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Cardiovascular and Cerebrovascular Effects in Response to Red Bull Consumption Combined With Mental Stress Erik Konrad Grasser, PhD, MD, Abdul G. Dulloo, PhD, and Jean-Pierre Montani, MD The sale of energy drinks is often accompanied by a comprehensive and intense marketingwith claims of benefits during periods of mental stress. As it has been shown that Red Bullnegatively impacts human hemodynamics at rest, we investigated the cardiovascular andcerebrovascular consequences when Red Bull is combined with mental stress. In a randomizedcross-over study, 20 young healthy humans ingested either 355 ml of a can Red Bull or waterand underwent 80 minutes after the respective drink a mental arithmetic test for 5 minutes.
Continuous cardiovascular and cerebrovascular recordings were performed for 20 minutesbefore and up to 90 minutes after drink ingestion. Measurements included beat-to-beat bloodpressure (BP), heart rate, stroke volume, and cerebral blood flow velocity. Red Bull increasedsystolic BP (D7 mm Hg), diastolic BP (D4 mm Hg), and heart rate (D7 beats/min), whereaswater drinking had no significant effects. Cerebral blood flow velocity decreased more inresponse to Red Bull than to water (L9 vs L3 cm/s, p <0.005). Additional mental stressfurther increased both systolic BP and diastolic BP (D3 mm Hg, p <0.05) and heart rate(D13 beats/min, p <0.005) in response to Red Bull; similar increases were also observed afterwater ingestion. In combination, Red Bull and mental stress increased systolic BP by about10 mm Hg, diastolic BP by 7 mm Hg, and heart rate by 20 beats/min and decreased cerebralblood flow velocity by L7 cm/s. In conclusion, the combination of Red Bull and mental stressimpose a cumulative cardiovascular load and reduces cerebral blood flow even under a mentalchallenge.
Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;115:183e189) Recently, we observed an overall negative hemodynamic questionnaire (daily intake of coffee, energy drinks, and other profile in response to ingestion of 335 ml of Red but, caffeinated beverages), the estimated daily caffeine intake of to date, there are no data available about whether ingesting study participants ranged from 1 to 4 drinks per day. All an energy drink modifies hemodynamic variables associated participants fasted for 12 hours and they were requested to with a short-term mental task using beat-to-beat cardiovas- avoid alcohol or caffeine for at least 24 hours before the test.
cular and cerebrovascular measurements. Hence, the The local ethics committee approved the study, and written purpose of the present study was to determine the hemo- informed consent was obtained from each subject.
dynamic impact of a simple mental arithmetic task com- All experiments took place in a quiet, temperature- bined with previous ingestion of Red Bull. As a second aim, controlled (22C) laboratory and started between 08.00 we investigated whether the perceived stress level and A.M. and 09.00 A.M. Every subject attended 2 separate number of mistakes during mental stress were improved in experimental sessions (each session separated at least by 2 response to previous consumption of Red Bull.
days) according to a randomized cross-over design. Onarrival at the laboratory, subjects were asked to empty their bladders if necessary and to sit in a comfortable armchair.
Equipment for cardiovascular and cerebrovascular re- Twenty healthy young adults (10 women), aged 19 to 29 cordings was then attached. After a variable period for (22.1
0.5) years, were recruited and paid for their partici- attainment of cardiovascular stability (usually 30 minutes), a pation. The mean height of the participants was 173.3
baseline recording was made for 20 minutes. Then, the test 2.0 cm, their body weight was 65.7
2.4 kg, and their body subjects ingested, not blinded, either 355 ml of a degassed mass index was 21.8
0.6 kg m2. None of the subjects had Red Bull drink containing caffeine (114 mg), taurine any diseases or were taking any medication affecting (1420 mg), and glucuronolactone (84.2 mg), sucrose, and cardiovascular or autonomic regulation. Based on a glucose (39.1 g) or 355 ml of tap water at room temperature.
Subjects were asked to ingest their drink in a convenient pace Division of Physiology, Department of Medicine, Laboratory of Inte- for over 4 minutes. After 80 minutes of postdrink cardio- grative Cardiovascular and Metabolic Physiology, University of Fribourg, vascular recordings, a mental arithmetic task was performed Fribourg, Switzerland. Manuscript received July 18, 2014; revised manu- for 5 minutes followed by 5 minutes recovery period.
script received and accepted October 14, 2014.
Subjects subtracted continuously the number 6 or 7 Research relating to this study was funded partially by the SNF (SNF (chosen at random) from a random 3 or 2 digit number for 5 number: 122554) to JPM.
minutes and were instructed to give the answer verbally.
See page 189 for disclosure information.
Each mental stress task comprised of 60 unique calculations, *Corresponding author: Tel: (þ41) 26 300 8675; fax: (þ41) 26 with 5 seconds interval between each calculation and was E-mail address: (E.K. Grasser).
presented to the subjects on a monitorImmediately after 0002-9149/14/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved.

The American Journal of Cardiology ( Figure 1. Left panel: Time course for changes in SBP (A) and DBP (B) starting 75 minutes (i.e., 5 minutes on the panel) after ingestion of Red Bull (full circle)or tap water (open rhomb). Right panel: Mean responses averaged over 5 minutes PDBL, 5 minutes MT, and 5 minutes RE relative to predrink baseline valuesand presented as a delta (i.e., average over the respective 5 minutes interval minus the average over the 20 minutes predrink baseline period) after tap water orRed Bull. *p <0.05, **p <0.01, and ***p <0.005 statistically significant differences over time from predrink baseline values (left and right panels). xp <0.05and #p <0.01, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means
SE. DBP ¼ diastolic bloodpressure; MT ¼ mental task; PDBL ¼ postdrink baseline; RE ¼ recovery period; SBP ¼ systolic blood pressure.
the mental task, subjects were asked to rate their perceived BP þ 1/3 (systolic BP  diastolic BP). Total peripheral stress using a standard 5-point Likert scale.
resistance was calculated as mean BP divided by cardiac Cardiovascular and electrocardiographic (cardiac in- output. Double product was calculated as heart rate  sys- tervals) recordings were performed using a Task Force tolic BP and provides valuable information for the oxygen Monitor (CNSystems, Medizintechnik, Graz, Austria) with consumption of the myocardium.Cerebrovascular resis- data sampled at a rate of 1,000 Hz as described previ tance index was calculated as the mean BP at brain level Cerebral blood flow velocity was measured using trans- (BPmean_brain) divided by mean cerebral blood flow velocity.
cranial Doppler ultrasonography (Doppler-Box, DWL, BPmean_brain was calculated as the difference between mean Sipplingen, Germany). The left and the right middle cerebral BP at heart level and the hydrostatic pressure (BPhydro) at the artery was insonated at a depth of 40 to 55 mm using a 2 MHz level of transcranial insonation (temporal bone window).
probe, and the probe was fixed in place with an adjustable Data are expressed as means
SEM. Statistical analysis headset. Beat-to-beat values of systolic, diastolic, and mean was performed by 2-way analysis of variance for repeated velocity were recorded and merged real time with the measures with time (6 time points: postdrink baseline, mental Task Force Monitor to allow synchronous cardiovascular and task 1 to 5 minutes) and treatment (water or Red Bull) as within-subject factors using statistical software (Statistix Beat-to-beat values of cardiac interval, systolic blood version 8.0; Analytical Software, St. Paul, Minnesota). The pressure (BP), diastolic BP, cerebral blood flow velocity, and effects of each drink over time were analyzed by comparing stroke volume were averaged over the 20 minutes predrink values at each time point over the mental task and recovery baseline period and minute by minute starting 5 minutes period with the averaged postdrink baseline values recorded before (postdrink baseline), during (mental task for 5 mi- during the 5 minutes immediately before the mental task nutes) and after the mental stress (recovery for 5 minutes).
(using repeated measures analysis of variance Heart rate was calculated by the appropriate RR interval.
with Dunnett's multiple comparison post hoc testing. Changes Cardiac output was computed as the product of stroke vol- between postdrink baseline, mental task, and recovery were ume and heart rate. Mean BP was calculated from diastolic evaluated using repeated measures analysis of variance with BP and systolic BP, respectively: mean BP ¼ diastolic Newman-Keuls post hoc testing (A Wilcoxon

Preventive Cardiology/Mental Stress and Red Bull: Detrimental Effects? Figure 2. Left panel: Time course for changes in HR (A) and CBFV (B) starting 75 minutes (i.e., 5 minutes on the panel) after ingestion of Red Bull (fullcircle) or tap water (open rhomb). Right panel: Mean responses averaged over 5 minutes PDBL, 5 minutes MT, and 5 minutes RE relative to predrink baselinevalues and presented as a delta (i.e., average over the respective 5 minutes interval minus the average over the 20 minutes predrink baseline period) after tapwater or Red Bull. *p <0.05, **p <0.01, and ***p <0.005 statistically significant differences over time from predrink baseline values (left and right panels).
xp <0.05 and zp <0.005, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means
SE.
CBFV ¼ cerebral blood flow velocity; HR ¼ heart rate; MT ¼ mental task; PDBL ¼ postdrink baseline; RE ¼ recovery period.
matched pairs test was used to elicit differences in mistakes with Red Bull (1.58 mm Hg min/L) and water (1.73 mm and stress perception in response to the drink (GraphPad Prism Hg min/L) in response to mental stress (Ingestion version 5, GraphPad Software, Inc, San Diego, California).
of Red Bull and water did not influence stroke volume in All reported p values were 2-sided and the level of statistical response to mental stress ().
significance was set as p <0.05.
Overall, the combination of Red Bull ingestion and mental stress application 80 minutes later caused total increases in systolic BP of þ10.2 mm Hg, diastolic BPof þ7.3 mm Hg, heart rate þ19.7 beats/min, cardiac output Predrink hemodynamic values were similar between the of þ1.6 L/min, double product of þ3,137 mm Hg beats/ drinks, whereas Red Bull elevated significantly systolic min, and cerebrovascular resistance index of þ0.32 mm Hg and diastolic BP, heart rate, cardiac output, double product, cm/s, whereas a decrease was found for cerebral blood flow cerebrovascular resistance, and decreased cerebral blood velocity of 7.1 cm/s and total peripheral resistance ow velocity over the postdrink period and of 2.3 mm Hg min/L ().
Cardiac output (þ0.01 vs þ0.37 L/min) and stroke vol- No significant interaction (drink  time) effects were ume (þ0.5 vs þ5.7 ml) were significantly higher in the 5 found for any variable tested. Addition of mental stress minute recovery period compared with postdrink values 80 minutes after ingesting Red Bull increased systolic BP before the mental task after ingestion of water, whereas and diastolic BP by about þ3 mm Hg, heart rate by þ12.8 ingestion of Red Bull increased stroke volume only (0.4 beats/min, cerebral blood flow velocity by þ 2.0 cm/s, vs þ2.9 ml; Moreover, water ingestion signifi- cardiac output by þ 1.0 L/min, and double product by þ 1857 mm Hg beats/min (). Mental stress vs 0.59 mm Hg min/L) in the recovery period compared applied after water ingestion invoked similar rises in systolic with postdrink values before the mental task BP and diastolic BP (þ4 mm Hg), heart rate (þ11.4 beats/ No significant differences between the drinks were found min), cerebral blood flow velocity (þ2.0 cm/s), cardiac for a total count of mistakes and for stress perception during output (þ1.0 L/min), and double product (þ1665 mm Hg the mental task ( beats/min). Total peripheral resistance decreased similarly

The American Journal of Cardiology ( Figure 3. Left panel: Time course for changes in SV (A), CO (B), and DP (C) starting 75 minutes (i.e., 5 minutes on the panel) after ingestion of Red Bull (fullcircle) or tap water (open rhomb). Right panel: Mean responses averaged over 5 minutes PDBL, 5 minutes MT, and 5 minutes RE relative to predrink baselinevalues and presented as a delta (i.e., average over the respective 5 minutes interval minus the average over the 20 minutes predrink baseline period) after tapwater or Red Bull. *p <0.05, **p <0.01, and ***p <0.005 statistically significant differences over time from predrink baseline values (left and right panels).
xp <0.05, #p <0.01, and zp <0.005, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means
SE.
CO ¼ cardiac output; DP ¼ double product; MT ¼ mental task; PDBL ¼ postdrink baseline; RE ¼ recovery period; SV ¼ stroke volume.
mental stress, thereby suggesting that the hemodynamicconsequences from a laboratory mental stress task are in- This study examined the influence of a commonly dependent from ingesting either energy drink or tap water.
available energy drink on cardiovascular and cerebrovas- Recently, we observed in response to one 355 ml can of cular parameters in response to a mental stress task in young Red Bull detrimental effects on cerebral blood flow velocity and healthy humans using beat-to-beat measurement tech- in young and healthy humans.These results cast doubt on a niques. Our results presented here provide evidence that better overall performance, in particular under conditions of mental stress applied after the consumption of Red Bull led mental stress. As yet, we are not aware of a study in which to a substantial augmentation of the heart's workload the impact of an energy drink was investigated on cardio- through elevations of BP, heart rate, and double product, vascular and cerebrovascular parameters in response to a which were accompanied by a sustained reduced cerebral mental stress task. The onset of mental stress is associated blood flow velocity. These cardiovascular changes have with an increase in heart rate, cardiac output, arterial BP, been found additive rather than synergistic in response to

Preventive Cardiology/Mental Stress and Red Bull: Detrimental Effects? Figure 4. Left panel: Time course for changes in TPR (A) and CVRI (B) starting 75 minutes (i.e., 5 minutes on the panel) after ingestion of Red Bull (fullcircle) or tap water (open rhomb). Right panel: Mean responses averaged over 5 minutes PDBL, 5 minutes MT, and 5 minutes RE relative to predrink baselinevalues and presented as a delta (i.e., average over the respective 5 minutes interval minus the average over the 20 minutes predrink baseline period) after tapwater or Red Bull. *p <0.05, **p <0.01, and ***p <0.005 statistically significant differences over time from predrink baseline values (left and right panels).
xp <0.05, #p <0.01, and zp <0.005, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means
SE.
CVRI ¼ cerebrovascular resistance index; MT ¼ mental task; PDBL ¼ postdrink baseline; RE ¼ recovery period; TPR ¼ total peripheral resistance.
and vasodilatation in the skeletal muscles through activation microvascular endothelial function and were not able to find of the autonomic nervous and endocrine systemsIn changes on acetylcholine or sodium-nitroprusside mediated contrast, oral ingestion of a 250 mg caffeine containing endothelial function in response to ingestion of an energy beverage was found to raise BP variables substantially 1 hour after consumPrevious studies investigated car- In response to the mental task, we observed a rapid and diovascular responses to the combination of 250 mg of substantial increase in heart rate, cardiac output, and double caffeine with a mental arithmetic task and reported additive product with no initial change in BP variables and a effects on BP in healthy men.In the present study, a decrease in total peripheral resistance. After this initial mental arithmetic task additionally increased systolic BP response, BP variables rose immediately to its peak values and diastolic BP after the consumption of a 355 ml can Red and gradually returned afterward to postdrink baseline Bull, which contains 115 to 123 mg caffeine,and values. Throughout the mental task, heart rate and cardiac caused total increases of 10.2 mm Hg for systolic BP and output values remained significantly over postdrink baseline 7.3 mm Hg for diastolic BP. Therefore, it seems reasonable levels whereas stroke volume remained unchanged. These to refer our observed changes in BP parameters, at least observations suggest a specific cardiac reaction pattern in partly, to the caffeine content in the Red Bull drink and to response to mental stress after consumption of energy drink the mental stress. What is of concern is that energy bever- and water because of constant elevated cardiac output values ages are being marketed for improving performance of which originated from increases in heart rate but not stroke mental work and physical exercise. However, during exer- volume. In agreement with our findings, a recent study cise, caffeine consumption has been noted to be associated observed increased cardiac output and heart rate values in with reduced myocardial blood flow.This could be response to a monotonous driving task after the ingestion of because of the effect of acute endothelial dysfunction, which a 250 ml can Red Bull which was mixed with 250 ml orange could also explain some of the hemodynamic changes noted in the present study of mental stress (which can often In response to the mental arithmetic test, cerebral blood simulate physical stress) in the presence of an acute expo- flow velocity rose immediately after the onset, plateaued for sure to an energy beverage. In contrast, we previously 3 minutes and gradually returned to postdrink baseline investigated the impact of a Red Bull energy drink on levels after cessation. This effect could be observed to a

The American Journal of Cardiology ( Table 1Individual cardiovascular pre- and post-drink parameters measured in 20 (first 10 are males and second 10 are females) young and healthy human subjects usinga randomized cross-over study design Pre-drink Post-drink Pre-drink Post-drink Pre-drink Post-drink Pre-drink Post-drink Pre-drink Post-drink Pre-drink Post-drink Pre-drink: Average over 20 minutes pre-drink baseline values; Post-drink: Average over the last 5 minutes before starting the mental task (i.e. average over the period from 75 to 80 minutes after the respective drink).
DBP ¼ diastolic blood pressure; HR ¼ heart rate; SBP ¼ systolic blood pressure; SEM ¼ standard error of means.
*p <0.005, comparing pre-drink Red Bull with post-drink Red Bull using a paired t-test. Data are presented as absolute values.
Figure 5. (A) Average over the test subject's mistake count for 60 arithmetic problems solved in 5 minutes (answers were given verbally). (B) Average overthe subject's subjective stress perception derived immediately after the mental task using a 5-point Likert-scale. 0 ¼ no stress; 1 ¼ light stress; 2 ¼ stressful;3 ¼ very stressful; 4 ¼ very, very stressful.
similar extent for Red Bull and for water (þ3.5% (0.8%). In line with this novel observation, our subjects' and þ3.1%, respectively) and agrees with a study in which mistake quote and their perceived stress level were not cerebral blood flow velocity was investigated in response to better after ingestion of Red Bull in comparison to the water mental actiHowever, the combination of mental stress and Red Bull consumption caused a 11% lower Therefore, the benefit of using energy drinks with the cerebral blood flow velocity compared with predrink base- intention to improve mental efforts or to cope better with line levels, whereas the water drink had just a small effect mental stress seems questionable.
Preventive Cardiology/Mental Stress and Red Bull: Detrimental Effects? The authors have no conflicts of interest to disclose.
Supplementary Data Supplementary data associated with this article can be found, in the online version, at

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