Skip to main content

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Abstract

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, 51Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 ± 10, Post 70 ± 18 mmol/kg/wt; PL Pre 52 ± 13, Post 46 ± 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42–45.8). No significant differences were observed for 51Cr-EDTA clearance (CR Pre 90.4 ± 16.9, Post 96.1 ± 15.0 mL/min/1.73 m2; PL Pre 97.9 ± 21.6, Post 96.4 ± 26.8 mL/min/1.73 m2; p = 0.58; estimated difference between means −0.3; 95% confidence interval −24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. Dalbo VJ, Roberts MD, Stout JR, Kerksick CM (2008) Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration. Br J Sports Med 42(7):567–573

    PubMed  Article  CAS  Google Scholar 

  2. 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(1):73–78

    PubMed  Article  CAS  Google Scholar 

  3. 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(9):1525–1529

    PubMed  Article  CAS  Google Scholar 

  4. 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(4):307–313

    PubMed  Article  CAS  Google Scholar 

  5. Gualano B, Novaes RB, Artioli GG, Freire TO, Coelho DF, Scagliusi FB, Rogeri PS, Roschel H, Ugrinowitsch C, Lancha AH Jr (2008a) Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training. Amino Acids 34(2):245–250. doi:10.1007/s00726-007-0508-1

    PubMed  Article  CAS  Google Scholar 

  6. Gualano B, Ugrinowitsch C, Novaes RB, Artioli GG, Shimizu MH, Seguro AC, Harris RC, Lancha AH Jr (2008b) Effects of creatine supplementation on renal function: A randomized, double-blind, placebo-controlled clinical trial. Eur J Appl Physiol 103(1):33–40. doi:10.1007/s00421-007-0669-3

    PubMed  Article  CAS  Google Scholar 

  7. Gualano B, Artioli GG, Poortmans JR, Lancha Junior AH (2009a) Exploring the therapeutic role of creatine supplementation. Amino Acids 38(1):31–44

    PubMed  Article  Google Scholar 

  8. Gualano B, Coelho DF, Seguro AC, Sapienza MT, Lancha Junior AH (2009b) Effect of short-term, high-dose creatine supplementation on measured GFR in a young man with a single kidney. Am J Kidney Dis 55(3):e7–e9

    Article  Google Scholar 

  9. 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(3):367–374

    CAS  Google Scholar 

  10. Koshy KM, Griswold E, Schneeberger EE (1999) Interstitial nephritis in a patient taking creatine. N Engl J Med 340(10):814–815

    PubMed  Article  CAS  Google Scholar 

  11. 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(1–2):95–104

    PubMed  Article  CAS  Google Scholar 

  12. Kuehl K, Goldberg L, Elliot D (1998) Renal insufficiency after creatine supplementation in a college football athlete (abstract). Med Sci Sports Exerc 30:S235

    Google Scholar 

  13. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G (2003) National kidney foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139(2):137–147

    PubMed  Google Scholar 

  14. Louis M, Lebacq J, Poortmans JR, Belpaire-Dethiou MC, Devogelaer JP, Van Hecke P, Goubel F, Francaux M (2003) Beneficial effects of creatine supplementation in dystrophic patients. Muscle Nerve 27(5):604–610

    PubMed  Article  CAS  Google Scholar 

  15. Op‘t Eijnde B, Urso B, Richter EA, Greenhaff PL, Hespel P (2001) Effect of oral creatine supplementation on human muscle glut4 protein content after immobilization. Diabetes 50(1):18–23

    Article  Google Scholar 

  16. Op’t Eijnde B, Jijakli H, Hespel P, Malaisse WJ (2006) Creatine supplementation increases soleus muscle creatine content and lowers the insulinogenic index in an animal model of inherited type 2 diabetes. Int J Mol Med 17(6):1077–1084

    PubMed  Google Scholar 

  17. Persky AM, Rawson ES (2007) Safety of creatine supplementation. Subcell Biochem 46:275–289

    PubMed  Article  Google Scholar 

  18. Poortmans JR, Francaux M (1999) Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 31(8):1108–1110

    PubMed  Article  CAS  Google Scholar 

  19. Poortmans JR, Francaux M (2000) Adverse effects of creatine supplementation: fact or fiction? Sports Med 30(3):155–170

    PubMed  Article  CAS  Google Scholar 

  20. 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(6):566–567

    PubMed  Article  CAS  Google Scholar 

  21. 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(10):1717–1720

    PubMed  Article  CAS  Google Scholar 

  22. Pritchard NR, Kalra PA (1998) Renal dysfunction accompanying oral creatine supplements. Lancet 351(9111):1252–1253

    PubMed  Article  CAS  Google Scholar 

  23. Sewell DA, Harris RC (2002) Effect of creatine supplementation in the thoroughbred horse. Equine Vet J 18:239–242

    Google Scholar 

  24. Shao A, Hathcock JN (2006) Risk assessment for creatine monohydrate. Regul Toxicol Pharmacol 45(3):242–251

    PubMed  Article  CAS  Google Scholar 

  25. 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 18:258–264

    Google Scholar 

  26. 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–R769

    Google Scholar 

  27. 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(4):341–345

    PubMed  Article  Google Scholar 

  28. Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80(3):1107–1213

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Bruno Gualano, Antonio Carlos Seguro and Guilherme G. Artioli received financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico. The authors declare that the present experiment complies with the current research ethics laws of the country it has been performed in. The experimental protocol has been approved by the institution’s Ethical Committee in Research and all the subjects have signed an informed consent.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Bruno Gualano.

Additional information

Communicated by Susan Ward.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gualano, B., de Salles Painelli, V., Roschel, H. et al. Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial. Eur J Appl Physiol 111, 749–756 (2011). https://doi.org/10.1007/s00421-010-1676-3

Download citation

Keywords

  • Phosphorylcreatine
  • Chronic kidney disease
  • Diabetes
  • Glomerular filtration rate