Table 2.
Clinical trials of energy drinks and related electrophysiological and ischemic abnormalities (36–54).
| Author, Year (Country) | Patient population, age* | Study design | Sample size | Energy drink (volume) | Control drink (volume) | Assessment duration | Electrophysiological endpoints† | Outcomes |
|---|---|---|---|---|---|---|---|---|
| Basrai et al., 2019 (38) (Germany) | Healthy, 18–25 y | R, DB, C, P, & CO | 38 | Red Bull (750 ml, 1,000 ml) | Non-caffeinated control drink (750, 1,000 ml) [CP] Non-caffeinated control drink with taurine (75, 1,000 ml) [CP + T] Caffeinated control drink (750, 1,000 ml) [CP + C] Caffeinated control drink with taurine (1,000 ml) [CP + C + T] Non-caffeinated control drink with glucuronolactone (1,000 ml) [CP + G] |
11 h | BP, HR, QTc | QTc prolongation at 1 h compared to control [8 ± 17 ms vs. 2 ± 15 ms (CP), 1 ± 16 ms (CP + C), −3 ± 17 ms (CP + T), −9 ± 16 ms (CP + C + T), and −9 ± 19 ms (CP + G), P = 0.0021] QTc shortened after 1 h compared to the baseline in the CP + C + T and CP + G group (p < 0.05) HR increased at 1 h compared to control [3.5 vs. 0 bpm (CP), 0 bpm (CP + C), 1.0 bpm (CP + T), −1.0 bpm (CP + C + T), and −1.0 bpm (CP + G), p = 0.017] No arrhythmias |
| Shah et al., 2019 (51) (United States) | Healthy, 22 ± 3 y | R, DB, PC, CO | 34 | Unstated caffeinated energy drink A (32 oz) Unstated caffeinated energy drink B (32 oz) | Non-caffeinated control drink (32 oz) | 240 min | QTcB, QTcF, QT, PR, QRS, HR | Maximum change from baseline in QTcB for Drink A and Drink B were higher than placebo (18 ± 14 ms, 20 ± 16 ms, and 12 ± 11 ms, for Drink A, Drink B, and placebo, respectively, p = 0.005) Maximum change from baseline in QTcF for Drink A and Drink B were higher than placebo (15 ± 12 ms, 15 ± 12 ms, and 7 ± 7 ms, for Drink A, Drink B, and placebo, respectively, p < 0.001) Two participants had a change from baseline in QTcB of >50 ms with Drink A and Drink B No significant change in PR, QRS, and HR |
| McGaughey et al., 2018 (46) (United States) | Heathy, 26 y | R, DB, C, CO | 1 | Unstated caffeinated energy drink (32 oz) with placebo capsule | Placebo drink (32 oz) with moxifloxacin 400 mg ×1 Placebo drink (32 oz) with placebo capsule | 6 h | QTcB, QTcF, QT, PR, QRS, HR | Maximum baseline-adjusted, placebo-corrected, change in QTcB was 29 and 12 ms with energy drink and moxifloxacin, respectively |
| Brothers et al., 2017 (39) (United States) | Healthy, 27 ± 4 y | R, DB, PC, CO | 15 for each protocol |
Protocol 1: Monster (2 mg caffeine/kg) Monster (3 mg caffeine/kg) Protocol 2: Monster (16 oz) Monster (24 oz) |
Protocol 1: Keurig K-cup (2 mg caffeine/kg) Water (250 ml) Protocol 2: Keurig K-cup (1 packet) Volume unknown Water (250 ml) |
6.5 h | QTcB, HR | No statistically significant difference in QTcB and HR in both protocols |
| Fletcher et al., 2017 (41) (United States) | Healthy, 27 ± 4 y | R, DB, C, CO | 18 | Unstated caffeinated energy drink (946 ml) | Caffeine-matched control drink (946 ml) | 24 h | QTc, QT, PR, QRS, HR | QTc prolongation 2 hrs after ED consumption when compared to caffeine control (0 ± 18 ms vs. −10 ± 15 ms; p = 0.02) No statistically significant difference in QT, PR, QRS and HR |
| Garcia et al., 2017 (42) (Columbia) | Healthy, 21 ± 2 y | R, DB, P, PC | 80 | Unstated caffeinated drink A (460 ml) Unstated caffeinated drink B (460 ml) Unstated caffeinated drink C (460 ml) |
Carbonated water (460 ml) | 1 h | QTc, PR, QRS, HR, T wave amplitude | Shortening of QTc in group B after drink intake Percent change in QTc not different in any groups compared to control No other significant ECG parameter changes Percent increase in HR was significant in A and C groups compared to control (p = statistically significant) |
| Gray et al., 2017 (43) (Australia) | LQTS, 29 ± 9 y | R, DB, PC, CO | 24 | Red Bull (500 ml) | Non-caffeinated control drink (500 ml) | 90 min | QTcB, HR | No statistically significant change in QTcB and HR 3 patients had QTcB changes ≥50 ms No arrhythmias |
| Tauseef et al., 2017 (53) (Pakistan) | Healthy, 19–21 y | R, C, P | 30 | Red Bull (500 ml) [High dose] Red Bull (250 ml) [Low dose] |
No drink | 2 h | QTc, HR | Statistically significant increase in QTc at 2 h: High dose ED vs. low dose ED (difference of 9 ± 3 ms; p = 0.038); high dose ED vs. control (difference of 13 ± 3 ms; p = 0.002) Statistically significant increase in HR at 1 and 2 h with high dose ED when compared to other groups (p ≤ 0.015 for all comparisons) |
| Hajsadeghi et al., 2016 (44) (Iran) | Healthy, 23 ± 4 y | OL, NC | 44 | Unstated caffeinated energy drink (250 ml) | N/A | 4 h | QTc, PR, QRS, ST-T changes, HR | No changes in PR, QRS, and QTc from baseline More frequent ST-T changes from baseline (p = 0.004) Significant reduction in HR at all times compared to baseline (p ≤ 0.043 for all comparisons) |
| Kozik et al., 2016 (45) (United States) | Healthy, 29 y | OL, NC | 14 | Monster (946 ml) | N/A | 4 h | QTcB, HR | Significant increase in maximum QTcB interval (baseline = 423 ± 23; post ED = 503 ± 25; p < 0.001) Maximum QTcB prolongation >500 ms: 8/14 subjects Maximum QTcB prolongation >50 ms from baseline: 8/12 subjects (missing baseline QTcB in 2 subjects) T-wave changes: 9/14 subjects |
| Shah et al., 2016 (48) (United States) | Healthy, 38 y | OL, C | 24 | 5-H Energy (60 ml daily) | No drink | 2 h (with exercise ECG stress test) | QTc, PR, QRS, HR, arrhythmias | QTc prolonged significantly before and after ED (412 to 434 ms; p ≤ 0.001) No change in PR, QRS, or HR No arrhythmias |
| Shah et al., 2016 (49) (United States) | Healthy, 22 ± 3 y | R, DB, PC, CO | 27 | Unstated caffeinated energy drink (946 ml) | Non-caffeinated control drink (946 ml) Non-caffeinated control drink with Panax Ginseng (946 ml) |
5.5 h | QTcB, PR interval, QRS duration, QT, HR | QTcB prolongation 2 h after ED consumption when compared to placebo-control (3 vs. −3 ms respectively; p = 0.03) PR interval significantly decreased after ED consumption compared to placebo at 1 h and ginseng control at 1 and 2 h (p ≤ 0.025 for all comparisons) No significant changes in QRS, QT, HR. |
| Shah et al., 2016 (49) (United States) | Healthy, 28 ± 6 y | R, DB, PC, CO | 26 | 5-H Energy (60 ml twice daily for 7 days) | Non-caffeinated control drink (60 ml) | 5 h on days 1 and 7 | QTcB, QT, PR, QRS, HR | No significant change in QTcB, PR, QRS, and HR after single ED shot or chronic consumption |
| Alsunni et al., 2015 (36) (Saudi Arabia) | Healthy, overweight/obese, 21 ± 1 y | OL, NC | 31 | Unstated caffeinated energy drink (5 ml/kg) | N/A | 1 h | QTcB, ECG, HR variability | QTcB significantly increased in the overweight/obese group after ED consumption (357 ± 54 ms to 340 ± 57 ms, p = 0.006) No changes in QTcB in the normal weight group HR variability (as indicated by the expiratory to inspiratory ratio, the mean heart rate range, and the mean percentage variability) was significantly less in overweight/obese as compared with normal weight after ED consumption (p ≤ 0.04 for all comparisons) |
| Elitok et al., 2015 (40) (Turkey) | Healthy, 25 ± 2 y | OL, NC | 50 | Red bull (355 ml) | N/A | 2 h | QTcB, Tp-e interval, Tp-e/QTc ratio, PR, QRS, HR | No significant change with QTcB, PR, QRS, Tp-e related parameters after ED consumption HR significantly increased after ED consumption at 1 h (78 ± 15 to 84 ± 12 bmp, p = 0.008) and 2 h (78 ± 15 to 85 ± 11 bmp, p = 0.005) |
| Arinc et al., 2013 (37) (Turkey) | Healthy, >17 y | OL, NC | 20 | Red bull (250 ml) | N/A | 2 h | QTcB, p-wave dispersion, QT dispersion, HR | No significant changes in QTcB, p-wave dispersion, QT dispersion, and HR after ED consumption |
| Ragsdale et al., 2010 (47) (United States) | Healthy, 20 ± 2 y | DB, PC, P | 68 | Red bull (250 ml, normal calorie) Red bull (250 ml, low calorie) |
Non-caffeinated control drink (250 ml, normal calorie) Non-caffeinated control drink (250 ml, low calorie) |
2 h | ECG (QTc, QT), consecutive NSR that exceed 50 ms, % RR with intervals > 50 ms, QRS, ST, count of t-wave inversion, HR, HR variation | No significant change in QTc, QRS, ST, T-wave inversion count, and HR |
| Steinke et al., 2009 (52) (United States) | Healthy, 26 ± 6 y | OL, NC | 15 | Unstated caffeinated energy drink (500 ml daily ×7 days) | N/A | 4 h on days 1 and 7 | ECG parameters (QTcB & QTcF), HR | No significant change in QTcB and QTcF with ED consumption on days 1 and 7 ~QTcB trending toward significance on day 7 (20 ms, p = 0.052) HR increased significantly after ED consumption on days 1(7.8%, p = 0.009) and 7 (11%, p < 0.001) |
| Wiklund et al., 2009 (54) (Sweden) | Healthy, 19–30 y | OL, C, CO | 10 | Red bull (750 ml) Red bull (750 ml with 0.4 g of ethanol/kg) |
No drink | 30 min of exercise | Changes in ECG (QTcB, PQ, QRS), HR, HR variability and recovery | No significant change in QTcB and QRS after ED consumption (alone or in combination with ethanol) Significant increase in PQ after ED consumption and before exercise (alone or in combination with ethanol, p < 0.05) No significant change in HR, but HR recovery and variability slower with ED and ethanol No arrhythmias |
R, randomized; DB, double-blind; C, controlled; P, parallel; CO, cross over; PC, placebo controlled; OL, open label; NC, non-controlled; bpm, beats per minute; ECG, electrocardiogram; ED, energy drink; HR, heart rate; LQTS, Long QT syndrome; NSR, normal sinus rhythm; O, obese; OW, overweight; Tp-e, interval from the peak to the end of the electrocardiographic T wave.
*
Age is reported as mean; mean ± standard deviation; or range.
†
QTcB, Corrected with Bazzett formula; QTcF, Corrected with Fridericia formula; QTc, Correction formula unknown.