Article, Cardiology

Cardiovascular responses to energy drinks in a healthy population: The C-energy study

a b s t r a c t

Background: energy drink consumption has increased significantly over the past decade and is associated with greater than 20,000 emergency department visits per year. Most often these visits are due to cardiovascular com- plaints ranging from palpitations to cardiac arrest.

Objective: To determine if energy drinks alter; blood pressure, electrolytes, activated bleeding time (ACT), and/or cardiac responses measured with a 12-lead electrocardiographic Holter.

Methods: Continuous ECG data was collected for five hours (30 minutes baseline and 4 hours post consumption [PC]). Subjects consumed 32 ounces of energy drink within one hour and data (vital signs and blood samples) was collected throughout the study period. Paired students t-test and a corresponding non-parametric test (Wilcoxon signed rank) were used for analysis of the data.

Results: Fourteen healthy young subjects were recruited (mean age 28.6 years). Systolic blood pressure (baseline = 132, +- 7.83; PC = 151, +- 11.21; P = .001); QTc interval (baseline = 423, +- 22.74; PC = 503,

+-24.56; P b .001); magnesium level (baseline 2.04, +- 0.09; PC = 2.13, +-0.15; P = .05); and calcium level (baseline = 9.31, +-.28; PC = 9.52, +-.22; P = .018) significantly increased from baseline. While potassium and ACT fluctuated (some subjects increased their levels while others decreased) these changes were not signif- icant. Eight of the fourteen subjects (57%) developed a QTc N 500 milliseconds PC. Other T-wave changes were noted in 9/14 (64.3%) subjects PC.

Conclusions: Energy drinks increased systolic blood pressure, altered electrolytes, and resulted in Repolarization abnormalities. These physiological responses can lead to arrhythmias and other abnormal cardiac responses highlighting the importance that emergency room personnel assess for energy drink consumption and potential toxicity.

(C) 2016

Introduction

Energy drinks are beverages containing caffeine and other herbal supplements such as Panax ginseng, guarana, and other vitamin and minerals. Each manufacturer of these drinks has their own proprietary blend of additives; ingredients are listed on the label but volumes or

? Research activities were performed at Dignity Health-St. Joseph’s Medical Center, Stockton CA.

?? This was a non-funded study. No authors have any conflicts of interest to report.

* Corresponding author at: Clinical Research Department, St. Joseph’s Medical Center, 1800 N. California Street, Stockton, CA 95204. Tel.: +1 209 329 6265, +1 209 461

5257(Office); fax: +1 209 467 6394.

E-mail address: [email protected] (T.M. Kozik).

percentages of each are not. These drinks are marketed as an aid to im- prove athletic performance, enhance concentration, and increase ener- gy and weight loss [1,2]. The first energy drink was introduced in the United States in 1997 [3] and by 2016, sales are expected to reach $52 billion [4]. Reported emergency department visits secondary to energy drinks skyrocketed from just over 1000 in 2005 to more than 20,000 in 2011 [4,5]. Most often, these visits are due to a cardiac issue ranging from rapid heart rate, palpitations, myocardial infarction, stroke, and even cardiac arrest [6-10]. Recent studies have demonstrated that ener- gy drink consumption may lead to altered platelet aggregation [11,12] altered endothelial function [12] increased systolic blood pressure and prolonged QTc intervals [6,13-15], suggesting a cardiovascular response that may lead to these pathologies.

http://dx.doi.org/10.1016/j.ajem.2016.02.068 0735-6757/(C) 2016

Table 1

Systolic blood pressure readings of all subjects

Subject #

Baseline

SBP (mmHg)

Maximum SBP (mmHg)

Time (mins) from PC of energy drink to Maximum SBP

Change in SBP (mmHg)

1

128

132

65

4

2

142

158

119

16

3

129

144

175

15

4

123

141

103

18

5

145

178

17

33

6

130

162

0

32

7

132

157

232

25

8

127

152

50

25

9

136

153

191

17

10

117

145

60

28

11

132

140

81

8

12

144

152

55

8

13

133

151

245

18

14

135

u = 132

146

u = 151

117

u = 108

11

u = 18

C-Energy study (Cardiovascular rEspoNses to EneRGy drinks in a healthy population) to determine if energy drinks alter: blood pressure, electrolytes (magnesium, potassium, calcium), activated bleeding time, and/or the ECG measured with 12-lead ECG Holter.

Table 2

QTc intervals of all subjects

Subject # Baseline QTc (mm)/Heart Rate

Maximum QTc (mm)/Heart Rate

Change QTc (mm)

Methods

This was a prospective observational study to examine cardiovascu- lar responses to energy drink consumption in healthy subjects 18-40 years old who were not energy drink naive. Subjects were excluded if they were on any prescription medications, pregnant, or had known cardiovascular, hepatic, or endocrine diseases. Prior to recruitment, ap- proval from the local institutional review board was obtained and pa- tients provided written informed consent.

Patients were enrolled Monday-Friday in a research lab located at a 337 bed, not-for-profit hospital in Stockton California. All females were tested for pregnancy prior to consumption of energy drink. Once con- sent was obtained, the 12-lead Holter recorder was applied and baseline data was collected for up to 30 minutes with subjects: [1] resting in a chair, [2] lying recumbent and [3] walking for 30 seconds. Baseline blood samples were also taken for potassium, magnesium, calcium and activated bleeding time (ACT).

For this study, Monster(R) energy drink was used which has a blend of glucose, taurine, Panax ginseng extract, L-carnitine, caffeine,

1 * 491/100 *

2 436/68 534/94 98

3 455/94 499/115 44

4 * 517/111 *

5 436/79 483/100 47

6 400/63 516/100 116

glucuronolactone, inositol, guarana extract, B-vitamins, maltodextrin, and preservatives. Once baseline data were obtained, subjects con- sumed two 16-ounce cans (32 ounces) within one hour and remained in the research lab with continuous ECG data collection for an additional four hours; completion of both cans of energy drink was the start of the

7

447/75

491/100

44

post consumption (PC) time period. During the four hour PC period,

8

405/71

509/120

104

vital signs (Blood pressure and heart rate) were taken every 30 minutes

9

439/67

516/100

77

and blood samples (potassium, magnesium, calcium, and ACT) were

10

11

12

400/60

438/65

390/79

437/88

509/88

490/115

37

71

100

collected at one, two and four hours PC and sent to the hospitals labora-

tory for analysis. Subjects were instructed to walk for 30 seconds in the

13

395/48

508/115

113

hallway just prior to or after the blood samples were obtained. This step

14

430/79

535/107

105

was done to examine cardiac responses to increased activity. Prior to

u = 423/71

u = 503/104

u = 80

discharge, blood pressure and heart rates returned to baseline, except

one subject remained an additional one hour due to an increased systol-

ic blood pressure reading.

Studies to date, have examined the electrocardiogram (ECG) at in-

cremental periods of time post energy drink consumption. We hypoth- esized that ECG changes may occur at different time periods which could lead to cardiac pathologies and conditions after the consumption of an energy drink. Little is known about the possible mechanisms seen in patients who develop serious cardiovascular conditions associated with energy drink consumption. As a first step to better understand the cardiac response to energy drink consumption, we conducted the

Analysis

The 12-lead ECG Holter data were downloaded to a research com- puter and analyzed after discharge using H-Scribe Analysis System (Mortara Instruments, Milwaukee, WI). The H-Scribe software displays hours of continuous ECG tracings (up to 24 hours) into trended data for easy inspection, and semi-automatically analyzes. While the H-Scribe

Table 3

blood levels of all subjects

Subject #

Baseline K

Greatest change K

Baseline Mag

Greatest change Mag

Baseline Calcium

Greatest change Calcium

Baseline ACT

Greatest change ACT

1

4.3

-0.2

2

0.1

9.8

-0.1

136

-15.5

2

4.5

0.3

2

0

9.4

0.1

130.5

-0.5

3

4

0.4

2.3

0.1

9.5

0.4

114

25

4

4.3

-0.5

1.9

0

9.8

0

133

6.5

5

4.2

-0.4

2

0

9

0.4

130

-6

6

4.2

-0.2

2

0.1

9.4

0

129

2.5

7

4.1

-0.3

2.1

0.2

9.1

0.3

132

-4.5

8

3.7

0.6

2

0.2

9.2

0.7

125

24

9

4.7

-0.6

2.1

-0.2

9.5

-0.2

126.5

7

10

3.6

0.5

2

0

9.2

0.1

126.5

-8.5

11

4.1

0

2

0.2

9.2

0.3

136

2.5

12

3.8

-0.4

2.1

0.2

9.3

0.1

137

-5.5

13

4.2

0

2

0.2

8.8

0.5

129.5

-4.5

14

4.1

0.5

2.1

0.1

9.1

0.4

123

6

u change =-.3

u change =.09

u change =.21

u change =28.5

P = .85

p = *.05

p = *.02

P = .51

provides semi-automated analysis, all of the ECG data were manually over read by the principal investigator (TMK).

Bazett’s formula was utilized to correct all QT intervals. Paired stu- dents t-test and a corresponding non-parametric test (Wilcoxon signed rank) were used for analysis of the data.

Results

Fourteen subjects were recruited (mean age 28.6 years; range 15), and twelve (86%) were male. All subjects completed the protocol with no adverse events. Systolic blood pressures (baseline = 132,

A B C

Figure. (A) Baseline; (B) 10 minutes post consumption of energy drinks; (C) End of study – 4 hours post energy drink consumption. Note the T-wave changes (Figure B) 10 minutes after consuming two energy drinks. Greatest effects are seen in leads II, III, aVF, V4-6.

+-7.83; PC = 151, +-11.21; P = .001) (Table 1). QTc intervals (base- line =423, +-22.74; PC = 503, +-24.56; P b .001) (Table 2); magnesium levels (baseline 2.04, +- 0.09; PC = 2.13, +-0.15; P = .05); and calcium levels (baseline =9.31, +-.28; PC = 9.52, +-.22; P = .018) significantly increased from baseline (Table 3). While potassium and ACT fluctuated (some subjects increased while others decreased), no significant chang- es were observed (Table 3). Eight of the fourteen subjects (57%) devel- oped a QTc N 500 milliseconds PC). QTc interval lengthening occurred most often with light activity (during walking). Once sitting and heart rates returned to normal resting state, QTc intervals normalized.

Other ECG changes noted were T-wave changes in 9/14 (64.3%) sub- jects. Of the nine subjects with T-wave changes, five developed flipped T-waves, nine developed flattened T-waves, and five experienced both. Mean time from start of energy drink consumption to T-wave changes was 48 minutes (SD +- 47; range 150 minutes) (see Figure).

Discussion

Energy drinks contain added caffeine and other supplements that pro- vide additional amounts of caffeine and other nervous system stimulating properties. Caffeine is a central nervous system stimulant routinely con- sumed as coffee or tea. When consumed in high doses, this chemical be- comes toxic and can result in seizures and even death [16-18]. Besides added caffeine, another supplement added to many energy drinks is Panax ginseng purported to improve alertness and memory. Several stud- ies looked at these claims, and all failed to find any connection between ginseng and energy [19-21]. Additionally, Panax ginseng has been associ- ated with health risks such as affective disorders, headache, sleep distur- bance, cardiovascular toxicity, hypertension and even fatalities [22,23]. Guarana, another substance added to energy drinks, is derived from the seeds of a South American plant and has amongst the highest concentra- tions of caffeine than any other plant (up to 6% by weight; coffee has up to 2%) [24]. Guarana has similar side effects as any other products that can cause caffeine toxicity. Interestingly, manufacturers of energy drinks are not required to list the caffeine content from supplement additives, there- fore the actual amount of caffeine in a single serving can be much higher than that listed [2] and potentially cause caffeine toxicity.

Manufacturers of energy drinks can label their products as dietary supplements which do not require premarket approval [4]. The FDA does require that serious adverse events be reported by the manufac- turers, packers, and distributors of energy drinks within 15 business days, however, the FDA must prove that a product is unsafe before it can be removed from the market [25]. Given the rapid rise in the energy drink market, emergency rooms visits, and in some cases serious events associated with their use, labeling of ingredients and actual caffeine levels from all sources should be disclosed.

In our study, we demonstrated more than 50% of the sample developed a long QTc interval with light activity after energy drink consumption. This is known as acquired Long QT syndrome (aLQTS) and is a reversible cardiac channelopathy which results from exposure to an environmental stressor such as hypothermia or Electrolyte disorders, but most often is associated with pharmacological therapies; the QT interval reverts back to normal once the stressor is removed [26-28]. aLQTS predisposes individuals to ventricular arrhythmias, in particular Torsade de pointes, a Polymorphic ventricular tachycardia which can lead to ventricular fibrillation [29,30]. With the recent reports of cardiac arrest in otherwise healthy individuals who had consumed energy drinks [7,31], this study and other studies [6,13-15] may have elucidated a potential mechanism which shows chang- es in repolarization after consuming energy drinks. Furthermore, with the continuous ECG data from our study, dangers of developing a repolarization abnormality tends to occur in the presence of an increased heart rate.

Conclusions

This study in healthy subjects demonstrates that energy drink con- sumption alters repolarization of the cardiac cycle possibly predisposing

consumers to aLQTS, increased blood pressure, and electrolyte alter- ations. Because these physiological responses can lead to arrhythmias and other abnormal cardiac responses, it becomes important that emer- gency room personnel assess for energy drink toxicity and recognize these potential life-threatening consequences. Additional studies with larger samples are needed to determine clinical implications and conse- quences of energy drink consumption.

SBP = systolic blood pressure; mmHg = millimeter of mercury; PC = post consumption; u = mean.

QTc = QT interval corrected; mm = millimeter; u = mean.

(*) indicated significance; K+ = potassium; Mag = magnesium; Cal = calcium; ACT = activated bleeding time; u = mean.

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