidase (a major source of
endogenous free radicals), tyrosine kinase, and protein
kinase based on varied hydroxylation/methylation pat-
terns.14,15
The number of hydroxyl groups on the B-ring and
the oxo group at the 4 position of the C-ring are also
important in the suppression of cyclooxygenase-2 (COX-
2), an inducible enzyme that is upregulated during in-
flammation and certain tumor formations.14 Due to this
structural feature, flavanols have been found to have
more suppressive activity on COX-2 than flavonols. It is
apparent that some functions of flavonoids are dependent
on structure. While the antioxidant properties require two
hydroxyl groups on the B-ring (with no carbonyl group
at C4 or unsaturation of the C-ring), the anti-proliferative
effects of flavonoids in many cancer studies require the
additional presence of a carbonyl group at C4 and un-
saturation of the C-ring. Catechins and epicatechins,
based on their catechol or dihydroxylated B-ring, appear
to have a relatively restricted diversity in physiological
activity. Flavonoids, depending on their structure, may
also affect pathways in a cell- or tissue-specific manner
depending on their structure.
Recent reviews also suggest that flavonoids exert
non-antioxidant mechanisms that may confer protection
such as binding to receptors, modulation of cellular
signaling (i.e., protein and lipid kinase pathways), and
gene expression.13,16 For example, flavonoids of the
catechin family, major constituents of red wine, have
been found to mediate the inhibitory effects of red wine
on ␤-platelet-derived growth factor (PDGF) receptor
signaling, PDGF-dependent proliferation, and migration
of vascular smooth muscle cells.17 PDGF is a potent
mitogenic and chemotactic factor and one of many in-
flammatory components that contribute to atherogenesis.
Interestingly, the findings of this study are believed to
provide a molecular explanation for the “French para-
dox” in that the French have a high consumption of red
wine and one of the lowest incidences of coronary heart
disease despite a diet with a high fat content.
Cocoa and chocolate contain both a high quantity
and quality of antioxidant flavonoids, even exceeding
black and green tea and red wine.18,19 Cocoa and choc-
olate, especially dark chocolate, have only recently been
110
identified as rich sources of flavonoids due to advances
in technology and analytical methods used in the detec-
tion of complex flavonoids. The high antioxidant capac-
ity of cocoa and chocolate are attributed to their signif-
icant amount of procyanidins, the oligomeric form of the
flavanol monomeric units, (–)-epicatechin and (⫹)-cate-
chin. These monomers, mainly (–)-epicatechin, provide
most of the total procyanidin content in chocolate; how-
ever, dimers (two monomer units) and up to 10 monomer
units are also present. The amount of flavonoids in
chocolate is not only dependent on the cacao bean, but
also on the processing steps involved in chocolate’s
manufacture. For example, excess heat and alkalization
(“Dutch” processing) can significantly reduce the
amount of flavonoids. Typically, dark chocolate contains
two to three times as many cocoa flavonoids as milk
chocolate.20
The antioxidant capacities of foods and beverages
measured by current methodology, i.e., oxygen radical
absorbance capacity (ORACFL) assay with fluorescein,
Trolox equivalent antioxidant capacity (TEAC), total
radical-trapping antioxidant parameter (TRAP), ferric-
reducing ability of plasma (FRAP), may not reflect in
vivo antioxidant effects.21 The measurement of antioxi-
dant capacity, which reflects the concentrated polyphe-
nolic content of the food or beverage, is also not com-
parable among the different methods.19 Measurement of
both the lipophilic and hydrophilic fractions in a given
sample are needed to obtain an accurate total ORACFL
(total antioxidant capacity) value.21
Other factors such as processing, plant genetics,
season, and growing conditions may also alter the phe-
nolic content and, thus, the antioxidant capacity of
foods.21 Therefore, the content of flavonoids in various
foods and beverages and their respective antioxidant
properties may be dependent on a number of factors.
Careful evaluation of these factors and the methodology
used for measurements are important. With these con-
siderations, flavonoids, specifically, the flavanols cate-
chin and epicatechin, may be beneficial in cardiovascular
health and disease based on their antioxidant properties,
anti-proliferative effects, and other emerging physiolog-
ically relevant mechanisms.
HISTORY
The cacao tree, Theobroma cacao or “food of the
gods,” was first cultivated in 250 –900 AD by the ancient
Maya civilization in the Mesoamerican (Mexico to Cen-
tral American) region.22,23 A typical football-shaped
fruit pod of the cacao (pronounced “kah-kow”) tree
contains approximately 25 to 75 cocoa beans. The Aztec
elite civilization in the 12th to 16th centuries drank
chocolate derived from the cocoa beans in combination
Nutrition Reviews姞, Vol. 64, No. 3
with spices as a nourishing staple beverage. Both Maya
and Aztec royal and religious events had offerings of
chocolate to the Aztec god Quetzalcoatl, who by legend
brought heavenly cacao down to earth. The beans were
also used as currency and for medicinal purposes to fight
fatigue and gastrointestinal distress.22,23
Following the Spanish conquest of Mexico by Her-
nán Cortés, the cocoa beans were brought back to Spain
in 1528. Over the next 100 years, chocolate swept across
Europe as a fad. Cane sugar, vanilla, cinnamon, and
aniseed were added to the bitter chocolate drink instead
of the peppers and other native herbs used by the Aztecs.
Sweet, hot chocolate had arrived. In France, only the
royal courts were allowed to drink chocolate due to its
status. In 1657, the first chocolate house opened in
London. Chocolate was not readily available in the
United States until the mid-1800s due to the high duties
on imports of cocoa beans and sugar. It was during
World War I that chocolate was provided as rations to
US servicemen in Europe.22,23 Interestingly, the choco-
late was found to be resistant to spoilage, which is now
believed to be due to the natural antioxidant flavonoids it
contains.
ANTIOXIDANT ACTIVITY
Decreased susceptibility of LDL oxidation has re-
cently been ascribed to the cocoa flavonoids.24-27 The
antioxidant capacity and diminished production of oxi-
dative products in plasma is related to increased concen-
trations of the cocoa and chocolate flavonoid (–)-epicat-
echin.28,29 A study on the plasma kinetics of epicatechin
showed significant increases in epicatechin 2 hours after
chocolate consumption. Plasma epicatechin levels reach
0.7␮mol/L following acute ingestion of 80 g of dark
chocolate (164 mg of epicatechin)30 and 0.2␮mol/L with
a 2-week daily consumption of 46 g (46 mg of epicat-
echin) dark chocolate.31,32
Table 1 lists the studies that have investigated the
effects of cocoa and chocolate on oxidation. Various
plasma measurements, including total antioxidant capac-
ity, LDL oxidation susceptibility or lag time, oxygen
radical absorbance capacity (ORAC), F2- or 8-isopros-
tanes, 2-thiobarbituric acid reactive substances (TBARS),
and malondialdehyde (MDA), were examined in these
investigations. Overall, favorable changes in oxidative
measurements and increases in plasma epicatechin con-

Table 1. Effects of Cocoa and Chocolate on Oxidation

Reference Type Subjects Antioxidant Effect
Wang et al., 2000 29
Dark chocolate, single dose (27 g, Healthy adults (N ⫽ 20) Weak ⫹
53 g, or 80 g)
Rein et al., 200052 Dark chocolate, single dose (80 g) Healthy adults (N ⫽ 10) ⫹
Wan et al., 200126 Cocoa powder (22 g) plus dark Healthy adults (N ⫽ 23) ⫹
chocolate (16 g/d) for 4 weeks
Osakabe et al., 200125 Cocoa powder (36 g/d) for 2 weeks Healthy adults (N ⫽ 15) ⫹
Mathur et al., 200227 Dark chocolate (36 g/d) plus Healthy adults (N ⫽ 25) ⫹ LDL oxidizability,
Cocoa powder (30 g/d) for 6 weeks ⫺ ORAC antioxidant
capacity, ⫺ urinary
F2 Isoprostanes
Steinberg et al., 200224 Cocoa powder, single dose (37.5 g) Healthy adults (N ⫽ 6) ⫹
Serafini et al., 200335 Dark chocolate, single dose (100 g, Healthy adults (N ⫽ 12) ⫹, ⫺, ⫺
100 g with 200 mL milk, or 200
g milk chocolate)
Murphy et al., 200349 Cocoa tablets (6/d) for 28 days Healthy adults (N ⫽ 32) ⫺
Engler et al., 200331 and Dark chocolate (46 g/d) for 2 Healthy adults (N ⫽ 21) ⫺
Engler et al., 200432 weeks
Mursu et al., 200464 Dark chocolate or high-polyphenol Healthy adults (N ⫽ 45) ⫺
dark chocolate (75 g/d) for 3
weeks
Wiswedel et al., 200466 Cocoa drink, single dose (100 mL) Healthy adults (N ⫽ 20) ⫹
Kurosawa et al., 200567 Cacao liquor-supplemented diet 1% Hypercholesterole mic ⫹
(w/w), 1–4 months Rabbits (N ⫽ 15)
Fraga et al., 200568 Flavanol-containing milk chocolate Healthy adults (N ⫽ 28) ⫹
(105 g) for 2 weeks
Vlachopoulos et al., Dark chocolate, single dose (100 g) Healthy adults (N ⫽ 17) ⫹
200569

Nutrition Reviews姞, Vol. 64, No. 3 111

centrations following cocoa or chocolate consumption
were found.
These changes are in agreement with a recent study
examining the effect of epicatechin and polyphenolic
cocoa extract in human caco-2 cells using functional
genomic analysis.33 Differential expression of the
MRP1, MAPKK1, STAT1, and FTH1 genes that are
involved in the cellular response to oxidative stress are
consistent with the antioxidant properties of cocoa fla-
vonoids. Multiple signal transduction pathways, includ-
ing those influencing the antioxidant responsive elements
in the promoter region of the respective genes, may also
be affected by many phytochemical antioxidants. This
effect on gene expression may result in the induction of
phase II metabolic enzymes involved in the detoxifica-
tion of carcinogens.
In the studies cited with negative findings related to
improvement in oxidative measurements, this may be
attributed to a number of factors including variability in
the subjects’ baseline epicatechin concentrations and/or
the percent increase in these levels seen after consump-
tion. This may be due in part to differences in baseline
diets or in the detection sensitivity of low concentrations
of plasma epicatechin.32,34 Moreover, the human health
effects seen with flavonoids may ultimately depend on
both their concentration in cells and tissues and on an
individual’s genetic makeup. These may also contribute
to the null observations seen with oxidative stress bi-
omarkers in some human studies with dietary flavonoids.
It is interesting that the presence of milk with chocolate
consumption was found to diminish the increase in both
total antioxidant capacity and epicatechin concentra-
tions,35 but others have found no such milk-related
connection under similar conditions.36
VASODILATION
Endothelial dysfunction is recognized as an early
event in the development of atherosclerosis, and is asso-
ciated with decreased bioavailability of the vasodilator
nitric oxide. Current evidence suggests that the consump-
tion of cocoa and chocolate, rich in flavonoids, may
provide protective vascular effects.34 In isolated rabbit
aortic rings, cocoa extracts were shown to induce endo-
thelium-dependent relaxation and to activate endothelial
nitric oxide synthase.37 Oligomeric forms of the mono-
meric units (–)-epicatechin and (⫹)-catechin, such as
tetramers and higher, were associated with these effects.
Additionally, a favorable balance in eicosanoid synthesis
has been reported in cultured human aortic endothelial
cells exposed to cocoa flavanols and in human plasma
samples from subjects 2 hours following the consump-
tion of high-flavanol chocolate (37 g).38 A decrease in
the plasma leukotriene-prostacyclin ratio was also found,
which would result in more vasodilation, less platelet
aggregation, and an anti-inflammatory profile. A signif-
icant rise in plasma epicatechin was also noted at the
2-hour time point following chocolate consumption.
Other recent studies (Table 2) in healthy subjects
following 4 days to 2 weeks of daily consumption of a

Table 2. Effects of Cocoa and Chocolate on Vasodilation

Cocoa Endothelium-
Flavanoids Dependent
Reference Type Amount Model Relaxation
Karim et al., 2000 27
Cocoa extracts — Isolated rabbit aorta ⫹
(10⫺7 to 10⫺5
mol/L)
Fisher et al., 200339 Cocoa beverage 821 mg/d Healthy adults (N ⫽ 27) ⫹
(230 mL/d) for 4 fingertip peripheral artery
days tonometry
Heiss et al., 200341 Cocoa beverage 176 mg/d Adults with one cardiovascular ⫹
(100 mL/d) for 2 risk factor or history of
days CAD (N ⫽ 26) brachial
artery
Engler et al., 200331 and Dark chocolate bars 259 mg/d Healthy adults (N ⫽ 21) ⫹
Engler et al., 200432 (46 g/d) for 2 brachial artery
weeks
Vlachopoulas et al., Dark chocolate, 2.62 g Healthy adults (N ⫽ 17) ⫹
200566 single dose (100 brachial artery
g)
Grassi et al., 200542 Dark chocolate bars 88 mg/d Hypertensive adults (N ⫽ 20) ⫹
(100 g) for 15 brachial artery
days

112 Nutrition Reviews姞, Vol. 64, No. 3

cocoa beverage or flavonoid-rich dark chocolate bar
reported increased vasodilation or improvement in endo-
thelial function.31,32,39,40 Participants who had at least
one cardiovascular risk factor, including hypertension,
hyperlipidemia, diabetes, smoking, or history of coro-
nary artery disease demonstrated a reversal of endothe-
lial dysfunction with just a single dose of a cocoa
beverage.41 An increase in nitric oxide bioactivity was
seen in this study,41 and further increases in vasodilation
were reversed with the nitric oxide synthase inhibitor NG
–nitro-L-arginine methyl ester (L-NAME), given intra-
venously in the study by Fisher et al.39 The improvement
in endothelial function was substantiated in a recent
investigation with hypertensive individuals who con-
sumed 100 g of dark chocolate for 15 days.42 It was
found that dark chocolate consumption also improved
insulin sensitivity in both healthy and hypertensive indi-
viduals.40,42 Plasma epicatechin concentrations were also
significantly increased following cocoa or chocolate con-
sumption in several of these studies.
The cardioprotective mechanisms, including vasodi-
lation, of the major flavanols found in cocoa and choc-
olate, epicatechin and catechin, are shown in Figure 1.
These mechanisms may be related to increases in plasma
epicatechin or catechin concentrations that signal the
release of vasoactive substances from the endothelium,
including nitric oxide and prostacyclin. Epicatechin has
been shown to preferentially inhibit nitric oxide-related
nitration and oxidation reactions without affecting nitric
oxide synthesis and cyclic GMP signaling.43 This effect
is also depicted in Figure 1. Overproduction of reactive
nitrogen species associated with inflammatory conditions
such as atherosclerosis and coronary artery disease may
be mitigated with epicatechin or catechin as selective
inhibitors of nitric oxide-related oxidation and nitration
reactions.
The above vascular studies also provide evidence for
increased nitric oxide synthesis and beneficial changes in
the eicosanoid ratio. Epicatechin in particular has been
recently found to protect the integrity of endothelial cells
by scavenging free radicals and by maintaining endothe-
lial nitric oxide synthase.44 Moreover, several of the
studies31,32,39,41,42 measured endothelium-dependent,
flow-mediated dilation, which reflects an increase in flow
and shear stress after reactive hyperemia, and is mediated
by endothelium-derived nitric oxide and possibly prosta-
noids derived from the endothelium.45 When considered
together with the increased expression and/or activity of
endothelial nitric oxide synthase seen with long-term
exposure to epicatechin and related polyphenols, this

Figure 1. In the endothelial cells, nitric oxide (NO•) is synthesized from L-arginine by the enzyme nitric oxide synthase. NO• then
diffuses into the vascular smooth muscle cells and activates the enzyme soluble guanylyl cyclase (sGC). Guanosine 3⬘,5⬘-cyclic
monophosphate (cGMP) is formed from GTP, resulting in vasodilation. Epicatechin and catechin may signal the release of NO• and
inhibit NO-related nitration and oxidation reactions that generate the reactive nitrogen species (RNS) nitrosonium (NO⫹), nitroxyl
anion (NO–), and peroxynitrite (ONOO–). These reactive species may be linked to NO• overproduction in inflammatory diseases such
as coronary artery disease. Formation of peroxynitrite (ONOO–) due to superoxide anions (O•– 2 ) reacting with NO
•
leads to
endothelial dysfunction and decreased vasodilation. This deleterious process may be inhibited by epicatechin and catechin.

Nutrition Reviews姞, Vol. 64, No. 3 113

research provides a molecular basis for the cardioprotec-
tive effects of high epicatechin/catechin-containing
foods and drinks.43
BLOOD PRESSURE EFFECTS
In healthy subjects, the effects of cocoa and choco-
late on blood pressure have been negative,28,32,39,46 with
the exception of two recent studies.40,68 Two random-
ized, crossover trials in untreated hypertensives have also
shown a blood pressure lowering effect following 14 to
15 days of consumption of 100 g of dark chocolate.42,47
A recent report suggests that cocoa flavanols may lower
blood pressure by acting as an angiotensin I converting
enzyme inhibitor, which also has antioxidant properties
and can modulate nitric oxide production.48
PLATELET FUNCTION EFFECTS
A suppressive effect on platelet reactivity and plate-
let-related primary hemostasis has been demonstrated in
many studies even after a single chocolate dose (Table
3).49-53 The anti-platelet effects of cocoa and chocolate
may be due to increased production of nitric oxide,
which not only causes vasodilation, as previously dis-
cussed, but also inhibits platelet aggregation. Increased
plasma epicatechin concentrations were reported in the
studies by Pearson et al.50 and Murphy et al.,49 and may
signal increased nitric oxide synthesis in both the endo-
thelial cells and platelets. Increased production of pros-
tacyclin, an inhibitor of platelet aggregation, has also
been proposed as a possible mechanism.54 These platelet
inhibitory effects by cocoa and chocolate may be bene-
Table 3. Effects of Cocoa and Chocolate on Platelet Function
Cocoa
Flavonoids
Reference Type Amount
52
Rein et al., 2000 Cocoa beverage, single dose
(300 mL)
Rein et al., 200053 Cocoa beverage, single dose
(300 mL)
Pearson et al., 200250 Cocoa beverage, single dose
(300 mL)
Holt et al., 200251 Semisweet chocolate chips,
single dose (25 g)
Murphy et al., 200349 Cocoa tablets (6/d) for 28
days
Innes et al., 200370 Dark chocolate, single dose
(100 g)
114
ficial due to the pathophysiological role of platelets in
atherosclerosis and thrombotic events.
INFLAMMATION AND IMMUNE FUNCTION
EFFECTS
It is now widely accepted that atherosclerosis is a
chronic inflammatory disease.55 Inflammation and in-
creased oxidative stress promote endothelial dysfunction
and atherogenesis.56 Nitric oxide normally inhibits nu-
clear transcription factor (NF␬B), which binds to the
promoter regions of genes coding for pro-inflammatory
proteins such as cytokines and adhesion molecules. In
endothelial dysfunction, which is manifested by de-
creased bioavailabilty of nitric oxide, this inhibition is
loss. Excess intracellular ROS in oxidative stress also
activates NF␬B. Cocoa flavonoids may prevent activa-
tion of NF␬B and subsequent cytokine transcription by
diminishing intracellular ROS.
In experimental studies, the expression of the pro-
inflammatory cytokines interleukin-␤ (IL-1␤) and inter-
leukin-2 (IL-2) is modulated by cocoa flavonoids. Spe-
cifically, IL-1␤ expression in phytohemagglutinin-
stimulated peripheral blood mononuclear cells is reduced
by purified monomer to tetramer cocoa flavonoids and
IL-2 mRNA expression of and secretion by T-cells have
also been shown to be inhibited with cocoa treat-
ment.57,58 Cocoa flavonoids (epicatechin, catechin,
dimeric procyanidins) are also incorporated into Jurkat
T-cells with pretreatment, which inhibits phorbol
miristate acetate (PMA)-induced NF␬B activation.59
This finding suggests that the immune response can be
Subjects Platelet Function
897 mg Healthy adults Decreased platelet activation
(N ⫽ 10)
897 mg Healthy adults Decreased platelet activation and
(N ⫽ 30) microparticle formation;
aspirin-like effect on primary
hemostasis
897 mg Healthy adults Decreased platelet activation and
(N ⫽ 16) induced platelet plug
formation
220 mg Healthy adults Decreased platelet-related
(N ⫽ 18) primary hemostasis
234 mg Healthy adults Decreased platelet activation and
(N ⫽ 32) induced aggregation
— Healthy adults Decreased platelet-induced
(N ⫽ 30) aggregation
Nutrition Reviews姞, Vol. 64, No. 3
regulated by cocoa flavonoids, in part by modulating the
oxidant-responsive transcription factor NF␬B.
Cocoa-derived dimers have recently been found to
protect Jurkat T-cells from oxidation and to increase
plasma membrane fluidity.60 They also maintain the
membrane integrity by preventing leakage of small mol-
ecules from vesicles. The increase in membrane fluidity
may be linked with functional changes in membrane-
associated receptors and enzymes as well as ion trans-
port. Mathur et al.27 recently reported that cocoa prod-
ucts have no effect on markers of inflammation (whole-
blood cytokines, IL-1␤, IL– 6, TNF-␣, high-sensitivity
C-reactive proteins, and P-selectin). The healthy subjects
in this study consumed the cocoa and chocolate supple-
mentation (651 mg of cocoa flavonoids) for 6 weeks.
Epicatechin was not detected in the subjects’ plasma, and
the lack of effect on inflammatory markers was attributed
to the short half-life of cocoa flavonoids. It is known that
epicatechin peaks in the plasma at 2 hours after cocoa or
chocolate consumption and is cleared approximately 8
hours later.
CONCLUSION
The investigations on the antioxidant, vasodilatory,
blood-pressure lowering, anti-platelet, and anti-inflam-
matory effects of cocoa and chocolate provide exciting
new evidence into the potential cardiovascular benefits
of flavonoid-rich foods. Balance and moderation are also
important in a healthy diet and must be considered for
foods such as chocolate, which is also high in calories
and fat. Interestingly, the fat in chocolate (cocoa butter)
contains approximately 35% oleic acid, the monounsat-
Figure 2. Possible inhibitory effects of cocoa flavonoids on oxidative stress and endothelial dysfunction.
Nutrition Reviews姞, Vol. 64, No. 3
urated fat found in olive oil, and 60% saturated fat (35%
stearic acid, 25% palmitic acid). Palmitic acid has cho-
lesterol-raising effects; however, it is believed to be
offset by the neutral cholesterol effects of stearic acid
and the slightly cholesterol-lowering effect of oleic acid.
Stearic acid can also be readily converted to oleic acid.61
Short-term31,32,40,42 and long-term clinical studies of
chocolate supplementation62-64 have shown neutral or
favorable changes in cholesterol levels. In fact, daily
consumption of the “polymeal,” a combined meal of
seven food components, including dark chocolate, wine,
fish, fruits, vegetables, garlic, and almonds, was recently
proposed as a strategy to reduce cardiovascular disease
events by 76% and increase total life expectancy by 4.8
to 6.6 years.65 It is clear that nutritional therapy with
flavonoid-rich foods, especially with those that raise
plasma epicatechin concentrations, may prove beneficial
in reducing or preventing oxidative stress and endothelial
dysfunction. As illustrated in Figure 2, the cocoa fla-
vonoids may inhibit both pathophysiological processes
that lead to atherosclerosis and eventual cardiovascular
events.
Based on the existing literature, it would be practical
to advise consumption of a wide range of flavonoid-rich
foods and beverages, especially those that contain sub-
stantial amounts of the same flavonoids (flavanols) found
in cocoa and dark chocolate. These include: green and
black tea (especially Ceylon), red wine, cherries (sweet),
apples, purple grapes, blackberries, raspberries, and
broad beans.34 Other common fruits and vegetables with
a high (⬎4000) total antioxidant capacity (calculated by
summing the lipophilic and hydrophilic ORACFL values)
per serving (ranked highest to lowest) include: blueberry,
115
cranberry, artichoke (cooked), blackberry, prunes, rasp-
berry, strawberry, Red Delicious and Granny Smith ap-
ples (with peel), pecans, sweet cherries, plums, and
russet potatoes (cooked).21 These foods represent plen-
tiful sources of flavonoids and, in moderation with a
healthy and active lifestyle, small amounts of dark choc-
olate may also be good for your heart.
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