ReviewCaffeine and Cardiac Arrhythmias: A Review of the Evidence
Section snippets
Caffeine and Cardiovascular Disease
Caffeine is a nonselective competitive antagonist of adenosine receptor subtypes A1 and A2A 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)
- et al.
Caffeine and coffee: effects on health and cardiovascular disease
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol
(1994) - et al.
Caffeine intoxication: a case of paroxysmal atrial tachycardia
JACEP
(1976) - et al.
Cardiac arrhythmias following the use of large doses of central nervous system stimulants
Am Heart J
(1952) - et al.
A survey of physician advice about caffeine
J Subst Abuse
(1988) - et al.
Cardiovascular effects of coffee and caffeine
Am J Cardiol
(1984) - et al.
Cardiovascular effects of caffeine in men and women
Am J Cardiol
(2004) - et al.
Caffeinated beverage intake and the risk of heart disease mortality in the elderly: a prospective analysis
Am J Clin Nutr
(2007) - et al.
Acute effects of caffeine ingestion on signal-averaged electrocardiograms
Am Heart J
(1998) - et al.
Effect of caffeine on the ventricular fibrillation threshold in normal dogs and dogs with acute myocardial infarction
Am Heart J
(1972) - et al.
Mechanism of caffeine-induced arrhythmias in canine cardiac Purkinje fibers
Am J Cardiol
(1984)
The effects of caffeine on the inducibility of atrial fibrillation
J Electrocardiol
Caffeine and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study
Am J Clin Nutr
Caffeine consumption and incident atrial fibrillation in women
Am J Clin Nutr
Coffee, tea and VPB
J Chronic Dis
Risk indicators for out-of-hospital cardiac arrest in patients with coronary artery disease
J Clin Epidemiol
Caffeine as a possible cause of ventricular arrhythmias during the healing phase of acute myocardial infarction
Am J Cardiol
The effect of caffeine on cardiac rate, rhythm, and ventricular repolarizationAnalysis of 18 normal subjects and 18 patients with primary ventricular dysrhythmia
Chest
Sex-specific triggers for right ventricular outflow tract tachycardia
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
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2021, NutritionCitation 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].
Caffeine: An evaluation of the safety database
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2019, Principles of Nutrigenetics and Nutrigenomics: Fundamentals of Individualized NutritionRefractory ventricular fibrillation caused by caffeine intoxication
2018, Journal of Cardiology CasesCitation Excerpt :It also inhibits phosphodiesterase with increased accumulation of intracellular cyclic adenosine monophosphate, which enhances the catecholamine-mediated effect [9]. Furthermore, it facilitates calcium release and prevents calcium uptake by the sarcoplasmic reticulum, increasing intracellular calcium concentrations [10]. Elevated calcium concentrations can generate a delayed afterdepolarization, which can lead to triggered arrhythmias.
Review of animal studies on the cardiovascular effects of caffeine
2018, Food and Chemical ToxicologyCitation Excerpt :The following sections provide results for: arrhythmias, heart rate and blood pressure, cholesterol, platelet function, and endothelial cell regeneration. In healthy humans, emerging evidence suggests that coffee consumption is associated with neutral to reduced risk for arrhythmias (Higdon and Frei, 2006; Pelchovitz and Goldberger, 2011). In contrast to the emerging human evidence, some animal studies (Bellet et al., 1972; Ishida et al., 1996; Mehta et al., 1997) have reported caffeine-induced ventricular arrhythmias; although this pro-arrhythmic effect has not been consistently found in all animal studies (Rashid et al., 2006; Ilback et al., 2007).
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.