Few Adverse Effects of Long-Term Creatine Supplementation in a Placebo-Controlled Trial
Abstract
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…
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The literature has not provided support that creatine promotes renal dysfunction.
“Nor has the literature provided any support that creatine promotes renal dysfunction [22, 51, 85, 114, 156, 172, 243–248]”
From International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine (2017) · cites this paper as [245]
Performance-related studies in adolescents, younger individuals, and older populations have consistently reported ergogenic benefits with no clinically significant side effects.
“Performance-related studies in adolescents, younger individuals, and older populations have consistently reported ergogenic benefits with no clinically significant side effects [5, 6, 22, 23, 53, 113, 129, 244, 245, 268].”
From International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine (2017) · cites this paper as [245]
The systematic review included 21 studies.
“Twenty-one studies were included in the systematic review”
From Effect of creatine supplementation on kidney function: a systematic review and meta-analysis (2025) · cites this paper as [20]
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Cited by 64
- Authors
- Groeneveld, G. J., Beijer, C., Veldink, J. H., Kalmijn, S., Wokke, J. H. J., & van den Berg, L. H.
- Affiliations
- University Medical Center Utrecht (NL)
- Rijnland Ziekenhuis (NL)
- Venue
- International Journal of Sports Medicine
- Publisher
- Georg Thieme Verlag KG
- Published
- 2005-05
- Volume
- 26
- Issue
- 4
- Pages
- 307-313
- ISSN
- 0172-4622 (ISSN-L)
- 1439-3964
- OpenAlex
- W2036609824
- Cited by
- 64
- References
- 0
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 1.76
- Type
- journal article
- Language
- de
- Open access
- closed
- Locations
- International Journal of Sports Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Biochemical effects in animals
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- creatine monohydrate, long-term supplementation, adverse effects, amyotrophic lateral sclerosis, renal function, serum urea, urinary albumin, microalbuminuria, water retention, diarrhea, nausea, neurodegenerative diseases
- MeSH terms
- Administration, Oral, Adolescent, Adult, Aged, Albuminuria, Amyotrophic Lateral Sclerosis, Creatine, Creatinine, Diarrhea, Double-Blind Method, Female, Humans, Kidney, Male, Middle Aged, Nausea, Time, Urea, Treatment Outcome, Dietary Supplements
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