Curr Atheroscler Rep (2011) 13:447–452

DOI 10.1007/s11883-011-0203-2

NUTRITION (WILLIAM S. HARRIS, SECTION EDITOR)

Chocolate and Coronary Heart Disease:

A Systematic Review
Owais Khawaja & J. Michael Gaziano & Luc Djoussé

Published online: 6 September 2011

# Springer Science+Business Media, LLC 2011

Abstract Coronary heart disease (CHD) is the leading
cause of death in the United States. The high content of
polyphenols and flavonoids present in cocoa has been
reported to play an important protective role in the
development of CHD. Although studies have demonstrated
beneficial effects of chocolate on endothelial function,
blood pressure, serum lipids, insulin resistance, and platelet
function, it is unclear whether chocolate consumption
influences the risk of CHD. This article reviews current
evidence on the effects of cocoa/chocolate on clinical and
subclinical CHD, CHD risk factors, and potential biologic
mechanisms. It also discusses major limitations of currently
available data and future directions in the field.
O. Khawaja : J. M. Gaziano : L. Djoussé
Massachusetts Veterans Epidemiology and Research Information
Center (MAVERIC), Boston Veterans Affairs Healthcare System,
Boston, MA, USA
O. Khawaja
e-mail: oajaz@yahoo.com
J. M. Gaziano
e-mail: JMGAZIANO@PARTNERS.ORG
J. M. Gaziano : L. Djoussé
Geriatric Research, Education, and Clinical Center (GRECC),
Boston Veterans Affairs Healthcare System,
Boston, MA, USA
O. Khawaja : J. M. Gaziano : L. Djoussé (*)
Divisions of Aging,
Brigham and Women’s Hospital and Harvard Medical School,
1620 Tremont St, OBC, 3rd floor,
Boston, MA 02120, USA
e-mail: ldjousse@rics.bwh.harvard.edu
J. M. Gaziano
Division of Preventive Medicine,
Brigham and Women’s Hospital and Harvard Medical School,
Boston, MA, USA
Keywords Chocolate . Cocoa . Flavanol . Polyphenols .
Coronary heart disease . Blood pressure . Epicatechin .
Catechin
Introduction
In the United States, approximately 19.2 million men and
8.4 million women have a history of heart attack, angina
pectoris, or both [1]. In 2007, coronary heart disease (CHD)
death rates per 100,000 people were about 165.6 for white
men, 191.6 for black men, 94.2 for white women, and
121.5 for black women [2]. Numerous studies have
demonstrated beneficial effects of lifestyle modification,
such as diet and exercise, on the prevention of CHD [3–6].
The high content of polyphenols present in grains, fruits,
vegetables, nuts, tea, and cocoa has been reported to play
an important role in reducing the risk of CHD [7, 8].
Although the Dietary Approaches to Stop Hypertension
(DASH) trial emphasized the importance of fruit and
vegetables, whole grains, low-fat dairy products, and low
sodium intake for cardiovascular health, limited data are
available in the literature on the role of cocoa products,
including chocolate, on CHD risk.
Chocolate consists of a number of raw and processed
foods derived from the seeds of the tree Theobroma cacao
[9]. Cocoa was first introduced in Europe during the 16th
century. Almost 75% percent of the world’s cocoa bean
production occurs in West Africa [9]. Cocoa-rich chocolate
is well known for its good taste, and an average American
consumes about 5.3 kg of chocolate per year [10]. Most of
the chocolate is a combination of cocoa solids, cocoa butter or
other fats, and sugar. Milk chocolate also contains milk
powder or condensed milk, whereas white chocolate contains
cocoa butter, sugar, and milk without any cocoa solids. Dark
chocolate contains added fat and sugar to the cacao mixture.
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Cocoa products contain polyphenols and flavonoids.
Catechins, including catechin and its isomer epicatechin,
are types of flavonoids with strong anti-oxidant properties
[11]. Cocoa contains high concentrations of epicatechin and
has been noted to have anti-oxidant content that is two
times higher than that of red wine and almost three times
higher than that of green tea [12]. Gu et al. [13]
demonstrated that milk chocolate contains 5 to 12 mg of
catechin per 100 g, 18 to 24 μg of epicatechin per 100 g,
and 0.22 to 0.31 mg of procyanidins per 100 g; for dark
chocolate, the corresponding concentrations were 11 to
33 mg, 52 to 125 μg, and 0.85 to 1.99 mg per 100 g,
respectively. Chocolate also contains important minerals
such as potassium, zinc, selenium, and magnesium along
with other nutrients including vitamin E, saturated fat
(60%), monounsaturated fat (35%), and linoleic acid (3%)
that might lower the risk of CHD [7, 14].
Despite available knowledge on nutrients contained in
cocoa products, there are limited data on the effects of
chocolate on clinical and subclinical CHD. Hence, this
review first evaluates available data on the effects of
cocoa on clinical and subclinical CHD, CHD death, CHD
risk factors, and potential biologic mechanisms. Then, it
discusses major limitations of currently available data and
future directions in the field.
Chocolate Consumption and Coronary Heart Disease
Although studies have demonstrated beneficial effects of
chocolate on various CHD risk factors, including endothelial
function [15–17], blood pressure (BP) [18, 19], serum lipids
[20, 21], insulin resistance [18, 22], and platelet function [23,
24], little is known about the effects of chocolate on CHD
events. We summarized studies that have examined associ-
ations between chocolate/cocoa consumption and CHD
prevalence, cardiovascular disease (CVD), and all-cause
mortality in Table 1.
In a cross-sectional study, Djousse et al. [25•]
reported an inverse relation between chocolate consump-
tion and prevalent CHD in 4,970 participants of the
National Heart, Lung, and Blood Institute (NHLBI)
Family Heart Study. Self-reported chocolate consumption
was inversely associated with the prevalence of CHD with
an odds ratio (OR) of 1.01 (95% CI, 0.76–1.37), 0.74
(95% CI, 0.56–0.98), and 0.43 (95% CI, 0.28–0.67) for
chocolate consumption of 1 to 3 times per month, 1 to 4
times per week, and ≥5 times per week, respectively. In
another prospective cohort study, Lewis et al. [26••]
reported that chocolate consumption of ≥1 time per week
was associated with a 35% lower risk of CHD compared
with intake of <1 time per week (multivariable adjusted
relative risk of 0.65 [95%CI, 0.46–0.94]).
Curr Atheroscler Rep (2011) 13:447–452
Chocolate Consumption and Subclinical Coronary
Heart Disease
Shiina et al. [27] in a single-blinded, randomized trial,
studied the effects of flavonoid- rich dark chocolate among 39
healthy men by measuring coronary flow velocity reserve
(CFVR) via noninvasive transthoracic Doppler echocardiog-
raphy (TTDE). Flavonoid-rich dark chocolate consumption
was noted to improve CFVR (3.38±0.49 before and 4.28±
0.85 after dark chocolate intake; P<0.01), whereas there was
no significant change noted in CFVR among those with
white chocolate consumption (3.28±0.49 before and 3.16±
0.49 after white chocolate intake; P=0.44), independent of
changes in the BP, lipid profile, or other oxidative stress
parameters. In a cross-sectional study, Djousse et al. [28••]
demonstrated an association between chocolate consumption
and calcified atherosclerotic plaques in coronary arteries
(CAC) in 2,217 participants of the NHLBI Family Heart
Study. They found an inverse association between chocolate
consumption and CAC with an OR of 0.94 (95% CI, 0.66–
1.35), 0.78 (95% CI, 0.53–1.13), and 0.68 (95% CI, 0.48–
0.97) for chocolate consumption of 1 to 3 times per month,
once per week, and ≥2 times per week, respectively,
compared to no chocolate intake as the reference group.
Chocolate Consumption and Coronary Heart
Disease Mortality
Janszky et al. [29••] observed a strong inverse association
between chocolate consumption and mortality in post–
myocardial infarction patients for people with chocolate
consumption of less than once per month, up to once per
week, and twice or more per week, (HR of 0.73 [95% CI,
0.41–1.31), 0.56 [95% CI, 0.32–0.99], and 0.34 [95% CI,
0.17–0.70], respectively). The Iowa Women’s Health Study
reported an inverse association between catechin and
epicatechin intake and CHD mortality in post-menopausal
women after 13 years of follow-up [30]. In another study,
Buijsse et al. [31] reported a relative risk (RR) of 0.50 (95%
CI, 0.32–0.78) for cardiovascular mortality and an RR of
0.53 (95% CI, 0.39–0.72) for all-cause mortality in elderly
men when comparing the highest to the lowest tertile of
cocoa intake. Mink et al. [32] demonstrated a lower risk of
CHD, CVD, and total mortality (RR 0.88 [95% CI, 0.78–
0.99], 0.91 [95% CI, 0.83–0.99], and 0.90 [95% CI, 0.86–
0.95], respectively) for those consuming any anthocyanidin
versus none; an RR of 0.90 (95% CI, 0.86–0.95) for
incident CHD, and 0.88 (95% CI, 0.82–0.96) for total
mortality comparing the highest to the lowest quintile of
flavanone consumption among post-menopausal women. A
similar pattern of decreased cardiovascular-related death
rates among those consuming flavanol-rich cocoa as their
Curr Atheroscler Rep (2011) 13:447–452 449

Table 1 Chocolate/cocoa and coronary heart disease mortality

Study Variables studied Study design Participants OR (95% CI), RR (95% CI), or HR

Djousse et al. [25•] Chocolate consumption Cross-sectional 4,970 OR: 1.01 (0.76–1.37), 0.74 (0.56–0.98), and 0.43
(NHLBI Family and prevalent CHD (0.28–0.67) for subjects consuming 1–3/month,
Heart Study) 1–4/week, and 5+/week, respectively
(P for trend <0.0001)
Lewis et al. [26••] Chocolate consumption Cohort study 1,216 OR: 0.76 (0.60–0.97) with an event rate of 158
and ASVD (27.3%) versus 132 (20.7%) for chocolate
consumption <1/week versus ≥1/week,
respectively
Shiina et al. [27] Acute effect of Randomized, 35 CFVR of 3.38±0.49 before intake, 4.28±0.85
flavonoid-rich dark single blind after intake for dark chocolate (P<0.01) vs
chocolate on coronary 3.28±0.49 before intake, 3.16±0.49 after intake
circulation by TTDE for white non-flavonoid chocolate (P=0.44)
Djousse et al. [28••] Chocolate consumption Cross-sectional 2,217 OR: 0.94 (0.66–1.35), 0.78 (0.53–1.13), and
(NHLBI Family and CAC 0.68 (0.48–0.97) for chocolate consumption
Heart Study) of 0, 1–3/month, 1/week, and 2+/week,
respectively (P for trend 0.022)
Janszky et al. [29•] Chocolate and mortality Cohort study 1,169 HR: 0.73 (0.41–1.31), 0.56 (0.32–0.99),
(Stockholm Heart following first AMI and 0.34 (0.17–0.70) for chocolate consumption
Epidemiology of <1/month, ≤ 1/week, and ≥ 2/week, respectively
Program)
Buijsse et al. [31] Cocoa intake and Prospective study 470 RR for men in the highest tertile was 0.50
(Zutphen Elderly CVD mortality (0.32-0.78; P=0.004 for trend) for cardiovascular
Study) mortality and 0.53 (0.39–0.72; P<0.001) for
all-cause mortality
Bayard et al. [33] Effect of flavonol-rich Case control study 77,375 in Mean age-adjusted death rate/100,000 over
cocoa beverage on Panama and 5 years due to CVD (8.7±3.02) was much
mortality 548 in San Blas lower in exposed vs non-exposed group
(43.94±0.64)

AMI—acute myocardial infarction; ASVD—atherosclerotic vascular disease; CAC—calcified atherosclerotic plaques in coronary arteries; CFVR—
coronary flow velocity reserve; CHD—coronary heart disease; CVD—cardiovascular disease; HR—hazard ratio; NHLBI—National Heart, Lung,
and Blood Institute; OR—odds ratio; RR—relative risk; TTDE—trans-thoracic Doppler echocardiography

main beverage were also noted in an observational study by
Bayard et al. [33].
Potential Biological Mechanisms of Chocolate
Consumption and Coronary Heart Disease
endothelial progenitor cells, which are critical for repair of
vasculature and endothelial function, along with a decrease
in systolic blood pressure among subjects in the high-flavanol
group compared with people in the low-flavanol group [36].
Epicatechin at low doses has also been shown to reduce
myocardial infarct size in mice [37].

Chocolate contains antioxidants that can scavenge free

radicals and reduce oxidative stress, thereby reducing the
risk of CHD [34]. Polyphenols may improve endothelial
function. The mechanism may involve polyphenol-induced
nitric oxide (NO) synthesis via redox-sensitive activation of
the phosphatidylinositol3-kinase/Akt pathway; an alterna-
tive mechanism could be an increased intracellular free
calcium concentration and activation of endothelial estro-
gen receptors [15]. Increased endothelial NO production
leads to endothelium-dependent relaxation [16, 17, 35].
In a randomized, controlled, double-blind, cross-over
trial [36], there was a 47% improvement of endothelial
vasomotor function in the high-flavanol group compared
with the low-flavanol group after 1 month of intervention in
16 CHD patients. There was also an increased number of
Chocolate Consumption and Coronary Heart Disease
Risk Factors
Chocolate Consumption and BP
Flavanol-rich chocolate and cocoa products have BP-lowering
effects and thereby have gained interest as a non-pharmacologic
treatment option for hypertension [38, 39]. Grassi et al. [18]
studied the effects of flavanol-rich dark chocolate on BP in
hypertensive patients with impaired glucose tolerance. They
noted a 3.83-mm Hg decrease in systolic and 3.92-mm Hg
decrease in diastolic BP among those who received flavanol-
rich dark chocolate compared with subjects assigned to
flavanol-free white chocolate. However, another trial [40]
450
failed to observe any beneficial effects of 50 g/d of dark
chocolate containing 70% cocoa on BP. In another study,
Persson et al. [41] showed that dark chocolate significant
inhibited angiotensin-converting enzyme activity and
increased NO in human endothelial cells (P<0.01). As
reviewed in a meta-analysis [19], there was a significant
BP-lowering effect for cocoa/chocolate with a mean
change in systolic BP of −3.2±1.9 mmHg and diastolic
BP of −2.0±1.3 mmHg (P=0.003).
Chocolate Consumption and Serum Lipids
Chocolate consumption has been shown to lower plasma
cholesterol. Grassi et al. [18] reported that dark chocolate
was associated with a decrease in total cholesterol (−6.5%;
P<0.0001) and low-density lipoprotein (LDL) cholesterol
(−7.5%; P<0.0001). No effect of dark chocolate was
observed on the concentrations of serum high-density
lipoprotein (HDL) cholesterol or triglycerides (TG). Mellor
et al. [21] also demonstrated a cholesterol-lowering effect
of polyphenol-rich chocolate along with an increase of HDL
cholesterol (1.16±0.08 vs 1.26±0.08 mmol/L; P=0.05) and
no effect on markers of inflammation, insulin resistance, or
weight.
Jia et al. [20], in their meta-analysis, demonstrated that
short-term chocolate consumption lowered LDL cholesterol
by 5.87 mg/dL and total cholesterol by 5.82 mg/dL. The
changes seen were highly dependent on the dose of cocoa
consumption and health status of the patients, with no
effects observed in healthy participants.
In a recent meta-analysis by Tokede et al. [42••],
intervention with dark chocolate was associated with a
statistically significant reduction in serum LDL (−5.90
[95% CI, -10.47 to −1.32] mg/dl) and total cholesterol
(−6.23 [95% CI, −11.60 to −0.85] mg/dL). However, no
statistically significant effect was seen on serum HDL
(−0.76 [95% CI, −3.02 to 1.51] mg/dL) or triglyceride
(−5.06 [95% CI, −13.45 to 3.32] mg/dl). The observed
effect was stronger in subjects with high cardiovascular
disease risk and in studies with a shorter duration of follow-up.
Chocolate Consumption and Insulin Resistance
Grassi et al. [18], in their interventional study, found that
flavanol-rich dark chocolate led to a decreased insulin
resistance (homeostasis model assessment of insulin resis-
tance [HOMA-IR]; P<0.0001), enhanced insulin sensitivity
(Insulin Sensitivity Index [ISI], ISI(0); P<0.05) as well as
improved beta-cell function (P= 0.035); in contrast,
flavanol-free white chocolate had no effects. In another
study, Davison et al. [22] found that an intervention with
high flavanol led to a 0.31% reduction in HOMA-IR.
Comparable findings have been reported in other studies
Curr Atheroscler Rep (2011) 13:447–452
and suggest beneficial effects of flavanol- rich compounds
on cardiovascular disease risk factors [43].
Chocolate Consumption and Inflammatory Markers
di Giuseppe et al. [44] reported a J- shaped association
between dark chocolate and C-reactive protein levels. A
beneficial effect of cocoa powder on inflammatory markers
(expression of VLA-4, CD40, and CD36 in monocytes, as
well as serum concentrations of endothelium-derived
adhesion molecules P-selectin and intracellular adhesion
molecule-1) has been reported by other investigators [45].
These results underscore the potential benefits of cocoa
polyphenols in the modulation of inflammatory mediators.
Chocolate Consumption and Platelets
Cocoa products have been shown to exert an inhibitory
effect on platelet aggregation in various studies [23, 46,
47]. Potential mechanisms include reduced ADP/collage-
activated platelet-related primary hemostasis, possibly due
to a reduction in activated glycoprotein IIb/IIIa surface
proteins [23]. Innes et al. [24] reported a reduction in platelet
aggregation after consumption of 100 g of dark chocolate
among healthy volunteers. Stearic acid, commonly found in
chocolate, has also been shown to reduce mean platelet
volume, which serves as an index of platelet activation
among humans [48].
Major Limitations of Current Data on Chocolate
and Coronary Heart Disease
Although chocolate consumption has been shown to be
associated with a number of beneficial effects on CHD,
there are several gaps in the current literature. Most of the
trials conducted were short term, making it difficult to
assess long-term effects of chocolate on CHD and other
cardiovascular endpoints. Limited prospective studies have
been conducted to assess long-term effect of dark chocolate
and account for dietary change over time. Few epidemiologic
studies have separated dark from milk chocolate, suggesting
that observed beneficial effects of total chocolate might have
underestimated the true relation between dark chocolate and
cardiovascular endpoint/risk factors. At this point, it is unclear
what amount of chocolate is optimal given the lack of
uniformity in dosage in randomized trials. Most of the studies
conducted did not specify the exact type or amount of chocolate
used in individual studies. Likewise, limited data are available
on polyphenolic content in chocolate or cocoa used in
intervention studies. Lastly, there was heterogeneity in the
quality of studies reviewed, making it more difficult to interpret
the data.
Curr Atheroscler Rep (2011) 13:447–452
Future Perspectives
Further research is needed to better elucidate the underlying
physiologic mechanisms by which chocolate/cocoa powder
favorably influence the risk of CHD. Special attention will
need to be given to potential confounding by other dietary
or lifestyle factors, especially in observational studies. Future
studies should carefully consider the dosage, polyphenol
content, type, duration, and frequency of cocoa/chocolate
consumption.
With steady progress in genomics, proteomics, transcrip-
tomics, and other areas, future studies may consider the role of
genetics and gene-environment interaction on the beneficial
effects of chocolate/cocoa on CHD. Increased caloric intake
with cocoa consumption in the form of chocolate, due to
addition of fats, milk, or sugar, will also need to be analyzed in
future studies (as supplemental calories from chocolate may
lead to weight gain if consumed in larger amounts). Long-
term, double-blind, randomized controlled trials with hard
clinical endpoints are needed before recommending cocoa or
its products as a treatment option in patients with high risk for
CHD or for healthy individuals. In the meantime, it would be
safer to consume dark chocolate only in moderate amounts (ie,
as substitute for sugared candy) while keeping track of the
overall daily energy intake.
Conclusions
Based on the available data from observational and interven-
tional studies, there is ample evidence in support of beneficial
effects of cocoa/dark chocolate on CHD risk. Future studies are
needed to confirm current data and elucidate underlying
physiologic mechanisms and identify the optimum daily dosage.
Disclosure O. Khawaja: none; J.M. Gaziano: none; L. Djoussé’s
institution received an investigator-initiated grant.
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