Skip to main content
Log in

Long-term creatine supplementation does not significantly affect clinical markers of health in athletes

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Creatine has been reported to be an effective ergogenic aid for athletes. However, concerns have been raised regarding the long-term safety of creatine supplementation. This study examined the effects of long-term creatine supplementation on a 69-item panel of serum, whole blood, and urinary markers of clinical health status in athletes. Over a 21-month period, 98 Division IA college football players were administered in an open label manner creatine or non-creatine containing supplements following training sessions. Subjects 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. Fasting blood and 24-h urine samples were collected at 0, 1, 1.5, 4, 6, 10, 12, 17, and 21 months of training. A comprehensive quantitative clinical chemistry panel was determined on serum and whole blood samples (metabolic markers, muscle and liver enzymes, electrolytes, lipid profiles, hematological markers, and lymphocytes). In addition, urine samples were quantitatively and qualitative analyzed to assess clinical status and renal function. At the end of the study, subjects were categorized into groups that did not take creatine (n = 44) and subjects who took creatine for 0–6 months (mean 4.4 ± 1.8 months, n = 12), 7–12 months (mean 9.3 ± 2.0 months, n = 25), and 12–21 months (mean 19.3 ± 2.4 months, n = 17). Baseline and the subjects' final blood and urine samples were analyzed by MANOVA and 2 × 2 repeated measures ANOVA univariate tests. MANOVA revealed no significant differences (p = 0.51) among groups in the 54-item panel of quantitative blood and urine markers assessed. Univariate analysis revealed no clinically significant interactions among groups in markers of clinical status. In addition, no apparent differences were observed among 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 in athletes undergoing intense training in comparison to athletes who do not take creatine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Williams MH, Branch JD: Creatine supplementation and exercise performance: An update. J Am Coll Nutr 17: 216-234, 1998

    Google Scholar 

  2. Kreider R: Creatine supplementation: Analysis of ergogenic value, medical safety, and concerns. J Exerc Physiol Online 1: 7-18, 1998. Available: http://www.css.edu/users/tboone2/asep/jan3.htm

    Google Scholar 

  3. Williams MH, Kreider R, Branch JD: In: Creatine: The Power Supplement. Human Kinetics Publishers, Champaign, IL, 1999

    Google Scholar 

  4. Balsom PD, Soderlund K, Ekblom B: Creatine in humans with special reference to creatine supplementation. Sports Med 18: 268-280, 1994

    Google Scholar 

  5. Greenhaff P: The nutritional biochemistry of creatine. J Nutr Biochem 11: 610-618, 1997

    Google Scholar 

  6. Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL: Muscle creatine loading in men. J Appl Physiol 81: 232-237, 1996

    Google Scholar 

  7. Kraemer WJ, Volek JS: Creatine supplementation. Its role in human performance. Clin Sports Med 18: 651-666, 1999

    Google Scholar 

  8. Bessman S, Savabi F: The role of phosphocreatine energy shuttle in exercise and muscle hypertrophy. In: M.A. Conway, J. F. Clark (eds). Creatine and Creatine Phosphate: Scientific and Clinical Perspectives. Academic Press, San Diego, CA, 1988, pp 185-198

    Google Scholar 

  9. Ma TM, Friedman DL, Roberts R: Creatine phosphate shuttle pathway in tissues with dynamic energy demand. In: M.A. Conway, J.F. Clark (eds). Creatine and Creatine Phosphate: Scientific and Clinical Perspectives. Academic Press, San Diego, CA, 1996, pp 17-32.

    Google Scholar 

  10. Wallimann T, Dolder M, Schlattner U, Eder M, Hornemann T, O'Gorman E, Ruck A, Brdiczka D: Some new aspects of creatine kinase (CK): Compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology. Biofactors 8: 229-234, 1998

    Google Scholar 

  11. Vorgerd M, Grehl T, Jager M, Muller K, Freitag G, Patzold T, Bruns N, Fabian K, Tegenthoff M, Mortier W, Luttmann A, Zange J, Malin JP: Creatine therapy in myophosphorylase deficiency (McArdle disease): A placebo-controlled crossover trial. Arch Neurol 57: 956-963, 2000

    Google Scholar 

  12. Leuzzi V, Bianchi MC, Tosetti M, Carducci C, Cerquiglini CA, Cioni G, Antonozzi I: Brain creatine depletion: Guanidinoacetate methyltransferase deficiency (improving with creatine supplementation). Neurology 55: 1407-1409, 2000

    Google Scholar 

  13. Stockler S, Hanefeld F: Guanidinoacetate methyltransferase deficiency: A newly recognized inborn error of creatine biosynthesis. Wiener Klinische Wochenschrift 109: 86-88, 1997

    Google Scholar 

  14. Stockler S, Hanefeld F, Frahm J: Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 21: 789-790, 1996

    Google Scholar 

  15. Ganesan V, Johnson A, Connelly A, Eckhardt S, Surtees RA: Guanidinoacetate methyltransferase deficiency: New clinical features. Pediatr Neurol 17: 155-157, 1997

    Google Scholar 

  16. Willer B, Stucki G, Hoppeler H, Bruhlmann P, Krahenbuhl S: Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis. Rheumatology (Oxford) 39: 293-298, 2000

    Google Scholar 

  17. Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W: Oral creatine supplementation in Duchenne muscular dystrophy: A clinical and 31P magnetic resonance spectroscopy study. Neurol Res 22: 145-150, 2000

    Google Scholar 

  18. Valtonen M, Nanto-Salonen K, Jaaskelainen S, Heinanen K, Alanen A, Heinonen OJ, Lundbom N, Erkintalo M, Simell O: Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinaemia. J Inherit Metab Dis 22: 855-866, 1999

    Google Scholar 

  19. Tarnopolsky MA, Parise G: Direct measurement of high-energy phosphate compounds in patients with neuromuscular disease. Muscle Nerve 22: 1228-1233, 1999

    Google Scholar 

  20. Heinanen K, Nanto-Salonen K, Komu M, Erkintalo M, Alanen A, Heinonen OJ, Pulkki K, Nikoskelainen E, Sipila I, Simell O: Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornith-inaemia. Eur J Clin Invest 29: 1060-1065, 1999

    Google Scholar 

  21. Tarnopolsky MA, Roy BD, MacDonald JR: A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve 20: 1502-1509, 1997

    Google Scholar 

  22. Hespel P, Eijnde BO, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, Dymarkowski S, Van Hecke P, Richter EA: Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol 536: 625-633, 2001

    Google Scholar 

  23. Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, Kraemer WJ, Meyer RA, Spriet LL, Tarnopolsky MA, Wagenmakers AJ, Williams MH: American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 32: 706-717, 2000

    Google Scholar 

  24. Benzi G: Is there a rationale for the use of creatine either as nutritional supplementation or drug administration in humans participating in a sport? Pharmacol Res 41: 255-264, 2000

    Google Scholar 

  25. Benzi G, Ceci A: Creatine as nutritional supplementation and medicinal product. J Sports Med Phys Fitness 41: 1-10, 2001

    Google Scholar 

  26. Graham AS, Hatton RC: Creatine: A review of efficacy and safety. J Am Pharm Assoc (Wash) 39: 803-810; quiz 875–807, 1999

    Google Scholar 

  27. Juhn MS, Tarnopolsky M: Potential side effects of oral creatine supplementation: A critical review. Clin J Sport Med 8: 298-304, 1998

    Google Scholar 

  28. Yu PH, Deng Y: Potential cytotoxic effect of chronic administration of creatine, a nutrition supplement to augment athletic performance. Med Hypotheses 54: 726-728, 2000

    Google Scholar 

  29. Papadopoulos C, Imamura R, Bandon LJ: The effect of creatine supplementation on repeated bouts of high-intensity exercise in the heat. Med Sci Sports Exerc 33: S203, 2001

    Google Scholar 

  30. Kern M, Podewils LJ, Vukovich M, Buono MJ: Physiological response to exercise in the heat following creatine supplementation. J Exerc Physiol Online 4: 18-27, 2001. Available:http://www.css.edu/users/tboone12/asep/Kern.pdf

    Google Scholar 

  31. Volek JS, Mazzetti SA, Farquhar WB, Barnes BR, Gomez AL, Kraemer WJ: Physiological responses to short-term exercise in the heat after creatine loading. Med Sci Sports Exerc 33: 1101-1108, 2001

    Google Scholar 

  32. McArthur PD, Webster MJ, Body JC, May RA, Eschbach LD, Eimer AF, Angelosoulos TJ, Zoeller RF, Krebs GV: Creatine supplementation and acute dehydration. Med Sci Sports Exerc 31: S263, 1999

    Google Scholar 

  33. Webster MJ, Vogel RA, Erdmann LD, Clark RD: Creatine supplementation: Effect on exercise performance at two levels of acute dehydration. Med Sci Sports Exerc 31: S263, 1999

    Google Scholar 

  34. Greenwood M, Kreider R, Rasmussen C, Ransom J, Melton C, Stroud T, Cantler E, Milnor P: Creatine supplementation does not increase incidence of cramping or injury during college football training II. J Strength Cond Res 13: 425-426, 1999

    Google Scholar 

  35. Kreider R, Melton C, Hunt J, Rasmussen C, Ransom J, Stroud T, Cantler E, Milnor P: Creatine does not increase incidence of cramping or injury during pre-season college football training 1. Med Sci Sports Exerc 31: S355, 1999

    Google Scholar 

  36. Greenwood M, Greenwood LD, Kreider R, Byars A: Effects of creatine supplementation on the incidence of cramping/injury during college football three a day training. Med Sci Sports Exerc 32: S136, 2000

    Google Scholar 

  37. Greenwood LD, Greenwood M, Kreider R, Byars A: Effects of creatine supplementation on the incidence of cramping/injury during collegiate fall baseball. Med Sci Sports Exerc 32: S136, 2000

    Google Scholar 

  38. Greenwood M, Farris J, Kreider R, Greenwood L, Byars A: Creatine supplementation patterns and perceived effects in select division I collegiate athletes. Clin J Sport Med 10: 191-194, 2000

    Google Scholar 

  39. Greenwood M, Kreider R, Melton C, Rasmussen C, Lancaster S, Cantler E, Milnor P, Almada AL: Creatine supplementation during college football training does not increase the incidence of cramping or injury. Abstracts of 6th International Conference on Guanidino Compounds in Biology and Medicine, Cincinnati, OH, September 1, 2001

  40. Hulver MW, Campbell A, Haff G, Schroeder C, Comeau M, Potteiger JA: The effects of creatine supplementation on total body fluids, performance, and muscle cramping during exercise. Med Sci Sports Exerc 32: S133, 2000

    Google Scholar 

  41. Hunt J, Kreider R, Melton C, Ransom J, Rasmussen C, Stroud T, Cantler E, Milnor P: Creatine does not increase incidence of cramping or injury during pre-season college football training II. Med Sci Sports Exerc 31: S355, 1999

    Google Scholar 

  42. Kreider R, Rasmussen C, Ransom J, Almada AL: Effects of creatine supplementation during training on the incidence of muscle cramping, injuries and GI distress. J Strength Cond Res 12: 275, 1998

    Google Scholar 

  43. Kreider R, Melton C, Ransom J, Rasmussen C, Stroud T, Cantler E, Greenwood M, Milnor P: Creatine supplementation does not increase incidence of cramping or injury during college football training I. J Strength Cond Res 13: 428, 1999

    Google Scholar 

  44. Almada AL, Kreider R, Melton C, Rasmussen C, Lundberg J, Ransom J, Greenwood M, Stroud T, Cantler E, Milnor P, Fox J: Long-term creatine supplementation does not affect markers of renal stress in athletes. J Strength Cond Res 14: 359, 2000

    Google Scholar 

  45. Earnest CP, Almada A, Mitchell TL: Influence of chronic creatine supplementation on hepatorenal function. FASEB J 10: A790, 1996

    Google Scholar 

  46. Kreider R, Ransom J, Rasmussen C, Hunt J, Melton C, Stroud T, Cantler E, Milnor P: Creatine supplementation during pre-season football training does not affect markers of renal function. FASEB J 13: A543, 1999

    Google Scholar 

  47. Kuehl K, Soehler S, Kulacki K, Goldberg L, Elliot D, Bennett W, Haddock B: Effects of oral creatine monohydrate supplementation on renal function in adults. Med Sci Sports Exerc 32: S168, 2000

    Google Scholar 

  48. Poortmans JR, Francaux M: Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 31: 1108-1110, 1999

    Google Scholar 

  49. Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR: Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol 76: 566-567, 1997

    Google Scholar 

  50. Rasmussen C, Kreider R, Melton C, Ransom J, Stroud T, Cantler E, Greenwood M, Milnor P: Long-term creatine supplementation during football training does not affect markers of renal stress. J Strength Cond Res 13: 431, 1999

    Google Scholar 

  51. Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL: Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med 34: 284-288, 2000

    Google Scholar 

  52. Bemben MG, Bemben DA, Loftiss DD, Knehans AW: Creatine supplementation during resistance training in college football athletes. Med Sci Sports Exerc 33: 1667-1673, 2001

    Google Scholar 

  53. Bermon S, Venembre P, Sachet C, Valour S, Dolisi C: Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiol Scand 164: 147-155, 1998

    Google Scholar 

  54. Eijnde BO, Hespel P: Short-term creatine supplementation does not alter the hormonal response to resistance training. Med Sci Sports Exerc 33: 449-453, 2001

    Google Scholar 

  55. Greenwood M, Kreider R, Melton C, Rasmussen C, Lundberg J, Stroud T, Cantler E, Milnor P, Almada AL: Short-and long-term creatine supplementation does not affect hematological markers of health. J Strength Cond Res 14: 362-363, 2000

    Google Scholar 

  56. Kreider R, Rasmussen C, Melton C, Greenwood M, Stroud T, Ransom J, Cantler E, Milnor P, Almada AL: Long-term creatine supplementation does not adversely affect clinical markers of health. Med Sci Sports Exerc 32: S134, 2000

    Google Scholar 

  57. Poortmans JR, Francaux M: Adverse effects of creatine supplementation: fact or fiction? Sports Med 30: 155-170, 2000

    Google Scholar 

  58. Sipila I, Rapola J, Simell O, Vannas A: Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. New Engl J Med 304: 867-870, 1981

    Google Scholar 

  59. Vannas-Sulonen K, Sipila I, Vannas A, Simell O, Rapola J: Gyrate atrophy of the choroid and retina. A five-year follow-up of creatine supplementation. Ophthalmology 92: 1719-1727, 1985

    Google Scholar 

  60. Schilling BK, Stone MH, Utter A, Kearney JT, Johnson M, Coglianese R, Smith L, O'Bryant HS, Fry AC, Starks M, Keith R, Stone ME: Creatine supplementation and health variables: a retrospective study. Med Sci Sports Exerc 33: 183-188, 2001

    Google Scholar 

  61. Stone MH, Schilling BK, Fry AC, Johnson M, Keith RE, Kearney JT, Coglianese RH, Stone ME, Utter A, Smith L, O'Bryant HS: A retrospective study of long-term creatine supplementation on blood markers of health. J Strength Cond Res 13: 433, 1999

    Google Scholar 

  62. Juhn MS, O'Kane JW, Vinci DM: Oral creatine supplementation in male collegiate athletes: a survey of dosing habits and side effects. J Am Diet Assoc 99: 593-595, 1999

    Google Scholar 

  63. Ray TR, Eck JC, Covington LA, Murphy RB, Williams R, Knudtson J: Use of oral creatine as an ergogenic aid for increased sports performance: Perceptions of adolescent athletes. South Med J 94: 608-612, 2001

    Google Scholar 

  64. Sheppard HL, Raichada SM, Kouri KM, Stenson-Bar-Maor L, Branch JD: Use of creatine and other supplements by members of civilian and military health clubs: Across-sectional survey. Int J Sport Nutr Exerc Metab 10: 245-259, 2000

    Google Scholar 

  65. Smith J, Dahm DL: Creatine use among a select population of high school athletes. Mayo Clin Proc 75: 1257-1263, 2000

    Google Scholar 

  66. Stephens MB, Olsen C: Ergogenic supplements and health risk behaviors. J Fam Pract 50: 696-699, 2001

    Google Scholar 

  67. Metzl JD, Small E, Levine SR, Gershel JC: Creatine use among young athletes. Pediatrics 108: 421-425, 2001

    Google Scholar 

  68. Greenwood M, Kreider R, Greenwood LD, Comeau M, Brown LE, Stahura K, Byars A: Perceived health status and side-effects associated with creatine supplementation during the collegiate baseball season. Med Sci Sports Exerc 33: S205, 2001

    Google Scholar 

  69. Kuehl K, Goldber L, Elliot D: Renal insufficiency after creatine supplementation in a college football athlete. Med Sci Sports Exerc 30: S235, 1998

    Google Scholar 

  70. Pritchard NR, Kalra PA: Renal dysfunction accompanying oral creatine supplements. Lancet 351: 1252-1253, 1998

    Google Scholar 

  71. Koshy KM, Griswold E, Schneeberger EE: Interstitial nephritis in a patient taking creatine. N Engl J Med 340: 814-815, 1999

    Google Scholar 

  72. Loud K, Rozycki A, Chobanian M: Creatine nephropathy — Lacrosse. Med Sci Sports Exerc 33: S10, 2001

    Google Scholar 

  73. Poortmans JR, Francaux M: Renal dysfunction accompanying oral creatine supplements. Lancet 352: 234, 1998

    Google Scholar 

  74. Greenhaff P: Renal dysfunction accompanying oral creatine supplements. Lancet 352: 233-234, 1998

    Google Scholar 

  75. Kreider RB, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinardy J, Cantler E, Almada AL: Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 30: 73-82, 1998

    Google Scholar 

  76. Ziegenfuss TN, Lowery LM, Lemon PWR: Acute fluid volume changes in men during three days of creatine supplementation. J Exerc Physiol Online 1: 1-9, 1998. Available: http://www.css.edu/users/tboone2/asep/jan3.htm

    Google Scholar 

  77. Rasmussen C, Kreider R, Ransom J, Hunt J, Melton C, Stroud T, Cantler E, Milnor P: Creatine supplementation during pre-season football training does not affect fluid or electrolyte status. Med Sci Sports Exerc 31: S299, 1999

    Google Scholar 

  78. Earnest CP, Almada A, Mitchell TL: High-performance capillary electrophoresis-pure creatine monohydrate reduced blood lipids in men and women. Clin Sci 91: 113-118, 1996

    Google Scholar 

  79. Arciero PJ, Hannibal III N, Hamed J, Gentile C: Effect of creatine on resting metabolic rate, body composition, strength, and blood cholesterol. Med Sci Sports Exerc 31: S264, 1999

    Google Scholar 

  80. Dulacki K, Kuehl K, Koehler S, Elliot D, Goldberg L: Effects of creatine on body composition, strength, maximal aerobic capacity, cholesterol and gender. Med Sci Sports Exerc 32: S135, 2000

    Google Scholar 

  81. Volek JS, Duncan ND, Mazzetti SA, Putukian M, Gomez AL, Kraemer WJ: No effect of heavy resistance training and creatine supplementation on blood lipids. Int J Sport Nutr Exerc Metab 10: 144-156, 2000

    Google Scholar 

  82. Melton C, Kreider R, Rasmussen C, Ransom J, Hunt J, Stroud T, Cantler E, Milnor P: Effects of ingesting creatine containing supplements during training on blood lipid profiles. FASEB J 13: A559, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kreider, R.B., Melton, C., Rasmussen, C.J. et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem 244, 95–104 (2003). https://doi.org/10.1023/A:1022469320296

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022469320296

Navigation