nutrients

Systematic Review
The Dark Side of Energy Drinks: A Comprehensive Review of
Their Impact on the Human Body
Andrea Costantino 1 , Aniello Maiese 1 , Julia Lazzari 1 , Chiara Casula 1 , Emanuela Turillazzi 1 , Paola Frati 2
and Vittorio Fineschi 2, *

1 Institute of Legal Medicine, Department of Surgical, Medical and Molecular Pathology and Critical Care
Medicine, University of Pisa, Via Roma, 55, 56126 Pisa, Italy; [email protected] (A.C.);
[email protected] (A.M.); [email protected] (J.L.); [email protected] (C.C.);
[email protected] (E.T.)
2 Institute of Legal Medicine, Department of Anatomical, Histological, Forensic and Orthopedic Sciences,
Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy; [email protected]
* Correspondence: [email protected]; Tel.: +39-0649912722

Abstract: In recent years, the consumption of energy drinks by young adults and athletes has risen
significantly, but concerns have been raised about the potential health risks associated with excessive
consumption. These concerns include cardiovascular problems, nervous system disorders, and
the potential for addiction. This review aims to examine the reported effects of acute or chronic
abuse of energy drinks on human health. The analysis shows a significant prevalence of adverse
effects, particularly on the cardiovascular and neurovegetative systems. In particular, the analysis
identified nine cases of cardiac arrest, three of which were fatal. The aetiology of these adverse effects
is attributed to the inherent neurostimulant properties of these beverages, of which caffeine is the
predominant component. A comparison of documented effects in humans with experimental studies
in animal models showed an overlap in results. This review highlights the need for greater rigour in
the assessment of sudden cardiac death, particularly in young people, as legal substances such as
energy drinks may be involved. We propose stricter limits on the consumption of these beverages
than for caffeine, based on the evidence found and the data in the literature. This review also calls
for the establishment of regulations governing the consumption of these products in view of their
Citation: Costantino, A.; Maiese, A.;
Lazzari, J.; Casula, C.; Turillazzi, E.;
potential impact on human health.
Frati, P.; Fineschi, V. The Dark Side of
Energy Drinks: A Comprehensive Keywords: energy drink; Red Bull; Monster; taurine; adverse effects; arrhythmia; death
Review of Their Impact on the
Human Body. Nutrients 2023, 15, 3922.
https://doi.org/10.3390/nu15183922
1. Introduction
Academic Editor: Maria Luz
Fernandez The Food and Drug Administration (FDA) defines energy drinks (EDs) as “a class of
products in liquid form that typically contains caffeine, with or without other added ingre-
Received: 30 July 2023 dients.” They typically contain large amounts of caffeine, added sugars, other additives,
Revised: 4 September 2023
and legal stimulants such as guarana, taurine, and L-carnitine. These legal stimulants can
Accepted: 8 September 2023
increase alertness, attention, and energy, as well as increasing blood pressure, heart rate,
Published: 9 September 2023
and breathing. These products are marketed as enhancers of mental acuity and physical
performance [1,2]. Prominent examples of energy drinks include Red Bull, Monster, NOS,
Rockstar, Lucozade, Eastroc Super Drink, Bang Energy, and 5 Hour Energy [3,4], as de-
Copyright: © 2023 by the authors.
scribed in Table 1. Adolescents gravitate towards these beverages to swiftly boost energy
Licensee MDPI, Basel, Switzerland. levels, enhance alertness, and increase scholastic or athletic performance.
This article is an open access article Consequences of this consumption pattern have led to a rising incidence of young
distributed under the terms and individuals seeking medical attention in emergency departments due to an array of ad-
conditions of the Creative Commons verse health outcomes, as documented in results section. Reports underscore that energy
Attribution (CC BY) license (https:// drinks have deleterious effects on a broad spectrum of bodily organs, culminating in mild
creativecommons.org/licenses/by/ adversities such as anxiety, gastrointestinal disturbances, dehydration, nervousness, and
4.0/). tachycardia, along with more severe outcomes like rhabdomyolysis, acute kidney injury

Nutrients 2023, 15, 3922. https://doi.org/10.3390/nu15183922 https://www.mdpi.com/journal/nutrients

Nutrients 2023, 15, 3922 2 of 31

(AKI), ventricular fibrillation, seizures, acute mania, and stroke. Furthermore, instances
linking energy drink consumption to fatalities have been documented.
The rise of the energy drink market, particularly within the younger demographic,
has caused a 70% escalation in caffeine ingestion among caffeine-consuming children and
adolescents from 1977 to 2009 [1]. Data sourced from the National Health and Nutrition
Examination Survey spotlight an average caffeine intake of 61 mg daily for teenagers [5].
While youth caffeine consumption has receded in recent decades, the utilisation of energy
drinks has concurrently surged [5].
These beverages substantially differ in both caffeine content (ranging from 50 to
505 mg per can or bottle) and caffeine concentration (ranging from 2.5 to 171 mg per
28 mL). By comparison, a 170 g cup of brewed coffee contains caffeine concentrations
varying between 77 and 150 mg [3].
As shown in Table 1, energy drinks are composed of a variety of ingredients, including
taurine, ginseng, sugar, guarana, etc.

Table 1. Most popular energy drinks and ingredients per 500 mL [3,4,6].

Energy Drink Caffeine (mg) Sugar (g) Other Ingredients

Taurine (2000 mg), gluconolactone (1200 mg), inositol N/S
Red Bull 160 54
[not specified] and vitamins B3, B5, B6 and B12 N/S
Taurine (2000 mg), gluconolactone N/S, carnitine N/S, inositol and
Monster 160 54 guarana N/S, ginseng (400 mg) and vitamins B2, B3, B6 and B12
(40 mg)
Taurine (2000 mg), carnitine (50 mg), inositol (50 mg) and
Rockstar 160 62 guarana (50 mg), ginseng (50 mg), gingko biloba (300 mg), milk
thistle (40 mg) and vitamins B2, B3, B5, B6 and B12 (50 mg)
Carbonated water, high-fructose corn syrup, concentrated orange
Mountain Dew 72 61 juice, citric acid, natural flavour, sodium benzoate, caffeine, sodium
citrate, gum arabic, erythorbic acid, calcium disodium, yellow 5
Race 160 0 N/S
Taurine (148 mg), inositol (21 mg), ginseng (9.7 mg), vitamin B3
Sting 290 50
(10.2 mg)
Magnus Omnilife N/S N/S N/S
Demon Energy Shot 1600 Taurine (10 g), glucuronolactone (N/S), inositol (N/S), B3 (N/S),
N/S
(sold in 60 mL) (200 mg per 60 mL) guarana (60 mg), B5 (N/S), B6 (N/S), B12 (N/S)
Taurine (N/S), guarana (N/S), B3 (N/S), B6 (N/S), B8 (N/S),
Full Throttle 141 57
carnitine (N/S)
Carbonated water (N/S), citric acid (N/S), sodium gluconate (N/S),
potassium sorbate (N/S), aspartame (N/S), acesulfame K (N/S),
Lucozade 60.5 23
flavourings (N/S), sunset yellow (N/S), ponceau 4R (N/S), ascorbic
acid (N/S).

In particular, taurine and gluconolactone are claimed to be the main components

responsible for the effects attributed to Red Bull. Taurine, a derivative of the amino
acid cysteine, is found abundantly in cardiac and skeletal muscles [7,8]. Its engagement
covers various physiological functions encompassing neuromodulation, cell membrane
stabilisation, and the regulation of intracellular calcium levels [9]. Acknowledged for its
anti-arrhythmic attributes, taurine’s capacity for cation transport regulation contributes
to its effect [10]. It is instrumental in modulating the inwardly rectifying K+ current and
action potential duration in cardiac muscles [11], along with inhibiting the fast Na+ current,
thereby evoking class I antiarrhythmic activity [12]. Its presence in significant concentra-
tions within the brain underscores its pivotal role in neuroprotection and neurotransmission
enhancement [13]. The prospect of taurine in tandem with caffeine bolstering concentra-
Nutrients 2023, 15, 3922 3 of 31

tion, reaction time, and emotional state has sparked investigation, although conclusive
evidence on combinatorial cognitive effects remains elusive. Seidl et al. conducted a
double-blind, placebo-controlled trial administering caffeine, taurine, and glucuronolac-
tone to the experimental group, yielding shorter motor reaction times and higher emotional
well-being scores [14]. While the study implied a positive cognitive impact, GABAergic,
glycinergic, cholinergic, and adrenergic neurotransmitter system interactions were posited,
acknowledging the caffeine factor [15].
Gluconolactone, an outcome of hepatic glucose metabolism, stands as a precursor
for ascorbic acid synthesis. In the 1960s, Japanese researchers [16] directed attention
toward its performance-amplifying attributes. A study demonstrated enhanced swimming
endurance in laboratory rats following the direct intestinal injection of glucuronolactone,
glucose, glycogen, and other agents, with the former group outperforming in two of three
instances. The findings suggest that the equivalent human dose could range from 1 to
2 g of glucuronolactone, compared to 600 mg in a Red Bull can. Detoxifying potential may
contribute to these results, as glucuronolactone supplementation may fortify the body’s
natural defences against carcinogens and tumour promoters [8].
Among the additional ingredients commonly found within energy drinks, carnitine,
guarana, and the vitamin B complex should be mentioned.
Carnitine, comprising several compounds, including L-carnitine, acetyl-L-carnitine,
and propionyl-L-carnitine [17], emerges as a derivative of an amino acid. It occurs nat-
urally in numerous foods, particularly animal-derived foods, and is available in dietary
supplement form. Carnitine synthesis transpires endogenously within the liver, kidneys,
and brain from the amino acids, lysine and methionine [18,19]. This compound plays a
pivotal role in energy production, serving as an indispensable cofactor that facilitates the
transport of long-chain fatty acids into mitochondria for oxidation, leading to adenosine
triphosphate (ATP) energy generation [20,21].
Guarana (Paullinia cupana), a climbing plant native to the Amazon, has historically
served as a stimulant and traditional medicine among Brazil’s indigenous peoples [22].
Guarana seeds notably surpass coffee beans in caffeine content, containing additional xan-
thine alkaloids such as theobromine and theophylline [23]. This botanical additive enhances
the caffeine content and stimulatory attributes of energy drinks (EDs), with its caffeine
content being unlisted on product labels due to its status as an herbal supplement [24].
Comprising eight B vitamins, the vitamin B complex includes thiamine (B1), riboflavin
(B2), niacin (B3), pantothenic acid (B5), pyridoxine hydrochloride (B6), biotin (B7), inositol
(B8), and cyanocobalamin (B12). These vitamins act as coenzymes that are integral to proper
cellular function, particularly in mitochondrial activity and energy production. Hence,
there is some conjecture that B vitamins might increase energy expenditure [25].
The aim of this review is to summarise all evidence on the adverse effects of energy
drink consumption.

2. Materials and Methods

This systematic review follows the Preferred Reporting Items for Systematic Review
(PRISMA) standards [26] (Figure 1). In the context of specific events, such as acute intoxica-
tion or preliminary reports of legal substances, we believe that case reports/studies and
case series involving human subjects with medical reports can provide valuable evidence
for systematic reviews. Therefore, descriptive observational study designs, including case
series, individual case reports, and descriptive cross-sectional studies, were considered for
inclusion in this review. We conducted a comprehensive literature search and critically
appraised the collected studies. An electronic search was conducted using PubMed, Google
Scholar and EBSCO search engines to identify peer-reviewed articles published between
5 January 2009 and 30 April 2023, using the search terms ‘energy drink’, ‘Red Bull’, ‘Mon-
ster’, ‘taurine’, ‘adverse effects’, ‘arrhythmia’, ‘renal failure’, ‘death’, ‘gastrointestinal’ in the
title, abstract and keywords. Internet search engines such as Google were also used to find
relevant information. In addition, the reference lists of all retrieved papers were reviewed
Nutrients 2023, 15, 3922 4 of 31

Nutrients 2023, 15, 3922 9 of 30

and cross-referenced to identify additional relevant literature. Only English-language
papers were included in this study. Data on each case were extracted, including age and
sex of
the the brand
case, case, brand of energy
of energy drinkdrink consumed
consumed (some(some
brandsbrands
werewere unknown),
unknown), mainmain
pathologies, type of event and onset. Two or more independent reviewers screened titlestitles
pathologies, type of event and onset. Two or more independent reviewers screened
and abstracts
and abstractsagainst
againstthetheinclusion
inclusion criteria
criteria forfor
thethe review.
review. TheThe results
results of search
of the the search
and and
study inclusion process were reported in detail in the final systematic
study inclusion process were reported in detail in the final systematic review according to review according
to the
the Preferred
Preferred Reporting
Reporting Items
Items for for Systematic
Systematic Reviews
Reviews andand Meta-analyses
Meta-analyses (PRISMA)
(PRISMA)
guidelines.InInaddition,
guidelines. addition,case–control
case–control studies
studies using
using animal
animal models
models werewere included
included in the
in the
review to
review tocompare
comparedatadatafrom
fromhuman
human case
case reports.
reports. TheThe above
above search
search identified
identified 458 articles,
458 articles,
which were
were screened
screenedtotoexclude
exclude duplicates.
duplicates. The resulting
The reference
resulting listslists
reference werewere
then then
screened
for titles and
screened abstracts,
for titles and leaving 442
abstracts, articles442
leaving forarticles
further for
consideration. Non-English
further consideration. articles
Non-
English articles were
were excluded. Theexcluded.
inclusionThe inclusion
criteria werecriteria were as(1)
as follows: follows:
original(1)research
original research
articles and
articles
(2) caseand (2) case reports/series.
reports/series. These publications
These publications were carefully
were carefully assessed,
assessed, taking taking
into into
account
account the main objectives of the review. Reviews and mini-reviews
the main objectives of the review. Reviews and mini-reviews were not included in the were not included
in the qualitative
qualitative synthesis
synthesis but were butused
weretousedchecktofor
check for missing
missing articles. articles.
After this After this
evaluation,
evaluation, 96 scientific
96 scientific papers remained. papers remained.

Figure
Figure 1.
1.Our
Ourreview
reviewstrategy
strategyfollowing PRISMA
following standards.
PRISMA standards.

3. Results
3. Results
The papers
The papersininour
ourstudy
studywere
were divided
divided in in seven
seven groups:
groups: cardiac
cardiac effects
effects (35 papers),
(35 papers),
gastrointestinal effects
gastrointestinal effects (12
(12papers),
papers),neurologic
neurologiceffects
effects(18(18
papers), renal
papers), effects
renal (7), gynaeco-
effects (7),
logical effects (2
gynaecological papers),
effects autoimmune
(2 papers), and skin
autoimmune andeffects (2 papers).
skin effects TableTables
(2 papers). 1, Table
1, 2,2,3,Table
4, 3,
Table
5, 6, 7 4, Table
show 5, Table
brief 6 and Table
descriptions 7 show
of these seven brief descriptions
groups of studies,ofrespectively.
these seven Furthermore,
groups of studies,
respectively.
we incorporated Furthermore,
case–controlwe incorporated
studies utilizing case–control
animal models studies utilizing animal models
(20 papers).
(20 papers).
Nutrients 2023, 15, 3922 5 of 31

Table 2. The results of our review on cardiac side effects.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathology Onset Adverse Event
Applicable) or Substances
Argano et al., Consumption of 5 cans of Red Bull per day Haemorrhagic aneurysm of the
1 38/M (Male) Red Bull N/A [not available]
2011 [27] 4 days before the onset of symptoms anterior communicating artery
Consumption of 3 cans of 250 mL energy
Avci et al., Death from sudden
1 28/M ED [generic energy drink] N/A drink 5 h before a basketball game. Taking
2013 [28] cardiac arrest.
one ED a day for 7 months
Ingestion of 7–8 cans of a caffeinated Resuscitated cardiac arrest with
Berger et Alford,
1 28/M ED N/A “energy drink” between 8 am and his anteroseptal ST Elevation
2009 [29]
collapse 7 h later Myocardial Infarction (STEMI).
Benjo et al., Symptoms started 1 or 2 h after drinking Left main coronary artery
1 24/M ED + vodka N/A
2012 [30] vodka mixed with an energy drink. acute thrombosis.
Consumption of a 55 mL shot of “Race 2005
Cannon et al., 25/F Race 2005 Energy Blast with Death after ventricular
1 Mitral valve prolapses Energy Blast with Guarana and Ginseng”
2001 [31] (Female) Guarana and Ginseng fibrillation.
before onset.
Ingestion of 2 cans of Red Bull shortly before the
Choudhury et al., Partial right bundle branch
1 53/M Red Bull N/A test, thinking it would improve his
2017 [32] block, hypertension.
performance on the treadmill.
Intake of an unknown amount of a highly
caffeinated drink the day before a race. He
14/M Red Bull + caffeinated drink N/A Arrhythmia
also reported drinking a Red Bull™ energy
Di Rocco et al., drink five days prior to enrolment.
2
2016 [33]
Attention deficit
Ingestion of an unknown quantity of Red Atrial tachycardia/atrial
16/M Red Bull + vodka hyperactivity disorder,
Bull™ mixed with vodka at a party. Fibrillation (AF)
asthma, and allergies
Consumption of at least one 16 oz (476 mL)
Dufendach et al., Idiopathic QT Palpitations and chest pain,
1 13/F ED can of an energy drink (160 mg caffeine)
2012 [34] prolongation associated with a QTc
before onset.
Enriquez et Consumption of three 8 fl oz (263 mL) cans of
2 19/F Monster ED N/A Resuscitated cardiac arrest.
Frankel, 2017 [35] Monster ED within 2 h of onset.
Nutrients 2023, 15, 3922 6 of 31

Table 2. Cont.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathology Onset Adverse Event
Applicable) or Substances
Peripartum
cardiomyopathy,
Enriquez et subcutaneous ICD Ingestion of a can of Red Bull for the first
2 23/F Red Bull Syncope
Frankel, 2017 [35] (Implantable Cardioverter time in her life
Defibrillator), left
ventricular ejection (20%)
Acute anterior ST-segment
Gharacholou Family history of coronary
1 27/M Rockstar energy Ingestion of 4–5 beverages in 12-h. elevation myocardial
et al., 2017 [36] artery disease.
infarction (STEMI)
Hanif et al., Consumption of two energy drinks (111 mg
1 22/M ED N/A Atrial fibrillation
2020 [37] of caffeine and taurine) before onset
Israelit et al., Ingestion about 20 cans of energy drink (XL) Death after ST elevation
1 24/M ED Obesity, hypertension.
2012 [38] over the previous night myocardial infarction (STEMI)
Subacute
Consumption of 4–5 high-energy drinks
54/M Red Bull Obesity, hypertension aortic dissection
(mostly Red Bull) per night.
(De Bakey type I)
Bicuspid aortic valve, Acute
Jonjev et Bala, Consumption of 5–6 high-energy drinks per
3 26/M ED dilation of the aortic dissection
2013 [39] night just after a party
ascending aorta (De Bakey type II)
Acute
Hypertension, myocardial Consumption of high energy drinks
48/M ED aortic dissection
infarction. before onset.
(De Bakey type I)
Kaoukis et al., Ingestion of a small amount of an energy Reverse Takotsubo
1 24/M ED N/A
2012 [40] drink in little cups one after another. Cardiomyopathy
Khan et al., PVCs (Premature Ingestion of 6 red bull energy drinks per day Resuscitated cardiac arrest with
1 27/M Red Bull
2015 [41] ventricular contractions) for over 6–8 months. ventricular fibrillation
Mattioli et al.,
3 22/M ED N/A Consumption of 750 mL of ED Atrial fibrillation (AF)
2018 [42]
Nutrients 2023, 15, 3922 7 of 31

Table 2. Cont.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathology Onset Adverse Event
Applicable) or Substances
23/M ED N/A Consumption of 600 mL of ED Atrial fibrillation (AF)
Mattioli et al.,
3 Consumption of an alcoholic beverage,
2018 [42]
26/M ED + alcohol N/A corresponding to 30 g of alcohol, associated Atrial fibrillation (AF)
with 600 mL of EDs
Ingestion of one can of GNC and one of
Nagajothi et al., GNC Speed Shot and
1 23/F N/A Mountain Dew (containing caffeine) before Supraventricular tachycardia
2008 [43] Mountain Dew soda drink
onset
Consumption of 48 cans of 250 mL ED (XXL,
Osman et al.,
1 32/M ED N/A containing a mixture of caffeine, vodka, and Ventricular fibrillation
2019 [44]
taurine) over the past three days.
Ingestion of one bottle (1000 mL) per week of
Peake et al., a highly caffeinated (caffeine content Atrial fibrillation-related
1 58/m ED N/A
2007 [45] 4.04 mg/mL) commercially available energy cardiomyopathy
drink for 6 months
Consumption of an energy drink for the first
Polat et al., time the night before. About 8 h after Spontaneous coronary artery
1 13/M ED N/A
2013 [46] consuming the energy drink, the patient’s dissection (SCAD)
chest pain started.
Roettlaender Consumption of six cans of a caffeinated Resuscitated cardiac arrest due
1 22/F ED N/A
et al., 2012 [47] energy drink within 4 h to long QT syndrome.
Consumption of a Red Bull energy drink
Rutledge et al., Unknown Brugada
1 24/M Red Bull + vodka (80 mg caffeine and 1000 mg taurine) Resuscitated cardiac arrest.
2012 [48] Syndrome
combined with vodka.
Ingestion of two Monster ED, two to
Sattari et al.,
1 28/M Monster ED N/A three beers, and chewing tobacco for AF
2016 [49]
several months.
Scott et al., Gastro-oesophageal reflux Ingestion of around two to three cans of
1 19/M Red Bull STEMI
2011 [50] disease ‘Red Bull’ daily
Solomin et al., Monster ED + Rockstar Consumption of any kind of energy drink:
1 26/M N/A STEMI
2015 [51] energy eight to ten 473 mL drinks per day
Nutrients 2023, 15, 3922 8 of 31

Table 2. Cont.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathology Onset Adverse Event
Applicable) or Substances
Ten Bos et al., Myocardial
1 45/F Red Bull N/A High consumption of Red Bull energy drinks.
2016 [52] ischaemia
Terlizzi et al., Consumption of four to five cans Reversible postural
1 16/F Red Bull N/A
2008 [53] before onset. tachycardia syndrome
Consumption of at least 70 cc of caffeine
Torbey et al.,
1 43/F Panax ginseng + ED N/A and 4 L of Korean Panax ginseng daily for Long QT syndrome.
2011 [54]
six months.
Ullah et al., Drinking large amounts of caffeinated ED
1 25/M ED N/A Acute coronary syndrome
2018 [55] every day for the past week.
Left main coronary artery
Unal et al., Consumption of 5 bottles of energy drink
1 32/M ED N/A thrombosis and acute anterior
2014 [56] before onset.
myocardial infarction
Usman et Jawaid, Consumption of about 80–100 cans in the
1 16/M “Sting” energy drink N/A Hypertension.
2012 [57] past 2 weeks, an average of 3 cans per day.
Uyanik et al., Ingestion of 8 to 10 cans of energy drinks per
1 24/M ED N/A Cardiomyopathy
2021 [58] day (3.5–4 L/day) in the past 2 weeks
Ward et al., Consumption of 3 Red Bull energy drinks Resuscitated cardiac arrest with
1 45/M Red Bull Tetralogy of Fallot
2014 [59] before onset. ventricular tachycardia.
Ingestion of caffeinated energy drinks
Wilson et al., (3–4 Red Bull 80 mg of caffeine/can and
1 17/M Red Bull + Monster Myopericarditis Coronary artery vasospasm
2012 [60] 2–3 Monster 160 mg of caffeine/can)
before onset.
Zacher et al., Ingestion of 8 cans, mixed with strong liquor, Spontaneous coronary
1 25/M ED + alcohol N/A
2018 [61] before onset. artery dissection
Nutrients 2023, 15, 3922 9 of 31

Table 3. The results of our review on gastrointestinal side effects.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
Acute pancreatitis,
Abdisamad et al., Daily consumption of 3–4 16 oz cans for the
1 46/M ED Diabetes mellitus hepatomegaly,
2019 [62] 2 weeks before onset.
hypertriglyceridemia.
Al Yacoub et al., Small-cell left lung Ingestion of five to six cans of a 16 fluid oz
1 62/F Sugar-free ED Acute hepatitis.
2020 [63] carcinoma. sugar-free ED daily.
Serine Protease Inhibitor
Al-Tamini et al., Regular consumption of Full Throttle and
1 19/M Full Throttle + Red Bull Kazal-type I (SPINK1) Acute pancreatitis
2018 [64] Red Bull.
gene mutation.
Consumption of 3 cans of Red Bull in 4 h to
stay fit for his examinations. The next day, he
Apestegui et al., Biliary tumour;
1 16/M Red Bull separately took 2 tablets (800 mg) of the Acute hepatitis
2011 [65] retransplantation
non-steroidal anti-inflammatory drug
ibuprofen for a headache.
Atrophic gastritis
Garg et al., Red Bull and Regular use of 1–2 ED/day for the
1 34/F N/A (AG) and Gastric intestinal
2020 [66] Monster Energy past 15 years.
metaplasia (GIM).
Harb et al.,
1 50/M ED N/A Ingestion of 4–5 ED before onset. Acute hepatitis.
2016 [67]
Huang et al., Consumption of 3 Rockstar energy drinks per
1 36/M Rockstar energy N/A Acute hepatitis.
2014 [68] day for the past year.
Consumed 5 to 6 energy drinks a day.
Randhawa et al.,
1 29/M ED N/A Consumed 7 16-ounce energy drinks the day Acute pancreatitis.
2022 [69]
before hospital admission.
Acute alcoholic
Shmelev et al., Consumption of Rockstar™ followed by
1 40/M Rockstar energy pancreatitis with Acute pancreatitis.
2015 [70] unexplained episodes of pancreatitis
pseudocyst formation.
Hypertension; benign
Takahashi et al., Drinking half a bottle of energy drink as a
1 76/M ED prostatic hypertrophy; Hypercobalaminemia.
2013 [71] dietary supplement after total gastrectomy.
total gastrectomy
Nutrients 2023, 15, 3922 10 of 31

Table 3. Cont.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
Type 2 diabetes,
Daily consumption of 2–3 16 oz cans Toxic triad syndrome of gastritis,
Uwaifo, 2019 [72] 1 46/M Monster energy nephrectomy,
for 4 months hepatitis and pancreatitis.
hyperuricemia.
Vivekanandarajah
1 22/F ED N/A Daily ingestion of 10 cans of an energy drink. Acute hepatitis.
et al., 2011 [73]

Table 4. The results of our review on neurological side effects.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
Casas-Gomez Ingestion of 20 cans of 250 cc of an ED in 24 h
1 22/M ED N/A Maniac episode.
et al., 2018 [74] because he was worried about flying.
Calabrò et al., Consumed 4 to 6 cans of Red Bull a day for
1 20/M Red Bull N/A Tonic–clonic seizure.
2012 [75] about 5 months before onset of seizures.
Consumption of energy drinks 8 weeks prior to Paranoia, internal
Schizophrenia, paranoid
Cerimele et al., presentation. After drinking his first can of the preoccupations, constricted
1 43/M ED type, and alcohol
2010 [76] drink, he decided to increase his daily affect, and delusional
dependence in remission
consumption to 8 to 10 cans (16 oz per can) a day. religious beliefs.
Increase consumption of filtered coffee from
Energy drink Magnus
2 to 5 cups a day and drink 3 to 4 rations of Delusional ideas of grandeur,
Omnilife products (each
Cruzado et al., the Magnus Omnilife Products energy drink auditory hallucinations, and
1 31/F ration contains 81 mg of N/A
2014 [77] a day. After a few days, up to 10 daily lacked awareness of disease
caffeine, 202 mg of taurine
portions of the energy drink (in addition to manic syndrome.
and 151 mg of glycine).
the five cups of filtered coffee per day).
Regularly consumed one or two energy
drinks a day in order to be more Hallucinations, disorganized
Gorgulu et al.,
1 21/M ED + vodka N/A energetic during his training, sometimes behavior, excitation, persecution,
2014 [78]
drank energy drink in combination with a mystic and grandious delusions.
small amount of vodka.
Nutrients 2023, 15, 3922 11 of 31

Table 4. Cont.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
Aneurysmal subarachnoid
Consumption of five oversized cans haemorrhage complicated by
Grant et al.,
1 44/F Monster Energy drink N/A (16 oz/can) of Monster Energy drink severe catheter-induced
2016 [79]
(totalling 800 mg of caffeine) vasospasm and symptomatic
thromboembolism.
Gupta et al., Consumption multiple energy drinks before Macular neuroretinopathy
1 34/F Multiple ED N/A
2019 [80] onset. (AMN)
Daily use of tobacco, daily
Hernandez- Consumption of 6 ED cans (80 mg caffeine
use of cannabis. A paternal
Huerta et al., 1 18/M ED + cannabis per can) per day during in the last seven days Psychotic disorder
uncle had an unspecified
2017 [81] before onset.
chronic mental illness.
Drink two 24 oz bottles of Rockstar energy
25/M Rockstar energy N/A drink on an empty stomach about 30 to Tonic–clonic seizure
60 min before the seizure.
Ingestion of energy drinks on an empty
Iyadurai et 19/M ED Complex migraine stomach approximately 2 h prior to each Tonic–clonic seizure
Chung 2007 [82] 4 “seizure” episode.
Regular consumption of an
28/F Monster energy + diet pills Migraine Tonic–clonic seizure
energy drink (Monster).
Ingestion of more than 2 24 oz
26/M Monster energy N/A Tonic–clonic seizure
cans before onset.
One episode of low mood
Consumed up to twelve 250 mL cans of Red
Kelsey et al., 12 years prior, and one
1 30/M Red Bull + alcohol Bull per day. Consumed 7 units of alcohol on Agitation and anxiety
2019 [83] deliberate over-dose
the day of arrest.
a year later.
Laiseca et al., Ingestion of energy drinks in the previous
1 8/M Monster energy N/A Rolandic epilepsy
2018 [84] week (500-mL cans of Monster Energy).
Consumed a 60 mL Demon Shot energy drink
Obesity (125 kg), and enjoyed an hour-long “buzz”. Repeating
Menkes, 2011 [85] 1 27/M Demon Shot energy drink Transient psychotic
schizophrenia the dose did not produce the desired effect.
One week later, three shots over 15 min.
Nutrients 2023, 15, 3922 12 of 31

Table 4. Cont.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
Consumption of seven times the
23/M Red Ginseng drink N/A recommended dose of ginseng Manic psychosis
Norelli et Xu, every day for months.
2
2014 [86] Ingestion of Korean red ginseng 3–4 times
Substance-induced
79/M Red Ginseng drink per day, everyday, during the two months Hypomanic psychosis
hypomanic episode
prior the episode
Consumption of three large cans (473 mL
Pagano et al.,
1 48/M ED Hypertension each) of an energy drink over 30–40 min Deep intraretinal haemorrhages
2017 [87]
before onset.
Occasional ‘mood swings’,
alcohol abuse. Family Consumption of 6–8 large cans (550 mL per
Substance-induced mood
Sharma, 2010 [88] 1 32/M Red Bull history: post-partum can) a day during the week preceding his
disorder with maniac features.
depression and hospitalisation.
a case of suicide.
Brain ischemia secondary to
Staikoglou et al., Consumption of 2 L of energy drink during
1 14/M ED N/A dissection of the posterior
2022 [89] the previous 10 h before onset.
cerebral artery (PCA)
Heroin and cocaine abuse,
chronic hepatitis C, severe
Trabulo et al., Ingestion of several cans (about 6) of Red Bull Clonic seizures + tonic clonic
1 28/M Red Bull mitral insufficiency and
2011 [90] together with coffee in the 4 h before onset. seizures
post-infectious
endocarditis.
Chronic schizophrenia,
obesity (142 kg), Consumption of energy drinks for weight
childhood asthma, loss, with daily caffeine consumption varying Hyperosmolar hyperglycaemic
Yartsev et Peisah,
1 35/M Red Bull gastro-oesophageal between 150 and 450 mg/day (between two syndrome with diabetic
2021 [91]
reflux disease, and six 250 mL cans of Red Bull per day, with ketoacidosis.
hypercholesterolaemia and a caffeine concentration of 30 mg/100 mL).
impaired glucose tolerance
Nutrients 2023, 15, 3922 13 of 31

Table 5. The results of our review on renal side effects.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
Al Yacoub et al., Small-cell left lung Consumption of five to six cans of a 16 fluid
1 62/F Sugar-free ED Acute kidney injury (AKI)
2020 [63] carcinoma. oz sugar-free ED daily.
Diabetes mellitus type 2,
hypertension, anxiety,
depression, alcohol abuse,
posttraumatic stress
disorder, chronic
Greene et al., Ingestion of at least 5 to 6 20 oz (590 mL) Red
1 40/M Red Bull obstructive pulmonary AKI
2014 [92] Bull energy drinks daily for several weeks.
disease, obstructive sleep
apnoea, gout, and
hypertriglyceridemia-
induced
pancreatitis.
Consumption of 5000 mL of beer, 400–500 mL
of liquor, and 2000 mL of energy drink
Icin et al., (containing 25 mL/100 mL of caffeine and Hyponatremia followed by
1 27/M ED N/A
2017 [93] taurine, vitamins, sugar, citric acid, and coma
caramel) during a 6-h period before the onset
of symptoms.
Iyer et al., Consumed 2 bottles of Neon Volt and then
1 35/M “Neon Volt” N/A Rhabdomyolysis
2016 [94] started training
The psychiatric history
consisted of a depressive
episode 12 years earlier
and a deliberate overdose Consumption of up to twelve 250 mL cans of
Kelsey et al.,
1 30/M Red Bull + alcohol one year later. On both Red Bull per day, and he also had consumed AKI
2019 [83]
occasions, no referral to 7 units of alcohol on the day of his arrest.
psychiatric services was
made and no treatment
was initiated.
Schoffl et al., Ingestion of 3 L of ED with 1 L of vodka
1 17/M ED + vodka N/A AKI
2011 [95] before onset
Nutrients 2023, 15, 3922 14 of 31

Table 6. The results of our review on gynaecological side effects.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
The infant was born with
West et Thorpe, Consumption of 2 L of “lucozade energy” per
1 23/F Lucozade energy N/A macrosomia because of
2011 [96] day in the last 3 months of pregnancy.
refractory hyperinsulinism
Ingestion of high-energy drinks with
Zekavat et al., Severe menorrhagia because of
1 23/F ED N/A inadequate dietary intake in the
2017 [97] vitamin K deficiency
past 6 months.
Tinawi, 2022 [98] 1 40/M ED N/A Consumption of 355 mL of ED after exercise Severe rhabdomyolysis

Table 7. The results of our review on autoimmune and skin side effects.

Energy Drink (If

References N◦ Cases Age/Sex Major Pathologies Onset Adverse Event
Applicable) or Substances
Gerqari et al., Every time, he drank the same
1 19/M ED N/A Erythema exudative multiforme
2016 [99] taurine-containing energy drink.
Lee et al., 2013 After taking ED containing 1000 mg of
1 33/F ED N/A Erythema, lips angioedema
[100] synthetic taurine.
 We evaluated a total of 86 cases (Figure 2). Most of the patients were young (median
age, 30 years; range, 8 to 62 years). Slightly more men (66 patients, 76.7%) than women
Nutrients 2023, 15, 3922 experienced an acute reaction and 35 of them (40.7%) had pathological remote 15 anamnesis
of 31

positive.
OfWetheevaluated
entire study population, 41 patients (47.7%) had cardiac outcomes, 12 patients
a total of 86 cases (Figure 2). Most of the patients were young (median
(13.9%)
age, 30had gastrointestinal
years; outcomes,
range, 8 to 62 years). 22 (25.7%)
Slightly more menhad (66neurological outcomes,
patients, 76.7%) 7 patients
than women
(8.1%) had renal outcomes, 2 patients (2.3%) had gynaecological outcomes, and
experienced an acute reaction and 35 of them (40.7%) had pathological remote anamnesis 2 patients
(2.3%) had dermatological outcomes.
positive.

Outcomes

Dermatological 2.3

Gynecological 2.3

Renal 8.1

Gastrointestinal 13.9

Neurological 25.7

Cardiac 47.7

0 10 20 30 40 50 60

Percentage on the entire study population

Figure 2. Different outcomes in our review.

Figure 2. Different outcomes in our review.

Specifically,
Of the entirethe cases
study (n = 41) with
population, a cardiac
41 patients adverse
(47.7%) had event
cardiac(Figure 3) were
outcomes, as follows:
12 patients
(13.9%) had gastrointestinal outcomes, 22 (25.7%) had neurological outcomes, 7
17 (41.5%) arrhythmias, 3 (7.3%) deaths, 6 (14.7%) resuscitated cardiac arrests, 1 (2.4%) patients
(8.1%) had
aneurysm, 5 renal outcomes,
(12.2%) arterial2dissections
patients (2.3%) had or
(aortic gynaecological
coronary), 2outcomes, and 2 patients
(4.9%) cardiomyopathies, 5
(2.3%) had dermatological outcomes.
(12.2%) cases of acute coronary syndrome, 1 (2.4%) case of hypertension, and 1 (2.4%) case
Specifically, the cases (n = 41) with a cardiac adverse event (Figure 3) were as follows:
of syncope. The median age of patients with cardiological outcomes was 27.7 years. Only
17 (41.5%) arrhythmias, 3 (7.3%) deaths, 6 (14.7%) resuscitated cardiac arrests, 1 (2.4%)
in aneurysm,
13 cases (31.7%) was a major pathology found (such as idiopathic QT prolongation,
5 (12.2%) arterial dissections (aortic or coronary), 2 (4.9%) cardiomyopathies,
obesity,
5 (12.2%) cases of acutebicuspid
hypertension, aortic valve,
coronary syndrome, dilatation
1 (2.4%) of the ascending
case of hypertension, aorta, and
and 1 (2.4%)
tetralogy of Fallot).The
case of syncope. Only nineage
median (21.9%) women
of patients had
with a cardiological
cardiological outcome.
outcomes was 27.7 years.
Only in 13 cases (31.7%) was a major pathology found (such as idiopathic QT prolongation,
obesity, hypertension, bicuspid aortic valve, dilatation of the ascending aorta, and tetralogy
of Fallot). Only nine (21.9%) women had a cardiological outcome.
A further 22 cases had neurological outcomes (Figure 4): 6 (27.3%) had clonic seizures,
9 (40.9%) experienced a psychotic event, 2 (9.1%) had manifest retinopathies, 1 (4.5%)
had cerebral ischaemia, 1 (4.5%) had aneurysmal subarachnoid haemorrhage, 1 (4.5%)
had agitation and anxiety, 1 (4.5%) had Rolandic epilepsy, 1 (4.5%) had hyperosmolar
hyperglycaemic syndrome with diabetic ketoacidosis. Only 4 cases (18.2%) were women. In
11 cases (50%) there were pre-existing major pathologies (such as schizophrenia, migraine,
obesity, hypertension, substance abuse).
 Cardiac outcomes

Nutrients 2023, 15, 3922 16 of 31

Nutrients 2023, 15, 3922 14 of 30
Syncope 2.4
Hypertension 2.4
Myocardial Ischemia 2.4
Cardiac outcomes
Aneurysm 2.4
Cardiomyopathy 4.9
Death
Syncope 2.4 7.3
Arterial Dissection
Hypertension 2.4 12.2
Acute Myocardial
Coronary Syndrome
Ischemia 2.4 12.2
Resuscitated Cardiac Arrest
Aneurysm 2.4 14.7
Arrhytmia
Cardiomyopathy 4.9 41.5

Death 0 5 7.3
10 15 20 25 30 35 40 45
Arterial Dissection 12.2
Percentage of specific cardiac outcome
Acute Coronary Syndrome 12.2
Figure 3. Cardiac
Resuscitated outcomes
Cardiac in our review.
Arrest 14.7

A further 22Arrhytmia
cases had neurological outcomes (Figure 4): 6 (27.3%) had 41.5clonic
seizures, 9 (40.9%) experienced 0 a psychotic
5 10 event,
15 220 (9.1%)
25had 30
manifest
35 retinopathies,
40 45 1
(4.5%) had cerebral ischaemia, 1 (4.5%) had aneurysmal subarachnoid haemorrhage, 1
(4.5%) had agitation andPercentage
anxiety, of1 specific
(4.5%)cardiac
had outcome
Rolandic epilepsy, 1 (4.5%) had
hyperosmolar hyperglycaemic syndrome with diabetic ketoacidosis. Only 4 cases (18.2%)
were
Figurewomen.
3. CardiacInoutcomes
11 cases (50%)
in our there were pre-existing major pathologies (such as
review.
Figure 3. Cardiac outcomes in our review.
schizophrenia, migraine, obesity, hypertension, substance abuse).
A further 22 cases had neurological outcomes (Figure 4): 6 (27.3%) had clonic
seizures, 9 (40.9%) experienced a psychotic event, 2 (9.1%) had manifest retinopathies, 1
(4.5%) had cerebral ischaemia,Neurologic outcomes
1 (4.5%) had aneurysmal subarachnoid haemorrhage, 1
(4.5%) had agitation and anxiety, 1 (4.5%) had Rolandic epilepsy, 1 (4.5%) had
hyperosmolar hyperglycaemic syndrome with diabetic ketoacidosis. Only 4 cases (18.2%)
were women. In 11 cases (50%) there were pre-existing major pathologies (such as
Hyperosmolar Hyperglycemic Syndrome 4.5
schizophrenia, migraine, obesity, hypertension, substance abuse).
Rolandic Epilepsy 4.5
Agitation and Anxiety
Neurologic4.5outcomes
Aneurysmal Subarachnoid Hemorrhage 4.5
Brain Ischemia 4.5
Hyperosmolar Hyperglycemic Syndrome
Retinopathies 4.5 9.1
Rolandic
ClonicEpilepsy
Seizure 4.5 27.3
Agitation and Anxiety
Psychosis Event 4.5 40.9
Aneurysmal Subarachnoid Hemorrhage
0 5 4.510 15 20 25 30 35 40 45
Brain Ischemia 4.5
Percentage of specific neurologic outcomes
Retinopathies 9.1
Figure 4. Neurologic outcomes in ourSeizure
review.
Figure 4. Neurologic outcomesClonic
in our review. 27.3
Psychosis Event 40.9
There were 12 cases of gastrointestinal problems (Figure 5): 4 (33.5%) had pancre-
atitis, 5 (41.6%) had hepatitis, 1 (8.3%) had0 toxic5 triad
10 syndrome
15 20 25(gastritis,
30 35 hepatitis
40 45 and
pancreatitis), 1 (8.3%) had hypercobalaminaemia and 1 (8.3%) had atrophic gastritis (AG)
Percentage
and gastrointestinal metaplasia of specific
(GIM). Seven neurologic outcomes
cases (58.3%) had major pathologies (such
as diabetes mellitus, small-cell left lung carcinoma, serine protease inhibitor Kazal type I
Figure 4. Neurologic outcomes in our review.
Nutrients 2023, 15, 3922 15 of 30

There were 12 cases of gastrointestinal problems (Figure 5): 4 (33.5%) had

There were 12 cases of gastrointestinal problems (Figure 5): 4 (33.5%) had
pancreatitis, 5 (41.6%) had hepatitis, 1 (8.3%) had toxic triad syndrome (gastritis, hepatitis
Nutrients 2023, 15, 3922 pancreatitis, 5 (41.6%) had hepatitis, 1 (8.3%) had toxic triad syndrome (gastritis, hepatitis
17 of 31
and pancreatitis), 1 (8.3%) had hypercobalaminaemia and 1 (8.3%) had atrophic gastritis
and pancreatitis), 1 (8.3%) had hypercobalaminaemia and 1 (8.3%) had atrophic gastritis
(AG) and gastrointestinal metaplasia (GIM). Seven cases (58.3%) had major pathologies
(AG) and gastrointestinal metaplasia (GIM). Seven cases (58.3%) had major pathologies
(such as diabetes mellitus, small-cell left lung carcinoma, serine protease inhibitor Kazal
(such as diabetes mellitus, small-cell left lung carcinoma, serine protease inhibitor Kazal
(SPINK1) gene mutation,
type I (SPINK1) and acute
gene mutation, andalcoholic pancreatitis).
acute alcoholic Only 3Only
pancreatitis). (25%)3 of the 12
(25%) of cases
the 12
type female.
were I (SPINK1) gene mutation, and acute alcoholic pancreatitis). Only 3 (25%) of the 12
cases were female.
cases were female.

Gastrointestinal outcomes
Gastrointestinal outcomes

Hypercobalaminemia 8.3
Hypercobalaminemia 8.3

Atrophic Gastritis 8.3

Atrophic Gastritis 8.3

Toxi Triad Syndrome 8.3

Toxi Triad Syndrome 8.3

Pancreatitis 33.5
Pancreatitis 33.5

Hepatitis 41.6
Hepatitis 41.6

0 5 10 15 20 25 30 35 40 45
0 5 10 15 20 25 30 35 40 45
Percentage of specific gastrointestinal outcomes
Percentage of specific gastrointestinal outcomes

Figure 5. Gastrointestinal outcomes in our review.

Figure5.5.Gastrointestinal
Figure Gastrointestinaloutcomes
outcomesin
inour
ourreview.
review.

WeWe foundseven
seven casesthat
that developedrenal
renal disease(Figure
(Figure 6):four
four hadAKIAKI (57.1%),
Wefound
found sevencases
cases thatdeveloped
developed renaldisease
disease (Figure6):
6): fourhadhad AKI (57.1%),
(57.1%),
two
two (28.6%) had rhabdomyolysis, one (14.3%) had hyponatraemia followed by a coma.
two (28.6%)
(28.6%) had
had rhabdomyolysis,
rhabdomyolysis, one
one (14.3%)
(14.3%) had
had hyponatraemia
hyponatraemia followed
followed byby aa coma.
coma.
Three ofthese
Three these cases(42.8%)
(42.8%) hadmajor
major comorbidities(such
(such astype
type 2 diabetesmellitus,
mellitus,
Threeofof thesecases
cases (42.8%)had
had majorcomorbidities
comorbidities (such asas type 22 diabetes
diabetes mellitus,
hypertension, alcoholabuse,
hypertension, abuse, PTSD,psychiatric
psychiatric history),and
and onlyoneone ofthe
the sevencases
cases
hypertension, alcohol
alcohol abuse, PTSD,
PTSD, psychiatric history),
history), and only
only oneof of theseven
seven cases
(14.3%)
(14.3%) was female.
(14.3%)was
wasfemale.
female.

Percentage of
Percentage of specific
specific renal
renal outcomes
outcomes

Hyponatremia 14.3
Hyponatremia 14.3
Rhabdomyolysis 28.6
Rhabdomyolysis 28.6
Acute Kidney Injury 57.1
Acute Kidney Injury 57.1
0 10 20 30 40 50 60
0 10 20 30 40 50 60

Percentage of specific renal outcomes

Percentage of specific renal outcomes

Figure 6. Renal outcomes in our review.

Figure6.6.Renal
Figure Renaloutcomes
outcomesin
inour
ourreview.
review.

We also had two cases with gynaecological findings; in one case (50%), we found
macrosomia and in the other (50%) severe menorrhagia. None of them had major pathologies.
 Nutrients 2023, 15, 3922 16 of 30

Nutrients 2023, 15, 3922 18 of 31

We also had two cases with gynaecological findings; in one case (50%), we found
macrosomia and in the other (50%) severe menorrhagia. None of them had major
pathologies.
InInaddition,
addition,two
twocases
casesofoferythema
erythemahavehavebeen
beenreported
reportedininthethescientific
scientificliterature.
literature.One
One
was in a man and the other in a woman. Neither had major
was in a man and the other in a woman. Neither had major pathologies. pathologies.
There
Therewere
wereatatleast
leasttwo
twocases
casesofofdeath.
death.InInone
onecase,
case,there
therewas
wassudden
suddencardiac
cardiacarrest
arrest
and
andininthe
theother
othercase
casedeath
deathdue
duetotoventricular
ventricularfibrillation.
fibrillation.One
Onewas
wasaamanmanand andthetheother
other
was
wasaawoman.
woman.Only Onlyone
oneofofthem
themhad hadaamajor
majorpathology
pathologysuch suchasasmitral
mitralvalve
valveprolapse.
prolapse.
Nine
Nineoutoutofofeight-six
eight-sixpatients
patients(10%)
(10%)drank
drankenergy
energydrinks
drinkswith
withalcohol,
alcohol,one onewith
with
cannabis,
cannabis, one (1%) with diet pills, one (1%) with another caffeinated drink, and five(6%)
one (1%) with diet pills, one (1%) with another caffeinated drink, and five (6%)
took
tookseveral
severalenergy
energydrinks.
drinks.
InIntotal,
total,23
23patients
patients(27%)
(27%)drank
drankRedRedBull
BullED,
ED,99(10%)
(10%)drank
drankMonster
MonsterED,ED,44(5%)
(5%)drank
drank
an energy drink with ginseng, 5 (6%) drank Rockstar ED, 1 (1%) drank
an energy drink with ginseng, 5 (6%) drank Rockstar ED, 1 (1%) drank Lucozade ED, Lucozade ED, 1 (1%)1
drank Sting ED,
(1%) drank 1 (1%)
Sting ED, 1drank
(1%) Neon
drankvolt
NeonED, 1 (1%)
volt ED, drank
1 (1%)Demon Shot ED,
drank Demon 1 (1%)
Shot ED,drank
1 (1%)
Magnus Omnilife, and 1 (1%) drank GNC Speed Shot and Mountain
drank Magnus Omnilife, and 1 (1%) drank GNC Speed Shot and Mountain Dew. Dew. Forty patients
Forty
(46%) drank a generic energy drink (Figure 7).
patients (46%) drank a generic energy drink (Figure 7).

Type of Energy Drink Involved

GNC Speed Shit and Mountain Dew Soda 1
Magnus Omnilife 1
Demon Shot 1
Neon Volt 1
Sting 1
Lucozade 1
ED with Ginseng 5
Rockstar 6
Monster 10
Redbull 27
Generic ED 46

0 5 10 15 20 25 30 35 40 45 50

Percentage of brand of Energy Drink involved

Figure 7. The different types of energy drinks used in our review.

Figure 7. The different types of energy drinks used in our review.

4.4.Discussion
Discussion
Consumptionofofenergy
Consumption energydrinks
drinkshashasincreased
increasedin inrecent
recentyears
yearsfor
forseveral
severalreasons
reasons[2].
[2].
Oneof
One ofthe
the main
main factors is the the aggressive
aggressivemarketing
marketingand andpromotion
promotionofofenergyenergydrinks
drinksby
bybeverage
beveragecompanies,
companies,primarily
primarilytargeting
targeting young
young adults
adults andand adolescents
adolescents [101].
[101]. This
This
marketingoften
marketing oftenfocuses
focuseson onthetheenergizing
energizingand andstimulating
stimulatingeffects
effectsofofenergy
energydrinks
drinksandand
their association with extreme sports and other high-energy activities.
their association with extreme sports and other high-energy activities. Another reason forAnother reason for
theincreasing
the increasingconsumption
consumptionofofenergyenergydrinks
drinksisisthe
thebelief
beliefthat
thatthey
theycan
canimprove
improvecognitive
cognitive
andphysical
and physicalperformance.
performance. Many Many people
people consume
consume energy
energy drinks
drinksto toboost
boosttheir
theirenergy
energy
levels,
levels,improve
improve focus
focusandand
concentration,
concentration,and enhance athletic
and enhance performance.
athletic However,
performance. while
However,
energy drinks may
while energy drinksprovide some short-term
may provide benefitsbenefits
some short-term in thesein areas,
thesetheir long-term
areas, effects
their long-term
on health
effects onand performance
health and performanceremainremain
unclear [102]. [102].
unclear Finally, the increasing
Finally, availability
the increasing of
availability
energy drinks in grocery stores, petrol stations, and other retail outlets
of energy drinks in grocery stores, petrol stations, and other retail outlets has alsohas also contributed
tocontributed
their increased consumption.
to their increased Energy drinks Energy
consumption. are oftendrinks
promoted as a convenient
are often promoted and as a
portable
convenientsource
andofportable
energy source
and stimulation,
of energy making them a popular
and stimulation, makingchoice
them afor peoplechoice
popular who
travel a lot or
for people who have busy
travel lifestyles.
a lot However,
or have busy the easy
lifestyles. availability
However, the easyofavailability
energy drinks also
of energy
means that they are more likely to be consumed in excess, which can increase the risk of
negative side effects.
Nutrients 2023, 15, 3922 19 of 31

The main psychoactive substance in an energy drink is caffeine. They also contain
other ingredients that are thought to increase energy and mental alertness, such as taurine,
guarana, ginseng, vitamins, and others [101].
The effects of these drinks on the human body are not fully understood, which is why
research into their negative effects has increased.

4.1. Effects on the Cardiovascular System

Effects on the cardiovascular system appear to be the most studied of all the side
effects of these substances, due to their potentially fatal properties. The European Cardiac
Arrhythmia Society (ECAS) has undertaken a critical review of the reported data on energy
drinks, in particular on cardiovascular events and their possible cause–effect relationship, in
order to provide recommendations on the safer use of these drinks [103]. High consumption
of these energy drinks is associated with an acute haemodynamic and adrenergic state [104],
which increases glucose and norepinephrine levels. Supraventricular and ventricular
arrhythmias, coronary vasospasm, ischaemia/myocardial infarction, atrial fibrillation,
syncope, aortic dissection, cardiomyopathy, cardiac arrest, and sudden cardiac death have
been reported in young and otherwise healthy patients [105–108] (Figure 8). We have
found that the risk of cardiovascular outcomes is increased in individuals with pre-existing
structural or inherited heart disease. In addition, the consumption of these beverages
may lead to the diagnosis of heart disease of which the subjects were previously unaware.
Adverse cardiovascular effects have also been found with the use of other substances,
such as alcohol. Caffeine [109] has direct chronotropic and positive inotropic effects on
the heart. At low concentrations, these effects appear to be due to increased release of
catecholamines (epinephrine and norepinephrine) as a result of antagonism of presynaptic
receptors for adenosine. At higher concentrations (>10 µM), caffeine can directly increase
calcium uptake by increasing cyclic AMP due to inhibition of phosphodiesterase. At
very high concentrations (>100 µM) it reduces calcium sequestration by the sarcoplasmic
reticulum. At high doses, it induces vascular smooth muscle contraction, except in cerebral
vessels. Habitual coffee consumption generally increases peripheral vascular resistance
and blood pressure slightly, probably through the release of catecholamines. Systolic and
diastolic blood pressure increases by 0.8 mmHg and 0.5 mmHg, respectively, per 100 mg of
caffeine. In particularly sensitive individuals, the consumption of a few cups of coffee may
cause cardiac arrhythmias, but in most people, parenteral administration of high doses
of coffee causes only tachycardia. The stimulation of cardiac RgR2 ryanodine receptors
and concomitant inhibition of phosphodiesterase cause a cardio-stimulatory effect, but
at high doses, this can cause arrhythmias, tachycardia, and ventricular fibrillation. The
ability of caffeine to induce arrhythmias in individuals with atrioventricular conduction
disorders or ectopic foci has not been conclusively demonstrated [110]. The inotropic
effect of caffeine is enhanced by the positive chronotropic effect of guarana, which contains
caffeine, theobromine, and teofiline.
As mentioned above, nine cases of cardiac arrest associated with the consumption of
high doses of these stimulants have been reported in literature. The primary triggering
mechanism is the occurrence of cardiac arrhythmias such as ventricular fibrillation or the
unmasking of previously unrecognised channelopathies. Of the nine cases mentioned
above, six required intensive cardiopulmonary resuscitation and no cardiac abnormalities
were found in these patients during follow-up visits in the following months, while the
other three individuals died (sudden cardiac arrest, STEMI, ventricular fibrillation), but we
couldn’t find any available information on their autopsy data in the literature.

4.2. Effects on the Neurological System

The consumption of energy drinks containing caffeine and other substances may also
have effects on the central nervous system, such as seizures, cerebral vasculopathy and
manic psychosis. Studies have shown that these ingredients overstimulate the adrenergic
Nutrients 2023, 15, 3922 20 of 31

Nutrients 2023, 15, 3922 1

system, leading to hyperglycaemia, hypokalemia, leukocytosis, and metabolic acidosis.
The psychostimulant effects of caffeine are evident at low doses.

Figureeffects
Figure 8. Pathological 8. Pathological
of energyeffects
drinksofonenergy drinks
cardiac tissue.on cardiac tissue.

Caffeine enhances
4.2. Effectsdopamine-related
on the Neurological behaviour
System by inhibiting adenosine A2A receptors
and increasing transmission via dopamine
The consumption of energy D2drinks
receptors. Lorist caffeine
containing and Tops and[111] used
other an
substances ma
echoencephalograph (EEG) to highlight the alpha wavelength of the brain (alpha
have effects on the central nervous system, such as seizures, cerebral vasculopath power).
They found that caffeine intake increased left frontal activation compared to the right,
manic psychosis. Studies have shown that these ingredients overstimulate the adre
suggesting that dopamine function may be linked to fatigue, with caffeine reducing fa-
system, leading to hyperglycaemia, hypokalemia, leukocytosis, and metabolic aci
tigue. Doses of less than 500 mg result in increased alertness, increased speed of thoughts
The psychostimulant effects of caffeine are evident at low doses.
and speech, decreased fatigue and reduced sleep. Higher doses may cause restlessness,
Caffeine enhances dopamine-related behaviour by inhibiting adenosine
anxiety, insomnia, tremors, and, in cases of acute toxicity, seizures that do not respond
receptors and increasing transmission via dopamine D2 receptors. Lorist and Tops
to antiepileptic drugs [112] (Figure 9). The ingestion of caffeine at very high (pharma-
used an echoencephalograph (EEG) to highlight the alpha wavelength of the brain (
cological) doses has been associated with the possible occurrence of seizures. In animal
power). They found that caffeine intake increased left frontal activation compared
models, intraperitoneal administration of caffeine produces convulsions associated with
right, suggesting that dopamine function may be linked to fatigue, with caffeine red
electroencephalography. In humans, seizures have been reported after the overdose or
fatigue. Doses of less than 500 mg result in increased alertness, increased spe
ingestion of drug preparations. The consumption of energy drinks has been associated
thoughts
with the occurrence and speech,
of seizures, both indecreased
patients with fatigue
known andepilepsy
reduced andsleep. Higher
in those withoutdoses may
restlessness,
a history of epilepsy anxiety,
[113]. This mayinsomnia,
be due to the tremors, and, in content
high caffeine cases ofof acute
energytoxicity,
drinks. seizures th
At normal average doses of caffeine in humans, caffeine acts as an adenosine receptor at very
not respond to antiepileptic drugs [112] (Figure 9). The ingestion of caffeine
antagonist with(pharmacological)
equal affinity fordosesA1 andhas A2A
been associated
receptors. with
When theadministered
possible occurrence
acutely, of seizu
caffeine acts dominantly on A1 receptors (as ambient adenosine activates them). The convu
animal models, intraperitoneal administration of caffeine produces
chronic use of associated withtoelectroencephalography.
caffeine leads the tolerance of A1 receptors. In humans,
Caffeine seizures
then hashave been reported aft
negligible
overdose or ingestion of drug preparations. The consumption
effects on the A1 receptor and dominant effects on A2A receptors. The endocannabinoids, of energy drinks has
associated with the occurrence of seizures, both in patients
endogenous ligands of the cannabinoid receptors, are synthesised as needed in response with known epilepsy a
those without a history of epilepsy [113]. This may be
to increased neuronal excitation and activate the presynaptic CB1 receptor, reduce thedue to the high caffeine cont
energy drinks.
levels of cyclic AMP (cAMP) released and decrease neurotransmitter release. Caffeine
At normal
increases neurotransmitter average
release by doses
removingof caffeine in humans,
the inhibitory caffeine
control acts as an adenosine
of acetylcholine in rec
the hippocampusantagonist with equal
and prefrontal affinity
cortex, for A1 the
regulating andopening
A2A receptors.
of potassium Whenchannels
administered ac
mediated by A1 caffeine actsand
receptors dominantly
increasingon theA1 receptors
firing rate of(as
A2A ambient
receptors adenosine activates them
in the striatum
chronic use of caffeine leads to the tolerance of A1 receptors.
dendritic spines of neurons. This inhibits glutamatergic thalamocortical neurons by induc- Caffeine then has neg
effects on the A1 receptor and dominant effects on A2A
ing cell activation and stimulating the adenylate cyclase pathway. Caffeine blocks A2A receptors. The endocannabi
endogenous
receptors and reduces ligands of the
the stimulatory cannabinoid
effects of adenosine receptors,
on cAMP.are synthesised
Caffeine canas needed in res
reduce
to increased
the inhibition on neuronaltransmission
striatal dopamine excitation and by activate
reducingthe thepresynaptic CB1 receptor,
activity of striatal neu- redu
levels
rons and causing the of cyclic AMPof(cAMP)
disinhibition released and
thalamo-cortical decrease
projection neurotransmitter
neurons. The activation release. Ca
increases
of A2A receptors neurotransmitter
leads to cAMP production, release
andby removing
the activation theofinhibitory
D2 receptors control of acetylchol
reduces
the hippocampus and prefrontal cortex, regulating the opening of potassium cha
mediated by A1 receptors and increasing the firing rate of A2A receptors in the str
dendritic spines of neurons. This inhibits glutamatergic thalamocortical neuro
 activation of A2A receptors leads to cAMP production, and the activation of D2 recep
reduces cAMP production and causes an inverse regulation of the activity of cA
dependent protein kinase (PKA) [114]. As caffeine mimics the effect of dopamin
striatopallidal neurons, it causes a progressive sensitisation of cannabinoid CB1 recep
which control GABAergic inhibitory postsynaptic currents (IPSCs) [115]. The caff
Nutrients 2023, 15, 3922 21 of 31
blockade of A2A receptors reduces the activation of cAMP-PKA pathways, resultin
increased glutamate release, the activation of mGlu5 metabotropic receptors,
endocannabinoid release. The blockade of adenosine A2A receptors in the striatum
cAMP production beenand causes
linked to theanpsychoactive
inverse regulation of the
properties activityThere
of caffeine. of cAMP-dependent
is also evidence that a sp
protein kinase genetic
(PKA) [114].
polymorphism of the adenosine A2A receptoroninfluences
As caffeine mimics the effect of dopamine striatopallidal
habitual caff
neurons, it causes a progressive sensitisation
consumption in humans [116]. of cannabinoid CB1 receptors, which control
GABAergic inhibitory postsynaptic
Richard and Smith currents (IPSCs)reviewed
[117] recently [115]. The
thecaffeine
literatureblockade of A2Amental h
on the chronic
receptors reduces the activation of cAMP-PKA pathways, resulting in increased glutamate
effects of energy drinks. They concluded that while the acute effects of energy drink
release, the activation of mGlu5
mood appear metabotropic
to be receptors,
positive, chronic and endocannabinoid
consumption is associatedrelease. The anxiety
with stress,
blockade of adenosine A2A receptors in the striatum has been linked to the psychoactive
depression. Taurine is a molecule that crosses the blood–brain barrier and binds to G
properties of caffeine. There
receptors. is also
It can mimicevidence that of
the effects a specific
GABA andgenetic polymorphism
glycine, resulting inofantheanticonvu
adenosine A2Aeffectreceptor influences habitual caffeine consumption in
that has a stabilising effect on membranes inside and outsidehumans [116].
the cell.

Figureeffects
Figure 9. Pathological 9. Pathological
of energyeffects
drinksofonenergy drinks
cerebral on cerebral tissues.
tissues.

Richard and 4.3.Smith

Effects[117] recently
on the reviewedand
Gastrointestinal theRenal
literature on the chronic mental health
System
effects of energy drinks. They concluded that while the acute
These drinks can also lead to the development effects of energy drinks
of gastrointestinal andon
renal disor
mood appear to be positive, chronic consumption is associated with stress, anxiety,
Some authors describe cases of acute hepatitis, acute pancreatitis, and renal and failure
depression. Taurine
acute iskidney
a molecule
injurythat crosses
(AKI). the blood–brain
As mentioned above,barrier and binds
all energy drinkstocontain
GABAhigh dos
receptors. It can mimic the effects of GABA and glycine, resulting in an anticonvulsant
caffeine, taurine, sugar, and vitamins. A megadose of vitamin B3 (niacin) is assoc
effect that has awith
stabilising effect on Niacin
hepatotoxicity. membranes inside andisoutside
hepatotoxicity thought thetocell.
be a dose-dependent, dir
toxic response. Vitamin B3 is associated with cellular metabolism and flushing
4.3. Effects on the Gastrointestinal and Renal System
hepatotoxicity at pharmacological doses. Hepatotoxicity manifests as a mild elevatio
These drinks can
liver also lead(ALT/AST),
enzymes to the development of gastrointestinal
hepatic steatosis, and renaland,
hepatic necrosis, disorders.
in rare cases,
Some authors describe
failure. The lowest dose of vitamin B3 known to cause hepatotoxicity, with
cases of acute hepatitis, acute pancreatitis, and renal failure as reported i
acute kidney injury (AKI).
literature, is As mentioned
1 g/day above,10).
[31] (Figure all energy
However,drinks contain
the main highofdoses
cause of most l
AKI was
caffeine, taurine, sugar, and vitamins. A megadose of vitamin B3 (niacin) is associated
taurine, which is used as a dietary supplement by athletes to enhance performance.
with hepatotoxicity. Niacin hepatotoxicity is thought to be a dose-dependent, directly toxic
response. Vitamin B3 is associated with cellular metabolism and flushing and hepato-
toxicity at pharmacological doses. Hepatotoxicity manifests as a mild elevation of liver
enzymes (ALT/AST), hepatic steatosis, hepatic necrosis, and, in rare cases, liver failure.
The lowest dose of vitamin B3 known to cause hepatotoxicity, as reported in the literature,
is 1 g/day [31] (Figure 10). However, the main cause of AKI was most likely taurine, which
is used as a dietary supplement by athletes to enhance performance.
Caffeine promotes digestion by stimulating salivation and gastric juice production due
to the presence of synergistic substances acting on H2 receptors. Caffeine is also known to
relax the gastroesophageal sphincter, which prevents the stomach contents from rising into
the oesophagus. In addition to its renal effects, caffeine is a weak diuretic. This effect may
be associated with an increase in glomerular filtration and a decrease in tubular sodium
reabsorption (Figure 11). There are also GABA receptors in the gastrointestinal tract. These
 Caffeine promotes digestion by stimulating salivation and gastric juice pro
Caffeine promotes digestion by stimulating salivation and gastric juice produ
due to the presence of synergistic substances acting on H2 receptors. Caffein
due to the presence of synergistic substances acting on H2 receptors. Caffeine is
known to relax the gastroesophageal sphincter, which prevents the stomach conte
known to relax the gastroesophageal sphincter, which prevents the stomach contents
rising into the oesophagus. In addition to its renal effects, caffeine is a weak diure
rising into the oesophagus. In addition to its renal effects, caffeine is a weak diuretic.
Nutrients 2023, 15, 3922 effect may be associated with an increase in glomerular filtration and a decrease
22 of 31 in
effect may be associated with an increase in glomerular filtration and a decrease in tub
sodium reabsorption (Figure 11). There are also GABA receptors in the gastroi
sodium reabsorption (Figure 11). There are also GABA receptors in the gastrointes
tract. These are located in the peripheral autonomic nervous system and are inv
tract. These are located in the peripheral autonomic nervous system and are involv
are located in the acid secretion and the nervous
peripheral protection of the gastric mucosa in from injury and motilit
acid secretionautonomic
and the protection system and
of the gastricaremucosa
involved from acid secretion
injury and motility. In
and the protection stomach, taurine
of thetaurine accumulates
gastricaccumulates
mucosa fromininjuryin the parietal cells
and motility. of the
In the gastric
stomach,glands.
taurineTaurine-co
stomach, the parietal cells of the gastric glands. Taurine-contai
cells
accumulates in cells
the are found
parietal cellsinofin thegastric
the myenteric
glands.plexus and submucosal plexus
Taurine-containing of the
in enteric
are found the myenteric plexus and submucosal cells plexusareof
found
the enteric ner
system.
the myenteric plexus
system. and The taurinergic
submucosal
The taurinergicplexus
neurons
of the
neurons
in the
enteric
in the
muscle
nervous
muscle
layer of
layersystem.
the
The taurinergic tracttract
gastrointestinal
of the gastrointestinal and
gastrointestinal
neurons in the muscle layer of the
gastrointestinal tract
tract maymaybe be
gastrointestinalinvolved
tract in
involved in
and gastrointestinal
the gastrointestinal
gastrointestinal motility
tractand
motility mayand endoc
endocrine
functions
be involved in gastrointestinal
functions [118].
[118]. motility and endocrine cell functions [118].

Figure 10. Pathological

Figure
Figure effects
10.10. of Energyeffects
Pathological Drinks
Pathological ofon
effects of gastrointestinal
Energy
Energy Drinks
Drinks tissues.
on gastrointestinal
on gastrointestinal tissues.
tissues.

Figure 11. Pathological effects of energy drinks on renal tissue.

Figure 11. Pathological effects of energy drinks on renal tissue.
Figure 11. Pathological effects of energy drinks on renal tissue.
4.4. Other Effects
4.4. Other
Finally, there are Effects
rare cases of obstetric, dermatological, and autoimmune compli-
4.4. Other Effects
Finally,
cations that are difficult there are rare cases of obstetric, dermatological,
drinks doesand autoimm
Finally,explain
to there or whose
are rare association with energy
cases of obstetric, dermatological, not
and auto
complications
seem to be reliable and well that are difficult
explained. to explain
Regarding or whoseand
autoimmune association
skin with energy drinks
complications,
complications that are difficult to explain or whose association with energy drin
some authors are notconvinced
seem to be therereliable and well explained. Regarding autoimmune and
not seem that are underlying
to be reliable and wellmechanisms
explained.ofRegarding
hypersensitivity to
autoimmune a
complications,
synthetic taurine,complications, some
which may besome authors
slightly are
differentconvinced
from that
natural there
taurineare underlying
[119]. mechanism
Although
authors are convinced that there are underlying mechan
the authors have not been able to elucidate the mechanism of anaphylaxis, they suggest
that the additives used to stabilise the amino acids, such as sulphites, butylated hydrox-
yanisole, butylated hydroxytoluene, and olysorbate emulsifier, may be the cause of the
symptoms [120]. There is also no clear association with energy drinks in obstetric compli-
cations. We reported two cases of such complications. In the first case, we had neonatal
hyperinsulinism due to isolated high maternal sugar intake, an event that has never been
reported in the literature. In the second case, we had menorrhagia due to secondary VKD
Nutrients 2023, 15, 3922 23 of 31

(acquired vitamin K deficiency) after consumption of high-energy drinks. There is no

evidence in the literature of ingredients in energy drinks that might correlate with the
development of VKD.

4.5. Experimental Studies on Animal Models

The adverse health effects have also been studied by various research groups using
animals as an experimental model. The summarised results of these studies, outlined below,
have shown effects similar to those observed in humans, with alterations affecting various
organs or systems.
Salih et al. [121] used rabbits as an animal model to observe the histopathological
effects of energy drinks (EDs) on various organs, including the brain, liver, kidneys, and
heart. Their findings suggest a direct correlation between tissue damage and the dose
administered. At higher doses, they observed renal vascular congestion, the bleeding
of interstitial tissue, focal atrophy, and the degeneration of the lining epithelium of the
proximal and distal convoluted tubules. Nieradko Iwanicka and colleagues [122] studied
the effects of the ad libitum consumption of energy drinks in mice on memory, body weight
and laboratory parameters. After 30 days of the experiment, the researchers observed
weight gain in male mice, an increase in serum transaminases and cholesterol concentration,
but no memory-related changes. Similar results were found by Sadowska [123], who
studied the effects of energy drink consumption in 30 mice and highlighted three main
consequences: reduced body weight gain despite increased energy expenditure, suggesting
an increased catabolic rate in the animals studied; reduced peri-intestinal fat deposition
and increased accumulation of peri-cardiac adipose tissue, which may act as a source
of chemokines and cytokines with pro-inflammatory properties. Finally, energy drink
consumption led to an increase in blood glucose concentration, most likely due to metabolic
changes leading to increased lipolysis and the development of insulin resistance.
Rasheed and colleagues [124] investigated the effects of energy drinks on renal tubules
using albino rats as an experimental animal model. Their research showed histopathological
changes in renal tubular cells, such as increased tubular vacuolisation, in rats exposed
to energy drinks. According to the researchers, this adverse effect is due to inhibition
of the A2A adenosine receptor, resulting in increased oxidative stress and production of
inflammatory stimuli.
Abonar et al. [125], Rehman et al. [126], and Haroun et al. [127] investigated the effect
of energy drinks on the pancreas of adult male albino rats. They performed histological,
immunohistochemical and biochemical studies that revealed alterations in pancreatic
cytoarchitecture. Specifically, damage to the pancreatic acini and islets of Langerhans was
observed, accompanied by an increase in collagen deposition in the pancreatic parenchyma,
a decrease in serum insulin levels, and an increase in blood glucose levels. There was also
an increase in TNF-a, NO, and malondialdehyde levels, indicating a global negative effect
on both exocrine and endocrine functions of the gland. Kassab et al. [128] also studied
the effects of energy drinks on the salivary glands of thirty adult albino rats and observed
parenchymal changes, including cytoplasmic vacuolisation, pyknotic nuclei and abundant
collagen fibre deposition, resulting in the displacement of striated muscle fibres. However,
these pathological changes in the glands were found to be transient upon cessation of
the substance.
Possible adverse effects of caffeine and taurine on cardiac electrophysiology were
investigated using twenty-five rabbits as an animal model [129]. The hearts of animals
perfused with caffeine and taurine showed shortened repolarisation times and refractory
periods on the ECG trace, followed by ventricular arrhythmias, confirming the potential
arrhythmogenic effect of these substances. In another study, Demirel et al. [130] investigated
the effects of the combined consumption of energy drinks and alcohol on the myocardium
and skeletal muscle system. In particular, the study highlighted damage to the cardiac and
endothelial cytoarchitecture, as well as an increased tendency towards anaerobic cellular
respiration in skeletal muscle tissue, resulting in increased lactate formation. Diaz et al. [131]
Nutrients 2023, 15, 3922 24 of 31

also investigated the effects of these two substances in combination. In their experimental
study of rats exposed to the substances for 90 days, changes in the temporal cortex and
hippocampus were analysed. The results show an inflammatory response associated
with oxidative stress, local gliosis, and increased levels of IL-1, TNF-1, iNOS, reactive
oxygen species, lipid peroxidation, and nitric oxide. In addition, at the neurological level,
Ulenius [132] and colleagues demonstrated that the combination of caffeine and taurine
enhances the stimulant properties of ethanol on the locomotor system, a phenomenon
previously associated with substance dependence and associated with increased dopamine
levels and reward circuits. Ugwuja [133] conducted experiments to assess the biochemical
effects of energy drinks alone or in combination with alcohol on albino rats. The study
showed changes in total white blood cell count, plasma potassium, calcium, renal function,
liver enzymes, and plasma triglycerides. Krahe et al. [134] also analysed the effects of
combined energy drink and alcohol consumption. Overall, animals treated with alcohol
and energy drinks showed increased locomotor activity and increased anxiety levels in
the open field test. They also showed an early loss of the righting reflex and poorer motor
coordination in the rotarod test. These effects on righting reflex and motor coordination
were associated with the over-activation of cerebellar GABAA receptors. The data also show
that exposure to alcohol in combination with energy drinks prolongs the duration of motor
impairment and ataxia in adolescent mice. This ability to prolong the effects of alcohol may
explain why this group performed worse in the righting reflex loss test after cumulative
administration of alcohol and energy drinks compared to animals receiving alcohol alone.
Reis et al. [135] investigated the effects of 14 days of energy drink consumption alone or in
combination with ethanol on oxidative stress parameters, including superoxide dismutase
(SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and the lipid peroxidation marker
malondialdehyde (MDA) in 40-day “adolescent” mice. The ethanol-treated group showed
a significant increase in SOD and GSH-Px activity in brain tissue compared with the control
group. The elevated MDA levels observed in rats co-exposed to energy drinks and ethanol,
as well as those exposed to energy drinks alone, may be a consequence of increased free
radical formation and altered cellular antioxidant defence status. Liver histopathology
results show that energy drinks may induce liver damage, and the combined effect of
ethanol and energy drinks may cause more significant damage than either substance alone,
as indicated by increased MDA levels. A histopathological examination of brain tissue
did not show any treatment-related abnormalities, possibly due to the short duration of
the experiment.
Nasi and colleagues [136] investigated the possible negative effect of energy drinks on
the gastrointestinal tract by administering different substances to rats for five consecutive
days. They did not observe any acute lesions in the gastrointestinal tract, but they did
observe an eosinophilic infiltration in the intestinal mucosa. This histopathological change
was also observed in rats treated with caffeine alone, suggesting that this inflammatory
effect is a direct consequence of this substance, which is also present in energy drinks.
Elçi et al. [137] investigated the effects of eight weeks of energy drink consumption
on the female reproductive system, specifically analysing follicular ovarian reserve and
anti-Müllerian hormone levels in the blood. They found a significant decrease in both
parameters. Instead, Oyelowo et al. [138] focused on the biochemical effects of both natural
and artificial energy drinks on testicular tissue after 28 consecutive days of consumption
in pubertal male rats. Their results showed negative effects of energy drink consumption,
whether natural or artificial, on male reproductive functions, including decreased testos-
terone steroidogenesis in Leydig cells, changes in gonadotropin synthesis, and disruption
of sperm homeostasis.
Al-Basher et al. [139] conducted a study on the effects of perinatal exposure to caffeine-
based energy drinks on the liver, kidneys, brain, locomotor activity, and anxiety in newborn
mice. Pregnant mice received 2.5 or 5 mL of energy drinks from the first day of pregnancy
until 15 days after birth. Perinatal exposure to energy drinks resulted in a significant
increase in lipid peroxidation (MDA) and a decrease in antioxidant defences in the liver,
Nutrients 2023, 15, 3922 25 of 31

kidneys, brain, cerebellum, and medulla oblongata of newborn mice on days 21 and
35 after birth. Energy drinks also induced various histological alterations, including
vacuolation and lipid infiltration of hepatocytes, developing degenerated glomeruli and
dilated interstitial spaces in the renal cortex, pyknosis and chromatolysis of cerebral and
medullary neurons, and degenerated and abnormal Purkinje cells in the cerebellum. In
addition, energy drinks increased locomotor activity and induced anxiety-like behaviour
in newborn mice.
Posokhov et al. [140] investigated the effects of two months of energy drink consump-
tion on red blood cell membranes. They used the fluorescent probe O1O (2-(20 -OH-phenyl)-
5-phenyl-1,3-oxazole), which localises to the area of glycerol backbones, carbonyl groups
of phospholipids, and hydrocarbon chains of phospholipids (near carbonyl groups) in the
bilayer. The consumption of energy drinks was associated with increased fluorescence
intensity in erythrocyte suspensions compared to control animals. The observed change in
probe fluorescence is attributed to an increase in the viscosity of the probe environment
within the membrane. Using the fluorescent probe O1O, it was shown that the long-term
oral administration of caffeine-based energy drinks to rats caused an increase in membrane
viscosity (resulting in reduced fluidity) in red blood cells.

5. Conclusions
This extensive literature review includes a large number of research studies on the
potentially fatal health effects of both acute and chronic abuse of these substances. These
consequences include cardiac arrhythmias, neurological and behavioural changes, acute
organ inflammation (including the liver, stomach, pancreas, and kidneys) and even cases of
rare dermatitis or autoimmune disorders. Furthermore, although based on a limited case
pool, it is noteworthy that there is a marked disparity in the literature between cases of car-
diac arrest requiring intensive cardiopulmonary resuscitation (nine cases) and documented
deaths (three cases) resulting from energy drink abuse. These statistics suggest a plausible
under-reporting of deaths associated with these substances, particularly among frequent
users such as adolescents and athletes. Consequently, in the investigation of sudden cardiac
death in young people, the role of the pathologist in meticulously collecting anamnestic and
circumstantial data from the deceased, recognising the potential involvement of non-illicit
substances such as energy drinks, becomes crucial [141].
The results of experimental studies in animal models echo the findings of the review,
demonstrating acute and chronic effects consistent with observations in humans.
Although individual components have been shown to be safe [142], excessive con-
sumption, especially among adolescents, often leads to potential adverse effects on human
health. As shown in this review, these effects can vary, particularly regarding the cardiovas-
cular and cerebral systems. It would therefore be important to consider the introduction of
precise limits on the consumption of these drinks. As caffeine is the most representative
ingredient in terms of composition, it is first necessary to consider the upper limits of safe
caffeine intake. Most cans of energy drinks (250 mL) contain 50 to 150 mg of caffeine, while
the EFSA upper safe intake limit for adults is up to 400 mg per day (about 5.7 mg/kg
bw per day for a 70 kg adult), with a single dose not exceeding 200 mg [143]. In fact, no
health concerns regarding acute toxicity, bone status, cardiovascular health, cancer risk, or
male fertility have been raised by other agencies in previous assessments at this level of
habitual caffeine consumption. The FDA (Food and Drug Administration) estimates that
toxic effects, such as seizures, may be observed following the rapid consumption of about
1200 mg of caffeine, or about 0.15 tablespoons of pure caffeine [144]. For pregnant or breast-
feeding women, the safe daily intake of caffeine is halved from 400 mg to 200 mg, or about
half a can. Finally, for children and adolescents, it is important to accentuate that neither
EFSA nor the FDA have indicated a safe limit, suggesting that these substances should be
avoided altogether, as further emphasised by the American Academy of Pediatrics due to
possible long-term negative effects on behavioural disorders.
Nutrients 2023, 15, 3922 26 of 31

Therefore, based on our observations and those found in the literature, we suggest that
the daily intake of energy drinks should not only not exceed the safety limits for caffeine
established by European and American regulatory authorities, but should be even lower.
Indeed, these drinks also contain other neurostimulants, the effects of which are not fully
understood. Furthermore, as this review points out, there are cases in the literature of
people with no known medical conditions who have suffered acute cardiac events after
consuming just a few 250 mL cans of these drinks. Given that the concentration of caffeine
in these drinks is between 50 and 150 mg per can (250 mL), we recommend no more than
one can at a time and two cans per day to remain within an acceptable safety limit. We also
believe that it is necessary to clearly state the daily intake limit for products containing
high levels of caffeine (such as ‘Demon Energy Shot’, which contains 200 mg of caffeine in
60 mL of product), given the potential risk of acute caffeine intoxication [145].
In addition, the sale and consumption of these drinks in minors should be regulated as,
although they are legal substances, their long-term effects are not yet known and may lead
to psychiatric pathologies or the aggravation of cardiac conduction disorders. Increased
public education on the potential risks associated with the misuse of energy drinks is
warranted to enable individuals to make informed decisions regarding consumption.
Furthermore, extensive research is needed to elucidate the long-term effects of energy
drink consumption on human health.

Author Contributions: Conceptualisation, A.M. and A.C.; methodology, V.F.; validation, P.F. and E.T.;
formal analysis, J.L.; investigation, C.C.; writing—original draft preparation, A.C.; writing—review
and editing, A.M.; supervision, V.F. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: The data presented in this study are available in Tables 2–7.
Conflicts of Interest: The authors declare no conflict of interest.

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