The Effect of Energy Drink Ingredients on Cardiovascular Function in Men and Women 18-39 Years Old (EEDICF)

The Effect of Energy Drink Ingredients on Cardiovascular Function

1. Statement of the research question:

   Does the caffeine in energy drinks interact with other ingredients to affect cardiovascular function in healthy male and female adults after exercise?

2. Purpose and significance of the study:

Energy drinks are beverages promoted to enhance alertness along with athletic and cognitive performance. The most common ingredients found in energy drinks include water, sugar, caffeine, taurine, and B-vitamins, with variable inclusion of other ingredients, such as carnitine, glucuronolactone, inositol, guarana, ginkgo biloba leaf extract, thistle extract, and ginseng root extract. Since the mid-1990s, the consumption of energy drinks has grown dramatically, with worldwide sales in 2017 exceeding $49 billion.

As the sale of energy drinks has grown, so has the number of adverse event case reports for patients who consumed energy drinks. Reported symptoms included cardiac arrhythmias such as ventricular fibrillation, atrial fibrillation, and cardiac arrest. A few small clinical studies have found that energy drinks can increase systolic and diastolic blood pressure and change electrical activity in the heart as measured by an electrocardiogram (ECG). The intent of the proposed study is to determine whether caffeine or the combination of caffeine with taurine and L-carnitine can alter cardiovascular function. Hypothesis: The effects of the ingredients of energy drinks on the heart are mediated in part by interactions between caffeine, taurine and carnitine. The amount of each ingredient in the study was based upon the amount commonly contained in two cans of energy drinks currently on the market.

Study Overview

• Status: Recruiting
• Conditions: Blood Pressure; Cardiac Arrhythmia
• Intervention / Treatment: Dietary supplement: Energy Drink Ingredients and Exercise

Detailed Description

Title: The Effect of Energy Drink Ingredients on Cardiovascular Function

1. Statement of the research question

   Does the caffeine in energy drinks interact with other ingredients to affect cardiovascular function, including QTc interval of the EKG, heart rate and blood pressure in healthy male and female adults after exercise?

2. Purpose and significance of the study

Energy drinks are beverages promoted to enhance alertness along with athletic and cognitive performance. The most common ingredients found in energy drinks include water, sugar, caffeine, taurine, and B-vitamins, with variable inclusion of other ingredients, such as carnitine, glucuronolactone, inositol, guarana, ginkgo biloba leaf extract, thistle extract, and ginseng root extract. Since the mid-1990s, the consumption of energy drinks has grown dramatically, with worldwide sales in 2017 exceeding $49 billion.

As the sale of energy drinks has grown, so has the number of adverse event case reports for patients who consumed energy drinks. Reported symptoms include cardiac arrhythmias such as ventricular fibrillation, atrial fibrillation, and cardiac arrest. A few small clinical studies have reported that energy drinks can increase systolic and diastolic blood pressure and change electrical activity in the heart as measured by an electrocardiogram (EKG). The intent of the proposed study is to determine whether caffeine or the combination of caffeine with taurine and L-carnitine can alter heart rate, blood pressure and the QTc interval of the EKG. Caffeine stimulates cardiovascular function primarily through antagonism of adenosine receptors. Taurine is a modulator of intracellular calcium ion concentrations which can affect the strength cardiac contraction. Carnitine facilitates fatty acid transport into the mitochondria, thereby increasing the production of adenosine triphosphate, the energy source of cells. Hypothesis: the effects of the ingredients of energy drinks on the heart are mediated in part by interactions between caffeine, taurine and carnitine. The amount of each ingredient in the study was based upon the amount commonly contained in two cans of energy drinks currently on the market.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David A Johnson, Ph.D.; Phone Number: 412-396-5952; Email: johnsond@duq.edu
• Study Contact Backup: Name: Courtney Montepara, Pharm.D.; Phone Number: 412-396-4335; Email: monteparac@duq.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15282
      • Recruiting
      • Duquesne University
      • Contact: David A Johnson, Ph.D.; Phone Number: 412-396-5952; Email: johnsond@duq.edu
      • Contact: Courtney Montepara, Pharm.D.; Phone Number: 4123964335; Email: monteparac@duq.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. No preexisting medical conditions (including pregnancy)
2. Subjects must be capable of exercising on a treadmill (Vigorous activity: more than 7 kcal/min; https://www.cdc.gov/nccdphp/dnpa/physical/pdf/PA_Intensity_table_2_1.pdf)
3. BMI within normal range (18.5 - 24.9 kg/m2)
4. Average daily caffeine intake between 1 and 5 caffeinated beverages

Exclusion Criteria:

1. Age below 18 or greater than 39 years
2. Unable to provide legal consent to participate in the study
3. Preexisting medical conditions including but not limited to: pregnancy, cardiovascular disease, endocrine disorders, psychiatric or neurological disorders, musculo-skeletal disorders, immune disorders, respiratory disorders, dermatological disorders, infections, blindness, hearing disabilities
4. BMI less than 18.5 or greater than 24.9 kg/m25.
5. Current or future students of Drs. Johnson and/or Montepara
6. Incarceration in local, state or federal justice systems

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Changes in BP, HR and EKG with Test Solution A and Exercise; Subject baseline HR, BP, EKG recorded.; Subject will ingest sucrose (150g):; 30 min later, subject will exercise on a treadmill; Subjects will return each week to repeat the above procedures with a different test solution.	Dietary supplement: Energy Drink Ingredients and Exercise; Subject will ingest 500 mL of one of three test solutions: A) sucrose (150g) B) sucrose (150g); caffeine (400 mg) C) sucrose (150g); caffeine (400 mg); taurine (4,000 mg); carnitine (400 mg) 3. 30 min later, subject will exercise on a treadmill using the Bruce Protocol maximum exercise test (https://www.aopa.org/go-fly/medical-resources/health-conditions/heart-and-circulatory-system/bru...). For one additional session, subjects will receive test solution C without exercise. 4. Each stage will last 3 minutes. Stage 1 = 1.7 mph at 2% Grade Stage 2 = 2.5 mph at 4% Grade Stage 3 = 3.4 mph at 6% Grade Stage 4 = 4.2 mph at 8% Grade Stage 5 = 5.0 mph at 10% Grade Stage 6 = 5.5 mph at 12% Grade Stage 7 = 6.0 mph at 14% Grade Stage 8 = 6.5 mph at 15% Grade Stage 9 = 7.0 mph at 15% Grade. The test will end when subjects reach exhaustion. 5. 1, 2, and 4 hrs following ingestion, HR, BP, and EKG will be recorded.
Experimental: Changes in BP, HR and EKG with Test Solution B and Exercise; Subject baseline HR, BP, ECG recorded.; Subject will ingest sucrose (150g); caffeine (400 mg); 30 min later, subject will exercise on a treadmill; Subjects will return each week to repeat the above procedures with a different test solution.	Dietary supplement: Energy Drink Ingredients and Exercise; Subject will ingest 500 mL of one of three test solutions: A) sucrose (150g) B) sucrose (150g); caffeine (400 mg) C) sucrose (150g); caffeine (400 mg); taurine (4,000 mg); carnitine (400 mg) 3. 30 min later, subject will exercise on a treadmill using the Bruce Protocol maximum exercise test (https://www.aopa.org/go-fly/medical-resources/health-conditions/heart-and-circulatory-system/bru...). For one additional session, subjects will receive test solution C without exercise. 4. Each stage will last 3 minutes. Stage 1 = 1.7 mph at 2% Grade Stage 2 = 2.5 mph at 4% Grade Stage 3 = 3.4 mph at 6% Grade Stage 4 = 4.2 mph at 8% Grade Stage 5 = 5.0 mph at 10% Grade Stage 6 = 5.5 mph at 12% Grade Stage 7 = 6.0 mph at 14% Grade Stage 8 = 6.5 mph at 15% Grade Stage 9 = 7.0 mph at 15% Grade. The test will end when subjects reach exhaustion. 5. 1, 2, and 4 hrs following ingestion, HR, BP, and EKG will be recorded.
Experimental: Changes in BP, HR and EKG with Test Solution C and Exercise; Subject baseline HR, BP, ECG recorded.; Subject will ingest sucrose (150g); caffeine (400 mg); taurine (4,000 mg); carnitine (400 mg); 30 min later, subject will exercise on a treadmill	Dietary supplement: Energy Drink Ingredients and Exercise; Subject will ingest 500 mL of one of three test solutions: A) sucrose (150g) B) sucrose (150g); caffeine (400 mg) C) sucrose (150g); caffeine (400 mg); taurine (4,000 mg); carnitine (400 mg) 3. 30 min later, subject will exercise on a treadmill using the Bruce Protocol maximum exercise test (https://www.aopa.org/go-fly/medical-resources/health-conditions/heart-and-circulatory-system/bru...). For one additional session, subjects will receive test solution C without exercise. 4. Each stage will last 3 minutes. Stage 1 = 1.7 mph at 2% Grade Stage 2 = 2.5 mph at 4% Grade Stage 3 = 3.4 mph at 6% Grade Stage 4 = 4.2 mph at 8% Grade Stage 5 = 5.0 mph at 10% Grade Stage 6 = 5.5 mph at 12% Grade Stage 7 = 6.0 mph at 14% Grade Stage 8 = 6.5 mph at 15% Grade Stage 9 = 7.0 mph at 15% Grade. The test will end when subjects reach exhaustion. 5. 1, 2, and 4 hrs following ingestion, HR, BP, and EKG will be recorded.
Experimental: Changes in BP, HR and EKG with Test Solution C; Subject baseline HR, BP, ECG recorded.; Subject will ingest sucrose (150g); caffeine (400 mg); taurine (4,000 mg); carnitine (400 mg)	Dietary supplement: Energy Drink Ingredients and Exercise; Subject will ingest 500 mL of one of three test solutions: A) sucrose (150g) B) sucrose (150g); caffeine (400 mg) C) sucrose (150g); caffeine (400 mg); taurine (4,000 mg); carnitine (400 mg) 3. 30 min later, subject will exercise on a treadmill using the Bruce Protocol maximum exercise test (https://www.aopa.org/go-fly/medical-resources/health-conditions/heart-and-circulatory-system/bru...). For one additional session, subjects will receive test solution C without exercise. 4. Each stage will last 3 minutes. Stage 1 = 1.7 mph at 2% Grade Stage 2 = 2.5 mph at 4% Grade Stage 3 = 3.4 mph at 6% Grade Stage 4 = 4.2 mph at 8% Grade Stage 5 = 5.0 mph at 10% Grade Stage 6 = 5.5 mph at 12% Grade Stage 7 = 6.0 mph at 14% Grade Stage 8 = 6.5 mph at 15% Grade Stage 9 = 7.0 mph at 15% Grade. The test will end when subjects reach exhaustion. 5. 1, 2, and 4 hrs following ingestion, HR, BP, and EKG will be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QTc interval of EKG	Lengthening or shortening of the corrected QT interval (QTc) of the subject EKG at 1, 2, and 4 hours post treatment will be compared to pre-treatment measurements. The QTc will be calculated utilizing Bezett's formula.	0, 1, 2, 4, hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Heart Rate	Increase or decrease in heart rate at 1, 2, and 4 hours post treatment compared to pre-treatment. Measurements of heart rate will be taken utilizing an automated sphygmomanometer	0, 1, 2, 4, hours post-dose
Change in Systolic and Diastolic Blood Pressure	Increase or decrease in systolic and diastolic blood pressure at 1, 2, and 4 hours post treatment compared to pre-treatment. Measurements of heart rate will be taken utilizing an automated sphygmomanometer.	0, 1, 2, 4, hours post-dose

Collaborators and Investigators

• Sponsor: Duquesne University
• Investigators: Study Chair: David Delmonico, Ph.D., Institutional Review Board, Chair, Duquesne University

Publications and helpful links

General Publications

• Fletcher EA, Lacey CS, Aaron M, Kolasa M, Occiano A, Shah SA. Randomized Controlled Trial of High-Volume Energy Drink Versus Caffeine Consumption on ECG and Hemodynamic Parameters. J Am Heart Assoc. 2017 Apr 26;6(5):e004448. doi: 10.1161/JAHA.116.004448.
• Kozik TM, Shah S, Bhattacharyya M, Franklin TT, Connolly TF, Chien W, Charos GS, Pelter MM. Cardiovascular responses to energy drinks in a healthy population: The C-energy study. Am J Emerg Med. 2016 Jul;34(7):1205-9. doi: 10.1016/j.ajem.2016.02.068. Epub 2016 Mar 2.
• Goldfarb M, Tellier C, Thanassoulis G. Review of published cases of adverse cardiovascular events after ingestion of energy drinks. Am J Cardiol. 2014 Jan 1;113(1):168-72. doi: 10.1016/j.amjcard.2013.08.058. Epub 2013 Oct 4.
• Shah SA, Szeto AH, Farewell R, Shek A, Fan D, Quach KN, Bhattacharyya M, Elmiari J, Chan W, O'Dell K, Nguyen N, McGaughey TJ, Nasir JM, Kaul S. Impact of High Volume Energy Drink Consumption on Electrocardiographic and Blood Pressure Parameters: A Randomized Trial. J Am Heart Assoc. 2019 Jun 4;8(11):e011318. doi: 10.1161/JAHA.118.011318. Epub 2019 May 29.
• Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta. 2016 Oct;1863(10):2422-35. doi: 10.1016/j.bbamcr.2016.01.023. Epub 2016 Jan 29.
• Turnbull D, Rodricks JV, Mariano GF, Chowdhury F. Caffeine and cardiovascular health. Regul Toxicol Pharmacol. 2017 Oct;89:165-185. doi: 10.1016/j.yrtph.2017.07.025. Epub 2017 Jul 26.
• Satoh H. Cardiac actions of taurine as a modulator of the ion channels. Adv Exp Med Biol. 1998;442:121-8. doi: 10.1007/978-1-4899-0117-0_16.

Helpful Links

• Energy drink consumption frequency in the U.S. 2016, by age
• Energy Drink Sales
• Bruce Protocol Stress Test
• General Physical Activities Defined by Level of Intensity

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: caffeine; taurine; carnitine; energy drink
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac
• Other Study ID Numbers: #2019/10/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No