REVIEW

URRENT
C
OPINION

Health benefits of cocoa

Rabia Latif

Purpose of review
In modern society, cocoa is being eaten as a confectionery, contrary to its medicinal use in the past.
However, since the last decade, there has been a revival of talks about cocoas health beneficial effects.
Development has been made at the molecular level recently. This review discusses the recent progresses on
potential health benefits of cocoa and/or its derivatives, with a focus on the areas that have been paid
little attention so far, such as the role of cocoa in immune regulation, inflammation, neuroprotection,
oxidative stress, obesity, and diabetes control.
Recent findings
Thanks to the advancement in analytical technologies, the cocoas metabolic pathways have now been
properly mapped providing essential information on its roles. Cocoa helps in weight loss by improving
mitochondrial biogenesis. It increases muscle glucose uptake by inserting glucose transporter 4 in skeletal
muscles membrane. Because of its antioxidant properties, cocoa offers neuron protection and enhances
cognition and positive mood. It lowers immunoglobulin E release in allergic responses. It can affect the
immune response and bacterial growth at intestinal levels. It reduces inflammation by inhibiting nuclear
factor-kB.
Summary
Keeping in view the pleiotropic health benefits of cocoa, it may have the potential to be used for the
prevention/treatment of allergies, cancers, oxidative injuries, inflammatory conditions, anxiety,
hyperglycemia, and insulin resistance.
Keywords
cocoa flavonoids, cognition, immune system, inflammation, insulin resistance, obesity, oxidative stress

INTRODUCTION
Cocoa and cocoa-based products such as chocolate
are one of the major natural sources of dietary flavonoids because of its high content of polyphenols,
epicatechin, catechin primarily and their oligomers,
and the procyanidins. Over the last decade, cocoa
research has become the center of growing attention.
The cardiovascular effects of chocolate/cocoa have
been investigated and reviewed thoroughly [1 ], and
even found to be cost-effective [2 ]; however, there is
dearth of studies dealing with other beneficial effects
such as immune modulation, antioxidative, antiinflammatory, neuroprotective, insulin resistance,
obesity, and so on. The aim of this review is to
bring into the limelight these unvisited, not too well
known effects and summarize the most recent evidence of the effects of chocolate/cocoa on body
systems other than cardiovascular.
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EFFECTS OF CHOCOLATE ON IMMUNE

SYSTEM
The cocoa/chocolate influences multiple aspects of
the immune system. The recent advances in this

context are the effect of cocoa/chocolate on allergy

and intestinal immune system.

ALLERGY
Allergy is characterized by dysregulated immune
response in atopic individuals. Various nutritional
interventions against allergic diseases have been
investigated recently, coca being one of these
emerging nutraceuticals [3]. In a recent experimental study of rat allergic model, cocoa diet caused
considerably lower concentrations of total serum
immunoglobulin E (IgE), decreased tumor necrosis
factor, and interleukin (IL)-10, signifying a possible

Department of Physiology, College of Medicine, University of Dammam,

Dammam, Kingdom of Saudi Arabia
Correspondence to Dr Rabia Latif, MBBS, MPhil, PhD, Department of
Physiology, College of Medicine, University of Dammam, Dammam,
Kingdom of Saudi Arabia. Tel: +966 596 212 648; e-mail: dr.rabialatif
@gmail.com, rlhussain@ud.edu.sa
Curr Opin Clin Nutr Metab Care 2013, 16:669674
DOI:10.1097/MCO.0b013e328365a235

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Functional foods and dietary supplements

KEY POINTS
 Cocoa reduces body weight by increasing
mitochondrial biogenesis, capillarity, and
muscular performance.
 Cocoa protects against insulin resistance and
hyperglycemia by inserting glucose transporter 4
(GLUT4) in skeletal muscle membranes.
 Cocoa causes considerably lower concentrations of
total serum IgE, decreased tumor necrosis factor, and
IL-10, signifying a possible role for cocoa flavonoids in
the treatment of allergic disorders.
 Cocoa has a positive effect on mood, neural efficiency,
and may enhance cognition.
 Cocoa reduces inflammatory potential by inhibiting
nuclear factor-kB (NF-kB).
 The cocoa-induced immune modulation may be
important in cancers, inflammation, diseases like celiac
or food allergies, and autoimmune pathogenesis.

immunity in autoimmune diseases and allograft

transplantation) percentage [9]. This immune
modulation may be important in cancers, inflammation, diseases like celiac or food allergies, and
autoimmune pathogenesis.

OXIDATIVE STRESS
There is a strong evidence for antioxidant effects of
cocoa in a variety of in-vitro studies. Recently, a
study has revealed that procyanidin flavonoids from
cocoa have the potential to protect colonic cells
from oxidative stress and chemical-induced injury
by modulating major antioxidant/detoxificant
enzymes involved in intestinal protection [10 ].
However, the antioxidant efficacy of flavonoids
in vivo is less recognized. Two recent studies have
investigated the effects of cocoa supplementation
in vivo in rat models of adjuvant and autoimmune
arthritis [11 ,12]. Cocoa supplementation resulted
in increased splenic catalase and less reactive oxygen
species (ROS) synthesis by macrophages [11 ]. This
decreased synthesis of ROS is most likely due to
cocoa flavonoids free radical quenching activity.
Cheng et al. [13 ] suggested that catechin supplementation significantly inhibited oxidative damage
and overturned the impairment of the antioxidant
system in the intestinal mucosa of Ketoprofenexposed rats. Cheng et al. showed that catechin,
one of the constituents of cocoa, effectively prevents
Ketoprofen-induced intestinal epithelial cell injury
and induces expression of heme oxygenase-1 (an
antioxidant enzyme associated with protection of
intestines) via modulation of nuclear factor erythroid 2-related factor 2 (a transcription factor that
regulates antioxidant enzymes) protein translocation. These findings strongly support the potential
use of cocoa as a dietary preventive agent against
intestinal injuries induced by oxidative stress.
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role for cocoa flavonoids in the treatment of allergic

disorders [4 ].
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INTESTINAL IMMUNE SYSTEM AND

MICROBIOTA
In the gut immune system, chocolate/cocoa alters
Toll-like receptors expression and downregulates
intestinal IgA by decreasing:
(1) IL-6, a cytokine essential for the conversion of
B cells to IgA-secreting cells;
(2) chemokine ligands and its chemokine receptors,
required for promoting cell recruitment in
intestinal lamina propria; and
(3) genes associated with gut homing of IgA-secreting cells [5 ].

&&

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Cocoa procyanidins and fiber reach the colon

intact and act as a bacterial growth substrate inside
the colon. Long-term cocoa intake can even modify
microbiota composition and immune response at
intestinal level [6], excellently reviewed recently
[7 ]. It results in a differential Toll-like receptors
pattern and a decrease in the intestinal IgA secretion
and IgA-coating bacteria associated with a significant decrease in the proportion of Bacteroides,
Clostridium, and Staphylococcus genera in the feces
[8].
The cocoa intake also reduces helper and regulatory T cells and increases natural killer T cell
(T lymphocytes that promote cellular immunity
in tumors and infections, and suppresses cellular
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NEUROPROTECTIVE EFFECTS
The neuroprotective effects of cocoa have been
recently reviewed by Nehlig [14 ].
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MOOD
The link between cocoa consumption and cardiovascular health is well documented. Good cardiovascular health is related to better cognitive
performance [15]. Cocoa flavonols have been shown
to significantly reduce mental fatigue and improve
cognitive thinking during sustained mental effort
[16]. Chocolate also reduces symptoms of anxiety
and depression in patients with chronic fatigue [17].
Recently, direct effects of high and low cocoa
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Health benefits of cocoa Latif

polyphenols on cognitive performance and mood in

healthy individuals have been revealed through a
double-blind, placebo-controlled study using highly
validated, computerized cognitive test battery
[18 ]. Cocoa improved self-rated calmness and contentedness following 30 days of treatment, most
probably by known actions of polyphenols on GABA
receptors [19] and by upregulating tryptophan
metabolism leading to the production of serotonin:
a calming neurotransmitter [20 ]. Cognitive performance was not altered significantly, a finding
contrary to Scholey et al. [16]. Pase et al. [18 ]
suggested that improved cognition following cocoa
may only arise under situations of high stress and
calm feelings perhaps may not lead to cognitive
enhancement. Another hypothesis was that the
participants were highly educated (average education
level was 16 years) and there was little scope for
cognitive enhancement as compared with participants who have suboptimal cognitive performance
[19].
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COGNITION
A note recently published in New England Journal of
Medicine reported a close, significant linear correlation between chocolate consumption per capita
and the number of Nobel laureates per in a total of
23 countries [21 ].
In another study, steady state visually evoked
potentials measured in response to a spatial working
memory task in cocoa supplemented group exhibited
some significant potential differences, suggesting
that cocoa supplementation may improve neural
efficiency [22 ]. The underlying mechanism of
enhanced neural efficiency might be improved vascular function and/or antioxidant processes within
the brain associated with cocoa intake.
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ALZHEIMERS DISEASE
Alzheimers disease is a neurodegenerative disorder
characterized pathologically by plaques made up
of amyloid beta peptide (Ab). Cocoa has been
shown to reduce Ab toxicity in an animal model
of Alzheimers disease by inhibiting oligomerization
through its antioxidant activity and upregulating
[20 ] the following pathways:
&&

(1) Pyruvate pathway in which pyruvate changes

to acetyl CoA, a key substance for the synthesis
of ATP and acetylcholine. Downregulation
of pyruvate pathway is associated with the
reduction of acetylcholine, ATP production,
glycolysis, mitochondrial dysfunction, and
neuronal death the features that are all present
in Alzheimers disease [23,24].

(2) Proteosome, a large protein complex that maintains protein homeostasis and inhibits Ab
peptide aggregation.
(3) Citric acid cycle pathway that is downregulated
in Alzheimers disease.
Thanks to the advancement in analytical technologies, the cocoas metabolic pathways have now
been properly mapped providing essential information on its roles in Alzheimers disease. Recently,
the effect of cocoa polyphenolic extract on a human
Alzheimers disease in-vitro model has been investigated, which revealed that cocoa polyphenols triggers neuroprotection by activating brain-derived
neurotrophic factor (BDNF) survival pathway, both
on Ab plaque-treated cells and on Ab oligomerstreated cells [25 ]. BDNF is a neurotrophin required
for the development and maintenance of the
nervous system. It plays an important role in cognition, learning, and memory formation and has
also been implicated in Alzheimers disease [26].
BDNF-boosting neuroprotective effects in vitro
suggest that the cocoa or its derivatives may have
a therapeutic potential for Alzheimers disease.
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STROKE
A recent study has examined the association
between chocolate consumption and risk of stroke
in Swedish men [27 ]. Previous studies have investigated this association, either in women only or in
both men and women [28,29]. Larsson et al. [27 ]
planned a large-scale (37 103 participants) and
longer duration (over 10 years) study in which
chocolate consumption was assessed using a foodfrequency questionnaire and stroke cases were
identified through a hospital discharge registry. It
was found that men, who ate the largest amount of
chocolate, had a 17% lower risk of stroke compared
to those who did not consume any chocolate.
Larsson et al. also conducted a meta-analysis using
the search terms chocolate and stroke and identified five studies. The analysis of these studies
showed an overall 19% decreased risk of stroke for
individuals with highest chocolate consumption
compared to nonchocolate consumers. The mechanisms responsible for this observed inverse association between chocolate intake and stroke risk may
include antioxidant, antiplatelet, and anti-inflammatory effects of chocolate flavonoids.
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INFLAMMATION
Cocoa supplementation results in less secretion
of inflammatory mediators from peritoneal macrophages [12], in line with the previous studies

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Functional foods and dietary supplements

documenting anti-inflammatory effects of cocoa in

healthy animals [30]. However, it [12] was unique in
the sense that it showed anti-inflammatory effects
of orally taken cocoa in a pathological state.
The suggested mechanism behind cocoa-induced
reduced inflammatory potential is inhibition of
NF-kB [31 ], which is a transcriptional modulator
of genes involved in inflammation. NF-kB plays a
pivotal role in the development of inflammatory
diseases and regarded as a key therapeutic target at
the moment [32]. It is present in the cell cytoplasm
as an inactive form. Upon activation, it migrates to
the nucleus to modulate the transcription of the
inflammatory cytokines such as tumor necrosis
factor-a (TNF-a) and adhesion molecules. Cocoa
flavonoids have been shown to prevent colon
inflammation in a rat model of colon cancer and
in TNF-a-stimulated Caco-2 cells (a well established
in-vitro model of human intestines), by decreasing
the nuclear levels of NF-kB and the expression of
proinflammatory enzymes such as cyclo-oxygenase2 and inducible nitric oxide [33 ]. Rodrguez-Ramiro
et al. [10 ,33 ] elucidated the mechanisms involved
at molecular level that turned out to be inhibition of
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NF-kB translocation and c-Jun N-terminal kinases

(JNK) phosphorylation. Hence, cocoa could be effective in the dietary prevention of intestinal inflammation and related cancer development.

OBESITY, HYPERGLYCEMIA, AND INSULIN

RESISTANCE
Hyperglycemia and obesity are closely related to
insulin resistance and type-2 diabetes mellitus.
Chocolate products are often high in sugar and
fat, leading to the assumption that eating chocolate
enhances BMI. However, a recent study has refuted
this belief by showing that frequency of chocolate
consumption is significantly related to lower BMI
after adjusting for age and sex [34 ]. This study does
not preclude the likelihood of some chocolate products or chocolate consumption profiles doing so.
Certainly this correlation does not establish causation. However, compatible experimental findings in
animal studies suggest the association could be
causal [35,36] and cocoa may reduce body weight
without changing calories or exercise by increasing
mitochondrial biogenesis, capillarity, and muscular
&&

Cocoa

Inhibition of lipases

Plasma adiponectin

AMP-K

UCP and PGC-1

Absorption of dietary fat

GLUT4

Fatty acid oxidation

Lipogenesis

Fecal lipid output

Mitochondrial biogenesis

Glucose uptake

Blood glucose

Body weight

Serum lipids

Insulin sensitivity

FIGURE 1. Proposed mechanism of cocoa-induced weight loss and improved insulin sensitivity. AMP-Ka, AMP activated
protein kinase a; GLUT4, glucose transporter 4; UCP, uncoupling protein; PGC-1a, proliferator-activated receptor c
coactivator-1a.
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Health benefits of cocoa Latif

performance. Underlying mechanism behind

cocoa-induced increased mitochondrial biogenesis
is high plasma adiponectin levels that then cause
activation of AMP-activated protein kinase (AMPKa)
in skeletal muscle, liver, and adipose tissue [37 ].
AMPKa regulates intracellular glucose and lipid
metabolism by translocating GLUT4 to the plasma
membrane in skeletal muscle and brown adipose
tissue; thus, preventing hyperglycemia and insulin
resistance. The activation of AMPKa also promotes
the expression of uncoupling protein (UCP); a family
of proton transporters located in the mitochondrial
inner membrane and causes increased thermogenesis
and energy expenditure and proliferator-activated
receptor c coactivator-1a (PGC-1a) in skeletal
muscle, adipose tissue and liver, thus preventing
obesity by increasing energy expenditure and/or
thermogenesis. Activation of AMPKa also helps to
prevent obesity by inhibiting lipogenesis, stimulating fatty acid oxidation in the liver and skeletal
muscles [38].
Cocoa also inhibits dietary fat absorption by
inhibiting the activity of pancreatic lipase and
secreted phospholipase A2 [39] leading to a
reduction in rate of body weight gain along with
an increase in fecal lipid output [40 ]. Suggested
mechanism of the role of cocoa in preventing
obesity, hyperglycemia, and insulin resistance has
been summarized in Fig. 1.
Min et al. [41 ] suggested that cocoa can avert
obesity by targeting insulin receptors in a tissuespecific manner. Min et al. [41 ] showed that cocoa
inhibits early stage of adipogenesis in preadipocytes
by decreasing insulin receptor kinase activity via
direct binding.
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CONCLUSION
Chocolate/cocoa therapy or its derivatives could
have a role in the prevention of, or offer a substitute
to or be used to complement drug therapy for
diseases such as inflammation, immune dysregulation/autoimmune pathogenesis, allergies, anxiety,
hyperglycemia, obesity, and insulin resistance.
However, this needs extensive interventional
studies evaluating the effects of cocoa products in
human populations as clinical evidence supporting
the health benefits of cocoa in humans is insufficient. Most reports documenting chocolates
beneficial effects are coming from animal research
that warrants extreme care in extrapolating the
results to human populations.
Acknowledgements
None.

Conflicts of interest
There are no conflicts of interest.

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&
of special interest
&& of outstanding interest
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Functional foods and dietary supplements

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&&
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