Creatine Kinase Elevated in Athletes: Truths About High CK After a Workout
Table of Contents
Introduction
In my clinical work, I occasionally see elevated creatine kinase (CK) in athletes. This usually causes clinicians difficulty in diagnosis. In addition, this is also a periodic concern for the athletes themselves. However, elevated CK is one of the most common findings in physically active patients. That’s why I wrote this blog post to explain when elevated CK should be a concern in an athletic patient.
Elevated creatine kinase is often also associated with muscle damage, and clinicians are naturally concerned about the possibility of rhabdomyolysis. Rhabdomyolysis is a condition in which skeletal muscle is extensively destroyed, resulting in the release of substances inside muscle cells, such as CK, myoglobin, potassium and other electrolytes into the bloodstream. Myoglobin in high concentrations can cause acute kidney injury or failure. For this reason, elevated CK is often a concern for doctors.
The challenge for clinicians is therefore to determine whether elevated CK is due to normal training adaptation or whether it is a case of true muscle damage. The assessment is complicated by the fact that athletes often have muscle damage due to physical exertion, unlike the general population, where CK is often elevated for a specific reason.
In this article I explain what it means when is creatine kinase elevated in athletes and when a creatine kinase elevated result may indicate something more serious.
The Role of Creatine and Creatine Kinase
Creatine kinase is an enzyme that is most abundant in skeletal muscle cells. It is involved in the rapid metabolism of the cell. CK acts as a catalyst for the reaction that forms adenosine triphosphate (ATP) from phosphocreatine and adenosine diphosphate (ADP). ATP is the cell’s energy molecule, needed for all functions, including muscle contraction.
The creatine phosphate reaction is dynamically reversible, meaning it can go in both directions depending on the concentrations of different substrates. Many athletes use creatine as a supplement specifically to replenish creatine phosphate stores, which has also been shown to have an enhancing effect on strength performance [9].
When muscle cells are damaged, either from hard training or injury, CK is released into the bloodstream. The amount of CK can be used to draw conclusions about the extent of muscle damage. However, any kind of muscle strain can release CK. For example, just hard exercise, especially strength training, can increase CK levels.
In endurance athletes, particularly runners, repeated mechanical loading can also cause red blood cell breakdown (footstrike hemolysis), which may coexist with elevated CK and contribute to post-exercise laboratory abnormalities.
Creatine Kinase Elevated in Athletes: What Counts as Normal?
The standard reference value for CK is upper limits around 200 U/L for men and 170 U/L for women. These values are simply defined so that 95% of the normal population falls within the reference values. However, a large proportion of competitive athletes often exceed this reference value physiologically without any pathological condition being involved.
Studies also support the finding that athletes have significantly higher CK reference values. A landmark study of 728 athletes found reference ranges of 82-1083 U/L for males and 47-513 U/L for females[1]. The upper limits were twice those of moderately active non-athletes and up to six times higher than sedentary individuals[1].
The type of sport also seems to matter significantly. In the same study football players showed upper reference limits of 1492 U/L, while swimmers peaked at just 523 U/L[1]. The increase in CK values depends on the nature of the sport. In sports that involve a lot of eccentric contractions, physical contact and weight-bearing stress, the increase in CK is much greater. This is why the increase in CK in football is significantly greater than in swimming.
There is also considerable individual variation in elevations in CK values. Some athletes show CK levels clearly above 1000 U/L without any pathology[2]. In military recruits’ basic training, peak CK levels averaged 1226 IU/L but ranged from 56 to a maximum of 35,056 IU/L. It should also be noted that none of those studied developed rhabdomyolysis[3]. Similarly, marathon runners can show CK elevations exceeding 20,000 IU/L without any signs of kidney compromise[4].
In summary, we can say that because individual variation is large and depends on the individual’s background, often the reliable measure is the patient’s own baseline. Therefore, individual blood samples in themselves may not have clinical significance without information about the patient’s baseline.
In practice, an increase in CK rarely alone is a reason to suspect rhabdomyolysis, but the diagnosis involves assessing the overall picture, which includes the CK trend, kidney values, potassium, and the possibility of hemoglobin in the urine, even though it is actually myoglobin.
Creatine Kinase Kinetics: When CK Peaks and Falls
CK kinetics help us distinguish physiological from pathological elevations. CK usually rises with a delay after exercise, often hours later. CK usually rises with a delay after exercise, often hours later. CK usually peaks within 24-72 hours and remains elevated for several days before slowly starting to decline, although this depends very much on the nature and intensity of the sport and individual differences [1].
In practice, people who exercise daily may have CK levels consistently above the reference value. Perhaps this is more indicative of the lack of movement in the normal population, as sedentary people are overrepresented in the reference values.
The time it takes for CK to normalize depends on the magnitude of CK release, but in practice the decline is roughly exponential, consistent with the half-life. Assuming that no further CK is released, the time it takes to recover depends roughly on the peak CK value.
As previously stated, the amount of CK release depends on the nature, intensity and duration of the exercise. Therefore, it is expected that after more strenuous and especially eccentric exercises, CK levels will be elevated for a longer period of time. In practice, the normalization of CK levels after a really strenuous sports performance can take up to two weeks, but often less [4]
In general, after strenuous exercise, CK should not be elevated for more than two weeks. If my patient has prolonged elevated CK or there is no clear underlying event or sport that could potentially cause muscle damage, I would suspect some other underlying pathology.
For us clinicians, the key is not whether creatine kinase is elevated, but whether the creatine kinase elevated finding reflects normal training adaptation or muscle injury significant enough to cause rhabdomyolysis.
Recognizing Rhabdomyolysis
The most feared complication of elevated CK is rhabdomyolysis. As the name suggests, rhabdomyolysis refers to the damage and breakdown of skeletal muscle cells. When skeletal muscle cells are destroyed, muscle cell contents such as CK, myoglobin, potassium, phosphate, lactate dehydrogenase (LD) and other intracellular proteins accumulate in the bloodstream.
The most concerning of these are myoglobin and potassium. Myoglobin can block the renal tubules and cause severe kidney damage. Extensive tubular necrosis and the resulting acute renal failure is often a life-threatening situation. In addition, elevated potassium levels can cause arrhythmias, in the worst case, cardiac arrest, which is also a life-threatening condition. CK is an indirect measure of potential muscle damage, which in itself is not harmful or dangerous to health.
The diagnosis of rhabdomyolysis is a combination of clinical presentation and laboratory findings. A history of a muscle-stressing or muscle-damaging condition and a laboratory test profile typical of rhabdomyolysis are usually required.
Rhabdomyolysis is typically defined as CK >5 times the upper limit of normal (ULN), which is approximately >1000 U/L [7]. However, because athletes may show large CK elevations without clinical rhabdomyolysis, some military-derived guidance uses higher CK thresholds (e.g., ≥5,000 IU/L) in the presence of severe symptoms and a clear exercise exposure [3].
It is often difficult to distinguish rhabdomyolysis from delayed onset muscle soreness (DOMS). In both cases, the muscles become sore and both symptoms overlap. However, usually the CK trend, urine sample and kidney values provide support for the differential diagnosis. Often the situation is closely monitored and rhabdomyolysis can only be ruled out if abnormalities in the aforementioned markers have not developed during the monitoring period.
Typical symptoms often help in diagnosing rhabdomyolysis. The classic triad of symptoms includes disproportionate muscle pain, weakness, and dark colored urine[7]. However, the absence of symptoms does not exclude rhabdomyolysis, as only 10-23% of patients present with all three symptoms[7]. For many, the symptoms are very mild, such as mild but often greater than normal DOMS muscle pain 1-3 days after training[7].
In a clinical situation, waiting for classic symptoms is often a risk, because they do not exclude major muscle damage. I usually schedule lab tests immediately if the patient has a history of exceptional muscle strain and unusual muscle pain, and I have sometimes encountered rhabdomyolysis with quite mild symptoms. For example, one of my patients developed rhabdomyolysis of the pectoral muscle 1-2 days after a hard CrossFit workout. The symptom was unusual pectoral muscle pain after the workout. The color of the urine had not changed to dark, but the urine sample showed “hemoglobin”, which actually indicated myoglobin, as well as a clearly elevated CK level.
The discoloration of urine is caused by myoglobin, which is found in muscle cells. Myoglobin is an oxygen-binding protein in muscle cells that helps muscle cells store oxygen locally. Myoglobin also contributes to the red color of muscle. This is why when it ends up in the urine, it can give the urine its characteristic dark color.
When myoglobin reaches the renal tubules, it precipitates and contributes to tubular obstruction. In addition, it is directly tubulotoxic due to the heme iron, and it causes oxidative stress and vasoconstriction in the tubular cells. This can lead to tubular necrosis and acute kidney injury and failure.
Acute kidney injury risk shows a general association with CK levels above 5000-6000 IU/L, though the relationship is imperfect and heavily modified by concurrent factors like dehydration, heat stress, acidosis, and individual susceptibility[4]. Other severe complications include life-threatening electrolyte disturbances, cardiac arrhythmias, compartment syndrome, disseminated intravascular coagulation, and even sudden death[3].
Conclusion
Elevated CK levels in athletes rarely indicate true pathology. A single elevated value without context tells the clinician little. Information about the type, type, intensity, and duration of exercise are essential clues in interpreting an elevated CK value.
CK levels usually rise within 1-3 days of exercise and often remain elevated for several days. Sometimes it can take up to two weeks before it returns to baseline levels.
Elevated CK is often a sign of muscle stress, less often of illness. Even a high CK value can be a physiological response to exercise. However, the possibility of rhabdomyolysis should be kept in mind when high CK is present. Rhabdomyolysis is a clinical diagnosis, not just a high CK value. The CK trend, symptoms, and laboratory tests are essential in the diagnosis.
Warning signs to watch for include unusual muscle pain, weakness, dark urine, and elevated CK and kidney function. If CK levels do not decrease after exercise after a delay and the clinical picture is not consistent with a normal exercise response, it is important to discuss the situation with your doctor.
References
1 https://doi.org/10.1136/bjsm.2006.034041
2 https://pmc.ncbi.nlm.nih.gov/articles/PMC4904530/
3 https://doi.org/10.1177/1941738114523544
4 https://pmc.ncbi.nlm.nih.gov/articles/PMC3263635/f
