Int J Sports Med 2005; 26(4): 307-313
DOI: 10.1055/s-2004-817917

© Georg Thieme Verlag KG Stuttgart · New York

Few Adverse Effects of Long-Term Creatine Supplementation in a Placebo-Controlled Trial

G. J. Groeneveld1 , C. Beijer2 , J. H. Veldink1 , S. Kalmijn1 , 3 , J. H. J. Wokke1 , L. H. van den Berg1
  • 1Department of Neurology, University Medical Centre Utrecht, The Netherlands
  • 2Department of Clinical Chemistry, Rijnland Hospital, Leiderdorp, The Netherlands
  • 3Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands
Further Information

Publication History

Accepted after revision: January 12, 2004

Publication Date:
26 August 2004 (online)


Although oral creatine supplementation is very popular among athletes, no prospective placebo-controlled studies on the adverse effects of long-term supplementation have yet been conducted. We performed a double-blind, placebo-controlled trial of creatine monohydrate in patients with the neurodegenerative disease amyotrophic lateral sclerosis, because of the neuroprotective effects it was shown to have in animal experiments. The purpose of this paper is to compare the adverse effects, and to describe the effects on indirect markers of renal function of long-term creatine supplementation. 175 subjects (age = 57.7 ± 11.1 y) were randomly assigned to receive creatine monohydrate 10 g daily or placebo during an average period of 310 days. After one month, two months and from then on every fourth month, adverse effects were scored using dichotomous questionnaires, plasma urea concentrations were measured, and urinary creatine and albumin concentrations were determined. No significant differences in the occurrence at any time of adverse effects due to creatine supplementation were found (23 % nausea in the creatine group, vs. 24 % in the placebo group, 19 % gastro-intestinal discomfort in the creatine group, vs. 18 % in the placebo group, 35 % diarrhoea in the creatine group, vs. 24 % in the placebo group). After two months of treatment, oedematous limbs were seen more often in subjects using creatine, probably due to water retention. Severe diarrhoea (n = 2) and severe nausea (n = 1) caused 3 subjects in the creatine group to stop intake of creatine, after which these adverse effects subsided. Long-term supplementation of creatine did not lead to an increase of plasma urea levels (5.69 ± 1.47 before treatment vs. 5.26 ± 1.44 at the end of treatment) or to a higher prevalence of micro-albuminuria (5.4 % before treatment vs. 1.8 % at the end of treatment).


L. H. Van den Berg

Department of Neurology, University Medical Centre Utrecht

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The Netherlands

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