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

Study Overview
=================
Brief Summary
-----------------
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? 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.

Detailed Description
-----------------
Title: The Effect of Energy Drink Ingredients on Cardiovascular Function 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? 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.

Official Title
-----------------
The Effect of Energy Drink Ingredients on Cardiovascular Function

Conditions
-----------------
Cardiac Arrhythmia, Blood Pressure

Intervention / Treatment
-----------------
* Dietary Supplement: Energy Drink Ingredients and Exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: No preexisting medical conditions (including pregnancy) 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) BMI within normal range (18.5 - 24.9 kg/m2) Average daily caffeine intake between 1 and 5 caffeinated beverages Exclusion Criteria: Age below 18 or greater than 39 years Unable to provide legal consent to participate in the study 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 BMI less than 18.5 or greater than 24.9 kg/m25. Current or future students of Drs. Johnson and/or Montepara Incarceration in local, state or federal justice systems

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: repeated measures, crossover design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Changes in BP, HR and EKG with Test Solution A and Exercise<br>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<br>* 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.<br>|
| Experimental: Changes in BP, HR and EKG with Test Solution B and Exercise<br>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<br>* 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.<br>|
| Experimental: Changes in BP, HR and EKG with Test Solution C and Exercise<br>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<br>* 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.<br>|
| Experimental: Changes in BP, HR and EKG with Test Solution C<br>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<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
caffeine, taurine, carnitine, energy drink