Metabolic Biomarkers: Creatine Kinase

Optimal Takeaways

Creatine kinase is an enzyme involved in energy generation. It is found in abundance in muscle, lung, and brain tissue. Elevated levels are seen with inflammation or tissue damage and can be associated with myocardial infarction, hypertension, muscle disorders, and strenuous exercise. Low levels may be related to decreased muscle mass or muscle atrophy.­­­­

Standard Range: 44.00 - 196.00 U/L (0.73 - 3.27 ukat/L)

The ODX Range: 65.00 - 135.00 U/L (1.09 - 2.25 ukat/L)

Low levels of CK may be seen with decreased muscle mass or small stature (Pagana 2022). Low CK may also be associated with an increased risk of asthma (Forno 2022). The synthesis of CK depends heavily on the availability of magnesium (Fiorentini 2021).

High levels of CK are associated with myocardial infarction, cardiac ischemia, myocarditis, ventricular arrhythmias, cardiac defibrillation, muscle damage or inflammation, rhabdomyolysis, myopathies, cerebrovascular disease, pulmonary infarction, hypokalemia, hypothyroidism, shock, malignant hyperthermia, increased muscle mass, intramuscular injections, surgery, trauma, convulsions, electroconvulsive therapy, alcoholism, delirium tremens, CNS disorders, and adenocarcinoma. Drugs that can increase CK include alcohol, aspirin, anticoagulants, statins, fibrates, captopril, colchicine, furosemide, dexamethasone, lidocaine, morphine, propranolol, succinylcholine, lithium, and antibiotics (Pagana 2022).

Higher levels are also associated with osteoarthritic disorders (Ganguly 2019), vigorous or excessive exercise (Backer 2020, Giechaskiel 2020), heavy manual labor, malignancy (Moghadam-Kia 2016), poorer outcomes for COVID-19 (Akbar 2021), severe hypertension (Sukul 2018), and amyotrophic lateral sclerosis (Tai 2017).

Overview

Creatine kinase (CK), also known as creatine phosphokinase (CPK), represents a group of enzymes found in high-energy tissues such as skeletal muscle (99% of total CK), as well as the heart and brain. Levels increase with inflammation or damage to these tissues within 6 hours of insult and usually return to normal within three to seven days. The test had been commonly used to diagnose myocardial infarction, in which case isoenzymes must be measured to identify their source: CK-MM from muscle, CK-MB from cardiac tissue, and CK-BB from the brain. A mild elevation may be seen with unstable angina without an MI. Measuring cardiac troponin levels is preferred over measuring CK for diagnosing MI (Pagana 2022).

Elevated CK may be associated with the severity of hypertension and may predict hypertensive treatment failure. One study observed mean CK levels of 72.66 U/L (1.21 ukat/L 1.21 umol/L) in normotensives, 99.55 UL (1.66 ukat/L) in controlled hypertensives, and 313.92 U/L (5.23 ukat/L) in subjects who failed antihypertensive therapy. Researchers suggest a cut-off of 168 U/L (2.8 ukat/L) for hypertension and increased risk of treatment failure (Sukul 2018)

A meta-analysis comprising four studies and 1,165 subjects examined the association between elevated CK after non-cardiac surgery and the risk of a major CVD event or death. Results indicate an independent association between elevated post-surgical muscle and brain CK and mortality risk, though elevated troponin was a more significant marker in the more extensive meta-analysis (Levy 2011).

Since CK is involved in energy production, it is abundant in highly metabolic muscle tissue. Exercise and strength training can cause transient elevations, but persistent elevations should be monitored to ensure recovery. Vigorous exercise can lead to significantly elevated CK due to associated muscle breakdown. A literature review reveals that CK levels may increase 2.5-5.5-fold above baseline 1-3 days following programmed exercise. Protocols calling for 5-15 sets with 6-15 repetitions increased serum CK in general to 400-700 U/L (6.7-11.7 ukat/L) from a baseline of 140-180 U/L (2.3-3 ukat/L) in both trained and untrained individuals. Researchers note that performance may be improved if CK levels remain below 550 U/L (9.2 ukat/L). However, performance was static or decreased if CK levels exceeded 550 U/L. A maximum CK level of 300-500 U/L (5.01-8.35 ukat/L) is recommended for endurance exercise (Giechaskiel 2020). Interestingly, a meta-analysis of 15 studies demonstrated that supplementation with whey protein significantly attenuated the elevated CK seen with exercise-related muscle breakdown (Lam 2019).

High levels of CK above 1,000 U/L (16.7 ukat/L) can be seen with excessive strength training and sports-related rhabdomyolysis, as demonstrated in a cross-sectional study of emergency department admissions. These high levels should be addressed accordingly, as they can cause irregular heart rhythms, acute kidney failure, and even death. Levels of CK decreased with aggressive hydration in the individuals involved (Backer 2020). Additional research indicated that statins may significantly increase CK levels and muscle-related injury following prolonged strenuous activity such as a marathon (Parker 2012).

References

Akbar, Mohammad Rizki et al. “The prognostic value of elevated creatine kinase to predict poor outcome in patients with COVID-19 - A systematic review and meta-analysis.” Diabetes & metabolic syndrome vol. 15,2 (2021): 529-534. doi:10.1016/j.dsx.2021.02.012

Backer, Henrik Constantin et al. “Exertional rhabdomyolysis and causes of elevation of creatine kinase.” The Physician and sportsmedicine vol. 48,2 (2020): 179-185. doi:10.1080/00913847.2019.1669410

Fiorentini, Diana et al. “Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency.” Nutrients vol. 13,4 1136. 30 Mar. 2021, doi:10.3390/nu13041136

Forno, Erick, and Paul D Robinson. “UnloCKing the Role of Creatine Kinase in Childhood Asthma.” American journal of respiratory and critical care medicine, 10.1164/rccm.202208-1552ED. 19 Aug. 2022, doi:10.1164/rccm.202208-1552ED

Ganguly, Apurba. “Levels of C-reactive protein, creatine kinase-muscle and aldolase A are suitable biomarkers to detect the risk factors for osteoarthritic disorders: A novel diagnostic protocol.” Caspian journal of internal medicine vol. 10,1 (2019): 25-35. doi:10.22088/cjim.10.1.25

Giechaskiel, Barouch. "Weight training and creatine kinase (CK) levels: a literature review." Int J Sci Res IJSR 9.1 (2020): 303-11.

Lam, Fui-Ching et al. “Effectiveness of whey protein supplements on the serum levels of amino acid, creatinine kinase and myoglobin of athletes: a systematic review and meta-analysis.” Systematic reviews vol. 8,1 130. 31 May. 2019, doi:10.1186/s13643-019-1039-z

Levy, Michael et al. “Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis.” Anesthesiology vol. 114,4 (2011): 796-806. doi:10.1097/ALN.0b013e31820ad503

Moghadam-Kia, Siamak et al. “Approach to asymptomatic creatine kinase elevation.” Cleveland Clinic journal of medicine vol. 83,1 (2016): 37-42. doi:10.3949/ccjm.83a.14120

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 16th ed., Mosby, 2022.

Parker, Beth A et al. “Effect of statins on creatine kinase levels before and after a marathon run.” The American journal of cardiology vol. 109,2 (2012): 282-7. doi:10.1016/j.amjcard.2011.08.045

Rafiq, M K et al. “Creatine kinase enzyme level correlates positively with serum creatinine and lean body mass, and is a prognostic factor for survival in amyotrophic lateral sclerosis.” European journal of neurology vol. 23,6 (2016): 1071-8. doi:10.1111/ene.12995

Sukul, Surankita, et al. "Serum Creatine Kinase Activity among Hypertensive Patients and its Role as a Predictor for Failure of Antihypertensive Treatment." Journal of Clinical & Diagnostic Research 12.11 (2018).

Tai, Hongfei et al. “Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis.” Frontiers in neurology vol. 8 322. 3 Jul. 2017, doi:10.3389/fneur.2017.00322