Endothelial function plays an important role in circulatory physiology. There has been differing reports on the effect of energy drink on endothelial function. We set out to evaluate the effect of 3 energy drinks and coffee on endothelial function. Endothelial function was evaluated in healthy volunteers using a device that uses digital peripheral arterial tonometry measuring endothelial function as the reactive hyperemia index (RHI). Six volunteers (25 ± 7 years) received energy drink in a random order at least 2 days apart. Drinks studied were 250 ml “Red Bull” containing 80 mg caffeine, 57 ml “5-hour Energy” containing 230 mg caffeine, and a can of 355 ml “NOS” energy drink containing 120 mg caffeine. Sixteen volunteers (25 ± 5 years) received a cup of 473 ml coffee containing 240 mg caffeine. Studies were performed before drink (baseline) at 1.5 and 4 hours after drink. Two of the energy drinks (Red Bull and 5-hour Energy) significantly improved endothelial function at 4 hours after drink, whereas 1 energy drink (NOS) and coffee did not change endothelial function significantly. RHI increased by 82 ± 129% (p = 0.028) and 63 ± 37% (p = 0.027) after 5-hour Energy and Red Bull, respectively. The RHI changed after NOS by 2 ± 30% (p = 1.000) and by 7 ± 30% (p = 1.000) after coffee. In conclusion, some energy drinks appear to significantly improve endothelial function. Caffeine does not appear to be the component responsible for these differences.
Energy drinks are consumed by millions, and consumption has been anecdotally linked to the development of adverse cardiovascular events, although clinical trials to support this association are lacking. Some studies report an increase in heart rate, whereas a number of studies did not report an increase in heart rate. Some report an increase in blood pressure, whereas others did not. Limited number of studies evaluated the effect of energy drinks on endothelial function. Noninvasive measurements of endothelial function may be considered a surrogate for the measurement of coronary blood flow.
The aim of this study was to evaluate the effect of 3 commonly consumed energy drinks on endothelial function using a standard consistently applied methodology. As the main active ingredient of energy drinks is caffeine, to place the observed changes in context, comparison was made to coffee, a drink with a substantial caffeine content.
Methods
The study was performed in the Clinical Testing Center of the American Institute of Therapeutics (Laker Bluff, Illinois). The study received institutional review board approval, and each participant gave written informed consent. A total of 19 healthy volunteers were recruited (8 women and 11 men): 10 Caucasian, 4 Hispanic, 4 Asian, and 1 Native American. Mean age was 24 ± 5 years, weight 72 ± 12 kg, height 168 ± 12 cm, systolic blood pressure 116 ± 11 mm Hg, and diastolic blood pressure 74 ± 10 mm Hg. None of the volunteers were smokers. To be eligible for the study, participants had to be in the age range of 18 to 35 years with no clinically important findings on medical history, 12-lead electrocardiogram, and physical examination, having body weight from 54 to 79 kg (120 to 175 pounds) for women and from 64 to 90 kg (140 to 200 pounds) for men, heart rate from 60 to 88 beats/min and blood pressure from 95 to 130 mm Hg systolic and 55 to 88 mm Hg diastolic after sitting for 5 minutes. Pregnancy, taking birth control pills, being on prescription medications, use of illegal drugs, having allergy to coffee, or any known components of the energy drinks were reasons for exclusion from the study.
This study was a single-center, open-label trial. The effects of energy drinks were evaluated in 6 volunteers (3 men and 3 women, age 25 ± 7 years, weight 71 ± 16 kg, and height 168 ± 12 cm). Four of the 6 volunteers were energy drink naive. Three consumed 1 cup coffee and 1 consumed 2 cups of coffee a day. Two volunteers did not consume any other caffeinated products, whereas 4 did occasionally. The following energy drinks were evaluated: (1) a can of 250 ml (8.4 oz) Red Bull Energy Drink containing 80 mg caffeine, (2) 57 ml (1.93 oz) “5-hour Energy,” extra strength, sugar-free drink containing 230 mg caffeine, and (3) a can of 355 ml (12 oz) “NOS” high-performance energy drink containing 120 mg caffeine. Participants were randomized to the sequence of drinks to be consumed. The shortest time between study days was at least 2 days.
The effect of coffee on endothelial function was evaluated in 16 volunteers (3 of them also participated in the energy drink evaluations). The volunteers consumed a cup of 473 ml (16 oz) Starbuck’s K-cup Breakfast Bland coffee (2 K-cups in 16 oz water) containing 240 mg caffeine. The mean age of these 16 participants was 25 ± 5 years, gender 7 women and 9 men, body weight 72 ± 11 kg, and height 169 ± 10 cm. Energy drink naive were 13 of the 16 volunteers, 10 consumed coffee on a daily basis and 6 were not coffee drinkers. Other source of caffeine intake (i.e., tea, Coca, or Pepsi Cola, etc.) was more common in 12 of the 16 volunteers.
On each study day, the effect of the study drink on endothelial function was evaluated by digital peripheral arterial tonometry (PAT) using the EndoPAT device (Itamar Medical, Caesarea, Israel). The method is based on a 5-minute occlusion of the brachial artery using a standard blood pressure cuff and quantifying the endothelium-mediated changes in vascular tone by comparing pre-occlusion and post-occlusion measurements through changes in finger arterial pulsewave amplitude from pre-occlusion to post-occlusion using digital PAT signals. The PAT signals were collected from both index fingers by the EndoPAT device, which automatically calculates a single measurement of the endothelial function, the reactive hyperemia index (RHI). The RHI is the post- to pre-occlusion PAT signal ratio in the occluded side, normalized to the control side, and further corrected for baseline vascular tone. This method will be referred to as PAT and the measurement as RHI in this study. This technique has been extensively used to evaluate endothelial function, has been validated, and the subject of a supporting editorial comment.
Participants had to be fasting from midnight the night before the study day, and no water consumption was allowed 2 hours before entering the study. Smoking was not allowed. No “soft drinks,” no coffee or tea, no hot chocolate, or other caffeinated products were permitted 24 hours before and during a study day. On the study day, a physical and brief history was taken that included discussing any clinically significant events since the pre-study screening and determining compliance with study restrictions.
The evaluations were undertaken in a closely monitored quiet test environment. Care was taken to maintain an ambient room temperature of 21°C to 24°C (70°F to 75°F) with dimmed lighting during the procedure. Blood pressure was measured from the leg as measurement in either arm could affect the result of endothelial function. PAT probes measuring digital pulse amplitude were placed on both index fingers. After a 6-minute baseline measurement, a 5-minute occlusion of the brachial artery of the nondominant arm was used at 220 mm Hg pressure. After the 5-minute occlusion, the cuff was deflated and PAT signals were measured for an additional 6 minutes. At the end of the measurements, EndoPAT automatically calculated the RHI.
The RHI was determined in each subject after 30 minutes of rest at baseline. After energy drink (consumed over >15 to 30 minutes), the RHI was determined at 1.5 and 4 hours. The end points of 1.5 and 4 hours were selected based on our previous experience. Additional time points were not measured because of the limited number of artery occlusions that can be performed without modifying endothelial hyperemic response.
Statistical analysis was performed by IBM SPSS Statistical program (version 22, IBM Corporation, Pittsburgh, PA). Statistical analysis consisted of computation of means and SDs for continuous variables and frequencies for categorical variables. Changes from baseline in continuous variables (i.e., RHI) after a study drink were analyzed by repeated-measures analysis of variance. For post hoc pairwise multiple comparisons, the Bonferroni test was used. Each variable was tested for normal distribution using the Kolmogorov-Smirnov and Shapiro-Wilk tests of normality. When data did not show normal distribution, nonparametric test was performed (Wilcoxon signed-ranks test). To increase the sensitivity of the testing, percent changes from baseline measurements were analyzed. Differences in continuous variables between the study drinks were analyzed by repeated-measures of analysis of variance. A 2-sided alpha error of p <0.05 was considered statistically significant.
Results
The RHI was obtained at baseline (before study drink) and at 1.5 and 4 hours with the results listed in Table 1 . There were significant differences between the study drink effects on endothelial function. The effects of 5-hour Energy and Red Bull were similar. Compared with baseline, endothelial function significantly improved after 5-hour Energy at 1.5 hours (RHI increased from 1.58 ± 0.54 to 2.37 ± 0.50, p = 0.008). After Red Bull, endothelial function significantly improved at 4 hours (RHI increased from 1.47 ± 0.35 to 2.31 ± 0.45, p = 0.009). Compared with baseline, NOS showed no significant change in RHI at 1.5 hours (p = 0.981) or at 4 hours (p = 1.000). Similarly, compared with baseline, coffee resulted in no significant change in RHI either at 1.5 hours (p = 1.000) or at 4 hours (p = 1.000, Table 1 ).
| Time | 5-Hour Energy | Red Bull | NOS | Coffee | ||||
|---|---|---|---|---|---|---|---|---|
| Mean ± SD | p | Mean ± SD | p | Mean ± SD | p | Mean ± SD | p | |
| Baseline | 1.58 ± 0.54 | 1.47 ± 0.35 | 1.60 ± 0.45 | 1.82 ± 0.48 | ||||
| 1.5 hour | 2.37 ± 0.50 | 0.008 | 2.12 ± 0.76 | 0.104 | 1.78 ± 0.40 | 0.981 | 1.91 ± 0.51 | 1.000 |
| 4 hours | 2.48 ± 0.80 | 0.228 | 2.31 ± 0.45 | 0.009 | 1.57 ± 0.41 | 1.000 | 1.88 ± 0.36 | 1.000 |
To account for individual differences in baseline measurements and the magnitude of changes in RHI, percent change from baseline were calculated at 1.5 and 4 hours in each subject after study drink ( Table 2 ). Compared with baseline, the greatest improvement in endothelial function was seen at 4 hours after 5-hour Energy and Red Bull ( Figure 1 ). After 5-hour Energy, RHI increased by 82 ± 129% (p = 0.028). After Red Bull, RHI increased by 63 ± 37% (p = 0.027). NOS resulted in no significant changes in RHI either at 1.5 hours (p = 1.000) or at 4 hours (p = 1.000). Similarly, coffee resulted in no significant changes in RHI at 1.5 hours (p = 0.935) or at 4 hours (p = 1.000). Multiple pairwise comparisons of the drinks showed no difference between 5-hour Energy and Red Bull (p = 0.491) and between NOS and coffee (p = 0.943). However, both the 5-hour Energy and Red Bull significantly differed from NOS and coffee (5-hour Energy vs NOS, p = 0.016; 5-hour Energy vs coffee, p = 0.004; Red Bull vs NOS, p = 0.028; and Red Bull vs coffee, p = 0.028).
| A. | 5-hour Energy | Red Bull | NOS | Coffee | ||||
|---|---|---|---|---|---|---|---|---|
| Time | Mean ± SD | p | Mean ± SD | p | Mean ± SD | p | Mean ± SD | p |
| Baseline | 0 ± 0% | 0 ± 0% | 0 ± 0% | 0 ± 0% | ||||
| 1.5 hour | 58 ± 36% | 0.028 | 44 ± 31% | 0.052 | 16 ± 38% | 1.000 | 8 ± 29% | 0.935 |
| 4 hours | 82 ± 129% | 0.028 | 63 ± 37% | 0.027 | 2 ± 30% | 1.000 | 7 ± 30% | 1.000 |
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