How to prepare for the 'Creatine phosphokinase (CPK)' test: rules for taking it

Creatine phosphokinase (CPK, or creatine kinase, CK) is an enzyme involved in the energy metabolism of muscles. When muscle fibers are damaged, CPK enters the blood, so the test is used to assess muscle damage, diagnose rhabdomyolysis and monitor the side effects of statins. In athletes this indicator almost always «wanders» because of training. The editorial team explains how to prepare in order to get the true baseline level.

What CPK is and where it comes from in the blood

Creatine kinase catalyzes the transfer of a phosphate group from creatine phosphate to ADP, ensuring the rapid restoration of ATP during muscle work. This enzyme is most abundant in skeletal muscles, less so in the myocardium and the brain.

There are three main isoenzymes: CK-MM predominates in skeletal muscles, CK-MB is more characteristic of the heart muscle, and CK-BB — of the brain. Total CPK in an ordinary test is the sum of all fractions, and in a healthy person it is almost entirely represented by the muscle form.

When the cell membrane of a muscle fiber is damaged, the enzyme enters the interstitial fluid and from there, via the lymph, into the blood. Therefore the rise in CPK lags behind the moment of damage: this is important to know when planning the test.

The CPK level in healthy people varies widely and depends on sex, muscle mass, level of physical activity and ancestry. In men and people with a large muscle mass, baseline values are usually higher, so standard laboratory references for athletes are often too low.

Training: the main factor of elevation

Intense physical exertion, especially with an eccentric component, is the most common cause of elevated CPK in healthy people. Downhill running, the negative phase in strength exercises, jumps, and exercises new to the body cause microdamage to the fibers.

According to sports medicine reviews, after such exertion CPK usually peaks after 24–96 hours and can remain elevated for up to a week. The amplitude is highly individual: in some people the level rises moderately, and in so-called «high responders» — dozens of times over.

Regular training creates a «repeated bout effect»: after getting used to an exercise, the rise in CPK becomes significantly smaller. However, even in trained athletes the baseline level is often higher than in people who do not do sports.

The conclusion for preparation: to determine the true baseline level, a period without intense training is needed. The editorial team recommends at least 3 days, and for the most accurate result — 5–7 days without heavy strength, eccentric and prolonged endurance exertion.

Other causes of false elevation

Besides training, CPK can rise due to factors unrelated to muscle disease. They are worth taking into account so as not to get a false alarm.

Intramuscular injections, in particular vaccines and any other drugs, can noticeably raise CPK due to damage to the muscle at the injection site. This nuance is often overlooked, but it is precisely what sometimes explains an unexpectedly high result.

Statins are the best-known group of drugs associated with muscle symptoms. The consensus of the European Atherosclerosis Society on statin-associated muscle symptoms recommends assessing CPK when muscle pain appears; an increase above 4 times the upper limit of normal requires decisions regarding therapy. For correct assessment the doctor must know about recent training.

Epileptic seizures, convulsions, prolonged immobilization, electrical injury and some infections also raise CPK. In such situations the result reflects real muscle damage and requires medical assessment.

Rules for taking the test

A practical list of rules that will help obtain an informative baseline result:

• 5–7 days without intense strength, eccentric and prolonged endurance training (minimum — 3 days);
• 2–3 days before — no alcohol, no deep massage, no contact sports;
• report intramuscular injections over the past week;
• in the morning, preferably fasting, if biochemical indicators are being taken at the same time;
• note the use of statins and other drugs that must not be discontinued on your own.

If the test is needed to assess the response to training, the conditions are different: blood is drawn at a defined time after exertion, for example 24 or 48 hours, and compared with the baseline value. It is important that the protocol be the same each time.

For monitoring while taking statins, the doctor often orders a baseline test before the start of therapy. For an athlete it is especially important that this baseline test not be done immediately after a hard workout — otherwise the subsequent interpretation will be complicated.

During the draw it is important to avoid hemolysis: a prolonged tourniquet, a thin needle, intense shaking of the tube can distort the result. If the laboratory reports hemolysis of the sample, the test should be redone.

An athlete's norm or an alarming signal

The reference intervals for CPK indicated on the report are calculated for the general population. In athletes, especially strength athletes, baseline values can be noticeably higher without any pathology. Sports medicine reviews propose using separate references for athletes.

However, there is a limit beyond which an elevation stops being physiological. Rhabdomyolysis — massive destruction of muscles — is diagnosed when CPK rises usually more than 5 times above the upper limit of normal together with symptoms: severe pain, swelling and weakness of the muscles, dark urine. This condition threatens acute kidney injury and requires emergency care.

The risk of exertional rhabdomyolysis is increased by training in the heat, dehydration, unusual high-volume exertion, and some drugs and stimulants. If after a workout your urine has turned the color of tea or cola, or the muscle pain is disproportionately severe — do not wait for a routine test, see a doctor.

Persistently elevated CPK at rest, after a week of rest, especially with muscle weakness, requires examination: the cause may be hypothyroidism, myopathies, or a side effect of drugs.

Editorial conclusions

CPK is a very training-sensitive indicator: after eccentric exertion it peaks after 1–4 days and can remain elevated for up to a week.

To determine the baseline level, 5–7 days without intense training are needed, and injections, massage, alcohol, statins and sample quality must also be taken into account.

High CPK combined with dark urine and severe pain is a sign of possible rhabdomyolysis, which requires immediate care.

We also recommend reading our articles on preparing for the urea test, on cortisol, and on ferritin in athletes.

References

1. Brancaccio P, Maffulli N, Limongelli FM. Creatine kinase monitoring in sport medicine. Br Med Bull. 2007;81–82:209–230.
2. Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J Phys Med Rehabil. 2002;81(11 Suppl):S52–S69.
3. Baird MF, Graham SM, Baker JS, Bickerstaff GF. Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab. 2012;2012:960363.
4. Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy — European Atherosclerosis Society Consensus Panel statement on assessment, aetiology and management. Eur Heart J. 2015;36(17):1012–1022.
5. Kenney K, Landau ME, Gonzalez RS, et al. Serum creatine kinase after exercise: drawing the line between physiological response and exertional rhabdomyolysis. Muscle Nerve. 2012;45(3):356–362.