title: Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels.
abstract: OBJECTIVE
  Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its' dose-response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism.
  
  
  METHODS
  Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine.
  
  
  RESULTS
  GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo (P < 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase (P < 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose-response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention (P > 0.05).
  
  
  CONCLUSIONS
  Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine.
  
  
  BACKGROUND
  ClinicalTrials.gov, identification number NCT01133899.
authors.affiliation: Exercise Physiology Laboratory, Center for Health, Exercise and Sport Sciences, Stari DIF, Deligradska 27, 11000, Belgrade, Serbia, sergej.ostojic@chess.edu.rs.
authors.forename: Sergej M
authors.initials: SM
authors.lastname: Ostojic
authors.forename: Marko
authors.initials: M
authors.lastname: Stojanovic
authors.forename: Patrik
authors.initials: P
authors.lastname: Drid
authors.forename: Jay R
authors.initials: JR
authors.lastname: Hoffman
mesh_terms: D000284:Administration, Oral; D003401:Creatine / Q000097:blood* / Q000652:urine; D003404:Creatinine / Q000652:urine; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000652:urine; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D014803:Vitamin B Complex / Q000097:blood*; D055815:Young Adult
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D003404:Creatinine; C004946:glycocyamine; D003401:Creatine; D005998:Glycine