title: Dietary guanidinoacetic acid increases brain creatine levels in healthy men.
abstract: OBJECTIVE
  Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention.
  
  
  METHODS
  Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity.
  
  
  RESULTS
  Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05). Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention.
  
  
  CONCLUSIONS
  Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease.
authors: Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia; University of Belgrade School of Medicine, Belgrade, Serbia. Electronic address: Sergej.ostojic@chess.edu.rs.
authors: Sergej M
authors: SM
authors: Ostojic
authors: University Clinical Center of Vojvodina, Novi Sad, Serbia.
authors: Jelena
authors: J
authors: Ostojic
authors: Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia.
authors: Patrik
authors: P
authors: Drid
authors: Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors: Milan
authors: M
authors: Vranes
authors: Institute of Food Technology, University of Novi Sad, Novi Sad, Serbia.
authors: Pavle
authors: P
authors: Jovanov
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000819:agonists / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D003401:Creatine / Q000819:agonists* / Q000097:blood / Q000378:metabolism / Q000652:urine; D019587:Dietary Supplements / Q000009:adverse effects*; D015536:Down-Regulation; D005500:Follow-Up Studies; D005998:Glycine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced; D008279:Magnetic Resonance Imaging; D008297:Male; D008745:Methylation; D059906:Neuroimaging; D009474:Neurons / Q000378:metabolism*; D058573:Performance-Enhancing Substances / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D023382:Toxicity Tests, Acute; D055815:Young Adult
chemical_list: D015415:Biomarkers; D058573:Performance-Enhancing Substances; D001224:Aspartic Acid; C000179:N-acetylaspartate; C004946:glycocyamine; D003401:Creatine; D005998:Glycine
keywords: Cerebellum; Creatine synthesis; Gray matter; MR spectroscopy; Side effects; White matter