BRIEF REPORT
Creatine Kinase Levels During Preseason Camp in National Collegiate Athletic Association Division I Football Athletes M. Kyle Smoot, MD,*† Joseph E. Cavanaugh, PhD,‡ Annunziato Amendola, MD,†§ Douglas R. West, PhD, ATC,¶ and Loreen A. Herwaldt, MDk**††
Objective: To investigate mean creatine kinase (CK) levels in National Collegiate Athletic Association (NCAA) Division I football athletes and the relationship between mean CK levels and demographic variables.
Design: Observational cohort. Setting: NCAA Division I football program. Participants: NCAA Division I football athletes. Interventions: Blood and urine samples were obtained from 32 athletes on the first (time 1), third (time 2), and seventh (time 3) days of football camp.
Main Outcome Measures: Mean CK levels. The hypotheses were formulated before the data were collected. Results: All urine samples tested negative for blood. Mean CK levels were 284.7 U/L at time 1, 1299.8 U/L at time 2, and 1562.4 U/L at time 3. The increases in means were statistically significant (P , 0.005 for all pairwise comparisons). Most demographic variables were not related to mean CK levels. The number of days in the precamp conditioning program was negatively associated with mean CK levels (P = 0.0284). Conclusions: Mean CK levels in NCAA Division I football athletes during camp were higher than the serological criteria for rhabdomyolysis commonly used in clinical practice. More data are needed to assess if the number of days of participation in precamp conditioning is related to lower CK levels in NCAA Division I football athletes during camp. Key Words: creatine kinase, athletes (Clin J Sport Med 2014;24:438–440)
Submitted for publication March 22, 2013; accepted October 9, 2013. From the *Department of Family Medicine; and †Institute for Orthopaedics, Sports Medicine & Rehabilitation, The University of Iowa Carver College of Medicine, Iowa City, Iowa; ‡Department of Biostatistics, The University of Iowa College of Public Health, Iowa City, Iowa; §Department of Orthopaedics & Rehabilitation, The University of Iowa Carver College of Medicine, Iowa City, Iowa; ¶Department of Athletics, The University of Iowa, Iowa City, Iowa; kDepartment of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, Iowa; and **Department of Epidemiology; and ††Program of Hospital Epidemiology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Corresponding Author: M. Kyle Smoot, MD, Department of Family Medicine, The University of Iowa Carver College of Medicine, 01106 PFP, 200 Hawkins Dr, Iowa City, IA 52242-1097 ([email protected]). Copyright © 2013 by Lippincott Williams & Wilkins
438
| www.cjsportmed.com
INTRODUCTION Exertional rhabdomyolysis (ER) occurs when strenuous exercise causes excessive skeletal muscle cell breakdown resulting in the release of intracellular contents including creatine kinase (CK). Exertional rhabdomyolysis can result in life-threatening complications including renal failure, compartment syndrome, and cardiac arrhythmia. Severe muscle pain, muscle swelling, and “tea-colored” urine are hallmark signs and symptoms. Numerous potential associated factors for ER have been presented in the literature including heat illness, medications and supplements, recent infection, intense exercise regimes, and genetic polymorphisms.1 In January 2011, 13 University of Iowa football athletes developed ER during off-season workouts.2 The authors used serum CK levels to diagnose rhabdomyolysis, to manage affected players, and to monitor their return-to-play process. Affected athletes’ CK levels ranged from 96 987 to 331 044 U/L,2 which caused us to ask what CK levels are typical for Division I football players after strenuous activity. Ehlers et al3 investigated CK levels in 12 football athletes the morning before “2-a-day” practices and the morning of the 4th, 7th, and 10th day of “2-a-days.” The peak mean CK level was 5124.7 U/L (range, 602-18,823 U/L) on the fourth day. Hoffman et al4 studied 21 National Collegiate Athletic Association (NCAA) Division III football athletes at days 0 and 10 of preseason camp and the 3rd, 7th, and 11th weeks of the season. “Starters” had a peak mean CK level of ;400 U/L on day 10 of preseason camp. Kraemer et al5 assessed 28 Division I football athletes before (1 day) and after (18-20 hours and 42-44 hours) a game. The highest mean CK levels, 330 U/L, occurred 18-20 hours after the game in athletes that played the entire game. Subsequently, Kraemer et al6 found peak mean CK levels of 495 U/L before game 9 of the season. We conducted this study to answer several questions: (1) What CK levels are expected after football training? (2) Are mean CK levels and demographic variables related? and (3) How do CK levels change over time during preseason football camp? Thus, we measured CK levels in Division I football athletes during preseason camp.
METHODS Thirty-two Division I football athletes volunteered for the study. Blood and urine samples were obtained before practice on the first (time 1), third (time 2), and seventh (time 3) days of preseason football camp in August 2011. At each Clin J Sport Med Volume 24, Number 5, September 2014
Clin J Sport Med Volume 24, Number 5, September 2014
time, athletes were screened for evidence of rhabdomyolysis: extreme muscle soreness, swelling, weakness, and “teacolored urine.” Data were collected on age, race, weight, height, body mass index, position, history of rhabdomyolysis, semesters in the program, and number of days of precamp conditioning—34 voluntary workouts during June and July. Data were analyzed using a linear mixed model. CK levels were log transformed to attenuate positive skewness in the distribution and make the assumption of normality defensible.7 A random effect was included in the model for each player to account for the correlation among his 3 CK measurements. An exchangeable correlation structure was employed. Standard errors were estimated using the empirical approach. To assess the relationship between mean CK levels and demographic variables, variables were added to the linear mixed model with time as an explanatory variable. Analyses were conducted using SAS version 9.2 (SAS Institute, Cary, North Carolina).
RESULTS Urine samples were negative for blood and athletes denied symptoms of rhabdomyolysis. Mean CK levels (normal ,200 U/L) were 284.7 U/L (SD = 800.9; range, 72-4659; time 1), 1299.8 U/L (SD = 2283.9; range, 217-12067; time 2), and 1562.4 U/L (SD = 1497.4; range, 229-7453; time 3) (Figure 1) (P , 0.005 for all pairwise comparisons; Figure 2). Most demographic variables were not meaningfully related to mean CK levels (P . 0.05; Table). The number of days of precamp conditioning had a significant (P = 0.0284) negative association with mean CK levels. However, 26 of 32 athletes participated in precamp conditioning for 34 days, and the evidence favoring the decreasing trend is based primarily on CK levels of 5 athletes that participated 20-26 days (Figure 3).
DISCUSSION Our study evaluated the effect of vigorous football training on mean serum CK levels. Our study population was larger than those previously evaluated.3–6 Moreover, our study was the first to assess the relationship between mean
CK Levels in Football Athletes
FIGURE 2. Mean log CK versus time.
CK levels and demographic variables and to ruling out rhabdomyolysis by testing urine samples for blood. At time 2 and time 3, our football athletes’ mean CK levels were higher than 5 times the upper limit of normal, an accepted diagnostic criterion for rhabdomyolysis,8 but athletes did not have symptoms of rhabdomyolysis and their urinalyses were negative for blood. Thus, our data suggest that using CK levels alone to diagnose rhabdomyolysis may not be appropriate for NCAA Division I football athletes and other athletes that undergo similar training. Diagnostic criteria for ER are controversial and experts have not established a consensus clinical or laboratory definition. Our data suggest that more days of precamp conditioning may have been associated with lower CK levels and thus may help protect athletes against muscle damage. However, this observation must be interpreted cautiously because the trend was based primarily on data from 5 athletes. Other studies have supported that conditioning may decrease the risk of exercise-induced muscle damage.9,10 Thus, future studies should assess whether the days of precamp conditioning affect the risk of muscle damage. Such information could help sports medicine providers optimize the duration of precamp conditioning programs. Similar to results from other studies,3–6,9,10 the CK response varied considerably. Hody et al reported that subjects with increased CK response (high responders) demonstrated decreased muscle performance over serial standardized TABLE. Relationships of Demographic Variables with Mean CK Levels P
Variable Age Race Previous diagnosis of rhabdomyolysis No. semesters in football program Weight Height Body mass index Position No. days of precamp conditioning
FIGURE 1. CK levels in football athletes. Ó 2013 Lippincott Williams & Wilkins
0.2621 0.1804 0.6826 0.7773 0.1330 0.2645 0.2293 0.2428 0.0284*
*P # 0.05.
www.cjsportmed.com |
439
Smoot et al
Clin J Sport Med Volume 24, Number 5, September 2014
ACKNOWLEDGMENTS The authors thank the student–athletes for participating in this study and Y. Xu for assistance with formatting the figures. REFERENCES
FIGURE 3. Mean log CK versus days of participation in the precamp conditioning program.
eccentric exercise sessions and had more muscle soreness. These investigators postulated that “high responders” may be at higher risk than “middle responders” and “low responders” for muscle injury or rhabdomyolysis.10 Therefore, we are evaluating epidemiological data to determine if CK response and subsequent muscle injury are related in this cohort. Like Ehlers et al, we evaluated CK levels during the first week of preseason football camp. However, the mean CK levels in our study were much lower than those reported by Ehlers et al.3 Our cohort likely underwent less intense physical activity than athletes evaluated by Ehlers et al because the NCAA now requires an acclimatization period during the initial 5 days of preseason camp.11 This preliminary study has limitations. We did not collect information on sickle cell trait status or history of heat illness and we investigated CK levels over 1 week. A longer study evaluating CK levels throughout the season and during off-season workouts might provide important information about the effect of strenuous athletic activity throughout the year. Despite these limitations, these data will help sports medicine providers because they attempt to diagnose and treat athletes with exertional muscle injury.
440
| www.cjsportmed.com
1. Deuster PA, Contreras-Sesvold CL, O’Connor FG, et al. Genetic polymorphisms associated with exertional rhabdomyolysis. Eur J Appl Physiol. 2013;113:1197–2004. 2. Smoot MK, Amendola A, Cramer E, et al. A cluster of exertional rhabdomyolysis affecting a Division I football team. Clin J Sport Med. 2013; 23:365–372. 3. Ehlers GG, Ball TE, Liston L. Creatine kinase levels are elevated during 2-a-day practices in collegiate football players. J Athl Train. 2002;37: 151–156. 4. Hoffman JR, Kang J, Ratamess NA, et al. Biochemical and hormonal responses during an intercollegiate football season. Med Sci Sports Exerc. 2005;37:1237–1241. 5. Kraemer WJ, Spiering BA, Volek JS, et al. Recovery from a National Collegiate Athletic Association Division I football game: muscle damage and hormonal status. J Strength Cond Res. 2009;23:2–10. 6. Kraemer WJ, Looney DP, Martin GJ, et al. Changes in creatine kinase and cortisol in National Collegiate Athletic Association Division I American football players during a season. J Strength Cond Res. 2013; 27:434–441. 7. Brewster LM, Mairuhu G, Bindraban NR, et al. Creatine kinase activity is associated with blood pressure. Circulation. 2006;114:2034–2039. 8. O’Connor FG, Brennan FH Jr, Campbell W, et al. Return to physical activity after exertional rhabdomyolysis. Curr Sports Med Rep. 2008;7: 328–331. 9. Hody S, Leprince P, Sergeant K, et al. Human muscle proteome modifications after acute or repeated eccentric exercises. Med Sci Sports Exerc. 2011;43:2281–2296. 10. Hody S, Rogister B, Leprince P, et al. Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response [published online ahead of print November 23, 2011]. Scand J Med Sci Sports. doi: 10.1111/j.1600-0838.2011.01413.x. 11. NCAA Academic and Membership Affairs Staff. 2012-2013 NCAA Division I manual [NCAA Publications website]. Article 17.9.2.3 FiveDay Acclimatization Period. [FBS/FCS]. Page 269. http://www. ncaapublications.com/productdownloads/D113.pdf. Accessed September 7, 2012.
Ó 2013 Lippincott Williams & Wilkins
Creatine Kinase Levels During Preseason Camp in National Collegiate Athletic Association Division I Football Athletes M. Kyle Smoot, MD,*† Joseph E. Cavanaugh, PhD,‡ Annunziato Amendola, MD,†§ Douglas R. West, PhD, ATC,¶ and Loreen A. Herwaldt, MDk**††
Objective: To investigate mean creatine kinase (CK) levels in National Collegiate Athletic Association (NCAA) Division I football athletes and the relationship between mean CK levels and demographic variables.
Design: Observational cohort. Setting: NCAA Division I football program. Participants: NCAA Division I football athletes. Interventions: Blood and urine samples were obtained from 32 athletes on the first (time 1), third (time 2), and seventh (time 3) days of football camp.
Main Outcome Measures: Mean CK levels. The hypotheses were formulated before the data were collected. Results: All urine samples tested negative for blood. Mean CK levels were 284.7 U/L at time 1, 1299.8 U/L at time 2, and 1562.4 U/L at time 3. The increases in means were statistically significant (P , 0.005 for all pairwise comparisons). Most demographic variables were not related to mean CK levels. The number of days in the precamp conditioning program was negatively associated with mean CK levels (P = 0.0284). Conclusions: Mean CK levels in NCAA Division I football athletes during camp were higher than the serological criteria for rhabdomyolysis commonly used in clinical practice. More data are needed to assess if the number of days of participation in precamp conditioning is related to lower CK levels in NCAA Division I football athletes during camp. Key Words: creatine kinase, athletes (Clin J Sport Med 2014;24:438–440)
Submitted for publication March 22, 2013; accepted October 9, 2013. From the *Department of Family Medicine; and †Institute for Orthopaedics, Sports Medicine & Rehabilitation, The University of Iowa Carver College of Medicine, Iowa City, Iowa; ‡Department of Biostatistics, The University of Iowa College of Public Health, Iowa City, Iowa; §Department of Orthopaedics & Rehabilitation, The University of Iowa Carver College of Medicine, Iowa City, Iowa; ¶Department of Athletics, The University of Iowa, Iowa City, Iowa; kDepartment of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, Iowa; and **Department of Epidemiology; and ††Program of Hospital Epidemiology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Corresponding Author: M. Kyle Smoot, MD, Department of Family Medicine, The University of Iowa Carver College of Medicine, 01106 PFP, 200 Hawkins Dr, Iowa City, IA 52242-1097 ([email protected]). Copyright © 2013 by Lippincott Williams & Wilkins
438
| www.cjsportmed.com
INTRODUCTION Exertional rhabdomyolysis (ER) occurs when strenuous exercise causes excessive skeletal muscle cell breakdown resulting in the release of intracellular contents including creatine kinase (CK). Exertional rhabdomyolysis can result in life-threatening complications including renal failure, compartment syndrome, and cardiac arrhythmia. Severe muscle pain, muscle swelling, and “tea-colored” urine are hallmark signs and symptoms. Numerous potential associated factors for ER have been presented in the literature including heat illness, medications and supplements, recent infection, intense exercise regimes, and genetic polymorphisms.1 In January 2011, 13 University of Iowa football athletes developed ER during off-season workouts.2 The authors used serum CK levels to diagnose rhabdomyolysis, to manage affected players, and to monitor their return-to-play process. Affected athletes’ CK levels ranged from 96 987 to 331 044 U/L,2 which caused us to ask what CK levels are typical for Division I football players after strenuous activity. Ehlers et al3 investigated CK levels in 12 football athletes the morning before “2-a-day” practices and the morning of the 4th, 7th, and 10th day of “2-a-days.” The peak mean CK level was 5124.7 U/L (range, 602-18,823 U/L) on the fourth day. Hoffman et al4 studied 21 National Collegiate Athletic Association (NCAA) Division III football athletes at days 0 and 10 of preseason camp and the 3rd, 7th, and 11th weeks of the season. “Starters” had a peak mean CK level of ;400 U/L on day 10 of preseason camp. Kraemer et al5 assessed 28 Division I football athletes before (1 day) and after (18-20 hours and 42-44 hours) a game. The highest mean CK levels, 330 U/L, occurred 18-20 hours after the game in athletes that played the entire game. Subsequently, Kraemer et al6 found peak mean CK levels of 495 U/L before game 9 of the season. We conducted this study to answer several questions: (1) What CK levels are expected after football training? (2) Are mean CK levels and demographic variables related? and (3) How do CK levels change over time during preseason football camp? Thus, we measured CK levels in Division I football athletes during preseason camp.
METHODS Thirty-two Division I football athletes volunteered for the study. Blood and urine samples were obtained before practice on the first (time 1), third (time 2), and seventh (time 3) days of preseason football camp in August 2011. At each Clin J Sport Med Volume 24, Number 5, September 2014
Clin J Sport Med Volume 24, Number 5, September 2014
time, athletes were screened for evidence of rhabdomyolysis: extreme muscle soreness, swelling, weakness, and “teacolored urine.” Data were collected on age, race, weight, height, body mass index, position, history of rhabdomyolysis, semesters in the program, and number of days of precamp conditioning—34 voluntary workouts during June and July. Data were analyzed using a linear mixed model. CK levels were log transformed to attenuate positive skewness in the distribution and make the assumption of normality defensible.7 A random effect was included in the model for each player to account for the correlation among his 3 CK measurements. An exchangeable correlation structure was employed. Standard errors were estimated using the empirical approach. To assess the relationship between mean CK levels and demographic variables, variables were added to the linear mixed model with time as an explanatory variable. Analyses were conducted using SAS version 9.2 (SAS Institute, Cary, North Carolina).
RESULTS Urine samples were negative for blood and athletes denied symptoms of rhabdomyolysis. Mean CK levels (normal ,200 U/L) were 284.7 U/L (SD = 800.9; range, 72-4659; time 1), 1299.8 U/L (SD = 2283.9; range, 217-12067; time 2), and 1562.4 U/L (SD = 1497.4; range, 229-7453; time 3) (Figure 1) (P , 0.005 for all pairwise comparisons; Figure 2). Most demographic variables were not meaningfully related to mean CK levels (P . 0.05; Table). The number of days of precamp conditioning had a significant (P = 0.0284) negative association with mean CK levels. However, 26 of 32 athletes participated in precamp conditioning for 34 days, and the evidence favoring the decreasing trend is based primarily on CK levels of 5 athletes that participated 20-26 days (Figure 3).
DISCUSSION Our study evaluated the effect of vigorous football training on mean serum CK levels. Our study population was larger than those previously evaluated.3–6 Moreover, our study was the first to assess the relationship between mean
CK Levels in Football Athletes
FIGURE 2. Mean log CK versus time.
CK levels and demographic variables and to ruling out rhabdomyolysis by testing urine samples for blood. At time 2 and time 3, our football athletes’ mean CK levels were higher than 5 times the upper limit of normal, an accepted diagnostic criterion for rhabdomyolysis,8 but athletes did not have symptoms of rhabdomyolysis and their urinalyses were negative for blood. Thus, our data suggest that using CK levels alone to diagnose rhabdomyolysis may not be appropriate for NCAA Division I football athletes and other athletes that undergo similar training. Diagnostic criteria for ER are controversial and experts have not established a consensus clinical or laboratory definition. Our data suggest that more days of precamp conditioning may have been associated with lower CK levels and thus may help protect athletes against muscle damage. However, this observation must be interpreted cautiously because the trend was based primarily on data from 5 athletes. Other studies have supported that conditioning may decrease the risk of exercise-induced muscle damage.9,10 Thus, future studies should assess whether the days of precamp conditioning affect the risk of muscle damage. Such information could help sports medicine providers optimize the duration of precamp conditioning programs. Similar to results from other studies,3–6,9,10 the CK response varied considerably. Hody et al reported that subjects with increased CK response (high responders) demonstrated decreased muscle performance over serial standardized TABLE. Relationships of Demographic Variables with Mean CK Levels P
Variable Age Race Previous diagnosis of rhabdomyolysis No. semesters in football program Weight Height Body mass index Position No. days of precamp conditioning
FIGURE 1. CK levels in football athletes. Ó 2013 Lippincott Williams & Wilkins
0.2621 0.1804 0.6826 0.7773 0.1330 0.2645 0.2293 0.2428 0.0284*
*P # 0.05.
www.cjsportmed.com |
439
Smoot et al
Clin J Sport Med Volume 24, Number 5, September 2014
ACKNOWLEDGMENTS The authors thank the student–athletes for participating in this study and Y. Xu for assistance with formatting the figures. REFERENCES
FIGURE 3. Mean log CK versus days of participation in the precamp conditioning program.
eccentric exercise sessions and had more muscle soreness. These investigators postulated that “high responders” may be at higher risk than “middle responders” and “low responders” for muscle injury or rhabdomyolysis.10 Therefore, we are evaluating epidemiological data to determine if CK response and subsequent muscle injury are related in this cohort. Like Ehlers et al, we evaluated CK levels during the first week of preseason football camp. However, the mean CK levels in our study were much lower than those reported by Ehlers et al.3 Our cohort likely underwent less intense physical activity than athletes evaluated by Ehlers et al because the NCAA now requires an acclimatization period during the initial 5 days of preseason camp.11 This preliminary study has limitations. We did not collect information on sickle cell trait status or history of heat illness and we investigated CK levels over 1 week. A longer study evaluating CK levels throughout the season and during off-season workouts might provide important information about the effect of strenuous athletic activity throughout the year. Despite these limitations, these data will help sports medicine providers because they attempt to diagnose and treat athletes with exertional muscle injury.
440
| www.cjsportmed.com
1. Deuster PA, Contreras-Sesvold CL, O’Connor FG, et al. Genetic polymorphisms associated with exertional rhabdomyolysis. Eur J Appl Physiol. 2013;113:1197–2004. 2. Smoot MK, Amendola A, Cramer E, et al. A cluster of exertional rhabdomyolysis affecting a Division I football team. Clin J Sport Med. 2013; 23:365–372. 3. Ehlers GG, Ball TE, Liston L. Creatine kinase levels are elevated during 2-a-day practices in collegiate football players. J Athl Train. 2002;37: 151–156. 4. Hoffman JR, Kang J, Ratamess NA, et al. Biochemical and hormonal responses during an intercollegiate football season. Med Sci Sports Exerc. 2005;37:1237–1241. 5. Kraemer WJ, Spiering BA, Volek JS, et al. Recovery from a National Collegiate Athletic Association Division I football game: muscle damage and hormonal status. J Strength Cond Res. 2009;23:2–10. 6. Kraemer WJ, Looney DP, Martin GJ, et al. Changes in creatine kinase and cortisol in National Collegiate Athletic Association Division I American football players during a season. J Strength Cond Res. 2013; 27:434–441. 7. Brewster LM, Mairuhu G, Bindraban NR, et al. Creatine kinase activity is associated with blood pressure. Circulation. 2006;114:2034–2039. 8. O’Connor FG, Brennan FH Jr, Campbell W, et al. Return to physical activity after exertional rhabdomyolysis. Curr Sports Med Rep. 2008;7: 328–331. 9. Hody S, Leprince P, Sergeant K, et al. Human muscle proteome modifications after acute or repeated eccentric exercises. Med Sci Sports Exerc. 2011;43:2281–2296. 10. Hody S, Rogister B, Leprince P, et al. Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response [published online ahead of print November 23, 2011]. Scand J Med Sci Sports. doi: 10.1111/j.1600-0838.2011.01413.x. 11. NCAA Academic and Membership Affairs Staff. 2012-2013 NCAA Division I manual [NCAA Publications website]. Article 17.9.2.3 FiveDay Acclimatization Period. [FBS/FCS]. Page 269. http://www. ncaapublications.com/productdownloads/D113.pdf. Accessed September 7, 2012.
Ó 2013 Lippincott Williams & Wilkins
