Dose–response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels

Sergej M. Ostojic, Marko Stojanovic, Patrik Drid, Jay R. Hoffman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Purpose: 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.

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).

Conclusion: 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. Clinical trial registration:, identification number NCT01133899.

Original languageEnglish
Pages (from-to)1637-1643
Number of pages7
JournalEuropean Journal of Nutrition
StatePublished - 2014
Externally publishedYes


  • Bioenergetics
  • Creatine
  • Creatinine
  • Homocysteine
  • Supplementation


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