American football players practice and play at high levels of intensity, often in environmentally stressful conditions. Studies related to muscle cell damage in response to American football practice have not been widely done. Skeletal muscle fiber damage is considered a normal physiological response to sport activity,1 but excessive amounts can be dangerous to an athlete. Specifically, exertional rhabdomyolysis can occur in response to strenuous exercise when mechanical or metabolic stress damages the skeletal muscle and causes significant leakage of muscle cell contents into the plasma, including potassium, myoglobin, and creatine kinase.2,3 The criteria for exertional rhabdomyolysis are somewhat controversial, but a serum creatine kinase level of at least 5 times the upper limit is often used as a diagnostic tool.3,4 Exertional rhabdomyolysis can result in life-threatening complications including renal failure, compartment syndrome, and cardiac arrhythmia.2,5 Examination of serum creatine kinase levels can be used to highlight activities and populations at risk.5,6
Exertional rhabdomyolysis classically presents with severe muscle pain, muscle swelling, and “tea-colored” urine.2 Associated risk factors for exertional rhabdomyolysis that have been presented include medications and supplements, infection, genetic polymorphisms, and exertional heat illness.2,3,6 Focusing on the latter, the risk for exertional rhabdomyolysis is increased when strenuous body-contact exercise is performed in the heat.3,6–12 Specifically, peripheral tissue damage occurs in individuals who suffer from exertional hyperthermia and can also result in elevated serum creatine kinase levels.13 Complicating the issue, the cardiovascular response to an elevated core temperature from exercise in extreme environmental conditions is to increase skin blood flow to dissipate heat and may create competition for blood between the skeletal muscle, heart, skin, and the production of sweat from filtering blood plasma.13
Athletes participating in daily training have been shown to have higher resting creatine kinase values than non-athletes. Mougios1 examined serum creatine kinase levels in 485 male athletes and determined a serum creatine kinase reference interval of 82 to 1,083 U/L−1 based on his analysis, but indicated that sports with higher levels of intensity and contact performed in harsh environmental conditions resulted in higher serum creatine kinase levels. American football practices during preseason training are consistently the most rigorous and are performed in the month of August, which is a historically hot and humid month across the country.
In 2002, Ehlers et al.14 examined serum creatine kinase levels in 12 Division I American football players during preseason training. They were able to demonstrate significant increases in serum creatine kinase levels during the first 10 days of preseason training.14 Notably, the serum creatine kinase levels peaked on day 4 of “2-a-day” practices with a mean value of 5,124.7 ± 2,283.9 U/L−1 (range: 602 to 18,823 U/L−1) compared to the baseline value of 2,013.8 ± 67 U/L−1.
In 2003, there was a change in the National Collegiate Athletic Association (NCAA) practice guidelines for American football that allowed for a 5-day acclimatization period during preseason training, which significantly decreased the number of 2-a-day practices and volume of full-contact hitting within.15 Following this mandate, Smoot et al.2 examined creatine kinase levels in Division I American football players on days 1, 3, and 7 of preseason training and also demonstrated creatine kinase levels above the reference limits for male athletes on days 3 and 7 (1,299.8 ± 2,283.9 and 1,562.4 ± 1,497.4 U/L−1, respectively). However, the mean values were much lower than those reported by Ehlers et al.,14 supporting the increase in safety with the acclimatization mandate.2
In 2005, Hoffman et al.16 examined creatine kinase levels in the Division III setting, but only captured days 0 and 10 of the critical preseason time frame. Nonetheless, creatine kinase levels were significantly higher at day 10 (range: 350 to 580 U/L−1) when compared to their baseline values, but did not reveal values outside of the reference interval for male athletes.16
Although advances have been made, there are still few studies that have examined serum creatine kinase levels in American football during the critical preseason period to provide a clearer understanding of the expected serum creatine kinase levels. There are also no reports of mean serum creatine kinase levels in the Division II setting of American football. Therefore, the purpose of this study was to examine serum creatine kinase levels in American football at the Division II level during preseason practices. We hypothesized that serum creatine kinase levels would significantly increase during the first 10 days of preseason training similar to previous reports and the values would exceed the reference intervals for male athletes.1 An additional goal of this study was to examine whether body mass index (BMI) or hydration status (measured via serum osmolality) influenced the serum creatine kinase levels of American football players during preseason training.
Twelve NCAA Division II collegiate football players from West Chester University volunteered for participation in this study. To reflect previous data collection procedures by Ehlers et al.,14 we recruited participants with wide ranges in size and from various positions. Participants had a mean age of 22 ± 0.9 years, height of 182.3 ± 4.7 cm, weight of 101.8 ± 20.5 kg, and BMI of 30.5 ± 5.1 kg/m2. Player positions included wide receiver (n = 1), tight end (n = 1), quarterback (n = 1), defensive back (n = 1), nose guard (n = 1), running back (n = 2), linebacker (n = 3), and offensive tackle (n = 3). No participant had a current or recent muscular injury, reported any use of prescription drugs, or suffered from any muscular or valvular diseases.
Participants volunteered from a group of returning players who were accustomed to the preseason training schedule. Prior to the start of camp, participants were required to perform resistance and endurance training as provided to them by the strength and conditioning staff. Therefore, it was assumed that the participants were acclimated and in proper condition. However, it should be noted that specific data on the number of precamp conditioning sessions that each participant performed were not collected.
All participants were informed of the minimal risks involved with the blood draws and signed an informed consent prior to participation. The study was approved by the West Chester University Institutional Review Board of Human Subjects Subcommittee.
Throughout the preseason training collection period, the environmental conditions and practice frequency were tracked and monitored by the athletic training staff to ensure that all NCAA guidelines were followed. Prior to beginning preseason football training, each participant's BMI was calculated (body weight in kg/height in square meters) and baseline serum creatine kinase and osmolality levels were determined. For BMI calculations, body mass was assessed using the ProDoc PD100 scale (Detecto, Webb City, MO) and height was calculated using the SECA Height Rod (Seca GmbH, Hamburg, Germany). The methods and days for serum creatine kinase and osmolality levels collection mirrored those used in the study by Ehlers et al.14 Blood was drawn during the preseason physical examination (baseline), which was taken in the morning on the day before the first official practice. Blood samples were then taken on the mornings (typically between 6:00 AM and 8:00 AM, before any practice or weight-lifting session) of days 4, 7, and 10 of the preseason football practices. In addition to mirroring previous methods,12 these dates were chosen to exhibit serum creatine kinase levels prior to the initiation of full pads and 2-a-day practices (day 4), after the initiation of full pads and 2-a-day practices (day 7), and after repeated 2-a-day practices (day 10) (Table 1).
Practice Descriptions and Environmental Data During the First 10 Days of Preseason Training
All blood samples were obtained from an antecubital vein using an 18-gauge needle into a serum vacutainer tube (Becton, Dickinson, and Co., Franklin Lakes, NJ) by an experienced phlebotomist (SFG). For each specimen, approximately 5 cc of blood was drawn. Allowing 15 to 20 minutes for clotting at room temperature, the serum tubes were then spun at 2,500 rpm for 10 minutes using the IEC Centra CL2 (Thermo Fischer Scientific Inc., Pittsburgh, PA). To assess for hydration status, 1 cc of serum was immediately analyzed for serum osmolality by freezing point depression (Osmette Osmometer; Precision Systems, Inc., Natick, MA). The remaining serum was transferred to cryovials and refrigerated. One 2-cc serum sample was generated for each participant for creatine kinase level analysis, which provided an adequate amount of serum to be assayed in duplicate. The refrigerated serum samples were transported within 24 hours to the LabCorp laboratory in Raritan, New Jersey, for analysis of serum creatine kinase levels. The serum creatine kinase levels were assayed spectrophotometrically through the use of the Roche Hitachi Modular CK analyzer (Roche Diagnostics, Indianapolis, IN) for analysis.
Statistical analysis was performed using SPSS software (version 18.0; IBM Corporation, Armonk, NY). A one-way repeated measures analysis of variance test with Tukey's post-hoc analysis was calculated to test for differences in mean serum creatine kinase levels between days. Pearson's correlations were used to evaluate the relationships between serum creatine kinase levels and BMI and serum creatine kinase and osmolality levels on each collection day. The alpha level was set at a P value of less than .05.
The mean serum creatine kinase levels for the participants for each collection day are presented in Figure 1. Results from the analysis of variance test revealed statistically significant main effects for serum creatine kinase levels between days (F3,33 = 4.72, P = .006). Tukey's post hoc analysis revealed that, compared to serum creatine kinase levels at baseline (299 ± 205 U/L−1), levels were significantly higher on days 4 (1,497 ± 1,087 U/L−1, P = .035), 7 (1,773 ± 1,404 U/L−1, P = .006), and 10 (1,463 ± 1,073 U/L−1, P = .043) (Figure 1). No significant differences were found between serum creatine kinase levels on days 4, 7, and 10. There was no correlation between BMI and serum creatine kinase levels on days 4 (R = 0.112, P = .73), 7 (R = −0.143, P = .66), or 10 (R = −0.028, P = .93), or at baseline (R = −0.008, P = .98). Serum osmolality values for each collection day can be viewed in Table 2. There were no significant correlations between serum osmolality and creatine kinase levels on days 4 (R = 0.362, P = .25), 7 (R = −0.373, P = .23), or 10 (R = −0.182, P = .57), or at baseline (R = 0.137, P = .67).
Mean serum creatine kinase levels (CK) over 4 test days. *Significantly different (P < .05) when compared to CKBline. CKBline = baseline/day 0; CK4 = day 4; CK7 = day 7; CK10 = day 10
Serum Osmolality (mOSM/kg) Across Days
The main purpose of this study was to measure serum creatine kinase levels in Division II American football players during preseason training. Serum creatine kinase levels significantly increased throughout the first 10 days of practice when compared to baseline. The preseason practices coincided with the rules described in the 2003 NCAA mandate for acclimatization.15 This included a ramping period to full-padded activity from days 1 to 5 and multiple practice sessions per day did not occur (Table 1).
The significant increase in serum creatine kinase levels on day 4 may be due to the fact that day 3 was the first time that the participants practiced with any padding in addition to the increase in activity on days 1 and 2. Studies indicate that serum creatine kinase levels remain elevated for several days after exercise and peak between 24 hours and 4 days after exercise.1,17 Thus, these values can be attributed to the cumulative effect of recent training sessions.1,17 Days 1 and 2 consisted of light practice in shorts. These days were the least intense in the preseason training schedule and included 24 5-minute periods that consisted of drills, individual work, team work, and “7 versus 7” scrimmages without contact. Contact was first initiated while in shells, but players were not tackled to the ground. Notably, this was also 24 to 48 hours after consecutive days with a weight lifting session and a football practice session. The weight lifting session was broken up into stations that focused on the chest and triceps musculature and included isotonic exercises with an equal amount of concentric and eccentric demand.
The serum creatine kinase levels measured on day 7 were the highest reported during data collection. Day 5 was the first day of pads, which indicated the first day of full contact, and day 6 was the first 2-a-day preseason football practice. On this day, participants also participated in the situational scrimmage “Omaha” drill, which involved substantial tackling to the ground. The increase in collision activity would conceivably cause more skeletal muscle cell damage than practice in either shorts or shells. This, in combination with the increase in activity leading up to day 7, was likely why these values increased significantly.
Serum creatine kinase levels reported on day 10 were lower than days 7 and 4 (Figure 1), which may be due to the participants becoming heat acclimatized and physically conditioned to the exercise intensity.18 Although we do not have any physiological data on the participants to provide a profile for their acclimatization status, they were within the time frame of 7 to 14 days of exercise in the heat wherein full adaptations occur.19 Serum creatine kinase levels have been previously demonstrated to be more elevated after the onset of exercise and have been shown to decrease around day 10.1,14 This can also be attributed to the repeated-bout effect, in which repetition of an exercise after several days causes less muscle fiber damage than that caused by previous exercise.1,17
The mean serum creatine kinase levels obtained on days 4 (1,497 ± 1,087 U/L−1), 7 (1,773 ± 1,404 U/L−1), and 10 (1,463 ± 1,073 U/L−1) are greater than some normal ranges reported in the literature15 and fall outside the reference interval set by Mougios1 for male athletes (range: 82 to 1,083 U/L−1). However, the mean serum creatine kinase level on day 7 exceeded the confidence interval for the upper reference limit (range: 881 to 1,497 U/L−1). This supports the notion presented by Mougois1 that male sports with higher mechanical impacts with other players may result in increases of serum creatine kinase levels.
Although no participant in this study reported symptoms of exertional rhabdomyolysis, these serum creatine kinase levels would be considered high enough for some diagnoses of exertional rhabdomyolysis, which has been classified as 5 to 10 times greater than normal resting serum creatine kinase levels (range: 55 to 170 U/L−1).4,20,21 Literature also suggests that a creatine kinase level range of more than 10,000 to 20,000 U/L−1 is a more appropriate threshold to begin treatment for rhabdomyolysis complications.22,23 It is unknown whether the athletes in this study exhibited any other laboratory evidence of exertional rhabdomyolysis, such as pH disturbances, creatinine and lactate dehydrogenase increases, or the presence of myoglobinuria, because these were not measured. Although there is no commonly accepted algorithm for determining when to hospitalize and treat individuals who present with elevated creatine kinase levels,4,24 these data support that using serum creatine kinase levels alone to diagnose rhabdomyolysis may not be appropriate for NCAA American football athletes. Similar mean creatine kinase levels were reported by Smoot et al.2 during preseason training at the Division I setting with no cases of exertional rhabdomyolysis reported.
Several cases of rhabdomyolysis during preseason American football training have been recounted in the literature.8,12,25–29 The creatine kinase levels in these published cases range from 5,727 to 130,899 U/L−1, thus highlighting the variation in reported levels.8,12,25–29 Common themes surrounding the epidemiology of exertional rhabdomyolysis in this population and others include sudden alterations in training regimens, hot environmental conditions, poor conditioning, and exertional sickling.25 Dehydration has also been associated with rhabdomyolysis cases and can exacerbate muscle damage and necrosis in untrained individuals performing unaccustomed exercises in the heat.26,28,29 In this study, serum creatine kinase levels were not correlated to hydration status as measured by serum osmolality,30 which is the accepted gold standard for measuring hydration status. Several of the athletes in this study presented with serum osmolality levels above a hypohydrated range (> 295 mOsm/kg),30,31 but this showed no relationship to serum creatine kinase levels. Once again, serum creatine kinase levels may not be the only factor in determining the diagnosis of exertional rhabdomyolysis.
It has been suggested that heat acclimatization can lead to decreased serum creatine kinase levels, especially when examining athletes participating in physical activity.18 Terblanche and Nel18 reported significantly lower creatine kinase levels in the working muscles and vital organs of rats after heat acclimatization. To compare these levels to those reported by Ehlers et al.14 prior to the acclimatization mandate, we used the same number of participants with similar demographics and mirrored the creatine kinase level collection methods. The serum creatine kinase levels we observed during preseason practices were markedly lower than those reported in 2002.14 Specifically, they were considerably reduced during days 4 to 7. Traditionally, this is a high-risk time frame for the development of exertional heat illness and rhabdomyolysis, although the risk remains high throughout day 14.8,12,25–29 Possible explanations for these contrasting creatine kinase levels may be attributed to the 2003 NCAA mandate. Comparisons are only anecdotal because participants, coaches, practice intensity, geographical area, and climate may have been different.
Looking at baseline levels, our findings were similar to others demonstrated in American football athletes,2,14,32 indicating that these athletes come into preseason with slightly elevated creatine kinase levels and the levels are not abnormal.32 The creatine kinase levels found by Ehlers et al.14 on day 4 were 3.4 times higher than those that were found in this study. In addition, their day-7 serum creatine kinase levels14 were 1.9 times higher than our reported day-7 levels. Although the authors did not provide a detailed practice description or environmental data, they were not restricted in the amount of practices in pads or consecutive 2-a-day practices. Their day-10 serum creatine kinase levels14 were not markedly different than our day-10 values (1,463 ± 1,074 vs 1,263 ± 990.6 U/L−1, respectively).
Our mean serum creatine kinase levels were similar to those reported by Smoot et al.,2 which were collected after the acclimatization mandate. Specifically, Smoot et al.'s study2 examined serum creatine kinase levels in 32 Division I football players during preseason training and reported mean levels before practice on days 1 (284.7 ± 800.9 U/L−1), 3 (1,299.8 ± 2,283.9 U/L−1), and 7 (1,562.4 ± 1,497.4 U/L−1). They also acknowledged that their values were lower than those reported by Ehlers et al.14 and suggested that the acclimatization mandate for preseason training may have influenced these values.2
Limitations to this study include the lack of control over the participants' physical activity because they were not monitored to ensure that no other exercise occurred outside of the sanctioned team preseason training sessions. Moreover, the exercise intensity of each player during practice was also not controlled, which would influence the serum creatine kinase levels in each participant. Most importantly, we did not collect data on other clinical biomarkers for muscle damage such as myoglobinuria. Therefore, we cannot make firm conclusions on the diagnosis of rhabdomyolysis in any participant. Additionally, we did not collect information on sickle cell trait status, biological race, or heat illness history. Other limitations include the small participant number and the inability to control the environmental conditions during or between each practice. As with any field study, some control was compromised to ensure practical application.
The findings reported in this study contribute to the literature on serum creatine kinase levels in American football players during preseason training. For a more comprehensive understanding of the physical stresses incurred by this population during preseason training, other biomarkers for muscle damage should be explored. In particular, monitoring myoglobin, lactate dehydrogenase, and alpha-actin may provide further insight into the occurrence and extent of muscle cell damage.
Implications for Clinical Practice
In this observational field study, we report serum creatine kinase levels in Division II American football players during preseason training. Our data indicate that this population experiences a surge in serum creatine kinase levels during the first week of preseason training and a subsequent decline on day 10. Implications for clinical practice are twofold.
First, athletic trainers working with American football must be continually aware of the potential risk for exertional rhabdomyolysis in this population due to high-intensity training and/or heat cytotoxicity during preseason training. However, this study does indicate that serum creatine kinase levels are often above the normal range for male athletes reported in the literature, without the presence of exertional rhabdomyolysis. Recognizing the signs and symptoms of rhabdomyolysis such as myalgia, limb weakness, and tea-colored urine should be a continued priority of athletic training staff during preseason training.
Second, the results of this study and that by Smoot et al.2 demonstrate lower average creatine kinase levels during preseason training when compared to Ehlers et al.,14 which was conducted prior to the NCAA acclimatization mandate. Although there certainly are limitations to this comparison, it supports such mandates outside of the NCAA in the American football population. Specifically, it provides an objective rationale for the implementation of suggested heat acclimatization guidelines in the secondary school setting across all states.33 The primary goal of the acclimatization guidelines is to allow for physiological adaptations to exercising in the heat and to minimize heat-related injury. However, the decreased practice sessions and elimination of consecutive days of multiple practices also reduce the amount of skeletal muscle activity and direct trauma during preseason training, which is indicated by lower serum creatine kinase levels than previously reported. Athletic trainers should continue to support these mandates in states that continue to not provide these guidelines to increase the health and safety of American football players.
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- Smoot MK, Cavanaugh JE, Amendola A, West DR, Herwaldt LA. Creatine kinase levels during preseason camp in National Collegiate Athletic Association division I football athletes. Clin J Sport Med. 2014;24:438–440. doi:10.1097/JSM.0000000000000057 [CrossRef]
- Capacchione JF, Muldoon SM. The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia. Anesth Analg. 2009;109:1065–1069. doi:10.1213/ane.0b013e3181a9d8d9 [CrossRef]
- Warren JD, Blumbergs PC, Thompson PD. Rhabdomyolysis: a review. Muscle Nerve. 2002;25:332–347. doi:10.1002/mus.10053 [CrossRef]
- Munjal DD, McFadden JA, Matix PA, Coffman KD, Cattaneo SM. Changes in serum myoglobin, total creatine kinase, lactate dehydrogenase and creatine kinase MB levels in runners. Clin Biochem. 1983;16:195–199. doi:10.1016/S0009-9120(83)90279-5 [CrossRef]
- Clarkson PM. Worst case scenarios: exertional rhabdomyolysis and acute renal failure in marathon runners. Sports Medicine. 2007;37:361–363. doi:10.2165/00007256-200737040-00022 [CrossRef]
- Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: rhabdomyolysis: an overview for clinicians. Crit Care. 2005;9:158–169. doi:10.1186/cc2978 [CrossRef]
- Rosenthal MA, Parker DJ. Collapse of a young athlete. Ann Emerg Med. 1992;21:1493–1498. doi:10.1016/S0196-0644(05)80068-X [CrossRef]
- O'Connor FG, Brennan FH Jr, Campbell W, Heled Y, Deuster P. Return to physical activity after exertional rhabdomyolysis. Curr Sports Med Rep. 2008;7:328–331. doi:10.1249/JSR.0b013e31818f0317 [CrossRef]
- Epstein Y. Clinical significance of serum creatine phosphokinase activity levels following exercise. Isr J Med Sci. 1995;31:698–699.
- Kahanov L, Eberman LE, Wasik M, Alvey T. Exertional rhabdomyolysis in a collegiate American football player after preventive cold-water immersion: a case report. J Athl Train. 2012;47:228–232. doi:10.4085/1062-6050-47.2.228 [CrossRef]
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- 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.
- NCAA Academic and Membership Affairs Staff, ed. 2011–2012 NCAA Division II Manual. Indianapolis, IN: The National Collegiate Athletic Association; 2011: 199–200.
- Hoffman JR, Kang J, Ratamess NA, Faigenbaum AD. Biochemical and hormonal responses during an intercollegiate football season. Med Sci Sport Exerc. 2005;37:1237–1241. doi:10.1249/01.mss.0000170068.97498.26 [CrossRef]
- McHugh MP. Recent advances in the understanding of the repeated bout effect: the protective effect against muscle damage from a single bout of eccentric exercise. Scand J Med Sci Sports. 2003;13:88–97. doi:10.1034/j.1600-0838.2003.02477.x [CrossRef]
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- Wednt D, van Loon LJ, Lichtenbelt WD. Thermoregulation during exercise in the heat: strategy for maintaining health and performance. Sports Med. 2007;37:669–682. doi:10.2165/00007256-200737080-00002 [CrossRef]
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Practice Descriptions and Environmental Data During the First 10 Days of Preseason Training
|Day||Practice Time||Activity||Average Temperature||Average Relative Humidity|
|1||9:00 to 11:15 AM||Light practice in shorts||77°F / 25.0°C||44%|
|2||9:00 to 11:15 AM||Light practice in shorts||76°F / 24.4°C||46%|
|3||2:00 to 4:15 PM||Practice in shellsa,b||79°F / 26.1°C||46%|
|4||2:00 to 4:15 PM||Practice in shellsa,b||75°F / 23.9°C||59%|
|5||9:00 to 11:15 AM||Practice in full padsc||74°F / 23.3°C||67%|
|6||9:00 to 11:15 AM||Practice in full padsd||74°F / 23.3°C||64%|
|6||2:45 to 5:00 PM||Practice in shellsa||74°F / 23.3°C||64%|
|7||9:00 to 11:15 AM||Practice in full pads||78°F / 25.6°C||57%|
|7||2:45 to 5:00 PM||Practice in shellsa||78°F / 25.6°C||57%|
|8||9:00 to 11:15 AM||Practice in full pads||76°F / 24.4°C||74%|
|8||2:45 to 5:00 PM||Practice in shellsa||76°F / 24.4°C||74%|
|9||2:00 to 4:00 PM||Practice in shellsa,b||74°F / 23.3°C||77%|
Serum Osmolality (mOSM/kg) Across Days
|Participant||Baseline||Day 4||Day 7||Day 10|
|Mean ± SD||291.28a ± 9.32||293.96b ± 10.29||291.29a ± 4.52||305.17 ± 10.21|