title: Creatine supplementation decreases homocysteine in an animal model of uremia.
abstract: 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 micromol/L vs. 15.4 +/- 1.7 micromol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Clinical Chemistry, University Hospital Ghent, Ghent, Belgium. Youri.Taes@UGent.be
authors.forename: Youri E C
authors.initials: YE
authors.lastname: Taes
authors.forename: Joris R
authors.initials: JR
authors.lastname: Delanghe
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
authors.forename: Roeland
authors.initials: R
authors.lastname: Rombaut
authors.forename: John
authors.initials: J
authors.lastname: Van Camp
authors.forename: Norbert H
authors.initials: NH
authors.lastname: Lameire
mesh_terms: D000818:Animals; D001699:Biometry; D003401:Creatine / Q000494:pharmacology*; D005492:Folic Acid / Q000097:blood / Q000378:metabolism; D006710:Homocysteine / Q000037:antagonists & inhibitors* / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D014805:Vitamin B 12 / Q000097:blood / Q000378:metabolism
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D003401:Creatine; D014805:Vitamin B 12