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The cacao, as part of the wonderful nature, provides the mankind a wide variety of valuable food products and health benefits. The most known and universally relished product derived from this fruit is chocolate, an amazing and unique food for the human nutrition with records of consumption of similar products dating to 1000 years B.C. In fact, the cocoa is a complex food that includes over 300 different components. This review is designed to inform scientists, technicians, academicians, farmers, and interested communities of numerous studies that have been conducted worldwide to investigate the properties of various cocoa constituents, their relations to human health, and their potential role in the prevention and treatment of many medical conditions. The general population, for example in Brazil, despite being one of the major producers of cocoa, is poorly informed of the significant and beneficial properties of cocoa. The present review covers important topics linking cocoa to human health and show the state of the art of effect of cocoa in different systems that comprise the human body. The paper is organized based on the main human organ system and includes: Cardiovascular / Circulatory, Neurological / Nervous, Oral health, Endocrine, Lymphatic and Immunological, Respiratory, Reproductive, Dermatological systems. Scientific findings tend to confirm the historic designation of cacao as “food of the Gods”.
Cacao and Human Health: from Head to Foot A Review
¹ CEPLAC - Executive Commission for the Cocoa Farming Plan / Cocoa Research Centre, Road Ilhéus-Itabuna, km 22,
45600-970, Itabuna, Bahia, Brazil; ² State University of Santa Cruz, Road Ilhéus-Itabuna, km 16, 45662-900, Ilhéus,
Bahia, Brazil; ³ Queen Margaret University / Department of Dietetics, Nutrition and Biological Sciences, Queen
Margaret Drive, Musselburgh EH21 6UU, UK;
UniJorge, Luis Viana Anenue / Paralela, 6775, 41745-130, Salvador,
Bahia, Brazil.
Corresponding Author:
Quintino Reis de Araujo
Road Ilhéus-Itabuna, km22.
CEP 45600-970, Itabuna, Bahia, Brazil.
Tel. +55 73 3214 3256
Fax. +55 73 3214 3204
(Short Title: Cacao and Health)
Cacao and Human Health: from Head to Foot A Review
The cacao, as part of the wonderful nature, provides the mankind a wide variety of valuable food
products and health benefits. The most known and universally relished product derived from this
fruit is chocolate, an amazing and unique food for the human nutrition with records of consumption
of similar products dating to 1000 years B.C. In fact, the cocoa is a complex food that includes over
300 different components. This review is designed to inform scientists, technicians, academicians,
farmers, and interested communities of numerous studies that have been conducted worldwide to
investigate the properties of various cocoa constituents, their relations to human health, and their
potential role in the prevention and treatment of many medical conditions. The general population,
for example in Brazil, despite being one of the major producers of cocoa, is poorly informed of the
significant and beneficial properties of cocoa. The present review covers important topics linking
cocoa to human health and show the state of the art of effect of cocoa in different systems that
comprise the human body. The paper is organized based on the main human organ system and
includes: Cardiovascular / Circulatory, Neurological / Nervous, Oral health, Endocrine, Lymphatic
and Immunological, Respiratory, Reproductive, Dermatological systems. Scientific findings tend to
confirm the historic designation of cacao as "food of the Gods".
Key Words: Theobroma cacao L., food, antioxidant, heart, neurology, immunology.
The nature has a huge, effective and wonderful collection of plant species that offer several
beneficial properties to human nutrition and health. These plant species represent important sources
of raw materials essential for maintaining human existence and improving its quality of life.
The cocoa tree, which forms the basis for one of the world’s most popular food products-
chocolate, has a rich history involving many cultures and carrying important economical and social
implications to millions of peoples worldwide. In recognition of its multiple health benefits, the
Maya gave cocoa its ancient name kakawa which translates into ‘‘Food of the Gods”. The Maya
of Central America are credited for being the first people to consume cocoa. The health-promoting
properties of cocoa have also been celebrated by the ancient Mesoamerican society with historical
records revealing more than 150 applications of cocoa for medicinal purposes. Christopher
Columbus was the first European to encounter cocoa in around 1502 A.D. But it was not until a
quarter of a century later that the great Spanish conqueror Hernán Cortéz introduced cocoa into
Europe. By the mid-1600s, cocoa was used in Europe as a medicine that promotes health, and as a
cure for all manner of aliments (Pucciarelli and Grivetti, 2008). Cocoa was particularly valued for
its ability to treat upper respiratory tract conditions such as colds and coughs, enhance mental well-
being and to protect against nutritional deficiencies (Pucciarelli and Grivetti, 2008; Selmi et al.,
2008; Tomaru et al., 2007).
In 2005, a meeting was set at Lucerne, Switzerland, where scientists and medical experts
gathered to discuss the latest evidence on the potential health properties of cocoa. Since then,
numerous studies have appeared in the literature indicating that the value of cocoa goes beyond its
nutritional properties to potentially disease prevention. Chocolate have for several years been
studied for its possible beneficial health effects (Cooper et al., 2008; Sarmadi et al., 2011).
Cocoa is a complex plant product that contains over 300 different constituents (Fung, 2011),
even in roasted beans (Keeney, 1972). Its major components include: cocoa butter (oleic, stearic,
and palmitic fatty acids), minerals (magnesium, potassium, iron and zinc), methylxanithines
(theobromine and caffeine), polyphenols in addition to other compounds such as tyramine,
tryptophan, and serotonin. Polyphenols are a large group of compounds found in fruits and
vegetables. Recently attention has been drawn to these compounds because of their ability to
improve health and prevent numerous diseases owing to their antioxidant properties and their
potential anti-inflammatory and cardio-protective properties (Wollgast and Anklam, 2000). For
these compounds from chocolate were directed the cause of significantly improved Chalder Fatigue
Scale score, a measurement of symptoms for subjects with chronic fatigue syndrome (Sathyapalan,
2010). One class of polyphenols is the flavonoids which is present in high concentration in cocoa
(Stoclet et al., 2011; Tzounis et al., 2011; Jalil and Ismail, 2008; Mehrinfar and Frishman, 2008),
and because this, cacao seeds was recently called as “Super Fruit” (Crozier, 2011). The fiber of
cocoa can be considered as an excellent source of dietary fiber, and therefore could be used as an
ingredient in functional foods rich in fiber. Besides this, fiber cocoa would provide protection
against oxidative damage through its content in phenolic compounds (epicatechin) (Lecumberri et
al., 2007). The pharmacokinetics of cocoa flavanols are rapidly absorbed in the intestine and
metabolized (Spencer et al., 2001).
The present reviews deals with some of the literature concerning the health properties of
cocoa and its related products and constituents. It is aimed at researchers, academics, farmers, and
general public who would like to gain a broad knowledge of the most recent evidence. The structure
of the review spans round the main systems in the human organ and include:
1. Cardiovascular / Circulatory system
2. Neurological / Nervous system
3. Endocrine system
4. Oral health
5. Lymphatic and Immunological system
6. Dermatological system
7. Respiratory system
8. Reproductive system
Cardiovascular / Circulatory
The cradioprotective effects of cocoa can be summarized to include effects on blood
pressure, endothelium function, lipid profile and platelet function (Beckett, 2008)
Blood pressure
The interest in the effects of cocoa intake on the cardiovascular system was initially
triggered by the observation that the indigenous Kuna Indians, a population living in an island off
the coast of Panama, have a very low incidence of ischemic heart disease, stroke and hypertension
(Bayard et al., 2007; Hollenberg et al., 1997). These Kuna Indians consumed over 5 cups of
flavanol-rich cocoa containing 900mg of polyphenols per day (Hollenberg et al., 2006). These
observations are supported by several European epidemiological studies. In the Zutphen Elderly
cohort, in particular, habitual intake of cocoa has been found to be inversely associated with
approximately 50 % reduction of 15-year cardiovascular and all-cause mortality (Buijsse et al.,
2006). Individuals from the highest tertile of cocoa also had lower blood pressure compared to those
from lowest tertile (Buijsse et al., 2006). Similar observations have been made in the Potsdam
European Prospective Investigation into Cancer and Nutrition cohort (Buijsse et al., 2010).
Consumption of polyphenol-rich chocolate has been associated with lower risk of cardiac mortality
after first myocardial infarction in the Stockholm Heart Epidemiology Program (Janszky et al.,
2009). Nonetheless, in a more recent cohort, only moderate habitual intake (1-2 servings per week
or 1-3 servings per month) was found to be protective against heart failure while no effect was
observed for cohorts members who consumed more than 3 servings of chocolate per week
(Mostofsky et al., 2010). In general, the value of epidemiological findings is limited by the possible
correlation between individual food or nutrient intake and other dietary and non-dietary factors that
may confound associations. This may explain some of the differences in findings. Likewise, data
from epidemiological studies could often under-estimate the true effect of cocoa and chocolate
consumption since most cocoa products available on the market are poor in polyphenols. As such
evidence from cohorts studies need to be reinforced by randomised controlled trials.
To date, findings from randomised controlled trials suggest a potential role for flavanol-rich
chocolate and cocoa products in non-pharmacological treatment of high blood pressure (Hernández
et al., 2011; Sanchez et al., 2010; Corti et al., 2009; Selmi et al., 2008). A recent literature
evaluation by Ried et al. (2010) has concluded that dark chocolate is superior to placebo in reducing
systolic hypertension or diastolic prehypertension. Taubert et al. (2007) were amongst the first
researchers to report the blood-pressure lowering effects of chocolate in a randomised controlled
trial. In their trial, 14-day consumption of polyphenol-rich chocolate induced a 5.1 (SD 2.4) and 1.8
(2.0) mm Hg reduction in systolic and diastolic blood pressure compared to white chocolate,
respectively. This study was followed by a series of evaluations confirming on the consumption of
100g dark chocolate containing 500mg polyphenols was found to reduce blood pressure in healthy
adults (Grassi et al., 2005a) and patients with essential hypertension (Grassi et al., 2005b, 2008).
Recently efforts have been to develop commercially available polyphenol-rich cocoa products. One
such product, CocoanOx, has been shown to produce similar reduction in blood pressure in rats to
Captopril (Cienfuegos-Jovellanos et al., 2009).
Much speculation exists as to the cocoa constituent responsible for the blood-pressure
lowering effects of cocoa. Earlier, studies used white chocolate as placebo which apart from not
permitting effective blinding of human volunteers also differs in its nutrient composition since it
does not contain minerals like magnesium and methyxanithines. In a recent study by van den
Bogaard et al. (2010), theobromine-enriched cocoa was found to significantly increase 24-hour
ambulatory systolic blood pressure while lowering central systolic blood pressure. These findings
suggest that caution need to be exercised when interpreting the findings from earlier cross-sectional
studies. Moreover, the use of high quantities of chocolate, sometimes 100g per day, might not be
feasible because of the high-fat content and energy density of chocolate. The effective polyphenol
dose required to induce clinically relevant reduction in blood pressure also remains unclear.
Recently, Almoosawi et al. (2010) has also shown that in overweight subjects intake of 20g of
polyphenol-rich chocolate containing 500mg polyphenols produces similar reductions in blood
pressure as 20g of polyphenol-rich chocolate containing 1000mg polyphenols chocolate. Regardless
of these findings, evidence from long-term studies suggest that use of doses as low as 6.5g per day
induces clinically relevant reduction in blood pressure by increasing bioactive nitric oxide levels
(Taubert et al., 2007).
In relation to the mechanism by which polyphenol-rich chocolate reduces blood pressure it
appears to be related to increased nitric oxide bioavailability, or a maintenance of optimal nitric
oxide levels, that could be associated with lowering superoxide anion production in the vasculature
(Fraga et al., 2011); which then translated into improvement in arterial stiffness and endothelial
function, as outlined below.
Endothelium function
Cocoa and chocolate produce their cardio-protective effects via modulation of nitric oxide
bioavailability, hence endothelium function. In-vitro and in-vivo studies have shown that flavanol-
rich cocoa reduces the activity of arginase, the main enzyme involved in the inactivation of nitric
oxide (Schnorr et al., 2008). This results in a rise in the plasma concentration of nitrose compounds,
which can then be expressed as improved brachial artery flow-mediated dilation (Yokoi et al., 2011;
Sies et al., 2005). Endothelial dysfunction is an early marker of atherosclerosis development. Thus,
the ability of polyphenol-rich cocoa and its products to reverse endothelial dysfunction suggests that
such products could be used at early stages of disease to prevent or delay progression to
cardiovascular events such as stroke. Evidence of the beneficial effects of cocoa and its related
products on endothelium function are consistent and range from effects on healthy volunteers
(Fisher et al., 2006a; Schroeter et al., 2006) to individuals with high cardiovascular risk factors such
as hypertensives (Grassi et al., 2005b), insulin-resistant (Grassi et al., 2008) and obese subjects
(Davison et al., 2008). Currently there is even data to suggest that polyphenol-rich chocolate
consumption improves endothelium-dependent responses in the coronary circulation, in addition to
decreasing shear stress-induced platelet adhesion in heart transplant recipients (Flammer et al.,
2007). Interestingly, flavanol-rich cocoa appears to improve blood pressure and endothelial
function to a greater extent in the elderly compared to younger healthier subjects (Fisher et al.,
2006a). This is unsurprising elderly (Fisher et al., 2006b). Currently debate still exists as to
whether polyphenol-rich products can be of any benefit to healthy young adults. What remains
evident is that the timing of dietary intervention is critical to ensuring maintenance of health and
disease prevention, since the use of diet, on its own, may be less effective at more advanced stages
of disease.
Lipid profile and peroxidation
In a meta-analysis of eight short-term trials, consumption of cocoa was found to elicit a 5.87
mg/dL (95% CI: −11.13, −0.61; P < 0.05) reduction in LDL cholesterol (Jia et al., 2011). This
effect was only observed in individuals who consumed low doses of cocoa and in those with high
cardiovascular disease risks. By contrast, only a marginal reduction in total cholesterol (mean
reduction = -5.82 mg/dL; 95% CI: −12.39, 0.76; P = 0.08) was detected, and no significant change
in HDL cholesterol. Similar observation, have been made in a recent systematic review which
included 10 short-term trials (Tokede et al., 2011). However, in the latter meta-analysis, a
significant reduction in total cholesterol was seen (mean reduction = -6.23 mg/dl (−11.60, −0.85
mg/dl). Moreover, short-term trials showed greater improvements in lipid profile compared to long-
term clinical trials, possibly implying a potential physiological adaptation to high polyphenol intake
with long-term intake. The minor differences between the two meta-analyses could be related to
differences in the studies included in analysis. In the meta-analysis conducted by Tokede et al.
(2011), both short-term (2 week) and long-term trials (up to 12 weeks) as well as studies on
overweight individuals (Almoosawi et al., 2010, Davison et al., 2008) and elderly were included
(Crews et al., 2008). Alternatively, inter-individual variations in the absorption of cocoa
polyphenols could dictate the extent of the lipid-lowering effects of cocoa products, which may then
produce differences in results. In a randomised-controlled trial involving forty-two volunteers with
high cardiovascular risk, consumption of 40g of polyphenol-rich cocoa dissolved in 500ml of
skimmed milk reduced oxidised LDL levels and increased HDL cholesterol (Khan et al., 2011).
However, the increment in HDL cholesterol and the reduction in oxidised LDL were found to
strongly correlate with urinary cocoa polyphenol metabolites excretion. More recently, consumption
of polyphenol-rich cocoa was shown to even protect Type 2 diabetes patients against an atherogenic
lipid profile when cocoa is consumed as part of a balanced diet. Thus, consumption of 45g of
polyphenol-rich chocolate for 16 weeks was found to significantly reduce HDL cholesterol
(1.16 ± 0.08 vs 1.26 ± 0.08 mmol/l, P = 0.05) and cholesterol: HDL ratio (4.4 ± 0.4 vs
4.1 ± 0.4 mmol/l, P = 0.04) in patients with type 2 diabetes, without producing any changes in
weight or glycaemic control (Mellor et al., 2010).
It is important to note that it is the polyphenol composition of cocoa and not the amount of
cocoa solids that determine the beneficial properties of cocoa and chocolate (Efraim et al, 2011;
Coper et al., 2008; Gu et al., 2006; Miller et al., 2006). In young (18-20 years old) male soccer
players, consumption of flavonol-rich milk chocolate, with a low cocoa solids content, has been
shown to be associated with improvements in several parameters associated with cardiovascular
health and oxidant stress in healthy young soccer players (Fraga et al., 2005). Thus consumption of
milk chocolate was found to decrease diastolic blood pressure (- 5 mm Hg), mean blood pressure (-
5 mm Hg), plasma cholesterol (-11%), LDL-cholesterol (-15%), malondialdehyde (- 12%), urate (-
11%) and lactate dehydrogenase (LDH) activity (- 11%), and to increase in vitamin E/cholesterol (+
12%) (Fraga et al., 2005). The fatty acid compsotion of cocoa butter may also explain the lipid-
lowering or neutral effects of chocolate. The main saturated fatty acid found in cacao butter is
stearic acid. Stearic acid has a neutral effect on blood lipids (Hannum and Erdman, 2000). Cocoa
also contains high amounts of monounsaturated fatty acids which are known to have a favorable
effect on lipid profile.
In addition to improving lipid profile, cocoa polyphenols can influence LDL oxidation.
Oxidative modification of LDL is a critical stage of atherogenesis, and one of the mediators is the
pro-inflammatory pro-atherogenic enzyme myeloperoxidase. Micromolar concentrations of (-)-
epicatechin or other flavonoids can suppress myeloperoxidase-induced lipid peroxidation of LDL
(Sies et al., 2005). Consumption of cocoa fiber has also been shown to reduce lipid peroxidation in
animal models (Lecumberri et al., 2007). Earlier, it was observed that soluble cocoa fiber product
in an animal model of dietary-induced hypercholesterolemia, diminished the negative impact of the
cholesterol-rich diet, buffering the decrease of high density lipoprotein-cholesterol, and the increase
of total and low density lipoprotein-cholesterol levels, and lipid peroxidation (malondialdehyde
levels) induced by the fatty diet. The soluble fiber product also decreased triglyceride levels to
values lower than those in the group fed the cholesterol-free diet (Ramos et al., 2008)
Platelet activation and aggregation play a key role in inflammatory processes and form part
of the initial stages of arterial thrombosis development. Factors such as ADP, thrombin or collagen
activate platelets and stimulate their aggregation while prostaglandins inhibit these processes.
Cocoa, like aspirin, possesses potential anti-thrombotic properties. The ability of
polyphenol-rich cocoa and chocolate to modulate platelet function has been observed both ex-vivo
(Rein et al, 2000a-c) and in-vivo (Schramm et al., 2003; Holt et al., 2002; Pearson et al., 2005).
Some inconsistencies remain with regard to the magnitude of cocoa’s anti-platelet effects.
According to Pearson et al. (2005) cocoa has a less profound inhibitory effect on epinephrine-
stimulated platelet activation and function than aspirin. However, the combination of the two
produces an additive effect (Pearson et al., 2005). Heptinstall et al. (2006), on the other hand,
reported similar inhibitory effects of cocoa flavanols/ metabolites and aspirin on platelet
activation/aggregation, platelet-monocyte conjugate formation platelet-neutrophil conjugate
formation in-vitro, with no additive effect when combining cocoa flavanols and aspirin.
Differences in the results could be attributed to differences in the techniques used to assess platelet
function or variations in the products used. Regardless of these inconsistencies, several studies
have revealed potential mechanisms by which cocoa ad its related products can protect against
thromboemolic diseases. Cocoa procyanidins can inhibit platelet activation by altering eicosanoid
synthesis. Treatment of aortic endothelial cells with chocolate procyanidins doubles keto-
prostaglandin F
production and reduces leukotriene production by 16% (Schramm et al., 2003).
When high-procyanidin chocolate (37g containing 4.0 mg/g procyanidins) is acutely consumed, this
produces a 37% increase and a 29% decrease in plasma prostacyclin and leukotrienes
concentrations, respectively, in healthy volunteers (Schramm et al., 2003). Cocoa can also diminish
platelet function by significantly reducing P selectin expression and by lowering ADP- and
collagen-induced aggregation (Murphy et al., 2003, Innes et al., 2003). This effect correlates with a
rise in plasma ascorbic acid, epicatechin and catechin concentrations (Murphy et al., 2003). Pre-
treatment of human aortic endothelial cells with catechin and quercetin metabolites has also been
shown to influence monocyte adhesion (Koga and Meydani, 2001). According to Koga and
Meydani (2001), the flavonoid metabolites, as opposed to the intact flavonoids, are responsible for
the ability of flavonoids to modulate platelet function. In a double-blind, randomized study
involving 22 heart transplant recipients, consumption of 40 g of dark (70% cocoa) chocolate
reduced platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) (Flammer et al.,
In a large cross-sectional analysis assessing habitual chocolate consumption in 1535
subjects, chocolate consumers showed longer platelet function analyzer closure times (130 vs 123
seconds, P=.005) and decreased 11-dehydro thromboxane B2 (175 vs 290 ng/mol creatinine, P=.03)
(Bordeaux et al., 2007). Chocolate remained an independent predictor of both ex vivo and in vivo
platelet function testing after controlling for age, sex, education level, race, cigarette smoking, and
BMI and values of glucose, blood pressure, total cholesterol, fibrinogen, and Von Willbrand Factor.
Bordeaux et al. (2007) concluded that consumption of small quantities of chocolate (5.9g) can
improve platelet function.
Neurological/ Nervous System
Interest in the neurological and neuroprotective effects of cocoa and chocolate polyphenols
stemmed from findings that cocoa and chocolate can enhance vascular function by modulating
nitric oxide bioavailability. Nitric oxide is central to the regulation of peripheral vascular.
However, it also plays a key role in the cerebral circulation where it promotes brain perfusion.
Studies suggest that daily intake of cocoa flavanols can enhance blood flow and perfusion of the
brain via its stimulatory effect on nitric oxide bioavailability (Pate et al., 2008). Indeed, in a study
conducted on thirty-four healthy elderly volunteers aged 72±6 years, Sorond (2008) used
transcranial Doppler ultrasound to measure blood flow velocity in the middle cerebral artery.
Sorond (2008) observed a consistent increase in blood flow velocity from 8% after 1 week of cocoa
consumption to 10% following 2-week consumption of flavanol-rich cocoa. These findings were
validated in a later study in which changes in middle cerebral artery flow, assessed by transcranial
Doppler ultrasound, strongly correlated with changes in perfusion measured by gadolinium-
enhanced MRI and arterial spin labelling (Sorond et al., 2010). Increased blood oxygenation and
blood flow to brain grey matter have also been reported (Field et al., 2011; Francis et al., 2006).
These findings suggest a potential role for cocoa flavanols in the treatment and prevention of
cerebrovascular diseases such as dementia and stroke.
Indeed, several studies indicate that polyphenols can reduce the risk of neurodegenerative
diseases particularly those stemming from oxidative stress, such as Alzheimer's and Parkinson's
disease. Incubation of neuronal cells with cocoa extract or (-)-epicatechin dose-dependently
reduces reactive oxygen species production and down regulates the stress-kinases: pJNK and p38,
which are involved in activation mitogen-activated protein kinase pathway (Ramiro-Puig and
Castell, 2009). In models of Parkinson’s disease, pretreatment of male adult Sprague-Dawley rats
with cocoa extract at a dose of 100 mg/kg/day has also been reported to diminish oxidative stress-
induced 6-hydroxydopamine-induced dopaminergic loss (Datla et al., 2007). Pre-treatment of
neurons with cocoa extract has also been reported to reduce expression and release of calcitonin
gene-related peptide expression, a factor that promotes neural inflammation (Abbey et al., 2008)
and migraine development (Li et al., 2008). Cocoa also exerts protective effects against amyloid β
protein-induced neurotoxicity (Yasuda et al., 2011; Heo and Lee, 2005), which is relevant to
Alzheimer’s disease, a neurological dementia caused by accumulation of amyloid plaques and
neurofibrillary tangles in the brain and which is characterised by memory loss and progressive
decline in cognitive function. Indeed, cocoa can protect against cognitive decline associated with
normal aging. In old Wister-Unilever rats, 1-year oral administration of a cocoa polyphenolic
extract, at a dose of 24 mg/kg per day, delays the onset of age-related cognitive deficits and
maintains high urinary free dopamine levels (Bisson et al., 2008b). In a large trial involving 2031
human subjects, habitual chocolate consumption predicted improved cognitive performance (Nurk
et al., 2009). In fact, the association between chocolate consumption and cognitive performance was
dose-dependent, with maximum beneficial effect achieved at intakes of 10 g of chocolate per day
(Nurk et al., 2009).
It is important to state that chocolate is also rich in fat and contains amines such as tyramine,
histamine and phenylethylamine that can be linked to headaches. In a double blind study of
headache was performed using chocolate as the active agent and carob as the placebo. Sixty-three
women with chronic headache (50% migraine, 37.5% tension-type, 12.5% combined migraine and
tension-type) participated in the study. Diaries were maintained by the subjects throughout the
study, monitoring diet and headache. But contrary to the commonly held belief of patients and
physicians, chocolate didn’t play a significant role in trigger headaches in typical migraine, tension-
type, or combined headache sufferers (Marcus, 1997). However, in patients with migraine who
believed that chocolate could provoke their attacks, chocolate ingestion was followed by a typical
migraine episode in 5 out of 12 patients, while none of the 8 patients challenged with placebo had
an attack (p = 0.051) (Gibb, 1991). And in other study with four hundred twenty-nine patients that
had migraine, 16.5% reported that headaches could be precipitated by cheese or chocolate, and
nearly always by both. There was a statistical association between sensitivity to cheese/chocolate
and to red wine in patients with migraine, and related more to migraine than to more chronic
tension-type headache (Peatweld, 1995). Therefore, evidence of the association between chocolate
consumption and headaches remains conflicting.
In addition to age-associated neurodegenerative diseases, cocoa and chocolate consumption
can play a role in the prevention of neurological disorders such as depression. Depression is a
common condition that affects a large proportion of the population nowadays. A recent study found
that the addition of high-flavanol cocoa extract given to rats in a forced swimming test reduces
depression (Messaoudi et al., 2008). This effect has been attributed to the conversion of tryptophan
from cocoa into serotonin and the presence of some compounds in cocoa that alleviate mood,
thereby protecting against depression. Raikkonen et al., (2004) evaluated prenatal frequency of
chocolate consumption and its relation to intensity of psychological stress in 305 mothers. The
temperament of infants at 6 months postpartum was also evaluated. Chocolate was found to
produce subjective feelings of psychological well being, to reduce maternal stress and improve
infant temperant. Similar observations have been made in elderly men where consumption of
chocolate was associated with improved overall health and better psychological well-being
(Strandberg et al., 2008). Together this evidence favors a potential role for cocoa and chocolate
polyphenols in maintaining cognitive function through the life course and preventing age-related
development of cerebrovascular disease.
Growing evidence suggests that polyphenols in cocoa can modulate the endocrine system.
In studies on diabetic-obese mice, administration of cocoa liquor procyanidins for 3 weeks have
been shown to dose-dependently reduce fasting glucose and fructosamine levels (Tomaru et al.,
2007). Likewise, acute reductions in postprandial glucose have been reported by Jalil et al. (2008),
with this effect coinciding with an improvement in antioxidant defense mechanism as demonstrated
by enhanced superoxide dismutase activity and reduction in 8-isoprostanes. Cocoa supplementation
can also reduce free fatty acids, which is important since fatty acids can impair glucose metabolism.
Despite this evidence, no changes in fasting glucose have yet been reported with long-term
administration of cocoa extract (4 weeks) in neither mice nor humans. The reason behind these
differences in effect remains to be clarified, but could be related to the short half-lives of cocoa
polyphenols which leads to rapid metabolism and excretion. As a result, the benefit of cocoa
consumption may lie in its transient effects on postprandial glucose levels.
Despite this evidence, recent trials in humans show that consumption of polyphenol-rich
dark chocolate can improve insulin sensitivity in healthy subjects (Grassi et al., 2005a),
hypertensives (Grassi et al., 2005b), insulin-resistant individuals (Grassi et al., 2008) and
overweight subjects (Almoosawi et al., 2010). These effects could be attributed to the ability of
polyphenol-rich dark chocolate to improve endothelium function and antioxidant status. Only two
studies have so far investigated the effect of cocoa consumption on glucose and insulin regulation in
diabetics. None of these studies observed any significant improvement in glucose levels or insulin
resistance. Several explanations could be provided to explain such inconsistencies. First, most
previous trials conducted on non-diabetic patients compared the effect of polyphenol-rich dark
chocolate to polyphenol-deficient white chocolate. This implies that volunteers were not blinded to
treatment allocation which may have biased the results. Additionally, white chocolate differs in its
macro- and micro-nutrient composition to dark chocolate since it does not contain methylxanithines
or minerals such as magnesium. This implies that differences in the effect of dark chocolate and
white chocolate may be related to components other than polyphenols. Most of the above trials
were also of short duration (2 weeks) and used large amounts of chocolate (100g). Thus, the benefit
of cocoa or chocolate consumption may lie in its ability to reduce diabetes-related metabolic
complication as opposed to improving glycaemic control. This notion could be supported by
several studies. For instance, administration of proanthocyanidins derived from cacao has been
shown to inhibit diabetes-induced cataract formation, possibly by improving antioxidant activity
(Osakabe et al., 2004). Similarly, supplementing the diet with 1-2% cocoa extract of diabetic rats
has been shown to increase HDL-cholesterol and the reduction in LDL-cholesterol (Ruzuadi et al.,
2005). In humans, Balzer et al. (2008) demonstrated that thrice-daily consumption of polyphenol-
rich cocoa for 30 days reversed vascular dysfunction in medicated diabetic patients. Similarly, in a
study on type 2 diabetics, daily intake of cocoa for 16 weeks raised HDL-cholesterol and reduced
total cholesterol-to-HDL ratio (Mellor et al., 2010). All of these findings suggest that cocoa
consumption may benefit diabetics by reducing cardiovascular risk factors.
Cocoa consumption can also be of benefit to obese individuals because of its low calorie
density in comparison to chocolate. Consistent with this, cocoa polyphenols have been shown to
prevent diet-induced obesity by modulating lipid metabolism, especially by decreasing fatty acid
synthesis and transport systems, and enhancing thermogenesis in hepatic and white adipose cells
(Matsui et al., 2005). In humans, long-term ingestion of a polyphenol-rich cocoa drink has been
reported to improve endothelial function (Davison et al., 2008). Certain constituents in cocoa also
have the potential to modulate glucocorticoid metabolism which could be of relevance to obesity-
related complications (Almoosawi, 2011).
Oral health
Addai et al. (2002) screened a large selection of foods for their acidogenic effects on teeth.
To their surprise, they found that the Golden Tree brand of milk chocolate produced in Ghana,
which contained 30% cocoa solids, was not acidogenic. This finding prompted researchers to
conduct further trials in an attempt to understand the mechanisms underlying their observations.
Evidence of the protective effect of cocoa against dental caries has been, in fact,
documented as early as 1985, when Paolino and Kashket observed that cocoa inhibited plaque
accumulation and caries formation by reducing polysaccharide production. Since then, several
studies have shown the ability of cocoa to reduce the risk of dental caries and prevent periodontal
disease. Rats infected with Streptococcus sobrinus showed a significant reduction in caries scores
after administration of a water-soluble cacao extract compared to infected rats given a control diet
(Ito et al., 2003). This protective effect was attributed to the inhibitory activity of cocoa extract on
glucan synthesis by Streptococcus. Polymeric fractions from cocoa, in particular, appear to have
immunomudulatory effects on the production of cytokines IL-1β (IL-1β), IL-2 and IL-4 (Hirao et
al., 2010; Mao et al., 2002). Larger oligomeric fractions (hexamer through decamer) have also been
reported to inhibit IL-5 release, which may promote immunoglobulin A (Mao et al., 2002). More
recently, Percival et al. (2006) demonstrated that cocoa polyphenols can delay acid production by
Streptococcus mutans. The growth of streptococcus sanguins and formation of biofilm have also
been shown to be inhibited by cocoa dimer, tetramer and pentamer polymers (Percival et al., 2006).
Cocoa also contains tannins which possess anti-bacterial and anti-enzymatic properties (Beckett,
2008). Recently, Ferrazzano et al. (2009) reviewed the mechanisms of the anti-cariogenic effects of
cocoa polyphenols and concluded that products like cocoa may have potential applications in the
prevention of dental caries. Despite this evidence, it is important to highlight that findings from the
above experiments need to be interpreted with caution since the majority of cocoa and chocolate
products currently available on the market are low in polyphenols and high in simple sugars which
can be detrimental to oral health. Thus, the use of cocoa polyphenols as means of improving
periodontal health will only be possible once appropriate formulations and products are developed.
Lymphatic and Immunological
Chronic and acute inflammation underlies the molecular basis of many cardiovascular and
cerebrovascular diseases. The role of cocoa in modulating inflammatory markers and immune
responses has been reviewed by several researchers (Selmi et al., 2006; Selmi et al., 2008; Ramiro-
Puig and Castell, 2009). This role has been established in both in-vitro and in-vivo studies and
could be summarised to include effects on the innate and the acquired immune system.
Accordingly, isolated flavanols and procyanidins fractions have been shown to attenuate the
release of inflammatory cytokines: interleukin-1b and interleukin-2 from peripheral blood
mononuclear cells (Mao et al., 2002), and to promote the production of anti-inflammatory cytokines
such as interleukin-4 and interleukin-5 in an oligomer length-dependent manner (Mao et al., 2002).
It was also observed that the effect of cocoa flavanols and procyanidins on peripheral blood
mononuclear cells depends on the immunological status of an individual. Cocoa flavonols and
procyanidins stimulated peripheral blood mononuclear cells individuals with low cytokine
transforming growth factor
-1 but attenuated peripheral mononuclear cell isolated from individuals
with high baseline transforming growth factor
In addition to influencing peripheral mononuclear cell, cocoa flavonoids have been shown to
affect the release of inflammatory cytokines and chemokines from macrophages (Ramiro-Puig et
al., 2005). This inhibitory effect is achieved at the transcriptional level as evident by the down-
regulation of TNFα, interleukin (IL) 1α, and IL-6 mRNA expression.
Besides the innate immune response, cocoa can modulate the acquired immune response. In
a study conducted by Ramiro-Puig et al. (2005), incubation of cocoa extract with stimulated murine
EL4.BU.OU6 cells dose-dependently inhibited IL-2Rα (CD25) expression, an early marker of
lymphocyte T activation. This effect was likely to be modulated through epicatechin as both cocoa
extract and epicatechin produced similar levels of inhibition. Cocoa flavonoids also induced a 3-
fold rise in IL-4 release. These findings have been recently replicated in-vivo. Perez-Berezo et al.
(2009) demonstrated that supplementing the diet of adult Wistar rats with a cocoa-enriched diet for
9 weeks attenuates the Th2 immune response leading to reduced antibody synthesis. In another
study, weaned rats were given cocoa (4% or 10% food intake), containing 32 mg flavonoids/g, for
3 weeks (Ramiro-Puig et al., 2007b). The diet with the highest cocoa content was found to diminish
TNF-α secretion by peritoneal macrophages. The high-cocoa diet also promoted lymphocyte
proliferation rate but attenuated T helper 2-related cytokines and Ig secretion and decreased the
number of Th cells. Interestingly, one study has shown that the highest uptake and accumulation of
cocoa metabolites occurs in lymphoid tissues, particularly the thymus, which reinforces a role for
cocoa polyphenols in modulating lymphocyte composition in this tissue (Urpi-Sarda et al., 2010).
The ability of cocoa polyphenols to affect both the innate immune system and the adaptive
immunity has also been recently reported by Kenny et al. (2007). Kenny et al. (2007) demonstrated
that the chain length of flavanols determines the extent of cytokine release from both unstimulated
and LPS-stimulated peripheral blood mononuclear cells. Long-chain flavanols, in particular, were
found to increase LPS-induced synthesis of IL-1β, IL-6, IL-10,
and TNF- . By contrast, both long-
chain and short-chain flavanols increased expression of the B cell markers CD69 and
Cocoa polyphenols have been speculated to act as general leukotriene inhibitors. Schewe et
al. (2001) demonstrated that (-)-epicatechin and its low-molecular procyanidins, i.e. dimers and to a
lesser extent trimers through pentamers, inhibit both dioxygenase and LTA
synthase activities of
human 5-lipoxygenase. In earlier studies, Schewe et al. (2001) reported inhibition of 15-
lipoxygenase-1, an important catalyst of lipid peroxidation, by ()-epicatechin and cocoa
procyanidins (Schewe et al., 2001). Here, higher oligomers exhibited greater inhibitory activity
than monomers and medium-sized oligomers. Cocoa flavonoids were also found to inhibit
mammalian 12-lipoxygenases (Schewe et al., 2001).
It is important to observe that the value of some of the above findings is limited by the in-
vitro design of these studies and the use of pharmacological doses of cocoa polyphenols.
Nevertheless, because macrophages play an important role in the innate immune response and
inflammation and are implicated in the development of atherosclerotic lesions and cancer cell
proliferation, a potential role for cocoa polyphenols in preventing atherosclerosis and cancer
development could be speculated. Likewise, as suggested by Ramiro-Puig et al. (2007a), cocoa’s
capacity to modulate macrophage cytokine secretion and lymphocyte function could be relevant to
hypersensitivity and autoimmunity. Consequently, further research is required to replicate these
findings in humans and to evaluate the clinical implications of these findings. Finally, it could be
stated that some authors have also speculated a role for cocoa in the prevention of malaria by virtue
of cocoa’s ability and the ability of cocoa constituents (polyphenols, magnesium and zinc) to
improve nitric oxide bioavailability, increase antioxidant status and to boost the immune system
(Addai, 2010).
Immunostimulation have been also observed as a health-promoting effect of the microflora.
Among effective prebiotics, cacao-derived flavonols was identified affecting the growth of select
gut microflora in humans to a healthy composition (Tzounis, 2011).
In the past, chocolate has often been viewed as a food that promotes acne production.
However, this common belief has not been supported by scientific evidence. Among the first to
question the link between chocolate and acne were researchers from the University of Missouri in
the 1960s (Grant and Anderson, 1965). Grant and Anderson failed in their attempt to induce an acne
flare-up in eight individuals with mild to moderate acne by feeding them a large amount of
chocolate. The authors discredited the assertion that chocolate causes acne. In a study examining
the effect of chocolate intake on acne, 65 participants consumed 112g of dairy-free cocoa-enriched
bars of chocolate each day for 4 months. Researchers found no significant change in acne
production (Ferdowsian, 2010; Fulton et al., 1969). These findings were consistent with other
studies (Anderson, 1971; Grant and Anderson, 1965). In an extensive review of research on
chocolate and acne (Fries, 1978), it was concluded that the general trend of published reports
suggested that chocolate ingestion was unrelated to the cause of acne. In last years it was observed
the effect of other foods in acne occurrence. A positive association with acne for intake of total milk
and skim milk was identified in a study involving 47,355 women (Adebamowo, 2005), later
reinforced in an evaluation with 6,094 girls, aged 9-15 (Adebamowo, 2006) and with 4273 boys,
where a positive association between intake of skim milk and acne was found (Adebamowo, 2008).
This finding suggested that skim milk contains hormonal constituents, or factors that influence
endogenous hormones, in sufficient quantities to have biological effects in consumers (Danby,
2005; Melnik, 2009). Therefore, other compounds from chocolate, but not cocoa, can promote acne
occurrence giving the mistaken conclusion of chocolate as an acne promoter.
More attention has been drawn to the dermatological properties of cocoa polyphenols
recently. Dietary flavanols from cocoa have been shown to contribute to endogenous
photoprotection, to improve dermal blood circulation, and to affect cosmetically relevant skin
surface and skin hydration (Heinrich et al., 2006). Accordingly, consumption of high-flavanol cocoa
for 12 weeks has been shown to decrease skin roughness and scaling compared to low-flavanol
cocoa (Heinrich et al., 2006). This effect is potentially achieved through an increase in blood flow
in cutaneous and subcutaneous tissues which leads to higher skin density and hydration (Heinrich et
al., 2006). In another study the acute effects of a single dose of flavanol-rich cocoa on dermal
microcirculation was investigated (Neukam et al., 2007). Flavanol-rich cocoa consumption acutely
increased dermal blood flow and oxygen saturation. Pre-treatment with cocoa polyphenolic extract
have also been demonstrated to confer a significant protection against oxidation of cultured human
HepG2 cells submitted to oxidative stress induced by tert-butylhydroperoxide (t-BOOH) (Martin et
al., 2008). There is also evidence that flavonoid-rich products contribute to the protection of skin
against UV-induced damage at the molecular and cellular level, thereby improving overall skin
conditions (Stahl, 2011). This finding has also been observed by Jorge et al. (2011) who showed
that long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a
lowered transepidermal water loss (Jorge et al., 2011). A cosmetic formulation elaborated with 10%
ozonized theobroma oil was also observed as protector against oxidant radiation in exerting
beneficial effects in the restoring of the antioxidant activity on the skin of rats previously irradiated
with ultraviolet light (Sanches et al., 2011).
This area of research has not been widely investigated. One study has reported that dietary
supplementation of cacao liquor proanthocyanidins prevents lung injury induced by diesel exhaust
particles in mice (Yasuda et al., 2008). This effect was achieved through down-regulation of
vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and correlated with a
decline in oxidative stress and lipid peroxidation (Yasuda et al., 2008). The authors concluded that
these findings have potential relevance to asthma, tuberculosis and others respiratory conditions.
Other evaluation, showed that flavanol-rich cocoa has been acted to reverse endothelial dysfunction,
measured as flow-mediated dilation (FMD) of the brachial artery, in smokers (Heiss et al., 2005).
Most of the beneficial effects of cocoa on the reproductive system have been observed in
animal models. The highest accumulation of epicaetechin metabolites occurs in the testes which
has important implication for cancer prevention (Urpi-Sarda et al., 2010). Administration of a diet
containing 0.5 to 2% cocoa-rich flavanols to male rats for 2 weeks have been shown to dose-
dependently reduce oxidative DNA damage in rat testes (Urpi-Sarda et al., 2010). An in-vitro study
evaluated the inhibitory effect of different cocoa polyphenols extracts, alone or combined with beta-
sitosterol (a common phytosterol which plays a protective role in cancer development) on human
prostate cancer. The results showed that cocoa polyphenols extracts have antiproliferative effects on
prostate cancer cell growth (Jourdain et al., 2006). The effect of a commercially-available
polyphenol-rich cocoa on prostate carcinogenesis was evaluated in sixty Wistar-Unilever rats. Rats
were treated orally with cocoa powder 24mg/kg or 48mg/kg or vehicle, daily for nine months.
Cocoa markedly reduced prostate cancer incidence and increased the life span of the rats (Melnyk et
al., 2011; Bisson et al., 2008a; Bisson et al., 2006). The authors concluded that polyphenol-rich
cocoa can prevent prostate hyperplasia induced by testosterone propionate and therefore may be
beneficial in the treatment of benign prostatic hyperplasia.
Final Considerations
Chocolate induces, in general, a feeling of pleasure as postulate by scientists (Fung, 2011).
Because its composition cocoa mass remains solid at room temperature, but when consumed, its fat
content absorbs heat from the mouth and melts at body temperature, producing the effect of 'melt in
your mouth'.
Eating chocolate, as part of a healthful balanced diet, could potentially provide a beneficial
enjoyable way to improving wellbeing. Chocolate can be a very nutritional component in food and
the knowledge of its various medicinal properties represents a stimulus to those involved with its
production, processing and consumption.
Recently science has advanced significantly in improving our understanding of the various
features of chocolate that contribute to its popularity, and its after-effects of consumption on human
health have also been extensively studied. Although its marketing as a health product is not a
priority, eating in moderation, mainly the darker forms could potentially have many beneficial
results. But one thing is certain, both from a scientific viewpoint as sensory, chocolate is enjoyed as
a favorite food for most of the people.
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... The Maya civilization named chocolate the "food of the Gods" because of its perceived medical benefits (Araujo et al., 2016) and it remains a foodstuff whose effects are difficult to categorize simply. Chocolate consumption has been associated with reduced cardiovascular disease and diabetes (Veronese et al., 2019), and has also been suggested to improve mood and cognitive function in humans (Socci et al., 2017;Tuenter et al., 2018). ...
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Obesity is a major health risk, with junk food consumption playing a central role in weight gain, because of its high palatability and high-energy nutrients. The Cafeteria (CAF) diet model for animal experiments consists of the same tasty but unhealthy food products that people eat (e.g. hot dogs and muffins), and considers variety, novelty and secondary food features, such as smell and texture. This model, therefore, mimics human eating patterns better than other models. In this paper, we systematically review studies that have used a CAF diet in behavioral experiments and propose a standardized CAF diet protocol. The proposed diet is ad libitum and voluntary; combines different textures, nutrients and tastes, including salty and sweet products; and it is rotated and varied. Our summary of the behavioral effects of CAF diet show that it alters meal patterns, reduces the hedonic value of other rewards, and tends to reduce stress and spatial memory. So far, no clear effects of CAF diet were found on locomotor activity, impulsivity, coping and social behavior.
... The cacao tree (Theobroma cacao L.) is one of the oldest cultivated species (Araujo et al. 2016). Cacao is a high-value commodity with a global research network (Farrell et al. 2018). ...
The mineral nutrient ratios are parameters for evaluating the crop nutritional balance through foliar analysis. This study aimed to verify the correlations between the main mineral nutrient ratios in leaves and the cacao productivity of 48 cropping areas. The chemical analyses were carried out to determine foliar N, P, K, Ca, Mg, S, Fe, Zn, Cu and Mn nutrient concentrations. The Zn/Cu and the Ca/Mg ratios showed a positive nutritional relation with cacao productivity. The ratios with Cu as denominator – Mn/Cu, Ca/Cu, Mg/Cu, P/Cu, N/Cu and K/Cu – also showed a positive nutritional relation with cacao productivity. The P/Zn and N/Zn nutrient ratios showed a negative nutritional relation with the cacao productivity.
... The cacao tree (Theobroma cacao L.) is one of the oldest cultivated species (Araujo et al. 2016). Cacao is a high-value commodity with a global research network (Farrell et al. 2018). ...
The understanding of the mineral nutritional status of the cacao (Theobroma cacao L.) is one of the main strategies needed to increase the productivity of cacao beans. The main objective of this work is to verify the linear relationships, bivariate and multivariate analysis between the foliar nutrient concentrations of 48 cropping areas and graphically identifying the consistency of this information. For this study, foliar samples collected from cacao cropping areas, with known productivity of dry cacao beans (kg ha−1 year⁻¹), were analyzed for N, P, K, Ca, Mg, S, Fe, Mn, Zn and Cu concentrations. The interpretation of the results by the exploratory analysis technique linked to the linear correlation analysis proved to be an essential tool to support nutritional diagnosis systems. The cropping areas with very high productivity equal to or higher than 1600 kg of dry cacao beans ha−1 year⁻¹ were positively correlated with the macronutrients K, Ca, and Mg, and the micronutrients Fe, Mn and Zn. The negative correlation of these same high productivity cropping areas with the concentrations of the N and P macronutrients and with the Cu micronutrient may be a phenomenon related to the high nutritional demand for these nutrients in the productive phase.
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Biogenic amines (BAs), polyphenols, and aroma compounds were determined by chromatographic techniques in cocoa beans of different geographical origin, also considering the effect of roasting (95, 110, and 125 °C). In all samples, methylxantines (2.22–12.3 mg kg−1) were the most abundant followed by procyanidins (0.69–9.39 mg kg−1) and epicatechin (0.16–3.12 mg kg−1), all reduced by heat treatments. Volatile organic compounds and BAs showed variable levels and distributions. Although showing the highest BAs total content (28.8 mg kg−1), Criollo variety presented a good aroma profile, suggesting a possible processing without roasting. Heat treatments influenced the aroma compounds especially for Nicaragua sample, increasing more than two-fold desirable aldehydes and pyrazines formed during the Maillard cascade and the Strecker degradation. As the temperature increased, the concentration of BAs already present in raw samples increased as well, although never reaching hazardous levels.
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In recent years, epidemiological studies have shown that food is a very powerful means for maintaining a state of well-being and for health prevention. Many degenerative, autoimmune and neoplastic diseases are related to nutrition and the nutrient–organism interaction could define the balance between health and disease. Nutrients and dietary components influence epigenetic phenomena and modify drugs response; therefore, these food–host interactions can influence the individual predisposition to disease and its potential therapeutic response. Do nutraceuticals have positive or negative effects during chemotherapy? The use of nutraceutical supplements in cancer patients is a controversial debate without a definitive conclusion to date. During cancer treatment, patients take nutraceuticals to alleviate drug toxicity and improve long-term results. Some nutraceuticals may potentiate the effect of cytotoxic chemotherapy by inducing cell growth arrest, cell differentiation, and alteration of the redox state of cells, but in some cases, high levels of them may interfere with the effectiveness of chemotherapy, making cancer cells less reactive to chemotherapy. In this review, we highlighted the emerging opinions and data on the pros and cons on the use of nutraceutical supplements during chemotherapy.
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Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, “dialogue mapping™,” to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products 1) should be minimized, in part because of their saturated fat content, or 2) need not be minimized, despite their saturated fat content. The panel discussed the dairy-CVD relation through blood lipids, diabetes, obesity, energy balance, blood pressure, dairy bioactives, biobehavioral components, and other putative causal pathways. Associations and effects reported in the literature have varied by fat content of dairy elements considered, study design, intake methods, and biomarker versus disease outcomes. Two conceptual topics emerged from the discussion: 1) individual variability: whether recommendations should be targeted only to those at high CVD risk; 2) quality of evidence: whether data on dairy-CVD relations are strong enough for reliable conclusions—positive, negative, or null. Future procedural improvements for science dialog mapping include using singular rather than competing propositions for discussion.
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Theobroma cacao is a rich source of flavonoid compounds, which are potent antioxidants. Flavonoids are well-known for their health benefits against cardiovascular diseases, cancer, and improvement of blood pressure. For this reason, cacao mass production has drawn the attention from the functional foods industry. Furthermore, cacao cell suspensions can be used to evaluate complex biosynthetic pathways, such as flavonoids due to the homogeneity of the cell population, the unlimited availability of raw material, the high cell growth and division rates, and the reproducibility of in vitro growth conditions. However, the metabolome of cacao could be affected by exposure to light; especially shorter wavelengths such as blue light trigger targeted flavonoid synthesis. Here, we provide the first report of the metabolomic profile of cacao cell suspensions grown under white-blue and dark conditions. For this, targeted metabolomics was conducted on flavonoids, including bioactive compounds such as catechin, epicatechin and proanthocyanidins (PAs). Moreover, untargeted metabolomics was performed to evaluate the response of the endogenous metabolites exposed to darkness and light. For this, unsupervised and supervised multivariate methods were used. Additionally, a chemical annotation and classification was conducted for the top 50 features obtained from the PLS-DA, in order to identify metabolic pathways that are associated to the light treatments. An increase of glycosylated flavonoids and PAs with higher degrees of polymerization from cells grown under light compared to dark, suggested that light conditions may trigger mechanisms associated with moderate stress. Additionally, lipids, flavonoids, and phytosterols increased after light treatment. The potential of cacao cell suspensions in food biotechnology is discussed, considering that the characterization and quantification of the cacao flavonoid composition are the first steps to evaluate the putative contribution of chocolate to human health. Key message Metabolomic profiles of cacao cell suspensions under light and dark conditions suggest that flavonoid modification processes could be involved in defense response under light stress.
Cocoa beans and their co-products are a rich source of beneficial compounds for health promotion, including polyphenols and methylxanthines. Knowledge of bioavailability and in vivo bioactivity of these phytochemicals is crucial to understand their role and function in human health. Therefore, many studies concerning bioavailability and bioactivity of cocoa bioactive compound have been done in both in vivo animal models and in humans. This critical review comprehensively summarizes the existing knowledge about the bioavailability and the major metabolic pathways of selected cocoa bioactive compounds (i.e. monomeric flavan-3-ols, procyanidins, anthocyanins, flavonols, phenolic acids, N-phenylpropenoyl-L-amino acids, stilbenes, and methylxanthines). The compiled results indicated that many of these compounds undergo extensive metabolism prior to absorption. Different factors have been suggested to influence the bioavailability of polyphenols and methylxanthines among them the role of gut microbiota, structure of these compounds, food matrix and occurrence of other substances were the most often considered. Aforementioned factors decided about the site where these bioactive compounds are digested and absorbed from the alimentary tract, as well as the pathway by which they are metabolized. These factors also determine of the type of transport through the intestine barrier (passive, involving specific enzymes or mediated by specific transporters) and their metabolic path and profile. Free online copies
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Introducción: Existe evidencia de que el chocolate, que es rico en flavonoides, favorece la salud cardiovascular al mejorar la función endotelial por mayor liberación de óxido nítrico y así contribuye a disminuir la presión arterial. Objetivo: Examinar los efectos del consumo de una bebida láctea a base de cocoa rica en flavonoides, comparados con un grupo placebo sobre la función endotelial y la presión arterial en pacientes con insuficiencia cardiaca. Método: Ensayo clínico aleatorizado controlado con placebo. Se incluyeron 30 sujetos a los cuales se asignó aleatoriamente el tipo de bebida; el grupo intervención recibió 100 g/día de bebida láctea con cocoa y el grupo control recibió una bebida placebo con leche sabor chocolate. Se evaluó: composición corporal (CC) por el método de impedancia bioeléctrica (RJL), presión arterial en reposo/esfuerzo (banda sin fin) y función endotelial mediante el índice TAM/TT por fotopletismografía al inicio y 4 semanas después. Resultados: Grupo control: edad 75,8±8,35; IMC 28,5±4,68 y grupo intervención: edad 64,7±12,188; IMC 35,6±10,16; en este último el peso disminuyó (90,9±27,4 comparado con 89,6±28,6 p=0,05) mientras que en el grupo placebo hubo una tendencia hacia aumento del peso. En el grupo de intervención se encontró una reducción significativa en la presión arterial diastólica (-11%). El índice TAM/TT (función endotelial) mejoró en el grupo de intervención (40,50±12,3 comparado con 32,18±6,5, p=0,05) y en el grupo control la mejoría no fue significativa (42,57±15,4 comparado con 36,48 ± 10,9, p=0,12). Conclusión: Los pacientes con insuficiencia cardiaca que consumieron la bebida láctea a base de cocoa durante 4 semanas mejoraron síntomas, presión diastólica y función endotelial. Palabras clave: insuficiencia cardiaca, chocolate, presión arterial, función endotelial, flavonoides.
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O número de estudos sobre os polifenóis presentes no cacau tem aumentado consideravelmente nos últimos anos, principalmente relacionando-os aos benefícios à saúde humana. Mais recentemente, alguns trabalhos têm procurado prever o teor de polifenóis em produtos derivados de cacau com base no teor de sólidos desengordurados de cacau (SDC) e como o processamento afeta os polifenóis do cacau. As compilações da literatura, em geral, aprofundam os mecanismos dos efeitos benéficos dos compostos fenólicos do cacau no organismo humano. Esta revisão fornece um panorama das principais pesquisas relacionadas aos altos teores de polifenóis presentes no cacau e produtos derivados, bem como aos seus benefícios à saúde. Além disso, busca apresentar aspectos tecnológicos que influenciam o perfil dos compostos fenólicos durante as etapas de processamento. Pelas pesquisas científicas, a destruição dos compostos fenólicos naturalmente presentes nas sementes se dá principalmente nas etapas realizadas para o desenvolvimento do sabor de chocolate, as quais favorecem a diminuição da adstringência e do amargor. Os polifenóis, responsáveis pela capacidade antioxidante do cacau, são drasticamente reduzidos durante a fermentação das sementes e a alcalinização dos nibs e liquors, etapas que envolvem a ocorrência de complexas reações bioquímicas ou uma significativa variação do pH. A produção de chocolate ao leite ou amargo, excluindo o chocolate branco, apresenta um enorme potencial para inovação tecnológica, visto a necessidade da manutenção destes compostos importantes para a saúde, sem prejuízo do sabor agradável, atributo esperado e de grande importância em produtos como o chocolate.
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Recently, polyphenols have gained much more attention, owing to their antioxidant capacity (free radical scavenging and metal chelating) and their possible beneficial implications in human health, such as in the treatment and prevention of cancer, cardiovascular disease, and other pathologies. Cocoa is rich in polyphenols particularly in catechins (flavan-3-ols) and procyanidins. Polyphenol contents of cocoa products such as dark chocolate, milk chocolate and cocoa powder have been published only recently. However, the data vary remarkably due to the quantity of cocoa liquor used in the recipe of the cocoa products but also due to the analytical procedure employed. For example, results obtained by a colourimetric method were 5–7 times higher for the same type of product than results obtained by high performance liquid chromatography (HPLC). In 1994, the per head consumption of chocolate and chocolate confectionery in the European Union ranged from 1.3 kg/year in Portugal to 8.8 kg/year in Germany. In general, consumers in the Northern countries consume on average more than people in the South. Thus, chocolate can be seen as a relevant source for phenolic antioxidants for some European population. However, this alone does not imply, that chocolate could be beneficial to human health. Some epidemiological evidence suggests a beneficial effect to human health by following a polyphenol-rich diet, namely rich in fruits and vegetables and to a less obvious extent an intake of tea and wine having a similar polyphenol composition as cocoa. In many experiments cellular targets have been identified and molecular mechanisms of disease prevention proposed, in particular for the prevention of cancer and cardiovascular diseases as well as for alleviating the response to inflammation reactions. However, it has to be demonstrated, whether polyphenols exert these effects in vivo. One pre-requisite is that the polyphenols are absorbed from the diet. For monomeric flavonoids such as the catechins, there is increasing evidence for their absorption. For complex phenols and tannins (procyanidins) these questions have to be addressed for the future. Some indication for the absorption of procyanidins derive from studies with the human colon cancer cell line Caco-2, believed to be a valuable model for passive intestinal absorption as proposed for polyphenols. However, it has to be clarified which concentration is effective and what concentrations can be expected from food intake. Another open question is related to polyphenol metabolism. For example, much effort has been invested to show antioxidative effects of free unbound polyphenols, especially of catechins and the flavonol quercetin. However, only a very small part can be found in plasma in the free form but conjugated or even metabolised to several phenolic acids and other ring scission products. From the papers reviewed, it is as yet to early to give an answer to the question, whether chocolate and/or other sources rich in catechins and procyanidins are beneficial to human health. Even though some data are promising and justify further research in the field, it has to be shown in future, whether the intake of these functional compounds and/or their sources is related to measurable effects on human health and/or the development of diseases.
To test the widespread idea that chocolate is harmful in instances of acne vulgaris, 65 subjects with moderate acne ate either a bar containing ten times the amount of chocolate in a typical bar, or an identical-appearing bar which contained no chocolate. Counting of all the lesions on one side of the face before and after each ingestion period indicated no difference between the bars. Five normal subjects ingested two enriched chocolate bars daily for one month; this represented a daily addition of the diet of 1,200 calories, of which about half was vegetable fat. This excessive intake of chocolate and fat did not alter the composition or output of sebum. A review of studies purporting to show that diets high in carbohydrate or fat stimulate sebaceous secretion and adversely affect acne vulgaris indicates that these claims are unproved.
We examined the antibacterial effects of cocoa on periodontal pathogenic bacteria, including Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia, compared with its effects on indigenous oral streptococci. A colony-forming unit (CFU) assay in the presence and absence of 1.0% and 3.0% (w/v) cocoa revealed that the growth of periodontal pathogenic bacteria was significantly suppressed by cocoa in concentration- and incubation time-dependent manners, although cocoa had no effect on the growth of indigenous streptococci. Methanol- and ethanol-extractable fractions from cocoa were also subjected to the CFU assay to determine and characterize the component (s) responsible for these effects. Fractions containing mainly cocoa polyphenols showed antibacterial effects. After treatment with polyvinylpolypyrrolidone, an absorbent of polyphenols, the methanol-extractable fraction lost its effect. These results suggest that cocoa has significant antibacterial effects against periodontal pathogenic bacteria and that polyphenols are responsible.
Due to antioxidant properties linked to their polyphenolic structure, dietary flavonoids are supposed to protect the organism against deleterious effects of environmental oxidants. Indeed prospective epidemiologic studies on cohorts have shown inverse correlations between consumption of some foods or beverages with high flavonoid content, (especially flavanols and anthocyanins), and coronary stroke mortality or prevalence of neurodegenerative diseases including Alzheimer's and Parkinson's diseases. These include red wine, some grape juices, red fruits, tea and cocoa, The hypothesis of cause effect relationship between dietary flavonoid intake and observed protection is further supported by several short term controlled randomised clinical trials. However composition of ingested food or beverage is complex and poorly defined, especially their content in different flavonoids. In addition, knowledge on bioavailability of these compounds and their fate in the organism is still limited. The best documented effect is protection or restoration of the vascular endothelium function, principally involving nitric oxide (*NO). It is not established that ingested flavonoids produce a direct antioxidant effect in vivo. By contrast, at the cell level, some flavonoids can modify protein kinases mediated signal transmission, thereby inducing antioxidant and anti-inflammatory genes expression, and, vice versa, inhibiting oxidant and inflammatory gene expression. Presently available information and the important health challenge justify enhanced research in the field.
There is considerable interest in the bioavailability of flavan-3-ols such as tea catechins and cocoa-derived procyanidin components of the diet and their bioactivity in vivo. Their hydrogen-donating abilities and their propensity for nitration make these compounds powerful scavengers of reactive oxygen and nitrogen species. In addition, recent evidence has suggested that these compounds may interact with redox-sensitive cell signaling pathways. However, their bioactivity in vivo will be dependent on the absorption and metabolism of these compounds after ingestion and the reducing properties of resulting metabolites. Many cell, animal, and human studies have shown that flavanol monomers, such as epicatechin, are extensively metabolised to O-methylated forms and/or conjugated to glucuronides and sulphates during absorption into the circulation. The cleavage of higher procyanidin oligomers to mixtures of monomer and dimer in the stomach may act to enhance the potential for their absorption in the small intestine as higher oligomers; have very limited absorption. Studies suggest that the major bioactive forms of flavanol monomers and procyanidins in vivo are likely to be metabolites and/or conjugates of epicatechin. One such metabolite, 3'-O-methylepicatechin, has been shown to exert protective effects against oxidative stress-induced cell death. Future studies will continue to concentrate on the exact mechanism of action of the bioactive forms of flavan-3-ols in vivo.
Background: Previous studies suggest possible associations between Western diet and acne. We examined data from the Nurses Health Study II to retrospectively evaluate whether intakes of dairy foods during high school were associated with physician-diagnosed severe teenage acne.