Download SUMMARY - Submission on Review of Liquor Control Act 1988 (WA

SUMMARY - Submission on Review of Liquor Control Act 1988 (WA)
Provided by: Red Bull Australia Pty Ltd
Contact: Zac Rich, Corporate & Regulatory Affairs Manager ([email protected]; 02 9023 2892)
Date: 25 February, 2012
1. CONTEXT
This submission provides the Committee with some insights into the non-alcoholic energy drink category. Having been
established in 1987 in Austria, Red Bull is now available in 165 countries. As the global energy drink manufacturer, we
look to develop cooperative relationships with regulators. This includes the federal, state, and territory governments of
Australia where Red Bull has been sold for 13 years.
Like soda water, lemonade, cola, fruit juices and other mixers, some consumers choose to mix energy drinks with
alcohol. To that end, we draw the Committee’s attention to the most recent research in the area of non-alcoholic energy
drinks mixed with alcohol (AmED). For the Committee’s benefit, copies of the research are appended to this submission.
2. KEY FACTS
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Energy drinks represent less than one per cent of beverage sales in licensed venues in Australia.1
A standard 250mL can of energy drink contains a maximum of 80mg of caffeine. This is equivalent to a cup of instant
coffee.
All energy drinks in Australia are stringently regulated by Food Standard 2.6.4 (Formulated Caffeinated Beverages).
This limits the amount of caffeine, imposes mandatory advisory statements, and requires caffeine content to be
disclosed.2
When 30mL of alcohol is mixed with a standard 250mL can of energy drink, the alcoholic content is equivalent to
approximately five per cent. This equates to a beer.
A 2012 study of over 6,000 Dutch students by Utrecht University compared those that consumed AmED versus those
that drank alcohol alone. The results show that consuming AmED does not increase overall alcohol consumption
and/or alcohol-related consequences: on a night out, students consumed less alcohol overall when mixing with
energy drink, versus drinking alcohol alone. This resulted in fewer alcohol related consequences.3
Both the Scientific Committee on Food (SCF) in 2003 and the European Food Safety Authority (EFSA) in 2009
addressed the issue of possible interactions between AmED in their corresponding opinions. The SCF 2003 opinion
concluded that ‘there is no confirmation of a causal relationship between the reported effects of the consumption of
alcohol and the consumption of energy drinks’ containing taurine and glucuronolactone. The 2009 EFSA opinion
agreed with the considerations of the SCF and stated that ‘it is unlikely that glucuronolactone would have any
interaction with caffeine, taurine, alcohol or the effects of exercise.’
A 2012 literature review this conclusion. The review found that there was little evidence that energy drinks altered
intoxication levels. It also found no evidence that mixing energy drinks and alcohol increased consumption levels.4
The 2012 findings of the UK Government’s Committee on Toxicity concluded that the current balance of evidence
does not support a harmful toxicological or behavioural interaction between caffeine and alcohol.5
BarScan Energy Category Report 2012
By comparison, the US does not have an equivalent standard. Red Bull (and other major manufacturers) maintain a global formula
and always disclose caffeine content. Other US manufacturers to not adhere to the same standards.
3
de Haan L, de Haan HA, Olivier B, Verster JC, Alcohol mixed with energy drinks: methodology and design of the Utrecht Student
Survey, International Journal of General Medicine, 2012: 5 889–898
4
Joris C Verster, Christoph Aufricht, Chris Alford “Energy drinks mixed with alcohol: misconceptions, myths and facts” (International
Journal of Medicine, 2012, Volume 5) at 187.
5
Committee on Toxicity of Chemical in Food, Consumer Products and the Environment, “COS Statement on the interaction of caffeine
and alcohol and their combined effects on health and behaviour” (December 2012).
2
SUBMISSION BY RED BULL AUSTRALIA TO
THE REVIEW OF THE LIQUOR CONTROL ACT 1988
Introduction
Red Bull is a non-alcoholic energy drink that has enjoyed a successful history since its inception in Austria
in 1987. It is available in 165 countries and has been available in Australia for 13 years.
As a market leader in the non-alcoholic energy drink sector, Red Bull cooperates with scientific, regulatory
and health bodies internationally and in Australia. Red Bull assisted Food Standards Australia and New
Zealand to develop Standard 2.6.4, which is considered one of the most stringent standards in the world.
Background to energy drinks in Australia
In Australia, all ingredients in a standard 250 mL energy drink are clearly labelled, including caffeine
content (80mg) which is equivalent to a cup of instant coffee, in addition to a maximum daily consumption
recommendation.
This is in stark contrast with the United States where there is no regulation on caffeine content in these
products or any requirement for energy drink manufacturers to list ingredients or provide advisory
statements on its products.
While Red Bull (and other major manufacturers) maintains the same formula in Australia and the United
States, there are a number of rogue products in the US that do not observe comparable limits or disclose
caffeine content. A significant portion of the negative debate and commentary surrounding energy drinks
emanates from the United States and has been generated by outlier products. In response, Red Bull has
invested significant resources to assist regulators and other industry representatives to access the latest
information and science available to clarify these key issues.
Alcohol and Energy Drinks
In any discussion about the sale of energy drinks in licenced premises in Western Australia, it is important
for the Committee to have an understanding of the context of energy drink sales. According to figures
provided by BarScan, energy drinks comprise less than one per cent of overall sales over the bar
nationally. BarScan sources primary sales information from cash registers in more than 950 bars and 330
liquor venues across Australia and tracks more than 60 million beverage serves across licenced premises
each year.
Like other non-alcoholic mixers, some consumers chose to mix energy drinks with alcohol. When a 250mL
can of energy drink is mixed with 30mL of alcohol, the concentration of alcohol is approximately 5 per cent
which is equivalent to beer.
In licenced venues in which Red Bull is available, the product is sold for approximately $6 per can. Patrons
purchasing a vodka and can of Red Bull will pay $12-$15. This fits within the premium pricing range and is
the approximate equivalent of two vodka and lemonades. The premium price position of an energy drink
purchased with alcohol does provide a price disincentive for over consumption.
Research and Science
Red Bull has long believed and remains firm in its view that sound policy and regulation must be
underpinned by evidence-based research.
Following negative publicity and concerns about the use of energy drinks as a mixer, a number of research
papers and studies have been conducted to examine this issue further. Copies of this research are
attached to this submission.
Both the Scientific Committee on Food (SCF) in 2003 and European Food Safety Authority (EFSA) in 2009
addressed the issue of mixing alcohol and energy drinks in their corresponding opinions. The SCF
concluded that “there is no confirmation of a causal relationship between the reported effects of the
consumption of alcohol and/or drugs and the consumption of energy drink” containing taurine and
glucuronolactone. In 2009, EFSA agreed with the conclusions from the SCF. Both SCF and EFSA in their
respective opinions do not support the assumption of any combined effect or interaction between alcohol
and energy drinks.
There have also been concerns raised that mixing energy drinks with alcohol could result in the subjective
perception by consumer that he/she is less intoxicated than if alcohol was consumed on its own. There is
also concern raised that people would consume more alcohol when mixed with energy drinks compared
with the consumption of alcohol beverages on their own.
These concerns/views are not supported by science. For example, Energy Drinks Mixed with Alcohol,
Misconceptions, Myths and Facts (Verster et al) is a scientific review which concludes that there is no
consistent evidence that energy drinks alter the perceived level of intoxication of people who mix energy
drinks with alcohol and there is no evidence that co-consumption of energy drinks causes increased alcohol
consumption.
In addition, a recent study Effects of Consuming Alcohol Mixed with Energy Drinks versus Consuming
Alcohol Only (de Haan et al) of more than 6,000 Dutch students comparing those who consumed alcohol
mixed with energy drinks compared with those that drank alcohol alone, provides scientific evidence that
mixing energy drinks with alcohol does not increase overall alcohol consumption and/or alcohol-related
consequences.
“The study also shows clearly that mixing alcohol with energy drinks does not increase the
likelihood of potentially dangerous activities or serious negative consequences, such as driving
while intoxicated, being injured, or getting involved in a flight, unplanned sexual activity, or taking
foolish risks”
Furthermore, the UK Government’s Committee on Toxicity’s Statement on the Interaction of Caffeine and
Alcohol and their Effects on Health and Behaviour has concluded that the current balance of evidence does
not support a harmful toxicological or behavioural interaction between caffeine and alcohol.
“A number of studies have suggested that caffeine can reduce the outward effects of alcohol,
especially on reaction times, but other investigations have failed to support this. The evidence that
perceptions of alcohol intoxication are modified by caffeine is conflicting. Overall, the range of
methods used in reported studies prevents firm conclusions on whether caffeine counteracts the
short-term effects of alcohol on brain function.”
WA liquor licensing landscape
Western Australia has the strictest liquor licensing regime across Australia with regard to energy drink
restrictions and it appears that regulatory authorities are taking a precautionary approach as evidenced by
a study of recent liquor applications (Public Interest Applications).
Red Bull is aware that despite there being no clear scientific basis to do so, and despite the limited amount
of energy drinks being sold in licenced premises, the WA Police in conjunction with the Department of
Health often object to energy drinks being supplied or sold in new liquor licence applications, as well as
applications to renew Extended Trading Permits.
Consequently, applicants — many of which could be considered low risk in terms of incidents of anti-social
behaviour — volunteer in their applications not to sell energy drinks to avoid objections from these two
agencies and the subsequent extension of time required to obtain a liquor licence.
While WA Police and the Department of Health may argue that there has been a reduction in antisocial
behaviour as a consequence of the current restrictions there is no conclusive evidence to defend this
position. Indeed, there may be other factors which can be attributed to this outcome.
What is clearly lacking in the debate is the absence of empirical data that demonstrates the efficacy of the
bans and restrictions placed on energy drinks as they apply to community safety outcomes in Western
Australia. Red Bull believes that, given the absence of such data, the Committee has a role to provide
clear guidance on the issue of restrictions to deliver a balanced approach on this matter. For example,
external agencies currently are able to influence unfairly liquor licence applications outcomes, particularly in
regard to low risk venues such as small bars.
Recommendations
To assist the Committee, Red Bull respectfully makes the following recommendations:
1. Given the available scientific evidence, the current restrictions and bans on energy drinks in venues
across WA should be removed.
2. Restrictions on the sale of energy drinks for new liquor applications, for example low risk venues,
such as small bars, should not be imposed.
3. That policy and regulation must be underpinned by robust evidence-based research.
Submitted by:
Zac Rich
Regulatory Affairs Manager – Australia and New Zealand
Red Bull Australia
[email protected]
02 9023 2892
25 February 2013
Enclosures
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8.
Scientific Committee on Food (SCF) in 2003
European Food Safety Authority (EFSA) in 2009
Energy Drinks mixed with alcohol; misconceptions, myths and facts – Verster et al
The effects of energy drink in combination with alcohol on performance and subjective awareness –
Alford et al
Effects of consuming alcohol mixed with energy drinks versus consuming alcohol only on overall
consumption and negative alcohol related consequences – de Haan et al
Committee on Toxicity – CoT Statement on the interaction of caffeine and alcohol and their
combined effects on health and benaviour
Committee on Toxicity – Cot Statement on the interaction of caffeine and alcohol and their
combined effects on health and behaviour – Lay Summary
BarScan Energy Category Report – October 2012
EUROPEAN COMMISSION
HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL
Directorate C - Scientific Opinions
C2 - Management of scientific committees II; scientific co-operation and networks
Scientific Committee on Food
SCF/CS/PLEN/ENDRINKS/16 Final
Opinion of the Scientific Committee on Food
on
Additional information on “energy” drinks
(expressed on 5 March 2003)
Rue de la Loi 200, B- 1049 Bruxelles/Wetstraat 200, B-1049 Brussel- Belgium-Office: G-1 01/242
Telephone: direct line (+32-2) 29 84698, swithboard 299.11.11 Fax: (+32-2) 2994891
http://europa.eu.int/comm/food/fs/sc/scf
Opinion on Additional information on “energy” drinks
Terms of reference
The Committee is asked to review additional information submitted on energy drinks and
indicate if the conclusions in its opinion of 21 January 1999 need to be modified.
Background
The SCF opinion of 1999
The Committee adopted an opinion on so-called “energy” drinks in 1999, which
evaluated the safety of caffeine, taurine and D-glucurono-g-lactone as constituents of
“energy” drinks (SCF, 1999).
For caffeine, it was concluded that the contribution of “energy” drinks to overall caffeine
intake was not a matter of concern for non-pregnant adults. For children who do not
normally consume much tea or coffee, and who might substitute “energy” drinks for cola
or other soft drinks, consumption of “energy” drinks might represent an increase in daily
caffeine exposure compared with their previous intake. The Committee considered that
this could result in transient behavioural changes, such as increased arousal, irritability,
nervousness or anxiety. For pregnant adults, the Committee concluded that while intakes
of caffeine up to 300mg/day appeared to be safe, the question of possible effects on
pregnancy and the offspring at regular intakes above 300mg/day remained open. This
suggested that moderation of caffeine intake, from whatever source, was advisable during
pregnancy.
For taurine and glucuronolactone, the Committee was unable to conclude that the
safety-in-use of these constituents in the concentration ranges reported for "energy"
drinks had been adequately established. Further studies would be required to establish
upper safe levels for daily intake of taurine and glucuronolactone.
The Committee noted that possible interactions of constituents of "energy" drinks have
not been well studied and considered that possible interactions between caffeine, taurine
and alcohol may warrant investigation in humans, particularly under conditions of
exercise and consequent dehydration through sweating.
Submission of further data
Since the publication of its 1999 opinion, four further submissions of data have been
received from one manufacturer of “energy” drinks (Red Bull GmbH, 2000, 2001,
2002a,b). These comprised:
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a 13-week oral toxicity study in the mouse on Red Bull® given in the drinking
water
a 13-week oral gavage study in rats on taurine;
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a 13-week oral gavage study in rats on glucuronolactone;
a review of other toxicology studies on taurine and glucuronolactone;
information on the use of taurine in human medicine;
an evaluation of the possibility of interactions between taurine, caffeine and
glucuronolactone;
an evaluation of the possibility of interactions between taurine and alcohol
and caffeine and alcohol;
results from a survey of the consumption of “energy” drinks in Austria and
derived new exposure estimates;
remarks on the SCF opinion of 1999.
The Committee was also asked by the petitioner to take into account published reports
and statements from the Australian New Zealand Food Authority (ANZFA, 2000) and the
UK Food Standards Agency (FSA, 2001a).
Other relevant developments in the EU
The Committee also noted other developments in the EU since its last opinion in 1999:
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The Agence Française de Sécurité Sanitaire des Aliments, reviewed the 13-week
mouse oral toxicity study on Red Bull®, concluding that authorisation of the use
of various substances in “energy” drinks was not acceptable since harmlessness at
the concentrations recommended by the petitioner had not been demonstrated
(AFSSA, 2001).
The UK Committee on Toxicity published a statement on the reproductive effects
of caffeine in the context of intakes from all food sources, including “energy”
drinks (COT, 2001). It drew similar conclusions to those in the 1999 SCF opinion,
commenting that caffeine intakes above 300 mg/day show a plausible association
with low birth weight and spontaneous abortion. Based on this, the UK Food
Standards Agency issued advice for pregnant women that they should limit their
intake of caffeine to less than the equivalent of four average cups of coffee a day;
the estimated “energy” drink equivalent to this was 4 cans a day (FSA, 2001b).
A review of the health effects of “energy” drinks (stimulant drinks),
commissioned by the Minister of State at the Department of Health and Children
in the Republic of Ireland, has been published (Stimulant Drinks Committee,
2002). It made a number of recommendations covering labelling, concerns about
marketing and promotion, further research needs, and advice to pregnant women,
and cautioning against both consumption by children under 16 years of age and
consumption in association with sport or exercise.
A number of EU Member States have raised concerns about “energy” drinks in
response to anecdotal cases of acute symptoms requiring medical attention in
young people consuming “energy” drinks, in most cases in conjunction with
alcohol and/or drugs used socially.
A meeting of EU Member States in February 2002 to discuss perceived safety
issues around “energy” drinks, concluded that the Commission should not take
any action, but noted that new data had been submitted to the SCF and the
position should be reconsidered once a new SCF opinion became available (FSA,
2
2002). An amendment to the EC labelling directive (EC, 2000) was agreed, to
come into effect by July 2004, requiring that beverages, other than those based on
coffee or tea, containing more than 150 mg caffeine/l should be labelled “high
caffeine content” and the exact amount present indicated on the label (EC, 2002).
Intake data
The Committee noted that in its earlier opinion it used a figure of 500 ml of “energy”
drink as the “likely consumption on any one day by regular consumers” (SCF, 1999).
Two new surveys of intake of “energy” drinks have become available, one from Austria
(Red Bull GmbH, 2001) and one from Ireland (Stimulant Drinks Committee, 2002).
Details of these surveys are given in Annex 1. For this evaluation, the Committee has
chosen from the new data mean chronic, high chronic and acute consumption estimates
for regular consumers, as shown in Table 1. The estimate for acute consumption of 750
ml/day would give intakes of 240 mg caffeine/day, 3000 mg taurine/day and 1800
mg/day glucuronolactone, assuming the “energy” drinks contained maximum levels of
320, 4000 and 2400 mg/l of caffeine, taurine and glucuronolactone respectively.
Table 1: Intake estimates used by the Committee
Consumption
Mean chronic
High chronic
Acute
No. of 250ml cans/day
0.5
1.4
3.0
ml/day
125
350
750
Note that for acute consumption the Committee used 3 cans/day as a reasonable high
consumption, this amount being higher than the 90th percentile recorded in the Austrian
survey (2.6 cans/day) and being the average reported in the Irish survey for the most
number of cans consumed in a single session. The Committee was aware that amounts up
to 8-12 cans/day were reported by a few extreme consumers in both surveys.
Toxicological studies
A 13-week mouse oral toxicity study on Red Bullâ (RCC, 2000) and 13-week rat oral
toxicity and toxicokinetic studies on taurine (WIL, 2001a) and on glucuronolactone
(WIL, 2001b) have been submitted. The key findings in these new studies are
summarised and discussed below, in the context of data reviewed previously by the
Committee (SCF, 1999). Details of the studies are given in Annex 2.
13-week mouse oral toxicity study on Red Bullâ
Mice were given Red Bullâ (RB) either undiluted or as a mixture with tap water at
concentrations of 0, 33, 50 or 100% in the drinking water ad libitum for 13 weeks from 6
weeks of age (RCC, 2000). There were significant reductions in body weight in all
treated groups, most likely attributable to observed reductions in food intake.
Considerable dose-related increases in water/fluid intake, ranging from 27% to 115%
compared with controls, were seen in all treated groups. These were not unexpected,
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given the proportions of tap water replaced by RB, a fluid of much higher osmolarity.
Many of the statistically significant findings in haematology, clinical chemistry and
urinalysis, which were seen mainly in the 100% RB groups, are almost certainly
attributable to the increased fluid intakes and glucose loading from the sucrose in RB.
Disturbances in fluid balance would not be expected to occur in humans consuming
“energy” drinks as part of their normal diet. Due to the effects on body weight, an overall
no-observed-adverse-effect level (NOAEL) cannot be determined from this study.
Neither does this study provide any useful data for the safety assessment of the individual
constituents, caffeine, taurine or glucuronolactone, since the mode of administration did
not allow very high amounts of the individual constituents to be consumed by the mice
(see Annex 2).
Studies on taurine
The new toxicokinetic data on taurine in rats (WIL, 2001a), showing ready bioavailability
and peak plasma levels one hour after oral administration, are in accordance with findings
from the limited published data on humans. Human studies showed significant increases
in plasma taurine 90 minutes after consumption of a taurine-rich meal with levels
declining to background within 180-270 minutes (Trautwein and Hayes, 1995). These
results also corroborate those from an unpublished human study by Taisho
Pharmaceuticals, using radiolabelled taurine, which showed peak serum levels at 1-2
hours after oral administration, declining by 7 hours (Watanabe, cited in Red Bull GmbH,
2001). Other human data suggest that taurine is absorbed orally via an active transport
mechanism in the gut wall (Ahlman et al., 1993, 1995a,b).
The possible accumulation of taurine has also been investigated. The new rat
toxicokinetic study only sampled on study days 0 and 90 but the results did not indicate
any accumulation (WIL, 2001a). On the other hand, Trautwein and Hayes (1995)
concluded, from a study in which 400 mg taurine was given daily for 7 days to humans,
that there was accumulation of taurine in the plasma and a slight increase in whole blood
taurine levels.
In the new 13-week oral toxicity study, rats were given taurine at doses of 0, 300, 600
and 1000 mg/kg bw/day, dissolved in deionised water, orally by gavage once daily for 13
weeks from 6 weeks of age (WIL, 2001a). There were no persistent effects on body
weight or food consumption and no histopathological changes in organs or tissues in any
dose group. However, there were dose-related behavioural changes in both sexes of all
three dosed groups. These were persistent increased activity most noticeable 1 hour after
dosing, occasional chewing of limbs, and a possible decrement in motor performance on
a rotarod. These findings, together with the toxicokinetic data, showing peak plasma
levels at 1 hour, and the lack of increased locomotor activity when measured some hours
after dosing, suggest that taurine may have exhibited an acute, central pharmacological
effect in this study. Taurine is known to be present at high concentrations in the brain
where it acts as a neuromodulator (see later). Previous sub-chronic studies on rats,
reviewed earlier by the Committee (SCF, 1999), mostly involving administration of
taurine in the drinking water or by intraperitoneal injection have, if anything, reported
unchanged or reduced activity, though one study did report enhanced exploratory
activity. The results of the new sub-chronic study show that 1000 mg/kg bw/day is a clear
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effect level for behavioural changes while the lower doses of 300 and 600 mg/kg bw/day
are marginal effect levels in males but clear effect levels in females. Thus, a NOAEL for
behavioural effects in rats has not been established.
Of the other studies on taurine mentioned by the petitioner (Red Bull® GmbH, 2001), all
have been reviewed previously by the Committee (SCF, 1999), with the exception of a
developmental toxicity study by Yamada et al. (1981), which showed no adverse effects,
either prenatally or postnatally, from gavage administration of taurine at 300, 1000 or
3000 mg/kg bw/day to rats on days 7-17 of gestation.
The submission (Red Bull GmbH, 2001) also included an extensive review of the clinical
use of taurine in humans in conditions including diabetes, epilepsy, congestive heart
failure, hypertension, liver disease and cystic fibrosis, concluding that “No adverse health
effects attributable to taurine have been reported in more than 30 clinical investigations
reported over a period of 30 years. In many cases taurine has proved medically
beneficial.” The Committee was aware of these studies at the time of its earlier opinion
(SCF, 1999).
Studies on glucuronolactone
The new toxicokinetic data on glucuronolactone in rats, showing bioavailability and lack
of accumulation, with peak plasma levels 1-2 hours after oral administration (WIL,
2001b), are in accordance with findings from the limited published data on humans.
In the new 13-week toxicity study, rats were given glucuronolactone at doses of 0, 300,
600 and 1000 mg/kg bw/day, dissolved in deionised water, orally by gavage once daily
for 13 weeks from 6 weeks of age (WIL, 2001b). There were no significant, treatmentrelated effects, apart from vacuolation and inflammatory changes localised to the papilla
of the kidney in females at 600 and 1000 mg/kg/day, with a NOAEL of 300 mg/kg
bw/day. The petitioner has commented that the occurrence of the lesions only in females
may be related to the higher acidity and osmolality of urine in the female rat and went on
to comment that the osmolality of human urine is considerably less than that of the
Sprague-Dawley rat. However, in the Committee’s view, the mechanistic cause of the
kidney lesions remains unclear.
The submission (Red Bull GmbH, 2001) reviewed some additional studies on
glucuronolactone, including a study on growing hamsters (Di Filippo and Blumenthal,
1972) that had not previously been seen by the Committee. The previous SCF opinion
specifically commented that there were no studies in mammalian species that included
administration of high doses of glucuronolactone to growing animals, and that knowledge
of the influence, if any, of high doses of glucuronolactone on blood glucose homeostasis
and metabolic pathways involving glucose would be relevant for risk assessment in
relation to children and diabetics (SCF, 1999). The purpose of the 28-day hamster study
was to investigate whether glucuronolactone could prevent experimental cholelithiasis
when given in the drinking water at doses up to 5.25%, equivalent to an intake of
approximately 500 mg/kg bw/day. There were no clinical signs of toxicity and body
weights in treated groups were comparable to controls.
5
Potential for interactions between constituents of “energy” drinks
The petitioner submitted an evaluation by an outside expert, based on the existing
literature, which discussed the possibility of interactions between caffeine, taurine and
glucuronolactone (Red Bull GmbH, 2002a). The evaluation considered the fate of the
compounds in the body (toxicokinetics) and their known effects (toxicodynamics).
There are extensive data on the toxicokinetics of caffeine and taurine but less information
on glucuronolactone. Consideration of the chemical nature of the three parent compounds
and their metabolites, and the fact that differing processes are involved in their
absorption, distribution, metabolism and excretion did not, in the expert’s view, raise any
a priori reasons to expect any toxicokinetic interactions, even at high intakes of any one
constituent. This was supported by known physiology and citation of existing studies.
The physiological handling and lack of toxicological effects of glucuronolactone (other
than on the female rat kidney - see above) did not, in the expert’s view, raise any a priori
reasons to expect toxicodynamic interactions from this constituent. Caffeine and taurine,
on the other hand, each affect the functioning of the central nervous system, kidneys and
heart, thus there is a need to consider the potential for toxicodynamic interactions
between these two constituents. Data relevant to these possible interactions are discussed
below.
Some of the data on caffeine derives from in vitro studies using high concentrations that
would not be achieved in vivo following ingestion. For example, caffeine mobilises
calcium, decreasing intracellular calcium concentrations (Otun et al., 1991), but only at in
vitro concentrations that are around 200-fold higher than the plasma/tissue concentrations
that would be achieved after consuming 160 mg of caffeine as a single dose, say, from
0.5 l of “energy” drink (Red Bull GmbH, 2002a). Nevertheless it should be noted that
calcium disturbances (reduced blood levels) were seen in the mouse study on Red Bullâ.
Central nervous system
Caffeine is a central nervous system stimulant whereas taurine generally act as an
inhibitory neuromodulator. Caffeine exerts stimulatory effects by blocking the inhibitory
action of adenosine at its binding sites, with subsequent increases in the levels in some
brain regions of several neurotransmitters, including adrenaline, noradrenaline,
tryptophan and dopamine (Schlosberg, 1984; Hadfield and Milio, 1989; Kirch et al.,
1990; Hughes 1996; Dager et al., 1999; Schuckit, 2000). It also modulates the effects of
GABA and serotonin (Kaplan et al., 1992; Nehlig, 1999). Taurine, on the other hand,
depresses the activity of excitable membranes in the brain (Iida and Hikichi, 1976;
Huxtable, 1992). Centrally, taurine acts as an agonist of the more sedating glycine
receptors and inhibits the more excitatory actions of NMDA receptors and glycine
neurotransmitter function (De Saint et al., 2001; Font et al., 2001). It therefore could
modulate the excitatory actions of some other amino acids (Saransaari and Oja, 1999,
2000).
6
While these data may appear to indicate that if there were any interaction, taurine might
reduce caffeine-mediated excitation, the Committee noted that caffeine and taurine act on
different receptors and moreover, in the rat study on taurine (see earlier), there was a
stimulatory action on locomotor activity 1 hour after administration in all treated groups.
Kidney
Both caffeine and taurine can have short-term diuretic actions, causing loss of body water
and sodium. Taurine acts via inhibition of central release of the anti-diuretic hormone,
vasopressin (Hussy, 2001). Caffeine does not inhibit vasopressin release but has a direct
action on kidney tubule functions, such as ionic reabsorption and renal perfusion,
probably via adenosine receptor blockade (Daly, 1993). A high dose of taurine in the
drinking water, equivalent to about 1500 mg/kg bw, was required to elicit diuresis and
natriuresis in rats (Mozaffari and Schaffer, 2001), whereas 1g or more intravenously over
15 minutes (about 15 mg/kg bw) was sufficient in sensitive humans with liver cirrhosis
and ascites (Gentile et al., 1994).
Bearing in mind that taurine is rapidly absorbed across the gut via an active transport
mechanism, the diuretic effects in normal subjects with an acute consumption of 750 ml
of “energy” drink containing 3g of taurine are difficult to predict. The Committee noted
that since caffeine and taurine act via different mechanisms, any diuretic effects could be
additive.
Cardiovascular system
Caffeine can increase heart rate, force of contraction of heart muscle and blood pressure.
Taurine, on the other hand, depresses the activity of excitable membranes in the heart
(Huxtable, 1992). Caffeine enhances catecholamine synthesis and release from adrenal
cells in vitro, probably related to its effects on intracellular calcium (Matsumura et al.,
2000; McKenzie and Marley, 2002). Numerous in vivo studies have shown oral caffeine
at doses of 6 mg/kg bw or more increases plasma catecholamine concentrations,
especially adrenaline, in a dose-related manner during exercise (Bangsbo et al., 1992;
Van Soeren et al., 1993; Anderson and Hickey, 1994; Graham and Spriet, 1995; Jackman
et al., 1996; Kamimori et al., 2000), though one study giving 8.8 mg/kg in an “energy”
drink found no increase (Wemple et al., 1997). The acute consumption estimate for
“energy” drinks of 750 ml is equivalent to a caffeine intake of 4 mg/kg bw for a 60 kg
adult. There is no evidence that taurine increases catecholamine release; if anything it has
an inhibitory effect on excessive sympathetic activity in rat models of hypertension, with
reduction of plasma catecholamines (Yamamoto et al., 1985; Sato et al., 1987; Trachtman
et al., 1989). Neither does taurine given alone have any effect on heart rate or blood
pressure in rats or humans (Mozaffari and Schaffer, 2001; Gentile et al., 1994).
Both taurine and caffeine influence the activity of angiotensin II, an endogenously
formed substance that raises arterial blood pressure and reduces the excretion of sodium
and water by the kidney, but their action on angiotensin II is in opposite directions. In
vivo caffeine augments the action of angiotensin II on the kidney and may raise plasma
renin levels (Ohnishi et al., 1987; Holycross and Jackson, 1992; Brown et al., 1993;
7
Tseng et al., 1993), whereas taurine attenuates the effects of circulating angiotensin II
(Schaffer et al., 2000).
In view of the above data, the Committee considered that if there are any cardiovascular
interactions between caffeine and taurine, taurine might reduce the cardiovascular effects
of caffeine.
Potential for interactions between constituents of “energy” drinks and alcohol
In its earlier opinion (SCF, 1999), the Committee commented on the lack of research on
the effects of “energy” drinks in combination with alcohol and/or fluid loss during
exercise. The petitioner commented that there would be serious ethical problems in
conducting research to study directly the combined effects of high blood alcohol
concentrations with exercise, dehydration and consumption of “energy” drinks in
humans. The petitioner therefore submitted an evaluation by an outside expert (Red Bull
GmbH, 2002b), based on the existing literature, which discussed the possibility of
interactions between alcohol and taurine or caffeine, including consideration of whether
sweating and dehydration might predispose to additional effects.
The expert (Red Bull GmbH, 2002b) considered the acknowledged health risks in
situations of fluid and electrolyte loss through excessive sweating, pointing out that when
more than 7% of body water is lost or hyponatraemia (blood sodium below 135 mEq/l)
occurs, symptoms such as lung congestion, confusion, disorientation, muscle weakness,
loss of coordination, headache, nausea and vomiting can occur, and that in extreme
situations these can progress to cardio-respiratory arrest and death.
Taurine and alcohol
Studies on the effect of co-administration of alcohol and taurine on behaviour have used
different routes of administration of alcohol, varying doses, and differ in the order in
which taurine and alcohol were administered (Ferko, 1987). The results were inconsistent
and showed little or no clinical interaction (Aragon et al., 1992; Boggan et al., 1978;
Ferko and Bobyock, 1987). Taurine has antagonistic activity to alcohol in several
situations, including ethanol-induced sleep time (McBroom et al., 1986; Ferko, 1987),
effects of acute ethanol on memory (Vohra and Hui, 2000), and alcohol-induced liver and
gastric mucosal damage (Timbrell et al., 1995; Xieyonglixiao et al., 1998). These effects
are possibly mediated through taurine’s facilitation of the activity of the liver enzyme,
aldehyde dehydrogenase, which metabolises alcohol, thereby reducing blood levels of
alcohol (Messiha, 1979; Theofanopoulos et al., 1998a,b). In contrast, intraventricular coadministration of alcohol and taurine may increase the sedating effects of alcohol in mice
and rats (Ferko, 1987; Mattucci-Schiavone and Ferko, 1985; Yarbrough et al., 1981), a
situation in which taurine’s influence on aldehyde dehydrogenase in the liver would not
be evident. Alcohol intoxication or hypo-osmotic stress cause release of endogenous
taurine in several areas of the brain (Lallemand et al., 1998,200: Quertemont et al., 2000;
Ward et al., 2000; Guizouarn et al., 2000), but the significance, if any, of this observation
for exogenous taurine is unclear. These co-administration studies indicate that some
alcohol-taurine interactions are possible, including protective ones, but the effects are
neither marked nor consistent.
8
Both taurine (Gentile et al., 1994) and alcohol centrally inhibit the release of the
antidiuretic hormone, vasopressin, and the Committee considered that they could act
additively to increase water and sodium loss from the body in the short-term.
Caffeine and alcohol
The widely held belief that caffeine can antagonise the depressant effects of alcohol and
drugs is generally supported by the extensive literature on this subject. Both animal and
human studies indicate a modest, antagonistic effect of caffeine on the effects of alcohol,
but the effects are usually only seen with simpler tasks and at lower blood alcohol
concentrations (Moskowitz and Burns, 1971; Osborne and Rogers, 1983; Kerr et al.,
1991; Liguori et al., 1997; Kerr and Hindmarch, 1998; Liguori and Robinson, 2001;
Warburton et al., 2001). In humans, for example, the antagonistic activity of caffeine has
been shown in driving-related tasks of tracking, divided attention and some aspects of
reaction time after 2-5 standard alcoholic drinks. Most of the studies show the effects of
caffeine are dose-dependent and that caffeine does not affect blood alcohol
concentrations. Other studies have shown little if any ability of caffeine to antagonise the
psychomotor effects of alcohol (Newman and Newman, 1956; Forney and Hughes, 1965;
Mushill, 1979; Nuotto et al., 1982) and some have even raised the possibility that
caffeine might enhance the effects of alcohol, especially during the early phase of
drinking where some stimulatory properties of alcohol predominate (Hughes and Forney,
1961; Lowe, 1981; Osborne and Rogers, 1983; Dews, 1984). The majority of studies
suggest that caffeine would not exacerbate the adverse effects of alcohol and at lower
blood alcohol levels caffeine may improve performance.
Human case reports
The Committee was aware of a number of anecdotal reports of acute, adverse effects in
young persons consuming “energy” drinks, usually together with alcohol and/or drugs
used socially, such as ecstasy and amphetamines. The effects mentioned included,
tremors, seizures, drowsiness, muscle weakness, dizziness, nervousness, tachycardia,
palpitations, nausea, vomiting, headache, bronchospasm and hyperventilation. One case
of myocardial infarction in a 23-year-old playing football (Rallis, 2001) and one case of
sudden unexplained adult death syndrome, possibly resulting from cardiac dysrhythmia,
in an 18-year old playing basketball (Stimulant Drinks Committee, 2002) have also been
reported. The Committee had very little information about any of these cases and was not
aware that any had been written up in the medical literature. The co-consumption of
alcohol and/or drugs noted in most of these cases makes interpretation particularly
difficult. Thus, there is no confirmation of any causal relationship between the reported
effects and the consumption of “energy” drinks. Under these circumstances, the reports
can only be noted.
9
Conclusions
Taurine
In its previous opinion on “energy” drinks, the SCF commented as follows on taurine
(SCF, 1999):
“Toxicological studies did not reveal any indication for a genotoxic, carcinogenic
or teratogenic potential of taurine. However, there is no adequate study on chronic
toxicity/carcinogenicity. Investigation of subacute/subchronic toxicity has also
been fragmentary. Overall, the available data are insufficient to establish an upper
safe level for daily intake of taurine.”
The new 13-week study in rats provided further useful information in that it showed no
significant changes in pathological measures, but it did show the occurrence of
significant behavioural effects (increased activity and self-chewing), and possibly
impaired motor performance, which could be mediated via a pharmacological action on
the central nervous system. In view of this the Committee is of the opinion that focused
neurological studies are now needed.
The Committee concluded that these effects should be taken into account in human risk
assessment, noting that behavioural effects were observed at the lowest dose tested of 300
mg/kg bw/day. This effect level is 36-fold above the estimated human intake of taurine
(8.3 mg/kg bw for a 60 kg adult) at the mean chronic daily intake for “energy” drinks,
and 6-fold above the more relevant estimate for acute intake (50 mg/kg bw for a 60 kg
adult). The absence of a NOAEL for these effects precludes the setting of an upper safe
level for daily intake of taurine. The Committee’s reservations are expressed in the
context of an estimated acute intake of taurine of up to 3000 mg/day from consumption
of “energy” drinks, compared with the highest estimated intake of taurine from naturally
occurring sources in the diet of 400 mg/day.
Glucuronolactone
In its previous opinion on “energy” drinks, the SCF commented as follows on
glucuronolactone (SCF, 1999):
“Human metabolic considerations indicate the body is likely to handle small
quantities of glucuronolactone without any problems. However, the intake of
glucuronolactone from consumption of some "energy" drinks is possibly as much
as two orders of magnitude greater than that from the rest of the diet. There is
very little information available for risk assessment of glucuronolactone at such
intakes. While there is no indication from the available data that there is any risk
to health from consumption of high amounts of glucuronolactone, there is a lack
of scientific evidence to support the safety of glucuronolactone present in
beverages at concentrations that may result in intakes as much as two orders of
magnitude greater than that obtained from the rest of the diet. As was the case
with taurine, there is insufficient information on which to set an upper safe level
for daily intake of glucuronolactone.”
10
The new 13-week study provided useful information indicating that in rats, there were no
adverse effects except on the kidney. The NOAEL for these effects was 300 mg/kg bw,
which is around 20-fold above the estimate of high chronic intake of glucuronolactone of
14 mg/kg bw/day for a 60 kg adult. The hamster study and the new 13-week rat study
both provided information showing no effects on body weight gain in growing animals.
However, the 1999 opinion also pointed out that rodents may not be an appropriate model
for man since they can metabolise exogenous glucuronolactone to vitamin C whereas
primates, including man, do not possess this metabolic pathway.
The Committee therefore reiterates its earlier conclusion (SCF, 1999) that there is a lack
of scientific evidence to support the safety of glucuronolactone present in beverages at
concentrations that may result in intakes several-fold higher than that usually obtained
from the rest of the diet. Due to the lack of relevant data it is not possible to set an upper
safe level for daily intake of glucuronolactone. The Committee’s reservations are
expressed in the context of an estimated high chronic intake of glucuronolactone of 840
mg/day and an acute intake of up to 1800 mg/day from consumption of “energy” drinks,
compared with the estimated intake of glucuronolactone from naturally occurring sources
in the diet of 1-2 mg/day.
Caffeine
The Committee’s earlier opinion on caffeine (SCF, 1999) remains unchanged (see
“Background”).
Interactions between constituents of energy drinks, alcohol and exercise
The Committee considers it unlikely that glucuronolactone would have any interaction
with caffeine, taurine, alcohol or the effects of exercise.
The Committee concluded that consideration of the potential for interactions between
caffeine and taurine has not ruled out the possibility of stimulatory effects from both
substances at the level of the central nervous system. At the cardiovascular level, if there
are any interactions between caffeine and taurine, taurine might reduce the cardiovascular
effects of caffeine. The main area for likely additive interactions is in the diuretic actions
of caffeine and taurine, which could be further enhanced by ingestion of alcohol. This,
coupled with loss of body fluids via sweating on exercise, could, theoretically, result in
short-term dehydration. While the Committee notes that some of the anecdotally reported
symptoms in humans are compatible with loss of body water and sodium, it is also
apparent that they may equally well be related to the intake of high amounts of alcohol
and/or drugs reported in many of these cases. It is therefore not possible to draw
definitive conclusions about effects in humans.
11
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WIL (2001a). A 13-week oral (gavage) toxicity study of taurine in rats. Final Report,
December 26, 2001, WIL-423002. WIL Research Laboratories Inc., Ohio, USA.
Submitted to the European Commission by Red Bull GmbH, Brunn 115, A-5330 Fuschl
am See, Austria, 31 December 2001.
WIL (2001b). A 13-week oral (gavage) toxicity study of D-glucuronolactone in rats.
Final Report, December 21, 2001, WIL-423001. WIL Research Laboratories Inc., Ohio,
USA. Submitted to the European Commission by Red Bull GmbH, Brunn 115, A-5330
Fuschl am See, Austria, 31 December 2001.
Xieyonglixiao P-W, Huagde Q-Q, Zhangkun H (1998). Ethanol-induced gastric mucosal
injury and the protection of taurine against the injury in rats. Clin Pharmacol Bull 14:
140-142.
Yamada T, Nogariya T, Nakane S, Sasajima M (1981). Reproduction studies of taurine teratogenicity study in rats. Japan Pharmacology and Therapeutics 15: 87-98.
Yamamoto S (1996). Plasma taurine in liver cirrhosis with painful muscle cramps.
Advances in Experimental Medicine and Biology 403: 597-600.
Yamamoto J, Akabane S, Yoshimi H, Nakai M, Ikeda M (1985). Effects of taurine on
stress-evoked hemodynamic and plasma catecholamine changes in spontaneously
hypertensive rats. Hypertension 7: 913-922.
Yamashiro Y, Shimizu T, Ohtsuka Y, Nittono H, Miyano T, Kawakami S, Hayasawa H
(1994). Docosahexanoic acid status of patients with extrahepatic biliary atresia. Journal
of Pediatric Surgery 29: 1455-1458.
Yarbrough GG, Singh DK, Taylor DA (1981). Neuropharmacological characterisation of
a taurine antagonist. Journal of Pharmacology and Experimental Therapeutics 219: 604613.
19
ANNEX 1
Intake data on “energy” drinks from recent surveys
Austrian survey
A new intake survey has been conducted in Austria (Red Bull GmbH, 2001), the EU
country with the highest per capita “energy” drink consumption. Consumption has not
significantly changed in recent years, indicating, according to the petitioner, that Austria
can be regarded as a saturated market. The aim of the survey was to record chronic and
acute consumption patterns among ‘regular users’ of “energy” drinks. ‘Regular users’
were defined as those who consumed at least one “energy” drink per week.
The survey was conducted in 2001 on 8500 Austrians aged 15 years and over. Forty-two
percent of the sample consumed “energy” drinks at least occasionally and 12% were
regular users. The 1007 regular users were further questioned in detail about their
consumption habits. “Energy” drink consumers were more often male (55% of
consumers, 59% of regular users) than female and were also largely in the age range 1530 years (46% of consumers, 61% of regular users).
Chronic consumption
Regular users were asked to recall the number of cans of “energy” drink they had
consumed the previous week (7 day recall - 7DR), the number of cans they usually drank
in one week (food frequency questionnaire - FFQ), and the number of cans they had
consumed in the previous 24 hours (24-hour recall - 24HR). From these, estimates of
both mean and high consumption may be made. The statistical distribution of intake was
very skewed with a large number of “small” consumers and a few “extreme” consumers.
There was good consistency between the estimates obtained using the three different
indicators (7DR, FFQ and 24HR) for the mean daily quantities consumed by regular
users, as shown in Table 1.
Table 1: Mean daily chronic consumption of “energy” drink by regular users
Indicator
7DR
FFQ
24HR
No. of 250 ml cans/day
0.45
0.47
0.52*
* Including consumers and non-consumers on that day
20
Intakes by high consumers are shown in Table 2. Again there was good agreement
between the two indicators. Note that the 24HR data cannot be used for this estimate.
Table 2: High chronic consumption of “energy” drink by regular users*
Indicator
7DR
FFQ
No. of 250 ml cans
90th percentile
7/week = 1/day
6/week = 0.9/day
No. of 250 ml cans
95th percentile
10/week = 1.4/day
10/week = 1.4/day
* N = 1007 regular users
Acute consumption
Acute intakes are shown in Table 3. Regular users were asked both about the maximum
amount of “energy” drinks they had ever consumed at one time and for their 24HR. The
first question could lead to biased answers and the so the 24HR figures are shown below
as these are considered more likely to be accurate.
Table 3: Acute consumption of “energy” drink by regular users
Indicator
24HR
No. of 250 ml cans/day
Mean
1.7
No. of 250 ml cans/day
90th percentile
2.6
Irish survey
The review commissioned in Ireland (Stimulant Drinks Committee, 2002) included
information on consumption of “energy” drinks, as part of a market research survey
conducted during July 2001, using face-to-face interviews with 625 people in the
Republic of Ireland and 635 people in Northern Ireland, aged 11-35 years. In Northern
Ireland and Republic of Ireland respectively, 51% and 37% of participants reported ‘ever’
consuming “energy” drinks and 10% and 11% reported consuming “energy” drinks
frequently. Among ‘ever’ consumers, average consumption was 3 (250 ml) cans/week
and for the 95th percentile consumers it was 8 cans/week. The most number of cans
consumed in a single session among ‘ever’ consumers averaged approximately 3 cans,
rising to 8 cans among the highest consumers; the comparable figure for 11-14 year-olds
was approximately 2 cans. These results are similar to those obtained in the Austrian
survey.
21
ANNEX 2
Details of toxicological studies submitted on Red Bullâ, taurine and
glucuronolactone
13-week mouse oral toxicity study on Red Bullâ
Groups of 20 mice/sex/dose were given Red Bullâ either undiluted or as a mixture with
tap water at concentrations of 0, 33, 50 or 100% in the drinking water ad libitum for 13
weeks from 6 weeks of age. The study (RCC, 2000) was conducted in compliance with
Good Laboratory Practice (GLP) regulations and conforming to 1981 OECD Guidelines
(OECD, 1981).
Mean intakes of Red Bullâ (RB) during the study period were equivalent to 89, 145 and
427 g/kg bw/day and 126, 188 and 520 g/kg bw/day in 33, 50 and 100% RB male and
female groups respectively. Intakes of the individual constituents of interest were as
shown in Table 5:
Table 1: Intakes of caffeine, taurine and glucuronolactone
Percentage RB
in drinking
water
33
50
100
Caffeine
mg/kg bw/day
Male
Female
Taurine
mg/kg bw/day
Male
Female
27
44
131
342
554
1625
39
58
159
483
720
1989
Glucuronolactone
mg/kg bw/day
Male
Female
205
333
981
290
432
1194
The significant findings were a reduction in mean body weight in all groups receiving RB
compared with controls. Terminal body weights were significantly reduced by 11%, 12%
and 15% in males and 8%, 6% and 12% in females in 33, 50 and 100% RB groups
respectively. Food intake was transiently reduced at the start of the study in the 33 and
50% RB groups and during most of the study, by around 9%, in both sexes given 100%
RB. Water/fluid consumption was significantly higher in all treated groups compared
with controls throughout the study. Average differences from controls were +40%, +48%
and +115% in males and + 27%, +27% and + 67% in females, in 33, 50 and 100% RB
groups respectively.
There were statistically significant increases in blood glucose in females given 33 or 50
% RB and in both sexes at 100% RB. Other significant findings were decreases in mean
corpuscular haemoglobin concentration, platelet count and reticulocyte count in males
receiving 100% RB. Creatinine was reduced in 100% RB females. Alkaline phosphatase
levels were raised in 100% RB males. Calcium was reduced in 50% RB males and 100%
RB males and females. Sodium was reduced in 100% RB males and chloride increased in
100% RB females. Total protein and absolute albumin concentrations were reduced in
22
100% RB males and females. The urine of 100% RB males had increased specific gravity
and osmolality.
Both absolute and relative weights of the inguinal fat pad were reduced in all treated male
groups, suggesting the reductions in body weight may have been attributable to a reduced
proportion of body fat. There were no treatment-related macroscopical or microscopical
findings, apart from a reduction in liver centrilobular fat vacuolation in 100% RB males.
13-week rat oral toxicity study on taurine
Groups of 20 rats/sex/dose were given taurine at doses of 0, 300, 600 and 1000 mg/kg
bw/day, dissolved in deionised water, orally by gavage once daily for 13 weeks from 6
weeks of age (WIL, 2001a). The study was conducted in compliance with GLP
regulations and to a protocol in accordance with US Food and Drug Administration
Redbook II Guidelines (FDA, 1993).
In a concurrent toxicokinetic study on separate animals, 12 animals/sex/dose were given
the same dosages as in the main toxicology study and blood samples taken from 3
animals/sex/dose, at time 0 (immediately prior to dosing), 1, 2, 4, 8 and 24 hours
following dosing on days 0 and 90 of the study, for estimation of plasma taurine levels.
Blood samples were collected from concurrent controls (6 animals/sex) on the same days
at 0, 2 and 8 hours following dosing with vehicle.
There were no treatment-related deaths and only transient higher body weight gains in
some treated groups. Food consumption was unaffected by treatment. There were some
statistically significant differences in haematological and clinical chemistry parameters
measured at 4, 8 and 13 weeks between treated and control groups, but the differences
were small and none were seemingly treatment-related. There was a dose-related
reduction in urinary pH in both sexes, which was probably attributable to the presence of
acidic taurine in the urine.
Small but significant reductions in absolute and relative thyroid/parathyroid gland
weights in males at 1000 mg/kg and in females at 300, 600 and 1000 mg/kg were
attributable to control values that were relatively high compared with laboratory
historical controls and concurrent controls in the glucuronolactone study (see later).
Because of the differences in thyroid weights at necropsy, serum TSH and T4 were
measured. The only finding was a significant reduction in TSH levels in 600 mg/kg
males at 4 weeks. There were no treatment-related gross or microscopic findings in any
organs or tissues, including the thyroid.
Clinical observations were performed on all animals at the time of dosing and about 1
hour after dosing. Significant behavioural changes were observed 1 hour after dosing.
Table 6 shows the results of the 1-hour observations over the 13 weeks of the study.
23
Table 2: Clinical observations (Total occurrences/No. of animals) 1 hour after
dosing with taurine
Dose (mg/kg bw/day)
Number of animals
Observations
Increased activity
Chewing of forelimb(s)
Chewing of hindlimb(s)
Chewing of cage
Hyper-reactive to touch
0
20
Males
300
600
20
20
1000
20
1/1
0/0
0/0
0/0
0/0
5/4
0/0
0/0
0/0
0/0
11/8
3/3
1/1
1/1
1/1
4/4
2/2
0/0
0/0
0/0
0
20
Females
300
600
20
20
1000
20
3/2
0/0
0/0
0/0
0/0
36/10
3/2
1/1
0/0
0/0
62/16
11/7
2/2
2/2
0/0
29/10
3/3
2/2
1/1
0/0
Increased activity was recorded in all treated groups compared with controls, particularly
in females. The increase in frequency and number of animals exhibiting this behaviour
was similar in 300 and 600 mg/kg males and females and greatest in the 1000 mg/kg
groups. The frequency was similar in the first and last months of the study showing that
tolerance did not develop over time. Chewing on forelimbs and hindlimbs was also seen
in a few animals among 600 and 1000 mg/kg males and in all groups of treated females.
The frequency was highest among 1000 mg/kg females.
These findings were followed up in a functional observation battery conducted at 6 and
12 weeks on control and 1000 mg/kg groups. There were occasional observations in the
treated group, mostly in females, of greater alertness in the home cage, cage biting,
higher arousal in the open field, more energetic reactions to approach, touch and startle
response stimuli and jumping, biting or attacking in response to tail pinch. However, all
but one of these behaviours was seen in only single animals and none of the differences
were statistically significant. Impaired performance on the rotarod was seen in both sexes
of the 1000 mg/kg group; the mean length of time they remained on the rotarod compared
with controls was reduced by 49% and 52% in males and females respectively at 6 weeks
and by 24% and 18% in males and females respectively at 12 weeks. Due to high
variability within groups, none of these reductions were statistically significant. In a 60
minute test for locomotor activity run on individual animals at 6 and 12 weeks, a
significant reduction in mean ambulatory activity and a non-significant reduction in mean
total activity were seen in 1000 mg/kg males at 6 weeks. There were no effects in males
at 12 weeks or in females at 6 or 12 weeks.
In the toxicokinetic study, plasma taurine levels increased in a dose-related manner,
reaching peak Cmax values at around 1 hour after dosing and generally returning to
baseline values by 24 hours. Plasma taurine levels 2 hours after dosing were 21-51% of
the values measured at one hour. Initial half-life was less than 1 hour and terminal halflife ranged from 8.7 to 40 hours. Plasma concentrations 24 hours after dosing were
comparable with control values both on study day 0 and on day 90. Area under the
plasma-time concentration curve (AUC) values were similar on study days 0 and 90.
Both Cmax and AUC were proportional to dose. This study showed that taurine is readily
bioavailable following oral administration and that it does not accumulate.
24
13-week rat oral toxicity study on glucuronolactone
Groups of 20 rats/sex/dose were given D-glucuronolactone at doses were 0, 300, 600 and
1000 mg/kg bw/day, dissolved in deionised water, orally by gavage once daily for 13
weeks from 6 weeks of age (WIL, 2001b). The study was conducted in an almost
identical manner to the study on taurine described above, in compliance with GLP
regulations and to a protocol in accordance with FDA Redbook II Guidelines (FDA,
1993). In this study no functional observation battery was performed. A concurrent
toxicokinetic study on separate animals was conducted to the same protocol as described
earlier for the taurine study.
There were no deaths and only transiently higher body weight gains in some treated
groups. There were no significant effects on food consumption, apart from higher food
consumption in 300, 600 and 1000 mg/kg females in week 10-11.
There were some statistically significant differences in haematological and clinical
chemistry parameters measured at 4, 8 and 13 weeks between treated and control groups,
but the differences were small and none were seemingly treatment-related. In urinalysis,
the only significant differences were in males: an increase in total volume at 600 mg/kg, a
lower specific gravity at 600 and 1000 mg/kg and a lower pH at 1000 mg/kg at 13 weeks.
There were no significant effects on organ weights, but histopathological changes were
found in the kidneys of females in the 600 and 1000 mg/kg groups. These changes
included cytoplasmic vacuolation, and inflammatory changes. Cytoplasmic vacuolation
was present in 50% of all groups including controls but the incidence of mild as opposed
to minimal change was dose-related (1/20, 1/20, 5/20, 8/20 in control, 300, 600 and 1000
mg/kg groups). No inflammatory changes were seen in the controls or 300 mg/kg group,
but they were seen in 2/20 females in the 600 mg/kg group and in 3/20 females in the
1000 mg/kg group. Although inflammatory changes are typically seen in the presence of
mineralisation, calculi or crystaluria, none of these types of change were observed,
neither was there any evidence of urinary bladder irritation. No treatment related effects
were seen in the kidneys of males.
In the toxicokinetic study, plasma glucuronolactone levels increased in a dose-related
manner, reaching peak Cmax values at around 1-4 hours on study day 0 and at 1 hour on
study day 90. The half-life ranged from 0.89 to 3.9 hours. AUC values were similar on
study days 0 and 90. Both Cmax and AUC were proportional to dose. These results show
that glucuronolactone is bioavailable following oral administration and that it does not
accumulate.
25
The EFSA Journal (2009) 935, 1-31
SCIENTIFIC OPINION
The use of taurine and D-glucurono-γ-lactone as constituents of
the so-called “energy” drinks 1
Scientific Opinion of the Panel on Food Additives and Nutrient
Sources added to Food
(Question No EFSA-Q-2007-113)
Adopted on 15 January 2009
PANEL MEMBERS
F. Aguilar, U.R. Charrondiere, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R.
Guertler, G.E.N. Kass, J. Koenig, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D.
Parent-Massin, I. Pratt, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R.A.
Woutersen.
SUMMARY
Following a request from the Commission, the Scientific Panel on Food Additives and
Nutrient Sources added to Food (ANS) has been asked to evaluate the safety-in-use of taurine
and D-glucurono-γ-lactone as constituents of the so-called “energy” drinks.
In the present opinion the Panel evaluates the safety of taurine and D-glucurono-γ-lactone as
individual ingredients of so-called “energy” drinks based on the new studies provided by the
petitioner.
The Panel does not evaluate the safety of “energy” drinks as such.
Taurine and D-glucurono-γ-lactone are constituents of the so-called “energy” drinks, but they
also occur at much lower levels as natural ingredients in food, and they are also normal
human metabolites. Previous Scientific Committee on Food (SCF) Opinions have
summarized safety studies of taurine and D-glucurono-γ-lactone, but the safety-in-use of these
1
For citation purposes: Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food
on a request from the Commission on the use of taurine and D-glucurono-γ-lactone as constituents of the socalled “energy” drinks. The EFSA Journal (2009) 935, 1-31.
© European Food Safety Authority, 2009
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
two ingredients at the levels of exposure expected from their use in “energy” drinks could not
be established at that time.
In the absence of new chronic and acute exposure data, the exposures used in this opinion are
based on the data reported by the SCF in 2003, i.e. a daily mean chronic consumption of 0.5
cans per person and a high chronic exposure at the 95th percentile of 1.4 cans per regular
consumer. The Panel notes that actual exposure data on “energy” drink consumption,
especially for adolescents and young adults, may need to be collected. Based on the
assumption that a can contains 250 mL and 4000 mg/L taurine and 2400 mg/L D-glucurono-γlactone, the SCF calculated that these values result in a mean daily exposure to 500 mg
taurine (8.3 mg taurine/kg bw/day for a 60 kg person) and 300 mg D-glucurono-γ-lactone (5.0
mg D-glucurono-γ-lactone/kg bw/day for a 60 kg person). The 95th percentile exposure of
regular users would amount to 1400 mg taurine/day (23.3 mg/kg bw/day for a 60 kg person)
and 840 mg D-glucurono-γ-lactone /day (14 mg/kg bw/day for a 60 kg person).
If it is assumed that this amount of chronic consumption is relevant to occasional exposure of
children of 25 kg body weight, then their exposure (on a body weight basis) would be about
2.5 times higher than that for adults (60-65 kg body weight). It must be emphasized that these
estimates relate to chronic exposures by average and high consuming adults, and would not
reflect the occasional and sporadic exposure that might occur in children. If the frequency of
exposure for children would be 2.5 times lower than for adults, then the average chronic
exposure for children, on a body weight basis, would be the same as for adults. If children
were to consume the adult intake of 0.5 and 1.4 cans per person only once per week, then the
average chronic exposure to “energy” drinks and their constituents for children, on a body
weight basis, would be one third of that for adults.
These estimates for the daily exposure to taurine and D-glucurono-γ-lactone from “energy”
drinks are higher than the estimated mean daily exposure to taurine from omnivore diets
which was estimated to be at most 400 mg/day, and that of D-glucurono-γ-lactone from
naturally occurring sources in the diet estimated to amount to 1-2 mg/day.
The SCF Opinion of 2003 used 3 cans/day as a reasonable high (acute) consumption, this
amount being higher than the 90th percentile recorded in the Austrian survey (2.6 cans/day)
and being the average reported in the Irish survey for the highest number of cans consumed in
a single session. The SCF also indicated that it was aware that amounts of up to 8-12 cans/day
were reported by a few extreme consumers in both surveys, which would result in an intake of
4800-7200 mg D-glucurono-γ-lactone and 8000-12000 mg taurine per day, equivalent to 80120 mg D-glucurono-γ-lactone/kg bw/day and 133-200 mg taurine/kg bw/day for a 60 kg
person.
The SCF Opinion of 2003 and the recent BfR Opinion mention a number of anecdotal and
case reports of acute, adverse effects, including fatalities, in individuals consuming “energy”
drinks, containing caffeine, taurine and D-glucurono-γ-lactone. In these cases “energy” drinks
had either been consumed in very high amounts (1420 mL), in combination with physical
exercise, or more frequently together with alcohol. The Panel considers that it is possible that
the effects reported in recent publications by Iyadurai and Chung, Nagajothi et al. and Terlizzi
et al. could be due to the well known side effects of high caffeine intake, while the
assumption of a causal relationship with taurine intake is lacking scientific evidence.
Taurine
Upon oral exposure taurine is readily bioavailable in the systemic circulation. The Panel
concludes that new ADME data support the contention that oral exposure to taurine was not
The EFSA Journal (2009) 935, 2-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
increasing taurine levels in the brain, because in rat studies, brain taurine levels did not
increase after dosage.
The SCF already concluded in 1999 that toxicological studies did not reveal any indication for
a genotoxic, teratogenic or carcinogenic potential of taurine.
It can be concluded that the NOAEL derived from a new 13-week oral neurotoxicity study in
male and female rats including functional observational battery and locomotor activity tests,
confirmed the NOAEL established in the prior 13-week study, described already by the SCF
in 2003, of 1000 mg taurine/kg bw/day, and provided evidence for a NOAEL of 1500 mg
taurine/kg bw/day for behavioural effects. The results of this study were sufficient to address
the concerns raised previously, notably the observation of increased activity and possible
decrements in motor skills on the rotarod.
The NOAEL of at least 1000 mg/kg bw/day for pathological changes is respectively 120-fold
higher than the estimated mean and 43-fold higher than the estimated 95th percentile exposure
to taurine from “energy” drinks only, when calculated for a 60 kg person. Given that taurine is
a natural body constituent, the Panel concludes that these margins of safety are sufficiently
large to conclude that exposure to taurine at the levels mentioned above is not of safety
concern.
D-glucurono-γ-lactone
The SCF already concluded that the available data indicate that D-glucurono-γ-lactone
administered orally to humans is rapidly absorbed, metabolised and excreted as glucaric acid,
xylitol and L-xylulose. Animals, such as rodents, which can synthesise vitamin C
endogenously do so from glucuronic acid and such animals can also convert exogenously
administered D-glucurono-γ-lactone into vitamin C. However, primates, including man, and
guinea pigs do not possess this metabolic pathway. The SCF concluded that for this reason,
the rodent may be an inappropriate model for man in the study of the effects of D-glucuronoγ-lactone. The Panel concludes that data in the literature indicate that synthesis of vitamin C is
only a minor pathway of D-glucurono-γ-lactone metabolism in the rat and of limited
relevance to the safety assessment of exogenous D-glucurono-γ-lactone.
In 2003 the SCF evaluated a 13-week oral toxicity rat study with D-glucurono-γ-lactone and
concluded that the cause of the kidney lesions remained unclear.
The petitioner has now provided data from a new 13-week oral (gavage versus drinking
water) toxicity study of D-glucurono-γ-lactone in rats, with specific focus on the kidneys.
This study used the same rat strain as the previous study reported in the SCF Opinion of 2003.
Extensive urinalysis and histopathological examinations demonstrated no treatment-related
effects. Based on the results of this study, the NOAEL for daily oral administration of Dglucurono-γ-lactone in rats was 1000 mg/kg bw/day, the highest dose tested.
Toxicological studies on the genotoxic, teratogenic or carcinogenic potential of D-glucuronoγ-lactone were not available. However, D-glucurono-γ-lactone is a normal human metabolite
formed from glucose and there are no structural alerts for mutagenicity or carcinogenicity. At
physiological pH it is in equilibrium with glucoronic acid, its immediate precursor. Dglucurono-γ-lactone and its hydrolysis product glucuronic acid are endogenous metabolites in
humans and other mammals, they occur naturally in several dietary sources and are readily
metabolized to innocuous products and excreted. Furthermore, in the high dose 13-week rat
studies there was no evidence of any effect on the gonads which might indicate the need for
reproductive toxicity studies.
The EFSA Journal (2009) 935, 3-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
The NOAEL for D-glucurono-γ-lactone of 1000 mg/kg bw/day is 200-fold higher than the
estimated mean and 71-fold higher than the estimated 95th percentile exposure to Dglucurono-γ-lactone from “energy” drinks only, when calculated for a 60 kg person.
Given the fact that D-glucurono-γ-lactone is a natural body constituent the Panel concludes
that these margins of safety are sufficiently large to conclude that exposure to D-glucurono-γlactone at the levels mentioned above is not of safety concern.
Overall, the Panel concludes that the exposure to taurine and D-glucurono-γ-lactone at the
levels currently used in “energy” drinks and mentioned in the present opinion is not of safety
concern.
The ANS Panel agrees with the considerations of the SCF Opinion from 2003 on the fact that
it is unlikely that D-glucurono-γ-lactone would have any interaction with caffeine, taurine,
alcohol or the effects of exercise. The Panel also concludes, based on the new data available,
that additive interactions between taurine and caffeine on diuretic effects are unlikely. Other
interactions between taurine and caffeine were not investigated.
Key words:
Taurine, CAS No. 107-35-7, D-glucurono-γ-lactone, CAS No. 32449-92-6, “energy” drinks.
The EFSA Journal (2009) 935, 4-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
TABLE OF CONTENTS
Panel Members .........................................................................................................................................1
Summary ..................................................................................................................................................1
Background as provided by the Commission...........................................................................................6
Terms of reference as provided by the Commission ................................................................................7
Acknowledgements ..................................................................................................................................7
Assessment ...............................................................................................................................................8
1.
Technical data ................................................................................................................................8
1.1. Chemistry..................................................................................................................................8
1.2. Manufacturing Process..............................................................................................................9
1.3. Specifications............................................................................................................................9
1.4. Methods of analysis in foods ....................................................................................................9
1.5. Reaction and fate in foods, stability..........................................................................................9
1.6. Case of need and use levels ......................................................................................................9
1.7. Exposure .................................................................................................................................10
1.8. Existing authorisations and evaluations..................................................................................11
2.
Biological and toxicological data.................................................................................................12
2.1. Absorption, distribution, metabolism and excretion ...............................................................12
2.2. Toxicological data...................................................................................................................14
2.2.1.
Acute oral toxicity....................................................................................................14
2.2.2.
Short-term and sub-chronic toxicity ........................................................................14
2.2.3.
Reproductive and developmental toxicity................................................................17
2.2.4.
Mutagenicity ............................................................................................................17
2.2.5.
Carcinogenicity and long-term studies ....................................................................18
2.2.6.
Human data ..............................................................................................................18
3.
Discussion ....................................................................................................................................20
Conclusions and Recommendations.......................................................................................................23
Documentation provided to EFSA .........................................................................................................23
References ..............................................................................................................................................23
Glossary / Abbreviations ........................................................................................................................31
The EFSA Journal (2009) 935, 5-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
BACKGROUND AS PROVIDED BY THE COMMISSION
On 21 January 1999 the Scientific Committee on Food (SCF) expressed an opinion on
caffeine, taurine and D-glucurono-γ-lactone as constituents of the so-called “energy” drinks.
For taurine and D-glucurono-γ-lactone, the SCF was unable to conclude that the safety-in-use
of taurine and D-glucurono-γ-lactone in the concentration ranges reported for these
constituents in “energy” drinks had been adequately established. It indicated that further
studies would be required to establish upper safe levels for daily intake of taurine and Dglucurono-γ-lactone.
In 2002, following the submission of new information by a manufacturer of “energy” drinks
and the publication of reports and statements on the issue by the Australian New Zealand
Food Safety Authority and the UK Food Standard Agency, the SCF was asked by the
Commission to indicate if the conclusions of its opinion of 1999 needed to be revised. On 5
March 2003, the SCF expressed an opinion on additional information on “energy” drinks.
Concerning taurine, the SCF indicated that the new 13-week study in rats provided further
useful information and that it showed no significant changes in pathological measures, but it
did show the occurrence of significant behavioural effects (increased activity and selfchewing), and possibly impaired motor performance, which could be mediated via a
pharmacological action on the central nervous system. In view of this, the SCF was of the
opinion that focused neurological studies were needed. The SCF concluded that these effects
should be taken into account in human risk assessment, noting that behavioural effects were
observed at the lowest dose tested of 300 mg/kg bw/day. This effect level is 36-fold above the
estimated human intake of taurine (8.3 mg/kg bw/day for a 60 kg adult) at the mean chronic
daily intake for “energy” drinks, and 6-fold above the more relevant estimate for acute intake
(50 mg/kg bw/day for a 60 kg adult). The absence of a NOAEL for these effects precludes the
setting of an upper safe level for daily intake of taurine. The SCF’s reservations were
expressed in the context of an estimated acute intake of taurine up to 3000 mg/day from
consumption of “energy” drinks, compared with the highest estimated intake of taurine from
naturally occurring sources in the diet of 400 mg/day.
Concerning D-glucurono-γ-lactone, the new 13-week study provided useful information
indicating that in rats there were no adverse effects except on the kidney. The NOAEL for
these effects was 300 mg/kg bw/day, which is around 20-fold above the estimate of high
chronic intake of D-glucurono-γ-lactone of 14 mg/kg bw/day for a 60 kg adult. The hamster
study and the new 13-week rat study both provided information showing no effects on body
weight gain in growing animals. However, the 1999 Opinion also pointed out that rodents
may not be an appropriate model for man since they can metabolise exogenous
glucuronolactone to vitamin C whereas primates including man do not possess this metabolic
pathway. The SCF therefore reiterated its earlier conclusion (SCF, 1999) that there is lack of
evidence to support the safety of D-glucurono-γ-lactone present in beverages at
concentrations that may result in intakes several-fold higher than that usually obtained from
the rest of the diet. Due to the lack of relevant data, it was not possible to set an upper safe
level for daily intake of D-glucurono-γ-lactone. The SCF’s reservations were expressed in the
context of an estimated high chronic intake of D-glucurono-γ-lactone of 840 mg/day and an
acute intake of up to 1800 mg/day from consumption of “energy” drinks, compared with the
estimated intake of D-glucurono-γ-lactone from naturally occurring sources in the diet of 1-2
mg/day.
The EFSA Journal (2009) 935, 6-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
Following these opinions, and taking into account the remarks made by the SCF, a
manufacturer of “energy” drinks has submitted new data on the safety-in-use of taurine and
D-glucorono-γ-lactone as constituents of the so-called “energy” drinks.
TERMS OF REFERENCE AS PROVIDED BY THE COMMISSION
In accordance with Article 29 (1) (a) of Regulation (EC) No 178/2002, the European
Commission asks the European Food Safety Authority to:
-
review the data submitted on the safety-in-use of taurine and D-glucurono-γ-lactone as
constituents of the so-called “energy” drinks
-
consider, if appropriate, to provide a scientific opinion on the safety-in-use of taurine
and D-glucurono-γ-lactone as constituents of the so-called “energy” drinks.
ACKNOWLEDGEMENTS
The European Food Safety Authority wishes to thank the members of the Working Group B
on Food Additives and Nutrient Sources for the preparation of this opinion: D. Boskou, U.R.
Charrondiere, B. Dusemund, D. Gott, T. Hallas-Møller, K.F.A.M. Hulshof, J. König, D.
Parent-Massin, I.M.C.M. Rietjens, G.J.A. Speijers, P. Tobback, T. Verguieva, R.A.
Woutersen.
The EFSA Journal (2009) 935, 7-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
ASSESSMENT
In the present opinion the Panel evaluates the safety of taurine and D-glucurono-γ-lactone as
individual ingredients of the so-called “energy” drinks based on the new toxicological studies
provided by the petitioner. The Panel does not evaluate the safety of “energy” drinks as such.
1. Technical data
1.1. Chemistry
Taurine
Taurine (CAS No. 107-35-7) occurs naturally in food, especially in seafood and meat, and it
is a normal metabolite in humans. It is a metabolic product of sulphur-containing amino acids,
and it is mainly biosynthesised from cysteine in the liver (SCF, 1999). Its molecular weight is
125.15 g/mol, the molecular formula is C2H7NO3S and the structural formula is as shown:
D-glucurono-γ -lactone
D-glucurono-γ-lactone (CAS No. 32449-92-6) is a normal human metabolite formed from
glucose. At physiological pH it is in equilibrium with glucuronic acid, its immediate precursor
(see figure below). Glucuronic acid occurs in plants, mainly in gums, but as it is in polymeric
combination with other carbohydrates it is not readily available. Glucuronic acid is also an
important constituent of fibrous and connective tissues in all animals (SCF, 1999). The
molecular weight of D-glucurono-γ-lactone is 176.12 g/mol, the molecular formula is C6H8O6
and the structural formula is as shown:
O
O
O
HO
OH
HO
O
+
H2O
OH
HO
D-glucurono-γ-lactone
OH
HOOC
OH
D-glucuronic acid
The EFSA Journal (2009) 935, 8-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
1.2.
Manufacturing Process
The petitioner provided adequate information on the production process of taurine, retrieved
from supplier information describing the general principle of the process. Taurine can be
made from monoethanolamine and sulphuric acid as the starting materials or from ethylene
oxide and sodium hydrogen sulphate as the starting materials. The crude production is
followed by purification steps.
The petitioner provided adequate information on the production process of D-glucurono-γlactone, retrieved from supplier information describing the general principle of the process.
D-glucurono-γ-lactone is made from nitric acid and starch as the starting materials. The crude
production is followed by purification steps.
1.3.
Specifications
The petitioner indicated that taurine used in “energy” drinks complies with US
pharmacopoeia specifications (US Pharmacopeia, 2005). Purity is not less than 98.5 %.
The petitioner provided the following specifications for D-glucurono-γ-lactone and indicated
that the methods for determining these specifications meet the requirements of several
pharmacopoeias or regulations describing testing methods. D-glucurono-γ-lactone is a white
crystalline powder and its purity is not less than 98.5 %. Impurities identified by HPLC
include glucuronic acid <0.19%, other identified constituents each at <0.05 % and in total
<0.15% and unknown constituents each at <0.05 % in total <0.15 %. Melting range is 170176 oC, its appearance in solution is clear and colourless, the acidity of a 10% solution in
water is 3.7-4.1, the loss on drying is <0.2%, heavy metals are present at <0.001% (10
mg/kg), arsenic at <2 mg/kg, iron at < 2 mg/kg, copper at < 2 mg/kg, chloride at <100 mg/kg,
ammonia at < 200 mg/kg and sulphate at < 100 mg/kg. Specifications for microbial purity
were also provided by the petitioner.
1.4.
Methods of analysis in foods
The petitioner indicated that taurine can be determined in “energy” drinks after derivatization
with dabsylchloride by HLPC with UV detection, and that D-glucurono-γ-lactone can be
quantified in “energy” drinks by HPLC without derivatization.
1.5.
Reaction and fate in foods, stability
The petitioner indicates that samples of “energy” drinks were stored at 20 0C for 24 months
and tested at defined time-points for the levels of taurine and D-glucurono-γ-lactone. Based
on the results obtained it could be concluded that taurine and D-glucurono-γ-lactone in the
“energy” drink were stable during these 24 months of storage at 20 0C.
1.6.
Case of need and use levels
According to the petitioner taurine and D-glucurono-γ-lactone are to be used as constituents
of so-called “energy” drinks together with caffeine.
The EFSA Journal (2009) 935, 9-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
A submission from the Austrian National Food Authority (1996) included a list of the content
of 32 “energy” drinks taken from a published review of drinks on the Austrian market. Some
“energy” drinks did not contain taurine. In those drinks in which taurine was present and its
concentration declared, one contained 300 mg/L, one 2000 mg/L and 11 contained 4000
mg/L. For the exposure estimates done in 2003 the SCF assumed that the “energy” drinks
contained maximum levels of 4000 mg/L taurine and 2400 mg/L of D-glucurono-γ-lactone
(SCF, 2003).
1.7.
Exposure
No new data on exposure were available to the Panel.
In 2003 the SCF established a mean chronic consumption of 0.5 cans per person per day (250
mL per can) (SCF, 2003). High chronic exposure was estimated by the SCF to be 1.4 cans per
person per day. This figure was based on the 95th percentile exposure of regular users, a group
which represents 12% of the total population.
Based on the assumption that a can contains 250 mL and 4000 mg/L taurine and 2400 mg/L
D-glucurono-γ-lactone the SCF calculated that these values result in a mean daily exposure to
500 mg taurine (8.3 mg taurine/kg bw/day for a 60 kg person) and 300 mg D-glucurono-γlactone (5.0 mg D-glucurono-γ-lactone /kg bw/day for a 60 kg person). The 95th percentile
exposure to regular users would amount to 1400 mg taurine/day (23.3 mg/kg bw/day for a 60
kg person) and 840 mg D-glucurono-γ-lactone /day (14 mg/kg bw/day for a 60 kg person).
The mean daily exposure to taurine from omnivore diets was determined to be around 58 mg
(range from 9 to 372 mg) and to be low or negligible from a strict vegetarian diet (Rana and
Sanders, 1986). In another study, taurine exposure was estimated to be generally less than 200
mg/day, even in individuals eating a high meat diet (Laidlaw et al., 1990). And in another
study, taurine consumption was estimated to vary between 40 and 400 mg/day (Hayes and
Trautwein, 1994).
The SCF Opinion mentioned an estimated exposure to D-glucurono-γ-lactone from naturally
occurring sources in the diet of 1-2 mg/day (SCF, 2003). The SCF also concluded that
“Human metabolic considerations indicate the body is likely to handle small quantities of
glucuronolactone without any problems. However, the exposure to glucuronolactone resulting
from consumption of “energy” drinks is possibly as much as two orders of magnitude greater
than that from the rest of the diet.” The mean exposure to D-glucurono-γ-lactone would be
300 mg/day, and at the 95th percentile exposure would be 840 mg/day.
The chronic exposures by average and high adult consumers have been estimated by the SCF
(2003) to be 0.5 and 1.4 cans per person per day. The petitioner indicates that if it was
assumed that this level of chronic consumption is relevant to occasional exposure of children
of 25 kg body weight (about 6 to 7 years of age), then their exposure (on a body weight basis)
would be about 2.5 times higher than that of adults (60-65 kg body weight). The petitioner
emphasizes that these estimates relate to chronic exposures by average and high consuming
adults, and would not reflect the occasional and sporadic exposure that might occur in
children. If the frequency of exposure of children would be 2.5 times lower than in adults,
then the average chronic exposure of children, on a body weight basis, would be the same as
for adults. If children were to consume the adult intake of 0.5 and 1.4 cans per person only
once per week, then the average chronic exposure of children, on a body weight basis, would
be one third of that in adults.
The EFSA Journal (2009) 935, 10-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
The SCF Opinion (2003) used 3 cans/day as a reasonable high (acute) consumption, this
amount being higher than the 90th percentile recorded in the Austrian survey (2.6 cans/day)
and being the average reported in the Irish survey for the most number of cans consumed in a
single session. The SCF also indicated that it was aware that amounts up to 8-12 cans/day,
were reported by a few extreme consumers in both surveys, which would result in an intake of
4800-7200 mg D-glucurono-γ-lactone and 8000-12000 mg of taurine per day, equivalent to 80
- 120 mg D-glucurono-γ-lactone/kg bw/day and 133-200 mg taurine/kg bw/day.
1.8.
Existing authorisations and evaluations
In 1999, the SCF adopted an opinion on so-called “energy” drinks, which evaluated the safety
of caffeine, taurine and D-glucurono-γ-lactone as constituents of “energy” drinks (SCF,
1999). The SCF (1999) concluded that toxicological studies did not reveal any indication for a
genotoxic, teratogenic or carcinogenic potential of taurine.
At that time, the SCF was unable to conclude that the safety-in-use of taurine and
glucuronolactone in the concentration ranges reported for "energy" drinks had been
adequately established. The SCF commented that “there is insufficient information on which
to set an upper safe level for daily intake of these constituents.”
In 2001, the Agence Française de Sécurité Sanitaire des Aliments (AFSSA), reviewed a 13week mouse oral toxicity study on “energy” drinks, concluding that authorisation of the use of
various substances in “energy” drinks was not acceptable since harmlessness at the
concentrations recommended by the petitioner had not been demonstrated (AFSSA, 2001).
The AFSSA reiterated the same conclusions in three subsequent opinions (AFSSA, 2003,
2006a, 2006b).
In 2003 the SCF was asked to review additional information submitted on “energy” drinks
and indicate if the conclusions in its opinion of 21 January 1999 needed to be modified. The
SCF was also asked by the petitioner to take into account published reports and statements
from the Australian New Zealand Food Authority (ANZFA, 2000) and the UK Food
Standards Agency (FSA, 2001; 2002).
The SCF (2003) concluded the following on taurine:
“The new 13-week study in rats provided further useful information in that it showed no
significant changes in pathological measures, but it did show the occurrence of significant
behavioural effects (increased activity and self-chewing), and possibly impaired motor
performance, which could be mediated via a pharmacological action on the central
nervous system. In view of this, the Committee is of the opinion that focused
neurological studies are now needed and that the effects reported in a 13-week study
should be taken into account in human risk assessment, noting that behavioural effects
were observed at the lowest dose tested of 300 mg/kg bw/day. This effect level is 36-fold
above the estimated human intake of taurine (8.3 mg/kg bw/d for a 60 kg adult) at the
mean chronic daily intake for “energy” drinks, and 6-fold above the more relevant
estimate for acute intake (50 mg/kg bw/d for a 60 kg adult). The absence of a NOAEL for
these effects precludes the setting of an upper safe level for daily intake of taurine. The
Committee’s reservations are expressed in the context of an estimated acute intake of
taurine of up to 3000 mg/day from consumption of “energy” drinks, compared with the
highest estimated intake of taurine from naturally occurring sources in the diet of 400
mg/day.”
The EFSA Journal (2009) 935, 11-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
The SCF (2003) concluded the following on glucurono-γ-lactone:
“The new 13-week study provided useful information indicating that in rats, there were
no adverse effects except on the kidney. The NOAEL for these effects was 300 mg/kg
bw/d, which is around 20-fold above the estimate of high chronic intake of
glucuronolactone of 14 mg/kg bw/d for a 60 kg adult. The hamster study and the new 13week rat study both provided information showing no effects on body weight gain in
growing animals. However, the 1999 Opinion also pointed out that rodents may not be an
appropriate model for man since they can metabolise exogenous glucuronolactone to
vitamin C whereas primates, including man, do not possess this metabolic pathway.
The Committee therefore reiterates its earlier conclusion (SCF, 1999) that there is a lack
of scientific evidence to support the safety of glucuronolactone present in beverages at
concentrations that may result in intakes several-fold higher than that usually obtained
from the rest of the diet. Due to the lack of relevant data it is not possible to set an upper
safe level for daily intake of glucuronolactone. The Committee’s reservations are
expressed in the context of an estimated high chronic intake of glucuronolactone of 840
mg/day and an acute intake of up to 1800 mg/day from consumption of “energy” drinks,
compared with the estimated intake of glucuronolactone from naturally occurring sources
in the diet of 1-2 mg/day.”
In 2005, a statement was expressed by the EFSA Scientific Panel on food additives,
flavourings, processing aids and materials in contact with food (AFC) on studies designed to
investigate the safety-in-use of taurine and D-glucurono-γ-lactone in "energy" drinks (EFSA,
2005).
2.
Biological and toxicological data
Previous SCF Opinions have summarized safety studies of taurine and D-glucurono-γ -lactone
(SCF, 1999; SCF, 2003) and a previous EFSA Statement from the AFC Panel commented on
studies designed to further investigate the safety-in-use of taurine and D-glucurono-γ-lactone
in “energy” drinks (EFSA, 2005).
The present opinion only describes in detail those studies that were submitted after the
publication of the SCF Opinion in 2003 and the EFSA Statement in 2005.
2.1.
Absorption, distribution, metabolism and excretion
Taurine
The SCF Opinion already concluded that new toxicokinetic data submitted at that time on
taurine in rats showing ready bioavailability and peak plasma levels one hour after oral
administration are in accordance with findings from the limited published data for humans
(SCF, 2003). Human studies showed significant increases in plasma taurine 90 minutes after
consumption of a taurine-rich meal with levels declining to background within 180-270
minutes (Trautwein and Hayes, 1995). The SCF indicates that these results also corroborate
those from an unpublished human study using radiolabelled taurine, which showed peak
serum levels at 1-2 hours after oral administration, declining by 7 hours (SCF, 2003). Other
The EFSA Journal (2009) 935, 12-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
human data suggest that taurine is absorbed orally via an active transport mechanism in the
gut wall (Ahlman et al., 1993; 1995a, b).
Results from a new study on absorption, tissue distribution, metabolism and elimination of
taurine given orally to rats were provided by the petitioner. In this study (Sved et al., 2007)
three biodisposition studies with taurine were performed in male and female adult rats at
dosages of 30 and 300 mg/kg bw. A single dose of 14C taurine was rapidly absorbed,
distributed to tissues and excreted unchanged in the urine. Elimination of radioactivity from
intracellular pools was slow. Pre-treatment of animals for 14 days with unlabelled taurine did
not significantly affect the fate of 14C taurine. Daily administration of unlabelled taurine for
14 days did not result in an increase in total taurine in the brain. It was concluded that the data
indicated that exogenous taurine rapidly equilibrates with endogenous body pools and that
any excess is rapidly eliminated by the kidneys.
Based on these data which revealed that brain taurine levels did not increase after dosing, the
petitioner concluded that the possibility that taurine may exhibit acute, central
pharmacological effects mediated by an action on the central nervous system was
scientifically improbable.
D-glucurono-γ-lactone
The SCF (1999) already concluded that the available data indicate that when D-glucurono-γlactone is administered orally to humans it is rapidly absorbed, metabolised and excreted as
glucaric acid, xylitol and L-xylulose.
The SCF Opinion of 2003 stated that the toxicokinetic data on D-glucurono-γ-lactone in rats,
showing bioavailability and lack of accumulation, with peak plasma levels 1-2 hours after oral
administration, were in accordance with findings from the limited published data on humans
(SCF, 2003).
Animals, such as rodents, which can synthesise vitamin C endogenously do so from
glucuronic acid and such animals can also convert exogenously administered D-glucurono-γlactone into vitamin C (SCF, 1999). However, primates, including man, and guinea pigs do
not possess this metabolic pathway. The SCF concluded that for this reason, the rodent may
be an inappropriate model for man in the study of the effects of D-glucurono-γ-lactone.
In 2003, the SCF reiterated the 1999 Opinion that rodents may not be an appropriate model
for humans since they can metabolise exogenous D-glucurono-γ-lactone to vitamin C whereas
guinea pigs and primates, including humans, do not possess this metabolic pathway.
However, the petitioner indicates that synthesis of vitamin C is only a minor pathway of Dglucurono-γ-lactone metabolism in the rat and argues that, although of nutritional importance,
it is of limited relevance to the safety assessment of exogenous D-glucurono-γ-lactone. This is
supported by more recent literature data demonstrating that D-glucurono-γ-lactone is
predominantly metabolised in rats via the pentose pathway and that the flux through the
pathway that results in synthesis of ascorbic acid from D-glucurono-γ-lactone is relatively
small (Kondo et al., 2006; Linster and Van Schaftingen, 2007).
The EFSA Journal (2009) 935, 13-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
2.2.
Toxicological data
2.2.1.
Acute oral toxicity
In an acute toxicity study of taurine in Wistar rats, a 50% taurine suspension in 1.0%
carboxymethylcellulose (CMC) solution was administered in a volume of 10 mL/kg bw. No
dead animals were observed during the observation period of 14 days, and the authors indicate
that this suggests that the LD50 value of taurine is higher than 7000 mg/kg bw upon oral
administration (Kihara et al., 1991).
2.2.2.
Short-term and sub-chronic toxicity
Taurine
In 2003 the SCF evaluated a newly submitted 13-week rat study with taurine at dose levels of
0, 300, 600 and 1000 mg/kg bw/day which showed no significant changes in pathological
measures, but did show the occurrence of significant behavioural effects (increased activity
and self-injury such as self-chewing), and possibly impaired motor performance, which could
have been mediated via a pharmacological action on the central nervous system. In view of
this, the SCF was of the opinion that focused neurological studies were needed. The absence
of a NOAEL for these effects precluded the setting of an upper safe level for daily exposure to
taurine.
The petitioner argued that there had been bias in the original study observations and the EFSA
Working Group (EFSA, 2005) agreed that the observations reported in this study on certain
behavioural patterns of the animals had not been well described in the original submission and
could be discounted since there was no evidence of self-injury. However, the EFSA Working
Group also concluded that, even combined with the expert analyses provided, this information
was insufficient in itself to address all the concerns raised previously, notably the observation
on increased activity and possible decrements in motor skills on the rotarod.
Therefore, the petitioner has now provided data from a specifically-designed, new 13-week
oral (gavage and drinking water) neurotoxicity study of taurine in male and female rats which
was performed according to FDA and OECD principles of Good Laboratory Practice. The
objective of this study was to evaluate any potential neurotoxic effects of taurine when
administered to rats for 13 weeks either by gavage or by way of drinking water, and to
address the reliability of observations noted in the previous 13-week taurine toxicity study.
Beginning in the second week of the acclimatization period, all animals (180 males and 180
females) were tested twice in the functional observational battery (FOB) and locomotor
activity paradigms. After initial evaluations, outliers in locomotor activity were eliminated
from the study. The remaining animals were randomized based on their performance on the
rotarod test. Finally, the mean and standard deviation of the locomotor activity results were
analyzed to ensure that group means and variances were approximately equal before initiation
of dosing, thereby minimizing subsequent skewing of these data. Potential functional deficits
were assessed using a FOB and a measure of spontaneous locomotor activity. This study was
conducted in a “blinded” manner, in which the actual dose level for each group (gavage and
drinking water) were unknown to the personnel conducting the study, in order to remove
human bias from all aspects of the study.
The EFSA Journal (2009) 935, 14-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
Taurine in the vehicle, deionized water, was administered orally by gavage once daily for 13
weeks to 2 groups of 20 male and 20 female Cr1:CD(SD) rats at dose levels of 600 and 1000
mg/kg bw/day. In addition taurine was administered ad libitum in drinking water for 13 weeks
to 2 groups of 20 male and 20 female Cr1:CD(SD) rats at target dose levels of 1000 and 1500
mg/kg bw/day (actual mean taurine intake levels obtained with drinking water were 1095 and
1117 mg/kg bw/day for the males and females respectively in the low dose group and 1647
and 1656 mg/kg bw/day for the males and females respectively in the high dose group).
Concurrent control groups received the vehicle by gavage and drinking water respectively, on
comparable regimes. Clinical examinations were performed daily and detailed physical
examinations were performed weekly. These examinations were conducted “blinded” with
respect to treatment. Individual body weights and water consumption were recorded twice
weekly and food consumption was recorded weekly. Functional observational battery and
locomotor activity data were recorded for all animals prior to the initiation of dose
administration and during study weeks 0, 6 and 12. Complete necropsies were conducted on
all animals, and selected tissues and organs were collected at the scheduled necropsy.
The results indicated that there were no test-article-related deaths, clinical findings or
macroscopic findings. No test-article-related effects were observed on body weights or food
consumption. Some differences were observed in water consumption when rats were supplied
taurine ad libitum in the drinking water. Increases in water consumption in the 1000 and 1500
mg/kg bw/day group males were noted only for study days 0 to 3 and/or 3 to 7 (both in
g/animal/day and g/kg bw/day). The petitioner indicates that these differences were
considered test-article-related, but not considered adverse effects and that they occurred
temporarily and were considered to reflect adaptation to the osmotic property of the test
article.
There were no test-article-related effects on FOB parameters (home cage, handling, open
field, sensory, neuromuscular and physiological observations). Locomotor activity counts
(total and ambulatory) and patterns were unaffected by test article administration.
Based on these results the petitioner concluded that the oral administration of taurine at dose
levels of 600 and 1000 mg/kg bw/day was well tolerated by male and female rats and did not
result in any behavioural changes. The Panel concluded that this study confirmed the NOAEL
derived from the earlier study which included histopathology (1000 mg/kg bw/day – the
highest dose tested). In addition, it provided evidence of a NOAEL of 1500 mg/kg bw/day
(actual level approximately 1650 mg/kg bw/day) for behavioural effects.
D-glucurono-γ-lactone
For D-glucurono-γ-lactone the SCF concluded that the 13-week study in Crl:CD(SD) rats
showed that there were no significant, treatment-related effects, “apart from vacuolisation and
inflammatory changes localised to the papilla of the kidney in females at 600 and 1000 mg/kg
bw/day, with a NOAEL of 300 mg/kg bw/day” (SCF, 2003).
The study reported cytoplasmic vacuolation in 6/20 and 4/20 males in the control and 1000
mg/kg bw/day groups respectively and in 11/20, 9/20, 11/20 and 11/20 females in the control,
300, 600 and 1000 mg/kg bw/day groups respectively. The incidence was not increased by
treatment. The lesions were described as mild (grade 2) rather than minimal (grade 1) in 1/20
and 0/20 males in the control and 1000 mg/kg bw/day groups and in 1/20, 1/20, 5/20 and 8/20
females in the control, 300, 600 and 1000 mg/kg bw/day groups respectively. Therefore the
data indicated that there was a slight dose-related increase in severity in the treated females in
comparison to the treated males. However the petitioner noted that for all rats used in the
The EFSA Journal (2009) 935, 15-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
study, a range of other effects in the kidneys were reported, such as inflammatory changes,
nephropathy, pyelitis, indicative of renal problems.
The petitioner argued that the occurrence of the renal observations were incidental, related to
background lesions usually occurring in this rat strain. The SCF concluded that the cause of
the kidney lesions remained unclear. The petitioner also indicated that the occurrence of the
lesions only in females may be related to the higher acidity and osmolality of urine in the
female rat and went on to comment that the osmolality of human urine is considered less than
of the Sprague-Dawley rat. However, the SCF stated that in their view the mechanistic cause
of the kidney lesions remains unclear (SCF, 2003).
In a statement (EFSA, 2005) the Working Group on Additives of the AFC Panel noted that
the guinea pig might be a better model for human, in terms of its metabolism of D-glucuronoγ-lactone. But they expressed considerable reservations about a study on D-glucurono-γlactone in guinea pigs as proposed by the petitioner. The Working Group particularly noted
that the proposed study in guinea pigs with D-glucurono-γ-lactone in drinking water could be
difficult to perform (e.g. mortality) and interpret (e.g. lack of extensive background data on
this species), and that in view of these potential difficulties, consideration should be given to
whether this study could be justified on animal welfare grounds.
The Working Group suggested that a more productive strategy might be to undertake
mechanistic studies to support the hypothesis put forward by the petitioner that the rat kidney
effects were not relevant for human risk assessment.
The petitioner has now provided data from a new 13-week oral (gavage versus drinking
water) toxicity study of D-glucurono-γ-lactone in the Crl:CD(SD) rat strain, with specific
focus on the kidneys. This study used the same rat strain as the previous study reported in the
SCF Opinion of 2003 and was performed according to FDA and OECD principles of Good
Laboratory Practice. In this new study, D-glucurono-γ-lactone was administered orally by
gavage once daily for 13 consecutive weeks to 4 groups of Cr1:CD(SD) rats at dose levels of
0, 300, 600 and 1000 mg/kg bw/day. In addition D-glucurono-γ-lactone was administered ad
libitum in drinking water for 13 weeks to another 4 groups of Cr1:CD(SD) rats at target dose
levels of 0, 300, 600 and 1000 mg/kg bw/day. Each group consisted of 20 males and 20
females. Actual mean D-glucurono-γ-lactone intake levels obtained in the drinking water
groups were 311 and 322 mg/kg bw/day for the males and females respectively in the low
dose group, 598 and 635 mg/kg bw/day for the males and females respectively in the mid
dose group and 980 and 1066 mg/kg bw/day for the males and females respectively in the
high dose group. Concurrent control groups of 20 males and 20 females received the vehicle
by gavage and drinking water respectively on comparable regimens.
Clinical examinations were performed daily, and detailed physical examinations were
performed weekly. Individual body weights and water consumption were recorded twice
weekly. Serum chemistry evaluations were performed on all animals prior to the initiation of
dose administration (study week 2), during study weeks 4 and 8, and at the scheduled
necropsy (study week 13) and at time-points during 0 to 6 hours and 6 to 24 hours after dose
administration from the gavage groups during study weeks 4, 8 and 13. Urine samples were
collected from the drinking water groups on the same schedule (same time of day). Complete
necropsies were conducted on all animals, and selected organs were weighed at the scheduled
necropsy. Selected tissues were examined microscopically from all animals. Results revealed
no test article-related deaths. There were no effects on clinical observations, food or water
consumption, body weights, clinical pathology parameters, organ weights or clinical
chemistry parameters representing renal function. Extensive urinalysis demonstrated no
The EFSA Journal (2009) 935, 16-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
treatment related effects, and no differences between gavage and drinking water groups.
There were no test article-related macroscopic or microscopic findings.
Histopathological examinations revealed focal inflammation in the kidneys in a few male and
female animals, scattered among the groups, including controls. The petitioner indicates that
inflammation was observed in only a small number of animals at each dose level, that it was
unilateral and not treatment-related and that these background lesions are typical for this
strain of rats.
There were no compound-related observations of vacuolization of the cells lining the
collecting tubules. The petitioner also indicated that a greater number of rats in this new study
had healthy kidneys in comparison to the first study. There were no differences between the
gavage and drinking water groups. There was no significant incidence of cytoplasmic
vacuolization in any groups. The petitioner also indicated that in light of the difference
between the two studies the slides have been carefully reassessed, and that cytoplasmic
vacuolization has been confirmed not to be present. The petitioner also stated that the
pathologist who undertook the histopathological examination has indicated that the effect in
the previous study was most likely a preparation artifact which was exacerbated by the
generally poor health status of the kidneys in the rats at that time. Vacuolisation of renal
collecting tubules may arise as an artifact using normal fixation techniques.
The petitioner concluded that based on the results of this and the previous study, the NOAEL
for daily oral administration of D-glucurono-γ-lactone to rats was 1000 mg/kg bw/day, the
highest dose tested in both studies. The Panel agrees with this NOAEL derived from the
recent 13-week rat study which was performed under GLP.
2.2.3.
Reproductive and developmental toxicity
The SCF already concluded in 1999 that toxicological studies did not reveal any indication for
a teratogenic potential of taurine (SCF, 1999).
Studies on reproductive and developmental toxicity for D-glucurono-γ-lactone were not
available. However the petitioner indicates that this substance and its hydrolysis product
glucuronic acid are endogenous metabolites in humans and other mammals, that they occur
naturally in several dietary sources and are readily metabolized to innocuous products and
excreted. Furthermore there were no effects on the gonads in the 13-week rat studies.
Therefore the Panel concluded that there was no need for reproductive toxicity studies.
There are no new studies available.
2.2.4.
Mutagenicity
The SCF already concluded that toxicological studies did not reveal any indication for a
genotoxic potential of taurine (SCF, 1999).
In a study on the antimutagenic activity of lactones in Escherichia coli, D-glucurono-γlactone was reported to be not mutagenic to E. coli strains WP2 and WPs (Kuroda et al.,
1986).
There are no new studies available.
The EFSA Journal (2009) 935, 17-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
2.2.5.
Carcinogenicity and long-term studies
The SCF already concluded that toxicological studies did not reveal any indication for a
carcinogenic potential of taurine (SCF, 1999). But the SCF also indicated that there is no
adequate chronic toxicity/carcinogenicity study for taurine.
Long term studies on D-glucurono-γ-lactone were not available. However this substance and
its hydrolysis product glucuronic acid are endogenous metabolites in humans and other
mammals, they occur naturally in several dietary sources and are readily metabolized to
innocuous products and excreted. Furthermore, there was no evidence of any putative
preneoplastic or hyperplastic lesions in the 13-week rat studies, which might indicate the need
for a long term carcinogenicity study.
2.2.6.
Human data
Available human data from the use of taurine in human medicine do not give any indication
of safety concerns (Franconi et al., 1995; Takahashi and Nakane, 1978; Fukuyama and
Ochiai, 1982; Airaksinen et al., 1980; Mantovani and DeVibo, 1979; Marchesi et al., 1975;
Mutani et al., 1975; Azuma et al., 1983a; 1983b; 1985; 1992; 1994; Fujita et al., 1987;
Yamori et al., 1996; Krøll and Lund, 1966; Yamamoto et al., 1994; Gentile et al., 1994;
Matsuyama et al., 1983; Podda et al., 1990; Kimura et al., 1992; Obinata et al., 1996; Durelli
et al., 1982; 1983; Nyland et al., 1989; Kopple et al., 1990; Thompson 1988; Darling et al.,
1985; Carrasco et al., 1990; Belli et al., 1987; Colombo et al., 1988; Smith et al., 1991; De
Curtis et al., 1992; Skopnik et al., 1991; Colombo et al., 1990).
In these separate studies taurine has been administered, mostly by oral ingestion on a daily
basis for periods up to one year, and with daily doses generally in the 3-6 g range, to a large
number of patients (adults, children and even infants) suffering from a wide variety of serious
diseases. Taurine has also been administered parenterally at a daily dose of 0.64 g for 20
months or by intravenous administration at daily doses of 12 g for 15 days and 18 g for 60
days. Although the principal aim of these clinical studies was not to evaluate potential adverse
effects of chronic administration of taurine it is apparent that these doses produced no adverse
health effects. Such information has revealed that oral daily ingestion of taurine doses in the
3-6 g range for periods up to one year, did not produce adverse health effects.
The SCF Opinion of 2003 refers to a number of anecdotal reports of acute, adverse effects in
young persons consuming “energy” drinks, containing caffeine, taurine and D-glucurono-γlactone, usually together with alcohol and/or ‘social drugs’, such as ecstasy and
amphetamines. The adverse effects reported included tremors, seizures, drowsiness, muscle
weakness, dizziness, nervousness, tachycardia, palpitations, nausea, vomiting, headache,
bronchospasm, hyperventilation and also myocardial infarction and sudden unexplained death
possibly resulting from cardiac dysrhythmia (SCF, 2003). The SCF already concluded the
following: “The co-consumption of alcohol and/or drugs noted in most of these cases makes
interpretation of effects due to the “energy” drinks particularly difficult. Thus there is no
confirmation of any causal relationship between the reported effects and the consumption of
“energy” drinks. Under these circumstances, the reports can only be noted”.
New human data on the assessment of “energy” drinks have been compiled in a recent BfR
Opinion (BfR, 2008) reporting recent Swedish and American studies (Lehtihet et al., 2006;
Wiklund et al., 2004; Steinke et al., 2007; American Heart Association; 2007; Iyadurai and
Chung; 2007). In a Swedish publication possible adverse reactions of “energy” drinks
The EFSA Journal (2009) 935, 18-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
including three cases of death are discussed, focussing on a potential contributing role of
taurine associated with its known effects e.g. in osmoregulation and on the cardiovascular
system. The three fatalities occurred after “energy” drinks had been consumed in combination
with alcohol, whereby the forensic examinations including autopsy yielded negative results
concerning medicaments and drugs, values between 0.59 and 0.87 parts per thousand of
ethanol in blood samples, but no clear causes of death. In a further case, severe adverse effects
arose after consumption of an “energy” drink in combination with physical efforts: A 31-yearold regularly trained man consumed 750 mL of an “energy” drink while taking part in a 3,000
m competition. He developed a poor general condition with a rhabdomyolysis and acute
kidney failure with tubular necrosis diagnosed one week after the competition (Lehtihet et al.,
2006).
Two new cases of “energy” drink-related tachycardias, in one individual associated with
orthostatic intolerance, were reported by other authors (Nagajothi et al., 2008; Terlizzi et al.,
2008). In the Terlizzi study, consumption was reported to amount to 4 to 5 cans of “energy
drinks” a day.
In addition, cases of four patients who suffered generalised cerebral seizures after consuming
a high dose of “energy” drinks, without there being any reports of parallel alcohol
consumption were reported (Iyadurai and Chung, 2007).
Overall, the results also raised the issue of combination effects and possible interactions
between, amongst others, taurine and alcohol, between taurine and caffeine and between
taurine and D-glucurono-γ-lactone.
The SCF Opinion already evaluated the possibility of interactions between taurine, caffeine
and D-glucurono-γ-lactone and considered it unlikely that D-glucurono-γ-lactone would have
any interaction with caffeine and taurine. The SCF concluded (2003) “that consideration of
the potential for interactions between caffeine and taurine has not ruled out the possibility of
stimulatory effects from both substances at the levels of the central nervous system”.
The SCF also noted that “since caffeine and taurine act via different mechanisms, any diuretic
effects could be additive” and that “Both taurine (Gentile et al., 1994) and alcohol centrally
inhibit the release of the antidiuretic hormone, vasopressin and the Committee considered that
they could act additively to increase water and sodium loss from the body in the short-term”.
New data have recently been published (Riesenhuber et al., 2006) describing results from a
study investigating the possible additive diuretic effects of caffeine and taurine in a cross-over
design in which 12 healthy male volunteers each received four different test drinks (750 mL
of “energy” drink containing 240 mg caffeine and 3 g taurine, the three other test drinks that
lacked caffeine, taurine or both). Effects on urinary output, urinary osmolarity and natriuresis
were compared by mixed model analyses. Urinary output and natriuresis increased
significantly with caffeine alone and in the caffeine-taurine group. This study demonstrated
that the diuretic potential and natriuretic effects of the tested “energy” drinks were largely
mediated by caffeine and that there were no additive interactions between taurine and
caffeine. The petitioner concluded that this study does not support the possibility of
interactions between taurine and caffeine.
To investigate possible cardiovascular effects of the combined exposure to caffeine and
taurine with “energy” drinks an orientational study was conducted in healthy volunteers with
low blood pressure (8 women, 7 men, average age of 26 years) in a state of physical rest
(Steinke et al., 2007; American Heart Association, 2007). The test persons had abstained from
caffeine for 48 h before the start of the study and throughout the study period. After an initial
examination during which blood pressure and heart rate were measured and an ECG was
The EFSA Journal (2009) 935, 19-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
carried out, each participant consumed 500 mL of “energy” drink containing a total of 80 mg
caffeine and 1000 mg taurine. The examinations were repeated at intervals of up to 4 hours.
On each of the following five days the participants again drank 500 mL and on the seventh
day the procedure of the first day was repeated. Four hours after consumption of the beverage,
systolic blood pressure had increased by 7.9 % (day one) or 9.6 % (day seven) and heart rate
had been raised by 7.8 % (day one) or 11 % (day seven). Over the duration of the study this
means an increase of blood pressure by 10 mm Hg and of heart rates of 5 to 7 beats per
minute. No habituation could be determined following several days exposure since the effects
were slightly enhanced on the seventh day. Until the submission of further findings the
researchers recommended that patients with high blood pressure or cardiac diseases and
corresponding medication should refrain from consuming “energy” drinks because of a
possible health risk.
3.
Discussion
In the absence of new chronic and acute exposure data, the exposure assessment is based on
the data reported by SCF (2003), i.e. a daily mean chronic consumption of 0.5 cans per person
and a high chronic exposure at the 95th percentile of 1.4 cans per regular consumer. The Panel
notes that actual exposure data on “energy” drink consumption, especially for adolescents and
young adults, may need to be collected.
These estimates for the daily exposure to taurine (mean 500 mg/day; 95th percentile 1400
mg/day) or D-glucurono-γ-lactone (mean 300 mg/day; 95th percentile 840 mg/day) from
“energy” drinks are higher than the estimated mean daily exposure to taurine from omnivore
diets which was estimated to be at most 400 mg/day and that of D-glucurono-γ-lactone from
naturally occurring sources in the diet estimated to amount to 1-2 mg/day (SCF, 2003).
The Panel concludes that assuming that children were to consume within the adult intake
range of 0.5 and 1.4 cans per person only once per week, then the average chronic exposure of
children to “energy” drinks and their constituents, on a body weight basis, would be one third
of that in adults.
The SCF Opinion (2003) used 3 cans/day as a reasonable high (acute) consumption, this
amount being higher than the 90th percentile recorded in the Austrian survey (2.6 cans/day)
and being the average reported in the Irish survey for the most number of cans consumed in a
single session. The SCF also indicated that it was aware that amounts of up to 8-12 cans/day
were reported by a few extreme consumers in both surveys.
Taurine
Results from a new study on absorption, tissue distribution, metabolism and elimination of
taurine given orally to rats were provided by the petitioner (Sved et al., 2007). The Panel
concludes that these new ADME data support the contention that oral exposure to taurine was
not increasing taurine levels in the brain.
In 2003 the SCF evaluated a 13-week rat oral toxicity study of taurine and concluded that
focused neurological studies were needed and that the absence of a NOAEL for these effects
precluded the setting of an upper safe level for daily exposure to taurine.
The EFSA Journal (2009) 935, 20-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
The Panel evaluated a new 13-week oral rat toxicity and neurotoxicity study in male and
female rats which included FOB and locomotor activity tests. The new study confirmed the
NOAEL of 1000 mg/kg bw/day for pathological changes established in the earlier 13-week
study described already by the SCF in 2003 and provided evidence for a NOAEL of 1500
mg/kg bw/day for behavioural effects. The results of this study were sufficient to address the
concerns raised previously, notably the observation of increased activity and possible
decrements in motor skills on the rotarod.
The NOAEL of at least 1000 mg/kg bw/day for pathological changes is 120-fold higher than
the estimated mean and 43-fold higher than the estimated 95th percentile exposure to taurine
from “energy” drinks only, when calculated for a 60 kg person.
Given that taurine is a natural body constituent, the Panel concludes that these margins of
safety are sufficiently large to conclude that exposure to taurine at the levels mentioned above
is not of safety concern.
D-glucurono-γ-lactone
In 2003 the SCF evaluated a 13-week rat oral toxicity study with D-glucurono-γ-lactone and
concluded that the cause of the kidney lesions remained unclear.
The petitioner has now provided data from a new 13-week oral (gavage versus drinking
water) toxicity study of D-glucurono-γ-lactone in rats, with specific focus on the kidneys.
This study used the same rat strain as the previous study reported in the SCF Opinion of 2003.
Extensive urinalysis and histopathological examinations demonstrated no treatment-related
effects. Based on the results of this study, the NOAEL for daily oral administration of Dglucurono-γ-lactone was 1000 mg/kg bw/day, the highest dose tested.
Toxicological studies on genotoxic, teratogenic or carcinogenic potential of D-glucurono-γlactone were not available. However, D-glucurono-γ-lactone is a normal human metabolite
formed from glucose and there are no structural alerts for mutagenicity or carcinogenicity. At
physiological pH it is in equilibrium with glucuronic acid, its immediate precursor. Dglucurono-γ-lactone and its hydrolysis product glucuronic acid are endogenous metabolites in
humans and other mammals, they occur naturally in several dietary sources and are readily
metabolized to innocuous products and excreted. Furthermore there was no evidence of any
effect on the gonads in the high dose 13-week studies which might indicate the need for
reproductive toxicity studies.
The NOAEL for D-glucurono-γ-lactone of 1000 mg/kg bw/day is 200-fold higher than the
estimated mean and 71-fold higher than the estimated 95th percentile exposure to Dglucurono-γ-lactone from “energy” drinks only, when calculated for a 60 kg person.
Given the fact that D-glucurono-γ-lactone is a natural body constituent the Panel concludes
that these margins of safety are sufficiently large to conclude that exposure to D-glucurono-γlactone at the levels mentioned above is not of safety concern.
Combined exposure
The SCF Opinion of 2003 and the recent BfR Opinion (BfR, 2008) mention a number of
anecdotal and case reports of acute, adverse effects, including fatalities, in individuals
consuming “energy” drinks, containing caffeine, taurine and D-glucurono-γ-lactone. In these
cases, “energy” drinks had either been consumed in very high amounts (1420 mL), in
combination with physical exercise or more frequently together with alcohol. The SCF
The EFSA Journal (2009) 935, 21-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
Opinion of 2003 also takes into account that drugs, such as ecstasy and amphetamines may
have been involved. The effects mentioned included tremors, seizures, drowsiness, muscle
weakness, dizziness, nervousness, tachycardia, palpitations, nausea, vomiting, headache,
bronchospasm, hyperventilation and also myocardial infarction and sudden unexplained death
possibly resulting from cardiac dysrhythmia (SCF, 2003; BfR, 2008; Lehtihet et al., 2006;
Iyadurai and Chung; 2007, Nagajothi et al., 2008; Terlizzi et al., 2008). The SCF concluded
the following: “The co-consumption of alcohol and/or drugs noted in most of these cases
makes interpretation particularly difficult. Thus there is no confirmation of any causal
relationship between the reported effects and the consumption of “energy” drinks. Under
these circumstances, the reports can only be noted”. With regard to some actual reports (e.g.
Iyadurai and Chung; 2007, Nagajothi et al., 2008; Terlizzi et al., 2008) the Panel considers
that it is possible that the effects could be due to the well known side effects of high caffeine
intake, while the assumption of a causal relationship with taurine intake is lacking scientific
evidence.
These results also raised the issue of combination effects and possible interactions between,
amongst others, taurine and alcohol, between taurine and caffeine and between taurine and Dglucurono-γ-lactone.
The SCF Opinion (SCF, 2003) already evaluated the possibility of interactions between
taurine, caffeine and D-glucurono-γ-lactone and considered it unlikely that D-glucurono-γlactone would have any interaction with caffeine and taurine. The SCF concluded “that
consideration of the potential for interactions between caffeine and taurine has not ruled out
the possibility of stimulatory effects from both substances at the level of the central nervous
system”.
Results from a new study provided by the petitioner (Sved et al., 2007) revealed that brain
taurine levels did not increase after dosing. The Panel concludes that these new ADME data
support the contention that oral exposure to taurine was not increasing taurine levels in the
brain and that this largely rules out the possibility of stimulatory effects from taurine at the
level of the central nervous system.
The SCF (2003) also noted that “since caffeine and taurine act via different mechanisms, any
diuretic effects could be additive” and that “Both taurine (Gentile et al., 1994) and alcohol
centrally inhibit the release of the antidiuretic hormone, vasopressin and the Committee
considered that they could act additively to increase water and sodium loss from the body in
the short-term”.
New data have recently been published (Riesenhuber et al., 2006) describing results
demonstrating that the diuretic potential and natriuretic effects of the tested “energy” drinks
were largely mediated by caffeine and that there were no additive interactions between taurine
and caffeine. The Panel concludes that the diuretic potential and natriuretic effects of
“energy” drinks may be largely mediated by caffeine and not by taurine.
In a recent study, possible cardiovascular effects of the combined exposure to caffeine and
taurine with “energy” drinks were investigated (Steinke et al., 2007; American Heart
Association, 2007). Four hours after consumption of 500 mL of “energy” drink containing a
total of 80 mg caffeine and 1000 mg taurine, systolic blood pressure had increased by 7.9 %
(day one) or 9.6 % (day seven) and heart rate had been raised by 7.8 % (day one) or 11 %
(day seven). Over the duration of the study this means an increase of blood pressure by 10
mm Hg and of heart rates of 5 to 7 beats per minute. Until the submission of further findings
the researchers recommended that patients with high blood pressure or cardiac diseases and
corresponding medication should refrain from consuming “energy” drinks because of a
The EFSA Journal (2009) 935, 22-31
The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
possible health risk. The Panel notes that the studies were not designed to show whether the
effects were due to caffeine or taurine.
Overall, the ANS Panel concludes that the diuretic potential and natriuretic effects of the
tested “energy” drinks are largely mediated by caffeine. Other interactions between taurine
and caffeine were not investigated.
CONCLUSIONS AND RECOMMENDATIONS
In the present opinion the Panel evaluates the safety of taurine and D-glucurono-γ-lactone as
individual ingredients of the so-called “energy” drinks based on the new studies provided by
the petitioner. The Panel does not evaluate the safety of “energy” drinks as such.
In the absence of new chronic and acute exposure data, the exposure is based on the data
reported by the SCF in 2003. The Panel concluded that actual exposure data on “energy”
drink consumption, especially for adolescents and young adults, may need to be collected.
The Panel concludes that the exposure to taurine and D-glucurono-γ-lactone at the levels
presently used in “energy” drinks and mentioned above is not of safety concern.
The ANS Panel agrees with the considerations of the SCF Opinion from 2003 that it is
unlikely that glucurono-γ-lactone would have any interaction with caffeine, taurine, alcohol or
the effects of exercise. The Panel also concludes, based on the new data available, that
additive interactions between taurine and caffeine on diuretic effects are unlikely. Other
interactions between taurine and caffeine were not investigated.
DOCUMENTATION PROVIDED TO EFSA
1. Kroes R. and Renwick, A.G. Summary report regarding the safety in Use of Taurine and
D-glucuronolactone as constituents of “energy” drinks.
2. Final report. A 13-week oral (gavage and drinking water) neurotoxicity study of taurine in
male and female rats (WIL-42306). Submitted by Red Bull GmbH.
3. Final report. A 13-week oral (gavage versus drinking water) toxicity study of Dglucuronolactone in rats (WIL-423012). Submitted by Red Bull GmbH.
4. Final report. A-13 week oral (gavage) toxicity study of D-glucuronolactone in rats (WIL423001-A).Submitted by Red Bull GmbH.
5. Striker, G. Expert report of Professor Gary Striker, in concurrence with professor Robert
Kroes, concerning the pathological kidney lesions found in toxicity studies.
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The use of taurine and D-glucurono-γlactone as constituents of the so-called “energy” drinks
GLOSSARY / ABBREVIATIONS
ADME
Absorption, Distribution, Metabolism, Excretion
AFSSA
Agence Française de Sécurité Sanitaire des Aliments
ANZFA
Australia New Zealand Food Authority
BfR
Federal Institute for Risk Assessment
CMC
Carboxymethylcellulose
EFSA
European Food Safety Authority
FSA
Food Standards Agency
HPLC
High performance liquid chromatography
NOAEL
No Observable Adverse Effect Level
SCF
Scientific Committee on Food
The EFSA Journal (2009) 935, 31-31
International Journal of General Medicine
Dovepress
open access to scientific and medical research
R eview
Open Access Full Text Article
Energy drinks mixed with alcohol:
misconceptions, myths, and facts
This article was published in the following Dove Press journal:
International Journal of General Medicine
1 March 2012
Number of times this article has been viewed
Joris C Verster 1
Christoph Aufricht 2
Chris Alford 3
1
Utrecht University, Utrecht Institute
for Pharmaceutical Sciences, Division
of Pharmacology, Utrecht, The
Netherlands; 2Medical University
of Vienna, Department of Pediatrics
and Adolescent Medicine, Währinger
Gürtel, Wien, Austria; 3University
of the West of England, Psychology
Department, Faculty of Health and
Life Sciences, Frenchay Campus,
Coldharbour Lane, Bristol, UK
Background: Whilst energy drinks improve performance and feelings of alertness, recent
articles suggest that energy drink consumption combined with alcohol may reduce perception
of alcohol intoxication, or lead to increased alcohol or drug use. This review discusses the
available scientific evidence on the effects of mixing energy drinks with alcohol.
Methods: A literature search was performed using the keywords “energy drink and Red Bull®”
and consulting Medline/Pubmed, PsycINFO, and Embase.
Results: There is little evidence that energy drinks antagonize the behavioral effects of alcohol,
and there is no consistent evidence that energy drinks alter the perceived level of intoxication of
people who mix energy drinks with alcohol. No clinically relevant cardiovascular or other adverse
effects have been reported for healthy subjects combining energy drinks with alcohol, although
there are no long-term investigations currently available. Finally, whilst several surveys have
shown associations, there is no direct evidence that coadministration of energy drinks increases
alcohol consumption, or initiates drug and alcohol dependence or abuse.
Conclusion: Although some reports suggest that energy drinks lead to reduced awareness
of intoxication and increased alcohol consumption, a review of the available literature shows
that these views are not supported by direct or reliable scientific evidence. A personality with
higher levels of risk-taking behavior may be the primary reason for increased alcohol and drug
abuse per se. The coconsumption of energy drinks being one of the many expressions of that
type of lifestyle and personality.
Keywords: energy drink and Red Bull®, Red Bull®, alcohol, intoxication, caffeine, masking
Introduction
Correspondence: Joris C Verster
Utrecht University, Utrecht Institute
for Pharmaceutical Sciences, Division
of Pharmacology, Universiteitsweg 99,
3584 CG Utrecht, The Netherlands
Tel +31 03 0253 6909
Email [email protected]
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http://dx.doi.org/10.2147/IJGM.S29313
Although energy drinks comprise only 1% of the total soft drink market, these ­products
are becoming increasingly popular.1 The market leader, Red Bull® Energy Drink is
available in over 160 countries and, although some local sales restrictions may apply,
energy drinks are not banned in any country. The most important functional ingredient
of energy drinks is caffeine. Table 1 lists some of the well known energy drink brands,
and their caffeine content.
It is evident from Table 1 that popular energy drinks such as Red Bull (250 mL, 8.4 oz)
contain a similar amount of caffeine (ie, 80 mg) to that present in one regular cup of
coffee (240 mL, 8 oz).2,3 However, less popular brands may have a higher caffeine
content. Caffeine does not have adverse effects for the general population of healthy
adults if they limit caffeine intake to 400 mg per day.4 Various experimental studies
have examined the behavioral effects of energy drinks when consumed alone. Most
studies have shown that energy drink consumption can significantly improve ­cognitive
International Journal of General Medicine 2012:5 187–198
187
© 2012 Verster et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.
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Verster et al
Table 1 Caffeine content of some well known energy drinks2,3
Red bull
Monster
Rockstar
Full throttle
No fear
Amp
SoBe
Tab energy
Cola
Coffee
Tea
Bottle/can
mL (oz)
Caffeine mg/100 mL
(mg/oz)
Total caffeine
mg (range)
250 (8.4)
473 (16)
473 (16)
473 (16)
473 (16)
250 (8.4)
250 (8.4)
311 (10.5)
355 (12)
237 (8)
237 (8)
32 (9.6)
34 (10)
34 (10)
30 (9)
37 (10.9)
30 (8.9)
32 (9.5)
31 (9.1)
11 (3.3)
36 (10.6)
17 (5)
80
160
160
144
174
75
79
95
40 (30–60)
85 (65–120)
40 (20–90)
and psychomotor functioning5–10 and driving ability,10–12 preexercise consumption can significantly improve endurance
and physical performance,7,13–15 and whilst some studies
have reported small changes in heart rate or blood pressure,
no clinically relevant adverse cardiovascular effects have
been reported after normal use of energy drinks in healthy
volunteers,7,16–21 although there is currently a lack of longterm data.
Health regulatory authorities across the world have
concluded that energy drinks are safe to consume, although
some authorities have expressed concerns about the potential
health risks associated with mixing alcohol and caffeine. It
should also be noted that there are anecdotal and case reports
of acute adverse effects, including fatalities, in individuals
consuming energy drinks combined with alcohol, but no
confirmation of any causal relationship between the reported
effects and the consumption of energy drinks.22
Research and media attention has recently been drawn to
alcohol mixed with energy drinks (AmED). In this context, it
has been suggested that AmED consumption may reduce the
perception of alcohol intoxication or that coconsumption may
lead to increased alcohol consumption. This paper aims to
review and put into perspective the current scientific evidence
on the combined use of energy drinks and alcohol.
Methods
A literature search was performed (updated December 1,
2011) using the keywords “energy drink” and “Red Bull”,
consulting Medline/Pubmed, PsycINFO, and Embase for
clinical trials and surveys examining the effects of energy
drinks consumed together with alcohol. Cross-references
were checked for additional research papers. This literature
search yielded 23 research articles that were included in
this review.
188
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Results
Most people consume energy drinks only occasionally (eg,
less than 6% of college students consume energy drinks
daily).23 Surveys among students reveal that they consume
energy drinks to counteract sleepiness, to enhance energy
and concentration,24 or because they simply like it.25 Reasons
given for consuming energy drinks combined with alcohol
include “during partying”,24 to celebrate,26 because they like
the taste,26 to hide the flavor of alcohol,27 or to get drunk.26
However, only 2% of all students (and 15% of those who
combined alcohol with energy drinks) indicated they did so in
an attempt to be able to drink more and not feel as drunk.27
Surveys among students have found that 6%–44% report
consumption of AmED.24–32 Price et al interviewed 72 regular consumers of energy drinks about their past week and
lifetime energy drink and alcohol intake, applying the timeline follow-back approach.33 Thirteen percent of past-week
alcohol consumption sessions involved the co-use of energy
drinks. Analysis of survey data revealed that students who
consume AmED were significantly more often young white
males.27,31,34 Taken together, these surveys suggest that a relative minority of students occasionally consume AmED.
Do energy drinks antagonize
alcohol-induced performance impairment?
Seven studies examined the possible antagonizing effects of
energy drinks on alcohol-induced performance impairment,
including both recovery from physical exercise and cognitive
testing.16,35–40 The results of these studies are summarized in
Table 2.
A significant limitation of two of these studies36,37 is that
alcohol was not tested alone, so it cannot be determined if
the effects caused by AmED are actually the same as when
administering alcohol alone. Ferreira et al failed to find
significant differences on a variety of physical performance
and recovery parameters.16 The statistical analysis reported
by Marczinski et al, based on significant changes from
baseline, found that some aspects of cognitive performance
were poorer for alcohol alone compared with the energy
drink, placebo, or AmED groups, but not for all tests.38 In a
second study, Marczinski et al did not find any significant
difference between impairment on information processing
and motor coordination tasks between AmED and alcohol
only.39 Ferreira et al also failed to show differences between
alcohol and AmED,35 whilst Alford et al showed improvement with AmED in one test, but not others, compared with
alcohol.40 Therefore, there is mixed evidence that energy
drink consumption antagonizes some performance effects
International Journal of General Medicine 2012:5
International Journal of General Medicine 2012:5
12 healthy volunteers received lower
dose, 14 higher alcohol dose, both
also receiving energy drink or water
control, or alcohol + energy drink
in a mixed, blind design with random
allocation
Double-blind, crossover trial
to examine heart rate variability
and ECG changes in 10 healthy
volunteers
Ferreira et al35
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Double-blind,
placebo-controlled
study in18 healthy
volunteers
Marczinski et al39
Placebo, energy drink
(3.57 g/kg), alcohol
(0.65 g/kg), AmED
Placebo, energy drink, alcohol
(0.072%–0.089% BrAC),
AmED
(0.07%–0.08% BrAC)
AmED
(6% alcohol by volume),
energy drink alone,
and a noncaffeinated
placebo drink
Alcohol or AmED
in a rising dose
(0.046% and 0.087% BrAC)
3 cans (750 mL) of energy
drink alone or in
combination with alcohol
(vodka, 0.4 g/kg body weight)
or no drink at all
Abbreviations: BrAC, breath alcohol concentration; AmED, alcohol mixed with energy drink; ECG, electrocardiogram.
Double-blind, placebo-controlled,
between subjects comparison
in 56 healthy volunteers,
divided into four groups
Double-blind, placebo-controlled
study in two groups of 10 healthy
volunteers
Alford et al40
Marczinski et al38
Double-blind, placebo-controlled
trial in 27 healthy females
Curry and
Stasio36
Wiklund et al37
Alcohol (1.0 g/kg),
energy drink
(3.57 mL/kg body weight),
and their combination
Double-blind crossover trial
in 14 healthy volunteers
Ferreira et al16
Alcohol (0.6 and 1.0 g/kg);
energy drink, or same
volume water
(3.57 mL/kg body weight)
Dosing
Subjects and design
Reference
Subjects performed a maximal bicycle ergometer
exercise for 30 minutes. Postexercise recovery
in heart rate and heart rate variability was
slower after energy drink and alcohol than
after exercise alone. No clinically significant
arrhythmias or ECG changes were observed
AmED significantly impaired neuropsychological
function (in particular visuospatial and
language skills), whereas the energy drink
alone nonsignificantly improved performance
(in particular attention scores)
Reaction time and memory were impaired by
both alcohol and AmED, although Stroop performance
was improved for AmED compared with alcohol
suggesting partial antagonism. No significant difference
in breath alcohol concentration between alcohol
and AmED
Compared with alcohol, coadministration
of energy drink counteracted some but not
all performance impairment. No significant
difference in breath alcohol concentration
between alcohol and AmED
Compared with alcohol,
AmED did not significantly alter
performance on tests of information
processing and motor coordination
No significant difference on maximal effort test
(cycle ergometer) or recovery for a number
of physiological and biochemical parameters
between alcohol alone, and alcohol administered
in combination with energy drink
Breath alcohol concentration, visual reaction time,
and grooved peg-board reported as not showing
differences between alcohol
alone and AmED
Findings highlighted by authors
Table 2 Studies examining potential antagonizing effects of energy drinks on alcohol-induced performance impairment
No evidence of energy drink
antagonizing effects of alcohol
Possible antagonism of alcohol
seen in three out of four
performance tests for AmED
compared with alcohol alone
Possible antagonism of alcohol
seen in one out of three
tests for AmED compared
with alcohol alone
Alcohol alone not tested,
therefore no comparison can
be made between alcohol
and AmED
Alcohol alone not tested,
therefore no comparison
can be made between
alcohol and AmED
No evidence of energy drink
antagonizing effects of alcohol
No evidence of energy drink
antagonizing effects of alcohol
Comment
Dovepress
Energy drinks mixed with alcohol
189
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Verster et al
caused by alcohol intoxication but not others. This suggests
no consistent antagonism of alcohol-induced impairment
by coconsumption of energy drinks. A recent double-blind,
placebo-controlled study by Howland et al did not observe
any significant differences on simulated driving, sustained
attention, or reaction time between caffeinated and noncaffeinated beer (383 mg caffeine, peak breath alcohol
concentration [BrAC] of 0.12%), suggesting no consistent
antagonism of alcohol-induced impairment by coconsumption of caffeine.41
Do energy drinks change the drinker’s
perception of intoxication?
It has been claimed that people consume energy drinks
because they presume it will counteract the impairing
effects of alcohol. For example, O’Brien et al reported
this for 15% of students who consumed AmED. 27 Few
experimental ­studies actually examined the perception of
intoxication after consuming AmED. One of the most cited
studies in this context was performed by Ferreira et al, who
evaluated breath alcohol concentration (0.04%–0.1% BrAC),
psychomotor functioning, and subjective intoxication after
administration of an energy drink, alcohol (vodka, 0.6 or
1.0 g/kg), or AmED.35 Twenty-six subjects participated in
this randomized, controlled trial. Coadministration of energy
drink did not affect breath alcohol concentration. Symptoms
during intoxication were scored using the Bond and Lader
13-item somatic symptoms scale,42,43 extended with five
additional items, giving 18 items in all. The paper revealed
that alcohol and AmED similarly impaired psychomotor
performance. The results section reports that AmED reduced
the perception of headache, dry mouth, and impairment of
motor coordination compared with alcohol alone. However,
the appropriateness of using these symptoms as a measure
of intoxication should be questioned, especially because
most other symptoms, of which several are related to feelings of intoxication (eg, dizziness, speech, tiredness, vision,
walking, wellbeing), did not show a significant reduction
for AmED compared with alcohol alone. Consequently,
the interpretation of these results as showing a reduction in
perceived intoxication after AmED compared with alcohol
alone cannot be taken as consistent and reliable on the basis
of this single study.
Alford et al found participants felt significantly impaired
after alcohol (0.05%–0.09% BrAC) and significantly
impaired by the higher compared with lower alcohol dose
(4/5 scales), but no overall difference between alcohol alone
and energy drink combined with alcohol.40
190
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Marczinski et al reported that alcohol alone (0.07–0.09
BrAC) significantly increased ratings of feeling the drink,
liking the drink, impairment, and level of intoxication,
whereas it reduced the rating of ability to drive.38 AmED
showed no significant difference for these ratings. The
abstract of this article implies that self-reported stimulation
was increased for AmED compared with alcohol alone,
and that this might contribute to a higher risk scenario.
However, their data showed that subjective stimulation was
significantly increased from baseline for both the alcohol
and AmED groups. Unfortunately, in this paper, no direct
­statistical comparisons were made between the AmED and
alcohol group. In a second study, Marczinski et al reported
that consumption of AmED reduced mental fatigue and
increased feelings of stimulation, when compared with consuming alcohol alone.39 No significant difference between
AmED and alcohol alone was reported on subjective intoxication or ability to drive. Taken together, the results from these
studies do not show a change in perceived intoxication on
the majority of subjective scales, including intoxication and
ability to drive, when alcohol is mixed with energy drink.
Higher levels of alcohol have been compared with alcohol
and caffeine in combination, though not using energy drinks.
Howland et al investigated higher doses of alcohol comparing
the effects of caffeinated beer versus noncaffeinated beer,
and nonalcoholic beer in 127 nondependent, heavy episodic
drinkers, aged 21–30 years.41 When a peak BrAC of 0.12%
was achieved, there was no significant difference in estimated
BrAC between caffeinated and noncaffeinated beer, indicating that caffeine (a total dose of 383 mg on average) did not
mask the alcohol intoxication effects, and thereby supporting
the majority of findings observed with energy drinks.
Do energy drinks enhance alcohol
consumption?
Given the stimulant effects of caffeine-containing energy
drinks, it has been suggested that when consumed together
with alcohol, energy drinks would increase alcohol ingestion.
Although no experimental data are available, several surveys
examined the coconsumption of energy drinks and alcohol.27–34,44–48 The design and results of these studies, which
are nearly all from the US, are summarized in Table 3. In
addition to the conclusions drawn by the respective authors,
Table 3 also includes our interpretation of the data in the
comment column.
Arria et al conducted a 3-year longitudinal study aiming
to examine illicit drug use patterns among college students
(the 2003 College Life Study).49 Annually, they interviewed
International Journal of General Medicine 2012:5
International Journal of General Medicine 2012:5
Jock identity (mediated by masculine
norms and risk-taking behavior) was
positively related to energy drink
consumption (without alcohol)
AmED consumption was associated with
significantly increased heavy episodic
drinking, episodes of weekly drunkenness,
and alcohol-related consequences
795 undergraduate
students
4271 college students;
697 AmED (16%);
2189 alcohol alone (52%);
1351 nondrinkers (32%);
between-subject
comparison
1060 college students;
264 energy drink users;
796 nonusers;
between-subject
comparison
Miller44
US
O’Brien
et al27
US
Arria et al28
US
Attila and Cakir30 439 Turkish students;
Turkey
between-subject
comparison
Frequency of energy drink consumption
was positively associated with marijuana
use, sexual risk-taking, fighting,
not wearing a seat belt, risk-taking,
smoking, drinking, alcohol problems,
and illicit prescription drug use
602 undergraduate
students
Miller34
US
Those who consume energy drinks are
more likely to smoke and drink alcoholic
beverages. 40% of current users report
mixing energy drinks with alcohol
Compared with nonusers of energy
drinks, energy drink users had a heavier
alcohol consumption pattern, and were
more likely to have used other drugs.
Year 2 energy drink consumption
correlated significantly with year 3
nonmedical use of prescription stimulants
and analgesics, but not other drugs
Findings highlighted by authors
Subjects
and design
Reference
Consumption of energy drinks
is quite common among students.
Their knowledge of ingredients
and potential health hazards is low
Energy drink users tend to have
greater involvement in alcohol
and other drug use
Risk-taking behavior partly
mediates the relationship
between jock identity
and AmED consumption
With AmED consumption
students are at increased risk
for alcohol-related consequences
(also after adjustment for the
amount of alcohol consumed)
Energy drink consumption is
closely associated with a problem
behavior syndrome
Authors’ conclusion
Table 3 Surveys and on-premise studies that examined the relationship between alcohol and energy drink consumption
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(Continued)
• The authors show that those who consume more
alcohol experience more alcohol-related consequences
• The authors do not provide evidence that during the
days of heavy episodic drinking or reported drunkenness
alcohol was mixed with energy drinks
• No evidence of a causal relationship between energy
drink and alcohol consumption is provided
• Only a relative minority (16%) mixed alcohol with energy drinks
• The study was designed for another purpose, and those with past
experience of illicit and/or prescription drugs were oversampled
• The difference between alcohol consumption of energy drink
users and nonusers is statistically significant but of no clinical
relevance (6.0 versus 4.7 drinks per drinking day); similarly for
the past year count of drug use (1.5 versus 1.0 occasions)
• It is not determined whether energy drinks and alcohol
were consumed together or alone
• Prescription and illicit drug use was measured using a binary
(yes or no) scale
• No evidence of a causal relationship between energy drink
and alcohol consumption is provided
• Only 15.2% of current users reported that the main reason to
consume energy drinks is to mix with alcohol. Most students
consumed energy drinks to feel energetic (24.2%), boost
performance during exercise (21.4%), or because of its taste (17.0%)
• No information on quantity of energy drink consumption was
provided
• No information was provided on whether alcohol
and drugs were consumed together with energy drink or alone
• No information was provided on whether alcohol-related
consequences were experienced when alcohol
was consumed together with energy drinks or alone
• Energy drink consumption explains only a small part
of the variance of ten domains of problem behavior
that were examined (R2 = 0.23 or less)
• The presented associations prove no causal relationship
• No evidence of a causal relationship is provided
Comment
Dovepress
Energy drinks mixed with alcohol
191
192
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328 bar patrons:
180 alcohol only,
n = 64 cola-caffeinated
alcohol only,
n = 10 AmED only;
onpremise study
413 bar patrons
For secondary analyses,
see data references 29
and 45
Thombs
et al45
US
Arria et al46
US
Rossheim and
Thombs32
US
1097 fourth-year college
students, 975 entered
analyses (338 nonusers,
518 low-frequent users
1–51 times/year),
802 bar patrons
(people who visit a bar
and consume alcohol):
602 alcohol only,
45 AmED;
onpremise study
Thombs
et al29
US
Woolsey
et al48
US
72 subjects, of which
10 consumed AmED and
alcohol alone during the
past week; within-subject
comparison
401 student athletes:
165 alcohol only;
150 AmED; 194 energy
drinks alone.
Both within-group
and between-subject
comparison
Subjects
and design
Price et al33
Canada
Reference
Table 3 (Continued)
Comparing n = 69 alcohol mixed with
regular cola, n = 24 alcohol mixed with
diet cola, n = 19 AmED, and n = 147
alcohol only, n = 129 noncaffeinated
mixers and alcohol. Those who mix
alcohol with diet-cola have a significantly
higher BrAC when leaving the bar.
No significant difference between alcohol
only and AmED was found
Energy drink consumers consumed
more alcohol (both quantity
and frequency) and a significant
association was reported between
high-frequency energy drink users
Cola-caffeinated alcoholic beverages
consumers and AmED consumers leave
the bar significantly more intoxicated
than those who consume alcohol alone
Weekly or daily energy drink
consumption is strongly associated
with alcohol dependence
Reported risks associated with
on premise AmED drinking may be
reduced by greater attention given
to other types of mixers,
particularly diet cola
Mixing alcohol with cola poses a
similar level of risk for bar patrons
to those associated with AmED
consumption
Combined users consumed
significantly more alcohol and had
riskier drinking habits than those who
consume alcohol only. The combined
use of alcohol and energy drinks
may increase alcohol consumption,
risk-taking behavior, and the chance of
experiencing negative alcohol-related
consequences
Energy drink consumption
by young adults at bars is a marker
for elevated involvement in
night-time risk-taking behavior
Combined users consumed
significantly more alcohol and had
riskier drinking habits than those
who consume alcohol only, and
experience more negative
alcohol-related consequences
Patrons who consumed AmED were
at three-fold increased risk of leaving the
bar highly intoxicated (BrAC . 0.08%),
and a four-fold increased risk of intending
to drive upon leaving the bar district
AmED consumption seems
associated with increased
alcohol ingestion
Authors’ conclusion
Subjects (10) consumed significantly more
alcohol when mixed with energy drinks
(8.6 drinks) when compared with
consuming alcohol alone (4.7 drinks)
Findings highlighted by authors
• The survey fails to indicate whether or not energy drinks
were consumed with alcohol, or separately. Hence,
the authors do not rule out the possibility that energy
drinks were consumed during the day. For example,
to compensate for alcohol-related hangover effects
• Mixing alcohol with caffeinated cola (22.5%) was more
popular than mixing with energy drinks (6%)
• No significant difference was found between alcohol
only and AmED
• Relatively low power (AmED group, n = 19)
limits conclusions
• Within-subject comparisons show that combined users (AmED,
n = 150) report drinking significantly less (27%) alcohol
when mixing alcohol with energy drinks
(and 41% less on the heaviest drinking day)
• Within-subject comparison provides much more reliable
evidence than between-subject comparison. Nevertheless,
authors do not discuss their within subject findings
• No significant within-subject differences were found on the major
risk-taking items
• It was not verified if they indeed drove a car (no actual risk-taking
was determined, only the intention to do so)
• The quantity of energy drink consumption was not determined
• No significant difference in AUDIT-C (alcoholic drink
consumption) score between AmED and alcohol alone
• BrAC difference between AmED (0.1%) and alcohol alone
(0.08%) was equivalent to just one alcoholic drink
• AmED group (n = 10) has insufficient power to draw
reliable conclusions
• Low sample size does not have sufficient power to draw
any conclusion
• Short time-frame (one week)
Comment
Verster et al
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International Journal of General Medicine 2012:5
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International Journal of General Medicine 2012:5
Abbreviations: AmED, alcohol mixed with energy drink; US, United States; BrAC, breath alcohol concentration; AUDIT-C, Alcohol Use Disorders Identification Test, version C; DSM-IV, Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition.
• The number of subjects who consumed energy drinks
was low (n = 24) and this limits conclusions
• The data did not allow a within-subject comparison
• A heavy drinking night that caused a hangover may not reflect
a regular night of alcohol consumption
Mixing with caffeinated beverages
does not change overall alcohol
consumption, nor does it affect
next-day hangover severity
549 Dutch students,
who reported on their
latest hangover;
between-subject
comparison
Penning et al47
The
Netherlands
Compared with nonconsumers, ED
drinkers were predominantly male,
non-Black, and young (18–29 years old),
AmED drinkers white and young.
Hazardous drinkers (AUDIT-C 4 or more)
were four times more likely to
consume energy drinks
No significant difference was found in the
number of alcoholic drinks consumed on
the night before their latest hangover
between those who consumed AmED
and those who consumed alcohol alone
946 adults aged
18–92 years;
between-subject
comparison
Berger et al31
US
119 high-frequent users
(52+ times/year);
between-subject
comparison
and having a DSM-IV diagnosis
of alcohol dependence
There are population differences
between those who mixed alcohol
with energy drinks and those who
consume alcohol alone
• The authors show that those who consume more alcohol (quantity
and frequency) also consume more energy drinks. The correlation
reported does not imply a cause-and-effect relationship
• Those who consume more alcohol are more likely to meet
the criteria of alcohol dependence
• Only a minority of college students (10.1%) was classified as
high-frequency energy drink consumers (52+ times/year)
• No information on amount of alcohol consumed or
AUDIT-C scores was provided
• 6% mixed energy drinks with alcohol during the past year
Energy drinks mixed with alcohol
1063 college students. To ensure a sufficient number of
eligible subjects, those with past experience of illicit and/or
prescription drugs were oversampled. An exploratory analysis of the data was performed comparing those who consume
energy drinks and those who do not.28 Since the study was not
set up for this purpose, only two questions about energy drink
consumption were asked. These questions were “What types
of caffeinated products do you consume?” and “Estimate
the typical, minimum, and maximum number of caffeinated
drinks you consume during a typical week”. Based on the
first question, subjects were classified as energy drink users
(n = 264) and those who do not consume energy drinks
(n = 796). Energy drink consumers reported significantly
more alcohol intake (both quantity and frequency). Illicit drug
use was not significantly higher in energy drink consumers,
nor was the use of medicinal drugs, except for prescription
stimulants and analgesics. Subjects also completed the short
form of the Zuckerman–Kuhlman Personality Questionnaire.
Energy drink consumers scored significantly higher on the
subscale of impulsive, sensation-seeking behavior.
Unfortunately, the authors did not gather any specific
data on whether energy drinks were mixed with alcohol or
not. Also, prescription and illicit drug use was only measured using a binary (yes or no) scale. Recently, Arria et al
published data from the fourth yearly interview of students
participating in the 2003 College Life Study.46 In this interview, students estimated the types of energy drinks and the
number of days and usual quantity of energy drinks they
consumed during the previous 12 months. The statistical
analysis showed an association between energy drink and
alcohol consumption, and reported that those who “frequently” consume energy drinks ($52 days per year, ie, $1
per week; representing 10.1% of the sample) significantly
more often met the Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV) criteria for alcohol dependence. However, the survey also failed to indicate
whether or not energy drinks were consumed together with
alcohol, or separately. In fact, in both studies, the authors do
not rule out the possibility that energy drinks were consumed
separately during the day, or the day after to compensate for
alcohol-related hangover effects.28,46
A survey among 4271 college students by O’Brien et al
showed that consumption of AmED was associated with
increased heavy episodic drinking (6.4 days versus 3.4 days
in the past 30 days) and weekly drunkenness (1.4 days/week
versus 0.73 days/week), and experiencing negative alcoholrelated consequences significantly more often.27 Again,
this study also does not provide any evidence for a causal
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Verster et al
r­ elationship, but does support the association that when
people drink more alcohol they may also mix some of their
alcohol with energy drinks.
Price et al interviewed 10 regular energy drink users about
their past week and lifetime energy drink and alcohol use.33
These 10 subjects consumed significantly more alcohol on the
occasion that they also consumed energy drinks (8.4 versus
4.7 alcoholic consumptions, respectively). The authors
acknowledge the small sample size and recommend additional research, but nevertheless conclude that using energy
drinks is associated with increased alcohol consumption.
Thombs et al examined energy drink and alcohol use in
a naturalistic setting, ie, college bars, between 10.00 pm and
03.00 am.29 In a bar district, 802 subjects were interviewed
about their alcohol use and energy drink consumption and
performed a breath analysis test to estimate BrAC. Subjects
also completed the shortened Alcohol Use Disorders
­Identification Test (AUDIT-C), a measure of quantity/
frequency of consumption, and were asked how likely it was
that they would drive home by car at the end of their night
out. Significant differences were observed between those
who consumed alcohol only (n = 602) and those who mixed
energy drinks with alcohol (n = 46); the differences included
mean BrAC (0.08% versus 0.11%), alcohol consumed (95.3 g
versus 152.2 g), and total hours of drinking (2.9 hours versus
3.9 hours) for these two groups, respectively. AUDIT-C
scores did not significantly differ between the groups.
Logistic regression analysis revealed that those who mixed
alcohol and energy drinks were 3.32 times more likely to leave
the bar intoxicated (BrAC $ 0.08%) and had a 4.26 times
increased risk of intending to drive a car after ­leaving. The
authors concluded that the latter suggests perception of
alcohol-induced impairment is reduced when coconsumed
with energy drinks. An alternative explanation may be that
the groups already differed at baseline in alcohol consumption and risk perception. In a second study by Thombs et al,
only 10 people reported consuming AmED.45 Therefore, the
conclusions drawn based on the data from this small study
should be interpreted with caution. Rossheim and Thombs
then combined the data from both onpremise studies.32 Based
on the combined data, they concluded that energy drink
consumption was not associated with an increased risk of
being intoxicated.
Miller conducted a survey among 602 undergraduate
students that indicated energy drink consumption was associated with problem behaviors, particularly among white
students.34 Frequency of energy drink consumption was
positively associated with marijuana use, smoking, drinking,
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alcohol ­problems, illicit drug use, and risk-taking behavior.
In a second survey among 795 undergraduate students,
Miller confirmed that levels of conformity to masculine
norms, risk-taking behavior, and sport-related (“jock”)
identity significantly predicted the frequency of energy drink
consumption.44
Berger et al reported ethnic and other differences between
those who consume alcohol alone compared with energy
drink users, or those who consume AmED.31 These differences were noted by the authors, who then suggest subgroup
targeting for health information. However, they fail to point
out that the observed increase in “hazardous drinking” for
the AmED group may be accounted for by intergroup differences alone (eg, age, ethnicity), rather than to AmED
consumption.
A finding from several surveys has been that AmED
consumption was associated with increased alcohol
consumption.27,28,46 These surveys show that research comparing different groups (eg, those who combine alcohol with
energy drinks and those who do not) is always difficult to
interpret, and can yield potentially biased results because
baseline and other characteristics of the groups have not been
controlled for and may differ significantly. This potential
bias can be prevented by conducting research using a withinsubject design, ie, comparing drinking occasions in the same
subjects with and without energy drink consumption and
using an appropriate sample size. This design was applied
in a recent survey by Woolsey et al among athletes.48 When
comparing drinking habits of those who drink alcohol only
(n = 165) and those who mixed alcohol with energy drinks
(n = 150) these researchers showed that those who consumed
AmED drank alcohol significantly more often, drank more
alcohol on single occasions, reported more heavy drinking
episodes, and had consumed twice the amount of alcohol
during the past year when compared with the group that
never mixed alcohol with energy drinks.
However, when looking at the group that combined
energy drinks with alcohol, it was shown that on occasions
when they did mix alcohol and energy drinks they consumed
significantly less alcohol (6.28 drinks) when compared with
occasions when they consumed alcohol without energy drinks
(8.60 drinks) a reduction of 27%. Also, when reporting on
the greatest number of alcoholic drinks consumed on a single
occasion during the past year, the combined group reported
significantly less alcohol consumption (10.83 drinks) when
combining alcohol with energy drinks compared with a
session of alcohol without energy drinks (18.23 drinks),
ie, a reduction of 41%. Also, no significant within subject
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d­ ifferences were found on the major risk-taking items “­taking
risks”, “being brave and daring”, and “being likely to fight”,
whereas the statistically significant differences found for
“acting aggressively” (2.46 versus 2.76) and “driving a
motor vehicle” (1.57 versus 1.75) for alcohol versus AmED,
respectively, reflect only small numerical differences and
therefore have no clinical relevance.
Unfortunately, the authors concluded their article with
a discussion of the potential dangers of energy drinks and
a call for action to protect the public, and disregarded their
own findings showing that alcohol consumption within
subjects was substantially reduced when mixing alcohol
with energy drinks.
Interestingly, recent onpremise studies reveal that the
single focus on energy drinks as a mixer for alcohol may be
unjustified and misplaced, because other caffeinated mixers such as cola beverages are more popular than energy
drinks.29,32,45 They showed that mixing alcohol with caffeinated cola (22.5%) was much more popular than mixing with
energy drinks (6%). Breathalyzer assessment on leaving the
bar revealed that BrAC levels were similar in those who consumed alcohol mixed with cola (BrAC 0.108%) or consumed
AmED (BrAC 0.106%), and somewhat higher than found in
those who consumed alcohol only (BrAC 0.091%). A recent
survey confirmed these findings among Dutch students, when
reporting on their latest night out that caused a hangover.47 No
difference in total alcohol consumption was found between
those who consumed alcohol alone or AmED, whereas
those who mixed alcohol with cola beverages consumed
­significantly more alcohol.
In conclusion, the specific nature of the relationship
between energy drink consumption and alcohol consumption,
if any, cannot be established from these surveys. The fact that
two things occur together (ie, the presented correlations in the
surveys between energy drink and alcohol consumption) does
not imply that one causes the other.50 More direct and reliable
within-subject comparisons comparing occasions of alcohol
intake both with and without energy drink ­consumption, such
as performed by Woolsey et al,48 are necessary to establish
if there is an actual difference, and to what extent energy
drinks influence alcohol consumption, or not.50
Discussion
Excessive and irresponsible consumption of alcoholic drinks
has adverse effects on human health and behavior, but it
should be clear that this is due to the alcohol, and not the
mixer. When presenting their data, several authors fail to
acknowledge that correlations between energy drink and
International Journal of General Medicine 2012:5
Energy drinks mixed with alcohol
alcohol consumption do not provide any cause-and-effect
relationship.50,51 Instead, they describe the “high” risk of
combined use of energy drinks and alcohol52 as “a growing
problem”3 or “a new hazard for adolescents”,53 without providing supportive scientific evidence, or they simply copy
the conclusions of other authors without having a closer look
at the methodology of the surveys and the way the data were
analyzed and presented.54 This way of presenting and interpreting scientific data may raise unsubstantiated concerns
among consumers and parents about the use of energy drinks
(alone or in combination with alcohol) and may actually trigger unjustified regulations in the absence of appropriate data.
Some recent reviews have copied the conclusions of these
authors, summarizing the data and its interpretation as offered
by the authors that conducted these studies, draw unjustified
conclusions, or present recommendations for legislation that
are not supported by the available scientific data.53–55
However, other authors have commented on the current energy drink debate and disputed the conclusions
drawn in these reviews.50,51,56 Other criticism focuses on the
methodology and setup of previous studies, some of which
were underpowered or were not specifically designed to
examine the association between energy drink consumption and alcohol consumption.49 Given the limitations of
these studies (summarized in Tables 2 and 3), Skeen and
Glenn56 concluded that there is an “imaginary link between
alcoholism and energy drinks”, and Verster and Alford50
concluded that the concerns about energy drinks are not
justified by the currently available scientific data. But most
importantly, when judging articles on energy drinks mixed
with alcohol, it should be kept in mind that correlation does
not mean causation.51
In fact, there are many alternative explanations. Several
surveys compared groups of subjects who do and do not
combine alcohol with energy drinks. As some surveys on
energy drink consumption suggested, it is possible that the
groups of subjects that were compared already differed at
baseline regarding the level of risk-taking behavior and
other personality traits.28,34,44,46,48 This may explain the
observed differences in alcohol and drug use between the
groups. People who are high risk-takers are more likely to
exhibit life-style behaviors characterized by disinhibition
and loss of moderation. These behaviors include increased
frequency and amount of alcohol consumption, caffeine
consumption, smoking, and recreational drug use, as well
as gambling and engagement in risk-taking behavior.57,58
Being a high risk-taker may then be the cause of increased
alcohol consumption.
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Verster et al
A significant association between levels of risk-taking
behavior (measured as sensation-seeking, impulsivity, and
related traits) has been reported for alcohol and drug use,59,60
as well as energy drinks.28,34,44,46,48 These surveys link the
consumption of energy drinks with a risk-taking lifestyle
that is already characterized by higher levels of alcohol
consumption. In other words, a personality with higher
levels of risk-taking behavior may be the primary reason
for increased alcohol and drug abuse. The coconsumption
of energy drinks is just one of the many expressions of such
a lifestyle and personality.
Given that energy drink companies often market their
products by relating them to extreme sports and adventurous activities, it is understandable that individuals who are
attracted to energy drinks more often have a higher risktaking profile.
Seven main conclusions can be drawn from the available
scientific literature:
• There are currently insufficient properly controlled studies to draw any firm conclusions regarding the effects of
energy drinks mixed with alcohol
• A relative minority of students occasionally mix energy
drinks with alcohol, and there is no evidence that energy
drinks are consumed more than other caffeinated drinks
(eg, colas) combined with alcohol
• There is some evidence that energy drinks may antagonize
some, but not all, aspects of alcohol-induced performance
impairment
• There is no consistent evidence that energy drinks alter
the perceived level of intoxication of people who mix
energy drinks with alcohol
• Whilst there are associations between the levels of alcohol
and energy drink consumption, there is no evidence that
coconsumption of energy drinks causes increased alcohol
consumption
• There is no direct evidence that coconsumption of alcohol
and energy drinks initiates drug and alcohol dependence
or abuse
• A personality with higher levels of risk-taking behavior
may be the primary reason for increased alcohol and
drug abuse. The coconsumption of energy drinks may
be one of the many expressions of their lifestyle and
personality type.
These conclusions are drawn from the limited evidence
available at this time. Hence, more and better research is
needed. Properly controlled clinical studies, surveys, and
prospective studies are required before definite conclusions
can be drawn. In order to define the effects of an energy drink,
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such clinical studies must include sessions of administration of
both energy drink or placebo drink (ie, an energy drink without
the active ingredients) as well as alcohol alone, and whenever
possible applying a within-subject design. Such designs are
more complex but essential if the focus is on the effects of
energy drinks on alcohol consumption. Until these data are
available, interventions with the primary goal of reducing
alcohol consumption and related problems should focus on
the availability and consumption of alcohol per se.
Disclosure
Over the last 3 years, Joris Verster has received research
funding from Takeda Pharmaceuticals, Deenox, and Red Bull
GmbH, and done consultancy work for Takeda, Sepracor,
Sanofi Aventis, Deenox, Red Bull GmbH, CBD, Trimbos
Institute, and Transcept. Chris Alford has received funding
from the UK Ministry of Defence, Red Bull GmbH, and
Sanofi-Aventis. Christoph Aufricht has received research
funding from the Austrian Science Fund, the European
Community, Fresenius Medical Care, Baxter Healthcare,
and Zytoprotec.
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International Journal of General Medicine 2012:5
Psychopharmacology (2012) 222:519–532
DOI 10.1007/s00213-012-2677-1
ORIGINAL INVESTIGATION
The effects of energy drink in combination with alcohol
on performance and subjective awareness
Chris Alford & Jennifer Hamilton-Morris &
Joris C. Verster
Received: 30 August 2011 / Accepted: 22 February 2012 / Published online: 29 March 2012
# Springer-Verlag 2012
Abstract
Rationale This study investigated the coadministration of
an energy drink with alcohol to study the effects on subjective intoxication and objective performance.
Objectives This study aims to evaluate the objective and
subjective effects of alcohol versus placebo at two alcohol
doses, alone and in combination with an energy drink, in a
balanced order, placebo-controlled, double-blind design.
Methods Two groups of ten healthy volunteers, mean (SD)
age of 24 (6.5), participated in the study. One group consumed energy drink containing 80 mg of caffeine and the
other consumed a placebo drink, with both receiving two
alcohol doses (0.046 and 0.087% breathalyser alcohol concentration). Tests included breath alcohol assessment, objective measures of performance (reaction time, word
memory and Stroop task) and subjective visual analogue
mood scales.
Results Participants showed significantly impaired reaction
time and memory after alcohol compared to the no alcohol
condition and had poorer memory after the higher alcohol
dose. Stroop performance was improved with the energy
drink plus alcohol combination compared to the placebo
drink plus alcohol combination. Participants felt significant
subjective dose-related impairment after alcohol compared
C. Alford (*) : J. Hamilton-Morris
Psychology Department, Faculty of Health and Life Sciences,
University of the West of England,
Frenchay Campus, Coldharbour Lane,
Bristol BS16 1QY, UK
e-mail: [email protected]
J. C. Verster
Division of Pharmacology, Utrecht Institute for Pharmaceutical
Sciences, Utrecht University,
Universiteitsweg 99,
3584 CG, Utrecht, The Netherlands
to no alcohol. Neither breath alcohol concentration nor the
subjective measures showed a significant difference between the energy drink and the placebo energy drink when
combined with alcohol.
Conclusions Subjective effects reflected awareness of alcohol intoxication and sensitivity to increasing alcohol dose.
There were no overall significant group differences for
subjective measures between energy drink and placebo
groups in the presence of alcohol and no evidence that the
energy drink masked the subjective effects of alcohol at
either dose.
Keywords Alcohol . Antagonism . Caffeine . Energy drink .
Intoxication . Performance . Subjective awareness
Introduction
Energy drinks are sold in more than 160 countries, and sales
are increasing. Energy drinks contain caffeine, taurine and
carbohydrates in the form of sugars as principal ingredients
(Heckman et al. 2010). They are popular with young people,
and students report their use for a variety of reasons including to enhance memory and concentration or to counteract
sleepiness (Malinauskas et al. 2007; O’Brien et al. 2008).
Whilst a minority of students combine energy drinks with
alcohol (Arria et al. 2010; Attila and Cakir 2010; Berger et
al. 2010; Malinauskas et al. 2007; O’Brien et al. 2008; Oteri
et al. 2007; Rossheim and Thombs 2011), this still represents a significant number and so they are becoming a
popular mixer. Caffeine and alcohol are two of the oldest
commonly consumed psychoactive compounds, and caffeinated drinks have been mixed with alcohol for many
years.
520
There are some recent claims that energy drinks may
mask the subjective effects of alcohol, and this may either
lead people to drink more or that they may be unaware of
how intoxicated they are (Arria et al. 2010; Arria and
O’Brien 2011; O’Brien et al. 2008), although these views
on masking have been challenged (Verster and Alford 2011)
and an alternative explanation for enhanced intoxication
with novel drink flavours has been offered by Siegel
(2011). A brief review of the effects of caffeine and energy
drinks alone and in combination with alcohol is provided in
order to establish whether or not energy drinks appear
different to other caffeinated drinks when mixed with
alcohol.
Mechanisms of action
Folklore tells how caffeine has long been used as a stimulant
to help maintain wakefulness, including helping monks with
their nightly prayers, and early studies found that caffeine
improved performance including the speed of response
(Hollingworth 1912; Ritchie 1980; Schilling 1921). The
primary action of caffeine as an adenosine inhibitor is well
established, thus counteracting the actions of this inhibitory
neurotransmitter and increasing the release of other neurotransmitters including noradrenaline and dopamine, producing a moderate stimulant and mood-enhancing effect.
Blockade of the A2A receptor by caffeine inhibits the sleeppromoting effect with adenosine levels increasing across the
hours of wakefulness (Davis et al. 2003; Ferré 2008; Huang
et al. 2007; Landolt 2008; Sturgess et al. 2010).
In contrast to caffeine, alcohol has long been found to
have detrimental effects on both judgement and performance (Cohen et al. 1958; Wallgren and Barry 1970), with
Miller (1992) concluding‚ ‘In general, alcohol has an adverse effect on cognitive performance’. Alcohol may have
more complex effects than caffeine, with regions of the CNS
affected differentially by dose (Rivers 1994) and with multiple actions including depressing the ion channel function
controlled by the excitatory neurotransmitter glutamate at
the NMDA receptor, inhibiting acetylcholine release and
potentiating GABA resulting in impaired cognition, inability to form new memories and sedation (Braun 1996;
McKim 1997). Alcohol has a wide spectrum of action
within the CNS affecting many neurotransmitter systems
including major neurotransmitters adenosine, dopamine,
GABA, glutamate and serotonin. Interaction with the mesolimbic dopamine reward pathways may well contribute to
the process of addiction and alcohol misuse (Lovinger
2008). The comparatively restricted action spectrum of caffeine, focused on adenosine inhibition, may account for its
more limited misuse potential seen in caffeinism, although it
is not recognized as a dependence-inducing substance (APA
1994).
Psychopharmacology (2012) 222:519–532
Effects on subjective state and performance
Alcohol impairs a wide range of psychomotor and cognitive
tasks, slowing reaction times, impairing memory formation
and increasing errors (Cameron et al. 2001; Hindmarch et al.
1991; Mackay et al. 2002; Maylor and Rabbitt 1993; Millar
et al. 1995; Moskowitz et al. 1985; Ogden and Moskowitz
2004; Tiplady et al. 2009). The differential effects on
regions of the CNS may be linked to lower doses affecting
higher-level processing (Jääskeläinen et al. 1995) and genetic differences contribute to overall variation in sensitivity
to alcohol (Tagawa et al. 2000). Koelega (1995) concluded
that the effects on information processing and divided attention tasks are important because of their relevance to
everyday life. Therefore, it is not surprising that alcohol
impairs driving and driving-related skills (Holloway 1995;
Starmer 1989; Verster et al. 2009). The dose–response curve
linking blood alcohol level and relative probability of causing
a driving accident has long been established and applied in
setting legal limits for alcohol levels and driving (Borkenstein
et al. 1964) with limits in Europe, US and UK currently set
around 0.05–0.08% blood alcohol concentration (BAC) levels. Laboratory studies show that driving-related skills are
significantly impaired at the 0.05% BAC level (Ogden and
Moskowitz 2004).
Alcohol intoxication has been linked to riskier sexual
behaviour (Fromme et al. 1999), although there may problems with the use of retrospective accounts (Halpern-Fischer
et al. 1996). Judgement may also be affected with people
overestimating their abilities (Flanagan et al. 1983; Tiplady
et al. 2004), including being able to deal with a potentially
risky situation or acting on immediate short-term consequences rather than longer-term consequences (Farquhar et
al. 2002). Specific to driving, alcohol may cause a ‘risky
shift’, resulting in hitting the test bollards and failing the gap
acceptance test (Alford and Starmer 1990, personal communication; Betts et al. 1984).
In contrast to alcohol, the moderate stimulant effects of
caffeine are associated with improved performance. Doses
typically in the 100- to 200-mg dose range result in improved mood (Mumford et al. 1994), shorter reaction time
and improved attention and vigilance (Frewer and Lader
1991; Koelega 1998; Nehlig et al. 1992; Robelin and Rogers
1998; Smit and Rogers 2000; Smith 2002; Van der Stelt and
Snel 1998) in a dose-dependent way (Smith et al. 2005).
However, significant effects are not always seen, which may
be due to the limited effect size and possible ceiling effects
in that it is harder to enhance performance in healthy young
adults. There is also genetic variation in response to caffeine
(Nehlig 2010) so that sampling will affect observed response. Caffeine and glucose are both contained in energy
drinks, and studies have found improved performance when
they are taken together. Both Adan and Serra-Grabulosa
Psychopharmacology (2012) 222:519–532
(2011) and Scholey and Kennedy (2004) found faster speed
of response with attentional tasks, as well as improved
memory, with caffeine and glucose combined in comparison
to the individual constituents, although significant changes
in mood were not seen.
Overnight withdrawal from caffeine can itself result in improved performance following morning caffeine: the caffeine
reinstatement or withdrawal hypothesis (James 1997; James
and Rogers 2005), although improvements in performance
are still seen independently of this when additional caffeine is
consumed after the usual caffeine intake (Christopher et al.
2005; Smith et al. 2005; Warburton 1995; Watson et al.
2002). Beneficial effects are more clearly seen when participants are sleep-deprived or fatigued (Alford 2009; Davis et al.
2003; Fagan et al. 1998; James 1997; James and Gregg 2004;
Ker et al. 2010; Nehlig 2010; Rogers et al. 2005; Smith 2002;
Swift and Tiplady 1988), with a recent review (Glade 2010)
concluding that caffeine has a beneficial effect increasing energy availability and expenditure whilst decreasing the subjective
effort linked to physical activity, enhancing physical, motor and
cognitive ability including neuromuscular coordination, speeding and increasing accuracy of reactions, increasing concentration, focus and short-term memory and problem solving,
increasing correct decision making, and increasing subjective
feelings of alertness and energy (for physical performance, see
Astorino and Roberson 2010; Sokmen et al. 2008).
521
or through proximal consumption of alcohol and caffeine
such as dinner with alcohol followed by coffee. Given that
caffeine is a weak stimulant and alcohol is a sedative, a
predicted outcome would be that caffeine would antagonize
the effects of alcohol, reducing both subjective and objective impairment. However, whilst some studies have shown
antagonism (Hasenfratz et al. 1993), some others have
found no effect (Nuotto et al. 1982) and yet others have
shown that caffeine may even increase the impairing effects
of alcohol (Oborne and Rogers 1983). A recent view is that
caffeine can antagonise some, but not all, behavioural
effects of alcohol (Azcona et al. 1995; Liguori and Robinson
2001; Marczinski and Fillmore 2006), although expectancy
may be involved (Fillmore et al. 2002; Fillmore and VogelSprott 1995). Azcona et al. suggested that caffeine antagonism may more readily be seen in tasks where caffeine itself
has a more positive effect on performance.
An important safety-related aspect of psychopharmacological investigations is whether or not subjective awareness
parallels objective impairment or behavioural toxicity
(Hindmarch et al. 1992). Laboratory investigations have
shown that caffeine and alcohol in combination do not alter
the ‘high’ or perceived or actual BAC with caffeine levels
up to around 400 mg and alcohol 0.012% BAC (Howland et
al. 2010; Liguori and Robinson 2001; Rush et al. 1993).
Energy drinks and alcohol
Effects of energy drinks
Since their introduction into Europe in the late 1980s, there
has been interest in the performance-enhancing effects of
energy drinks. Popular brands contain around 80 mg of
caffeine per 250 ml which places them above colas but on
a similar level to coffee, although some minority brands can
contain higher doses as can other preparations of coffee
(IFIC 1998; Reissig et al. 2009). Other key ingredients
include taurine, carbohydrates in the form of sugars and
glucoronolactone (a sugar metabolite) and B complex
vitamins.
Energy drink consumption has been shown to improve
physical performance in several but not all studies (Alford et
al. 2001; Hoffman 2010; Ivy et al. 2009; Klepacki 2010; Walsh
et al. 2010). In addition, improvements have been shown for
both psychomotor and cognitive functioning, as well as driving
and driving-related skills (Alford et al. 2001; Gershon et al.
2009; Horne and Reyner 2001; Mets et al. 2010; Reyner and
Horne 2002; Seidl et al. 2000; Smit et al. 2006).
Caffeine and alcohol
Caffeine and alcohol are commonly combined either
through consumption of alcohol with caffeinated mixers
including colas or energy drinks (Thombs et al. 2010a, b)
Given the increasing popularity of energy drinks and that
caffeine is a principal ingredient, it is logical to raise questions regarding their interaction with alcohol on both subjective and objective measures. A recent commentary
claimed that individuals who combined energy drinks with
alcohol underestimate their true level of impairment and that
the drink combination could lead to engaging in risky behaviour, whilst others have claimed that these effects could
have an increased accident risk (Arria and O’Brien 2011;
Riesselmann et al. 1996).
Currently, there are only a few studies investigating the
combined effects of energy drink and alcohol compared to
alcohol alone. Ferreira et al. (2004) investigated the effects
on physical performance of alcohol (1.0 g/kg) and energy
drink (3.57 ml/kg equivalent to a standard 250 ml can) alone
and in combination. Whilst alcohol impaired maximal effort
assessed using a cycle ergometer, no significant differences
were found between alcohol alone and energy drink combined with alcohol. A recent study by Marczinski et al.
(2011) compared the effects of alcohol alone to alcohol
combined with energy drink at 0.06–0.07% breath alcohol
concentration (BrAC). They found no differences in breath
alcohol or level of impaired performance. They undertook
over 20 individual subjective ratings, including perceived
intoxication and ability to drive, which again found no
522
differences between alcohol and energy drink in combination with alcohol. However, the authors focused in on two
subjective measures that failed to show significant effects
with ANOVA but did show reduced mental fatigue and
increased stimulation for the energy drink and alcohol combination compared to alcohol, but not against placebo for the
latter, using paired comparisons. They interpreted this as
potentially dangerous despite the lack of difference in a
direct subjective measure of intoxication, as well as ability
to drive.
Several authors have recently claimed that energy drink
when combined with alcohol produces a reduction in perceived intoxication or ‘masking’ of subjective awareness
(Arria and O’Brien 2011), although this appears to be based
on a single study which is, therefore, considered in some
detail.
Ferreira et al. (2006) compared the effects of two doses of
alcohol (0.04–0.05 and 0.097–0.099% BrAC) assessed using two participant groups, when given alone and in combination with energy drink. Psychomotor performance was
assessed (reaction time and grooved peg board) and found to
be impaired with both alcohol alone and the alcohol and
energy drink combination. An 18-item modified somatic
symptom scale assessed subjective intoxication at 2 time
points (18×2 scales). Dry mouth, headache, motor impairment and weakness (4), i.e. not all were typical alcohol
impairment assessment scales, showed reduced perception
for the alcohol energy drink combination compared to alcohol at 1 of the 2 time points (4/18×2) for alcohol doses
combined. More scales, though including 2 from the above:
dizziness, motor impairment, speech, tiredness, vision,
walking, weakness and well-being (8), showed impairment
with alcohol at more time points (10/18×2) that were not
reduced for the alcohol and energy drink combination.
However, the authors concluded that energy drink reduced
the perception of alcohol impairment.
Given the variability of results regarding the perception
of impairment, further studies are required to clarify the
effects of energy drink when combined with alcohol on
the subjective perception of intoxication. The current study
examined these effects with the use of both objective performance measures to establish impairment and subjective
ratings to assess perceived impairment.
Methods
Design
The present study investigated the effects of alcohol alone
and in combination with an energy drink in a placebocontrolled, rising dose, double-blind design. There were
two groups of participants with random allocation to
Psychopharmacology (2012) 222:519–532
treatment. One group received energy drink and the other
received placebo energy drink in a balanced order for both
the alcohol and placebo alcohol treatments on two separate
occasions.
Participants
Ten female and 10 male participants provided 2 mixed
gender groups of 10 volunteers, with the mean age of
24.5 years and range of 19–33 years. Average weight was
70.7 kg; for these light to moderate social drinkers, range
was 4–30 units, averaging 17 units per week (females 13.4,
males 20.6), with daily caffeine of 350 mg. Prior to participation, the study was approved by a University of the West
of England Ethics Committee and each participant signed an
informed consent. All participants reported that they were in
good health, not pregnant, taking illicit or social drugs, ‘over
the counter’ or prescribed medication with the exception of
the contraceptive pill. None reported adverse reactions to
either alcohol, caffeine or energy drinks and all consumed
weekly alcohol and had tried an energy drink at least once,
but not on a regular basis.
Assessments
Breath alcohol concentration Alcometer readings were taken by the experimenter who kept their hand over the visual
display so that participants were blind to their alcohol concentration readings.
Subjective impairment was measured using the Bond and
Lader (1974) 100-mm visual analogue scales (VAS) representing bipolar adjective pairs for the assessment of both
alerting and sedating CNS drug effects with clearheaded–
muzzy, clumsy–well coordinated, energetic–lethargic,
drowsy–alert, and mentally slow–quick witted selected for
analysis of alcohol-induced impairment. These scales have
previously been used to assess both energy drinks and
alcohol (Alford et al. 2001; Tiplady et al. 2004; Warburton
et al. 2001).
Critical flicker fusion threshold This was assessed by viewing four red-coloured light-emitting diodes set 1 cm apart in
a square formation on a black background providing foveal
fixation when viewed at 1 m. The diodes flickered on/off at
a constantly varying rate of 1 Hz/s with participants pressing
a response button at the point of perceiving either fusion or
flicker for three ascending and descending repetitions using
the psychophysical method of limits (Hindmarch et al.
1991).
Choice reaction time Psychomotor speed was measured
using a free standing box which comprised a touchsensitive home pad around which six equally spaced
Psychopharmacology (2012) 222:519–532
response pads were situated at 150 mm from the home pad
in a 120° arc with a red light-emitting signal diode positioned distal to each response pad. Participants were required
to move their finger from the home pad to the appropriate
pad as quickly and accurately as possible in response to
illumination of one of the stimulus diodes which were lit in
a random sequence over 20 trials (Hindmarch et al. 1991).
Word memory Printed sheets each containing a vertical
list of 30 words based on Pavio’s word lists balanced
for concreteness, imagery and meaningfulness were used
to assess memory (Paivio et al. 1968). Participants had
1 min to view and memorise the list, followed by a
further minute to write down as many words as they
could from the original list.
Stroop cognitive interference task (Stroop) Participants
were required to say out loud the colour of the ink, and
not the printed word, whilst reading down each of 4 columns totalling 100 printed colour words. For example, with
the word ‘RED’ printed in green ink, a correct response
would be to say ‘green’, ignoring what the letters spelt
(Stroop 1935). The time taken to complete the list and the
number of errors was recorded.
Equipment
Critical flicker fusion (CFF) and choice reaction time
(CRT) were tested using dedicated hardware supplied by
Comstat Medical based on the Leeds psychomotor tester
(Hindmarch et al. 1991). %BrAC was used to estimate
%BAC using a Lion Alcometer SD-400, Lion Laboratories, Barry, UK.
Treatments
Alcohol was given as vodka (37.5% by volume) with
amount adjusted for body weight using the formula adapted
from McKim (1997) to achieve an estimated blood alcohol
level of approximately 0.1% BAC divided across two
drinks. The energy drink treatment comprised a standard
can of Red Bull® Energy Drink (250 ml) containing
80 mg caffeine to which was added peppermint cordial
and Robinson’s apple and black currant (no added sugar)
concentrate to mask the flavour of the energy drink. The
placebo comprised 250 ml soda water together with peppermint cordial and Robinson’s apple and black currant (no
added sugar) concentrate with equal total volumes for alcohol and non-alcohol conditions. Supercook black/blue food
colouring was added to help mask the presence of energy
drink, with two drinks presented in each treatment condition
in glasses after the rim was swabbed with alcohol to help
further mask treatments.
523
Procedure
An opportunity sample of potential participants completed
screening questionnaires to assess health status, exclude
nondrinkers, excessive drinkers, none or high caffeine users,
or experience of an adverse reaction to test compounds, or
those who may be pregnant. On test days, health status and
the preceding night’s sleep was checked. They were asked to
abstain from alcohol and caffeine from the preceding night,
not drive to the university on test days, and have a light
lunch an hour before testing which was undertaken in the
psychology laboratories starting between 1 and 2 pm. A
practice session, weighing, explanation of study procedures
and random allocation to treatment group preceded testing
on the first test day with test sessions averaging 2.5 h for the
two test days which were separated by a week. Treatments
were administered double-blind with the assistance of an
additional experimenter who prepared the drinks. Participants were assessed three times on each test day, first at
baseline then 45 min after starting the first drink, with
10 min for drinking, and similarly after the second with
about an hour between drinks. The fixed test order, though
different word lists, started with subjective VAS assessment,
then breathalyser, followed by word list memory, Stroop,
CFF, CRT and finally delayed memory recall all administered with standardised instructions. After completing the
test sessions, participants were escorted home and later
followed up to check they had not experienced any adverse
reaction to treatment. Debriefing followed the final test day.
Data handling
All data were analysed blind. Raw data were collated and
transcribed into Excel spreadsheets. The Comstat Medical
equipment provided numerical values for ascending and
descending CFF thresholds, resulting in an overall mean.
Similarly, separate component means were given for CRT
including recognition reaction time (RRT) representing
elapsed time from stimulus signal onset to initiation of
response when the finger is lifted from the home pad.
Movement reaction time (MRT) is the time taken for the
finger to be moved from the home pad to the target pad and
total CRT is the sum of these two elements (RRT + MRT)
combined. For word memory, the correct number recalled
within the 60 s immediate or delayed recall period was
entered. For the Stroop task, the number of errors and time
taken to complete the task were recorded. The VAS scales
assessing subjective impairment were scored by measuring
the distance along the 100-mm line separating the adjective
pairs (e.g. drowsy–alert) for each of the five adjectives.
These values were also entered onto the results spreadsheet
together with the alcometer readings which were manually
recorded at each breath analysis session.
524
Psychopharmacology (2012) 222:519–532
Results
Choice reaction time
Statistical analysis
Alcohol slowed total CRT, although differences failed to
achieve significance for the main effects of alcohol and
drink; the energy drink produced a trend (P<0.1) for faster
responses compared to placebo. RRT showed a significant
slowing after alcohol (F1,18 06.5, MSe00.00, P00.02) and
trends for faster responses with the energy drink (P<0.1)
and for an interaction between alcohol and drink (P<0.1),
reflecting slower responses after the second alcohol drink
compared to faster responses after alcohol placebo for both
the energy drink and placebo energy drink groups combined. Means are plotted in Fig. 1.
Data were analysed using SPSS V17 (SPSS 2010). Placebo
baselines were compared for the energy drink and placebo
energy drink groups with t tests. Neither subjective impairment measures nor performance measures produced significant contrasts, demonstrating the comparability of the two
participant groups. To help standardise results between the
two groups of participants (energy drink and placebo energy
drink), as well as helping to control for variation between
test days, baseline difference scores were calculated. These
scores were then analysed using a three-factor 2 × 2 × 2
ANOVA (treatment group 2: energy drink and placebo
energy drink; alcohol 2: alcohol and placebo alcohol; drinks
2: drink 1 and drink 2). Statistical significance was set at the
5% level (P<0.05 or better) to assess main effects and
interactions. The analysis was, therefore, focused on assessing the overall effects of alcohol (alcohol vs placebo alcohol), increasing dose (drink 1 vs drink 2) and energy drink
(energy drink vs placebo energy drink). A simple main
effects analysis was additionally employed to specifically
assess differences between alcohol and energy drink contrasted with alcohol and energy drink placebo. A summary
table including means (SEM), together with associated
P values and effect sizes, for both subjective and performance measures are included in Table 1.
Word memory
Similar effects were found for both immediate and delayed
word memory recall. Alcohol markedly reduced the number
of words recalled (immediate: F1,18 023.8, MSe012.3, P0
0.001; delayed: F1,18 023.9, MSe019.5, P00.001) and in a
dose-dependent way (drinks—immediate: F 1,18 028.6,
MSe 03.46, P 00.001; delayed: F1,18 022.0, MSe 07.52,
P00.001), resulting in an alcohol × drink interaction reflecting the decrease in words recalled with increased alcohol
compared to alcohol placebo (interaction—immediate:
F1,18 015.8, MSe 06.57, P 00.001; delayed: F1,18 018.0,
MSe013.0, P00.001). These highly significant effects for
immediate recall are shown in Fig. 1.
Stroop task
Alcohol dose
All participants produced zero BrAC at each baseline and
for the placebo alcohol treatment. Mean BrAC after drink 1
was 0.046% BrAC and after drink 2 was 0.087% BrAC. The
mean (SD) results for the energy drink group were 0.044
(0.01) and 0.081 (0.02)% BrAC and for the placebo energy
drink group were 0.047 (0.01) and 0.094 (0.02)% BrAC
after drinks 1 and 2, respectively. Differences between treatment groups were nonsignificant (t test), facilitating comparison between the two groups for alcohol versus placebo
and between drinks 1 and 2, though noting highest breath
alcohol levels were recorded after drink 2 for the placebo
energy drink group.
Performance tests
Critical flicker fusion
Whilst no significant main effects or interactions were
found, the lowest thresholds were recorded in the alcohol
condition for both groups, consistent with a sedative effect.
Error rate was not significantly affected by alcohol overall,
although the highest error scores were recorded after the
second alcohol drink for the placebo energy drink group and
with a trend for lower error scores in the energy drink group
(P<0.1). Stroop completion time was faster with energy drink
(F1,18 011.1, MSe00.035, P00.004) and unexpectedly faster
still for alcohol combined with energy drink, resulting in a
main effect for alcohol (F1,18 06.06, MSe00.03, P00.024), as
well as a significant interaction between alcohol and treatment
group (F1,18 04.59, MSe 00.03, P 00.046). Simple main
effects analysis revealed that, in addition to completion time
(F1,18 011.2, MSe00.05, P00.004), Stroop errors were also
significantly reduced (F1,18 05.71, MSe03.68, P00.028) by
alcohol combined with energy drink contrasted with the alcohol and energy drink placebo combination.
Effect sizes (Cohen’s d) can be characterised as follows:
small d00.2; medium d00.5; large d00.8 (Cohen 1992).
Effect sizes of d≥0.2 were generally associated with statistically significant results, although both CRT overall and RRT
produced effect sizes for energy drink contrasted with energy
drink placebo of just over d00.2, reflecting faster responses
after energy drink that approached significance (P00.06).
1.41 (0.07)
1.21 (0.04)
ED
EDPla
ED
EDPla
ED
EDPla
ED
EDPla
RRT (s)
Memory
immediate
recall (N)
Memory delayed
recall (N)
Stroop errors
(N)
Stroop completion ED
EDPla
time (min)
ED
EDPla
ED
EDPla
ED
EDPla
ED
EDPla
Clumsy (mm)
Drowsy (mm)
Energetic (mm)
Mentally slow
(mm)
37.5 (3.6)
43.0 (3.6)
55.1 (3.8)
45.3 (4.2)
36.1 (5.1)
43.5 (4.8)
38.3 (4.0)
37.5 (3.6)
68.0 (4.1)
63.5 (4.6)
10.85 (0.96)
12.45 (0.56)
12.65 (0.96)
13.05 (0.42)
0.345 (0.01)
0.313 (0.01)
−0.25 (0.57)
0.34 (0.76)
0.43 (0.63) NS
0.78 (0.95)
−0.26 (0.07)
−0.02 (0.02)
−0.23 (0.07)
−0.02 (0.02)
12.4 (6.7)
5.1 (3.1)
−13.3 (7.4)
8.7 (10.8)
−1.8 (7.5)
0.4 (9.5)
9.8 (4.3)
−3.5 (2.7)
31.5 (8.1)
2.4 (10.6)
24.0 (5.9)
17.4 (4.9)
14.8 (9.5)
−0.9 (5.8)
16.3 (5.2)
6.4 (3.0)
−32.9 (7.9)
−17.5 (8.9)
0.30 (0.40)
1.80 (0.59)
−0.40 (0.54)
1.00 (0.45)
−21.0 (6.8)
−13.7 (7.5)
−8.2 (1.65)
−9.3 (1.01)
−2.7 (1.13)
−2.2 (1.36)
Alc, D2<D1
4.3 (3.2)
−5.1 (1.5)
−3.6 (3.3)
−2.9 (4.4)
−5.6 (9.9)
−1.9 (5.3)
−5.7 (6.4)
−3.8 (8.5)
5.6 (7.8)
2.7 (6.4)
1.0 (7.3)
1.2 (3.1)
−6.8 (6.6)
−3.3 (4.1)
8.6 (5.9)
1.3 (8.0)
−5.2 (7.2)
−8.2 (2.4)
Alc>Pla, 0.01
NS
Alc, D2>D1
Alc>Pla, 0.05
Alc×Drink, 0.05
Alc>Pla, 0.001
Alc<Pla, 0.02
ED, Alc<Pla
Alc×Treat, 0.05
−0.08 (0.05) Alc, 0.03
−0.02 (0.07) Alc<Pla
0.80 (0.51) NS
1.20 (0.36)
Alc, D2<D1
Alc×Drink, 0.001
0.1 (0.85) Alc, 0.001
−1.1 (1.17) Alc<Pla
−0.2 (6.1)
−9.0 (4.6)
−0.05 (0.03)
0.00 (0.01)
1.40 (0.58)
0.80 (0.33)
−1.3 (1.74)
−0.8 (0.79)
Alc×Drink, 0.001
0.21 D2>D1, 0.05
0.08 NS
0.22 NS
0.38 D2>D1, 0.001
0.26 D2<D1, 0.03
0.20 NS
0.08 NS
0.38 D2<D1, 0.001
0.38 D2<D1, 0.001
0.8 (0.99) Alc, 0.001
0.1 (0.99) Alc<Pla
−6.3 (1.27)
−5.0 (0.82)
−1.5 (0.79)
−0.8 (1.38)
1.0 (1.11)
−0.2 (0.57)
0.23 NS
0.15 NS
0.13 NS
Treatment
(ED vs EDPla)
Alc+ED vs
Alc+EDPla
0.15 Alc+ED<Alc
+EDPla, 0.03
0.02 NS
0.00 NS
0.23 NS
0.22 NS
0.04 NS
d
0.32
0.02
0.09
0.15
0.19
0.02
d
0.13 NS
0.06 NS
0.04 NS
0.11 NS
EDPla, D2>D1
0.20 NS
0.02 Treat×Drink, 0.04 0.05 NS
ED, D2<D1
0.07 NS
0.15 NS
0.08 NS
0.26
0.15
0.29
0.18
0.16
0.04 ED<EDPla, 0.004 0.31 Alc+ED<Alc
0.50
+EDPla, 0.004
0.07 NS
0.21 NS
0.20 NS
0.01 NS
0.03 NS
0.05 NS
Drink (D1 vs D2) d
0.001 (0.01) 0.002 (0.01) −0.033 (0.02) −0.043 (0.02) Alc, 0.02
0.009 (0.01) 0.0189 (0.01) 0.004 (0.00) −0.002 (0.01) Alc>Pla
0.024 (0.03) −0.079 (0.05) −0.095 (0.06) NS
0.045 (0.02) 0.014 (0.02) 0.010 (0.04)
−0.11 (0.46)
−0.66 (0.47)
Alcohol (Alc vs Pla) d
Main effects, interactions, P values, effect sizes (Cohen’s d)
Alc alcohol, AlcPla alcohol placebo, Alc+ED alcohol and energy drink combined, Alc+EDPla Alcohol and energy drink placebo combined, CFF critical flicker fusion, CRT total choice reaction
time, D1 drink 1, D2 drink 2, ED energy drink, EDPla energy drink placebo, Pla placebo, RRT recognition reaction time, Treat treatment group, + increase in values compared to baseline, −
decrease in values compared to baseline
ED
EDPla
Clearheaded
(mm)
Subjective
0.75 (0.27)
0.60 (0.20)
ED
EDPla
CRT (s)
−0.59 (0.36)
−0.20 (0.46)
AlcPla D2
AlcPla D1
Alc D1
Alc D2
Alcohol placebo
Alcohol
0.649 (0.05) −0.044 (0.04)
0.562 (0.02) 0.047 (0.03)
ED
EDPla
30.82 (0.48)
29.47 (0.68)
Treatment group Baseline
CFF (Hz)
Performance
Measure (units)
Table 1 Baseline means (SEM) and post drink baseline differences—performance and subjective awareness measures for alcohol and energy drink alone, alcohol combined with energy drink and
their respective placebo conditions
Psychopharmacology (2012) 222:519–532
525
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Psychopharmacology (2012) 222:519–532
placebo. Although with energy drink, improvements in reaction time approached significance.
These results clearly show the overall performanceimpairing effects of alcohol in this study, which then provide a useful basis from which to evaluate the subjective
perception of impairment.
Subjective measures
Fig. 1 Performance results—RRT and immediate memory recall, contrasting alcohol and energy drink alone, as well as in combination, and
against their respective placebos
In summary, alcohol significantly impaired both reaction
time and memory performance. The Stroop task results were
more complex. Whilst alcohol was associated with the most
errors in the placebo energy drink group and completion
time was faster after energy drink, the combination of energy drink and alcohol produced the fastest completion times,
as well as reducing errors.
Therefore, either trends or significant impairments were
seen with alcohol for five out of seven variables derived
from the four performance tests. The most significant effects
were seen with memory, including a dose-related increase in
impairment with alcohol. The effects of energy drink were
relatively weak in overcoming the effects of alcohol so that
only one (Stroop) out of four separate tests resulted in a
significant improvement with energy drink, reflecting improved scores for alcohol and placebo alcohol combined, as
well as alcohol combined with energy drink showing improvement when contrasted with alcohol and energy drink
The subjective response to both energy drink and alcohol
followed a consistent pattern for four of the five subjective
measures. Energy drink with alcohol placebo was associated
with participants feeling more clearheaded and energetic,
whilst less clumsy and drowsy. However, energy drink combined with alcohol resulted in participants feeling least clearheaded and energetic, together with being most clumsy,
drowsy and mentally slow, precluding the significant effects
for the energy drink treatment group compared to the placebo
energy drink group. The results for the placebo energy drink
group generally fell within these levels, with alcohol again
increasing subjective impairment relative to alcohol placebo,
although compared to the lower dose, the higher dose was
associated with feeling more energetic. The general pattern of
subjective impairment after alcohol for both the energy drink
and placebo energy drink groups are plotted in Fig. 2, showing
dose–response effects for the clearheaded and clumsy
descriptors.
Statistical analysis supported the graphical presentations
with alcohol producing significant increases in subjective
impairment for feelings of being less clearheaded and more
clumsy, drowsy and mentally slow (alcohol—clearheaded:
F1,18 06.41, MSe0761, P00.02; clumsy: F1,18 024.7, MSe0
263, P00.001; drowsy: F1,18 04.40, MSe01193, P00.05;
mentally slow: F1,18 08.20, MSe0148, P00.01). Significant
dose-related increases in perceived impairment between
drink 1 to drink 2 were seen for clearheaded (F1,18 05.47,
MSe090.6, P00.03), clumsy (F1,18 014.9, MSe080.5, P0
0.001) and mentally slow (F1,18 04.61, MSe 077.4, P 0
0.046). Whilst there were no overall significant differences
between the energy drink and placebo energy drink groups,
feelings of being energetic were associated with a drink ×
treatment group interaction (F1,18 04.84, MSe0151, P0
0.04), as after the second drink, those in the energy drink
group felt less energetic, whilst the placebo energy drink
group felt more energetic. There was also an alcohol × drink
interaction (F1,18 04.46, MSe090.8, P00.049) with perceived drowsiness increasing after the second drink with
alcohol compared to placebo alcohol.
Effect sizes of ≥0.2 were again generally associated with
statistically significant contrasts, although increased feelings of
being drowsy and mentally slow that were experienced after
the alcohol and energy drink combination contrasted with
alcohol and energy drink placebo with effect sizes of d>0.2
Psychopharmacology (2012) 222:519–532
Fig. 2 Subjective awareness—clearheaded and clumsy, contrasting
alcohol and energy drink alone, as well as in combination, and against
their respective placebos
and associated P<0.1. Interestingly, the drink factor produced
three significant contrasts between drink 1 and drink 2, although the associated effect sizes were d<0.2.
The subjective assessment revealed significant increases
in impairment for four out of five descriptors with alcohol
for the combined treatment groups and increases from drink
1 to drink 2 for three descriptors, but no overall significant
differences between the energy drink and placebo energy
drink groups. Significant interactions reflected a doserelated increase in drowsiness after alcohol and a reduction
in feeling energetic after the second drink for the energy
drink treatment group.
Discussion
The performance tests showed the expected impairment
after alcohol. With laboratory tests, significant impairment
527
is generally seen in 50% of studies at the 0.05% BAC and
90% at the 0.08% BAC (Moskowitz and Fiorentino 2000),
and therefore, similar to the concentration recorded here for
the combined treatment groups (0.046 and 0.087% BrAC).
The similarity in BrAC between the energy drink and placebo energy drink group allowed between-group comparisons for both alcohol doses and alcohol versus placebo
comparisons.
Objective performance measures found statistically significant impairments with alcohol for both reaction time and
memory, whilst CFF, which may be relatively insensitive to
alcohol (Ogden and Moskowitz 2004), showed only trends
for reduced flicker fusion thresholds with alcohol for both
the energy drink and placebo energy drink groups. The
results for Stroop performance were more complicated, with
the greatest number of errors recorded at the higher dose for
the placebo energy drink group, consistent with previous
work reporting increased errors after alcohol (Tiplady et al.
2004, 2009). However, the combination of energy drink and
alcohol significantly reduced completion time and errors,
reflecting improved performance. Therefore, overall, alcohol was associated with impaired performance and greater
impairment was seen at the higher dose for three out of four
tasks.
Whilst studies assessing the effects of energy drink in
combination with alcohol are very limited, it was noted in
the ‘Introduction’ that the addition of caffeine has either
antagonised the effects of alcohol, had no effect, or further
increased impairment (Azcona et al. 1995; Liguori and
Robinson 2001; Marczinski and Fillmore 2006; Nuotto et
al. 1982; Oborne and Rogers 1983). From examining the
means or graphical plots for the current study, energy drink
and alcohol, when compared to placebo energy drink with
alcohol, showed lower levels of impairment at the higher
dose with CFF, total reaction time and RRT and a reduction
in Stroop errors and completion time. However, no reduction was seen with memory.
These relative reductions in alcohol-induced impairment
after coadministration of energy drink suggest at least some
possible antagonism by caffeine or a combination of energy
drink constituents. However, statistical evaluation only provided a trend (P00.06) for Stroop errors and a significant
(P00.004) difference in completion time between the energy drink group and placebo energy drink group, although
this may have been partially obscured by the combination of
factors in the overall ANOVA. In comparison, the reduced
simple main effects model demonstrated significant
improvements for the alcohol and energy drink combination
compared to alcohol and energy drink placebo for both
Stroop errors (P00.028) and completion time (P00.004).
The notable improvement in Stroop completion time seen
here, also reflecting a reduction in errors, when alcohol was
combined with energy drink may reflect an anomaly of the
528
Stroop assessment. Participants were asked to name the ink
colour and ignore the printed word. There are different
possible assessments that can be undertaken (Stroop
1935); for example, participants could have been asked to
name the printed word and ignore the ink colour. By asking
participants to name the ink colour and ignore the printed
word, a reduction in focus or visual acuity as occurs with
alcohol (Moskowitz et al. 1993) would aid perception and
dominance of the ink colour as the printed letters became
potentially more ambiguous. This would reduce the interference effect and possibly improve performance. However,
greatest errors were seen after the higher dose of alcohol in
the placebo energy drink group, though speed was not
increased, supporting earlier findings of increased errors
after alcohol (Starmer 1989; Tiplady et al. 2009). In contrast, Liguori and Robinson (2001) failed to find significant
effects with either CFF or Stroop in their investigation of
caffeine and alcohol.
The results for word memory were stronger and more
consistent with both immediate and delayed recall producing highly significant results (P00.001) for alcohol impairment and increase with the higher dose. There was no
evidence of energy drink antagonism of alcohol impairment.
The results with alcohol are generally in keeping with the
literature as memory impairment is a robust and common
feature of alcohol intoxication (Maylor and Rabbitt 1993)
and provide further support for the results of the current
study.
Therefore, three out of four tests showed either trends
(CFF) or significant impairment (reaction time, word memory) after alcohol, but no significant differences between the
energy drink or placebo energy drink groups. One test
(Stroop) showed a significant improvement in both completion time and errors after the alcohol and energy drink
combination.
The five scales selected from the Bond and Lader (1974)
VAS scales were comprised of bipolar opposites (e.g. alert–
drowsy), with the midpoint representing a neutral position.
The scales are suitable for assessing both stimulant (e.g.
more alerting) as well as sedative (e.g. increased drowsiness) effects and are, therefore, suitable for assessing both
the individual and combined effects of caffeine-based energy drinks (stimulant) and alcohol (sedative), although noting
that rising blood alcohol levels can be associated with feelings of increased activation (Rueger et al. 2009).
The results showed significant and consistent increases in
subjective impairment after alcohol for four out of five scales,
although feelings of being energetic showed a dose-related
reduction with alcohol in the energy drink group but contrasted with an increase after the second drink for the placebo
energy drink group, precluding an overall effect of alcohol for
the two groups combined. Dose-related increases in subjective
impairment were reflected in significant increases for the
Psychopharmacology (2012) 222:519–532
drinks factor with three of the five descriptors (less clearheaded, more clumsy and mentally slow), whilst a significant
interaction between alcohol and drink reflected the increase
in drowsiness after the second alcohol drink for both treatment
groups combined.
There was no evidence of antagonism of alcohol-induced
subjective impairment by energy drink as there were no
overall significant differences between the energy drink
and placebo energy drink groups, nor specifically between
the alcohol and energy drink combination compared to
alcohol and energy drink placebo with simple main effects
analysis. Although, as mentioned, feelings of energy were
decreased for the energy drink group after the second drink
compared to the placebo energy drink, reflecting a divergence in the perception of alcohol-induced sedation between
groups. Overall, in comparison to the other treatment conditions, energy drink without alcohol consistently resulted in
the least levels of sedation or greatest subjective stimulation
for all but the mentally slow descriptor. In contrast, energy
drink combined with alcohol produced the highest levels of
subjective impairment and sedation including effect sizes of
d≥0.2 for drowsy and mentally slow, although this may
partially reflect differences between the two participant
groups.
What is clear is that the subjective perception of impairment was reliably and consistently seen after alcohol and
that several descriptors were sensitive to the increase in
dose. None of the descriptors showed overall significant
differences between the energy drink combined with alcohol
and alcohol alone. There was no evidence of a possible
masking effect with energy drink, reducing the perception
of intoxication; indeed, the mean trends were for the energy
drink and alcohol combination to show greater levels of
subjective impairment compared to alcohol alone, although
differences were not statistically significant.
These findings receive some support from the recent
study by Marczinski et al. (2011) who compared the effects
of alcohol alone and in combination with energy drink
assessing breath alcohol, performance and subjective measures. They also found no significant differences between
breath alcohol levels, performance and for subjective effects
including intoxication and ability to drive with ANOVA.
However, paired comparisons showed reduced subjective
mental fatigue and increased stimulation for the alcohol
and energy drink combination compared to alcohol alone.
These 2 findings, out of over 20 individual ratings taken, are
in contrast to the present study where mean values for
energetic and mentally slow were not reduced with the
alcohol and energy drink combination.
These results clearly contrast with the only other currently published study directly comparing the effects of alcohol
and energy drink alone and in combination on both psychomotor performance and subjective intoxication. The study of
Psychopharmacology (2012) 222:519–532
Ferreira et al. (2006) interpreted the findings as demonstrating that energy drink reduced the perception of alcohol
intoxication although they had more descriptors registering
impairment with the energy drink and alcohol combination,
as well as alcohol alone, than showed reduced impairment
after coadministration of energy drink with alcohol. Therefore, their overall results were more in line with the findings
of the present study. Other similarities between these two
studies include the two alcohol levels. Further, the findings
of significant objective performance impairment in both
studies provided a suitable basis from which to assess subjective awareness of impairment. One difference between
the studies was that, in the Ferreira study, one participant
group received the lower alcohol dose and the other the
higher dose, whilst in the present study, participant groups
were split by energy drink and placebo energy drink.
The sample size of 10 participants per group is a limitation with the present study through limiting power which
may then impact on the number of statistically significant
contrasts observed and requiring caution in interpreting
these results. However, the results showed that the study
was sufficiently powered to produce significant contrasts for
all three factors analysed, i.e. alcohol compared to placebo
alcohol, energy drink compared to placebo energy drink,
and drink 1 compared to drink 2, as well as significant
interactions between them. The inclusion of effect size values (Cohen’s d) found that, generally, effect sizes of d≥0.2,
and therefore classified as at least ‘small’ (Cohen 1992),
were associated with statistically significant effects, although improvements in reaction time after energy drink
were associated with effect sizes of d≥0.2 but failed to
achieve significance (P00.06). Similarly, increased feelings
of drowsiness and being mentally slow for the alcohol and
energy drink combination compared to alcohol also
achieved the ‘small’ effect size threshold but failed to
achieve significance (P<0.1). These might reflect sample
size as well as between-group differences.
Future studies might benefit from using a larger sample
to increase power and a fully repeated-measures design to
enable more sensitive comparisons between all four treatment combinations of alcohol, energy drink and their respective placebos, although repeated testing can itself
impact on results.
Indirect support for our findings comes from studies
investigating the combined effect of caffeine and alcohol
compared to alcohol alone, including higher alcohol and
caffeine concentrations than investigated here, but also failing to find any difference in either BAC or perception of
alcohol intoxication. These laboratory investigations have
shown that caffeine and alcohol in combination do not alter
the ‘high’ or perceived or actual BAC with caffeine levels
up to around 400 mg and alcohol 0.012% BAC (Howland et
al. 2010; Liguori and Robinson 2001; Rush et al. 1993).
529
In conclusion, the present study found that alcohol at
doses of 0.046 to 0.087% BrAC impaired psychomotor
and cognitive performance. The combination of energy
drink with alcohol failed to show consistent differences
from alcohol alone on several performance measures,
although Stroop performance was improved. The combination of energy drink with alcohol did not change
subjective perceptions of impairment when contrasted
with alcohol alone. There was no evidence of a reduced
perception of impairment or masking effect for energy
drink combined with alcohol compared to alcohol
alone.
Conflict of interest Over the last 3 years, Chris Alford has received
funding from the UK Ministry of Defence, Red Bull GmbH and
Sanofi-Aventis and was scientific adviser to Red Bull GmbH and
Sanofi-Aventis, Japan. Joris Verster has received research funding from
Takeda Pharmaceuticals and Red Bull GmbH and was scientific advisor for Takeda, Sanofi-Aventis, Transcept, Sepracor, Red Bull GmbH,
Deenox, Trimbos Institute and CBD.
Funding This study was undertaken at the University of the West of
England without support from a sponsor.
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International Journal of General Medicine
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open access to scientific and medical research
O riginal R esearch
Open Access Full Text Article
Effects of consuming alcohol mixed with energy
drinks versus consuming alcohol only on overall
alcohol consumption and negative alcohol-related
consequences
This article was published in the following Dove Press journal:
International Journal of General Medicine
14 November 2012
Number of times this article has been viewed
Lydia de Haan 1
Hein A de Haan 2,3
Job van der Palen 4,5
Berend Olivier 1
Joris C Verster 1
Utrecht University, Utrecht Institute
for Pharmaceutical Sciences,
Division of Pharmacology, Utrecht,
2
Tactus Addiction Treatment,
Deventer, 3Nijmegen Institute
for Scientist-Practitioners in
Addiction, Nijmegen, 4Medical School
Twente, Medisch Spectrum Twente,
Enschede, 5Department of Research
Methodology, Measurement, and
Data Analysis, University of Twente,
Enschede, The Netherlands
1
Background: The aim of this study was to examine differences in alcohol consumption and
its consequences when consumed alone and when mixed with energy drinks.
Methods: A survey was conducted among Dutch students at Utrecht University and the College
of Utrecht. We collected data on alcohol consumption and alcohol-related consequences of
alcohol consumed alone and/or alcohol mixed with energy drinks (AMED). The data were
analyzed using a retrospective within-subject design, comparing occasions when subjects consumed AMED with those when they consumed alcohol only in the past 30 days.
Results: A representative sample of 6002 students completed the survey, including
1239 who consumed AMED. Compared with consuming alcohol only, when consuming
AMED, students consumed significantly fewer alcoholic drinks on an average drinking day
(6.0 versus 5.4, respectively), and reported significantly fewer drinking days in the ­previous month
(9.2 versus 1.4), significantly fewer days being drunk (1.9 versus 0.5), and ­significantly fewer
occasions of consuming more than four (female)/five (male) alcoholic drinks (4.7 versus 0.9).
The maximum number of mixed alcoholic drinks (4.5) in the previous month was significantly
lower when compared with occasions when they consumed alcohol only (10.7). Accordingly,
the mean duration of a drinking session was significantly shorter when mixing alcoholic drinks
(4.0 versus 6.0 hours). Finally, when consuming AMED, significantly fewer alcohol-related
consequences were reported (2.6) for the previous year, including driving a car while intoxicated,
taking foolish risks, or being injured or hurt, as compared with alcohol-related consequences
when consuming alcohol only (4.9).
Conclusion: Mixing alcohol with energy drinks decreases overall alcohol consumption, and
decreases the likelihood of experiencing negative alcohol-related consequences.
Keywords: alcohol, energy drinks, AMED, alcohol consumption, consequences
Introduction
Correspondence: Joris C Verster
Utrecht University, Utrecht Institute
for Pharmaceutical Sciences, Division
of Pharmacology, Universiteitsweg 99,
CG3584, Utrecht, The Netherlands
Tel +313 0253 6909
Email [email protected]
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http://dx.doi.org/10.2147/IJGM.S38020
Alcohol abuse is a major problem worldwide. It has been estimated that 42% of
males and 20% of females in the US will experience an alcohol use disorder (abuse
or dependence) during their lifetime, and approximately 12.5% of males and 5% of
females meet the criteria for an alcohol use disorder in the previous year.1 Excessive
alcohol consumption is ranked as the third leading cause of death in the US, and is
also associated with marked functional impairment.1–3 According to the World Health
Organization, 6.2% of all deaths worldwide are related to alcohol consumption, which
makes it one of the leading causes of death.4 There is global concern about drinking
International Journal of General Medicine 2012:5 953–960
953
© 2012 de Haan et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.
de Haan et al
trends among young people, particularly with regard to
heavy episodic or “binge” drinking.5 For example, in the US,
about 500,000 college students are injured every year due to
drinking alcohol, with about 1700 of them dying annually
due to extreme binge-drinking.6 During adolescence, several
neural systems undergo alterations, and during maturation,
some of these systems modulate sensitivity to a variety of
the effects of alcohol, potentially increasing the propensity
for relatively high levels of adolescent alcohol use. This
might set the stage for later alcohol use disorders.7 Hence, it
is important to study factors that may contribute to increased
alcohol consumption among young adults.
Concerns have been raised regarding the potential negative
consequences of consumption of alcohol mixed with energy
drinks (AMED). The relevant ingredient in this context is
caffeine, of which most popular energy drinks contain 80 mg
per 250 mL or 8.4 fl oz.8,9 The stimulant effect of caffeine is
thought to counteract the sedative effect of alcohol, possibly
leading to increased alcohol consumption and experiencing
of more negative alcohol-related consequences. Only a few
studies have investigated whether use of AMED is indeed
associated with more alcohol consumption. O’Brien et al
questioned 4271 college students, of whom 52% had consumed alcohol without mixing with energy drinks and 16.3%
(N = 697) had consumed AMED in the previous 30 days, and
concluded the AMED consumers to be at increased risk for
alcohol-related consequences, even when adjusted for the
amount of alcohol consumed.10 This conclusion was based
on a between-subjects comparison of AMED consumers and
alcohol-only consumers. A similar design was used by Arria
et al, comparing college students who consumed energy
drinks versus those who did not consume energy drinks in a
3-year longitudinal study. It was concluded that consumers of
energy drinks tend to have a greater involvement in alcohol
and drug use and have higher levels of sensation-seeking,
compared with students who do not consume energy drinks.11
Other surveys reported similar significant correlations
between energy drink and alcohol consumption, and reported
that those who consume AMED generally consume more
alcohol and experience more alcohol-related consequences
than those who consume alcohol alone.12–15
These conclusions have raised concerns regarding AMED
consumption. However, some researchers have questioned
the methodology of these surveys and the interpretation
of the results regarding designs used to research AMED
consumption,8,16,17 and two studies did not find comparable
results while using a between-groups design.18,19 Penning
et al reported that those who consume AMED do not
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consume more alcohol than those who consume alcohol
only. Rossheim and Thombs found no significant relationship between AMED consumption and the chances of being
intoxicated (ie, having a blood alcohol content . 0.08%).
However, the main reason for criticism of existing surveys is
that the majority of them have compared AMED consumers
with those who consume alcohol only, using a betweengroups design. Unfortunately, by comparing an AMED group
with an alcohol-only group, it is not possible to determine if
there is any causal relationship between energy drink consumption and overall alcohol consumption. In other words,
it cannot be established from a between-group comparison
whether mixing alcohol with energy drinks had any influence on overall alcohol consumption. Also, between-group
analyses introduce the influence of potential confounders,
such as differences between groups regarding personality
characteristics. To verify whether mixing alcohol with energy
drinks increases overall alcohol consumption, studies using a
within-subject design are needed. A within-subject comparison is essential to determine whether AMED groups consume
more alcohol on occasions when they consume AMED
compared with occasions when they consume alcohol only.
Another important advantage of a within-subject design is
that if a sufficient sample size is obtained, the actual response
rate to the survey is of minor concern. As long as the sample
that completed the survey reflects the basic demographics
and characteristics of the general population, a large enough
sample size with adequate power for the statistical analyses
is sufficient to yield reliable research results. Nevertheless, it
remains important to compare the demographic characteristics of the sample with those of the total population to ensure
that the sample studied is representative of this population.
Two studies have reported the results of a within-subject
comparison.20,21 Price et al found that AMED consumption was associated with increased alcohol consumption,
but their sample size of 10 subjects was too small to draw
conclusions. A second within-subject comparison was presented by Woolsey et al. These authors only drew conclusions
based on their between-group comparison (AMED versus
alcohol-only groups), but together with the within-subject
comparison (ie, within the AMED group) presented, important results were revealed, supporting the hypotheses that
AMED and alcohol-only groups differ from each other in
critical characteristics (eg, alcohol consumption when not
mixing with energy drinks), and that within the AMED group,
mixing alcohol with energy drinks does not increase overall
alcohol consumption when compared with occasions on
which they consume alcohol only. Woolsey et al found that
International Journal of General Medicine 2012:5
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when mixing energy drinks with alcohol, AMED consumers drink significantly less alcohol than on occasions when
they consume alcohol only (6.28 drinks versus 8.60 drinks,
respectively). Because the within-subject comparison by
Woolsey et al was performed in a relatively small sample of
AMED consumers (n = 150), surveys with a larger sample
size are needed to confirm these findings. Given the limitations of previous survey research on mixing energy drinks
with alcohol, an extensive online survey was developed and
conducted in The Netherlands. The aim of this survey was
to examine alcohol consumption and its consequences when
consumed alone or when mixed with energy drinks using a
within-subject design. Given the current scientific evidence
available, it was hypothesized that there is no difference
in total alcohol consumption (frequency and quantity) and
alcohol-related negative consequences when alcohol is consumed alone or when mixed with energy drinks.
Materials and methods
Sample
All 70,000 students from the Utrecht University and the
College of Utrecht were invited by email to complete an
online survey on consumption of energy drinks and alcohol.
Two teams approached students at the campuses, and distributed leaflets to remind them to complete the survey. The
study protocol was reviewed by the Twente medical ethics
committee, but no formal medical ethics approval needed
to be obtained. Participation was anonymous and voluntary,
and a prize draw was held among those who completed the
survey. In total, 7158 students opened the link to the survey.
After cleaning the data set the final dataset comprised 6002
students. For the analyses in this paper, data were used for the
alcohol-only group (ie, those who only consumed alcohol,
n = 3185), and the AMED-group (consisting of participants
who consumed both alcohol only and AMED, n = 1239).
Data concerning the group that consume both alcohol and
energy drinks but never mix these and the group that do not
consume alcohol will be discussed elsewhere.
Survey outline
After obtaining demographic data from the participants,
questions were asked about alcohol use when consumed
alone and when mixed with energy drinks. The consumption questions were standard ones investigating the subject´s
consumption habits (frequency and quantity) considering
the particular drink asked about, with a focus on the past
30 days, and adapted from the Quick Drinking Screen, which
contains four consumption questions that have been shown
International Journal of General Medicine 2012:5
Consuming alcohol mixed with energy drinks
to be highly reliable and consistent when compared with the
12-month Timeline Follow Back method.22,23 Mixing was
defined as consuming energy drinks within a time frame of
2 hours before or after drinking alcohol.
The Dutch version of the Brief Young Adult Alcohol
Consequences Questionnaire (BYAACQ) was included to
study alcohol-related negative consequences.24 The BYAACQ
consists of 24 possible consequences of alcohol consumption that can be answered by “yes” or “no”. The outcome
score ranges from 0 to 24. The BYAACQ was completed for
alcohol only and for mixing with energy drinks depending
on the specific drinking behavior of the participant. In addition to the BYAACQ, two additional items were included
to determine whether participants were injured or got into a
fight after alcohol consumption (with or without mixing with
energy drinks). A detailed description of the survey design
and its questions can be found elsewhere.25 Furthermore, it
should be taken into account that alcoholic drinks in The
Netherlands, when obtained in a bar, pub, or restaurant,
contain a standardized amount of alcohol.
Data collection and statistical analyses
The survey went online on June 6, 2011 and remained online
for 10 days. Data were collected online via SurveyMonkey
and analyzed using the Statistical Package for the Social
Sciences version 18 (SPSS Inc, Chicago, IL). The mean,
standard deviation, and frequency distribution was computed
for alcohol consumption questions and BYAACQ scores for
occasions on which subjects consumed AMED or alcohol
only. Variables with a normal distribution were tested with
the Student t-test. For nominal variables, a χ2-test was performed. To analyze within-subject differences within the
AMED group (drinking AMED versus drinking alcohol
only), a paired t-test was used for consumption questions,
and intraclass correlations were calculated to look for interindividual correlations where appropriate. For the BYAACQ
data, a McNemar test was performed on the single items, and
a paired t-test and intraclass correlation on the BYAACQ
total scores. All tests were two-tailed, and differences were
regarded as significant at P , 0.05.
Results
Between-group comparisons
The demographics of the participants are summarized in
Table 1. The age and gender distribution of the sample
obtained did not differ significantly from the total Utrecht
student population.25 The alcohol-only group comprised
3185 subjects and the AMED group comprised 1239 subjects.
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de Haan et al
Table 1 Demographics of study participants
Male/female ratio
Age (years), mean (SD)
Weight (kg), mean (SD)
Height (m), mean (SD)
Sorority/fraternity member
Medication use
Drug use
Tobacco use
Alcohol-only group
(n = 3185)
Alcohol mixed with energy
drinks group (n = 1239)
P value
32.5%/67.5%
22.1 (2.6)
68.9 (11.8)
1.75 (0.1)
20.6%
23.2%
22.0%
23.2%
39.1%/60.9%
21.5 (2.3)
70.4 (12.3)
1.76 (0.1)
22.8%
23.0%
38.3%
41.7%
,0.001
,0.001
,0.001
,0.001
0.113
0.905
,0.001
,0.001
Abbreviation: SD, standard deviation.
Between-group analyses showed that the groups differed
significantly from each other on variables related to alcoholonly consumption, smoking, and drug use, as summarized
in Tables 1 and 2. Between-group analyses also revealed a
consistent pattern of significant differences on most variables,
in that AMED consumption was greater than alcohol-only
consumption, as summarized in Table 2.
Within-subject analyses for AMED group
To establish whether mixing energy drinks with alcohol
has an impact on total alcohol consumption, withinsubject comparisons were performed for members of the
AMED group (n = 1239), comparing occasions on which
they consumed AMED with occasions on which they
consumed alcohol only. The results of these comparisons
are summarized in Figure 1. Intraclass correlations were
calculated when appropriate to examine these within-subject
comparisons further.
The within-subject analyses revealed generally lower
consumption of alcohol when combining alcohol with
energy drinks. Compared with consuming alcohol only,
when consuming AMED, students consumed significantly
fewer alcoholic drinks (mean 6.0 ± 3.9 versus 5.4 ± 3.7,
respectively; intraclass correlation 0.636, P # 0.001) during an average drinking session, and reported significantly
fewer drinking days in the previous month (9.2 ± 6.4 versus
1.4 ± 1.8), significantly fewer days being drunk (1.9 ± 2.7
versus 0.5 ± 1.0), and significantly fewer occasions of
consuming more than four (female)/five (male) alcoholic
drinks (4.7 ± 4.7 versus 0.9 ± 1.7). Furthermore, compared
with consuming alcohol only, when consuming AMED,
students consumed significantly fewer maximum number of
alcoholic drinks on a single occasion in the previous month
(10.7 ± 6.8 versus 4.5 ± 5.7, respectively; intraclass correlation 0.185, P # 0.001). Accordingly, duration of alcohol
consumption on this occasion was significantly shorter
Table 2 Between-group comparison of those who consumed alcohol only and those who mixed alcohol with energy drinks with
regard to their alcohol consumption on occasions when they consume alcohol only (without mixing with energy drinks)
At what age did you first consume alcohol?
At what age did you consume alcohol regularly?
How many standard drinks do you usually have on one occasion?
In the past 30 days, how many days did you drink alcohol?
In the past 30 days, how many days did you get drunk?
In the past 30 days, how many times did you have more than
five (male)/four (female) alcoholic drinks on one occasion?
In the past 30 days, what is the greatest number of alcoholic drinks
you had on one occasion?
On that occasion (previous question), how many hours did you
consume alcohol?
In the past 12 months, what was the greatest number of alcoholic drinks
you consumed on one occasion?
Total BYAACQ score for drinking alcohol only
Alcohol-only group
(n = 3185)
Alcohol mixed with
energy drinks group
(n = 1239)
P value
14.5 (2.0)
17.2 (1.9)
4.1 (3.1)
7.9 (6.3)
1.0 (1.9)
2.9 (3.9)
14.0 (1.9)
16.5 (1.7)
6.0 (3.9)
9.2 (6.4)
1.9 (2.7)
4.8 (4.8)
,0.001
,0.001
,0.001
,0.001
,0.001
,0.001
7.7 (6.0)
10.7 (6.7)
,0.001
5.1 (3.1)
6.0 (3.1)
,0.001
10.7 (7.1)
14.6 (7.9)
,0.001
3.1 (3.0)
4.9 (3.8)
,0.001
Abbreviation: BYAACQ, Brief Young Adult Alcohol Consequences Questionnaire.
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International Journal of General Medicine 2012:5
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Consuming alcohol mixed with energy drinks
Alcohol only (AO)
12
10.7
Alcohol mixed with energy drinks (AMED)
9.2
9
6
6.0
6.0
5.4
4.7
3
1.4
4.5
4.0
1.9
0.5
0.9
0
Standard drinks Drinking days Days got drunk >4/5 drinks
[occasion]
[past month]
[past month] [past month]
Max drinks
[past month]
Drinking hours
[max drinks
past month]
Figure 1 Means (SEM) for within-subjects analyses in the AMED group (n = 1189) on consumption questions for alcohol only and alcohol mixed with energy drinks.
Notes: Questions are specifically asked for both conditions (consuming solely alcohol/consuming alcohol mixed with energy drinks). All differences are significant at the
P , 0.001 level.
Abbreviations: AMED, alcohol mixed with energy drinks; SEM, standard errors of the mean.
when consuming AMED than when consuming alcohol only
(4.0 ± 3.3 versus 6.0 ± 3.0 hours, respectively; intraclass correlation 0.301, P # 0.001). All differences between consuming AMED and alcohol only were examined using a paired
t-test and are significant at the P , 0.001 level. Finally, the
highest number of AMED consumptions on one occasion
during the previous year was 4.8 ± 4.8.
BYAACQ
Confirmation of alcohol-related consequences after consuming AMED or alcohol only are summarized in Table 3. The
within-subject comparisons show that when consuming
AMED alcohol-related negative consequences are often
experienced significantly less when compared with consuming alcohol only. The total BYAACQ score shows a reduction
of 47% from 4.9 ± 3.8 for drinking alcohol only to 2.6 ± 3.5
for AMED (intraclass correlation 0.414, P # 0.001). For
two items (numbers 18 and 22) no significant difference
was found between the AMED and alcohol only occasions.
None of the individual items showed an increased chance
of experiencing an alcohol-related negative consequence
on AMED occasions compared with drinking alcohol only.
Discussion
The results of this survey show that people who mix alcohol
with energy drinks do not consume more alcohol when they
consume AMED compared with occasions on which they
consume alcohol only. In contrast, when consuming AMED,
International Journal of General Medicine 2012:5
students reported consuming significantly fewer alcoholic
drinks on average, having fewer drinking days in the past
month, less days of being drunk in the past month, and fewer
occasions of consuming more than 4–5 drinks in the past
month, compared with consuming alcohol only. Further,
when consuming AMED, the maximum number of alcoholic
drinks on one occasion during the past month was significantly lower when compared with occasions on which only
alcohol was consumed. In addition, no increase in alcoholrelated consequences was reported for occasions when they
consumed AMED; this finding is of importance, considering
that some authors have suggested otherwise.10–12,14 The current
study shows clearly that mixing alcohol with energy drinks
does not increase the likelihood of potentially dangerous
activities or serious negative consequences, such as driving
while intoxicated, being injured, or getting involved in a
fight, unplanned sexual activity, or taking foolish risks. The
within-subject analyses yield results that are comparable with
those reported by Woolsey et al,20 and our current results also
clearly show that mixing alcohol with energy drinks does not
increase overall alcohol consumption, nor the likelihood of
experiencing negative consequences. The large sample size
and robust findings of the current study are supportive of
this conclusion.
The fact that mixing alcohol with energy drinks has
no negative impact on overall alcohol consumption or its
negative consequences should not be interpreted as suggesting that alcohol abuse does not exist among Dutch students.
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de Haan et al
Table 3 Within-subjects comparison in the AMED group (N = 1110) on BYAACQ items for occasions on which they consumed
alcohol only compared with occasions on which they mixed alcohol with energy drinks
Item
1
5
10
3
9
7
2
11
4
12
24
16
6
13
15
21
20
17
14
8
23
19
18
22
*
*
BYAACQ
Within subject comparison
I have had a hangover (headache, sick stomach) the morning
after I had been drinking
I have had less energy or felt tired because of my drinking
I have felt very sick to my stomach or thrown up after drinking
I’ve not been able to remember large stretches of time
while drinking heavily
While drinking, I have said or done embarrassing things
I often have ended up drinking on nights when I had
planned not to drink
I have taken foolish risks when I have been drinking
I have not gone to work or missed classes at school because
of drinking, a hangover, or illness caused by drinking
The quality of my work or school work has suffered
because of my drinking
When drinking, I have done impulsive things I regretted later
I have found that I needed larger amounts of alcohol to feel any effect,
or that I could no longer get high or drunk on the amount that used to
get me high or drunk
I have felt badly about myself because of my drinking
My drinking has got me into sexual situations I later regretted
I have been overweight because of drinking
I have spent too much time drinking
I have often found it difficult to limit how much I drink
I have neglected my obligations to family, work, or school
because of drinking
My drinking has created problems between myself and
my boyfriend/girlfriend/spouse, parents, or other near relatives
I have woken up in an unexpected place after heavy drinking
My physical appearance has been harmed by my drinking
I have become very rude, obnoxious, or insulting after drinking
I have driven a car when I knew I had too much to drink to drive safely
I have felt like I needed a drink after I’d got up (that is, before breakfast)
I have passed out from drinking
Total BYAACQ score mean (SD)
I have physically injured myself or others after drinking –
separate to being in a fight
I have got into a fight after drinking
P value
Alcohol-only
Alcohol mixed
with energy drinks
861 (77.6%)
522 (47.0%)
,0.001
697 (62.8%)
412 (37.1%)
393 (35.4%)
330 (29.7%)
220 (19.8%)
198 (17.8%)
,0.001
,0.001
,0.001
386 (34.8%)
308 (27.7%)
193 (17.4%)
114 (10.3%)
,0.001
,0.001
300 (27.0%)
268 (24.1%)
169 (15.2%)
138 (12.4%)
,0.001
,0.001
252 (22.7%)
117 (10.5%)
,0.001
219 (19.7%)
182 (16.4%)
114 (10.3%)
122 (11.0%)
,0.001
,0.001
155 (14.0%)
152 (13.7%)
151 (13.6%)
121 (10.9%)
92 (8.3%)
86 (7.7%)
82 (7.4%)
68 (6.1%)
77 (6.9%)
62 (5.6%)
56 (5.0%)
62 (5.6%)
,0.001
,0.001
,0.001
,0.001
,0.001
0.002
79 (7.1%)
50 (4.5%)
,0.001
76 (6.8%)
68 (6.1%)
66 (5.9%)
55 (5.0%)
26 (2.3%)
21 (1.9%)
4.9 (3.8)
112 (10.1%)
37 (3.3%)
51 (4.6%)
42 (3.8%)
31 (2.8%)
26 (2.3%)
26 (2.3%)
2.6 (3.5)
61 (5.5%)
,0.001
0.027
0.003
0.002
1.000
0.473
,0.001
,0.001
46 (4.1%)
45 (4.1%)
1.000
Notes: The percentage “yes” on a particular item is shown. *Additional question, added by the authors.
Abbreviations: AMED, alcohol mixed with energy drinks; BYAACQ, Brief Young Adult Alcohol Consequences Questionnaire; SD, standard deviation.
The data clearly show that alcohol consumption exceeds
levels of consumption that are generally accepted as safe, and
the majority of students engaged in binge drinking, especially
on days when they did not consume AMED (see Table 2).
Therefore, there is still a lot of work to do in preventing
excessive alcohol consumption amongst Dutch students. From
our data, it is apparent that focusing specifically on AMED
consumption is not warranted. The significance of the study
results lies in the fact that this is the first large-scale survey
using appropriate methodology (ie, a within-subject design)
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to determine whether mixing alcohol with energy drinks has
an effect on overall alcohol consumption when compared
with consuming alcohol only. This information cannot be
obtained reliably from between-group comparisons. It can
be argued that recall bias may interfere with obtaining reliable survey data. However, when applying a within-subject
design, there is no reason to assume that participants will
recall consumption characteristics differently between AMED
or alcohol-only occasions. To avoid the possibility of recall
bias entirely, a prospective study design may be a solution,
International Journal of General Medicine 2012:5
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but it would be expensive and time-consuming to achieve a
sample size as large as that in the current survey.
Interestingly, when applying a between-groups design,
as used by other researchers to compare alcohol-only and
AMED groups for demographics and alcohol-only consumption patterns, the groups differed from each other
on variables concerning alcohol-only consumption and its
consequences, drug use and smoking, following a standard
pattern of AMED > alcohol only. This observed pattern
could be caused by underlying personality characteristics
that might differ between the groups, for instance levels of
risk-taking behavior. The same authors that claim increased
alcohol consumption caused by energy drinks based on such
a between-groups design also report that AMED consumers
have higher scores on (impulsive) sensation-seeking and
childhood conduct problems.11,12 Moreover, having a sportsrelated identity is associated with frequency of energy drink
consumption, mediated by masculine norms and level of
risk-taking behavior.11,12,26 Increased levels of risk-taking
behavior may be reflected by a generally disinhibited behavioral pattern for an individual. The findings of the current
study and others11,12,26 confirm that individuals who consume
more alcohol also use more drugs.27 Taken together the
focus of research should not be on AMED consumption but
on persons who are involved in heavy alcohol consumption
per se. Future research is needed to explore the possibility
that this specific group of alcohol consumers have different
personality characteristics, ie, higher risk-taking, underlying
their pattern of increased substance use.
The reduction in alcohol consumption reported for the
AMED group when mixing alcohol with energy drinks as
compared with drinking alcohol only was not expected. It was
hypothesized that there would be no difference and we have
no clear explanation for this observed decrease in alcohol
­consumption. When looking at the ingredients of energy drinks,
it could be speculated that taurine (a nonessential amino acid
and an ingredient of most energy drinks) may have an effect
on alcohol consumption, given that a modest reduction of
voluntary ethanol consumption induced by taurine has been
found in rats.28 Other ingredients in energy drinks are unlikely
to play a role. However, the low intraclass correlations with a
maximum of 0.6 suggest interindividual differences, indicating that factors other than coconsumption of energy drinks
may explain the observed decrease in alcohol consumption.
A possible reason for decreased overall alcohol consumption
may be that spirits and energy drinks are generally more
expensive than beer and wine. Wagenaar et al showed that the
price of alcohol beverages is inversely related to the quantity
International Journal of General Medicine 2012:5
Consuming alcohol mixed with energy drinks
of alcohol consumed.29 However, it is unknown if and how
much students had to pay for their alcoholic and energy drinks
on the occasions they reported in our survey, or whether they
were consumed at home or in a bar.
Our data show that the maximum number of drinks
consumed when drinking alcohol only (10.7) was much
higher than last month’s maximum number of alcoholic
drinks on AMED occasions (4.5). In fact, the maximum
number of alcoholic drinks on AMED occasions equals that
of the 4–5 rule, whereas this is doubled for the maximum
monthly consumption of alcohol only (when not mixing).
Therefore, it is understandable that negative consequences
are experienced more commonly when people do not mix
alcohol with energy drinks. It is likely that alcohol-related
consequences occur most often on heavy drinking days and
less often on days during which few alcoholic drinks are
consumed. Although we have information on the number of
drinking days, it would not be correct to use this information as a covariate in statistical analysis. The main reason
for this is that it is unknown how many of the total drinking
days were heavy drinking days (ie, close to the maximum
monthly number of drinks) and how many were “normal”
drinking days (ie, without experiencing negative consequences). Although there are data on the number of days
spent intoxicated and the number of days on which more
than 4–5 alcoholic drinks were consumed, including these
values in the statistical analysis would result in speculative
interpretation of the data, because it can only be guessed if
and how many negative consequences subjects experienced
on each of these days. The most firm conclusion supported
by our data is that people consume less alcohol when they
mix alcohol with energy drinks, both on average drinking
days and on their maximum heavy drinking occasions. It is
understandable that fewer negative consequences are experienced when alcohol consumption is reduced by mixing it
with energy drinks.
Our analysis shows that the student sample obtained
does not differ significantly from the total Utrecht student
population.25 Also, there is no reason to assume that students
from Utrecht University are very different from those attending other universities in The Netherlands. Nevertheless, a
limitation of this survey is that it was conducted only in
The Netherlands, which may limit the generalizability of
its results to other countries. Therefore, this study will be
replicated in other parts of the world, including Australia
and the US. These surveys will also adopt a within-subject
design and include a sufficient number of participants in the
AMED group to ensure adequate statistical power in order to
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de Haan et al
have confidence in the results. Furthermore, any underlying
personality characteristics likely to cause differences in
alcohol-only consumption per se need to be examined in
greater detail. In conclusion, the results of this survey show
that mixing alcohol with energy drinks decreases overall
alcohol consumption, and decreases the likelihood of experiencing negative alcohol-related consequences.
Disclosure
This survey was supported by a grant from Red Bull GmbH.
Red Bull GmbH was not involved in the design and conduct
of the study, collection, management, analysis, interpretation
of the data, or preparation of the manuscript. JV has received
research support from Takeda Pharmaceuticals and Red Bull
GmbH, and has been a scientific advisor for Takeda, SanofiAventis, Transcept, Sepracor, Red Bull GmbH, Deenox,
Trimbos Institute, and CBD. BO is a scientific advisor for
Emotional Brain BV and has received research support from
Emotional Brain, PsychoGenics Inc, Sepracor, Servier,
Abbott, and the Dutch Brain Research Organization. The other
authors have no potential conflicts of interest to disclose.
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International Journal of General Medicine 2012:5
COMMITTEE ON TOXICITY OF CHEMICALS IN FOOD,
CONSUMER PRODUCTS AND THE ENVIRONMENT
COT Statement on the interaction of caffeine and alcohol and their combined
effects on health and behaviour
Introduction
1.
The Committee was asked by the Food Standards Agency to comment on
concerns that caffeine in energy drinks may interact with alcohol1 in causing adverse
behavioural or toxic effects.
Background
2.
Since 2004, energy drinks have been the fastest growing sector of the drinks
market in the UK, with an average growth of 12% per year (BSDA, 2011). The
popularity of consuming energy drinks mixed with alcoholic beverages has also
increased, especially amongst young males. Moreover, individuals who consume
high quantities of both energy drinks and alcohol, are perceived to engage in a
greater degree of risk-taking. This has raised concerns about the health effects of
caffeine and alcohol in combination. In particular, a phenomenon described as “wide
awake drunk” has been postulated, in which the stimulatory effect of caffeine
prevents consumers of alcohol from realising how intoxicated they are, thereby
increasing the potential for toxic injury and adverse behavioural effects (Reissig et al,
2009). In a report by the Scottish Prisons Service, “Buckfast Tonic Wine”, which
contains substantial quantities of caffeine as well as 15% alcohol by volume, was
linked with violence in young offenders in Scotland. Among a sample of 172 young
offenders, 43% admitted consumption of Buckfast Tonic Wine before their most
recent offence (Scottish Prisons Service, 2009). Most energy drinks contain levels of
caffeine approximately equivalent to those found in coffee (approximately 80mg
caffeine per 250ml can, although drinks with smaller volumes and higher caffeine
concentrations have appeared on the market in recent years) along with other
substances such as sugar, taurine and glucuronolactone.
3.
The Scientific Committee on Food (SCF), which advised the European
Commission before the creation of the European Food Safety Authority (EFSA),
looked at the safety of energy drinks in 1999 and 2003 (SCF, 1999; SCF, 2003). As
part of their second assessment, the SCF examined the evidence for a toxic
interaction between caffeine and alcohol. They concluded that most studies
1
In this document, the term alcohol will refer to ethanol present in alcoholic beverages.
suggested that caffeine would not exacerbate the adverse effects of alcohol, and that
at lower blood alcohol levels, caffeine may improve performance of simpler tasks
(SCF, 2003).
4.
The SCF also looked at evidence for interactions between alcohol and other
constituents of energy drinks such as taurine and glucuronolactone. They observed
that both taurine and alcohol inhibit the release of the antidiuretic hormone
vasopressin, and therefore might act in concert to increase loss of water and sodium
from the body, leading to a short-term risk of dehydration. In a 13-week study in
rats, taurine was shown to cause behavioural effects in all dose groups tested (300,
600 and 1000 mg/kg bw/day), including persistent increased activity, occasional
chewing of limbs, and in the 1000mg/kg bw group only, a possible decrement (not
statistically significant) in motor performance on a rotarod2. The lowest dose was
equivalent to 6 times the mean acute intake from energy drinks (50mg/kg bw). The
SCF concluded that some alcohol–taurine interactions were possible, including
“behavioural interactions”, but these were neither marked nor consistent in human
and animal studies. The SCF was of the opinion that focused neurological studies
should be carried out on taurine, and concluded that glucuronolactone would not be
expected to interact with alcohol or other constituents of energy drinks.
5.
The COT was asked to consider the literature published since the SCF
opinion of 2003, and to advise on the potential for interactions between caffeine and
alcohol.
Current European legislation on caffeine
6.
Under European Directive 2002/67/EC on the labelling of foodstuffs
containing quinine and foodstuffs containing caffeine, beverages containing more
than 150 mg/l caffeine (other than those based on coffee or tea) must carry the
statement ‘High caffeine content’ in the same field of vision as the name of the
product, followed by a reference in brackets to the caffeine content expressed in mg
per 100ml. Under the new Food Information Regulation (EU 1169/2011), which
comes into effect on the 13 December 2014, beverages containing more than 150
mg/l caffeine (other than those based on coffee or tea) must carry the statement
‘High caffeine content. Not recommended for children or pregnant or breast feeding
women’ in the same field of vision as the name of the beverage, followed by a
reference in brackets to the caffeine content expressed in mg per 100ml.
Consumption of caffeine
7.
Caffeine (1,3,7-trimethyl xanthine) is probably the most widely used
psychoactive substance worldwide (Benowitz, 1990). Its molecular structure is
shown in Figure 1:
2
Animals are trained to stay on a rotating bar which gradually accelerates. Animals that fall off receive a foot‐
shock. The speed of the rotating bar at which the animals fall off is taken as the performance score. Rotarod trials occur before and after treatment to compare performance. N
N
O
N
N
O
Figure 1: Caffeine
8.
In 2004, the Dietary Caffeine and Health Study estimated a mean caffeine
intake of 241mg/day in 6,000 individuals from the Bristol area who completed a
questionnaire quantifying consumption of coffee, tea, chocolate products, cola drinks
and energy drinks (Heatherley et al, 2006b; Heatherley et al, 2006a). This level of
intake is similar to those indicated by a UK survey of consumption of coffee, tea and
colas, carried out in 1988 – 3.98 mg/kg body weight per day (i.e. 279 mg/day for a 70
kg person) for the general population and 3.43 mg/kg body weight per day (i.e. 240
mg/day for a 70 kg person) for pregnant women (Barone and Roberts, 1996). In
terms of instant coffee, this would be equivalent to 2-2.5 average sized mugs
(260ml), assuming an average content of 100 mg caffeine per mug. The survey did
not address other sources of caffeine such as chocolate, cold and flu remedies,
headache treatments and energy drinks. In a more recent study, mean caffeine
intakes were found to be 238 mg/day in women before they became pregnant, and
reduced to 159 mg/day during pregnancy (CARE Study Group, 2008).
9.
Recently, estimates of caffeine intake in the UK were derived from the rolling
National Diet and Nutrition Survey (NDNS)3. These were based on the first two
years of the survey and applied to respondents who reported consuming foods
containing caffeine in 4-day food diaries (in which quantities were gauged
approximately and not by weighing). The intake assessment was restricted to foods
within 35 NDNS food groups that potentially contained caffeine (these included
coffee, tea, cocoa, energy and soft drinks and dietary supplements). The caffeine
content of dietary constituents was estimated from various sources, including
information received from food manufacturers and earlier MAFF surveys (MAFF,
1998). The mean (± standard deviation) total caffeine intakes of men and women
aged 19-64 were estimated to be 130 (±88) and 122 (±87) mg/d respectively. The
corresponding figures for older men and women in the 65+ age range were 143
(±94) and 131 (±88) mg/d. Boys and girls in the age range of 11-18 years had lower
intakes (46 (±43) and 44 (±45) mg/d) (Fitt et al, 2012). A breakdown of caffeine
intake from caffeinated beverages in all NDNS respondents who reported
consumption of such products indicated that coffee contributed more caffeine (49.5
3
The NDNS provides detailed, quantitative information on food consumption, nutrient intakes, nutritional status and related
characteristics. The NDNS is, in its current form, a four year rolling survey. The sample size for the survey is 500 adults and
500 children per year, covering people of all ages from 1½ years upwards living in private households. People living in
institutions are not covered, and pregnant and lactating women are also excluded. The survey includes boosted samples in
Scotland, Wales and Northern Ireland to enable cross-country comparisons. So far, only results from the first two years of the
survey have been published (Department of Health, 2011).
(±32.3) mg/d) than tea (36.2 (±11.3) mg/d) and energy and soft drinks (34.5 (±21.4)
mg/d). The inclusion of a larger range of products containing caffeine (e.g. chocolate
products and energy drinks) in the recent analysis of NDNS data, as well as
differences in the dietary assessment methods and in the assumed caffeine content
of dietary constituents, may account for the differences in estimation of caffeine
intake between different studies. High level intakes were not reported in these
studies.
Biochemistry and psychopharmacology of caffeine
10.
Caffeine is completely absorbed in the small intestine and the peak blood
concentration occurs around 1-2 hours after ingestion. Caffeine is distributed
throughout total body water and enters the brain quickly after absorption, but rate of
metabolic clearance is variable, the half-life ranging from 2.3 to 9.9 hours in adults
following single doses of caffeine (Arnaud, 2011), with a mean half-life of 4.3 hrs
being reported in healthy non-smoking adult males (Seng, 2009). Extensive interindividual variation occurs in caffeine metabolism due to factors such as alcohol and
smoking habits, pregnancy, genetic polymorphisms and level of caffeine
consumption. At low doses (<5mg/kg bw or 3-4 cups of coffee), pharmacokinetics
can be represented accurately using a one-compartment model with first order
absorption (Csajka et al, 2005). Metabolism of caffeine proceeds through three main
pathways illustrated in Figure 2 (percentages refer to the mean proportion of caffeine
converted to each metabolite). Some of the metabolites of caffeine themselves have
pharmacological activity (Casarett et al, 1996).
O
N
O
N
N
N
caffeine
CYP 1A2
CYP 2E1
CYP 2E1
O
O
O
HN
N
N
NH
N
N
O
O
N
N
O
N
H
N
N
N
1,7-dimethylxanthine
(paraxanthine)
84%
theobromine
12%
theophylline
4%
O
HN
O
O
NH
N
HN
N
O
NAT2
O
N
N
1-methylxanthine
N
O
5-acetylamino-6-formylamino-3-methyluracil
Figure 2: Metabolism of caffeine
11.
Caffeine’s primary biologically relevant mechanism of action is as a nonspecific adenosine antagonist. Adenosine receptors are found throughout the body,
and adenosine acts presynaptically to inhibit neuronal release of several neural
transmitters, reduces spontaneous firing of neurons, produces sedation and has
anticonvulsant activity (Benowitz, 1990). The pharmacologically active dose of
caffeine can vary considerably between individuals as tolerance is rapidly developed
to its effects. However, levels of 2-3 mg/kg bw have been shown to stimulate central
nervous system activity in humans (FDA, 1978).
12.
Adenosine is involved in a number of fundamental processes such as ATPrelated energy production and RNA synthesis, but it is also released in response to
metabolic stress and acts to protect the brain by suppressing neural activity (Latini
and Pedata, 2001). Adenosine A2A receptors are largely concentrated in the basal
ganglia region and may be involved in the dopamine system (which is involved in
reward and arousal). Adenosine may also be involved in the sleep-wake cycle
(Basheer et al, 2004; Latini and Pedata, 2001).
13.
Caffeine may also have secondary effects that are not related to adenosine,
since it acts also as a competitive non-selective phosphodiesterase inhibitor,
allowing the build up of cyclic AMP in cells and therefore modulation of many
biological processes (Essayan, 2001).
14.
In the central nervous system, caffeine acts primarily as a stimulant,
increasing arousal and vigilance, reducing fatigue and decreasing motor reaction
times in some tasks. At higher doses, caffeine can induce insomnia, anxiety,
tremors, and seizures (Benowitz, 1990). The ADORAA2A 1083TT genotype of the
adenosine A2A receptor has been associated with lower caffeine intakes, suggesting
a genetic link to the degree of caffeine consumption (Cornelis et al, 2007).
15.
Studies carried out in adults showed improvements in aerobic endurance,
anaerobic performance, choice reaction time, concentration and immediate-recall
memory following consumption of an energy drink (80 mg caffeine, equivalent to 1.1
mg/kg bw for a 70 kg adult; (Alford et al, 2001), and 0.58, 1.70 or 1.75mg/kg bw
(Howard and Marczinski, 2010)) in comparison with controls consuming a dummy
energy drink or water. Following a mental depletion task (designed to require
significant concentration on a number of tasks at one time), caffeine was found to
increase aggression compared to placebo, but no effects were observed in groups
which did not undertake the mental depletion task. In contrast, during a second
experiment when a no pill control group was included along with the caffeine and
placebo groups, no difference was observed in aggression between the caffeine and
no-pill control groups, following the mental depletion task (Denson et al, 2011).
Consumption of alcohol
16.
Alcohol is widely consumed in the UK with at least one alcoholic drink being
reported as consumed in the week before interview by 68% of men and 54% of
women in the 2009 General Lifestyle Survey carried out by the Office for National
Statistics. In the same report, mean weekly consumption of alcohol in the 12 months
before interview was 16.3 units for men and 8.0 units for women, equivalent to 2.33
g/kg bw for a 70kg man and 1.33 g/kg bw for a 60kg woman (Office of National
Statistics, 2009). However, these data were for the total population, including those
who did not drink alcoholic beverages, and the mean consumption of those who did
drink alcohol would have been higher. During the week before interview, 37% of
male participants exceeded the recommended limit for men of 4 units (32 g alcohol4)
in a single day, and 29% of female participants exceeded the corresponding limit for
women of 3 units (24 g alcohol).
Biochemistry and psychopharmacology of alcohol
17.
Alcohol is rapidly absorbed from the stomach and intestine, and distributed
widely through simple diffusion from blood into tissues. It is metabolised to
acetaldehyde, primarily through the action of alcohol dehydrogenase (ADH) using
the co-enzyme nicotinamide adenine dinucleotide (NAD), but also by CYP 2E1.
Acetaldehyde is converted to acetic acid, through the action of the NAD-dependent
enzyme acetaldehyde dehydrogenase (AcDH) (Casarett et al, 1996) (see Figure 3).
4
www.drinkaware.co.uk. One unit of alcohol equals 8g pure alcohol.
HO
HO
ethanol
ADH
(NAD)
O
acetaldehyde
AcDH
(NAD)
O
acetic acid
Figure 3: Metabolism of ethanol
18.
Alcohol is a central nervous system depressant, but its mode of action has not
been fully elucidated. It is thought to act in the central nervous system (CNS) by
binding to the GABA-A receptor, which mediates rapid inhibitory neurotransmission
throughout the CNS. The outward signs of alcohol intoxication, such as impaired
sensory and motor function, slowed cognition and stupefaction, are a result of this
receptor-binding activity (Kumar et al, 2009).
19.
A major effect of alcohol is to impair inhibitory responses. It is thought that
behaviour is governed by two distinct systems: one that activates a response and
one that inhibits a response. As an example, in tests for behavioural inhibition,
participants are required to respond appropriately to “go” signals on a computer, but
when a “stop” signal is observed then they should inhibit their response. The
impaired ability to inhibit responses when under the influence of alcohol has received
much attention because of the social implications of excessive consumption
(Marczinski and Fillmore, 2003). Doses of 0.62 g/kg bw absolute alcohol (43.4 g for
a 70 kg adult) have been shown to reduce response inhibition using “stop/go”
software as described above under laboratory conditions (Fillmore and Vogel-Sprott,
1999). The neuronal pathways directly responsible for the effects on responseinhibition are not clear.
20.
Studies looking at the effects of lower doses of alcohol on attention tasks
indicate that attention concentrated on a single source of information is not impaired
by alcohol, but in divided attention tasks, especially those where two tasks follow
each other closely, reaction time is increased (Moskowitz and Burns, 1971).
Co-consumption of alcohol, caffeine and other psychoactive substances
21.
Accurate estimates of the extent to which alcohol and caffeine are consumed
together are not available. One of the reasons for this is that drinks containing
alcohol and caffeine are often sold separately and mixed by the consumer rather
than being formulated in a single product – for example rum with cola or energy
drinks with vodka.
22.
Four studies looking at the energy drink and alcohol consumption of university
students in the US and Canada showed an association between consumption of
energy drinks and alcohol. Some of these studies investigated alcohol-related
adverse incidents, and showed that high consumers of both energy drinks and
alcohol were at greater risk of such incidents than consumers of alcohol alone (Arria
et al, 2011; O'Brien et al, 2008; Price et al, 2010; Velazquez et al, 2011). One
Canadian study found a significant association of combined energy drink and alcohol
consumption with risk-taking behaviours, including consumption of illicit drugs
(Brache and Stockwell, 2011). In another study, general caffeine consumption in 1213 year olds in high school was significantly associated with the use a year later, not
only of caffeine, but also of nicotine and alcohol (Collins et al, 2011).
23.
In a field study of 1255 bar patrons, individuals who consumed alcohol mixed
with energy drinks were at three-fold increased risk of leaving a bar highly
intoxicated and four-fold increased risk of intending to drive, when compared to other
patrons who consumed alcohol but not mixed with energy drinks. The mean quantity
of alcohol consumed by individuals who drank only alcohol was 95.3g, as compared
with 108.3g for those who also consumed energy drinks but not mixed with the
alcohol, and 152.2g for those who consumed alcohol mixed with energy drinks.
Group sizes for those consuming energy drinks and alcohol were small (46
consumed both but not mixed and 45 consumed both mixed) (Thombs et al, 2010).
24.
In contrast, in a survey of 1503 Dutch students, those who consumed alcohol
with an energy drink consumed less alcohol than those who drank alcohol alone,
although the difference did not reach statistical significance (p=0.056). Those who
consumed alcohol with a cola beverage consumed significantly more alcohol than
those who consumed alcohol alone (p=0.001) or those who combined energy drinks
with alcohol (p=0.001). The group sizes for those consuming cola and energy drinks
with alcohol were small; 45 and 24 respectively (Penning et al, 2011).
25.
There has been some suggestion that high intake of caffeine might be a
marker for the use of other drugs, both legal and illegal, and also for other addictive
behaviours such as excessive gambling and excessive use of the internet (Arria et
al, 2010; Istvan and Matarazzo, 1984; Kaminer, 2010; Pallanti et al, 2006).
26.
Studies based on a cohort of male and female mono- and dizygotic twin pairs,
looked at caffeine, smoking, alcohol and drug consumption habits. These
investigations suggested that the association between high consumption of caffeine
and alcohol depended on familial factors, which were primarily genetic. Modelling
indicated two genetic factors – one linked to illicit drug use and the other to use of
legal drugs including caffeine and alcohol (Hettema et al, 1999; Kendler et al, 2006;
Kendler et al, 2007; Kendler et al, 2008). However, this finding has yet to be
independently confirmed.
27.
In a cohort of male di- (n=183) and monozygotic (n=173) twins, heavy
consumption of alcohol and heavy smoking were significantly associated [phenotypic
Pearson correlation r=0.22 (p<0.001)], as were heavy smoking and heavy coffee
consumption [phenotypic Pearson correlation r=0.28 (p<0.001)]. In contrast, heavy
consumption of coffee and alcohol were more weakly related [phenotypic Pearson
correlation r=0.14 (p<0.001)] (Swan et al, 1997). Further comparisons between diand monozygotic twins suggested that co-consumption of coffee and alcohol had a
genetic basis, and co-consumption of alcohol, coffee and nicotine is determined in
part by genetic predisposition (Swan et al, 1996).
28.
In a population of 1925 patients who had voluntarily sought treatment for
substance abuse disorders, a statistically significant relationship was found between
the frequencies of using caffeine, nicotine and alcohol, but there was no significant
association of exposure to caffeine and nicotine with exposure to other substances
of abuse such as heroin, cannabis and glue (Kozlowski et al, 1993).
29.
In a sample of 105 Israeli alcoholics undergoing treatment, caffeine and
alcohol consumption were significantly correlated (p<0.05). When the sample was
subdivided into those with (n=62) and those without (n=43) a family history of
alcoholism (defined as at least one primary family member meeting the DSM-IV
criteria for alcohol dependence) no differences were observed between the two
groups in alcohol or caffeine consumption (Amit et al, 2004)
30.
The balance of evidence suggests that higher intake of caffeine is associated
not only with higher alcohol intakes but also with use of other psychoactive
substances. There is limited evidence that the relationship may be determined, at
least in part, by genetic predisposition. It appears that, at least in some population
groups, there is a correlation between high consumption of alcohol and of energy
drinks specifically. However, it is unclear whether this is because consumption of
energy drinks causes people to drink more alcohol, or because people who are
inclined to more risky behaviour tend generally to consume larger quantities of
psychoactive substances, including caffeine and alcohol.
Health effects of co-consumption of alcohol and caffeine
31.
It has been suggested that when consumed together, energy drinks and
alcohol might interact in several ways (Weldy, 2010):
•
•
•
•
•
•
Carbonation tends to increase the absorption of alcohol (although some noncarbonated energy drinks are available, the majority of sales are of
carbonated products)
Diluted alcohol is emptied from the stomach into the faster absorbing small
intestine more quickly than alcohol at higher concentrations.
Caffeine blunts the sedative effects of alcohol
Caffeine prevents sleep, allowing greater opportunity for consumption of
alcohol before loss of consciousness
At low blood alcohol levels, caffeine appears to decrease some of the
physical and mental impairment resulting from alcohol, although at higher
blood alcohol levels no such effects are observed.
Energy drink ingredients give the consumer a false sense of physical and
mental competence and decrease their awareness of impairment by alcohol.
Does caffeine counteract the neuro-cognitive effects of alcohol consumption?
32.
There is some evidence that caffeine can ameliorate some of the neurocognitive effects of alcohol, but the findings have not been consistent in all studies,
and the underlying mechanisms are unclear. In a review of the data published up to
1988, the authors concluded that because of variation in the doses of caffeine and
alcohol administered, the behavioural effects assessed, and other aspects of study
design, it was not possible to determine whether there was a counteracting effect of
caffeine (Fudin and Nicastro, 1988).
33.
A number of studies published since the SCF opinion of 2003 have
investigated the effects of combined alcohol and caffeine consumption on various
aspects of neurological function. Doses ranged from 1.1 to 5.6 mg/kg bw for caffeine
and 0.18 to 1.07 g/kg bw for alcohol. Many of these studies used driving simulators
and doses of approximately 2-3 cups of coffee or 1-2 cans of energy drink with 1-2
standard measures of vodka. Results have been inconsistent, with some studies
finding that caffeine did not antagonise the physiological effects of alcohol and others
suggesting that some important aspects of alcohol intoxication were ameliorated,
especially effects on motor reaction time, mean tracking performance and memory
reaction time (Alford et al, 2012; Attwood et al, 2011; Azcona et al, 1995; Burns and
Moskowitz, 1990; Ferreira et al, 2004; Ferreira et al, 2006; Fillmore et al, 2002;
Fillmore and Vogel-Sprott, 1999; Hasenfratz et al, 1993; Howland et al, 2011; Kerr et
al, 1991; Marczinski et al, 2011; Marczinski et al, 2012a; Marczinski et al, 2012b;
Marczinski and Fillmore, 2003; Marczinski and Fillmore, 2006). Conflicting results
have also been obtained in studies designed to test perceived degree of alcohol
intoxication with and without caffeine. The most direct subjective ratings of
intoxication5 were no different when alcohol was consumed with and without
caffeine. Where conflicts have been found, these were in less direct subjective6
measures (Alford et al, 2012; Ferreira et al, 2006; Marczinski and Fillmore, 2006). A
recent review concluded that the available literature did not support the argument
that energy drinks mask the effects of alcohol intoxication and increase alcohol
consumption (Verster et al, 2012). A more detailed description of the primary studies
can be found in Annex 1.
34.
In conclusion, the heterogeneity of methods and neurological end-points in
reported studies prevents firm conclusions on whether caffeine counteracts the acute
neuro-cognitive effects of alcohol. It should be noted that because of ethical
constraints, the levels of alcohol consumed in these studies were relatively low.
Case reports of deaths and acute illness following consumption of caffeine alone or
in combination with alcohol
35.
Through a literature search, the National Programme on Substance Abuse
Deaths has identified seven cases from the UK in which a coroner named caffeine
alone (five cases) or in combination with alcohol (two cases) as a factor contributing
to death. In another case report, the parents had linked the death of their son to
caffeine consumption (Corkery, 2012). One study in the peer-reviewed literature
describes acute renal failure following consumption of three litres of energy drink
mixed with one litre of vodka (Schoffl et al, 2011).
36.
Analysis of phone calls to the New South Wales Poisons Information Service
over a seven year period revealed that of 297 calls concerning caffeinated energy
drinks, 73% related to recreational exposures (others concerned accidental
consumption by children or deliberate self-poisoning). The median age of the cases
was 17 years. Co-ingestion of other substances was reported in 46% of calls
relating to recreational exposure, most frequently alcohol (23% of recreational users)
and other caffeine-containing products such as cola and caffeine tablets (20%).
Features of serious toxicity such as hallucinations, seizures and cardiac ischaemia
were described in 21 calls. Among the callers, 128 people sought or were advised to
5
Examples of direct subjective measures on intoxication include participants being asked how many drinks they had consumed, for an estimate of blood alcohol or being asked to rate their level of intoxication on a scale ranging from least ever to most ever. 6
Examples of less direct subjective measures of intoxication include participants being asked how competent they felt to drive a car or how fatigued they felt. seek, urgent medical attention, of whom 70 had co-consumed other substances
(Gunja and Brown, 2012).
37.
Although some of the cases described in this section suggest acute toxic
effects of caffeine and/or alcohol, they do not allow firm conclusions about the
contribution of either substance or of whether caffeine increases the acute toxicity of
alcohol.
Serious cardiac outcomes
38.
In its opinions of 1999 and 2003, the SCF noted anecdotal reports of serious
cardiac outcomes in young people following consumption of energy drinks with
alcohol, but observed that the reports were incomplete and that consumption of
energy drinks and alcohol often occurred in combination with other drugs, thus
limiting the conclusions that could be drawn. The Committee identified one paper on
cardiac effects of co-consumption of alcohol and caffeine that had been published
since the SCF opinion (Wiklund et al, 2009). However, because of the small size of
the study that it described, it did not allow useful conclusions.
The role of expectations
39.
The Committee noted evidence that individuals’ expectations of behavioural
effects following consumption of alcohol and/or caffeine may lead them to behave
differently when exposed (Fillmore et al, 2002; Fillmore and Vogel-Sprott, 1995;
Harrell and Juliano, 2009). However, it was not clear how far psychological
mechanisms of this sort contributed to behavioural outcomes following consumption
of caffeine and alcohol in combination.
Conclusions
40.
The increasing consumption of drinks containing caffeine mixed with alcohol
has raised concerns about the physical and mental health effects of these
psychoactive substances in combination. A phenomenon known as “wide awake
drunk” has been suggested, in which the stimulatory effects of caffeine may prevent
consumers of alcohol from realising how intoxicated they are, leading to increased
risk of toxic injury and adverse behavioural effects such as increased risk-taking,
violence and criminal activity.
41.
The balance of evidence suggests that higher intake of caffeine is associated
not only with higher alcohol intakes, but also with use of other psychoactive
substances. There is limited evidence that the relationship may be determined at
least in part, by genetic predisposition. It appears that, at least in some population
groups, there is a correlation between high consumption of alcohol and of energy
drinks specifically. However, it is unclear whether this is because consumption of
energy drinks causes people to drink more alcohol, or because people who are
inclined to more risky behaviour tend generally to consume larger quantities of
psychoactive substances, including caffeine and alcohol.
42.
A number of studies have suggested that caffeine can ameliorate some
effects of alcohol, especially on motor reaction time, mean tracking performance and
memory reaction time, but other investigations have failed to support this. The
evidence that perceptions of alcohol intoxication are modified by caffeine is
conflicting. Overall, the heterogeneity of methods and neurological end-points in
reported studies prevents firm conclusions on whether caffeine counteracts the acute
neuro-cognitive effects of alcohol
43.
Published case reports of deaths and acute illness following consumption of
caffeine and alcohol in combination do not allow conclusions as to whether caffeine
increases the acute toxicity of alcohol.
44.
Individuals’ expectations of behavioural effects following consumption of
alcohol and/or caffeine may lead them to behave differently when exposed.
However, it is unclear how far psychological mechanisms of this sort contribute to
behavioural outcomes following consumption of caffeine and alcohol in combination.
45.
Overall, the Committee concludes that the current balance of evidence does
not support a harmful toxicological or behavioural interaction between caffeine and
alcohol. However, because of limitations in the available data, there is substantial
uncertainty, and if important new evidence emerges in the future, then this
conclusion should be reviewed.
COT statement 2012/04
December 2012
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Annex 1: Studies on the effects of alcohol and caffeine on neurological function.
Reference
Alford et al, 2012
Caffeine dose
0, 2.2 mg/kg
bw (energy
drink)
Alcohol dose
0, 0.79 g/kg
bw
Attwood et al, 2012
0,2 mg/kg bw
(dissolved
caffeine
powder
0, 0.6 g/kg bw
Azcona et al, 1995
0, 5.6 mg/kg
bw
(encapsulated
caffeine
powder)
0, 2.93, 5.87
mg/kg bw
(encapsulated
caffeine
powder)
1.14 mg/kg
bw (energy
drink)
1.14 mg/kg
bw (energy
drink)
0, 0.8 g/kg bw
Burns &
Moscowitz, 1990
Ferreira et al, 2004
Ferreira et al, 2006
Observed effects
Recognition reaction time slowed by alcohol alone (p=0.02) but
similar to baseline following alcohol and caffeine consumption. Word
memory was impaired by alcohol regardless of whether or not
caffeine was co-consumed (p=0.001). Stroop test error rate was not
increased by alcohol alone and was actually improved in the alcohol
and energy drink group (p=0.028). Stroop completion times were
decreased by energy drink (p=0.004) and were decreased further still
by alcohol mixed with energy drink (p=0.024)
Subjective measures of intoxication did not differ between test and
control groups. Caffeine appeared to antagonise the effects of alcohol
on omission errors in the stop-signal task (p=0.016) but had no effect
on simple reaction time (p=0.34) or performance of go – no-go tasks
(P=0.95) and worsened the accuracy on the Stroop test (p=0.019).
Simple Reaction Time increased by alcohol and ameliorated by
caffeine (p <0.05).
0, 0.5, 0.99
g/kg bw
Alcohol had effects on alertness, tracking, visual search, reaction time
and information processing. Caffeine ameliorated all but information
processing (none of the results were statistically significant).
0.3 g/kg bw
Following a physical test on a cycle ergometer, no differences were
observed in physical parameters between the alcohol group and the
alcohol and energy drink group.
Alcohol and energy drink consumed together did not reduce deficits in
objective motor co-ordination (p=0.11) and visual reaction time
(p=0.12) caused by alcohol alone.
0, 0.18, 0.3
g/kg bw
Fillmore, Roach
and Rice, 2002
0, 4 mg/kg bw
(dissolved
caffeine
powder)
0.65 g/kg bw
Fillmore & VogelSprott, 1999
0, 4.4 mg/kg
bw (dissolved
caffeine
powder)
0, 3.3 mg/kg
bw (dissolved
caffeine
powder)
0, 0.62 g/kg
bw
0, 5.47 (men),
5.63 (women)
mg/kg bw
(Dissolved
caffeine
powder)
0, 5 mg/kg bw
(encapsulated
caffeine
powder)
0, 2, 4 mg/kg
bw (dissolved
caffeine
powder)
0, 2, 4 mg/kg
bw (dissolved
0, 1.07 (men),
0.92 (women)
g/kg bw
Hasenfratz et al,
1993
Howland et al,
2011
Kerr, 1991
Marczinski and
Filmore, 2003
Marczinski and
Filmore, 2006
0, 0.7 g/kg bw
0, 0.18 g/kg
bw
0, 0.65 g/kg
bw
0, 0.65 g/kg
bw
Groups led to expect that caffeine would counteract the effects of
alcohol showed greater impairment of performance in a pursuit rotor
task than groups led to expect no such counteracting effect (p=0.037).
No significant differences were found in subjective measures of
intoxication between the groups consuming caffeinated and noncaffeinated drinks.
No effects observed on reaction time. Mean number of inhibitions was
significantly reduced following alcohol consumption compared to
baseline whereas following alcohol and caffeine consumption number
of inhibitions was higher than baseline (p<0.002).
In a rapid information processing (RIP) task, mean reaction time and
processing rate were improved by caffeine (p<0.01; p<0.05); the
reaction time was increased by alcohol (p<0.05); the combination of
alcohol and caffeine did not differ from baseline suggesting that
caffeine was able to offset the alcohol induced performance
decrements.
Alcohol significantly impaired driving and sustained attention/reaction
time. Caffeine did not appear to antagonise the effects of alcohol. No
significant differences were found in subjective measures of
intoxication between the groups consuming caffeinated and noncaffeinated drinks.
Caffeine appeared to antagonise the effect of alcohol on short term
memory and choice reaction time (not statistically significant) and
mean tracking performance (p<0.05). No effects were observed on
critical flicker fusion (measures arousal).
Alcohol impaired inhibitory and activational aspects of behavioural
control. Caffeine antagonised response activation (p=0.03) but not
inhibition (p>0.81).
Alcohol impaired the speed of reaction time and accuracy of response
in go/no-go and auditory discrimination tasks. Caffeine antagonised
Marczinski et al,
2011.
Marczinski et al,
2012a
Marczinski et al,
2012b
caffeine
powder)
0, 1.2 mg/kg
bw (energy
drink)
0, 0.6 mg/kg
bw (energy
drink)
0, 1.2 mg/kg
bw (energy
drink)
0, 0.65 g/kg
bw
0, 0.36 g/kg
bw
0, 0.65 (men),
0.57 (women)
g/kg bw
the effects of alcohol on speed of reaction time (p<0.02), but not
accuracy (p>0.15).
Alcohol impaired the inhibitory failures and response times compared
to placebo in a cued go/no-go task. Caffeine ameliorated some
impairment of response times (p<0.05) but not inhibition (p>0.27).
Subjective measurements of intoxication were not significantly
different between those consuming alcohol alone and in combination
with caffeine. Subjects consuming energy drink and alcohol were
more likely to feel motivation to consume more alcohol at 10, 20, 40
and 60 mins after dosing (p<0.01) compared to baseline, whereas the
alcohol alone group felt motivation only 10 and 20 minutes after
dosing (p=0.01).
Subjective measurements of intoxication were not significantly
different between those consuming alcohol alone and in combination
with caffeine, but there were non-significantly reduced perceptions of
mental fatigue and stimulation in the caffeine and alcohol group
compared with the alcohol alone group. Alcohol slowed dual task
information processing and impaired simple and complex motor coordination. No antagonistic effects were observed from caffeine.
Annex Two: Search Criteria and databases used
As the Scientific Committee on Food (SCF) looked at alcohol and caffeine interactions in
2003, only references published after this time were included in the literature review. Some
references that were not included by the SCF but published prior to 2003 came to light
through searching the reference lists of later papers. When considered relevant, these were
also reviewed. Because of the availability of human studies, animal studies were not
considered unless they were considered particularly relevant.
Searches using Pubmed
Caffeine, alcohol, behaviour (limits 01/01/2003-present)
Caffeine, alcohol, interactions (limits 01/01/2003-present)
Energy drinks, alcohol, behaviour (limits 01/01/2003-present)
Energy drinks, alcohol, interactions (limits 01/01/2003-present)
Caffeine, alcohol, behaviour (limits 01/01/2003-present; human studies only)
Caffeine, alcohol, interactions (limits 01/01/2003-present; human studies only)
Energy drinks, alcohol, behaviour (limits 01/01/2003-present; human studies only)
Energy drinks, alcohol, interactions (limits 01/01/2003-present; human studies only)
Searches using Google Scholar
All in title: Caffeine, alcohol, (NOT rat, mice) (since 2003, articles excluding patents)
All in title: “Energy drinks”, alcohol, (NOT rat, mice) (since 2003, articles excluding patents)
February 2012
COMMITTEE ON TOXICITY OF CHEMICALS IN FOOD,
CONSUMER PRODUCTS AND THE ENVIRONMENT
COT STATEMENT ON THE INTERACTION OF CAFFEINE AND ALCOHOL AND
THEIR COMBINED EFFECTS ON HEALTH AND BEHAVIOUR: LAY SUMMARY
1.
The Committee on Toxicity (COT) was asked by the Food Standards Agency
to comment on concerns that caffeine in energy drinks may interact with alcoholic
beverages in causing adverse behavioural or toxic effects.
2.
Since 2004, energy drinks have been the fastest growing sector of the drinks
market in the UK. The popularity of consuming energy drinks mixed with alcoholic
beverages has also increased. Moreover, individuals who consume high quantities
of both energy drinks and alcohol, are perceived to engage in a greater degree of
risk-taking. This has raised concerns about the health effects of caffeine and alcohol
in combination. In particular, a phenomenon described as “wide awake drunk” has
been suggested, in which the stimulatory effect of caffeine prevents consumers of
alcohol from realising how intoxicated they are, thereby increasing the potential for
toxic damage to the body and adverse behavioural effects. Most energy drinks
contain levels of caffeine approximately equivalent to those found in a cup of coffee
(approximately 80mg caffeine per 250ml can).
3.
Currently beverages containing more than 150 mg/l caffeine (other than those
based on coffee or tea) must carry the statement ‘High caffeine content’. Under new
Regulations, which come into effect on the 13 December 2014, these beverages
must carry the statement ‘High caffeine content. Not recommended for children or
pregnant or breast feeding women’ in the same field of vision as the name of the
beverage, followed by a reference in brackets to the caffeine content expressed in
mg per 100ml. There are currently no legal restrictions on the amount of caffeine that
may be present in a food or drink product.
4.
Caffeine acts primarily as a stimulant, increasing arousal and vigilance,
reducing fatigue, and decreasing reaction times in some tasks. At higher doses, it
can induce insomnia, anxiety, tremors, and seizures. Susceptibility to the effects of
caffeine varies between individuals as people develop tolerance with repeated
exposure.
5.
Alcohol is widely consumed in the UK with at least one alcoholic drink being
reported as consumed in the week before interview by 68% of men and 54% of
women in the 2009 General Lifestyle Survey carried out by the Office for National
Statistics. It depresses brain function, and outward signs of intoxication including
impaired sensory perception and control of movements, slowed cognition, and
stupor. How exactly it causes these effects has not been fully elucidated.
6.
Accurate estimates of the extent to which alcohol and caffeine are consumed
together are not available. One of the reasons for this is that drinks containing
alcohol and caffeine are often sold separately and mixed by the consumer rather
than being formulated in a single product – for example rum with cola or energy
drinks with vodka.
7.
Various studies were identified which provided relevant information. These
included studies of the association between consumption of energy drinks and
alcohol, and whether this is influenced by genetic constitution; of risk-taking
behaviour, adverse alcohol-related incidents and use of illicit drugs in people who
consume alcohol with energy drinks; and of brain function following experimental
dosing with caffeine and alcohol in combination. In addition a number of published
reports described cases of illness or death following consumption of caffeine with
alcohol.
8.
The balance of evidence suggests that higher intake of caffeine is associated
not only with higher alcohol intakes but also with use of other psychoactive
substances. There is limited evidence that the relationship may be determined, at
least in part, by an individual’s genetic make-up. It appears that, at least in some
population groups, there is a correlation between high consumption of alcohol and of
energy drinks specifically. However, it is unclear whether this is because
consumption of energy drinks causes people to drink more alcohol, or because
people who are inclined to more risky behaviour tend generally to consume larger
quantities of psychoactive substances, including caffeine and alcohol.
9.
A number of studies have suggested that caffeine can reduce the outward
effects of alcohol, especially on reaction times, but other investigations have failed to
support this. The evidence that perceptions of alcohol intoxication are modified by
caffeine is conflicting. Overall, the range of methods used in reported studies
prevents firm conclusions on whether caffeine counteracts the short-term effects of
alcohol on brain function.
10.
Published case reports of illness or death following consumption of caffeine
and alcohol in combination do not allow firm conclusions about the contribution of
either substance, or of whether caffeine increases the toxicity of alcohol.
11.
Overall, the COT concludes that the current balance of evidence does not
support a harmful toxicological or behavioural interaction between caffeine and
alcohol. However, because of limitations in the available data, there is substantial
uncertainty, and if important new evidence emerges in the future, then this
conclusion should be reviewed.
12.
The full COT statement can be found at:
http://cot.food.gov.uk/pdfs/cotstatementcaffalco201204.pdf
Lay summary to COT statement 2012/04
December 2012
Beverage Category Value Share
BarScan Energy Category Report
Value Share, MAT to August 2012
Source: BarScan Weighted 12 Month Venues
October 2012
Beverage Category Shares
7%
3%
Tap Beer is by far the largest category generating 44
percent of total beverage sales revenue over the bar.
8%
The next largest category is spirits with 14 percent. Vodka
spirits makes up around 20 percent of the spirits category’s
sales.
7%
44%
The next largest categories are packaged beer (10%), wine
(8%), premixed spirits (7%), non-alcoholic drinks (7%) and
cider (3%).
Post mix drinks are the largest segment within the nonalcoholic category and generate 68 percent of revenue. The
remaining non-alcohol drinks segments are single serve
drinks including energy with 28 percent of sales and
‘poured’ drinks (i.e. juices, cordials etc.) with four percent
of non-alcoholic drinks revenue over the bar.
The Energy Category
The energy category drives only a small proportion of sales
over the bar with 0.44 percent of total beverage revenue.
Non-alcoholic energy accounts for 90 percent of the
segment’s sales (or 0.4% of total beverages) with alcoholic
drinks making up the remaining 10 percent of sales (or
0.04% of total beverages).
14%
10%
Tap Beer
Packaged Beer
Spirits
Premixed Spirits
Wine
Cider
Non Alcoholic
Category & Segments Share of Total Beverages
Value Share, MAT to August 2012
Source: BarScan Weighted 12 Month Venues
With respect to each of their categories, non-alcoholic
energy drinks make up five percent of the non-alcoholic
category and 20 percent of single serve segment.
0.45%
Total Energy
0.42%
Alcoholic energy drinks generate only a small proportion of
premixed spirits at 0.6 percent of the categories revenue.
0.40%
Energy Drinks for Occasions
BarScan measures the performance of bar departments
within each venue. This allows greater insights of what
patron’s drink based on the occasion. For example, noalcoholic energy drinks share of total beverage sales in
entertainment bars (i.e. night clubs, live music etc.) at
three percent is considerably higher than public bars,
bistro’s and gaming bars where the segment generate less
than 0.3 percent of beverage sales.
Confidential & Proprietary • Copyright © 2012 BarScan
BarScan Energy Drinks Report
Page 1 of 2
Non Alcoholic
Energy
0.38%
0.04%
Alcoholic Energy
0.04%
MAT August 2012
Quarter August 2012
Energy Brands’ Share
Top 5 Energy Brands Share of Total Energy
Value Share, Source: BarScan Weighted 12 Month Venues
Over three out of four energy drinks sold over the bar is a
Red Bull. The brands share of energy drinks for the year to
August is 76 percent and even higher for the quarter at 78
percent. Mother Energy, with eight percent share is the
second largest energy drink followed by Monster Energy
with six percent share for the year to August 2012.
Alcoholic energy drink brands shares are all relatively small.
Red Bull’s dominance is partly driven by distribution.
Eighty percent of venues selling energy drinks sold Red Bull.
In comparison, Mother Energy is sold in a little over 20
percent of venues - based on the quarter to August 2012.
Most venues only sell one brand of non-alcoholic energy
drink at a point in time.
Energy Brands’ Pricing
The average price paid for a can of Red Bull is $4.68 based
on the quarter to August 2012. This is virtually in line with
the other key brands.
A large proportion of energy drinks will also be sold with a
nip of vodka or a shot of Jagermeister.
On average, this would equate the purchase price of a
vodka and Red Bull to $10.60 and a Jagermeister and Red
Bull to $11.50 in the Hotels channel. This assumes that the
whole can is served to the patron as opposed to part
poured.
Energy Drinks’ Hotel Ranging
Three quarters of venues have sold a non-alcoholic energy
drink in the quarter to August 2012. In comparison, only
one in five venues have sold an alcoholic energy drink.
However, the proportion of bars selling energy drinks is
considerably smaller at 54 percent for non-alcoholic and
ten percent for alcoholic energy drinks.
76%
Red Bull
78%
8%
Mother Energy
8%
6%
Monster Energy
5%
6%
Pulse
5%
3%
Elevate
3%
MAT August 2012
Quarter August 2012
Top 5 Energy Brands Average Price per Serve
Price Incidence per Serve, Quarter August 2012
Source: BarScan Weighted 3 Month Venues
$4.58
Red Bull (250ml)
$4.39
Mother Energy
(250ml)
Monster Energy
(250ml)
$4.64
In other words, energy drink’s penetration within venues is
smaller than the category’s distribution across venues.
For more details on BarScan go to http://www.barscan.com.au
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Confidential & Proprietary • Copyright © 2012 BarScan
BarScan Energy Drinks Report
Page 2 of 2
$8.61 Pulse (300ml)
$6.98
Elevate (300ml)