Creatine is a naturally occurring amino acid that is obtained from the diet and synthesized from the amino acids glycine, arginine, and methionine [1, 2]. Approximately 95% of creatine is stored in skeletal muscle while the remaining 5% is stored the heart, brain, and testes . Many previous studys have shown creatine to be an effective ergogenic supplement for athletes.[2,3,4]
However, many concerns have been raised about its possible side effects when taken chronologically for longer periods of time. The only side effect that has been consistently reported has been weight gain [1–3, 7]. Despite this, safety concerns have been raised in popular media that creatine supplementation may promote long-term suppression of creatine synthesis, increase renal stress, promote muscle and liver damage, alter fluid and electrolyte status, and cause unknown long-term side effects [5, 6]
Kreider RB, Melton C, et al.  examined the effects of long-term creatine supplementation on some clinical markers of health including whole blood, and urinary markers in athletes.
One hundred and sixteen National Collegiate Athletic Association college football players volunteered to participate in this study over a 2 year period. Football players who ingested creatine were administered 15.75 g/day of creatine monohydrate for 5 days and an average of 5 g/day thereafter in 5-10 g/day doses. Urine and blood samples were collected at 0, 1, 1.5, 4, 6, 10, 12, 17, and 21 months of training.
At the end football players were categorized into placebo group (n = 44) and groups who took creatine for 0-6 months (n = 12), 7-12 months (n = 25), and 12-21 months (n = 17). After final blood and urine samples were analyzed there were no significant differences (p = 0.51) among groups. There were also no apparent differences between groups in the 15-item panel of qualitative urine markers.
Results indicate that long-term creatine supplementation (up to 21-months) does not appear to adversely effect markers of health status (including kidney and liver function) in athletes undergoing intense training in comparison to athletes who do not take creatine. These findings provide the strongest evidence to date that long-term creatine supplementation does not appear to pose a health risk for athletes.
Williams, Melvin H., and J. David Branch. “Creatine supplementation and exercise performance: an update.” Journal of the American College of Nutrition 17.3 (1998): 216-234.
Kreider, Richard B. “Creatine supplementation: analysis of ergogenic value, medical safety, and concerns.” J Exerc Physiol Online 1.1 (1998).
Williams, Melvin H., Richard B. Kreider, and J. David Branch. Creatine: The power supplement. Human Kinetics Publishers, 1999.
Kraemer, William J., and Jeff S. Volek. “Creatine supplementation: its role in human performance.” Clinics in sports medicine 18.3 (1999): 651-666.
Graham, Angie S., and Randy C. Hatton. “Creatine: a review of efficacy and safety.” Journal of the American Pharmaceutical Association (Washington, DC: 1996) 39.6 (1999): 803.
Juhn, Mark S., and Mark Tarnopolsky. “Potential side effects of oral creatine supplementation: a critical review.” Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine 8.4 (1998): 298.
Kreider, Richard B., et al. “Long-term creatine supplementation does not significantly affect clinical markers of health in athletes.” Molecular and cellular biochemistry 244.1 (2003): 95-104.