Ion Channels – Membrane Transport – Integrative Physiology
Kidney International (2003) 64, 1331–1337; doi:10.1046/j.1523-1755.2003.00206.x
Creatine supplementation decreases homocysteine in an animal model of uremia
Youri E C Taes, Joris R Delanghe, An S De Vriese, Roeland Rombaut, John Van Camp and Norbert H Lameire
Laboratory of Clinical Chemistry, University Hospital Ghent, Ghent, Belgium; Renal Unit, Department of Internal Medicine, University Hospital Ghent, Ghent, Belgium; and Department of Food Technology and Nutrition, Faculty of Agricultural and Applied Biological Sciences, Ghent University, Ghent, Belgium
Correspondence: Youri E.C. Taes, M.D., Laboratory Clinical Chemistry 2P8, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: Youri.Taes@UGent.be
Received 27 January 2003; Revised 20 March 2003; Re-revised 5 May 2003; Accepted 16 May 2003.
Abstract
Creatine supplementation decreases homocysteine in an animal model of uremia.
Background
Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is thought to contribute to the excess cardiovascular mortality and morbidity. Creatine is synthesized by methylation of guanidinoacetate with formation of S-adenosylhomocysteine and subsequently, homocysteine (Hcy). Creatine supplementation down-regulates its endogenous synthesis and, thus, may reduce Hcy production. The present study investigates the effect of creatine supplementation on Hcy concentrations in an animal model of uremia.
Methods
Male Wistar rats were either sham-operated and received a control diet (N = 8) or a 2% creatine-supplemented diet (N = 8), or underwent subtotal nephrectomy and received a control diet (N = 10) or a 2%-supplemented creatine diet (N = 10). After 2 weeks of treatment, total plasma Hcy, creatine, creatinine, folate, and vitamin B12 were determined, as well as hepatic folate and vitamin B12 concentrations.
Results
Plasma creatinine concentrations were higher in nephrectomized animals, but similar in creatine-supplemented and control diet–fed animals. Plasma Hcy was higher in nephrectomized animals but lower in creatine-supplemented nephrectomized animals compared to nephrectomized control diet–fed animals (12.1 
2.4 
mol/L vs. 15.4 1.7 mol/L; P < 0.01). Total plasma Hcy inversely correlated with plasma creatine concentrations (r =-0.39; P = 0.02). Plasma folate was higher in supplemented animals and hepatic tetrahydrofolate (THF) was higher in nephrectomized supplemented animals. Plasma vitamin B12 was similar in all groups, whereas hepatic vitamin B12 was higher in nephrectomized animals.
Conclusion
Creatine supplementation can effectively lower plasma Hcy concentrations in an animal model of uremia and should be further investigated as a potential treatment for hyperhomocysteinemia in patients with ESRD.
Keywords:
total plasma homocysteine, tetrahydrofolate, 5-methyltetrahydrofolate, end-stage renal disease, creatine
