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European Journal of Applied Physiology

, Volume 103, Issue 1, pp 33–40 | Cite as

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial

  • Bruno GualanoEmail author
  • Carlos Ugrinowitsch
  • Rafael Batista Novaes
  • Guilherme Gianini Artioli
  • Maria Heloisa Shimizu
  • Antonio Carlos Seguro
  • Roger Charles Harris
  • Antonio Herbert LanchaJr
Original Article
First Online:

Abstract

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18–35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) (∼10 g day−1 over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L−1) (PRE CR: 0.82 ± 0.09; PL: 0.88 ± 0.07 vs. POST 12 CR: 0.71 ± 0.06; PL: 0.75 ± 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

Keywords

Adverse effects Kidneys Cystatin C Exercise 
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Notes

Acknowledgments

We are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support. We would also like to express our thanks to the subjects who took part in the study.

References

  1. Bruce RA, Kusumi F, Hosmer D (1973) Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 85:546–562PubMedCrossRefGoogle Scholar
  2. Conway JM, Ingwersen LA, Moshfegh AJ (2004) Accuracy of dietary recall using the USDA five-step multiple-pass method in men: an observational validation study. J Am Diet Assoc 104:595–603PubMedCrossRefGoogle Scholar
  3. Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226PubMedCrossRefGoogle Scholar
  4. Edmunds JW, Jayapalan S, DiMarco NM, Saboorian MH, Aukema HM (2001) Creatine supplementation increases renal disease progression in Han:SPRD-cy rats. Am J Kidney Dis 37:73–78PubMedGoogle Scholar
  5. Ferreira LG, De Toledo Bergamaschi C, Lazaretti-Castro M, Heilberg IP (2005) Effects of creatine supplementation on body composition and renal function in rats. Med Sci Sports Exerc 37:1525–1529PubMedCrossRefGoogle Scholar
  6. Finkelstein J, Joshi A, Hise MK (2006) Association of physical activity and renal function in subjects with and without metabolic syndrome: a review of the Third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis 48:372–382PubMedCrossRefGoogle Scholar
  7. Fried LF, Orchard TJ, Kasiske BL (2001) Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int 59:260–269PubMedCrossRefGoogle Scholar
  8. Gaede P, Poulsen HE, Parving HH, Pedersen O (2001) Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients. Diabet Med 18:756–760PubMedCrossRefGoogle Scholar
  9. Groeneveld GJ, Beijer C, Veldink JH, Kalmijn S, Wokke JH, van den Berg LH (2005) Few adverse effects of long-term creatine supplementation in a placebo-controlled trial. Int J Sports Med 26:307–313PubMedCrossRefGoogle Scholar
  10. Gualano B, Novaes RB, Shimuzu HM, Artioli GG, Rogeri PS, Ugrinowitsch C, Seguro AC, Lancha AH Jr (2006) Aerobic training improves renal function and decreases oxidative stress in healthy sedentary males, despite high-dose creatine supplementation. J Am Soc Nephrol 203AGoogle Scholar
  11. Gualano B, Novaes RB, Artioli GG, Freire TO, Coelho DF, Scagliusi FB, Rogeri PS, Roschel H, Ugrinowitsch C, Lancha AH Jr (2008) Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training. Amino Acids (in press)Google Scholar
  12. Harris RC, Nevill M, Harris DB, Fallowfield JL, Bogdanis GC, Wise JA (2002) Absorption of creatine supplied as a drink, in meat or in solid form. J Sports Sci 20:147–151PubMedCrossRefGoogle Scholar
  13. Harris RC, Soderlund K, Hultman E (1992) Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 83:367–374Google Scholar
  14. Jaber BL, Madias NE (2005) Progression of chronic kidney disease: can it be prevented or arrested?. Am J Med 118:1323–1330PubMedCrossRefGoogle Scholar
  15. Kazama JJ, Kutsuwada K, Ataka K, Maruyama H, Gejyo F (2002) Serum cystatin C reliably detects renal dysfunction in patients with various renal diseases. Nephron 91:13–20PubMedCrossRefGoogle Scholar
  16. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G (1994) The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of diet in Renal Disease Study Group. N Engl J Med 330:877–884PubMedCrossRefGoogle Scholar
  17. Koshy KM, Griswold E, Schneeberger EE (1999) Interstitial nephritis in a patient taking creatine. N Engl J Med 340:814–815PubMedCrossRefGoogle Scholar
  18. Kreider RB (2003) Species-specific responses to creatine supplementation. Am J Physiol Regul Integr Comp Physiol 285:R725–R726PubMedGoogle Scholar
  19. Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, Milnor P, Almada AL (2003) Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem 244:95–104PubMedCrossRefGoogle Scholar
  20. Kuehl K, Goldberg L, Elliot D (1998) Renal insufficiency after creatine supplementation in a college football athlete (abstract). Med Sci Sports Exerc 30:S235Google Scholar
  21. Kuehl K, Goldberg L, Elliot D (2000) Re: long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 32:248–249PubMedCrossRefGoogle Scholar
  22. Littell RC, Milliken GA, Stroup WW, Wolfinger RD, Schabenberger O (2006) SAS system for mixed models. SAS Institute, CaryGoogle Scholar
  23. Pline KA, Smith CL (2005) The effect of creatine intake on renal function. Ann Pharmacother 39:1093–1096PubMedCrossRefGoogle Scholar
  24. Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR (1997) Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol 76:566–567PubMedCrossRefGoogle Scholar
  25. Poortmans JR, Francaux M (1999) Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 31:1108–1110PubMedCrossRefGoogle Scholar
  26. Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux M (2005) Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Med Sci Sports Exerc 37:1717–1720PubMedCrossRefGoogle Scholar
  27. Preiss DJ, Godber IM, Lamb EJ, Dalton RN, Gunn IR (2007) The influence of a cooked-meat meal on estimated glomerular filtration rate. Ann Clin Biochem 44:35–42PubMedCrossRefGoogle Scholar
  28. Pritchard NR, Kalra PA (1998) Renal dysfunction accompanying oral creatine supplements. Lancet 351:1252–1253PubMedCrossRefGoogle Scholar
  29. Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL (2000) Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med 34:284–288PubMedCrossRefGoogle Scholar
  30. Roos JF, Doust J, Tett SE, Kirkpatrick CM (2007) Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children-a meta-analysis. Clin Biochem 40:383–391PubMedCrossRefGoogle Scholar
  31. Sewell DA, Harris RC (1995) Effect of creatine supplementation in the Thoroughbred horse. Equine Vet J 18:239–242Google Scholar
  32. Shao A, Hathcock JN (2006) Risk assessment for creatine monohydrate. Regul Toxicol Pharmacol 45:242–251PubMedCrossRefGoogle Scholar
  33. Stengel B, Tarver-Carr ME, Powe NR, Eberhardt MS, Brancati FL (2003) Lifestyle factors, obesity and the risk of chronic kidney disease. Epidemiology 14:479–487PubMedGoogle Scholar
  34. Stevens LA, Coresh J, Greene T, Levey AS (2006) Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med 354:2473–2483PubMedCrossRefGoogle Scholar
  35. Taes YE, Delanghe JR, Wuyts B, van de Voorde J, Lameire NH (2003) Creatine supplementation does not affect kidney function in an animal model with pre-existing renal failure. Nephrol Dial Transplant 18:258–264PubMedCrossRefGoogle Scholar
  36. Tarnopolsky MA, Bourgeois JM, Snow R, Keys S, Roy BD, Kwiecien JM, Turnbull J (2003) Histological assessment of intermediate and long-term creatine monohydrate supplementation in mice and rats. Am J Physiol Regul Integr Comp Physiol 285:R762–R769PubMedGoogle Scholar
  37. Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, Kraemer WJ, Meyer RA, Spriet LL, Tarnopolsky MA, Wagenmakers AJ, Williams MH (2000) American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 32:706–717PubMedCrossRefGoogle Scholar
  38. Thorsteinsdottir B, Grande JP, Garovic VD (2006) Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate. J Ren Nutr 16:341–345PubMedGoogle Scholar
  39. Ugrinowitsch C, Fellingham GW, Ricard MD (2004) Limitations of ordinary least squares models in analyzing repeated measures data. Med Sci Sports Exerc 36:2144–2148PubMedCrossRefGoogle Scholar
  40. Volek JS, Duncan ND, Mazzetti SA, Putukian M, Gomez AL, Kraemer WJ (2000) No effect of heavy resistance training and creatine supplementation on blood lipids. Int J Sport Nutr Exerc Metab 10:144–156PubMedGoogle Scholar
  41. Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80:1107–1213PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Bruno Gualano
    • 1
    • 4
    Email author
  • Carlos Ugrinowitsch
    • 1
  • Rafael Batista Novaes
    • 1
  • Guilherme Gianini Artioli
    • 1
  • Maria Heloisa Shimizu
    • 2
  • Antonio Carlos Seguro
    • 2
  • Roger Charles Harris
    • 3
  • Antonio Herbert LanchaJr
    • 1
  1. 1.Laboratory of Applied Nutrition and Metabolism, School of Physical Education and SportUniversity of Sao PauloSao PauloBrazil
  2. 2.School of Medicine, Nephrology DepartmentUniversity of Sao PauloSao PauloBrazil
  3. 3.School of Sport, Exercise and Health SciencesUniversity of ChichesterChichesterUK
  4. 4.Sao PauloBrazil

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