THE EFFECTS OF CAFFEINE GUM ADMINISTRATION ON REACTION TIME AND LOWER BODY PAIN DURING CYCLING TO EXHAUSTION A Thesis Presented To The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Andrea Jankowski-Wilkinson August, 2008 THE EFFECTS OF CAFFEINE GUM ADMINISTRATION ON REACTION TIME AND LOWER BODY PAIN DURING CYCLING TO EXHAUSTION Andrea Jankowski-Wilkinson Thesis Approved: Accepted: ____________________________ Advisor Dr. Ronald Otterstetter ____________________________ Interim Dean of the College Dr. Cynthia Capers ____________________________ Committee Member Mrs. Stacey Buser ____________________________ Dean of the Graduate School Dr. George R Newkome ____________________________ Committee Member Mrs. Rachele Kappler ____________________________ Date ____________________________ Department Chair Dr. Victor Pinheiro ii ABSTRACT Caffeine is the most widely consumed drug in the world. In various forms, it has been shown to elicit some advantageous effects when ingested prior to exercise. Caffeine has been widely used in the liquid or capsule form for decades now; however caffeine in the chewing gum form is a much more recent development and hence has less established research on it. The purpose of this study is to examine the effects of caffeinated chewing gum on lower body pain and reaction time during exercise. Eight healthy, physically active male participants between 18 and 32 years of age were recruited to participate. Participants reported to the laboratory on five occasions. On the first visit, subjects underwent a graded exercise test on an Excalibur 1300W electronically braked cycle ergometer until volitional fatigue at which time expired air samples were analyzed for oxygen and carbon dioxide concentrations via an automated open circuit system to determine maximal oxygen consumption. The two highest 30-second oxygen consumption values were averaged to determine maximal oxygen consumption. Over the next four visits, 200 milligrams of caffeine chewing gum or placebo were administered in a randomized, counterbalanced, double blind manner at 35 minutes before exercise, 5 minutes before exercise, and 10 minutes following the initiation of exercise. Participants cycled on an Excalibur electronically braked cycle ergometer at 85% capacity as iii determined by expired air samples collected every 10 minutes of exercise which were analyzed for oxygen and carbon dioxide concentrations via an automated open circuit system (PARVO, Metabolic Cart, Sandy, Utah). Participants cycled until volitional fatigue. Lower body pain measurements were obtained every 10 minutes during exercise via a 1-10 pain scale. Reaction time was measured at three time points via a hand held psychomotor vigilance test. For statistics, a Mixed Model Analysis was run. There was no statistical significance in the reduction of reaction time with caffeine administration. Furthermore, there was not a significant decrease in pain levels with caffeine ingestion. With a larger sample size, it appears that there may have been a decrease in reaction time when caffeine is administered fifteen minutes into exercise. iv DEDICATION This study is dedicated to the brave Men and Women of The United States Armed Forces who have selflessly served our country so that we can all live a life of freedom. To those who are still with us and to those who have passed, we are forever indebted to you. Thank you for your courage, and for truly making America the land of the free. v ACKNOWLEDGEMENTS The author would like to give sincere thanks to Dr. Ronald Otterstetter of The University of Akron for his guidance and support as an advisor and mentor. Thanks to Dr. Gary Kamimori of Walter Reed Army Institute of Research for his wisdom, and generosity of his time and supplies. Deep appreciation to Dr. David Newman for his statistical wisdom and generous donation of his time. A special thanks to all of the fellow researchers, Morgan Russell, EJ Ryan, Chul-Ho Kim, David Bellar, and Matthew Muller for all of their hard work and devotion to this research. Lastly, sincere thanks and gratitude to all of the participants for their time and dedication throughout this process to ensure the success of the research. vi TABLE OF CONTENTS Page LIST OF TABLES……………………………………………………………………......ix LIST OF FIGURES……………………………………………………………………….x CHAPTER I. INTRODUCTION ………………………………………………...…………………...1 II. REVIEW OF LITERATURE …….……………...…………………………………….4 III. RESEARCH DESIGN AND METHODS ……………………………………..……10 IV. RESULTS AND DISCUSSION ………………………………………………….…15 V. SUMMARY ………………………………………………………………………….19 BIBLIOGRAPHY………………………………………………………………………..21 APPENDICES…...………………………………………………………………………24 APPENDIX A. HUMAN SUBJECT APPROVAL …………………………………..25 APPENDIX B. INFORMED CONSENT …………………………………………….26 APPENDIX C. BORG SCALE OF PERCEIVED EXERTION ……………………..31 APPENDIX D. PAIN SCALE ………………………………………………………..32 APPENDIX E. PAIN RESULTS ……………………………………………………..33 APPENDIX F. PSYCHOMOTOR VIGILANCE TEST CONTROL TRIAL: 50 MINUTES PRIOR TO EXERCISE………………………………34 APPENDIX G. PSYCHOMOTOR VIGILANCE TEST CONTROL TRIAL: 25 MINUTES PRIOR TO EXERCISE………………………………35 vii APPENDIX H. PSYCHOMOTOR VIGILANCE TEST : TREATMENT 35 MINUTES PRIOR TO EXERCISE TRIAL: PVT 50 MINUTES PRIOR TO EXERCISE…………………………36 APPENDIX I. PSYCHOMOTOR VIGILANCE TEST : TREATMENT 35 MINUTES PRIOR TO EXERCISE TRIAL: PVT 25 MINUTES PRIOR TO EXERCISE………………………37 APPENDIX J. PSYCHOMOTOR VIGILANCE TEST : TREATMENT 5 MINUTES PRIOR TO EXERCISE TRIAL: PVT 50 MINUTES PRIOR TO EXERCISE………………………38 APPENDIX K. PSYCHOMOTOR VIGILANCE TEST : TREATMENT 5 MINUTES PRIOR TO EXERCISE TRIAL: PVT 25 MINUTES PRIOR TO EXERCISE………………………39 APPENDIX L. PSYCHOMOTOR VIGILANCE TEST : TREATMENT 15 MINUTES INTO TO EXERCISE TRIAL: PVT 50 MINUTES PRIOR TO EXERCISE………………………40 APPENDIX M. PSYCHOMOTOR VIGILANCE TEST : TREATMENT 15 MINUTES INTO TO EXERCISE TRIAL: PVT 25 MINUTES PRIOR TO EXERCISE………………………41 viii LIST OF TABLES Table 3.1 Page Participant Profiles …………………………………………………………….11 ix LIST OF FIGURES Figure Page 4.1 Reaction Time Over Time: Treatment versus No Treatment……………………16 4.2 Pain Over Time: Treatment versus No Treatment....…………………………….16 4.3 Reaction Time Over Time ………………………………………………………17 4.4 Pain Over Time ………………………………………………………………….18 x CHAPTER I INTRODUCTION Caffeine is one of the most widely used drugs in the world.35 In moderate doses (<300 mg) caffeine is well tolerated and few significant side effects have been reported. Stay Alert chewing gum is a product developed by Amurol Confectioners (Specialty gum subsidiary of Wrigley’s, Yorkville, IL) that contains 100mg caffeine/stick. Caffeine in this form is considered a nutritional supplement and requires no additional FDA approval for use in this form. Caffeine acts as an adenosine receptor antagonist and several researchers have demonstrated that it can improve physical and cognitive performance.15, 16 Furthermore, the ergogenic effects of caffeine are well documented. Caffeine in various forms has been studied for over 200 years; however there is very little research incorporating this method of delivery on physical and cognitive performance. Caffeine delivery methods have been studied very extensively in many forms; however caffeine delivery using a chewing gum form has not been examined thoroughly. Caffeine gum delivery is unique because it is absorbed sublingually into the bloodstream. The advantage of sublingual absorption is that the caffeine is absorbed more quickly than alternative forms so the effects are felt sooner than alternative methods of absorption. 1 When you chew caffeine gum, the caffeine is released into the saliva and absorbed through the tissues in the mouth (the buccal cavity) which leads the caffeine directly into the bloodstream. Through this method of absorption, the effects of the caffeine reach the brain within approximately three to five minutes; caffeine in the liquid form can take up to 30-45 minutes. The purpose of this investigation is to determine the most efficacious time to administer caffeinated chewing gum in order to maximize reaction time and minimize the sense of lower body pain. Furthermore, we will then be able to compare the efficacy of caffeine on exercise when delivered through chewing gum versus alternative forms of ingestion. This will allow those using the product to better know the ideal timing of administration. This study is unique because of the chewing gum component. There has been very little research performed on the administration of caffeinated gum and the optimal timing of ingestion. Specifically, what was investigated (through multiple trials) was the optimal time to start chewing the caffeinated gum, how it affects psycho-motor skills, and lower body pain/tolerance. The result of this study could be used to guide the physically active population in the ideal usage and benefits of caffeinated chewing gum. If significant findings are found in the reduction of lower body pain, then this product could be used for a variety of purposes besides the ergogenic effects, such as therapeutic effects. If significant findings are documented with reaction time, then we can effectively administer the product when it would be most beneficial for alertness. 2 Research Question #1: How does the ingestion of caffeinated gum affect lower body pain throughout exercise? Research Question #2: How does the ingestion of caffeinated gum affect reaction time? 3 CHAPTER II REVIEW OF LITERATURE Caffeine is a natural stimulant that can be found in over sixty leaves, fruits, and seeds all over the world. It is considered to be the most popular drug in the world today. 35, 24 Caffeine is thought to be a relatively safe, inexpensive, and readily available drug. 11, 24 In the practical sense, caffeine can be found in numerous forms ranging anywhere from drinks, to foods, to chewing gum. We know that caffeine in various structures can produce some advantageous effects; however there is still question as to if these effects occur in the same manner when the caffeine is absorbed through the buccal cavity. Caffeine is a trimethylxanthine; it is made up of elements of carbon, hydrogen, nitrogen, and oxygen (C8H10N4O2). 28 The chemical name for caffeine is 3, 7 dihydro- 1, 3, 7-trimethyl-1H-purine-2, 6-dione; it is sometimes abbreviated 1, 3, 7trimethylxanthine. 28 Trimethylxanthine is catabolised by the cytichrin P450 in the liver. 11 Caffeine is further classified as an alkaloid.35 The compound is methylxanthine; substances in this compound group are easily oxidized to uric acid. 35 Caffeine is widely known for its stimulant effect, or its ability to decrease the sense of fatigue; it is mostly known for its’ effects on the cerebral cortex and the brain 4 stem in the central nervous system. 34 Caffeine is effective in increasing mental alertness, and reversing the effects of sleep deprivation. 12 Caffeine is unique from other stimulant drugs because there is a very low potential for addiction. 12 The mechanism of action is thought to be that caffeine blocks the adenosine receptors to the brain and other organs. 28 The blocking of the adenosine receptors slows down the ability of the adenosine to bind to the receptors which ultimately slows down cellular activity. 28 Adenosine receptors are found throughout the body including in the heart, brain, smooth muscle, most tissues, and skeletal muscle 11. Due to the unique nature of caffeine, and the various types of adenosine receptors, it can affect numerous different tissues and systems in the body. 11 Ingestion of caffeine causes an increase in neuron firing in the brain, this is largely due to a block of adenosine; in turn this causes the pituitary gland to go into emergency response mode. This emergency response mode of the pituitary gland releases hormones which then trigger the adrenal glands to produce adrenaline. 18 The emergency mode of the pituitary gland is the body’s reaction to fear, anxiety, or exercise Adrenaline is released as a result of the stimulated nerve cell. 28 Adrenaline is a catecholamine that belongs to the family of biogenic amines. It is made in the adrenal gland of the kidney, is carried in the bloodstream, and mainly affects the autonomous nervous system. The release of adrenaline in the body has many effects such as an increase in heart rate, dilation of the pupils, the liver releases extra glucose into the bloodstream, and secretion of saliva. Adrenaline is an important area to discuss due to its known affects during exercise. 5 Caffeine in other forms has established analgesic properties which is why it could prove to be a beneficial supplementation during moderate to high intensity level exercise. It has been shown that the ingestion of caffeine may enhance the adrenal medullary responses to normal stressors. 33 Caffeine in forms other than chewing gum is considered to be a rapidly absorbing drug being absorbed through the stomach lining and reaching the bloodstream is approximately 45 minutes. 34 Caffeine being absorbed through the stomach lining allows it to become distributed equally throughout all of the water in the body. The caffeine is later metabolized in the liver and eventually expelled through the kidneys. The typical half-life of caffeine is approximately 4 hours under normal conditions.34 On the contrary, caffeine being absorbed through the buccal cavity, such as through the chewing gum form will show effects in as little as five minutes; hence the importance of investigating caffeinated chewing gum more extensively. Caffeine ingested in the chewing gum form has several advantages based off of the method of absorption. The caffeine in caffeinated chewing gum form is absorbed through the buccal cavity in the mouth; this method of ingestion is credited with a faster absorption rate in part to the highly vascularized buccal cavity. 12, 28 Caffeine in the chewing gum form also has the advantage of bypassing the intestinal and hepatic systems; this is due to the fact that the oral veins drain into the vena cava. 12, 28 Ultimately, the bypass of these anatomical areas and the caffeine absorption through the oral mucosa lead to overall faster absorption rates. Adenosine concentrations increase during moderate or high intensity exercise.20,5 Peripherally, there are adenosine receptors (A1 and A2a) which are located on sensory 6 nerve endings in the skeletal muscles; these receptors are both influencers of pain signaling.20,30 The ingestion of caffeine during or slightly prior to exercise alters a participants perceptions. 7 This alteration could be due to the established analgesic effects of caffeine during ischemic muscle contractions. 7 Pain that develops as a result of exercise can theoretically be attributed to muscle contractions which place a mechanical force on pressure sensitive nociceptors; the mechanical aspect is associated with central sensitization. 19 Nociceptive pain is elicited when one of two situations occur; harmful stimulation of normal tissue occurs or when tissue is in a pathological state. 36 Nociceptive pain is often associated with inflamed or damaged tissue (which is likely to occur during exercise), and furthermore it may occur spontaneously or in response to a given stimulus. 36 Exercise is commonly used to study pain because it is one of the few activities that can be used to induce natural skeletal muscle pain. 20 Acute pain is often studied by artificially inducing symptoms; although this practice allows for a lot of valuable information to be discovered, a more practical approach could be studying pain in natural movement patterns such as through exercise. The mechanism of exercise induced skeletal muscle pain is ill understood and is still being extensively studied for further understanding. One theory behind the idea of caffeine masking pain is due to the fact that caffeine is a nonselective adenosine antagonist.20 The nonselective adenosine antagonist associated with caffeine has established antinociceptive actions.30 It has yet to be fully determined if adenosine has any responsibility for the perception of skeletal muscle pain during exercise.20 7 However, evidence supports the idea that caffeine can play an important role in the reduction of naturally occurring skeletal muscle pain during exercise; this is thought to be a natural response of the peripheral nervous system or the central nervous system acting independently. 20 Skeletal muscle pain is an area that is still being deeply investigated. Another advantageous effect of caffeine is the mental alertness that commonly accompanies ingestion. Along with mental alertness, often comes a reduction in reaction time. The effects of caffeine have shown a positive increase in psychomotor performance; however the psychomotor responses are known to be dependent on age, level of alertness, and caffeine abstinence. 18, 8, 24 Exercise at low to moderate intensity levels has also shown to have a positive influence on psychomotor performance which is thought to be a direct correlation to an increased mental alertness. 18, 13, 19 One common form of testing reaction time is through administering a psychomotor vigilance test. Advantages of using this method of testing include ease of test, portability, multiple participants can use the same unit, inexpensive, relatively simple to use, and can be tailored to right or left handed users. The psychomotor vigilance tests have been used extensively for various studies conducted by Walter Reed Army Institute of Research. In summary, this study is unique in the sense that we are testing both lower body pain perception during exercise and reaction action time in relationship to caffeinated chewing gum. Both of these variables have been extensively studied for effectiveness with other forms of caffeine ingestion; we are simply examining if the findings hold true with a different and faster method of absorption. If significant findings 8 are discovered, then we can administer caffeinated chewing gum with a greater sense of knowledge of its’ overall effects. The benefit of caffeinated gum is that it provides great ease of ingestion; for example no liquid needs to be consumed and it is simply convenient. Furthermore, the effects are felt quickly so there is little need to plan too far in advance for when you may want the caffeine. 9 CHAPTER III RESEARCH DESIGN AND METHODS The methods were approved by The University of Akron Institutional Review Board and Kent State University Institutional Review Board, and all participants were provided written informed consent. Participants (n=8), were males between 18-32 years of age, and were recruited via direct contact with the principle investigators. The participants needed to be non-to-moderate caffeine users; moderate caffeine use was defined as being less than 330mg/day. Participants must also have a body fat percentage below 30%; body fat was measured via a Dual Energy X-Ray Absorptiometry Scan (DEXA Scan) (Hologic QDR 4500 Elite-Acclaim Series, Hologic Inc., Bedford, MA). Furthermore, participants were excluded from the study if they have a prior history of smoking, have signs or symptoms of cardiovascular, metabolic, or respiratory disease, or if they are known to have any cardiovascular, metabolic, or respiratory disease as determined via a health history questionnaire. Participants were asked to report to the exercise physiology laboratory on five separate occasions with a one week washout period between each visit. Prior to reporting to the laboratory, participants were asked to refrain from eating or drinking (with the exception of water) for at least eight hours. On the first visit, participants underwent a 10 graded exercise test on an electrically braked cycle ergometer (Excalibur 1300W) until volitional fatigue at which time expired air samples were analyzed for oxygen and carbon dioxide concentrations via an automated open circuit system (PARVO, Metabolic Cart, Sandy, Utah) to determine maximal oxygen consumption. Table 3.1 Participant Profiles Participant Age Ethinicity 1 30 White 2 21 White 3 32 Asian 4 22 White/AA 5 28 White 6 23 Whte 7 24 White 8 24 White Average 25.5 Height 69 Inches 74 Inches 69 Inches 69 Inches 70 Inches 70 Inches 70 Inches 69 Inches 70 Inches Weight VO2max 82 KG 47.5 110 KG 44.5 66.8 KG 52 106 KG 44 78.5 KG 43.4 75.7 KG 52.2 72.8 KG 46 94 KG 34.1 85.7 KG 45.46 A three-liter syringe (Hans Rudolph Model 5530, Hans Rudolph, Inc., Kansas City, MO) and known concentration calibration gases were used to calibrate the automated open circuit system prior to each maximal oxygen consumption test. Heart rate was continuously measured via a heart rate monitor (Accurex Plus, Polar Electro, Inc., Woodbury, NY), and the heart rate values were recorded via telemetry every 30 seconds. The two highest 30-second oxygen consumption values were averaged to determine maximal oxygen consumption. The bicycle seat and handle bars were measured for each individual participant and documented to ensure consistency throughout all of the trials. 11 During the following four visits, two pieces of chewing gum were administered at three time points (35 minutes prior to exercise, 5 minutes prior to exercise, and 15 minutes following the initiation of exercise). In 3 of the 4 visits, at one of the administration time points, 200 milligrams of caffeine (Stay Alert chewing gum, Amurol Confectioners, specialty gum subsidiary of Wrigley’s, Yorkville, IL) was administered. During one of the four trials (the control trial), placebo gum was administered in all three of the time points. Caffeine was administered in a randomized, counterbalanced, double blind manner. The subjects were instructed to chew for five minutes before disposing of the gum. All of the trials were conducted in a temperature controlled chamber that was maintained at 23° Celsius. The participants were given a five minute warm up on the bicycle with a power output of 50 Watts. Throughout the five minute warm up period, the participants were ramped until they reached the appropriate wattage. Participants cycled on an Excalibur electronically braked cycle ergometer (Excalibur 1300W) at 85% capacity as determined by expired air samples collected every ten minutes of exercise; these air samples were analyzed for oxygen and carbon dioxide concentrations. Participants were instructed to cycle between 60-80 revolutions per minute. Participants cycled until volitional fatigue occurred, that is, until they failed to maintain the required work output. Failure to maintain the required output was defined as the participant reaching as low as 40 revolutions per minute. Ratings of Perceived Exertion and lower body pain were obtained 40 minutes prior to exercise, five minutes prior to exercise, every ten minutes during exercise, at exhaustion, and five minutes post-exercise. The Ratings of Perceived Exertion were 12 measured using Borg’s RPE 6-20 scale. The lower body pain was measured using a 0-10 scale where zero was no pain at all and 10 was maximal pain. The participants were asked to point to a number on the Borg Scale that corresponded to the level of perceived exertion for their legs, lungs, and an overall sense of exertion. The participants were then asked to point to a number that corresponded to their level of lower body pain. To measure vigilance the Palm hand held psychomotor vigilance task (PVT) was utilized. The Palm-PVT is a test of continuous vigilance. The test is comprised of the participant reacting to a stimulus (a bulls-eye) which appears in the middle of a Personal Data Assistant (PDA). The participant’s task is to press a designated key as soon as possible after the stimulus appears. The amount of time between each stimulus presentation is randomized between 1, 2, 3, 4, and 5 seconds. The total time of the task is five minutes. The PVT was administered 50 minutes prior to exercise, 10 minutes prior to exercise, and 5 minutes post exercise. During each psychomotor vigilance test (PVT), the participants sat in a chair within the chamber, facing the wall with one investigator standing behind them to minimize distractions. Prior to starting the PVT, the participants were given procedural instructions, and shown which button to push (based off of their dominant hand). The test from start to finish is five minutes per trial. The PVT’s were always administered in the same chair and position to maintain consistency. Once the participant completed the postexercise PVT, that individual trial was complete. Limitations for this study included the small subject population; due to the repeated measures of the study and procedural constraints, we were only able to test seven subjects. Another limitation could be that we did not dose by body weight; in other 13 words all of the participants were given the same dose of caffeine regardless of body composition. Another area that could be a limiting factor is the fitness level of the participants. Although all of the participants had to demonstrate a body fat percentage of less than 30% in order to qualify for participation, some of the participants were clearly more aerobically trained than others. 14 CHAPTER IV RESULTS AND DISCUSSION This was a repeated measures study in which the subjects were not all measured at all time points (due to the differences in cycling time to exhaustion); therefore a Repeated Measures ANOVA was not applicable. In order to analyze this study, Mixed Model analyses were conducted. Mixed Models, also referred to as HLM and Individual Growth Models allows one to model the appropriate covariance matrix while allowing for different test times for each subject. One research question was that there would be a significant decrease in reaction time with caffeine administration over the exercise period. This hypotheses was not statistically significant p=0.579 with an F=0.282 and a R2=0.003. As can be seen in the figure below (Figure 4.1), the reaction time was slightly but not significantly faster with the ingestion of caffeine. Another reseach area was would there be significant less increase in pain with caffeine administration over the exercise period? This hypothesis was not statistically significant p=0.993 with an F=0.0001 and a R2=0.000. As can be seen below (Figure 4.2), pain levels over time seem to be almost identical regardless if the participant ingested caffeine or not. 15 Figure 4.1 Reaction Time Over Time: Treatment versus No Treatment Figure 4.2 Pain Over Time: Treatment versus No Treatment The next research question was would there be a differential effect in reaction time depending on if the caffeine was administered at 35 minutes prior to exercise, five minutes prior to exercise, or fifteen minutes into exercise? These results were not statistically significant p=0.703 with an F=0.471 and a R2=0.005. 16 As can be seen below (Figure 4.3) in the figure, all of the reaction times were consistantly close with the exception of the participants who ingested the caffeine fifteen minutes after exercise had begun. With a larger sample or a smaller standard error this treatment group might have had significantly faster reaction times. Figure 4.3 Reaction Time Over Time The final area of exploration was whether or not there would be a differntial effect in reported pain levels depending on if the caffeine was administered at 35 minutes prior to exercise, five minutes prior to exercise, or fifteen minutes into exercise. There was not statistical significance in this area p=0.943 with an F=0.129 and a R2=0.001. As can be seen below (Figure 4.4), the pain levels increase almost identically regardless of the caffeine treatment. 17 Figure 4.4 Pain Over Time Previous research has shown that anxiety coupled with caffeine ingestion could play an important role in pain perception.10, 20 It has been shown that a dose of 10 milligrams of caffeine per kilogram of bodyweight significantly reduced pain in the quadriceps muscles during cycling.10 Further experimentation showed that doses as small as 5 milligrams of caffeine per kilogram of bodyweight produced similar effects in the reduction of leg pain.10, 20 These previous studies were based off of cycling at a moderate intensity that was defined as being 60% of the participants’ maximal volume of oxygen consumption (VO2max). Further studies that were conducted based off of the research findings of caffeine related hypoalgesia while exercising at 60% of VO2max, found similar reduction in leg pain when participants exercised at 80% of VO2max.10 It has been documented that when compared to a placebo, a 5 milligram dose of caffeine per kilogram of body weight has very significant hypoalgesic effects during cycling. 10 I believe that given a larger population size and dosing the caffeine by body weight would have elicited similar analgesic results as seen with previous research. 18 CHAPTER V SUMMARY Since caffeine is such a widely used substance in the world today, it is beneficial to understand all of the advantages that it may provide. Furthermore, understanding when to use caffeine to experience optimal performance of the drug is of equal importance. We have known for many years that caffeine has some advantageous effects, however the development and research of caffeinated chewing gum is relatively modern, and therefore requires further research to fully prove all of its’ benefits. The purpose of this study was to establish if there was a decrease in lower body pain with the ingestion of caffeine throughout exercise, and if so at what time point should the caffeinated gum be taken. The secondary purpose was to establish if there was a relationship between reaction time, exercise, and caffeinated gum, and again if there was a relationship established then at what time point is ingestion most advantageous. There is a lot of room for research in this area; dosing by body weight, and a larger population of participants would be beneficial. Another area to consider in future research would be to look at recovery time post exercise to see if caffeine helps to speed up that process. 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Multiple dose pharmacokinetics of caffeine administered in chewing gum to normal healthy volunteers, Biopharmaceutics & drug disposition. 26: 403-409. 32. VanSoeren, M & Graham (1998). Effect of caffeine on metabolism, exercise endurance, and catecholamine response after withdrawal. J applied physiology, 85, 1493. 33. Yeragani, V. M.D., Krishnan, S., Engels, H.J. Ph.D., & Gretebeck, R., Ph.D. (2005). Effects of caffeine on linear and nonlinear measure of heart rate variability before and after exercise. Depression and anxiety. 21:130-134. 34. Virtual Mass Spectrometry. Available at http://massspec.chem.cmu.edu/VMSL/Caffeine/Caffeine_effects.htm. Accessed July 19, 2008. 35. How Caffeine Effects the Body. Available at http://www.faqs.org/nutrition/CaDe/Caffeine.html. Accessed July 18, 2008. 36. Neuromuscular Website for WUSTL. Available at http://neuromuscular.wustl.edu/mother/mpain.html. Accessed July 17, 2008. 23 APPENDICES 24 APPENDIX A HUMAN SUBJECTS APPROVAL 25 APPENDIX B INFORMED CONSENT Title of Study: “The Effects of Caffeine Administration Timing on Cycling to Exhaustion” Introduction: You are invited to participate in a research study designed and conducted by Andrea Jankowski-Wilkinson and Morgan Russell, Masters’ students enrolled in the Exercise Physiology program at The University of Akron in the Department of Sport Science and Wellness Education and Edward Ryan, Doctoral student enrolled in the Exercise, Leisure and Sport program at Kent State University, under the advisement of Dr. Ronald Otterstetter, faculty member at The University of Akron in the Department of Sport Science and Wellness Education. Purpose: The main objective for this investigation is to determine the best time to administer caffeinated chewing gum in order to see how it affects exercise performance on a bicycle. This study will specifically look at the effect caffeine has on the body at rest and during exercise, how fast fatigue occurs, and mental alertness. Procedure: Ten subjects will individually participate in the research. If you volunteer for this study you will be required to take part in a preliminary visit and four testing trials. The preliminary visit will last approximately sixty minutes and each of the four testing trials will last approximately ninety minutes. During the preliminary visit, the testing protocol will be explained and you will complete a health history questionnaire as well as a Dual Energy X-ray Absorptiometry (DEXA) scan to determine baseline body composition. You will undergo a graded exercise test on a bicycle until you cannot exercise any longer to determine your highest level of fitness. The bicycle will be set to increase in resistance every minute. Throughout the test, you will be equipped with a mouthpiece similar to a scuba-diving snorkel, which you will breathe through for the entire exercise session. You will also be equipped with a heart rate monitor and a blood pressure cuff for the entire exercise session. The four testing trials will be separated by seven days, in which data will be collected. You will chew either two pieces of caffeinated gum containing 100 milligrams of caffeine each, or a placebo, 35 minutes pre-exercise, 5 minutes pre-exercise, and 10 minutes following the initiation of exercise. You will be required to complete a cardiovascular endurance capacity test. 26 The cardiovascular endurance test will be performed on a bicycle. You will cycle at a set intensity that will be predetermined until you cannot cycle any longer. During this test, the amount of oxygen that you breathe in will be measured using the mouthpiece every 10 minutes, heart rate will be measured, the effort you are cycling at will be determined using a chart, blood glucose and lactate levels will be measured by a finger prick, perceived leg pain will be determined by you determining your level of leg pain according to numbers on a chart, and reaction time will be determined using a Palm-held psychomotor vigilance task. The task will require you to react to a stimulus (a bulls-eye), which appears in the middle of a Personal Data Assistant (PDA). Your task will be to press a designated key as soon as possible after the stimulus appears, while on the bicycle. Two blood specimens of 5 ml each will be drawn three times during the trial. A total of 30 ml will be drawn, which is approximately one tablespoon per trial. The blood specimens will be taken 40 minutes pre-exercise, immediately pre-exercise, and immediately post-exercise. Blood glucose and blood lactate levels will be measured by a glucometer and lactate analyzer. Your finger will be pricked using stick that looks like a pen and then the blood will immediately be analyzed. You will be pricked 40 minutes pre-exercise, immediately pre-exercise, and every ten minutes during exercise. Prior to the four testing trials, you will be asked to not eat for 8 hours before each trial and to not consume any alcohol or caffeine containing drinks for 24 hours before each trial. Inclusion: Healthy males between the ages of 18 and 32 years. Exclusion: A Health History Questionnaire will be used to determine exclusion criteria. If you answer yes to any question on the questionnaire and do not fall within acceptable quantified limits, you will be disqualified from the study. The three quantified items on the health history questionnaire are alcohol consumption (< 3 drinks per day), caffeine consumption (< 300 mg per day), and if you have had mononucleosis within six months of first trial date. You will be excluded if you use caffeine supplements, smoke, show signs or symptoms of cardiovascular, metabolic, or respiratory diseases or you have a known cardiovascular, metabolic, or respiratory disease. You will also be excluded if you are >30% body fat, due to an increased chance of a cardiac event. Risk and Discomfort as Related to Caffeine: Risks associated with this investigation are related to the ingestion of caffeine. Although the caffeine doses used in this study are similar to those encountered in everyday life, over the counter supplements have the potential for minor side effects. Side effects for caffeine may include the possibility of headache, dizziness, nausea, and muscle tremor. Individuals who do not consume caffeine on a regular basis may be more prone to side effects than those who are habitual caffeine users. In addition, chewing gum may cause dental fillings to become loose. 27 Risk and Discomfort as Related to Blood Draws: Mild discomfort, or bruising due to venipuncture is possible. There is a slight risk of infection similar to any puncture in the skin, which will be minimized by using a sterile technique. The universal precautions to avoid transmission of blood borne pathogens between tester and subject will be observed. Venipuncture will be performed by trained, experienced personnel. Phlebotomy competency training will be completed and documented for all individuals performing blood draws. In the event of a medical emergency, all researchers are CPR, First Aid, and AED trained and certified. Should an emergency occur, the researchers will activate EMS. Risk and Discomfort as Related to Dual Energy X-Ray Absorptiometry: There is minimal radiation exposure through the DEXA scans. The amount of radiation in this investigation is less than 1/1000th of the exposure associated with an average dental X-ray (DEXA=1mR/18 sec vs. Dental X-ray=1138mR). Risk and Discomfort as Related to Exercise Tests: Mild and localized discomfort, not exceeding that incurred during a normal exercise session, associated with delayed onset muscle soreness due to exercise can be expected. You may experience fatigue and lightheadedness due to exercise. Throughout the test your nose will be clamped and you will breathe through a tube, which you may find uncomfortable. A health history will be taken to screen out anyone for who strenuous exercise may pose a higher than expected risk. It is important that you provide truthful and accurate information so as to not put yourself at unnecessary risk. Investigators have completed over 100 VO2max tests without a subject injury or critical event. An investigator will be monitoring the computer, as to stop the test at any point that the subject requests or if the researchers feels it is unsafe for you to continue based on guidelines set forth by the American College of Sports Medicine. The risk of serious injury is no greater than that which you may experience with a very intense, physical workout. There is an extremely small chance of a serious medical condition occurring, and according to National statistics, 4 out of every 10,000 people may experience a heart attack and 1 out of every 10,000 people may experience sudden death when engaging in intense physical exercise/exertion. You should inform the researchers immediately if you start to have pains in your chest, shoulder or legs, feel dizzy or weak, and experience any shortness of breath, difficulty breathing, or other distressing symptoms during the testing procedure. Risk and Discomfort as Related to Finger Pricks: Mild discomfort or soreness may occur due to finger pricks. There is a slight risk of infection similar to any puncture in the skin, which will be minimized by using a sterile technique. 28 The universal precautions to avoid transmission of blood borne pathogens between tester and subject will be observed. Finger pricks will be performed by the researchers. Benefits: Participating in this study will allow you to learn more about your fitness level from the bicycle exercise test, as well as your personal body composition and bone density via a DEXA scan. Payments for Participation: You will be monetarily compensated upon the completion of your individual participation in the study. You will be compensated $200, broken down into the following increments based on the completion of each trial: $25 for successful completion of trial 1, $25 for successful completion of trial 2, $50 for successful completion of trial 3 and $100 for successful completion of trial 4. If you are unable to participate in all four trials, your compensation will be prorated accordingly. Right to refuse or withdraw: Participation in the research is voluntary. You may withdraw consent and discontinue participation in the study at any time without any consequence to you. Anonymous and Confidential Data Collection: Any identifying information collected will be kept in a locked file cabinet, and only the researchers will have access to the data. As a participant, you will not be individually identified in any publication or presentation of the research results. Only comprehensive data will be used. To insure your privacy, the information found in his study will be subject to the confidentiality and privacy regulations of The University of Akron and Kent State University. Confidentiality of records: The project director will store all of your information in a locked research file and will identify you only by a number. The project director will keep the number key connecting your name to your number in a separate secure file. The data will be kept in two secure locations; The University of Akron, in Memorial Hall room 60E, and at Kent State University in the gym annex room 163. The data will be kept for three years and then shredded. Who to contact with questions: If you have any questions at any time, you may contact either of the researchers at (330) 972-7747 or our advisor, Dr. Ronald Otterstetter in the Department of Sport Science and Wellness Education at (330) 972-7738. This project has been reviewed and approved by The University of Akron Institutional Review Board. If you have any questions about your rights as a research participant, you may call Sharon McWhorter, the Associate Director of Research Services & Sponsored Programs at The University of Akron, at (330) 972-8311 of 1-888-232-8790. Thank you for your willingness to participate in this study. Andrea Jankowski-Wilkinson, B.S. Researcher Morgan Russell, B.S. Researcher 29 Edward Ryan, M.S. Researcher Ron Otterstetter, PhD Researcher, Advisor Acceptance & Signature: I have read the information provided above and all of my questions have been answered. I voluntarily agree to participate in this study. I will receive a copy of this consent form for my information. _________________________________ Participant Signature Date:_____________________ _________________________________ Signature of Witness Date:_____________________ 30 APPENDIX C BORG SCALE OF PERCEIVED EXERTION 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 very, very light very light fairly light somewhat hard hard very hard very, very hard 31 APPENDIX D PAIN SCALE 0 No Pain 1 Onset of Pain 2 3 Mild Pain 4 5 Moderate Pain 6 7 Severe Pain 8 9 Barely Tolerable 10 Overwhelming/Unable to Continue 32 APPENDIX E PAIN RATINGS P1 P2 P3 P4 P5 P6 P7 P8 Average -40 0 0 0 0 0 0 0 0 0 -10 0 0 0 0 0 0 0 0 0 P1 P2 P3 P4 P5 P6 P7 P8 Average -40 0 0 0 0 0 0 0 0 0 -10 0 0 0 0 0 0 0 0 0 P1 P2 P3 P4 P5 P6 P7 P8 Average -40 0 0 0 0 0 0 0 0 0 -10 0 0 0 0 0 0 0 0 0 P1 P2 P3 P4 P5 P6 P7 P8 Average -40 0 0 0 0 0 0 0 0 0 -10 0 0 0 0 0 0 0 0 0 Pain Ratings Placebo Trial 10 20 30 3 6 8 4 5 6 2 4 5 6 6 8 9 5 7 8 7 9 3 6 6 4.5 6.43 7 Pain Ratings -35 10 20 30 5 7 8 2 4 6 0 4 6 6 10 8 9 5 6 8 6 9 2 4 5 4.25 6.63 6.6 Pain Ratings -5 10 20 30 3 6 6 5 6 7 3 6 9 7 10 6 8 9 5 6 7 4 6 2 5 5 4.38 6.63 7.17 Pain Ratings +15 10 20 30 4 5 8 4 6 6 1 2 5 6 10 6 9 9 7 7 7 5 9 2 5 5 7 6.63 6.67 33 40 50 8 7 7.5 40 50 8 6 7 40 8 50 8 40 9 50 9 9 9 APPENDIX F PSYCHOMOTOR VIGILANCE TEST CONTROL TRIAL: 50 MINUTES PRIOR TO EXERCISE P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 89 88 88 87 88 85 88 85 87.25 Mean RT 0.284 0.271 0.312 0.273 0.273 0.405 0.33 0.273 0.303 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.21 0.19 0.24 0.19 0.21 0.24 0.22 0.17 0.19 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 0 0 0 0 0 0 Max RT 0.50 0.45 0.69 0.71 0.41 2.01 0.54 0.70 0.60 Others 0 0 0 0 0 0 0 0 0 Std Dev 0.057 0.04 0.07 0.081 0.051 0.251 0.067 0.084 0.088 Median 0.27 0.27 0.30 0.25 0.26 0.32 0.31 0.26 0.27 Duration 305 302 303 303 301 302 302 301 303 Major Lapses 0 0 0 0 0 0 0 0 0 34 Invalid RS 0 1 0 1 0 1 0 2 1 Minor Lapses 1 0 3 2 0 13 4 2 3 False Starts 0 1 0 1 0 1 0 2 1 APPENDIX G PSYCHOMOTOR VIGILANCE TEST CONTROL TRIAL: 25 MINUTES PRIOR TO EXERCISE Mean RT 0.268 0.281 0.324 0.253 0.268 0.336 0.283 0.281 0.275 Std Dev 0.034 0.032 0.139 0.048 0.066 0.079 0.046 0.089 0.062 P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 89 89 87 86 87 87 88 88 88.5 Median 0.26 0.28 0.3 0.24 0.25 0.32 0.28 0.27 0.27 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.21 0.22 0.24 0.19 0.20 0.23 0.21 0.17 0.19 Max RT 0.46 0.43 1.48 0.46 0.67 0.67 0.45 0.78 0.62 Duration 304 305 306 302 304 302 304 303 303.5 Invalid RS 0 0 0 2 1 0 1 2 1 False Starts 0 0 0 0 1 0 1 2 1 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 2 0 0 0 0 0 Others 0 0 0 0 0 0 0 0 0 Major Lapses 0 0 0 0 0 0 0 0 0 Minor Lapses 0 0 3 0 2 3 0 3 1.5 Deadlines 0 0 0 0 0 0 0 0 0 35 APPENDIX H PSYCHOMOTOR VIGILANCE TEST TREATMENT 35 MINUTES PRIOR TO EXERCISE TRIAL: PVT 50 MINUTES PRIOR TO EXERCISE P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 88 88 88 89 89 87 87 88 88 Mean RT 0.292 0.273 0.321 0.274 0.282 0.347 0.307 0.253 0.273 Std Dev 0.057 0.042 0.170 0.086 0.061 0.183 0.061 0.067 0.620 Median 0.28 0.27 0.28 0.26 0.78 0.31 0.29 0.24 0.26 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.21 0.20 0.23 0.20 0.21 0.23 0.21 0.16 0.19 Max RT 0.54 0.42 1.70 0.97 0.53 1.84 0.58 0.44 0.49 Duration 301 301 304 304 304 303 302 302 301.5 Invalid RS 0 1 0 0 0 1 2 1 0.5 False Starts 0 1 0 0 0 1 2 1 0.5 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 0 0 0 0 0 0 Others 0 0 0 0 0 0 0 0 0 Major Lapses 0 0 0 0 0 0 0 0 0 Minor Lapses 1 0 3 1 1 5 2 0 0.5 Deadlines 0 0 0 0 0 0 0 0 0 36 APPENDIX I PSYCHOMOTOR VIGILANCE TEST TREATMENT 35 MINUTES PRIOR TO EXERCISE TRIAL: PVT 25 MINUTES PRIOR TO EXERCISE P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 87 89 87 89 88 88 87 85 86 Mean RT 0.287 0.258 0.291 0.253 0.282 0.303 0.282 0.284 0.286 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.21 0.2 0.23 0.19 0.18 0.23 0.21 0.17 0.19 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 0 0 0 0 0 0 Max RT 0.41 0.50 0.73 0.38 0.82 0.83 0.42 0.70 0.56 Others 0 0 0 0 0 0 0 0 0 Std Dev 0.049 0.041 0.074 0.035 0.083 0.073 0.038 0.099 0.074 Median 0.28 0.25 0.28 0.25 0.26 0.29 0.28 0.25 0.27 Duration 302 302 303 306 304 302 304 300 301 Major Lapses 0 0 0 0 0 0 0 0 0 37 Invalid RS 0 0 0 1 1 0 1 1 0.5 Minor Lapses 0 1 3 0 2 2 0 4 2 False Starts 0 0 0 1 1 0 1 1 0.5 Deadlines 0 0 0 0 0 0 0 0 0 APPENDIX J PSYCHOMOTOR VIGILANCE TEST TREATMENT 5 MINUTES PRIOR TO EXERCISE TRIAL: PVT 50 MINUTES PRIOR TO EXERCISE P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 88 89 89 86 89 88 88 86 87 Mean RT 0.313 0.278 0.263 0.296 0.277 0.323 0.317 0.330 0.322 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.23 0.21 0.21 0.2 0.21 0.22 0.21 0.19 0.21 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 0 0 0 0 0 0 Max RT 0.95 0.48 0.48 0.56 0.53 1.71 0.72 0.69 0.82 Others 0 0 0 0 0 0 0 0 0 Std Dev 0.094 0.045 0.037 0.063 0.058 0.163 0.078 0.102 0.098 Median 0.29 0.27 0.26 0.28 0.26 0.30 0.30 0.31 0.30 Duration 303 304 305 302 304 303 302 301 302 Major Lapses 0 0 0 0 0 0 0 0 0 38 Invalid RS 0 0 1 1 0 0 0 1 0.5 Minor Lapses 0 0 0 1 1 2 3 5 2.5 False Starts 0 0 1 1 0 0 0 1 0.5 Deadlines 0 0 0 0 0 0 0 0 0 APPENDIX K PSYCHOMOTOR VIGILANCE TEST TREATMENT 5 MINUTES PRIOR TO EXERCISE TRIAL: PVT 25 MINUTES PRIOR TO EXERCISE P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 87 83 89 89 87 82 89 82 85 Mean RT 0.28 0.273 0.283 0.278 0.284 0.304 0.273 0.281 0.281 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.2 0.16 0.23 0.22 0.2 0.22 0.21 0.18 0.19 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 0 0 0 0 0 0 Max RT 0.65 2.15 0.79 0.48 0.7 0.48 0.39 0.72 0.69 Others 0 0 0 0 0 0 0 0 0 Std Dev 0.05 0.245 0.061 0.047 0.075 0.066 0.041 0.088 0.069 Median 0.28 0.23 0.27 0.27 0.26 0.28 0.27 0.25 0.27 Duration 302 304 304 305 302 302 304 301 301.5 Major Lapses 0 0 0 0 0 0 0 0 0 39 Invalid RS 0 4 0 1 0 4 0 6 3 Minor Lapses 0 2 1 0 2 0 0 3 1.5 False Starts 0 4 0 1 0 4 0 6 3 Deadlines 0 0 0 0 0 0 0 0 0 APPENDIX L PSYCHOMOTOR VIGILANCE TEST TREATMENT 15 MINUTES INTO TO EXERCISE TRIAL: PVT 50 MINUTES PRIOR TO EXERCISE -50 P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 87 89 88 89 88 87 86 85 86 Mean RT 0.348 0.265 0.259 0.272 0.277 0.317 0.290 0.281 0.315 -50 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.23 0.20 0.20 0.19 0.19 0.20 0.21 0.17 0.20 -50 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 0 0 0 0 1 0.5 Max RT 0.72 0.47 0.5 0.67 0.48 0.98 0.41 4.27 2.495 Others 0 0 0 0 0 0 0 0 0 Std Dev 0.093 0.042 0.046 0.059 0.054 0.101 0.052 0.442 0.268 Median 0.32 0.26 0.25 0.26 0.265 0.3 0.28 0.22 0.27 Duration 302 302 303 304 303 305 0.298 302 302 Major Lapses 0 0 0 0 0 0 0 1 0.5 40 Invalid RS 0 0 0 1 1 0 1 2 1 Minor Lapses 7 0 1 1 0 3 0 2 4.5 False Starts 0 0 0 1 1 0 1 1 0.5 Deadlines 0 0 0 0 0 0 0 0 0 APPENDIX M PSYCHOMOTOR VIGILANCE TEST TREATMENT 15 MINUTES INTO TO EXERCISE TRIAL: PVT 25 MINUTES PRIOR TO EXERCISE P1 P2 P3 P4 P5 P6 P7 P8 Average Valid RS 88 89 88 87 88 88 87 87 87.5 Mean RT 0.338 0.280 0.293 0.315 0.294 0.333 0.273 0.250 0.294 P1 P2 P3 P4 P5 P6 P7 P8 Average Min RT 0.23 0.20 0.22 0.19 0.19 0.21 0.21 0.18 0.21 P1 P2 P3 P4 P5 P6 P7 P8 Average Anticipations 0 0 0 0 0 0 0 0 0 Max RT 0.78 0.45 0.60 4.70 0.74 1.15 0.48 0.57 0.68 Others 0 0 0 0 0 0 0 0 0 Std Dev 0.089 0.038 0.046 0.478 0.086 0.120 0.046 0.067 0.078 Median 0.33 0.27 0.29 0.26 0.27 0.31 0.26 0.23 0.28 Duration 305 305 302 303 301 303 0.303 302 303 Major Lapses 0 0 0 1 0 0 0 0 0 41 Invalid RS 0 0 0 1 0 0 1 1 0.5 Minor Lapses 4 0 1 2 3 5 0 2 3 False Starts 0 0 0 1 0 0 1 1 0.5 Deadlines 0 0 0 0 0 0 0 0 0
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