Effects of oral creatine and resistance training on myogenic regulatory factor expression

Med Sci Sports Exerc. 2003 Jun;35(6):923-9. doi: 10.1249/01.MSS.0000069746.05241.F0.


Purpose: This study examined 12 wk of creatine (Cr) supplementation and heavy resistance training on skeletal muscle creatine kinase (M-CK) mRNA expression and the mRNA and protein expression of the myogenic regulatory factors Myo-D, myogenin, MFR-4, and Myf5.

Methods: Twenty-two untrained males were randomly assigned to either a control (CON), placebo (PLC), or Cr (CRT) group in a double-blind fashion. Muscle biopsies were obtained before and after training. PLC and CRT trained thrice weekly using 3 sets of 6-8 repetitions at 85-90% 1-RM on the leg press, knee extension, and knee curl exercises. CRT ingested 6 g.d-1 of Cr for 12 wk while PLC consumed the equal amount of placebo.

Results: After training, M-CK mRNA expression, as well as myogenin and MRF-4 mRNA and protein expression, were found to be significantly greater for CRT compared with PLC and CON, whereas PLC was also significantly different from CON (P < 0.05). For Myo-D mRNA and protein, both CRT and PLC were significantly different from CON (P < 0.05), but CRT and PLC were not different from one another. No significant differences were located for Myf5 mRNA or protein (P > 0.05). M-CK mRNA was correlated with myogenin (r = 0.916) and MRF-4 (r = 0.883) protein (P < 0.05).

Conclusion: When combined with heavy resistance training, Cr supplementation increases M-CK mRNA expression, likely due to concomitant increases in the expression of myogenin and MRF-4. Therefore, increases in myogenin and MRF-4 mRNA and protein may play a role in increasing myosin heavy chain expression, already shown to occur with Cr supplementation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Creatine / administration & dosage*
  • Creatine / pharmacology*
  • Creatine Kinase / analysis
  • Creatine Kinase / biosynthesis*
  • Double-Blind Method
  • Gene Expression Regulation*
  • Humans
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Myogenic Regulatory Factors / analysis
  • Myogenic Regulatory Factors / biosynthesis*
  • Placebos
  • RNA, Messenger / biosynthesis
  • Weight Lifting*


  • Myogenic Regulatory Factors
  • Placebos
  • RNA, Messenger
  • Creatine Kinase
  • Creatine