Caffeine and Cardiac Arrhythmias: A Review of the Evidence

doi:10.1016/j.amjmed.2010.10.017

The American Journal of Medicine

Volume 124, Issue 4, April 2011, Pages 284-289

https://doi.org/10.1016/j.amjmed.2010.10.017 Get rights and content

Abstract

Limited data exist on the safety and physiologic effects of caffeine in patients with known arrhythmias. The studies presented suggest that in most patients with known or suspected arrhythmia, caffeine in moderate doses is well tolerated and there is therefore no reason to restrict ingestion of caffeine. A review of the literature is presented.

Section snippets

Caffeine and Cardiovascular Disease

Caffeine is a nonselective competitive antagonist of adenosine receptor subtypes A₁ and A_2A in concentrations typically consumed by humans. At higher concentrations, caffeine can induce intracellular calcium release and phosphodiesterase inhibition, and at higher doses not typically consumed, can cause gamma-aminobutyric acid inhibition.⁸ It is suggested that 100 mg can increase alertness in humans. Increases in blood pressure are noted at 250 mg, and the lethal dose has been estimated to be 10

Effects of Caffeine on the Human Electrocardiogram

Donnerstein et al²⁶ performed signal-averaged electrocardiograms (ECGs) in 12 subjects given a 5 mg/kg dose of caffeine. Compared with placebo, there was an increase in QRS duration with caffeine ingestion; the small magnitude of this change, approximately 1 ms, is likely clinically insignificant, although it reached statistical significance. P-wave duration and heart rate remained unchanged. Caron et al²⁷ performed a study in which 10 healthy volunteers were given caffeine (400 mg) and

Animal Studies of Caffeine and Arrhythmia

Animal studies allow investigators to probe the link between caffeine and arrhythmia in ways that are impossible using human subjects. Higher-dose caffeine protocols are typically used. Additionally, invasive studies and evaluations of the concomitant effects of ischemia that would be impossible to perform on human subjects are frequently employed. Bellet et al²⁸ performed a pivotal study in 1972 examining the effect of caffeine on the ventricular fibrillation threshold. In this experiment, the

Human Studies of Caffeine and Arrhythmia

Several human studies have been performed to investigate the effect of caffeine on atrial and ventricular arrhythmias (Table).37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 Both physiologic and epidemiologic studies have been performed.

Early human studies were performed using invasive electrophysiology studies. Gould et al⁴⁸ obtained His bundle electrograms in 12 patients with known cardiovascular disease before and after ingestion of a 150-mg dose of caffeine.⁴⁸ There were no changes in

Discussion and Recommendations

With the conflicting data that are available, it is understandable that most physicians are unsure of the advice they can provide about caffeine intake and arrhythmias. A common idea in practice is that caffeine intake should be limited in patients at risk for arrhythmia; however, it is unclear what evidence provides support for this. Although this advice is frequently given to patients,⁷ many of the data that have been reviewed suggest that this advice is unnecessary.

Although animal studies

References (52)

T.M. Chou et al.
Caffeine and coffee: effects on health and cardiovascular disease
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol
(1994)
G.W. Josephson et al.
Caffeine intoxication: a case of paroxysmal atrial tachycardia
JACEP
(1976)
I.L. Bennett et al.
Cardiac arrhythmias following the use of large doses of central nervous system stimulants
Am Heart J
(1952)
J.R. Hughes et al.
A survey of physician advice about caffeine
J Subst Abuse
(1988)
T.L. Whitsett et al.
Cardiovascular effects of coffee and caffeine
Am J Cardiol
(1984)
T.R. Hartley et al.
Cardiovascular effects of caffeine in men and women
Am J Cardiol
(2004)
J.A. Greenberg et al.
Caffeinated beverage intake and the risk of heart disease mortality in the elderly: a prospective analysis
Am J Clin Nutr
(2007)
R.L. Donnerstein et al.
Acute effects of caffeine ingestion on signal-averaged electrocardiograms
Am Heart J
(1998)
S. Bellet et al.
Effect of caffeine on the ventricular fibrillation threshold in normal dogs and dogs with acute myocardial infarction
Am Heart J
(1972)
P. Paspa et al.
Mechanism of caffeine-induced arrhythmias in canine cardiac Purkinje fibers
Am J Cardiol
(1984)

A. Rashid et al.

The effects of caffeine on the inducibility of atrial fibrillation

J Electrocardiol

(2006)

L. Frost et al.

Caffeine and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study

Am J Clin Nutr

(2005)

D. Conen et al.

Caffeine consumption and incident atrial fibrillation in women

Am J Clin Nutr

(2010)

R.J. Prineas et al.

Coffee, tea and VPB

J Chronic Dis

(1980)

J.J. de Vreede-Swagemakers et al.

Risk indicators for out-of-hospital cardiac arrest in patients with coronary artery disease

J Clin Epidemiol

(1999)

M.G. Myers et al.

Caffeine as a possible cause of ventricular arrhythmias during the healing phase of acute myocardial infarction

Am J Cardiol

(1987)

D.J. Sutherland et al.

The effect of caffeine on cardiac rate, rhythm, and ventricular repolarizationAnalysis of 18 normal subjects and 18 patients with primary ventricular dysrhythmia

Chest

(1985)

F.E. Marchlinski et al.

Sex-specific triggers for right ventricular outflow tract tachycardia

Am Heart J

(2000)

W.H. Frishman et al.

Cardiovascular manifestations of substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine

Heart Dis

(2003)

A.J. Berger et al.

Cardiac arrest in a young man following excess consumption of caffeinated “energy drinks.”

Med J Aust

(2009)

P.M. Zimmerman et al.

Caffeine intoxication: a near fatality

Ann Emerg Med

(1985)

B.B. Fredholm et al.

Actions of caffeine in the brain with special reference to factors that contribute to its widespread use

Pharmacol Rev

(1999)

P. Nawrot et al.

Effects of caffeine on human health

Food Addit Contam

(2003)

D.E. Grobbee et al.

Coffee, caffeine, and cardiovascular disease in men

N Engl J Med

(1990)

J.D. Curb et al.

Coffee, caffeine, and serum cholesterol in Japanese men in Hawaii

Am J Epidemiol

(1986)

J.P. Reis et al.

Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in lifeThe CARDIA Study

Arterioscler Thromb Vasc Biol

(2010)

Cited by (64)

Caffeine supplementation in the hospital: Potential role for the treatment of caffeine withdrawal
2021, Food and Chemical Toxicology
Citation Excerpt :
The data also suggest that in most patients, even those with known arrhythmia, caffeine in moderate doses is well tolerated and should not be restricted. However, in patients who claim their arrhythmias are triggered by caffeine intake and whose arrythmias are thought to be driven by catecholamines, it is prudent to recommend abstaining from caffeine use (Pelchovitz and Goldberger, 2011). Caffeine has also been shown to cause an acute decrease in insulin sensitivity in young, non-diabetic adults.
Caffeine use in the population is widespread. Caffeine withdrawal in the hospital setting is an underappreciated syndrome with symptoms including drowsiness, difficulty concentrating, mood disturbances, low motivation, flu-like symptoms, and headache. Withdrawal may occur upon abstinence from chronic daily exposure at doses as low as 100 mg/day and following only 3–7 days of consumption at higher doses. There are limited data investigating how caffeine withdrawal contributes to hospital morbidity. Some studies suggest caffeine withdrawal may contribute to intensive care delirium and that caffeine may promote wakefulness post-anesthesia. Caffeine supplementation has also shown promise in patients at risk of caffeine withdrawal, such as those placed on nil per os (NPO) status, in preventing caffeine withdrawal headache. These data on caffeine supplementation are not entirely consistent, and routine caffeine administration has not been implemented into clinical practice for patients at risk of withdrawal. Notably, caffeine serves a therapeutic role in the hospital for other conditions. Our review demonstrates that caffeine is largely safe in the general population and may be an appropriate therapeutic option for future studies, if administered properly. There is a need for a randomized controlled trial investigating in-hospital caffeine supplementation and the population that this would best serve.
Association of urinary caffeine and caffeine metabolites with cardiovascular disease risk in adults
2021, Nutrition
Citation Excerpt :
Additionally, a number of studies have shown a negative correlation between the risk of Parkinson's disease and coffee consumption at certain doses [11]. Caffeine is associated with a transitory increase in blood pressure among non-habitual coffee drinkers, especially in those with hypertension, but not among habitual coffee drinkers [12,13]. Interestingly, many studies have suggested that the consumption of caffeinated beverages is beneficial for certain cardiovascular endpoints [14,15].
Studies have shown that the consumption of a moderate amount of caffeine is associated with a reduced risk of cardiovascular disease (CVD) and may even be protective against CVD. The purpose of the current study was to evaluate the association between urinary caffeine and its related metabolites and CVD risk in a national representative sample of US adults.
We analyzed cross-sectional data from the US National Health and Nutrition Examination Survey from 2009 and 2010. The associations between the levels of urinary caffeine metabolites and self-reported CVD, including congestive heart failure, coronary heart disease, angina, heart attack, and stroke, were examined separately in men and women using multivariate logistic regression models adjusted for covariates.
In total, 1916 participants (910 men and 1006 women) were included in the analysis. Among women, the odds ratios of CVD in the highest quartiles of 1,3-dimethylxanthine and 1,3,7-trimethylxanthine were 0.33 (95% confidence interval [CI], 0.12–0.92) and 0.35 (95% CI, 0.13–0.93), respectively, compared with the lowest quartiles. Each one-unit (µmol/L) increase in theophylline concentration was associated with a 0.24-mg/dL increase in high-density lipoprotein cholesterol in the fully adjusted model. Among men, no significant association was observed between urinary caffeine metabolites and CVD. Regarding the subtypes of CVD, compared with women in the lowest quartile for 1,3-dimethylxanthine and 1,3,7-trimethylxanthine, the odds of coronary heart disease decreased by 90% (95% CI, −99% to −11%) and 97% (95% CI, −99% to −47%), respectively, in those in the highest quartile.
Urinary 1,3-dimethylxanthine and 1,3,7-trimethylxanthine were significantly and inversely associated with CVDs in women. Additional studies are needed to further confirm the results of this study and explore the underlying mechanisms.<END ABSTRACT>
Caffeine: An evaluation of the safety database
2021, Nutraceuticals: Efficacy, Safety and Toxicity
Caffeine is the one of the most widely consumed food ingredients in the world. Every day, millions of people around the world enjoy beverages and other foods containing caffeine including coffee, tea, soft drinks, and chocolate. It has been estimated that in the order of 2.25 billion cups of coffee, the major source of dietary caffeine, are served every day, and that more than 80% of the world’s population consume at least one caffeine-containing beverage on a daily basis. Global consumption of coffee for the year 2018–19 was estimated in the order of 165.35 million bags (each bag weights approximately 60 kg) or approximately 10 million tons, making coffee the world's most consumed substance (ICA 2018–2019). As a food ingredient, caffeine also has one of the longest histories of human consumption due to its natural occurrence in the beans, leaves, or fruit of more than 60 different plants including coffee, tea, guarana, cola nuts, and cocoa pods.
Caffeine
2019, Principles of Nutrigenetics and Nutrigenomics: Fundamentals of Individualized Nutrition
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. Caffeine is indeed a methylxanthine alkaloid (1,3,7-trimethyl xanthine), and is chemically related to the purine adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It is contained in the seeds, nuts, and leaves of a number of plants native to South America and East Asia. The most abundant source of caffeine is the seed of Coffea plants, belonging to the botanical family of Rubiaceae, which includes about 80 species. The two main species are Coffea arabica (Arabica coffee) and Coffea canephora (Robusta coffee), accounting for 75% and 20% of the global coffee production, respectively. Caffeine-containing drinks, such as coffee, tea, and cola, are very popular. Particularly, coffee, after water, is probably the most frequently used beverage worldwide. Beverages containing caffeine are assumed to relieve or prevent drowsiness and to improve performance. Caffeine is indeed the most widely consumed psychoactive drug, legal and unregulated in nearly all parts of the world. To make these drinks, caffeine is extracted by steeping the plant product in water, a process called infusion, or by steam extraction at higher temperatures.
Refractory ventricular fibrillation caused by caffeine intoxication
2018, Journal of Cardiology Cases
A 30-year-old female with no history of cardiac or systemic disease presented with incessant ventricular fibrillation (VF) after an intake of 12 g of over-the-counter caffeine tablets for a suicidal purpose. Her VF was refractory, and repeated defibrillations were needed to attain a recovery of sinus rhythms. We then performed percutaneous cardiopulmonary support and therapeutic hypothermia to stabilize her circulation and prevent anoxic brain damage, respectively. A blood examination revealed an extremely high concentration of caffeine (172 mg/L). She fully recovered 16 days after her admission. Our findings reveal the potentially lethal arrhythmogenic nature of caffeine.
<Learning objective: Several reports have described lethal cardiac events with caffeine intoxication. However, clinical observations on patients with pure caffeine intoxication are extremely rare. Since the pharmacological actions and proarrhythmic mechanism of caffeine are not fully understood, intensive treatment against refractory arrhythmia may have an impact upon the prognosis of patients with caffeine intoxication.>
Review of animal studies on the cardiovascular effects of caffeine
2018, Food and Chemical Toxicology
To address the safety of caffeine levels in energy drinks, we previously conducted a detailed evaluation of epidemiology studies in humans consuming coffee/caffeine, in which we assessed multiple health effects (unpublished). To further evaluate the effects of caffeine on the cardiovascular system, we turned to animal studies, which often use pure caffeine (not coffee), frequently at higher doses than those typical of human exposure. We identified key scientific studies and reviews in which effects of coffee or caffeine were evaluated in animals by conducting a comprehensive PubMed literature search and analyzing the results. We found that the human equivalent dose (HED) for the no observed adverse effect level (NOAEL) for cardiovascular effects was 260 mg caffeine (2-3 cups of coffee) for a single dose of caffeine for a 70-kg adult, while the lowest observed adverse effect level (LOAEL) was 770 mg (7-8 cups of coffee) for a 70-kg adult. Overall, the doses associated with possible adverse cardiovascular effects were more than either the amount of caffeine consumed over a 24-hour period in two regular energy shots (400 mg/day) or the amount in two extra strength energy shots (460 mg/day).

View all citing articles on Scopus

: Funding: None.

: Conflict of Interest: Jeffrey J. Goldberger, MD, is a consultant for Red Bull GmbH.

: Authorship: Both authors had access to the data and had a key role in writing the manuscript.

View full text

ReviewCaffeine and Cardiac Arrhythmias: A Review of the Evidence

Abstract

Section snippets

Caffeine and Cardiovascular Disease

Effects of Caffeine on the Human Electrocardiogram

Animal Studies of Caffeine and Arrhythmia

Human Studies of Caffeine and Arrhythmia

Discussion and Recommendations

Comp Biochem Physiol C Pharmacol Toxicol Endocrinol

JACEP

Am Heart J

J Subst Abuse

Am J Cardiol

Am J Cardiol

Am J Clin Nutr

Am Heart J

Am Heart J

Am J Cardiol

J Electrocardiol

Am J Clin Nutr

Am J Clin Nutr

J Chronic Dis

J Clin Epidemiol

Am J Cardiol

Chest

Am Heart J

Cardiovascular manifestations of substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine

Heart Dis

Cardiac arrest in a young man following excess consumption of caffeinated “energy drinks.”

Med J Aust

Caffeine intoxication: a near fatality

Ann Emerg Med

Actions of caffeine in the brain with special reference to factors that contribute to its widespread use

Pharmacol Rev

Effects of caffeine on human health

Food Addit Contam

Coffee, caffeine, and cardiovascular disease in men

N Engl J Med

Coffee, caffeine, and serum cholesterol in Japanese men in Hawaii

Am J Epidemiol

Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in lifeThe CARDIA Study

Arterioscler Thromb Vasc Biol

Review
Caffeine and Cardiac Arrhythmias: A Review of the Evidence