Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery

Abstract

The appearance of creatine kinase (CK) in blood has been generally considered to be an indirect marker of muscle damage, particularly for diagnosis of medical conditions such as myocardial infarction, muscular dystrophy, and cerebral diseases. However, there is controversy in the literature concerning its validity in reflecting muscle damage as a consequence of level and intensity of physical exercise. Nonmodifiable factors, for example, ethnicity, age, and gender, can also affect enzyme tissue activity and subsequent CK serum levels. The extent of effect suggests that acceptable upper limits of normal CK levels may need to be reset to recognise the impact of these factors. There is a need for standardisation of protocols and stronger guidelines which would facilitate greater scientific integrity. The purpose of this paper is to examine current evidence and opinion relating to the release of CK from skeletal muscle in response to physical activity and examine if elevated concentrations are a health concern.

Figure 1

Phosphocreatine (PCr) circuit showing the rephosphorylation of creatine (Cr) in mitochondria using ATP derived from oxidative phosphorylation (oxid phos) and subsequent use of mitochondrial PCr by cytosolic creatine kinase (CK) to resupply ATP for muscle activity, adapted from Saks [5].

Figure 2

Theoretical model of muscle damage and repair cycle reproduced from Kendall and Eston [11].

Figure 3

(a) Changes in serum creatine kinase (CK) activity during 90-minute cycling exercise on three consecutive days (Ex1, Ex2, and Ex3), reprinted from Totsuka et al. with permission from American Physiological Society [6]. (b) Creatine kinase (CK) response to eccentric exercise between immobilisation and control group. PRE refers to the baseline period before exercise. Days 1–4 represent the 4-day immobilization and days 5–9 are the recovery period. Reprinted from Sayers and Clarkson [4]. (c) Creatine kinase (CK) activity in women and in men before (pre), immediately after (post), and 15 days after step exercise. +++ Significant difference from preexercise level (P < 0.001). $$$ Significant difference between men and women (P < 0.001), reprinted from Fredsted et al. [12].

Figure 4

Potential roles of adenylate kinase (AK) and AMP-activated protein kinase (AMPK) in gross control of creatine kinase (CK) activity by promoting expulsion of CK from the cytosol to limit CK utilisation of ATP for PCr resynthesis adapted from Saks [5].