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Cardiovascular and Cerebrovascular Effects in Response to Red Bull Consumption Combined With Mental Stress

Published:October 29, 2014DOI:https://doi.org/10.1016/j.amjcard.2014.10.017
      The sale of energy drinks is often accompanied by a comprehensive and intense marketing with claims of benefits during periods of mental stress. As it has been shown that Red Bull negatively impacts human hemodynamics at rest, we investigated the cardiovascular and cerebrovascular consequences when Red Bull is combined with mental stress. In a randomized cross-over study, 20 young healthy humans ingested either 355 ml of a can Red Bull or water and underwent 80 minutes after the respective drink a mental arithmetic test for 5 minutes. Continuous cardiovascular and cerebrovascular recordings were performed for 20 minutes before and up to 90 minutes after drink ingestion. Measurements included beat-to-beat blood pressure (BP), heart rate, stroke volume, and cerebral blood flow velocity. Red Bull increased systolic BP (+7 mm Hg), diastolic BP (+4 mm Hg), and heart rate (+7 beats/min), whereas water drinking had no significant effects. Cerebral blood flow velocity decreased more in response to Red Bull than to water (−9 vs −3 cm/s, p <0.005). Additional mental stress further increased both systolic BP and diastolic BP (+3 mm Hg, p <0.05) and heart rate (+13 beats/min, p <0.005) in response to Red Bull; similar increases were also observed after water ingestion. In combination, Red Bull and mental stress increased systolic BP by about 10 mm Hg, diastolic BP by 7 mm Hg, and heart rate by 20 beats/min and decreased cerebral blood flow velocity by −7 cm/s. In conclusion, the combination of Red Bull and mental stress impose a cumulative cardiovascular load and reduces cerebral blood flow even under a mental challenge.
      Recently, we observed an overall negative hemodynamic profile in response to ingestion of 335 ml of Red Bull,
      • Grasser E.K.
      • Yepuri G.
      • Dulloo A.G.
      • Montani J.P.
      Cardio- and cerebrovascular responses to the energy drink Red Bull in young adults: a randomized cross-over study.
      but, to date, there are no data available about whether ingesting an energy drink modifies hemodynamic variables associated with a short-term mental task using beat-to-beat cardiovascular and cerebrovascular measurements. Hence, the purpose of the present study was to determine the hemodynamic impact of a simple mental arithmetic task combined with previous ingestion of Red Bull. As a second aim, we investigated whether the perceived stress level and number of mistakes during mental stress were improved in response to previous consumption of Red Bull.

      Methods

      Twenty healthy young adults (10 women), aged 19 to 29 (22.1 ± 0.5) years, were recruited and paid for their participation. The mean height of the participants was 173.3 ± 2.0 cm, their body weight was 65.7 ± 2.4 kg, and their body mass index was 21.8 ± 0.6 kg m−2. None of the subjects had any diseases or were taking any medication affecting cardiovascular or autonomic regulation. Based on a questionnaire (daily intake of coffee, energy drinks, and other caffeinated beverages), the estimated daily caffeine intake of study participants ranged from 1 to 4 drinks per day. All participants fasted for ≥12 hours and they were requested to avoid alcohol or caffeine for at least 24 hours before the test. The local ethics committee approved the study, and written informed consent was obtained from each subject.
      All experiments took place in a quiet, temperature-controlled (22°C) laboratory and started between 08.00 a.m. and 09.00 a.m. Every subject attended 2 separate experimental sessions (each session separated at least by 2 days) according to a randomized cross-over design. On arrival at the laboratory, subjects were asked to empty their bladders if necessary and to sit in a comfortable armchair. Equipment for cardiovascular and cerebrovascular recordings was then attached. After a variable period for attainment of cardiovascular stability (usually 30 minutes), a baseline recording was made for 20 minutes. Then, the test subjects ingested, not blinded, either 355 ml of a degassed Red Bull drink containing caffeine (114 mg), taurine (1420 mg), and glucuronolactone (84.2 mg), sucrose, and glucose (39.1 g) or 355 ml of tap water at room temperature. Subjects were asked to ingest their drink in a convenient pace for over 4 minutes. After 80 minutes of postdrink cardiovascular recordings, a mental arithmetic task was performed for 5 minutes followed by 5 minutes recovery period.
      Subjects subtracted continuously the number 6 or 7 (chosen at random) from a random 3 or 2 digit number for 5 minutes and were instructed to give the answer verbally. Each mental stress task comprised of 60 unique calculations, with 5 seconds interval between each calculation and was presented to the subjects on a monitor.
      • Lackner H.K.
      • Goswami N.
      • Papousek I.
      • Roessler A.
      • Grasser E.K.
      • Montani J.P.
      • Jezova D.
      • Hinghofer-Szalkay H.
      Time course of cardiovascular responses induced by mental and orthostatic challenges.
      Immediately after the mental task, subjects were asked to rate their perceived stress using a standard 5-point Likert scale.
      • Callister R.
      • Suwarno N.O.
      • Seals D.R.
      Sympathetic activity is influenced by task difficulty and stress perception during mental challenge in humans.
      Cardiovascular and electrocardiographic (cardiac intervals) recordings were performed using a Task Force Monitor (CNSystems, Medizintechnik, Graz, Austria) with data sampled at a rate of 1,000 Hz as described previously.
      • Girona M.
      • Grasser E.K.
      • Dulloo A.G.
      • Montani J.P.
      Cardiovascular and metabolic responses to tap water ingestion in young humans: does the water temperature matter?.
      Cerebral blood flow velocity was measured using transcranial Doppler ultrasonography (Doppler-Box, DWL, Sipplingen, Germany). The left and the right middle cerebral artery was insonated at a depth of 40 to 55 mm using a 2 MHz probe, and the probe was fixed in place with an adjustable headset. Beat-to-beat values of systolic, diastolic, and mean velocity were recorded and merged real time with the Task Force Monitor to allow synchronous cardiovascular and cerebrovascular recordings.
      Beat-to-beat values of cardiac interval, systolic blood pressure (BP), diastolic BP, cerebral blood flow velocity, and stroke volume were averaged over the 20 minutes predrink baseline period and minute by minute starting 5 minutes before (postdrink baseline), during (mental task for 5 minutes) and after the mental stress (recovery for 5 minutes). Heart rate was calculated by the appropriate RR interval. Cardiac output was computed as the product of stroke volume and heart rate. Mean BP was calculated from diastolic BP and systolic BP, respectively: mean BP = diastolic BP + 1/3 (systolic BP − diastolic BP). Total peripheral resistance was calculated as mean BP divided by cardiac output. Double product was calculated as heart rate × systolic BP and provides valuable information for the oxygen consumption of the myocardium.
      • Van Vliet B.N.
      • Montani J.P.
      Baroreflex stabilization of the double product.
      Cerebrovascular resistance index was calculated as the mean BP at brain level (BPmean_brain) divided by mean cerebral blood flow velocity. BPmean_brain was calculated as the difference between mean BP at heart level and the hydrostatic pressure (BPhydro) at the level of transcranial insonation (temporal bone window).
      • Brys M.
      • Brown C.M.
      • Marthol H.
      • Franta R.
      • Hilz M.J.
      Dynamic cerebral autoregulation remains stable during physical challenge in healthy persons.
      Data are expressed as means ± SEM. Statistical analysis was performed by 2-way analysis of variance for repeated measures with time (6 time points: postdrink baseline, mental task 1 to 5 minutes) and treatment (water or Red Bull) as within-subject factors using statistical software (Statistix version 8.0; Analytical Software, St. Paul, Minnesota). The effects of each drink over time were analyzed by comparing values at each time point over the mental task and recovery period with the averaged postdrink baseline values recorded during the 5 minutes immediately before the mental task (Figure 1, Figure 2, Figure 3, Figure 4) using repeated measures analysis of variance with Dunnett's multiple comparison post hoc testing. Changes between postdrink baseline, mental task, and recovery were evaluated using repeated measures analysis of variance with Newman-Keuls post hoc testing (Figure 1, Figure 2, Figure 3, Figure 4). A Wilcoxon matched pairs test was used to elicit differences in mistakes and stress perception in response to the drink (GraphPad Prism version 5, GraphPad Software, Inc, San Diego, California). All reported p values were 2-sided and the level of statistical significance was set as p <0.05.
      Figure thumbnail gr1
      Figure 1Left 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 values 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 tap water 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). §p <0.05 and #p <0.01, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means ± SE. DBP = diastolic blood pressure; MT = mental task; PDBL = postdrink baseline; RE = recovery period; SBP = systolic blood pressure.
      Figure thumbnail gr2
      Figure 2Left 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 (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 values 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 tap water 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). §p <0.05 and ‡p <0.005, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means ± SE. CBFV = cerebral blood flow velocity; HR = heart rate; MT = mental task; PDBL = postdrink baseline; RE = recovery period.
      Figure thumbnail gr3
      Figure 3Left 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 (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 values 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 tap water 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). §p <0.05, #p <0.01, and ‡p <0.005, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means ± SE. CO = cardiac output; DP = double product; MT = mental task; PDBL = postdrink baseline; RE = recovery period; SV = stroke volume.
      Figure thumbnail gr4
      Figure 4Left 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 (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 values 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 tap water 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). §p <0.05, #p <0.01, and ‡p <0.005, statistically significant differences between PDBL, MT, and RE (right panel). All values are reported as means ± SE. CVRI = cerebrovascular resistance index; MT = mental task; PDBL = postdrink baseline; RE = recovery period; TPR = total peripheral resistance.

      Results

      Predrink hemodynamic values were similar between the drinks, whereas Red Bull elevated significantly systolic and diastolic BP, heart rate, cardiac output, double product, cerebrovascular resistance, and decreased cerebral blood flow velocity over the postdrink period (Table 1 and Supplementary Tables 1 and 2).
      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 using a randomized cross-over study design
      TreatmentWaterWaterRed BullRed BullWaterWaterRed BullRed BullWaterWaterRed BullRed Bull
      ConditionPre-drinkPost-drinkPre-drinkPost-drinkPre-drinkPost-drinkPre-drinkPost-drinkPre-drinkPost-drinkPre-drinkPost-drink
      CaseSBP

      [mmHg]
      SBP

      [mmHg]
      SBP

      [mmHg]
      SBP

      [mmHg]
      DBP

      [mmHg]
      DBP

      [mmHg]
      DBP

      [mmHg]
      DBP

      [mmHg]
      HR

      [bpm]
      HR

      [bpm]
      HR

      [bpm]
      HR

      [bpm]
      1 (20 years)1301301201308082707762616467
      2 (23 years)1151221081197477697863666772
      3 (29 years)1291271221328581809070686870
      4 (20 years)1131171131217677788458586572
      5 (24 years)1331451461557981817967626359
      6 (22 years)1141151101297375717956746577
      7 (22 years)1221191161208587828695768186
      8 (19 years)1431341331378682808169706482
      9 (23 years)1171191211227476817958655867
      10 (24 years)1011161111156980717658606266
      11 (23 years)1151191201357675788553535966
      12 (20 years)104106991056670636463535558
      13 (22 years)1141151111136872717250654759
      14 (23 years)1131171241357476808861626668
      15 (20 years)1161241171287980819369787189
      16 (20 years)1121151071116770666860615661
      17 (21 years)105951091146559697273656971
      18 (22 years)1121061201257775878664666869
      19 (21 years)1201081161167664677064556877
      20 (23 years)1111101201207472868480727489
      Average117118117124*75767680*65646571*
      SEM222311122222
      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 = diastolic blood pressure; HR = heart rate; SBP = systolic blood pressure; SEM = 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.
      No significant interaction (drink × time) effects were found for any variable tested. Addition of mental stress 80 minutes after ingesting Red Bull increased systolic BP and diastolic BP by about +3 mm Hg, heart rate by +12.8 beats/min, cerebral blood flow velocity by + 2.0 cm/s, cardiac output by + 1.0 L/min, and double product by + 1857 mm Hg beats/min (Figure 1, Figure 2, Figure 3). Mental stress applied after water ingestion invoked similar rises in systolic BP and diastolic BP (+4 mm Hg), heart rate (+11.4 beats/min), cerebral blood flow velocity (+2.0 cm/s), cardiac output (+1.0 L/min), and double product (+1665 mm Hg beats/min). Total peripheral resistance decreased similarly with Red Bull (−1.58 mm Hg min/L) and water (−1.73 mm Hg min/L) in response to mental stress (Figure 4). Ingestion of Red Bull and water did not influence stroke volume in response to mental stress (Figure 3).
      Overall, the combination of Red Bull ingestion and mental stress application 80 minutes later caused total increases in systolic BP of +10.2 mm Hg, diastolic BP of +7.3 mm Hg, heart rate +19.7 beats/min, cardiac output of +1.6 L/min, double product of +3,137 mm Hg beats/min, and cerebrovascular resistance index of +0.32 mm Hg cm/s, whereas a decrease was found for cerebral blood flow velocity of −7.1 cm/s and total peripheral resistance of −2.3 mm Hg min/L (Figure 1, Figure 2, Figure 3, Figure 4).
      Cardiac output (+0.01 vs +0.37 L/min) and stroke volume (+0.5 vs +5.7 ml) were significantly higher in the 5 minute recovery period compared with postdrink values before the mental task after ingestion of water, whereas ingestion of Red Bull increased stroke volume only (−0.4 vs +2.9 ml; Figure 3). Moreover, water ingestion significantly decreased total peripheral resistance (+0.14 vs −0.59 mm Hg min/L) in the recovery period compared with postdrink values before the mental task (Figure 4).
      No significant differences between the drinks were found for a total count of mistakes and for stress perception during the mental task (Figure 5).
      Figure thumbnail gr5
      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 over the subject's subjective stress perception derived immediately after the mental task using a 5-point Likert-scale. 0 = no stress; 1 = light stress; 2 = stressful; 3 = very stressful; 4 = very, very stressful.

      Discussion

      This study examined the influence of a commonly available energy drink on cardiovascular and cerebrovascular parameters in response to a mental stress task in young and healthy humans using beat-to-beat measurement techniques. Our results presented here provide evidence that mental stress applied after the consumption of Red Bull led to a substantial augmentation of the heart's workload through elevations of BP, heart rate, and double product, which were accompanied by a sustained reduced cerebral blood flow velocity. These cardiovascular changes have been found additive rather than synergistic in response to mental stress, thereby suggesting that the hemodynamic consequences from a laboratory mental stress task are independent from ingesting either energy drink or tap water.
      Recently, we observed in response to one 355 ml can of Red Bull detrimental effects on cerebral blood flow velocity in young and healthy humans.
      • Grasser E.K.
      • Yepuri G.
      • Dulloo A.G.
      • Montani J.P.
      Cardio- and cerebrovascular responses to the energy drink Red Bull in young adults: a randomized cross-over study.
      These results cast doubt on a better overall performance, in particular under conditions of mental stress. As yet, we are not aware of a study in which the impact of an energy drink was investigated on cardiovascular and cerebrovascular parameters in response to a mental stress task. The onset of mental stress is associated with an increase in heart rate, cardiac output, arterial BP, and vasodilatation in the skeletal muscles through activation of the autonomic nervous and endocrine systems.
      • Freyschuss U.
      • Hjemdahl P.
      • Juhlindannfelt A.
      • Linde B.
      Cardiovascular and sympathoadrenal responses to mental stress: influence of beta-blockade.
      In contrast, oral ingestion of a 250 mg caffeine containing beverage was found to raise BP variables substantially 1 hour after consumption.
      • Robertson D.
      • Frolich J.C.
      • Carr R.K.
      • Watson J.T.
      • Hollifield J.W.
      • Shand D.G.
      • Oates J.A.
      Effects of caffeine on plasma renin activity, catecholamines and blood pressure.
      Previous studies investigated cardiovascular responses to the combination of 250 mg of caffeine with a mental arithmetic task and reported additive effects on BP in healthy men.
      • France C.
      • Ditto B.
      Cardiovascular responses to the combination of caffeine and mental arithmetic, cold pressor, and static exercise stressors.
      • Lane J.D.
      • Williams R.B.
      Caffeine affects cardiovascular responses to stress.
      In the present study, a mental arithmetic task additionally increased systolic BP and diastolic BP after the consumption of a 355 ml can Red Bull, which contains 115 to 123 mg caffeine,
      • Vochyánová B.
      • Opekar F.
      • Tůma P.
      Simultaneous and rapid determination of caffeine and taurine in energy drinks by MEKC in a short capillary with dual contactless conductivity/photometry detection.
      • Sereshti H.
      • Samadi S.
      A rapid and simple determination of caffeine in teas, coffees and eight beverages.
      and caused total increases of 10.2 mm Hg for systolic BP and 7.3 mm Hg for diastolic BP. Therefore, it seems reasonable to refer our observed changes in BP parameters, at least partly, to the caffeine content in the Red Bull drink and to the mental stress. What is of concern is that energy beverages are being marketed for improving performance of mental work and physical exercise. However, during exercise, caffeine consumption has been noted to be associated with reduced myocardial blood flow.
      • Higgins J.P.
      • Babu K.M.
      Caffeine reduces myocardial blood flow during exercise.
      This could be because of the effect of acute endothelial dysfunction, which could also explain some of the hemodynamic changes noted in the present study of mental stress (which can often simulate physical stress) in the presence of an acute exposure to an energy beverage. In contrast, we previously investigated the impact of a Red Bull energy drink on microvascular endothelial function and were not able to find changes on acetylcholine or sodium-nitroprusside mediated endothelial function in response to ingestion of an energy drink.
      • Grasser E.K.
      • Yepuri G.
      • Dulloo A.G.
      • Montani J.P.
      Cardio- and cerebrovascular responses to the energy drink Red Bull in young adults: a randomized cross-over study.
      In response to the mental task, we observed a rapid and substantial increase in heart rate, cardiac output, and double product with no initial change in BP variables and a decrease in total peripheral resistance. After this initial response, BP variables rose immediately to its peak values and gradually returned afterward to postdrink baseline values. Throughout the mental task, heart rate and cardiac output values remained significantly over postdrink baseline levels whereas stroke volume remained unchanged. These observations suggest a specific cardiac reaction pattern in response to mental stress after consumption of energy drink and water because of constant elevated cardiac output values which originated from increases in heart rate but not stroke volume. In agreement with our findings, a recent study observed increased cardiac output and heart rate values in response to a monotonous driving task after the ingestion of a 250 ml can Red Bull which was mixed with 250 ml orange juice.
      • Yamakoshi T.
      • Matsumura K.
      • Hanaki S.
      • Rolfe P.
      Cardiovascular hemodynamic effects of Red Bull® Energy Drink during prolonged, simulated, monotonous driving.
      In response to the mental arithmetic test, cerebral blood flow velocity rose immediately after the onset, plateaued for 3 minutes and gradually returned to postdrink baseline levels after cessation. This effect could be observed to a similar extent for Red Bull and for water (+3.5% and +3.1%, respectively) and agrees with a study in which cerebral blood flow velocity was investigated in response to mental activities.
      • Droste D.W.
      • Harders A.G.
      • Rastogi E.
      A transcranial Doppler study of blood flow velocity in the middle cerebral arteries performed at rest and during mental activities.
      However, the combination of mental stress and Red Bull consumption caused a −11% lower cerebral blood flow velocity compared with predrink baseline levels, whereas the water drink had just a small effect (−0.8%). In line with this novel observation, our subjects' mistake quote and their perceived stress level were not better after ingestion of Red Bull in comparison to the water control.
      Therefore, the benefit of using energy drinks with the intention to improve mental efforts or to cope better with mental stress seems questionable.

      Disclosures

      The authors have no conflicts of interest to disclose.

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