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Keywords:

  • arrhythmia;
  • HRR;
  • HRV;
  • physical exercise;
  • taurine

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References

Background:  Media have anecdotally reported that drinking energy drinks in combination with alcohol and exercise could cause sudden cardiac death. This study investigated changes in the electrocardiogram (ECG) and heart rate variability after intake of an energy drink, taken in combination with alcohol and exercise.

Methods:  Ten healthy volunteers (five men and five women aged 19–30) performed maximal bicycle ergometer exercise for 30 min after: (i) intake of 0·75 l of an energy drink mixed with alcohol; (ii) intake of energy drink; and, (iii) no intake of any drink. ECG was continuously recorded for analysis of heart rate variability and heart rate recovery.

Results:  No subject developed any clinically significant arrhythmias. Post-exercise recovery in heart rate and heart rate variability was slower after the subjects consumed energy drink and alcohol before exercise, than after exercise alone.

Conclusion:  The healthy subjects developed blunted cardiac autonomic modulation after exercising when they had consumed energy drinks mixed with alcohol. Although they did not develop any significant arrhythmia, individuals predisposed to arrhythmia by congenital or other rhythm disorders could have an increased risk for malignant cardiac arrhythmia in similar situations.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References

During the 1990s, several beverage companies introduced energy drinks containing caffeine, taurine and carbohydrates. These drinks have become very popular not only as sport drinks, but also in a mix with alcohol. Three Swedish sudden deaths after consuming energy drinks and then exercising (Finnegan, 2003; Lehtihet et al., 2006) has been reported and the question has been raised whether the intake of energy drinks together with physical exercise, and possibly also in combination with alcohol, could increase the risk of sudden death – presumably by an arrhythmic origin. However, no empirical link has been found between the intake of energy drink and the time of death, or between the intake of energy drink and the mechanisms responsible for the deaths.

Few studies have examined how energy drinks combined with alcohol affects the heart (Baum & Weiss, 2001; Ferreira et al., 2004). To our knowledge no previous study has investigated the possible arrhythmogenic effects of this combined intake. Increased risk of cardiac arrhythmia could be manifested by changes in the morphology of the electrocardiogram (ECG) or by changes in the mechanisms that trigger individual heartbeats. In particular, malignant cardiac arrhythmia can also be caused by autonomic imbalance with low parasympathetic activity and high sympathetic activity (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996). Several studies in clinical settings correlate reduced cardiac autonomic modulation, as reflected by the beat-to-beat changes in heart rate (heart rate variability, HRV) with the risk of sudden death (Wolf et al., 1978; Ewing et al., 1985; Every et al., 2002). Several studies have also shown that the decrease of heart rate after peak exercise, also called Heart Rate Recovery (HRR), can be used as a marker of parasympathetic activity and also as a predictor of mortality (Cole et al., 1999; Gorelik et al., 2006).

The aim of this study was to examine ECG changes in healthy subjects after the consumption of energy drink combined with alcohol followed by exercise. In particular, our aim was to investigate if the combined intake of energy drink and alcohol caused abnormal patterns in post-exercise HRR or in HRV. Such changes could contribute to an increased risk of cardiac arrhythmia.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References

The study was carried out in 10 healthy volunteers – five men and five women aged 19–30. Their background anthropometrical data are listed in Table 1. The investigations were performed in several steps with at least a 1-week wash out period. All tests included sequential laboratory tests (electrolytes, caffeine and glucose), 12-lead ECGs, and Holter monitoring. All subjects gave informed consent, and the local ethical committee of Umeå University approved the study protocol.

Table 1.   Baseline values for the healthy volunteers.
 Men (= 5)Women (= 5)
Mean (SD)Mean (SD)
Age (years)26·2 (1·5)26·8 (4·7)
BMI (kg m−2)23·9 (1·8)23·5 (2·4)
Systolic blood pressure (mmHg)122·8 (7·7)116·8 (8·1)
Diastolic blood pressure (mmHg)68·6 (10·0)72·4 (13·5)
Heart rate (beats/minute)73·6 (11·8)66·4 (8·0)
S-Mg (mmol l−1)0·8 (1·1)0·8 (3·0)
S-Glucose (mmol l−1)5·0 (0·4)4·7 (0·7)
S-K (mmol l−1)4·1 (0·5)3·9 (0·3)
S-Na (mmol l−1)141·8 (1·0)140·0 (1·6)
S-Creatinine (mmol l−1)80·8 (10·5)84·8 (10·7)
S-Albumin (g l−1)41·8 (2·8)36·6 (3·0)
PQ time (ms)157·2 (21·7)130·0 (16·9)
QRS duration (ms)95·6 (8·6)87·6 (12·4)
QT time (ms)387·2 (25·4)406·4 (27·8)
QT time, corrected (ms)417·0 (16·9)417·4 (18·9)

The subjects performed a physical and laboratory baseline screening, followed by four tests, all performed in the same order with 1–3 months between each test:

  • 1
     Consumption of 0·75 l of energy drink (three cans of RedBull®, containing 0·4% of taurine, 0·032% of caffeine, totally 3000 mg of taurine and 240 mg of caffeine) after an overnight fast.
  • 2
     Consumption of 0·75 l of energy drink mixed with vodka, corresponding to 0·4 g of ethanol per kg body weight, and a maximal bicycle ergometer exercise 30 min later. This trial, laboratory analysis also included s-ethanol (ED/ET).
  • 3
     Consumption of 0·75 l of energy drink and a maximal bicycle ergometer exercise 30 min later (ED).
  • 4
     Maximal bicycle ergometer exercise after 30 min rest (EX).

The subjects consumed the amount of energy drink within 30 min. The maximal bicycle ergometer exercise was designed to be maximal and last for up to 15 min, following the protocol suggested by Nordenfelt et al. (Nordenfelt et al., 1985). The subjects returned to the supine position directly after exercise. They stayed in the supine position at least for 1 h in all tests and remained in the laboratory up to 6 h after the bicycle ergometer exercise test (Tests ED/ET and ED).

The local laboratory performed analyses (s-glucose, s-potassium, s-sodium, s-creatinine, s-magnesium, ionised s-calcium) using routine biochemical methods. Caffeine and ethanol were analysed at the Department of Forensic Chemistry, National Board of Forensic Medicine, Linköping, Sweden. A standard ECG recorder (Siemens-Elema AB, Solna, Sweden) was used to record twelve-lead ECGs to calculate PQ and QT/QTc times, and QRS duration. QT was corrected for heart rate according to Bazett (Bazett, 1920).

During the tests, ECG was recorded with an ambulatory recorder unit (Braemer DL 700; Braemer inc. Burnsville, MN, USA) with a sample rate of 128 Hz. Cardiac conduction and rhythm disturbances were automatically analysed by a Holter-ECG system (Danica Holter Replay Unit, Danica Biomedical, Borlänge, Sweden). One investigator examined all recordings, confirmed pathological events, and corrected detection errors. ECG and R-R intervals were exported from the Holter-ECG system. HRR and HRV were analysed with custom-designed software using the Matlab software (Mathworks, Natick, MA, USA).

HRR was determined by fitting a first order exponential decay curve to the post-exercise heart rate recovery according to Javorka et al. (Javorka et al., 2003):

  • image

where the decay constant (T), peak heart rate (HRPeak) and final heart rate (HRRest) were determined by using the simplex search method (Lagarias et al., 1998), with data from the first 300 s after the maximal bicycle exercise.

The R-R interval data were transformed to an evenly sampled (2 Hz) time series by cubic spline interpolation before HRV was analysed. Spurious arrhythmic beats and artefacts were replaced using interpolation. Recordings from Test 1 were analysed as non-overlapping 10-min sequences. Data from Tests 2 to 4 were analysed as 2-min sequences because of the non-stationary HRV during the recovery after exercise. The mean heart rate was calculated for each sequence. Data were detrended by removing the mean value and the linear trend.

Heart rate variability was analysed in the frequency domain: the power spectral density was estimated by auto-regressive modelling using the Burg algorithm with 30 parameters. HRV was measured by calculating the total spectral power (PTOT), the power of the low-frequency component (PLF; 0·04–0·15 Hz), and the power of the high-frequency component (PHF; 0·15–0·50 Hz). Often, the low-frequency (LF) component is associated with baroreceptor mediated blood-pressure control, reflecting both sympathetic and parasympathetic activity. In most subjects, the high-frequency (HF) component peaks at the respiration frequency, reflecting parasympathetic activity (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996). The ratio PLF/PHF was calculated as an indicator of sympathovagal balance. All spectral indices were logarithmically transformed.

Statistical methods

Data were analysed by repeated measures analysis of variance (ANOVA) with time and test as factors. Statistically significant main effects were analysed with a simple contrast, where, e.g. the first sequence (baseline) was compared with the other sequences. Data from Test 1 were analysed using paired t-tests. Statistical significance was defined as a P-value <0·05 (two-sided).

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References

Baseline examination

All subjects were healthy, had no record of present or former clinical significant disease, and were not using any medication. They had no clinically significant arrhythmias or other abnormalities in the ECG during the baseline recording. No abnormalities were found in the physical examinations or in the laboratory analyses.

Laboratory values

Electrolytes were within normal ranges in all tests. The mean value of S-glucose increased between 1·1 and 4·4 mmol l−1 from baseline to 30 min after consuming the energy drink. Caffeine increased with a mean value of 1·5 μg g−1, 2 h after intake of the energy drink. For ethanol, maximum serum levels were approximately 0·4 ‰ after intake of 0·07–0·11 l of vodka (40% volume of ethanol). No subject felt intoxicated; the alcohol concentrations disappeared within 2 h.

Electrocardiogram

Table 2 shows PQ time, QRS duration, and QTc time measured immediately before the test, measured before exercise (after 30 min rest), and measured immediately after exercise. ECG data from baseline and 30 min after intake of energy drink showed similar results in both ED and the first test without exercise (therefore data from the first test are not shown).

Table 2.   Twelve-lead ECG measures before the test, before maximal bicycle ergometer exercise (30 min. after intake in ED/ET and ED), and immediately after exercise.
 Exercise (EX)Energy drink and exercise (ED)Energy drink, exercise and alcohol (ED/ET)
  1. Data shown are mean value (SD).

  2. *P<0·05 when compared with the test with only physical exercise (derived from ANOVA for repeated measurements).

PQ time (ms)
 Before test142 (21)140 (20)
 Before exercise143 (20)154 (23)*158 (22)*
 After exercise129 (17)126 (24)141 (34)
QRS duration (ms)
 Before test96 (10)94 (12)
 Before exercise94 (12)98 (12)98 (14)
 After exercise98 (14)100 (14)99 (16)
QTc time (ms)
 Before test423 (19)413 (11)
 Before exercise 412 (25)423 (18)422 (20)
 After exercise400 (28)391 (13)406 (28)

PQ time was higher before exercise in both ED/ET and ED, compared with PQ before exercise in EX (P = 0·04 for interaction test versus time). QTc was statistically significantly reduced after exercise in all three tests (P = 0·02 for time). Unspecific T-wave changes were found in six subjects (one of five men and five of five women) after they consumed energy drinks. In six subjects (two men and four women), T-wave changes occurred after they consumed energy drink mixed with alcohol but before the ergometer test.

Heart rate variability before and after intake of the energy drink

Table 3 shows HRV data from 10-min sequences before and 30 min after intake of energy drink in the first test. Compared to the baseline value, PLF/PHF was statistically significantly decreased 30 min after intake of energy drink. There was also a tendency to increased PHF after intake of energy drink.

Table 3.   Heart rate variability before and after intake of energy drink (first test without exercise).
 Before intake30 min after intake of energy drinkP-value
  1. Data shown are mean value (SD).

  2. HR, heart rate; PTOT, total power; PLF, power of low frequency component; PHF, power of high frequency component.

HR (beats/min)68·2 (10·6)69·8 (11·4)0·38
PTOT (ms2, log)3·78 (0·38)3·83 (0·40)0·44
PLF (ms2, log)3·24 (0·34)3·21 (0·32)0·67
PHF (ms2, log)3·01 (0·53)3·11 (0·52)0·07
PLF/PHF0·22 (0·36)0·10 (0·32)0·03

Post-exercise heart rate recovery

Figure 1 shows examples of HRR curves from one participant who had a slower post-exercise heart recovery after intake of alcohol + energy drink than after exercise without intake of any drink. The following statistically significant differences were found when average HRR data were compared (Table 4): Final HR was higher in ED/ET and ED than in EX; T was higher in ED/ET than in EX. No statistically significant differences were found in peak heart rate.

image

Figure 1.  Heart rate recovery in one subject who had delayed post-exercise heart rate recovery after intake of alcohol and energy drink (bottom) as compared to after exercise without any intake of energy drink or alcohol (top).

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Table 4.   Post exercise heart rate recovery.
 Exercise (EX)Energy drink and exercise (ED)Energy drink, exercise and alcohol (ED/ET)ANOVA P-valuePost-hoc P-value ED versus EXPost-hoc P-value ED/ET versus EX
  1. Data shown are mean value (SD).

  2. Peak HR, heart rate at the end of the exercise; Final HR, heart rate 300 s after end of exercise; T, decay constant.

Peak HR (beats/min)173·8 (11·1)172·9 (7·6)172·2 (19·0) 0·97
Final HR (beats/min)98·8 (4·2)104·5 (8·2)104·3 (7·2) 0·030·030·02
T (s)53·6 (10·9)59·5 (15·4) 72·3 (20·5) 0·020·150·02

No subject had any severe cardiac arrhythmia in any recording. One subject had frequent premature atrial contractions in the recording from ED, starting approximately 10 min after energy drink intake and lasting for 40 min.

Heart rate variability before and after maximal bicycle ergometer exercise

Figures 2 and 3 show average HRV data from different 2-min sequences during the 6-min period before start of exercise, and during approximately 30 min of recovery after exercise. The non-stationary initial part of the recovery phase (the first 4 min) was excluded from statistical analysis of HRV data, because of the rapid change in heart rate.

image

Figure 2.  Heart rate (top) and total heart rate variability (bottom) before and after exercise with and without intake of energy drink and/or alcohol. Error bars represent means and SEM.

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image

Figure 3.  Low-frequency (top) and high-frequency (bottom) components of heart rate variability before and after exercise with and without intake of energy drink and/or alcohol. Error bars represent means and SEM.

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Before onset of exercise, PLF/PHF was statistically significantly higher in ED than in EX (P = 0·03), and HR was higher in ED/ET than in EX (P = 0·01).

Heart rate variability was decreased after maximal bicycle ergometer exercise in all tests, as compared with before exercise. The HRV reduction was seen in all participants and was even more pronounced with intake of energy drink mixed with alcohol before exercise (ED/ET) as compared with exercise only (EX). During recovery, the following statistically significant differences were found: heart rate was higher in both ED/ET and ED than in EX (P = 0·001); total power, PLF and PHF were lower in ED/ET than in EX (P = 0·01); PLF and PLF/PHF were lower in ED than in EX (P = 0·05). Reported P-values refer to statistically post-hoc tests for variables with significant main effects as derived from ANOVA. No statistically significant interaction was found between test and time.

After exercise, HRV gradually increased but did not reach the pre-exercise values within the analysed 30-min period. The heart rate remained elevated after the exercise in all tests.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References

The study investigated whether consumption of energy drinks – alone or in combination with maximal bicycle ergometer exercise with and without consumption of alcohol – caused any changes in the ECG or in HRV in healthy volunteers. No signs of any clinically significant arrhythmia were found in any of the tests, but small ECG changes were found that may be related to the consumption of energy drink and alcohol. The main finding was that consumption of energy drink mixed with alcohol influenced both the post-exercise recovery in heart rate and in HRV.

We have not found any previous studies linking the combination of taurine, caffeine and alchohol to changes in HRV. Taurine moderates the flow of cations, especially calcium, across the cell membranes, protecting the heart muscle from both high and low serum calcium concentrations (Huxtable, 1992; Schaffer & Azuma, 1992). Caffeine increases vagal autonomic nerve activity in resting subjects (Hibino et al., 1997; Yeragani et al., 2005). The intake of caffeine before exercise has also been associated with exaggerated vagal withdrawal during post-exercise recovery because of higher baseline level of vagal activity before exercise(Yeragani et al., 2005) There is also evidence that caffeine can improve physical performance (Doherty, 1998; Laurent et al., 2000; Cox et al., 2002). Our study showed a decreased PLF/PHF and a tendency to increased PHF, most likely reflecting an increased vagal modulation, when subjects were resting after consuming energy drinks.

Physical exercise reduces HRV, noted as a decreased parasympathetic and an increased sympathetic activity (Javorka et al., 2003), leading to an increase of heart rate, stroke volume, and myocardial contractility. After cessation of exercise, heart rate rapidly declines due to a vagal reactivation, which also results in successively increased HRV (Imai et al., 1994). In our study, all subjects had a reduced HRV during recovery after maximal bicycle ergometer exercise, independent of heart rate, as compared with HRV during the rest period. This reduction – signalling a reduced parasympathetic tone or the predominance of sympathetic over vagal stimulation – was enhanced when energy drink and alcohol was consumed before exercise.

Although no subject developed any significant arrhythmias during post-exercise recovery, we hypothesise that in predisposed individuals the blunted vagal reactivation, caused by the combined intake of energy drink and alcohol, might be arrhythmogenic. Reduced HRV has been linked to the degree of autonomic neuropathy in diabetic patients and linked with the risk for sudden death (Ewing et al., 1985, 1991). The relative risk of sudden cardiac death (SCD) is increased following vigorous physical exercise (Kohl et al., 1992; Alberti et al., 2000). Therefore, subjects having an inability to increase vagal activity could have an increased risk for sudden death during post-exercise recovery (Jouven et al., 2005). The majority of people who die because of SCD have a pre-existing disease; more than half of these cases have hypertrophic cardiomyopathy or coronary anomalies (Maron et al., 1996). A substantial number, however, die without receiving a definite diagnosis. In these cases, a genetic disorder causing a fatal arrhythmia could have existed. As most of these diagnoses only can be made by ECG analysis ante-mortem, it is not known whether the reported deaths after energy drink intake were afflicted by any of these diseases.

Intake of an energy drink alone appeared to increase vagal activity during rest in the supine position: On the other hand, intake of energy drink resulted in slower vagal reactivation after exercise, as compared to exercise alone. Although the pattern in post-exercise HRR mainly has been associated with vagal reactivation, the time constant of the exponential decay has been associated with sympathetic withdrawal (Buchheit et al., 2007). Therefore, our findings could also reflect delayed sympathetic withdrawal, probably due to stimulant effect of the energy drink.

The results showed changes in the standard ECG. The consumption of energy drink and alcohol caused an increase in PQ time. This finding indicates that electrophysiological changes are induced by the amount of energy drink and alcohol consumed. As the impact on the heart from the combination energy drink/alcohol/exercise was unknown, for ethical reasons, the limit of blood alcohol concentration was decided to not exceed 0·5%. Moreover, because this pilot study included only 10 healthy volunteers, further larger studies are needed to confirm our results.

In conclusion, we found no clinically significant arrhythmias in any part of our studies. Maximal bicycle ergometer exercise after consuming an energy drink and alcohol, led to delayed heart rate recovery with decreased HRV, as compared to recovery after only exercise. Physical exercise causes a parasympathetic withdrawal and an increased sympathetic activity, and the risk of arrhythmias is increased after physical exercise. This risk could be further accentuated with the intake of an energy drink and alcohol as this causes a blunted cardiac autonomic control. The arrhythmia risk is probably of most concern for predisposed individuals – such as individuals with congenital or other arrhythmia-causing disorders or for individuals with cardiac autonomic dysfunction.

Conflict of interest

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References

The authors have no associations that may pose a conflict of interest concerning the submitted article.

Acknowledgments

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References

The study was supported by grants from the Norrbotten County Council and the National Food Administration. We have much appreciated the skilful technical assistance of Julia Marainen, R.N., and the staff at the Intensive Care Unit, Kiruna District Hospital, Kiruna, Sweden. We also thank Per Holmgren for chemical analyses, and Rolf Hörnsten for analyses of Holter-ECG recordings.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conflict of interest
  8. Acknowledgments
  9. References
  • Alberti C, Mittleman M, Chae C, Lee I, Hennekens C, Manson J. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med (2000); 343: 13551361.
  • Baum M, Weiss M. The influence of a taurine containing drink on cardiac parameters before and after exercise measured by echocardiography. Amino acids (2001); 20: 7582.
  • Bazett H. An analysis of the time-relations of electrocardiograms. Heart (1920); 7: 353367.
  • Buchheit M, Papelier Y, Laursen PB, Ahmaidi S. Noninvasive assessment of cardiac parasympathetic function: postexercise heart rate recovery or heart rate variability? Am J Physiol (2007); 293: H8H10.
  • Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med (1999); 341: 13511357.
  • Cox GR, Desbrow B, Montgomery PG, Anderson ME, Bruce CR, Macrides TA, Martin DT, Moquin A, Roberts A, Hawley JA, Burke LM. Effect of different protocols of caffeine intake on metabolism and endurance performance. J Appl Physiol (2002); 93: 990999.
  • Doherty M. The effects of caffeine on the maximal accumulated oxygen deficit and short-term running performance. Int J Sport Nutr (1998); 8: 95104.
  • Every NR, Hallstrom AP, McDonald KM, Parsons L, Thom DH, Weaver WD, Hlatky MA. Risk of sudden versus nonsudden cardiac death in patients with coronary artery disease. Am Heart J (2002); 144: 390396.
  • Ewing DJ, Martin CN, Young RJ, Clark BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care (1985); 8: 491498.
  • Ewing DJ, Neilson JM, Shapiro CM, Steward TJ, Reid W. Twenty-four hour heart rate variability: effects of posture, sleep and time of day in healthy controls and comparison with bedside tests of autonomic function in diabetic patients. Br Heart J (1991); 65: 239244.
  • Ferreira SE, De Mello MT, Rossi MV, Souza-Formigoni ML. Does an energy drink modify the effects of alcohol in a maximal effort test? Alcohol Clin Exp Res (2004); 28: 14081412.
  • Finnegan D. The health effects of stimulant drinks. Br Nutr Found Nutr Bull (2003); 28: 147155.
  • Gorelik DD, Hadley D, Myers J, Froelicher V. Is there a better way to predict death using heart rate recovery? Clin Cardiol (2006); 29: 399404.
  • Hibino G, Moritani T, Kawada T, Fushiki T. Caffeine enhances modulation of parasympathetic nerve activity in humans: quantification using power spectral analysis. J Nutr (1997); 127: 14221427.
  • Huxtable RJ. Physiological actions of taurine. Phys Rev (1992); 72: 101163.
  • Imai K, Sato H, Hori M, Kusuoka H, Ozaki H, Yokoyama H, Takeda H, Inoue M, Kamada T. Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure. J Am Coll Cardiol (1994); 24: 15291535.
  • Javorka M, Zila I, Balharek T, Javorka K. On- and off-responses of heart rate to exercise – relations to heart rate variability. Clin Physiol Funct Imaging (2003); 23: 18.
  • Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetiere P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med (2005); 352: 19511958.
  • Kohl HW, Powell K, Gordon NF, Blair SN, Paffenbarger RJ. Physical activity, physical fitness, and sudden cardiac death. Epidemiol Rev (1992); 14: 3758.
  • Lagarias JC, Reeds JA, Wright MH, Wright PE. Convergence properties of the Nelder-Mead simplex method in low dimensions. SIAM J Optim (1998); 9: 112147.
  • Laurent D, Schneider KE, Prusaczyk WK, Franklin C, Vogel SM, Krssak M, Petersen KF, Goforth HW, Shulman GI. Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise. J clin endocrinol metab (2000); 85: 21702175.
  • Lehtihet M, Beckman Sund U, Andersson DEH. Energidryck – farligt eller inte? Fall med svåra symtom har möjligt samband med energidryck – fler fall efterlyses. Läkartidningen (2006); 103: 27382741.
  • Maron BJ, Thompson PD, Puffer JC, McGrew CA, Strong WB, Douglas PS, Clark LT, Mitten MJ, Crawford MH, Atkins DL, Driscoll DJ, Epstein AE. Cardiovascular preparticipation screening of competitive athletes. A statement for health professionals from the Sudden Death Committee (clinical cardiology) and Congenital Cardiac Defects Committee (cardiovascular disease in the young), American Heart Association. Circulation (1996); 94: 850856.
  • Nordenfelt L, Adolfsson L, Nilsson JE, Olsson S. Reference values for exercise tests with continuous increase in load. Clin Physiol (1985); 5: 161172.
  • Schaffer S, Azuma J. Review: myocardial, physiological effects of taurine and their significance. In: Taurine, Nutritional Value and Mechanisms of Action (eds Lombardini, JB, Schaffer, S, Azuma, J). (1992), pp. 245251. Plenum Press, New York.
  • Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur Heart J (1996); 17: 354381.
  • Wolf MM, Varigos GA, Hunt D, Sloman JG. Sinus arrhythmia in acute myocardial infarction. Med J Aust (1978); 2: 5253.
  • Yeragani VK, Krishnan S, Engels HJ, Gretebeck R. Effects of caffeine on linear and nonlinear measures of heart rate variability before and after exercise. Depress Anxiety (2005); 21: 130134.