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Am J Physiol Regul Integr Comp Physiol 285: R762-R769, 2003; doi:10.1152/ajpregu.00270.2003
0363-6119/03 $5.00
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DEVELOPMENT AND TISSUE PLASTICITY

Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats

M. A. Tarnopolsky,1,2 J. M. Bourgeois,3 R. Snow,4 S. Keys,5 B. D. Roy,1,2 J. M. Kwiecien,3 and J. Turnbull2

Departments of Pediatrics and Medicine (1Rehabilitation and 2Neurology), 3Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5; 4School of Health Sciences, Deakin University, Burwood, Victoria, Australia 3125; and 5Department of Biology/Chemistry, Springfield College, Springfield, Massachusetts 01109

Submitted 15 May 2003 ; accepted in final form 12 June 2003

Creatine monohydrate (CrM) supplementation appears to be relatively safe based on data from short-term and intermediate-term human studies and results from several therapeutic trials. The purpose of the current study was to characterize pathological changes after intermediate-term and long-term CrM supplementation in mice [healthy control and SOD1 (G93A) transgenic] and rats (prednisolone and nonprednisolone treated). Histological assessment (18-20 organs/tissues) was performed on G93A mice after 159 days, and in Sprague-Dawley rats after 365 days, of CrM supplementation (2% wt/wt) compared with control feed. Liver histology was also evaluated in CD-1 mice after 300 days of low-dose CrM supplementation (0.025 and 0.05 g · kg-1 · day-1) and in Sprague-Dawley rats after 52 days of CrM supplementation (2% wt/wt) with and without prednisolone. Areas of hepatitis were observed in the livers of the CrM-supplemented G93A mice (P < 0.05), with no significant inflammatory lesions in any of the other 18-20 tissues/organs that were evaluated. The CD-1 mice also showed significant hepatic inflammatory lesions (P < 0.05), yet there was no negative effect of CrM on liver histology in the Sprague-Dawley rats after intermediate-term or long-term supplementation nor was inflammation seen in any other tissues/organs (P = not significant). Dietary CrM supplementation can induce inflammatory changes in the liver of mice, but not rats. The observed inflammatory changes in the murine liver must be considered in the evaluation of hepatic metabolism in CrM-supplemented mice. Species differences must be considered in the evaluation of toxicological and physiological studies.

dietary supplements; hepatitis; drug toxicity; side effects



Address for reprint requests and other correspondence: M. A. Tarnopolsky, Dept. of Neurology, Rm. 4U4, McMaster Univ. Medical Centre, 1200 Main St. West, Hamilton, Ontario, Canada L8N 3Z5 (E-mail: tarnopol{at}McMaster.ca).




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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. B. Kreider
Species-specific responses to creatine supplementation
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R725 - R726.
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