Energy drinks

1. Center for Preventive and Genomic Cardiology, Divisions of Cardiology
and Clinical Epidemiology, Department of Medicine, McGill
University Health Centre, Montreal, Canada.
Am J Cardiol 2014;113:168e172

2. INTRODUCTION
• The rapid increase in energy drink (ED) consumption
has stimulated growing public concern with adverse
events related to ED consumption.
• The US Substance Abuse Services and Mental Health
Administration has reported that over a 4-year period
from 2007 to 2011, emergency department visits
related to EDs more than doubled to >20,000 visits
annually.
• Most of the adverse effects and toxicities associated
with EDs have been attributed to the high caffeine
content of EDs.

3. • In addition to the high caffeine content, EDs are
frequently consumed by younger segments of the
population who may be caffeine naive and more prone
to consume large quantities, often mixed with alcohol
and other substances, increasing the risk of adverse
events.
• EDs also contain several other ingredients that may
also increase these risks.
• Although the US FDA recently released a list of adverse
event reports allegedly related to EDs, extremely
limited data (product name, symptoms, and outcome)
regarding the clinical characteristics of these cases and
their ED consumption profile have been made available
to inform clinicians about this emerging health
problem.

4. • Accordingly, we systematically reviewed the
available literature for cases of cardiovascular
(CV) events temporally related to ED
consumption.
• We also included 2 additional cases from our
institution of cardiac arrest after ED
consumption.

5. METHODS
• A systematic review of the Medline and Embase databases
for peer-reviewed articles published between January 1,
1980, and February 1, 2013, containing the search terms
“energy drinks,” “adverse effects,” “myocardial infarction,”
“cardiac arrest,” and “arrhythmia” in various combinations.

6. • From each eligible case, we extracted available data
with regard to age and gender of the case, type of CV
event, brand of ED consumed, estimated caffeine-dose
ingested (as documented in the original report or
calculated based on reported ED consumption and
corresponding caffeine content disclosed on product
labels) within 24 hours of event, co-ingestions with
alcohol or other substances, preexisting CV disease,
and results of CV investigations.
• We considered an estimated acute ingestion of 480 mg
of caffeine within 8 hours as “acute heavy
consumption” because this corresponds to drinking >3
cans or bottles (16 oz) of several popular EDs in a short
time period.

7. • We also characterized “chronic heavy
consumption” as 200 mg/ day of caffeine from
EDs over 1 weeks.
• A serious CV event was defined as a cardiac
arrest, ventricular arrhythmia, or ST-segment
elevation.

8. RESULTS
• Total 17 cases (15 cases from the literature
and 2 cases from our institution).

10. DISCUSSION
• Our case series of 17 cases represents the first systematic review of
the literature of ED-associated acute adverse CV events and adds to
the growing number of adverse events related to EDs reported by
the FDA and by health authorities in Canada.
• Despite the many adverse events reported to regulatory agencies,
few data have been released regarding the clinical characteristics of
these cases to help inform the CV community about these events.
• Our results, although prone to publication bias, show that the
majority of affected cases involved teenagers and young adults, the
largest demographic of ED consumers.
• On the basis of our series, we cannot conclude that any specific
additive or brand appeared to be more frequently involved.

11. • However, we did find that heavy consumption of EDs was
implicated in at least 7 cases, and 5 cases were associated with co
ingestion of alcohol or other drugs.
• Of note, in all 4 reported cases of ST-elevation, the presenting
symptom was severe chest pain.
• We also report that 11 cases presented with serious adverse
events, including cardiac arrest. Of these serious cases, the majority
occurred either with acute heavy consumption of EDs or in
combination with alcohol or other drugs.
• In at least 2 of these cases, EDs may have unmasked an underlying
channelopathy that predisposed the patient to ventricular
arrhythmia.
• Importantly, in the remaining cases, no predisposing cardiac
abnormality to explain the CV event was found (although the
intensity of testing to uncover underlying cardiac abnormalities
varied in each case).

12. • In 1 case of aborted SCD in a 19-year-old man from our
institution (case 10), we performed detailed structural,
functional (including echocardiography, magnetic
resonance imaging, and coronary angiography) and
electrophysiologic testing and could not identify any
cardiac abnormality to explain the cardiac arrest
• There are several potential reasons EDs may predispose to
acute adverse CV events.
• Caffeine, in doses that might be consumed in a beverage
(250 mg), has been shown in normal subjects to increase
levels of circulating catecholamines.
• EDs are also often consumed in an excessive or rapid
manner, which may then lead to a surge in catecholamines.

14. • EDs have also been shown to increase platelet
aggregation and worsen endothelial function, reduce
myocardial blood flow when consumed before
exercise, and significantly increase myocardial oxygen
demand in experimental models, all of which could
result in cardiac ischemia.
• Hypokalemia, which occurs in a caffeine dose-related
manner, could contribute to ventricular arrhythmias
and sudden death.
• EDs may also unmask channelopathies by prolonging
the QT interval or suppressing sodium channel
conduction.

15. • EDs are often coingested with other substances, such
as alcohol and illicit drugs, which may potentiate the
effects of caffeine.
• Chronic alcohol consumption has been shown to
increase the half life of caffeine by up to 72%.
• Caffeine allows people to drink more alcohol without
becoming excessively sedated, resulting in a higher
likelihood of alcohol toxicity, which may include atrial
fibrillation and ventricular arrhythmias.
• Ingredients in EDs other than caffeine, most of which
have not been extensively studied, may also play a role
in contributing to adverse CV events .

17. • Although the prevalence of heavy ED use in our
case series (7 of 17 cases; 41%) is higher than the
reported prevalence of heavy ED use from a
control cohort of young military recruits (137 of
988; 14%), our findings neither imply nor rule out
a causal relation between ED consumption and
CV events.
• Given the increasing popularity of EDs, the
increase in emergency department visits related
to these drinks, the recent FDA report of several
potentially related deaths, and the seriousness of
many of the events in our series, ED-associated
adverse events may represent an emerging public
health problem.

18. • We acknowledge that the large number of
consumers and the few reported events suggests
that the risks related to EDs may, in fact, be small.
• However, because such adverse events are likely
severely underreported, additional epidemiologic
research is required to accurately estimate the
magnitude of risks related to EDs, identify
vulnerable populations (such as youth, patients
with heart disease, and caffeine-naive
consumers), and assess important interactions
with additives in EDs, alcohol, and other co-
ingestions

19. • Perhaps consideration of a nationwide registry
for ED cases may assist in determining the true
significance and the number of events.
• Until additional data become available, the
general public and especially potentially
vulnerable consumers such as youth and young
adults, who make up the largest demographic of
ED consumers, should be advised that caution is
warranted when consuming these drinks (and
consider avoiding them altogether in young
adult/youth or caffeine-naive populations),
specially in large quantities over short periods of
time or mixed with alcohol or other drugs.

20. • The FDA has been actively investigating adverse events related to
the consumption of EDs but has not yet further regulated EDs
because of insufficient data.
• Health Canada, on the recommendations of an expert advisory
panel, has recently reclassified EDs from “natural health product”
to “food product”.
• Among the more stringent requirements, the new regulations
involve limits on the amount of caffeine allowed per serving and
mandatory labeling of caffeine content.
• Although the evidence for harm from EDs remains incomplete,
given the potential public health concern, reductions in caffeine
content per serving to reduce the risk of caffeine intoxication,
improved labeling that fully discloses total caffeine content from all
sources (including natural) and advises against overconsumption,
and warnings that certain vulnerable populations (e.g., youth,
pregnant women, patients with cardiac conditions or caffeine
sensitivity) should avoid EDs is recommended until additional
evidence is available

21. LIMITATIONS
• The rates of co-ingestions with EDs may be underestimated
because toxicology results were not always reported.
• Heavy consumption of EDs were temporally associated with these
events and in many cases no alternative etiology could be
identified, we cannot exclude that some of these cases are rare
spontaneous CV events not directly related to ED consumption.
• we cannot accurately ascertain the prevalence of heavy ED use in a
control group of healthy individuals.
• Although, we provide data from a US military cohort, the low
numbers of cases in our series and potential selection bias limits
our ability to make definitive claims regarding the risks of EDs.

22. CONCLUSION
• Several adverse CV events after consuming ED
have been reported in the literature.
• Although causality cannot be inferred from
our series, physicians should routinely inquire
about ED consumption in relevant cases, and
vulnerable consumers such as youth should be
advised that caution is warranted with heavy
consumption and/or with concomitant alcohol
or drug ingestion