Kreider et al. 2003: 21-Month Long-Term Creatine Safety Study

Creatine.my Editorial Team · · 7 min read
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7 min read
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TL;DR — Kreider et al. 2003

Kreider and colleagues published one of the most comprehensive long-term safety studies on creatine supplementation, monitoring 98 serum health markers over 21 months in collegiate football players. The study found no clinically significant adverse changes in any health marker, including kidney function, liver function, blood lipids, electrolytes, and hematological parameters. This landmark safety data remains one of the strongest pieces of evidence for creatine’s long-term safety profile.

98
health markers monitored over 21 months — none showed adverse changes
Kreider et al., Molecular and Cellular Biochemistry, 2003

Background

Despite mounting evidence of creatine’s efficacy, concerns about long-term safety persisted in the early 2000s. Questions about kidney damage, liver stress, and metabolic disruption were common among the public and some healthcare professionals. Previous work by Poortmans and Francaux (2000) had shown no renal harm in up to 5 years of use (JR & M, 2000) , but comprehensive multi-marker monitoring over extended periods was lacking.

Kreider, a leading creatine researcher, designed this study to provide the most thorough safety assessment possible.

Study Design

  • Participants: NCAA Division IA college football players
  • Duration: 21 months (approximately 0 to 21 months of continuous monitoring)
  • Supplementation: Creatine monohydrate at standard dosing
  • Control: Athletes who chose not to use creatine
  • Monitoring: 98 serum clinical chemistry markers measured at multiple time points
  • Categories tested: Kidney function, liver function, blood lipids, electrolytes, complete blood count, metabolic markers, hormones

Key Findings

1. Kidney function remained normal

All renal function markers — blood urea nitrogen (BUN), serum creatinine, creatinine clearance, and estimated GFR — remained within normal clinical ranges throughout the 21-month period. No participant showed any sign of kidney stress or damage.

2. Liver function was unaffected

Hepatic markers including AST, ALT, GGT, and bilirubin showed no clinically significant changes. Creatine supplementation did not cause liver stress.

21 months
of continuous creatine supplementation with no adverse health effects detected
Kreider et al., 2003

3. Cardiovascular markers stable

Blood lipid profiles (total cholesterol, LDL, HDL, triglycerides) were not adversely affected by creatine supplementation. Heart health markers remained normal.

4. No metabolic disruption

Electrolytes (sodium, potassium, chloride, calcium), blood glucose, insulin, and thyroid markers all remained within normal limits. Creatine did not cause metabolic imbalance.

5. Hematological parameters normal

Complete blood count, red blood cell indices, white blood cell differential, and platelet counts were all unaffected.

Significance

This study is significant because it:

  • Represents one of the longest continuous monitoring periods for creatine safety
  • Tested the broadest panel of health markers in any creatine safety study
  • Used real-world athletes taking creatine as part of their normal training
  • Found zero clinically significant adverse effects across 98 markers over 21 months

This data was later cited in the comprehensive 2017 ISSN position stand by Kreider et al. (RB et al., 2017) and complemented by Antonio et al. (2013) who found similar safety over up to 5 years (J & V, 2013) .

Practical Implications

  1. Long-term creatine use is safe: 21 months of supplementation produced no health concerns across 98 markers
  2. Kidney fears are unfounded: Direct measurement of renal function markers confirmed no kidney damage
  3. Liver is not affected: Hepatic function remained normal throughout
  4. No need for “cycling”: Continuous use does not cause progressive organ damage
  5. Annual health checkups remain sensible: While creatine is safe, regular health monitoring is good practice for anyone

Malaysian Relevance

Malaysian athletes and fitness enthusiasts who take creatine continuously can be reassured by this comprehensive safety data. The study’s findings apply regardless of ethnicity or geography — the biological safety profile of creatine monohydrate is consistent across populations. For Malaysians concerned about kidney health, this study directly addresses those fears with extensive data.

Limitations

  • Observational design (not randomized) — athletes self-selected into creatine or control groups
  • All participants were young, healthy, male college athletes
  • Results may not directly generalize to elderly, clinical, or female populations
  • Exact daily doses were not tightly controlled

Full Citation

Kreider RB, Melton C, Rasmussen CJ, et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Molecular and Cellular Biochemistry. 2003;244(1-2):95-104. doi:10.1023/A:1022469320296

Sources & References

This article is based on the study by Kreider et al. published in Molecular and Cellular Biochemistry (2003) and contextualized with Poortmans et al. (2000), Antonio et al. (2013), and the 2017 ISSN position stand. All citations reference PubMed-indexed publications.

Further Reading

Frequently Asked Questions

Is creatine safe to take for 21 months continuously?

Yes. Kreider et al. (2003) monitored 98 health markers including kidney function, liver function, blood lipids, electrolytes, and hematological parameters over 21 months of creatine supplementation in college athletes. No clinically significant adverse changes were observed in any marker.

What health markers were tested in the Kreider 2003 long-term study?

The study comprehensively tested 98 blood serum markers including: kidney function (BUN, creatinine, GFR), liver function (AST, ALT, bilirubin), blood lipids (cholesterol, triglycerides), electrolytes, complete blood count, hormonal markers, and multiple metabolic indicators.

Does long-term creatine use damage the kidneys?

No. Kreider et al. (2003) found no evidence of kidney damage after 21 months of creatine use, consistent with earlier findings by Poortmans et al. (2000). All renal function markers remained within normal clinical ranges throughout the study period.