ArticlePDF AvailableLiterature Review

Caffeine and cardiovascular diseases: Critical review of current research

Authors:

Abstract and Figures

Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains “Which dose is safe?”, as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.
This content is subject to copyright. Terms and conditions apply.
1 3
Eur J Nutr
DOI 10.1007/s00394-016-1179-z
REVIEW
Caffeine and cardiovascular diseases: critical review of current
research
Anthony Zulli1 · Renee M. Smith1 · Peter Kubatka2 · Jan Novak3,4 · Yoshio Uehara5 ·
Hayley Loftus1 · Tawar Qaradakhi1 · Miroslav Pohanka6 · Nazarii Kobyliak7 ·
Angela Zagatina8 · Jan Klimas9 · Alan Hayes1 · Giampiero La Rocca10,11 ·
Miroslav Soucek3 · Peter Kruzliak12
Received: 29 August 2015 / Accepted: 6 February 2016
© Springer-Verlag Berlin Heidelberg 2016
Keywords Cardiovascular diseases · Caffeine ·
Cardioprotective effects · Pathogenesis · Clinical studies ·
Experimental studies
Introduction
Cardiovascular disease (CVD) is an indiscriminate lead-
ing cause of death worldwide. Given the potential burden
on the health system, there has been much effort put into
uncovering methods of decreasing risk and improving dis-
ease management.
Caffeine is one of the most commonly consumed phar-
macologically active substances worldwide and is read-
ily available from several sources including coffee, tea
and soft drinks. For decades, the association between caf-
feine consumption and CVD has been widely researched
Abstract Caffeine is a most widely consumed physiolog-
ical stimulant worldwide, which is consumed via natural
sources, such as coffee and tea, and now marketed sources
such as energy drinks and other dietary supplements. This
wide use has led to concerns regarding the safety of caf-
feine and its proposed beneficial role in alertness, perfor-
mance and energy expenditure and side effects in the car-
diovascular system. The question remains “Which dose is
safe?”, as the population does not appear to adhere to the
strict guidelines listed on caffeine consumption. Studies
in humans and animal models yield controversial results,
which can be explained by population, type and dose of
caffeine and low statistical power. This review will focus
on comprehensive and critical review of the current litera-
ture and provide an avenue for further study.
* Peter Kruzliak
kruzliakpeter@gmail.com
1 Centre for Chronic Disease (CCD), College of Health
and Biomedicine, Victoria University, Melbourne, VIC,
Australia
2 Department of Medical Biology, Jessenius Faculty
of Medicine, Comenius University in Bratislava, Martin,
Slovakia
3 2nd Department of Internal Medicine, St. Anne’s University
Hospital and Masaryk University, Brno, Czech Republic
4 Department of Physiology, Masaryk University, Brno, Czech
Republic
5 Division of Clinical Nutrition, Faculty of Home Economics,
Kyoritsu Women’s University, Tokyo, Japan
6 Faculty of Military Health Sciences, University of Defence,
Hradec Kralove, Czech Republic
7 Bogomolets National Medical University, Kiev, Ukraine
8 Cardiology Center Medika, St. Petersburg, Russia
9 Department of Pharmacology and Toxicology, Faculty
of Pharmacy, Comenius University, Odborarov 10,
832 32 Bratislava, Slovak Republic
10 Human Anatomy Section, Department of Experimental
Biomedicine and Clinical Neurosciences, University
of Palermo, Palermo, Italy
11 Euro-Mediterranean Institute of Science and Technology
(IEMEST), Palermo, Italy
12 Laboratory of Structural Biology and Proteomics, Faculty
of Pharmacy, University of Veterinary and Pharmaceutical
Sciences, Palackeho tr 1/1946, Brno 612 42, Czech Republic
Eur J Nutr
1 3
with conflicting results. In older studies, habitual caffeine
intake has been frequently reported to be associated with an
increased risk of CVD; however, these results have not been
reproducible in more recent studies. In fact, the opposite
holds true for recent studies which tend to report a neutral or
inverse relationship between habitual caffeine consumption
and CVD morbidity and mortality. Caffeine and its role in
CVD are yet to be fully understood. Caffeine acts via 3 dis-
tinct pathways, but it is the inhibition of the adenosine recep-
tor that appears to be the most important for typical human
consumption and its perceived cardioprotective properties.
Although there has been some disagreement as to the
efficacy of the proposed caffeine protective effect, recent
animal studies generally suggest that it may be protective,
at least for certain CVD parameters. Animal studies which
confer a protective role for caffeine have shown attenuation
of endothelial dysfunction, hypertension, inflammation and
increased apoptosis.
This review summarizes the effects of caffeine on the
risk of cardiovascular diseases based on available preclini-
cal and clinical studies. However, in worldwide population,
caffeine is consumed within natural or marketed sources.
Natural sources of caffeine, e.g. coffee or tea, are defined
as plant functional foods rich on the mixture of phytochem-
icals with a plethora of biological activities on the cell. It
is important to mention that coffee is a complex beverage
containing >1000 compounds—except of caffeine it con-
tains myriad bioactive substances with either health-pro-
moting effects (e.g. chlorogenic acid, phenolic compounds
and derived antioxidants, melanoidins, trigonelline-derived
niacin) or potentially negative health effects (diterpene
alcohols, acrylamide, 5-hydroxymethylfurfural metabo-
lized into potentially harmful 5-sulfooxymethylfurfural)
[1]. The presence of these substances depends among oth-
ers on industrial processing (e.g. natural, blend, torrefacto,
soluble coffee) as well as culinary preparation of coffee
(boiled, filtered, presso, etc.).
Caffeine: physical, chemical properties
Caffeine (1,3,7-trimethylpurine-2,6-dione in chemical
words) is a purine alkaloid produced by Coffea plants, such
as Coffea arabica and Coffea canephora [2], and tea plants
such as Camellia sinensis [3]. Harvesting of tea originated
in the mid of 3rd millennium BC, and Coffea plants have
been cultivated since fifteenth century [4]. Physiologically,
caffeine is excitatory, and it is able to ameliorate transient
cognitive impairments and fatigue [5]. Currently, many
countries do not ban the sale of products with caffeine
and do not impose taxes on its sale (such as alcohol). This
makes caffeine cost-efficient and accessible for the broad
population.
Solvents including water and ethanol can be used to make
solutions of caffeine. However, caffeine is only moderately
soluble in water and ethanol at room temperature [6]. Thus,
heated water is to be used for coffee or tea preparation to max-
imize caffeine concentration. Caffeine is dissolvable in flu-
idic carbon dioxide, and this is utilized in industrial processes
when decaffeinated coffee or tea is manufactured [7, 8].
Caffeine is a purine alkaloid. The biologically active
purine alkaloids are members of the main caffeine biosyn-
thetic pathway and hence present in products which con-
tain caffeine. These include xanthosine, 7-methylxantho-
sine and theobromine [9]. Caffeine is metabolized by liver
microsomal cytochrome P450. Two of the cP450 isoen-
zymes, 1A2 and 2C9, are important to demethylate caffeine
giving rise to paraxanthine, theobromine and theophylline
[10, 11]. The metabolism of caffeine should be taken into
consideration when the effect of caffeine is evaluated, as
the overall impact on homoeostasis is the sum of caffeine,
paraxanthine, theobromine and theophylline. The demeth-
ylation to other purine alkaloids by P450s in the liver is
depicted in Fig. 1. Caffeine reaches peak concentration in
plasma after 30–120 min, and half-life of caffeine in blood
is 3–6 h [12]. Pharmacokinetics of caffeine can be altered
by physical condition, gender, consumption of other active
compounds, which could explain why the extended half-
life of caffeine is 2.5–10 h [13]. Thus, the half-life of caf-
feine should be taken into consideration whenever results
from caffeine relating clinical studies discussed.
The nervous system is sensitive to caffeine as caffeine
can interact with several regulatory pathways. The major
effect of caffeine is mediated via adenosine receptors.
Adenosine is a simple compound interacting with G-pro-
tein-coupled adenosine receptors having broad physiologi-
cal importance. Currently, types A1, A2A, A2B and A3 of the
receptors are known and caffeine is able to act as an antag-
onist which prevents adenosine stimulation of the receptors
[14, 15]. Stimulation of the receptors can initiate disparate
effects including bronchospasm, inhibition of neutrophils
degranulation, smooth muscle contraction, vasodilatation
and regulation of heart rate [1618]. Caffeine can interfere
in these pathways. For example, tachycardia due to caffeine
agonism on receptor A1, mental excitation due to agonism
on A2A receptor, bronchodilatation due to A2B receptor ago-
nism, protection from neutrophil degranulation due to ago-
nism on A3 receptor can be observed (Fig. 2) [1923].
Though antagonism of caffeine on adenosine receptors
is suggested to be the major effect in the body, caffeine can
mediate its effect via other pathways. Impact of caffeine on
homoeostasis by these other pathways is underestimated. As
caffeine is a reversible inhibitor of enzyme monoamine oxi-
dase, exposure to caffeine can cause higher accessibility of
dopamine, epinephrine, norepinephrine and serotonin [24,
25]. Apart from monoamine oxidase, acetylcholinesterase
Eur J Nutr
1 3
is also inhibited by caffeine; thus, high dose of caffeine can
cause increased accessibility of the neurotransmitter, acetyl-
choline [26, 27]. Involvement of caffeine in neurotransmission
is followed by targeting of some intracellular signalling path-
ways. Phosphodiesterase, poly(ADP-ribose)polymerase-1
and ryanodine receptors interact with caffeine. Caffeine is an
inhibitor of phosphodiesterase; hence, intracellular messen-
gers, cAMP and cGMP, have protracted signal in the presence
of caffeine [28, 29]. Inhibition of poly(ADP-ribose)polymer-
ase-1 provides link between caffeine and control of cell cycle
[30, 31] and thus could also be implicated in the pathogenesis
of atherosclerosis [32] and oncogenesis [33], yet these are not
well supported by clinical trials. Lastly, caffeine is an agonist
of ryanodine receptors serving as a Ca2+-specific channel
on sarcoplasmic reticulum [3436]. Stimulation of ryano-
dine receptors is an essential step in muscle contraction and
thus has been used by sportsmen for increased performance,
although the benefits are probably overestimated [37, 38].
Effects of caffeine on heart and vessels: critical
review of results obtained from experimental
studies
Experimental studies using caffeine are focusing either
directly on the effects of caffeine on cells, heart and
Fig. 1 The demethylation of the caffeine to other purine alkaloids by
P450s in the liver
Fig. 2 Scheme on the caffeine
effects imposed by interaction
with different adenosine recep-
tors (A1, A2A, A2B, A3—differ-
ent adenosine receptors; Gi,
Gs—inhibitory or stimulatory
G-protein)
Eur J Nutr
1 3
vessels, or caffeine is used within these studies as a stimu-
lant to induce arrhythmias via ryanodine receptors and its
mutated forms [38]. By binding to ryanodine receptor, caf-
feine stimulates calcium fluxes that can result in arrhyth-
mias [e.g. in RyR2(R420W/R420W)] rats [38] which are
connected to the positive inotropic effect of caffeine [39,
40]; however, these effects can be observed only at high
caffeine concentrations that are usually not reached in clin-
ical studies or after drinking a moderate amount of coffee
[39, 40]. While past studies have focused mainly on direct
effects of caffeine on the cardiovascular system, studies
performed within the last few years are focusing on poten-
tial adverse effects of caffeine consumption in pregnancy
and on molecular mechanisms.
Cardiometabolic effects of caffeine
Using isolated vessels or cells (in vitro), usually vaso-
dilatory response is observed after caffeine application
[4143], and results from our laboratory on phenylephrine
precontracted rabbit aortic rings confirm a vasodilatory role
for caffeine. At the doses used within experimental stud-
ies—that are much higher than doses used in human stud-
ies—caffeine seems to inhibit phosphodiesterase, which
further results in increase in cAMP and cGMP (that are
under normal circumstances both degraded by phosphodi-
esterase), both resulting in vasodilation. Another important
aspect of in vitro models is the fact that usage of isolated
cells or denervated organs prevents action of contraregu-
latory mechanisms, which may be partly responsible for
opposite results observed in human studies, i.e. in vasocon-
striction and increase in blood pressure.
Interestingly, caffeine was shown to diminish NOS
expression in rat myocardium [44] and increased mean
arterial pressure [44] as well as with increase in heart rate,
systolic and diastolic blood pressures [45]. As well, meta-
bolic effects of caffeine were described—increase in LDL
cholesterol and decrease in HDL cholesterol were observed
after caffeine ingestion [45], and in animal model of meta-
bolic syndrome, decrease in total body fat (with adequate
increase in plasma lipid concentrations) was observed
together with improvement of insulin tolerance and lipid
resistance [46]. These results may partly explain the
decreased prevalence of type 2 diabetes (T2DM) in indi-
viduals drinking coffee in epidemiological studies [47, 48].
Insulin resistance and caffeine in CVD
Defects in hepatic fructose metabolism in certain groups,
such as T2DM and the metabolic syndrome (MS), could
affect the physiological effect of caffeine. The high-fruc-
tose-fed animal model is well established to study meta-
bolic syndrome, insulin resistance and T2DM [4951]. Yeh
et al. [51] showed that rats fed fructose (10 % of diet) sig-
nificantly increased BP, fasting serum glucose, insulin, IR
and plasma norepinephrine levels, while the HDL-C levels
decreased, compared to controls. Adding caffeine (equiva-
lent to 3–4 cups per day) to the fructose-fed group resulted
in a significant reduction of those parameters (compared to
fructose-only group) and was comparable to control. The
authors concluded that caffeine ameliorated a fructose-
induced defect in the insulin–PI3K–Akt signalling pathway
possibly via a reduction in superoxide production and also
an increase in NO production, which attenuated hyperten-
sion [51].
Interestingly, the autophagy–lysosomal pathway in
hepatic lipid metabolism has been described in a related
study [52]. Using both in vivo and in vitro techniques,
they found that caffeine-induced autophagy and lipoly-
sis was partly influenced by caffeine (moderate to heavy
intake; 2–3 cups of coffee per day). The authors suggest
that caffeine can inhibit the mammalian target of rapa-
mycin (mTOR), which is an important step for autophagy.
These are all potentially important, particularly for those
diagnosed with erratic liver fat oxidation, as reduced liver
lipid oxidation can lead to non-alcoholic fatty liver dis-
ease (NAFLD) which is a risk factor for T2DM [52, 53].
In another study looking at the effects of MS in male rats,
subjects were fed high fat and high carbohydrate plus caf-
feine [46]. The authors found that caffeine supplementation
reduced obesity, hypertension, heart remodelling, NAFLD
and improved metabolic markers such as insulin sensitiv-
ity but worsened dyslipidaemia. The authors also addressed
the role of A1 receptors, where caffeine acted as an antago-
nist, which increased lipolysis in abdominal adipocytes.
Interestingly, these results differ from Sacramento et al.
[54], who showed that agonism of A1 receptors in skeletal
muscle increases glucose uptake, but caffeine acted as an
antagonist to A1 which ultimately reduced insulin sensitiv-
ity. Thus, the caffeine/A1 receptor interaction requires fur-
ther research to understand its role in CVD.
Ischaemia, A2A adenosine receptor and caffeine
Ischaemic stroke is a leading cause of death worldwide,
and the risk is increased in those with impaired blood flow,
involving both an oxidative stress and inflammatory path-
way [55, 56]. Interestingly, Fronz et al. [55] report that
antagonism of the A2A receptor has potentially protective
properties if given immediately following ischaemia as
this receptor mediates NO release and vasodilation [57].
Caffeine is a non-selective adenosine receptor antago-
nist [58] resulting in different outcomes dependent on the
pathway inhibited. For example, Nishida et al. [59] used
caffeine to induce calcium (Ca2+) release from the myo-
cardial sarcoplasmic reticulum and found that this created
Eur J Nutr
1 3
an environment favourable to atrial fibrillation (AF) and
could be important to understanding AF pathophysiology
in coronary artery disease (CAD). Momoi et al. [57] also
assessed the role of caffeine in hypoxia. Levels of adeno-
sine could be protective as they showed that administration
of caffeine (10 mg/kg/dose) and hypoxia (100 % nitrogen
for 45 s) in pregnant mice resulted in negative effects on
foetal CV function and development, attributed to the inhi-
bition of the A2A adenosine receptor by caffeine. It should
be noted that foetal levels of adenosine are higher than in
adults; thus, they are probably required to protect the devel-
oping foetal organ system. Fronz et al. [55] also assessed
the role that caffeine might play in ischaemia, focusing on
cerebral artery occlusion. As they report, the A2A recep-
tor can be inhibited to reduce severity of stroke. They also
report, however, that the underlying mechanism is yet to be
fully elucidated, although an inflammatory link has been
proposed. Despite other laboratories providing evidence
that antagonism of the A2A receptor is neuroprotective, the
authors were unable to treat acute ischaemia in spontane-
ously hypertensive rats, possibly due to metabolism of the
compound. However, as Sun et al. [56] report, there is also
a suggestion that targeting inflammatory processes may be
a better option, as cerebral ischaemia–reperfusion injury
is accompanied by a changed local inflammatory environ-
ment. Using a tea compound, theanine, that has reactive
oxygen species (ROS)-scavenging properties, the authors
were able to reduce both infarct size and water content in
rats with a combined treatment of theanine and caffeine
(1 mg/kg body mass and 10 mg/kg, respectively), but not
caffeine alone, suggesting a role for ROS. Similarly, a
study assessing the combination of caffeine and ethanol
(caffeinol; caffeine 10 mg/kg + ethanol 0.32 g/kg) found
that the combination of the drugs, but not either drug on its
own, was able to ameliorate the effects of damage induced
by ischaemia via the N-methyl-d-aspartate (NMDA) recep-
tor in male rats [60].
Caffeine in foetal programming
Interesting studies using caffeine suggest that its use dur-
ing pregnancy results in adverse cardiac remodelling and
aberrant vessel formation. In pregnant dams treated chroni-
cally with caffeine, aberrant activation of local renin–angi-
otensin–aldosterone system was observed both in kidneys
and in hearts of the offspring rats. This was connected to
adverse cardiac remodelling (e.g. increased left ventricu-
lar wall thickness) and increase in blood pressure, which
further resulted in increased energy expenditure and heart
rate and reduction in body mass gain [61] and in decrease
in cardiac output [62]. Usage of caffeine also resulted in
intrauterine growth restriction, probably due to adenosine
2A receptor-mediated vasoconstriction and concomitant
flow reduction in umbilical arteries [63]. Generally, adeno-
sine 2A receptor seems to be more involved in foetal pro-
gramming compared to adenosine 1 receptor (A1R). Caf-
feine can affect A2A receptor at lower doses compared to
A1 receptor [64], and expression of A2A receptor was also
shown to be altered in maternal hearts exposed to caffeine
[65]. On the other hand, involvement of A1R in the hypoxic
response of neonatal myocardium was also shown [66].
Moreover, caffeine also inhibits angiogenesis, as shown
in mice [61] or zebrafish [67, 68]. Zebrafish is an accepted
model to study angiogenesis and treatment of zebrafish
embryos with caffeine resulted in defects in new vessels
formation [68] that are probably caused by decrease in
VEGF expression [67].
Molecular mechanisms leading to above-described
effects seem to be connected with DNA methylation [62]
or oxidative stress [69]. In ApoE/ mice, caffeine use
was shown to inhibit DNA damage [70] and it was shown
to inhibit formation or reactive oxygen species, partly by
restoring cytochrome oxidase activity in the animal model
of sepsis [71]. Recently, Fang et al. [72] showed that caf-
feine treatment affects expression of crucial cardiac genes
(e.g. myosin heavy chains or cardiac troponins) and it gen-
erally causes decrease in DNA methylation.
Effects of caffeine on heart and vessels: critical
review of results obtained from clinical studies
Cardiovascular effects of caffeine in studies involving
human subjects are generally mediated via its antagonism
of adenosine receptors, since binding to other receptors
occurs only at much higher doses than those reached after
drinking a moderate amount of coffee or tea [73]. Adeno-
sine receptors are distributed thorough the body, and caf-
feine thus has potential to directly affect the myocardium
(where it affects contractility and conduction), the vessel
wall (where it affects vascular tone) and also the auto-
nomic nervous system [73]. As results from human studies
are often different from the results obtained in preclinical
studies, this could be explained by other regulatory mecha-
nisms which are initiated after caffeine ingestion (involv-
ing, e.g. baroreflex, renin–angiotensin–aldosterone system
and others).
Caffeine, blood pressure and vessel wall
Caffeine ingestion in the form of caffeine pills, coffee,
tea or various energy drinks usually leads to increase in
blood pressure in human subjects [7478]. This is a result
of increase in total peripheral resistance [40, 79], which
occurs without any concomitant increase in stroke vol-
ume or cardiac output, although heart rate is reported to
Eur J Nutr
1 3
decrease, probably due to feedback mechanisms [40, 79].
Direct vasoconstriction of several intracranial arteries, e.g.
ophthalmic, central retinal and short nasal ciliary artery
[80, 81], was also described, which seems to be connected
with decreased cerebral blood flow and increased intracer-
ebral pressure [82].
Except of direct or indirect effects on vasoconstriction or
vasodilation, caffeine also affects endothelial function and
arterial stiffness. Endothelial function can be assessed either
by using flow-mediated dilation of brachial artery, which is
a parameter reflecting endothelial function and its values
also correlate with the number of cardiovascular events [83,
84], or by assessing post-occlusive reactive hyperaemia in
finger arteries [74]. Acute caffeine, but not nitroglycerine,
application in both healthy volunteers and patients with
coronary artery disease resulted in significant increase in
flow-mediated dilation and decrease in hs-CRP level, sug-
gesting positive effects of caffeine on endothelial function
and inflammation [83]. This result was not observed in
healthy subjects after coffee ingestion—flow-mediated dila-
tion was decreased in these individuals, and this decrease
was the most prominent within the first hour after coffee
ingestion [85]. Differences between these two studies may
be explained by different caffeine dosages (caffeine pills vs.
coffee drinking) and by differences between study groups
(the latter study involving regular non-heavy coffee drinkers
and the first study restricting individuals from any caffeine
intake prior study). Studying reactive hyperaemia of finger
arteries, Noguchi et al. [74] showed that caffeine ingestion
increased microvascular endothelial function. Whether the
impact of caffeine on endothelial function is positive or neg-
ative still needs to be determined by larger studies.
Arterial stiffness, another parameter reflecting cardio-
vascular system function, was also shown to be affected by
caffeine both positively and negatively. Arterial stiffness
may be assessed by various methods, using renal resistive
index (RRI) or pulse wave velocity (PWV). Coffee drink-
ing was shown to increase both pulse wave velocity [86,
87] and augmentation index [86, 88, 89], parameter reflect-
ing increase in pulse wave reflections. On the other hand,
RRI was shown to be inversely correlated with caffeine
intake, which suggests protective effect of coffee drink-
ing—higher RRI associates, e.g. with insulin resistance or
presence of renal insufficiency [90].
Also, studies were performed on preterm infants, where
caffeine application was associated with improved hemo-
dynamics [91] and increased cerebral cortical activity and
resulted in shorter stay at ICU [92]. This was accompa-
nied by increase in heart rate, mean arterial blood pressure
and oxygen saturation [92]. On the other hand, study by
Ulanovsky et al. [93] did not observe these effects. Thus,
caffeine use in this specific group of patients needs to be
validated to reveal whether its use is beneficial.
Caffeine and autonomic nervous system function
Autonomic nervous system function may be assessed using
various methods, mostly using either variability of blood
pressure, baroreflex sensitivity or heart rate variability
(HRV) [94, 95]. Already in 1990, it was shown that caffeine
decreases baroreflex sensitivity [96], which may partly
blunt cardiovascular response to caffeine administration.
Later studies then repeatedly showed that caffeine intake
increases high-frequency part of the HRV spectra that is
known to be connected with parasympathetic (or vagal)
activity [95, 97]; however, similar effect was observed after
ingestion of decaffeinated coffee or hot water. Although the
effects of caffeine on parasympathetic system activation
are present in young healthy individuals, its effects were
not shown in patients with heart failure, where diminished
HRV predicts poor prognosis [98].
Caffeine and sports performance
Numerous studies have emerged during the past few years
focusing on the potential ergogenic effect of caffeine. Most
are small in size enrolling from 6 to 20 individuals per-
forming various sporting activities, which could explain the
variability of results.
Considering the short-term performance activities, in
young adults during exercise (n = 14) [99], in soccer play-
ers during regular match [37, 100] or in judo fitness test
(n = 6) [101], caffeine did not increase their physical abil-
ity. Its usage was connected to reduction in perceived exer-
tion, reduced perception of muscle pain and with increase
in plasma lactate [101, 102]. It was also shown that inges-
tion of caffeine prior to exercise may result in increase
in post-exercise energy expenditure in young athletes
(n = 12) [103], which may be connected to increase in
post-exercise systolic blood pressure, preventing patients
from the development of post-exercise hypotension [77].
On the other hand, in the post-exercise period also blunted
autonomic system function recovery was observed—after
maximal treadmill test, heart rate, mean arterial pressure
and diastolic blood pressure remained elevated in individu-
als that received caffeine prior to exercise, which is known
to be connected to the development of various arrhythmias
[104].
Concerning endurance performance, caffeine chew-
ing gum was shown to improve mean and sprint perfor-
mance power in the cyclist in the last third of the 30-km
trail (n = 20) [105]; similarly, caffeine increased power and
speed only during the last 2 km of the 20-km trial [106]. In
2-km rowing competition, caffeine also showed beneficial
effects on rowing time (n = 13) [107], and in 8-km cross-
country skiing, caffeine also enhanced endurance perfor-
mance [108].
Eur J Nutr
1 3
In summary, caffeine does not seem to increase sig-
nificantly the power or strength of sportsmen; however,
it affects endurance, either by increasing the resistance to
fatigue or by increasing the activity of the nervous system.
Considering described effects of caffeine in post-exercise
period, drinking caffeine prior to sporting activities should
be carefully considered taking in mind all advantages and
disadvantages and individual characteristics of the person.
Caffeine and risk of cardiometabolic diseases
A wide variety of studies, both large and small, have been
carried out on both healthy participants and patients who
already suffer from cardiovascular affliction (cardiovascu-
lar disease, hypertension, stroke) or one of its risk factors.
Overall, there is no evidence to suggest a negative effect
of moderate coffee/caffeine consumption on cardiovascular
health [109111]. Previously, coffee intake was considered
a traditional risk factor for cardiovascular diseases. How-
ever, results from large epidemiological studies do not seem
to support this idea and it even appears that coffee drinking
may exert protective effect against some CV diseases. Cof-
fee drinking was associated with lower prevalence of sub-
clinical atherosclerosis (determined by CT coronary artery
calcium) [112], and there was no association between cof-
fee intake and markers of coronary or carotid atherosclero-
sis [113]. Coffee consumption neither associated with the
long-term risk of coronary heart disease development [114]
nor associated with stroke [115]. It thus seems that caffeine
intake does not promote atherosclerosis process and its use
even associates with lower cardiovascular mortality [116,
117].
The connection between caffeine and atrial fibrilla-
tion (AF) was also unconfirmed, and low doses of caffeine
were shown to have protective effects against atrial fibril-
lation development [118, 119]. Moreover, Cheng et al.
[120] conducted a meta-analysis to investigate the associa-
tion between chronic exposure of caffeine and the risk of
AF and to evaluate the potential dose–response relation.
They concluded that it is unlikely that caffeine consump-
tion causes or contributes to AF. Habitual caffeine con-
sumption might reduce AF risk. In another study, Larsson
et al. [121] investigated the association between coffee con-
sumption and incidence of AF in two prospective cohorts
and summarized available evidence using a meta-analysis.
They found no evidence that coffee consumption is associ-
ated with increased risk of AF. In a large population-based
cohort study (the Danish Diet, Cancer and Health Study),
higher levels of coffee consumption were associated with
a lower rate of incident AF [122]. If caffeine was applied
to patients prior to supraventricular tachyarrhythmias abla-
tion, no effects on cardiac conduction or refractoriness
were observed [75]. It thus seems that there is no need to
abstain patients with atrial fibrillation and even those after
myocardial infarction from drinking coffee [123].
The relationship between caffeine consumption and the
occurrence of arrhythmias remains controversial. Despite
the lack of scientific evidence, counselling to reduce caf-
feine consumption is still widely advised in clinical prac-
tice. Zuchinali et al. [124] conducted a systematical review
and meta-analysis of interventional studies of the coffee
and caffeine effects on ventricular arrhythmias. Their meta-
analysis demonstrates that data from human interventional
studies do not show a significant effect of coffee and caf-
feine consumption on the occurrence of ventricular prema-
ture beats. The harmful effects of caffeine on arrhythmias
observed in animal studies are most probably the result of
very high caffeine doses that are not regularly consumed in
a daily basis by humans.
Ding et al. [110] examined the associations of consump-
tion of total, caffeinated and decaffeinated coffee with risk
of subsequent total and cause-specific mortality among
74,890 women in the Nurses’ Health Study, 93,054 women
in the Nurses’ Health Study II and 40,557 men in the Health
Professionals Follow-up Study. Significant inverse associa-
tions were observed for decaffeinated coffee. Significant
inverse associations were observed between coffee con-
sumption and deaths attributed to cardiovascular disease,
neurologic diseases and suicide. No significant association
between coffee consumption and total cancer mortality was
found. A growing body of data suggests that habitual coffee
consumption is neutral to beneficial regarding the risks of a
variety of adverse CV outcomes including coronary heart
disease, congestive heart failure, arrhythmias and stroke.
Moreover, large epidemiological studies suggest that regu-
lar coffee drinkers have reduced risks of mortality, both CV
and all-cause [48, 125, 126].
In case of heart failure, association of caffeine intake
seems to be dose-dependent and it represents with J-shape
curve so only where high doses of coffee seems to increase
the risk of congestive heart failure development [47, 127].
In metabolic diseases, coffee intake was associated
with lower risk of obesity and T2DM [48, 127]. In a Bra-
zil study, daily drinking two to three cups of coffee were
inversely associated with metabolic syndrome in both
patients and healthy subjects [128]. The association
between coffee consumption, T2DM and impaired glu-
cose tolerance was examined in Swedish study [129]. In
subjects with T2DM and impaired glucose tolerance, high
coffee consumption (greater than or equal to 5 cups per
day) was inversely associated with insulin resistance. In
addition, in those with T2DM and in women (not in men)
with impaired glucose tolerance, high coffee consumption
was inversely associated with low beta-cell function. In
women, but not obviously in men, with normal glucose tol-
erance, coffee consumption was associated with a reduced
Eur J Nutr
1 3
risk of insulin resistance. The long-term use of coffee/caf-
feine was shown to decrease HbA1c and to increase levels
of adiponectin both in healthy individuals and in patients
with T2DM [130], and in patients with T2DM, it was also
shown to promote reduction in blood sugar levels during
exercise [131]. On the other hand, it negatively affects lipid
profiles if coffee is boiled or unfiltered [48]. Coffee intake
even seems to modestly participate on weight loss [132,
133].
Adverse effects of caffeine in overdosed individuals
The effects of “safe” caffeine doses reached either by caf-
feine pills or by coffee ingestion have been described.
However, as shown in experimental studies, higher doses
of caffeine activate or inhibit other signalling pathway
and since coffee is one of the most commonly used drugs,
effects of its overdosing have already been described in
various case reports.
Although usual intake of caffeine in coffee bever-
age is not associated with arrhythmias and atrial fibrilla-
tion, overdosing with caffeine may induce atrial fibrilla-
tion [134, 135] or other supraventricular tachyarrhythmias
[136]. In one case report, 27-year-old woman in an suicidal
attempt used 50 g of caffeine powder which resulted ini-
tially in simplex supraventricular tachycardia followed
by broad complex tachycardia and ventricular fibrillation
[137]. Higher doses of caffeine moreover seem to decrease
potassium levels, which is known to be proarrhythmogenic
[138]. This seems to be result of skeletal-muscle Na/K-
pump stimulation [139]. This may also be an underlying
mechanism for unmasking the congenital type 1 long QT
syndrome, as described in patients after usage of energy
drink with high caffeine content [140].
Toxic doses of caffeine thus seem to affect conductance
and refractoriness on the heart, which results in the devel-
opment of various arrhythmias. Moderate and rational cof-
fee intake thus should be recommended to all patients in
order to avoid these adverse effects.
Future perspectives and challenges
Studies in humans hold conflicting results due to the vari-
ability of population, dose and techniques, yet solid results
from animal studies studying the safe and toxic cardiovas-
cular effects of caffeine/coffee have not yet been reported.
As noted, there have been inconsistent reports regarding
the efficaciousness of caffeine as a protective agent. In a
study assessing the intake of green tea and the develop-
ment of atherosclerotic lesions, Cai et al. [141] suggests
that an active catechin, epigallocatechin-3-gallate (EGCG)
reduces markers associated with atherosclerosis in mice,
thus making it unlikely that caffeine in green tea is pro-
tective. In addition to this, Loopstra-Masters et al. [50]
reported that decaffeinated coffee was also significantly
associated with improved insulin biomarkers in non-dia-
betics, further supporting the important role that those
other compounds probably play in the protection against
CVD. Also, coffee fatty acids have been isolated and range
between 14 and 22 carbon chains [142], further complicat-
ing the identification of possible single beneficial factors.
It is therefore essential to make the appropriate distinc-
tions between the supposed protective effect of caffeine
and any other compounds that may be present and not
draw conclusions from one to the other. It will be a dif-
ficult and costly task to undertake a clinical study to deter-
mine which compounds of coffee are beneficial or detri-
mental to human health. Thus, further studies in animal
models are warranted to determine which factor and dose
are safe to prevent and protect against CVD, including ath-
erosclerosis and myocardial function. Regarding the effect
of industrial processing on the content of plethora biologi-
cally active chemicals in natural sources of caffeine (e.g.
coffee, tea) and thus their effect on CVD risk, available
clinical data are insufficient for relevant conclusions. As
for the culinary preparation, boiled and unfiltered coffee
appears to increase plasma cholesterol and triglycerides,
but for the overall metabolic syndrome, there appears to
be benefiting [143]. It seems that caffeine/coffee is neutral
in relation to atrial fibrillation and ventricular arrhythmias;
moreover, several large epidemiological studies demon-
strated that regular coffee drinkers have reduced risks of
mortality, both CV and all-cause.
Compliance with ethical standards
Conflict of interest Authors declare no conflict of interest.
References
1. Ferruzzi MG (2010) The influence of beverage composition on
delivery of phenolic compounds from coffee and tea. Physiol
Behav 100:33–41
2. Magalhães ST, Fernandes FL, Demuner AJ, Picanço MC,
Guedes RN (2010) Leaf alkaloids, phenolics, and coffee resist-
ance to the leaf miner Leucoptera coffeella (Lepidoptera:
Lyonetiidae). J Econ Entomol 103:1438–1443
3. Kravchenko LV, Trusov NV, Aksenov IV, Avren’eva LI, Guseva
GV, Lashneva NV, Tutel’ian VA (2011) Effects of green tea
extract and its components on antioxidant status and activities
of xenobiotic metabolizing enzymes of rats. Vopr Pitan 80:9–15
4. Zollner H, Giebelmann R (2004) Cultural-historical remarks
on caffeine, coffee and tea. Dtsch Lebensm-Rundsch
100(7):255–262
5. Singer P, McGarrity S, Shen HY, Boison D, Yee BK (2012)
Working memory and the homeostatic control of brain adeno-
sine by adenosine kinase. Neuroscience 213:81–92
Eur J Nutr
1 3
6. Paluch AS, Parameswaran S, Liu S, Kolavennu A, Mobley DL
(2015) Predicting the excess solubility of acetanilide, acetami-
nophen, phenacetin, benzocaine, and caffeine in binary water/
ethanol mixtures via molecular simulation. J Chem Phys
142:044508
7. Saldaña MD, Zetzl C, Mohamed RS, Brunner G (2002) Extrac-
tion of methylxanthines from guaraná seeds, maté leaves, and
cocoa beans using supercritical carbon dioxide and ethanol. J
Agric Food Chem 50:4820–4826
8. Tang WQ, Li DC, Lv YX, Jiang JG (2010) Extraction and
removal of caffeine from green tea by ultrasonic-enhanced
supercritical fluid. J Food Sci 75:363–368
9. Ashihara H, Sano H, Crozier A (2008) Caffeine and related
purine alkaloids: biosynthesis, catabolism, function and genetic
engineering. Phytochemistry 69:841–856
10. Utoh M, Murayama N, Uno Y, Onose Y, Hosaka S, Fujino H,
Shimizu M, Iwasaki K, Yamazaki H (2013) Monkey liver
cytochrome P450 2C9 is involved in caffeine 7-N-demethyla-
tion to form theophylline. Xenobiotica 43:1037–1042
11. Ohyama K, Murayama N, Shimizu M, Yamazaki H (2014) Drug
interactions of diclofenac and its oxidative metabolite with
human liver microsomal cytochrome P450 1A2-dependent drug
oxidation. Xenobiotica 44:10–16
12. Mort JR, Kruse HR (2008) Timing of blood pressure meas-
urement related to caffeine consumption. Ann Pharmacother
42:105–110
13. Magkos F, Kavouras SA (2005) Caffeine use in sports, pharma-
cokinetics in man, and cellular mechanisms of action. Crit Rev
Food Sci Nutr 45:535–562
14. Ribeiro JA, Sebastião AM (2010) Caffeine and adenosine. J
Alzheimers Dis 20:S3–S15
15. Chen JF, Eltzschig HK, Fredholm BB (2013) Adenosine recep-
tors as drug targets—What are the challenges? Nat Rev Drug
Discov 12:265–286
16. Gyoneva S, Shapiro L, Lazo C, Garnier-Amblard E, Smith
Y, Miller GW, Traynelis SF (2014) Adenosine A(2A) recep-
tor antagonism reverses inflammation-induced impairment of
microglial process extension in a model of Parkinson’s disease.
Neurobiol Dis 67:191–202
17. Hofer M, Pospisil M, Dusek L, Hoferova Z, Komurkova D
(2014) Combined pharmacological therapy of the acute radia-
tion disease using a cyclooxygenase-2 inhibitor and an adeno-
sine A(3) receptor agonist. Centr Eur J Biol 9:642–646
18. Vincenzi F, Targa M, Romagnoli R, Merighi S, Gessi S, Baraldi
PG, Borea PA, Varani K (2014) TRR469, a potent A(1) adeno-
sine receptor allosteric modulator, exhibits anti-nociceptive
properties in acute and neuropathic pain models in mice. Neu-
ropharmacology 81:6–14
19. Sullivan GW, Luong LS, Carper HT, Barnes RC, Mandell
GL (1995) Methylxanthines with adenosine alter TNF-alpha-
primed PMN activation. Immunopharmacology 31:19–29
20. Fukunaga AF, Alexander GE, Stark CW (2003) Characteriza-
tion of the analgesic actions of adenosine: comparison of aden-
osine and remifentanil infusions in patients undergoing major
surgical procedures. Pain 101:129–138
21. Chan ESL, Fernandez P, Cronstein BN (2007) Adenosine in
inflammatory joint diseases. Purinergic Signal 3:145–152
22. Joulia F, Coulange M, Lemaitre F, Costalat G, Franceschi F,
Gariboldi V, Nee L, Fromonot J, Bruzzese L, Gravier G, Kipson
N, Jammes Y, Boussuges A, Brignole M, Deharo JC, Guieu R
(2013) Plasma adenosine release is associated with bradycardia
and transient loss of consciousness during experimental breath-
hold diving. Int J Cardiol 168:E138–E141
23. Walaschewski R, Begrow F, Verspohl EJ (2013) Impact
and benefit of A2B-adenosine receptor agonists for the res-
piratory tract: mucociliary clearance, ciliary beat frequency,
trachea muscle tonus and cytokine release. J Pharm Pharmacol
65:123–132
24. Petzer A, Pienaar A, Petzer JP (2013) The interactions of caf-
feine with monoamine oxidase. Life Sci 93:283–287
25. Petzer A, Grobler P, Bergh JJ, Petzer JP (2014) Inhibition of
monoamine oxidase by selected phenylalkylcaffeine analogues.
J Pharm Pharmacol 66:677–687
26. Pohanka M (2014) The effects of caffeine on the cholinergic
system. Mini Rev Med Chem 16:543–549
27. Pohanka M, Dobes P (2013) Caffeine inhibits acetylcholinester-
ase, but not butyrylcholinesterase. Int J Mol Sci 14:9873–9882
28. Bhaskara S, Chandrasekharan MB, Ganguly R (2008) Caf-
feine induction of Cyp6a2 and Cyp6a8 genes of Drosophila
melanogaster is modulated by cAMP and D-JUN protein levels.
Gene 415:49–59
29. Herman A, Herman AP (2013) Caffeine’s mechanisms of action
and its cosmetic use. Skin Pharmacol Physiol 26:8–14
30. Geraets L, Moonen HJ, Wouters EF, Bast A, Hageman GJ
(2006) Caffeine metabolites are inhibitors of the nuclear
enzyme poly(ADP-ribose)polymerase-1 at physiological con-
centrations. Biochem Pharmacol 72:902–910
31. Kumala S, Fujarewicz K, Jayaraju D, Rzeszowska-Wolny J,
Hancock R (2013) Repair of DNA strand breaks in a minichro-
mosome in vivo: kinetics, modeling, and effects of inhibitors.
PLoS One 8(1):e52966
32. Li XY, Xu L, Lin GS, Li XY, Jiang XJ, Wang T, Lü JJ, Zeng B
(2011) Protective effect of caffeine administration on myocar-
dial ischemia/reperfusion injury in rats. Shock 36:289–294
33. Ku BM, Lee YK, Jeong JY, Ryu J, Choi J, Kim JS, Cho YW,
Roh GS, Kim HJ, Cho GJ, Choi WS, Kang SS (2011) Caffeine
inhibits cell proliferation and regulates PKA/GSK3 beta path-
ways in U87MG human glioma cells. Mol Cells 31:275–279
34. Arnáiz-Cot JJ, Damon BJ, Zhang XH, Cleemann L, Yamagu-
chi N, Meissner G, Morad M (2013) Cardiac calcium signalling
pathologies associated with defective calmodulin regulation of
type 2 ryanodine receptor. J Physiol 591:4287–4299
35. Shou Q, Pan S, Tu J, Jiang J, Ling Y, Cai Y, Chen M, Wang D
(2013) Modulation effect of Smilax glabra flavonoids on ryano-
dine receptor mediated intracellular Ca2+ release in cardiomyo-
blast cells. J Ethnopharmacol 150:389–392
36. Friedrich O, Yi B, Edwards JN, Reischl B, Wirth-Hücking A,
Buttgereit A, Lang R, Weber C, Polyak F, Liu I, von Wegner F,
Cully TR, Lee A, Most P, Völkers M (2014) IL-1 alpha revers-
ibly inhibits skeletal muscle ryanodine receptor a novel mecha-
nism for critical illness myopathy? Am J Respir Cell Mol Biol
50:1096–1106
37. Pettersen SA, Krustrup P, Bendiksen M, Randers MB, Brito
J, Bangsbo J, Jin Y, Mohr M (2014) Caffeine supplementation
does not affect match activities and fatigue resistance during
match play in young football players. J Sports Sci 32:1958–
1965. doi:10.1080/02640414.2014.965189
38. Okudaira N, Kuwahara M, Hirata Y, Oku Y, Nishio H (2014) A
knock-in mouse model of N-terminal R420W mutation of car-
diac ryanodine receptor exhibits arrhythmogenesis with abnor-
mal calcium dynamics in cardiomyocytes. Biochem Biophys
Res Commun 452:665–668. doi:10.1016/j.bbrc.2014.08.132
39. Yamakawa H, Murata M, Suzuki T, Yada H, Ishida H, Aizawa
Y, Adachi T, Kamiya K, Fukuda K (2014) Suppression of Rad
leads to arrhythmogenesis via PKA-mediated phosphorylation
of ryanodine receptor activity in the heart. Biochem Biophys
Res Commun 452:701–707. doi:10.1016/j.bbrc.2014.08.126
40. Miles-Chan JL, Charrière N, Grasser EK, Montani JP, Dul-
loo AG (2015) The blood pressure-elevating effect of Red
Bull energy drink is mimicked by caffeine but through dif-
ferent hemodynamic pathways. Physiol Rep. doi:10.14814/
phy2.12290
Eur J Nutr
1 3
41. Bardou M, Goirand F, Bernard A, Guerard P, Gatinet M, Dev-
illier P, Dumas JP, Morcillo EJ, Rochette L, Dumas M (2002)
Relaxant effects of selective phosphodiesterase inhibitors on
U46619 precontracted human intralobar pulmonary arter-
ies and role of potassium channels. J Cardiovasc Pharmacol
40:153–161
42. Brodmann M, Lischnig U, Lueger A, Pilger E, Stark G (2003)
The effect of caffeine on peripheral vascular resistance in iso-
lated perfused guinea pig hind limbs. J Cardiovasc Pharmacol
42:506–510
43. Sekiguchi F, Miyake Y, Kashimoto T, Sunano S (2002) Unal-
tered caffeine-induced relaxation in the aorta of stroke-prone
spontaneously hypertensive rats (SHRSP). J Smooth Muscle
Res 38:11–22
44. Corsetti G, Pasini E, Assanelli D, Bianchi R (2008) Effects of
acute caffeine administration on NOS and Bax/Bcl2 expres-
sion in the myocardium of rat. Pharmacol Res 57:19–25.
doi:10.1016/j.phrs.2007.07.007
45. El Agaty SM, Seif AA (2015) Cardiovascular effects of long-
term caffeine administration in aged rats. Ir J Med Sci 184:265–
272. doi:10.1007/s11845-014-1098-z
46. Panchal SK, Wong WY, Kauter K, Ward LC, Brown L (2012)
Caffeine attenuates metabolic syndrome in diet-induced obese
rats. Nutrition 28:1055–1062. doi:10.1016/j.nut.2012.02.013
47. Nordestgaard AT, Thomsen M, Nordestgaard BG (2015) Cof-
fee intake and risk of obesity, metabolic syndrome and type
2 diabetes: a Mendelian randomization study. Int J Epidemiol
44:551–565. doi:10.1093/ije/dyv083
48. O’Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan
SC, Lavie CJ (2013) Effects of habitual coffee consumption on
cardiometabolic disease, cardiovascular health, and all-cause
mortality. J Am Coll Cardiol 62:1043–1051. doi:10.1016/j.
jacc.2013.06.035
49. Basaranoglu M, Basaranoglu G, Bugianesi E (2015) Carbo-
hydrate intake and nonalcoholic fatty liver disease: fructose
as a weapon of mass destruction. Hepatobiliary Surg Nutr
4:109–116
50. Loopstra-Masters RC, Liese AD, Haffner SM, Wagenknecht
LE, Hanley AJ (2011) Associations between the intake of caf-
feinated and decaffeinated coffee and measures of insulin sensi-
tivity and beta cell function. Diabetologia 54:320–328
51. Yeh TC, Liu CP, Cheng WH, Chen BR, Lu PJ, Cheng PW,
Ho WY, Sun GC, Liou JC, Tseng CJ (2014) Caffeine intake
improves fructose-induced hypertension and insulin resist-
ance by enhancing central insulin signaling. Hypertension
63:535–541
52. Sinha RA, Farah BL, Singh BK, Siddique MM, Li Y, Wu Y,
Ilkayeva OR, Gooding J, Ching J, Zhou J, Martinez L, Xie S,
Bay BH, Summers SA, Newgard CB, Yen PM (2014) Caffeine
stimulates hepatic lipid metabolism by the autophagy–lysoso-
mal pathway in mice. Hepatology 59:1366–1380
53. Panchal SK, Poudyal H, Waanders J, Brown L (2012) Coffee
extract attenuates changes in cardiovascular and hepatic struc-
ture and function without decreasing obesity in high-carbohy-
drate, high-fat diet-fed male rats. J Nutr 142:690–697
54. Sacramento JF, Ribeiro MJ, Yubero S, Melo BF, Obeso A, Gua-
rino MP, Gonzalez C, Conde SV (2015) Disclosing caffeine
action on insulin sensitivity: effects on rat skeletal muscle. Eur J
Pharm Sci 70:107–116
55. Fronz U, Deten A, Baumann F, Kranz A, Weidlich S, Härtig W,
Nieber K, Boltze J, Wagner DC (2014) Continuous adenosine
A2A receptor antagonism after focal cerebral ischemia in spon-
taneously hypertensive rats. Naunyn Schmiedebergs Arch Phar-
macol 387:165–173
56. Sun L, Tian X, Gou L, Ling X, Wang L, Feng Y, Yin X, Liu
Y (2013) Beneficial synergistic effects of concurrent treatment
with theanine and caffeine against cerebral ischemia–reperfu-
sion injury in rats. Can J Physiol Pharmacol 91:562–569
57. Momoi N, Tinney JP, Keller BB, Tobita K (2012) Maternal
hypoxia and caffeine exposure depress fetal cardiovascular
function during primary organogenesis. J Obstet Gynaecol Res
38:1343–1351
58. Pagnussat N, Almeida AS, Marques DM, Nunes F, Chenet GC,
Botton PH, Mioranzza S, Loss CM, Cunha RA, Porciúncula
LO (2015) Adenosine A receptors are necessary and sufficient
to trigger memory impairment in adult mice. Br J Pharmacol
172:3831–3845
59. Nishida K, Qi XY, Wakili R, Comtois P, Chartier D, Harada M,
Iwasaki YK, Romeo P, Maguy A, Dobrev D, Michael G, Tala-
jic M, Nattel S (2011) Mechanisms of atrial tachyarrhythmias
associated with coronary artery occlusion in a chronic canine
model. Circulation 123:137–146
60. Zhao X, Strong R, Piriyawat P, Palusinski R, Grotta JC, Aro-
nowski J (2010) Caffeinol at the receptor level: anti-ischemic
effect of N-methyl-d-aspartate receptor blockade is potentiated
by caffeine. Stroke 41:363–367
61. Serapiao-Moraes DF, Souza-Mello V, Aguila MB, Mandarim-
de-Lacerda CA, Faria TS (2013) Maternal caffeine administra-
tion leads to adverse effects on adult mice offspring. Eur J Nutr
52:1891–1900. doi:10.1007/s00394-012-0490-6
62. Buscariollo DL, Fang X, Greenwood V, Xue H, Rivkees SA,
Wendler CC (2014) Embryonic caffeine exposure acts via A1
adenosine receptors to alter adult cardiac function and DNA
methylation in mice. PLoS One 9(1):e87547. doi:10.1371/jour-
nal.pone.0087547
63. Momoi N, Tinney JP, Liu LJ, Elshershari H, Hoffmann PJ, Ral-
phe JC, Keller BB, Tobita K (2008) Modest maternal caffeine
exposure affects developing embryonic cardiovascular func-
tion and growth. Am J Physiol Heart Circ Physiol 294:H2248–
H2256. doi:10.1152/ajpheart.91469.2007
64. Yang JN, Chen JF, Fredholm BB (2009) Physiological roles of
A1 and A2A adenosine receptors in regulating heart rate, body
temperature, and locomotion as revealed using knockout mice
and caffeine. Am J Physiol Heart Circ Physiol 296:H1141–
H1149. doi:10.1152/ajpheart.00754.2008
65. Iglesias I, Albasanz JL, Martín M (2014) Effect of caffeine
chronically consumed during pregnancy on adenosine A1
and A2A receptors signaling in both maternal and fetal heart
from wistar rats. J Caffeine Res 4:115–126. doi:10.1089/
jcr.2014.0010
66. Buscariollo DL, Breuer GA, Wendler CC, Rivkees SA (2011)
Caffeine acts via A1 adenosine receptors to disrupt embryonic
cardiac function. PLoS One 6(12):e28296. doi:10.1371/journal.
pone.0028296
67. Chakraborty C, Hsu CH, Wen ZH, Lin CS, Agoramoorthy G
(2011) Effect of Caffeine, norfloxacin and nimesulide on heart-
beat and VEGF expression of zebrafish larvae. J Environ Biol
32:179–183
68. Yeh CH, Liao YF, Chang CY, Tsai JN, Wang YH, Cheng CC,
Wen CC, Chen YH (2012) Caffeine treatment disturbs the angi-
ogenesis of zebrafish embryos. Drug Chem Toxicol 35:361–
365. doi:10.3109/01480545.2011.627864
69. Abdelkader TS, Chang SN, Kim TH, Song J, Kim DS, Park JH
(2013) Exposure time to caffeine affects heartbeat and cell dam-
age-related gene expression of zebrafish Danio rerio embryos
at early developmental stages. J Appl Toxicol 33:1277–1283.
doi:10.1002/jat.2787
70. Mercer JR, Gray K, Figg N, Kumar S, Bennett MR (2012)
The methyl xanthine caffeine inhibits DNA damage signaling
and reactive species and reduces atherosclerosis in ApoE(/)
Mice. Arterioscler Thromb Vasc Biol 32:2461–2467.
doi:10.1161/ATVBAHA.112.251322
Eur J Nutr
1 3
71. Verma R, Huang Z, Deutschman CS, Levy RJ (2009) Caffeine
restores myocardial cytochrome oxidase activity and improves
cardiac function during sepsis. Crit Care Med 37:1397–1402.
doi:10.1097/CCM.0b013e31819cecd6
72. Fang X, Mei W, Barbazuk WB, Rivkees SA, Wendler CC
(2014) Caffeine exposure alters cardiac gene expression in
embryonic cardiomyocytes. Am J Physiol Regul Integr Comp
Physiol 307:R1471–R1487. doi:10.1152/ajpregu.00307.2014
73. Riksen NP, Smits P, Rongen GA (2011) The cardiovascular
effects of methylxanthines. Handb Exp Pharmacol 200:413–
437. doi:10.1007/978-3-642-13443-2_16
74. Noguchi K, Matsuzaki T, Sakanashi M, Hamadate N, Uchida T,
Kina-Tanada M, Kubota H, Nakasone J, Sakanashi M, Ueda S,
Masuzaki H, Ishiuchi S, Ohya Y, Tsutsui M (2015) Effect of caf-
feine contained in a cup of coffee on microvascular function in
healthy subjects. J Pharmacol Sci 127:217–222. doi:10.1016/j.
jphs.2015.01.003
75. Lemery R, Pecarskie A, Bernick J, Williams K, Wells GA
(2015) A prospective placebo controlled randomized study of
caffeine in patients with supraventricular tachycardia under-
going electrophysiologic testing. J Cardiovasc Electrophysiol
26:1–6. doi:10.1111/jce.12504
76. Phan JK, Shah SA (2014) Effect of caffeinated versus noncaf-
feinated energy drinks on central blood pressures. Pharmaco-
therapy 34:555–560. doi:10.1002/phar.1419
77. Astorino TA, Martin BJ, Schachtsiek L, Wong K (2013) Caf-
feine ingestion and intense resistance training minimize postex-
ercise hypotension in normotensive and prehypertensive men.
Res Sports Med 21:52–65. doi:10.1080/15438627.2012.738443
78. Del Coso J, Salinero JJ, González-Millán C, Abián-Vicén
J, Pérez-González B (2012) Dose response effects of a
caffeine-containing energy drink on muscle performance:
a repeated measures design. J Int Soc Sports Nutr 9:21.
doi:10.1186/1550-2783-9-21
79. Farag NH, Vincent AS, McKey BS, Whitsett TL, Lovallo WR
(2005) Hemodynamic mechanisms underlying the incomplete
tolerance to caffeine’s pressor effects. Am J Cardiol 95:1389–
1392. doi:10.1016/j.amjcard.2005.01.093
80. Terai N, Spoerl E, Pillunat LE, Stodtmeister R (2012)
The effect of caffeine on retinal vessel diameter in
young healthy subjects. Acta Ophthalmol 90:e524–e528.
doi:10.1111/j.1755-3768.2012.02486.x
81. Ozkan B, Yüksel N, Anik Y, Altintas O, Demirci A, Cağlar Y
(2008) The effect of caffeine on retrobulbar hemodynamics.
Curr Eye Res 33:804–809. doi:10.1080/02713680802344708
82. Kennedy DO, Haskell CF (2011) cerebral blood flow and
behavioural effects of caffeine in habitual and non-habitual
consumers of caffeine: a near infrared spectroscopy study. Biol
Psychol 86:298–306. doi:10.1016/j.biopsycho.2010.12.010
83. Shechter M, Shalmon G, Scheinowitz M, Koren-Morag N,
Feinberg MS, Harats D, Sela BA, Sharabi Y, Chouraqui P
(2011) Impact of acute caffeine ingestion on endothelial func-
tion in subjects with and without coronary artery disease. Am J
Cardiol 107:1255–1261. doi:10.1016/j.amjcard.2010.12.035
84. Buscemi S, Mattina A, Tranchina MR, Verga S (2011) Acute
effects of coffee on QT interval in healthy subjects. Nutr J
10:15. doi:10.1186/1475-2891-10-15
85. Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN,
Stamatelopoulos KS, Vamvakou G, Lekakis JP, Mavrikakis
ME (2005) Effect of coffee on endothelial function in healthy
subjects: the role of caffeine. Clin Sci 109:55–60. doi:10.1042/
CS20040358
86. Mahmud A, Feely J (2001) Acute effect of caffeine on arte-
rial stiffness and aortic pressure waveform. Hypertension
38:227–231
87. Vlachopoulos C, Hirata K, Stefanadis C, Toutouzas P, O’Rourke
MF (2003) Caffeine increases aortic stiffness in hypertensive
patients. Am J Hypertens 16:63–66
88. Karatzis E, Papaioannou TG, Aznaouridis K, Karatzi K, Sta-
matelopoulos K, Zampelas A, Papamichael C, Lekakis J,
Mavrikakis M (2005) Acute effects of caffeine on blood pres-
sure and wave reflections in healthy subjects: should we con-
sider monitoring central blood pressure? Int J Cardiol 98:425–
430. doi:10.1016/j.ijcard.2003.11.013
89. Vlachopoulos C, Hirata K, O’Rourke MF (2003) Effect of caf-
feine on aortic elastic properties and wave reflection. J Hyper-
tens 21:563–570. doi:10.1097/01.hjh.0000052463.40108.b2
90. Trovato GM, Pirri C, Martines GF, Trovato F, Catalano D (2010)
Coffee, nutritional status, and renal artery resistive index. Renal
Fail 32:1137–1147. doi:10.3109/0886022X.2010.516853
91. Katheria AC, Sauberan JB, Akotia D, Rich W, Durham J, Finer
NN (2015) A pilot randomized controlled trial of early versus
routine caffeine in extremely premature infants. Am J Perinatol
32:879–886. doi:10.1055/s-0034-1543981
92. Hassanein SM, Gad GI, Ismail RI, Diab M (2014) Effect of caf-
feine on preterm infants’ cerebral cortical activity: an observa-
tional study. J Matern Fetal Neonatal Med 14:1–6. doi:10.3109/
14767058.2014.978757
93. Ulanovsky I, Haleluya NS, Blazer S, Weissman A (2014) The
effects of caffeine on heart rate variability in newborns with
apnea of prematurity. J Perinatol 34:620–623. doi:10.1038/
jp.2014.60
94. Nováková Z, Honzíková N, Závodná E, Hrstková H, Václavk-
ová P (2001) Baroreflex sensitivity and body growth parameters
in children and adolescents. Exp Clin Cardiol 6:35–37
95. Monda M, Viggiano A, Vicidomini C, Viggiano A, Iannaccone
T, Tafuri D, De Luca B (2009) Espresso coffee increases para-
sympathetic activity in young, healthy people. Nutr Neurosci
12:43–48. doi:10.1179/147683009X388841
96. Mosqueda-Garcia R, Tseng CJ, Biaggioni I, Robertson RM,
Robertson D (1990) Effects of caffeine on baroreflex activity in
humans. Clin Pharmacol Ther 48:568–574
97. Zimmermann-Viehoff F, Thayer J, Koenig J, Herrmann C,
Weber CS, Deter HC (2015) Short-term effects of espresso cof-
fee on heart rate variability and blood pressure in habitual and
non-habitual coffee consumers—a randomized crossover study.
Nutr Neurosci. doi:10.1179/1476830515Y.0000000018
98. Notarius CF, Floras JS (2012) Caffeine enhances heart rate vari-
ability in middle-aged healthy, but not heart failure subjects. J
Caffeine Res 2:77–82. doi:10.1089/jcr.2012.0010
99. Kammerer M, Jaramillo JA, García A, Calderón JC, Valbuena
LH (2014) Effects of energy drink major bioactive compounds
on the performance of young adults in fitness and cognitive
tests: a randomized controlled trial. J Int Soc Sports Nutr 11:44.
doi:10.1186/s12970-014-0044-9
100. Andrade-Souza VA, Bertuzzi R, de Araujo GG, Bishop D,
Lima-Silva AE (2015) Effects of isolated or combined carbo-
hydrate and caffeine supplementation between 2 daily train-
ing sessions on soccer performance. Appl Physiol Nutr Metab
40:457–463. doi:10.1139/apnm-2014-0268
101. Lopes-Silva JP, Felippe LJ, Silva-Cavalcante MD, Bertuzzi R,
Lima-Silva AE (2014) Caffeine ingestion after rapid weight loss
in judo athletes reduces perceived effort and increases plasma
lactate concentration without improving performance. Nutrients
6:2931–2945. doi:10.3390/nu6072931
102. Duncan MJ, Stanley M, Parkhouse N, Cook K, Smith M (2013)
Acute caffeine ingestion enhances strength performance and
reduces perceived exertion and muscle pain perception during
resistance exercise. Eur J Sports Sci 13:392–399. doi:10.1080/1
7461391.2011.635811
Eur J Nutr
1 3
103. Fernández-Elías VE, Del Coso J, Hamouti N, Ortega JF, Muñoz
G, Muñoz-Guerra J, Mora-Rodríguez R (2015) Ingestion of a
moderately high caffeine dose before exercise increases postex-
ercise energy expenditure. Int J Sport Nutr Exerc Metab 25:46–
53. doi:10.1123/ijsnem.2014-0037
104. Bunsawat K, White DW, Kappus RM, Baynard T (2014) Caf-
feine delays autonomic recovery following acute exercise. Eur J
Prev Cardiol. doi:10.1177/2047487314554867
105. Paton C, Costa V, Guglielmo L (2015) Effects of caffeine chew-
ing gum on race performance and physiology in male and
female cyclists. J Sports Sci 33:1076–1083. doi:10.1080/02640
414.2014.984752
106. Bortolotti H, Altimari LR, Vitor-Costa M, Cyrino ES (2014)
Performance during a 20-km cycling time-trial after caf-
feine ingestion. J Int Soc Sports Nutr 11:45. doi:10.1186/
s12970-014-0045-8
107. Scott AT, O’Leary T, Walker S, Owen R (2015) Improvement
of 2000-m rowing performance with caffeinated carbohy-
drate-gel ingestion. Int J Sports Physiol Perform 10:464–468.
doi:10.1123/ijspp.2014-0210
108. Stadheim HK, Kvamme B, Olsen R, Drevon CA, Ivy JL, Jensen
J (2013) Caffeine increases performance in cross-country dou-
ble-poling time trial exercise. Med Sci Sports Exerc 45:2175–
2183. doi:10.1249/MSS.0b013e3182967948
109. Chrysant SG (2015) Coffee consumption and cardiovas-
cular health. Am J Cardiol 116:818–821. doi:10.1016/j.
amjcard.2015.05.057
110. Ding M, Satija A, Bhupathiraju SN, Hu Y, Sun Q, Han J, Lopez-
Garcia E, Willett W, van Dam RM, Hu FB (2015) Association
of coffee consumption with total and cause-specific mortal-
ity in 3 large prospective cohorts. Circulation 132:2305–2315.
doi:10.1161/CIRCULATIONAHA.115.017341
111. Notara V, Panagiotakos DB, Kouvari M, Tzanoglou D, Kouli G,
Mantas Y, Kogias Y, Stravopodis P, Papanagnou G, Zombolos
S, Babatsikou F, Koutis C, Pitsavos C, GREECS Study Inves-
tigators (2015) The role of coffee consumption on the 10-year
(2004–2014) Acute Coronary Syndrome (ACS) incidence
among cardiac patients: the GREECS observational study. Int J
Food Sci Nutr 66:722–728. doi:10.3109/09637486.2015.10777
95
112. Choi Y, Chang Y, Ryu S, Cho J, Rampal S, Zhang Y, Ahn J, Lima
JA, Shin H, Guallar E (2015) Coffee consumption and coronary
artery calcium in young and middle-aged asymptomatic adults.
Heart 101(9):686–691. doi:10.1136/heartjnl-2014-306663
113. Reis JP, Loria CM, Steffen LM, Zhou X, van Horn L, Sis-
covick DS, Jacobs DR Jr, Carr JJ (2010) Coffee, decaffein-
ated coffee, caffeine, and tea consumption in young adult-
hood and atherosclerosis later in life: the CARDIA study.
Arterioscler Thromb Vasc Biol 30:2059–2066. doi:10.1161/
ATVBAHA.110.208280
114. Wu JN, Ho SC, Zhou C, Ling WH, Chen WQ, Wang CL, Chen
YM (2009) Coffee consumption and risk of coronary heart dis-
eases: a meta-analysis of 21 prospective cohort studies. Int J
Cardiol 137:216–225. doi:10.1016/j.ijcard.2008.06.051
115. Lopez-Garcia E, Rodriguez-Artalejo F, Rexrode KM, Logro-
scino G, Hu FB, van Dam RM (2009) Coffee consumption
and risk of stroke in women. Circulation 119:1116–1123.
doi:10.1161/CIRCULATIONAHA.108.826164
116. Zhang WL, Lopez-Garcia E, Li TY, Hu FB, van Dam RM
(2009) Coffee consumption and risk of cardiovascular events
and all-cause mortality among women with type 2 diabetes.
Diabetologia 52:810–817. doi:10.1007/s00125-009-1311-1
117. Mineharu Y, Koizumi A, Wada Y, Iso H, Watanabe Y, Date C,
Yamamoto A, Kikuchi S, Inaba Y, Toyoshima H, Kondo T,
Tamakoshi A, JACC study Group (2011) Coffee, green tea,
black tea and oolong tea consumption and risk of mortality
from cardiovascular disease in Japanese men and women.
J Epidemiol Community Health 65:230–240. doi:10.1136/
jech.2009.097311
118. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa
J (2013) Caffeine does not increase the risk of atrial fibrillation:
a systematic review and meta-analysis of observational studies.
Heart 99:1383–1389. doi:10.1136/heartjnl-2013-303950
119. Shen J, Johnson VM, Sullivan LM, Jacques PF, Magnani JW,
Lubitz SA, Pandey S, Levy D, Vasan RS, Quatromoni PA, Juny-
ent M, Ordovas JM, Benjamin EJ (2011) Dietary factors and
incident atrial fibrillation: the Framingham Heart Study. Am J
Clin Nutr 93:261–266. doi:10.3945/ajcn.110.001305
120. Cheng M, Hu Z, Lu X, Huang J, Gu D (2014) Caffeine intake
and atrial fibrillation incidence: dose response meta-analysis
of prospective cohort studies. Can J Cardiol 30:448–454.
doi:10.1016/j.cjca.2013.12.026
121. Larsson SC, Drca N, Jensen-Urstad M, Wolk A (2015) Coffee
consumption is not associated with increased risk of atrial fibril-
lation: results from two prospective cohorts and a meta-analy-
sis. BMC Med 13:207. doi:10.1186/s12916-015-0447-8
122. Mostofsky E, Johansen MB, Lundbye-Christensen S, Tjøn-
neland A, Mittleman MA, Overvad K (2015) Risk of atrial
fibrillation associated with coffee intake: findings from the
danish diet, cancer, and health study. Eur J Prev Cardiol.
doi:10.1177/2047487315624524
123. Glatter KA, Myers R, Chiamvimonvat N (2012) Recommen-
dations regarding dietary intake and caffeine and alcohol con-
sumption in patients with cardiac arrhythmias: What do you tell
your patients to do or not to do? Curr Treat Options Cardiovasc
Med 14:529–535. doi:10.1007/s11936-012-0193-6
124. Zuchinali P, Ribeiro PA, Pimentel M, da Rosa PR, Zimer-
man LI, Rohde LE (2015) Effect of caffeine on ventricular
arrhythmia: a systematic review and meta-analysis of experi-
mental and clinical studies. Europace. doi:10.1093/europace/
euv261
125. Saito E, Inoue M, Sawada N, Shimazu T, Yamaji T, Iwasaki M,
Sasazuki S, Noda M, Iso H, Tsugane S (2015) Association of
coffee intake with total and cause-specific mortality in a Japa-
nese Population: the Japan Public Health Center-based Pro-
spective Study. Am J Clin Nutr 101:1029–1037. doi:10.3945/
ajcn.114.104273
126. Malerba S, Turati F, Galeone C, Pelucchi C, Verga F, La Vec-
chia C, Tavani A (2013) A meta-analysis of prospective stud-
ies of coffee consumption and mortality for all causes, cancers
and cardiovascular diseases. Eur J Epidemiol 28:527–539.
doi:10.1007/s10654-013-9834-7
127. Mostofsky E, Rice MS, Levitan EB, Mittleman MA (2012)
Habitual coffee consumption and risk of heart failure: a
dose–response meta-analysis. Circ Heart Fail 5:401–405.
doi:10.1161/CIRCHEARTFAILURE.112.967299
128. Santos PR, Ferrari GSL, Ferrari CKB (2015) Diet, sleep and
metabolic syndrome among a legal Amazon population, Brazil.
Clin Nutr Res 4:41–45. doi:10.7762/cnr.2015.4.1.41
129. Agardh EE, Carlsson S, Ahlbom A, Efendic S, Grill V, Hammar
N, Hilding A, Ostenson CG (2004) Coffee consumption, type
2 diabetes and impaired glucose tolerance in Swedish men and
women. J Intern Med 255:645–652
130. Bhaktha G, Nayak BS, Mayya S, Shantaram M (2015) Rela-
tionship of caffeine with adiponectin and blood sugar levels in
subjects with and without diabetes. J Clin Diagn Res 9:BC01–
BC03. doi:10.7860/JCDR/2015/10587.5371
131. da Silva LA, de Freitas L, Medeiros TE, Osiecki R, Garcia
Michel R, Snak AL, Malfatti CR (2014) Caffeine modifies
blood glucose availability during prolonged low-intensity exer-
cise in individuals with type-2 diabetes. Colomb Med (Cali)
45:72–76
Eur J Nutr
1 3
132. Li MF, Cheung BM (2011) Rise and fall of anti-obesity drugs.
World J Diabetes 2:19–23. doi:10.4239/wjd.v2.i2.19
133. Cheung BMY, Cheung TT, Samaranayake NR (2013)
Safety of antiobesity drugs. Ther Adv Drug Saf 4:171–181.
doi:10.1177/2042098613489721
134. Ciszowski K, Biedron´ W, Gomólka E (2014) Acute caffeine
poisoning resulting in atrial fibrillation after guarana extract
overdose. Prz Lek 71:495–498
135. Rashid A, Hines M, Scherlag BJ, Yamanashi WS, Lovallo
W (2006) The effects of caffeine on the inducibility of atrial
fibrillation. J Electrocardiol 39:421–425. doi:10.1016/j.
jelectrocard.2005.12.007
136. Kinugawa T, Kurita T, Nohara R, Smith ML (2011) A case
of atrial tachycardia sensitive to increased caffeine intake. Int
Heart J 52:398–400
137. Bioh G, Gallagher MM, Prasad U (2013) Survival of a
highly toxic dose of caffeine. BMJ Case Rep. doi:10.1136/
bcr-2012-007454
138. Vukcević NP, Babić G, Segrt Z, Ercegović GV, Janković S,
Aćimović L (2012) Severe acute caffeine poisoning due to
intradermal injections: mesotherapy hazard. Vojnosanit Pregl
69:707–713
139. Clausen T (2010) Hormonal and pharmacological modifica-
tion of plasma potassium homeostasis. Fundam Clin Pharmacol
24:595–605. doi:10.1111/j.1472-8206.2010.00859.x
140. Dufendach KA, Horner JM, Cannon BC, Ackerman MJ (2012)
Congenital type 1 long QT syndrome unmasked by a highly caf-
feinated energy drink. Heart Rhythm 9:285–288. doi:10.1016/j.
hrthm.2011.10.011
141. Cai Y, Kurita-Ochiai T, Hashizume T, Yamamoto M (2013)
Green tea epigallocatechin-3-gallate attenuates Porphyromonas
gingivalis-induced atherosclerosis. Pathog Dis 67:76–83
142. Martína MJ, Pablosa F, Gonzáleza AG, Valdenebrob MS, León-
Camachob M (2001) Fatty acid profiles as discriminant param-
eters for coffee varieties differentiation. Talanta 54:291–297
143. Whayne TF Jr (2015) Coffee: a selected overview of benefi-
cial or harmful effects on the cardiovascular system? Curr Vasc
Pharmacol 13(5):637–648
... Coffee is comprised of many chemicals which produce both protective and detrimental effects on the cardiovascular system [1][2][3]. A high daily intake of caffeine, present in coffee, acutely increases blood pressure, heart rate and arterial stiffness [2], whereas coffee-contained phenolic compounds, trigonelline, quinides and lignans exert long-term impacts of lowering blood pressure, fatty acid and cholesterol synthesis and augmenting antioxidant activity [1]. ...
... Coffee is comprised of many chemicals which produce both protective and detrimental effects on the cardiovascular system [1][2][3]. A high daily intake of caffeine, present in coffee, acutely increases blood pressure, heart rate and arterial stiffness [2], whereas coffee-contained phenolic compounds, trigonelline, quinides and lignans exert long-term impacts of lowering blood pressure, fatty acid and cholesterol synthesis and augmenting antioxidant activity [1]. Conventional observational studies have found that moderate coffee drinking is linked to a lower risk of overall cardiovascular disease [4,5], coronary artery disease [4,6], stroke [7] and heart failure [8]. ...
Article
Full-text available
Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.
... It is known that caffeine has positive effects on mental state as well as reducing the risks of diabetes, Parkinson's and Alzheimer's disease (Kumar et al., 2018). In some recent animal studies, it has been shown that caffeine has a beneficial effect on some parameters which of indicators such as hypertension, endothelial dysfunction, and inflammation that are indicative of cardiovascular diseases (Turnbull et al., 2017;Zulli et al., 2016). ...
Article
Full-text available
Background: Caffeine in the safe dose range has been associated with a reduction in the risk of chronic diseases. There is evidence that caffeine intake has both protective and negative effects on cardiovascular diseases. Aim: This study aimed to investigate caffeine intake in cardiovascular patients. Methods: The study sample was selected from individuals who applied to the Cardiology policlinic of Tekirdağ Namık Kemal University Hospital. A questionnaire was applied using face-to-face interview method to determine their demographic information, nutritional status and anthropometric measurements. Moreover, the nutritional status of the participants was determined by the Food Frequency Questionnaire and the type of cardiovascular disease was determined by a physician. The blood parameters of the sample for the last three months were questioned. The sample has been ninety people of whom fifty cardiovascular diseases (CVDs) were diagnosed and forty were non-diagnosed (ND). Results: The mean age of individuals (n = 90) was 43.2 ± 14.4. The BMI and waist circumference of the CVDs group were statistically significantly higher than the ND group (p < 0.001). While the total caffeine consumption of the ND group was 209.34 ± 143.85 mg/day, consumption of the CVDs group was 209.99 ± 196.76 mg/day. LDL cholesterol and total cholesterol did not show statistically significant difference between the two groups. However, HDL cholesterol was significantly higher in the ND group (p ≤ 0.001). Conclusion: Present results show that daily caffeine consumption may partially affect blood parameters associated with cardiovascular diseases, especially in the presence of coronary artery disease.
... In contrast, a large dose of caffeine causes a negative impact on the human body. Excessive caffeine intake can cause obvious arrhythmias, palpitations, and other cardiovascular diseases (Hartley et al., 2004;Zulli et al., 2016). Caffeine has also been demonstrated to stimulate hypersecretion of stomach glands and increase in stomach acid, leading to the formation of gastric ulcers (Kwiecien and Konturek, 2003;Liszt et al., 2017). ...
Article
Full-text available
Caffeine is being increasingly used in daily life, such as in drinks, cosmetics, and medicine. Caffeine is known as a mild stimulant of the central nervous system, which is also closely related to neurologic disease. However, it is unknown whether caffeine causes hearing loss, and there is great interest in determining the effect of caffeine in cochlear hair cells. First, we explored the difference in auditory brainstem response (ABR), organ of Corti, stria vascularis, and spiral ganglion neurons between the control and caffeine-treated groups of C57BL/6 mice. RNA sequencing was conducted to profile mRNA expression differences in the cochlea of control and caffeine-treated mice. A CCK-8 assay was used to evaluate the approximate concentration of caffeine. Flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting were performed to detect the effects of SGK1 in HEI-OC1 cells and basilar membranes. In vivo research showed that 120 mg/ kg caffeine injection caused hearing loss by damaging the organ of Corti, stria vascularis, and spiral ganglion neurons. RNA-seq results suggested that SGK1 might play a vital role in ototoxicity. To confirm our observations in vitro , we used the HEI-OC1 cell line, a cochlear hair cell-like cell line, to investigate the role of caffeine in hearing loss. The results of flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting showed that caffeine caused autophagy and apoptosis via SGK1 pathway. We verified the interaction between SGK1 and HIF-1α by co-IP. To confirm the role of SGK1 and HIF-1α, GSK650394 was used as an inhibitor of SGK1 and CoCl 2 was used as an inducer of HIF-1α. Western blot analysis suggested that GSK650394 and CoCl 2 relieved the caffeine-induced apoptosis and autophagy. Together, these results indicated that caffeine induces autophagy and apoptosis in auditory hair cells via the SGK1/HIF-1α pathway, suggesting that caffeine may cause hearing loss. Additionally, our findings provided new insights into ototoxic drugs, demonstrating that SGK1 and its downstream pathways may be potential therapeutic targets for hearing research at the molecular level.
... Among the non-polyphenolic components, xanthines and proteic and non-proteic amino acids are the most representative categories. Tea beverages contain caffeine and, in lower amounts, theobromine and theophylline [11]. The total free amino acid content usually accounts for 1-4% of the dry weight of tea leaves, and the types of free amino acids and their proportion in tea are closely related to tea aroma and taste [12,13]. ...
Article
Full-text available
Untargeted (NMR) and targeted (RP-HPLC-PDA-ESI-MSn, RP-HPLC-FD) analytical methodologies were used to determine the bioactive components of 19 tea samples, characterized by different production processes (common tea and GABA tea), degrees of fermentation (green and oolong teas), and harvesting season (autumn and spring). The combination of NMR data and a multivariate statistical approach led to a statistical model able to discriminate between GABA and non-GABA teas and green and oolong teas. Targeted analyses showed that green and GABA green teas had similar polyphenol and caffeine contents, but the GABA level was higher in GABA green teas than in regular green tea samples. GABA oolong teas showed lower contents of polyphenols, caffeine, and amino acids, and a higher content of GABA, in comparison with non-GABA oolong teas. In conclusion, the results of this study suggest that the healthy properties of teas, especially GABA teas, have to be evaluated via comprehensive metabolic profiling rather than only the GABA content.
... Additionally, the affinity of adenosine receptors for caffeine is reported to be different among species which can impact the consistency of studies with different animal model (Momoi et al., 2008). Likewise, caffeine is a nonselective adenosine receptor antagonist which could have different results depending on the pathway inhibited (Zulli et al., 2016). ...
Article
We previously reported a study on 288 broiler (Gallus gallus) chicks who received caffeine in water between days 3 and 42, at levels of 0, 6.25, 12.5, 25, 50 and 100 mg/kg body weight (BW)/day. In the previous report, we found that caffeine caused pulmonary hypertension (PH)-associated mortality in a significant minority (20%–30%) of birds, including right ventricular hypertrophy and ascites. We have also shown a significant upregulation of the serotonin transporter (SERT), troponin T2, adenosine A1 receptor (ADORA1) and phosphodiesterase 5A (PDE5) in chicken suffering from PH. Here, we examine the resistant (survived) chicks from the first study that had not died due to acute heart failure and did not have clinical signs of pulmonary hypertension. Our goal was to determine whether birds who lacked overt signs of disease had subclinical manifestations, including similar changes in gene expression, growth rates and altered systemic haemodynamics. We found that growth was significantly increased by caffeine consumption (p < 0.01) at low doses; however, dosage over 50 mg/BW/d had remarkable adverse effects on growth (p < 0.01). Blood pressure, troponin T2 and PDE5 gene expression were not significantly altered by caffeine administration (p > 0.05). However, SERT gene expression linearly increased with increasing caffeine dosage (p < 0.01). The impact of caffeine on ADORA1 gene expression was dose dependent and nonlinear. In conclusion, despite the significant effects of caffeine on birds’ growth, no significant negative effects of caffeine were observed on the cardiovascular function of resistant chickens. This work provides valuable information for further study on different dosage of caffeine in an animal model.
... This caffeine accumulation has effect on blood pressure values, causing a rapid increase in its value. Regularly intake of high doses of caffeine may cause hypertension [31]. On the market, you can find energy drinks which, in their composition, have only caffeine, taurine, both these ingredients or only glucose. ...
Article
Full-text available
Background. The consumption of energy drinks is increasing, and there are more and more diseases caused by their abuse. Objectives. The aim of the study is to check the relationship between the characteristics of consumption of energy drinks by young adults and the occurrence of high blood pressure in the study group. Material and methods. The diagnostic survey method, estimation method and measurement were used in the research's implementation. The author's questionnaire was used as a tool. as part of the measurements, three measurements of blood pressure in basic conditions were made. a total of 309 students from two high school schools in Rzeszow took part in the study. Results. systolic hypertension amounted to 14.9% and diastolic 18.8% of the students. after consumption of energy drinks, it reached 45.3% of the students surveyed. People who drank energy drinks more often had higher systolic (56.5%) and diastolic hypertension (44.8%) values than in those who did not drink then (p < 0.001). Respondents who drank 3-4 cans (17.4%) and those who drank 5 or more energy drinks (10.9%) most often had systolic hypertension (p < 0.001, Kendall's tau = 0.39). There is a dependence between the level of intensiveness of consumption of energy drinks and the values of arterial blood pressure (p < 0.05). Conclusions. energy drinks were consumed by almost half of the students tested. The study of the relationship between the characteristics of energy drink consumption and the distribution of the blood pressure values of the studied group shows that the frequency, number and period of consumption of energy drinks have a significant impact on the distribution of blood pressure. This is an Open access article distributed under the terms of the Creative Commons attribution-NonCommercial-sharealike 4.0 international (CC BY-NC-sa 4.0). license (http://creativecommons.org/licenses/by-nc-sa/4.0/). martyn J, Chmiel Z. Consumption of energy drinks and assessment of blood pressure values among young adults. Fam Med Prim Care Rev 2019; 21(4): 335-342, doi: https://doi.
... Caffeine Molecular Targets (CMT) were derived from the literature [37,[60][61][62]. Expression of CMT genes was evaluated in the melanoma GDS1375 dataset, from the GEO database. ...
Article
Full-text available
The beneficial effects of coffee on human diseases are well documented, but the molecular mechanisms of its bioactive compounds on cancer are not completely elucidated. This is likely due to the large heterogeneity of coffee preparations and different coffee-based beverages, but also to the choice of experimental models where proliferation, differentiation and immune responses are differently affected. The aim of the present study was to investigate the effects of one of the most interesting bioactive compounds in coffee, i.e., caffeine, using a cellular model of melanoma at a defined differentiation level. A preliminary in silico analysis carried out on public gene-expression databases identified genes potentially involved in caffeine’s effects and suggested some specific molecular targets, including tyrosinase. Proliferation was investigated in vitro on human melanoma initiating cells (MICs) and cytokine expression was measured in conditioned media. Tyrosinase was revealed as a key player in caffeine’s mechanisms of action, suggesting a crucial role in immunomodulation through the reduction in IL-1β, IP-10, MIP-1α, MIP-1β and RANTES secretion onto MICs conditioned media. The potent antiproliferative effects of caffeine on MICs are likely to occur by promoting melanin production and reducing inflammatory signals’ secretion. These data suggest tyrosinase as a key player mediating the effects of caffeine on melanoma.
... Intracellular calcium release from cardiac muscle as a result of calcium-release channels activation has also been proposed as a possible mechanism for methylxanthines' effect: approximative concentrations from 971 to 3884 mg/L are necessary for substantial enhancement in calcium release, much higher than usual coffee or chocolate consumption. 28,29 Thus, this might exert a pivotal role in methylxantines' mechanisms maybe in case of large amount until toxic overdoses or in case of concomitant administration of certain medicaments. Similarly, caffeine also resulted to act as a potassium channel inhibitor at very elevated concentrations. ...
Article
Full-text available
The interrelation between arrhythmias and lifestyle factors is acknowledged. On the one side, there is a recognized interaction between atrial fibrillation and obesity, hypertension, dyslipidemia and type 2 diabetes mellitus. Saturated fats, excessive added salt, tea, coffee and energy drinks are often deleterious in rhythm disorders. The role of others, such as cocoa-rich foods, is less evident: several authors displayed the beneficial effect of the polyphenols content on numerous cardiovascular risk factors, while little is known about the potential link between diet and incident arrhythmias. Arrhythmias’ most frequent risk factors include aging, hypertension, congenital cardiopathy, heart failure, valvulopathy, thyroid diseases and diabetes. Nevertheless numerous arrhythmias are not related to any of these risk factors: in these cases, immunological, functional and even nutritional mechanisms might be involved in dysrhythmias’ genesis. Aim of this narrative review is to analyze the potential adverse effect of cocoa excessive consumption on cardiac rhythm and its mechanisms and to provide state-of-the-art knowledge on this topic.
Chapter
Caffeine is the most consumed psychostimulant drug with free access to all groups of people through a wide range of dietary and medicinal sources. Caffeine consumption and its effects on fecundability, fetal development, and neonatal life have been thoroughly investigated for a long time. In studies with animals, several negative outcomes related to reproduction and development with caffeine exposure are reported. For example, decrease in birth weight, cardiovascular defects, and behavioral sensitizations to illicit drugs have been observed. However, no animal study can predict accurately the caffeine effects in humans. Even though reproductive-aged women and children are indicated to be at risk, subgroups that may require specific advice on moderating their caffeine intake are yet to be established.
Article
Machine learning may improve use of observational data to understand the nutritional epidemiology of cardiovascular disease (CVD) through better modelling of non-linearity, non-additivity, and dietary complexity. Our objective was to develop machine learning prediction models for exploring how nutrients are related to CVD risk and to evaluate their predictive performance. We established a population-based cohort from the Canadian Community Health Survey and measured CVD incidence and mortality from 2004 to 2018 using administrative databases of national hospital discharges and deaths. Predictors included sixty-one nutrition variables and fourteen socioeconomic, demographic, psychological, and behavioural variables. Conditional inference forest models were interpreted and evaluated by permutation feature importance, accumulated local effects, and predictive discrimination and calibration. A total of 12 130 individuals were included in the study. Use of supplements, caffeine, and alcohol were the most important nutrition variables for prediction of CVD. Supplement-use was associated with decreased risk, caffeine was associated with increasing risk, and alcohol had a u-shaped association with risk. The model had an out-of-sample c-statistic of 0.821 (95% confidence interval = 0.801 – 0.842). Exploratory findings included both known and novel associations and predictive performance was competitive, suggesting that further application of machine learning to nutritional epidemiology may help elucidate risks and improve predictive models. Novelty Bullets • Machine learning prediction models were developed for CVD using dietary data • Models were interpreted with interpretable machine learning techniques, revealing diverse associations between diet and CVD • Models achieved comparable or superior predictive performance to existing CVD risk prediction models
Article
Full-text available
Aims The relationship between caffeine consumption and the occurrence of arrhythmias remains controversial. Despite this lack of scientific evidence, counselling to reduce caffeine consumption is still widely advised in clinical practice. We conducted a systematical review and meta-analysis of interventional studies of the caffeine effects on ventricular arrhythmias. Methods and results The search was performed on Pubmed, Embase, and Cochrane database, and terms related to coffee, caffeine, and cardiac arrhythmias were used. Methodological quality was assessed based on The Cochrane Collaboration recommendations and the ARRIVE guidelines. There were 2016 citations retrieved on the initial research. After full-text assessment, seven human and two animal studies were included in the meta-analysis. In animal studies, the main outcome reported was the ventricular fibrillation threshold. We observed a significant mean difference of −2.15 mA (95% CI −3.43 to −0.87; I² 0.0%, P for heterogeneity = 0.37). The main outcome evaluated in human studies was the rate of ventricular premature beats (VPBs). The overall relative risk for occurrence of VPBs in 24 h attributed to caffeine exposure was 1.00 (95% CI 0.94–1.06; I² 13.5%, P for heterogeneity = 0.32). Sensitivity analysis for caffeine dose, different designs, and subject profile was performed and no major differences were observed. Conclusion Our meta-analysis demonstrates that data from human interventional studies do not show a significant effect of caffeine consumption on the occurrence of VBPs. The effects observed in animal studies are most probably the result of very high caffeine doses that are not regularly consumed in a daily basis by humans.
Article
Full-text available
Background: Whether coffee consumption affects the risk of developing atrial fibrillation (AF) remains unclear. We sought to investigate the association between coffee consumption and incidence of AF in two prospective cohorts, and to summarize available evidence using a meta-analysis. Methods: Our study population comprised 41,881 men in the Cohort of Swedish Men and 34,594 women in the Swedish Mammography Cohort who had provided information on coffee consumption in 1997 and were followed up for 12 years. Incident cases of AF were ascertained by linkage with the Swedish Hospital Discharge Register. For the meta-analysis, prospective studies were identified by searching PubMed and Embase through 22 July 2015, and by reviewing the reference lists of retrieved articles. Study-specific relative risks were combined using a random effects model. Results: We ascertained 4,311 and 2,730 incident AF cases in men and women, respectively, in the two cohorts. Coffee consumption was not associated with AF incidence in these cohort studies. The lack of association was confirmed in a meta-analysis, including six cohort studies with a total of 10,406 cases of AF diagnosed among 248,910 individuals. The overall relative risk (95 % confidence interval) of AF was 0.96 (0.84-1.08) for the highest versus lowest category of coffee consumption, and 0.99 (0.94-1.03) per 2 cups/day increment of coffee consumption. Conclusions: We found no evidence that coffee consumption is associated with increased risk of AF.
Article
Full-text available
This investigation reports the effects of chewing caffeinated gum on race performance with trained cyclists. Twenty competitive cyclists completed two 30-km time trials that included a maximal effort 0.2-km sprint each 10-km. Caffeine (~3-4 mg · kg(-1)) or placebo was administered double-blind via chewing gum at the 10-km point following completion of the first sprint. Measures of power output, oxygen uptake, heart rate, lactate and perceived exertion were taken at set intervals during the time trial. Results indicated no substantial differences in any measured variables between caffeine and placebo conditions during the first 20-km of the time trial. Caffeine gum did however lead to substantial enhancements (mean ± 90% confidence limits (CLs)) in mean power during the final 10-km (3.8% ± 2.3%), and sprint power at 30-km (4.0% ± 3.6%). The increases in performance over the final 10-km were associated with small increases in heart rate and blood lactate (effect size of 0.24 and 0.28, respectively). There were large inter-individual variations in the response to caffeine, and apparent gender related differences in sprint performance. Chewing caffeine gum improves mean and sprint performance power in the final 10-km of a 30-km time trial in male and female cyclists most likely through an increase in nervous system activation.
Article
The purine derivative caffeine (1,3,7-trimethylxanthine) is the main alkaloid of coffee and tea. It is used pharmacologically due to its effects on the central nervous, heart and vascular system. Coffee plants were taken to Yemen and placed successfully under cultivation in the 15 th century. Coffee drinking spread rapidly among the whole Islamic world. During the 16 th and 17 th centuries, coffee was introduced into European countries and gained popularity. Many accounts are recorded of its prohibition or approval as a religious, political, or medical potion. The coffeehouses were founded, which became centres of political and cultural influence. With the increasing popularity of the beverage, the propagation of the plant spread rapidly. Coffee cultivation was started in Java in 1671, Ceylon and Surinam followed later Central America and South America, and finally Africa. The history of tea started in 2737 BC in the ancient China. The later developed tea ceremony in Japan is associated with Zen Buddhism. At first in the 17 th century tea arrived in Europe by land and sea. Today tea is cultivated in more than 30 countries and is consumed worldwide. The popular consumption of coffee and tea beverages is also reflected in art, especially in literature.
Article
Background: There have been discrepant findings on whether coffee consumption is associated with the rate of developing atrial fibrillation (AF). Methods and results: We used data on 57,053 participants (27,178 men and 29,875 women) aged 50-64 years in the Danish Diet, Cancer and Health study. All participants provided information on coffee intake via food-frequency questionnaires at baseline. Incident AF was identified using nationwide registries. During a median follow-up of 13.5 years, 3415 AF events occurred. Compared with no intake, coffee consumption was inversely associated with AF incidence, with multivariable-adjusted hazard ratios of 0.93 (95% confidence interval [CI] 0.74-1.15) for more than none to <1 cup/day, 0.88 (95% CI 0.71-1.10) for 1 cup/day, 0.86 (95% CI 0.71-1.04) for 2-3 cups/day, 0.84 (95% CI 0.69-1.02) for 4-5 cups/day, 0.79 (95% CI 0.64-0.98) for 6-7 cups/day and 0.79 (95% CI 0.63-1.00) for >7 cups/day (p-linear trend = 0.02). Conclusions: In this large population-based cohort study, higher levels of coffee consumption were associated with a lower rate of incident AF.
Article
Background: -The association between consumption of caffeinated and decaffeinated coffee and risk of mortality remains inconclusive. Methods and results: -We examined the associations of consumption of total, caffeinated, and decaffeinated coffee with risk of subsequent total and cause-specific mortality among 74,890 women in the Nurses' Health Study (NHS), 93,054 women in the NHS 2, and 40,557 men in the Health Professionals Follow-up Study. Coffee consumption was assessed at baseline using a semi-quantitative food frequency questionnaire. During 4,690,072 person-years of follow-up, 19,524 women and 12,432 men died. Consumption of total, caffeinated, and decaffeinated coffee were non-linearly associated with mortality. Compared to non-drinkers, coffee consumption one to five cups/d was associated with lower risk of mortality, while coffee consumption more than five cups/d was not associated with risk of mortality. However, when restricting to never smokers, compared to non-drinkers, the HRs of mortality were 0.94 (0.89 to 0.99) for ≤ 1 cup/d, 0.92 (0.87 to 0.97) for 1.1-3 cups/d, 0.85 (0.79 to 0.92) for 3.1-5 cups/d, and 0.88 (0.78 to 0.99) for > 5 cups/d (p for non-linearity = 0.32; p for trend < 0.001). Significant inverse associations were observed for caffeinated (p for trend < 0.001) and decaffeinated coffee (p for trend = 0.022). Significant inverse associations were observed between coffee consumption and deaths due to cardiovascular disease, neurological diseases, and suicide. No significant association between coffee consumption and total cancer mortality was found. Conclusions: -Higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was associated with lower risk of total mortality.
Article
The association between long-term coffee consumption and 10-year cardiovascular disease incidence among Acute Coronary Syndrome (ACS) patients was evaluated. From 2003 to 2004, 2172 ACS consecutive patients from six major Greek hospitals were enrolled. During 2013-2014, the 10-year follow-up was performed (88% participation rate) and recurrent fatal or non-fatal ACS was recorded. Baseline coffee consumption (cups/day) was assessed using a semi-quantitative Food Frequency Questionnaire. Multi adjusted analysis revealed that 1-2 cups of coffee/day versus no consumption had an adverse effect on the ACS incidence [odds ratio (OR) = 1.35, 95% confidence interval (CI) 1.01, 1.79]. In subgroup analysis, with hypertension as strata, only the normotensive reached significance. Odds ratios for 1-2 and ≥3 cups relative to no consumption were [OR = 1.66, 95% CI 1.07, 2.60] and [OR = 1.86, 95% CI 1.06, 3.27], respectively, after controlling for potential confounders. Thus, avoidance of coffee may be of high importance to ameliorate disease prognosis among cardiac patients.
Article
Coffee is the most widely consumed beverage worldwide and is only second to water drinking and is consumed by 83% of adults in the United States. The long-held controversy regarding the association of coffee consumption with an increased incidence of cardiovascular diseases (CVDs) and hypertension has been reversed by several recent prospective cohort studies and meta-analyses, which have demonstrated that coffee consumption is not associated with increased incidence of CVDs and hypertension and instead it could have a beneficial effect. To get a better understanding of the effects of coffee consumption on cardiovascular health, a Medline search of the English language literature was conducted from 2010 to early 2015 and 25 pertinent reports with information on the effects of coffee drinking, the incidence of CVDs, and hypertension and its mechanism of action were selected for inclusion in this commentary. These studies have shown either a neutral or beneficial effect of coffee on cardiovascular health. In conclusion, coffee is safe to drink by both normal subjects and by those with preexisting CVDs and hypertension. Copyright © 2015 Elsevier Inc. All rights reserved.