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Advanced physiological roles of guanidinoacetic acid

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Abstract

Dietary guanidinoacetic acid (GAA) seems to improve cellular bioenergetics by stimulating creatine biosynthesis. However, GAA could have other biological functions that might affect its possible use as a food ingredient in human nutrition. In this paper, we identified several alternative physiological roles of supplemental GAA, including the stimulation of hormonal release and neuromodulation, an alteration of metabolic utilization of arginine, and an adjustment of oxidant–antioxidant status. A better knowledge of how GAA affects human physiology may facilitate its use as an experimental nutritional intervention for novel purposes and conditions.

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References

  1. Weber CJ (1934) Isolation of glycocyamine from urine. Exp Biol Med 32:172–174

    Article  Google Scholar 

  2. Davenport HW, Fisher RB, Wilhelmi AE (1938) The metabolism of creatine: the role of glycocyamine in creatine synthesis. Biochem J 32(2):262–270

    Article  CAS  Google Scholar 

  3. Edison EE, Brosnan ME, Meyer C, Brosnan JT (2007) Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo. Am J Physiol Renal Physiol 293(6):F1799–F1804

    Article  CAS  Google Scholar 

  4. Tsubakihara Y, Suzuki A, Hayashi T, Shoji T, Togawa M, Okada N (1999) The effect of guanidinoacetic acid supplementation in patients with chronic renal failure. In: Mori A, Ishida M, Clark JF (eds) Guanidino compounds in biology and medicine, vol 5. Blackwell Science Asia, Tokyo, pp 139–144

    Google Scholar 

  5. Ostojic SM, Stojanovic MD, Hoffman JR (2015) Six-week oral guanidinoacetic acid administration improves muscular performance in healthy volunteers. J Investig Med. doi:10.1097/JIM.0000000000000212

    Google Scholar 

  6. Ostojic SM, Hoffman JR, Stojanovic M, Drid P (2015) 28-day GAA supplementation improves clinical outcomes in patients with chronic fatigue syndrome. Med Sci Sport Exerc 48(5):S47

    Google Scholar 

  7. McBreairty LE, Robinson JL, Furlong KR, Brunton JA, Bertolo RF (2015) Guanidinoacetate is more effective than creatine at enhancing tissue creatine stores while consequently limiting methionine availability in Yucatan miniature pigs. PLoS One 10(6):e0131563

    Article  Google Scholar 

  8. Van Zandt V, Borsook H (1951) New biological approach to the treatment of congestive heart failure. Ann West Med Surg 5(10):856–862

    Google Scholar 

  9. Borsook ME, Billig HK, Golseth JG (1952) Betaine and glycocyamine in the treatment of disability resulting from acute anterior poliomyelitis. Ann West Med Surg 6(7):423–427

    CAS  Google Scholar 

  10. Aynsley-Green A, Alberti KG (1974) In vivo stimulation of insulin secretion by guanidine derivatives in the rat. Horm Metab Res 6(2):115–120

    Article  CAS  Google Scholar 

  11. Alsever RN, Georg RH, Sussman KE (1970) Stimulation of insulin secretion by guanidinoacetic acid and other guanidine derivatives. Endocrinology 86(2):332–336

    Article  CAS  Google Scholar 

  12. Marco J, Calle C, Hedo JA, Villanueva ML (1976) Glucagon-releasing activity of guanidine compounds in mouse pancreatic islets. FEBS Lett 64(1):52–54

    Article  CAS  Google Scholar 

  13. Charles S, Tamagawa T, Henquin JC (1982) A single mechanism for the stimulation of insulin release and 86Rb+ efflux from rat islets by cationic amino acids. Biochem J 208(2):301–308

    Article  CAS  Google Scholar 

  14. Meglasson MD, Wilson JM, Yu JH, Robinson DD, Wyse BM, de Souza CJ (1993) Antihyperglycemic action of guanidinoalkanoic acids: 3-guanidinopropionic acid ameliorates hyperglycemia in diabetic KKAy and C57BL6Job/ob mice and increases glucose disappearance in rhesus monkeys. J Pharmacol Exp Ther 266(3):1454–1462

    CAS  Google Scholar 

  15. Baker DH (2009) Advances in protein-amino acid nutrition of poultry. Amino Acids 37(1):29–41

    Article  CAS  Google Scholar 

  16. Ringel J, Lemme A, Redshaw MS, Damme K (2008) The effects of supplemental guanidino acetic acid as a precursor of creatine in vegetable broiler diets on performance and carcass parameters. Poult Sci 87(Suppl 1):72

    Google Scholar 

  17. Michiels J, Maertens L, Buyse J, Lemme A, Rademacher M, Dierick NA, De Smet S (2012) Supplementation of guanidinoacetic acid to broiler diets: effects on performance, carcass characteristics, meat quality, and energy metabolism. Poult Sci 91(2):402–412

    Article  CAS  Google Scholar 

  18. Dilger RN, Bryant-Angeloni K, Payne RL, Lemme A, Parsons CM (2013) Dietary guanidino acetic acid is an efficacious replacement for arginine for young chicks. Poult Sci 92(1):171–177

    Article  CAS  Google Scholar 

  19. Tong BC, Barbul A (2004) Cellular and physiological effects of arginine. Mini Rev Med Chem 4(8):823–832

    Article  CAS  Google Scholar 

  20. De Deyn PP, Macdonald RL (1990) Guanidino compounds that are increased in cerebrospinal fluid and brain of uremic patients inhibit GABA and glycine responses on mouse neurons in cell culture. Ann Neurol 28(5):627–633

    Article  Google Scholar 

  21. Neu A, Neuhoff H, Trube G, Fehr S, Ullrich K, Roeper J, Isbrandt D (2002) Activation of GABA(A) receptors by guanidinoacetate: a novel pathophysiological mechanism. Neurobiol Dis 11(2):298–307

    Article  CAS  Google Scholar 

  22. Ostojic SM, Stojanovic MD (2015) Guanidinoacetic acid loading affects plasma & #x03B3;-aminobutyric acid in healthy men. Eur J Nutr 54(5):855–858

    Article  CAS  Google Scholar 

  23. James E, Morrison JF (1966) The reaction of phosphagens with ATP: creatine phosphotransferase. Biochim Biophys Acta 128(2):327–336

    Article  CAS  Google Scholar 

  24. Rowley GL, Greenleaf AL, Kenyon GL (1971) On the specificity of creatine kinase. New glycocyamines and glycocyamine analogs related to creatine. J Am Chem Soc 93(12):5542–5551

    Article  CAS  Google Scholar 

  25. Lygate CA, Aksentijevic D, Dawson D, ten Hove M, Phillips D, de Bono JP, Medway DJ, Sebag-Montefiore L, Hunyor I, Channon KM, Clarke K, Zervou S, Watkins H, Balaban RS, Neubauer S (2013) Living without creatine: unchanged exercise capacity and response to chronic myocardial infarction in creatine-deficient mice. Circ Res 112(6):945–955

    Article  CAS  Google Scholar 

  26. Boehm EA, Radda GK, Tomlin H, Clark JF (1996) The utilisation of creatine and its analogues by cytosolic and mitochondrial creatine kinase. Biochim Biophys Acta 1274(3):119–128

    Article  Google Scholar 

  27. Kan HE, Renema WK, Isbrandt D, Heerschap A (2004) Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase. J Physiol 560(1):219–229

    Article  CAS  Google Scholar 

  28. Zugno AI, Stefanello FM, Scherer EB, Mattos C, Pederzolli CD, Andrade VM, Wannmacher CM, Wajner M, Dutra-Filho CS, Wyse AT (2008) Guanidinoacetate decreases antioxidant defenses and total protein sulfhydryl content in striatum of rats. Neurochem Res 33(9):1804–1810

    Article  CAS  Google Scholar 

  29. Mori A, Kohno M, Masumizu T, Nosa Y, Packer I (1996) Guanidino compounds generate reactive oxygen species. Biochem Mol Biol Int 40(1):135–143

    CAS  Google Scholar 

  30. Wang LS, Shi BM, Shan AS, Zhang YY (2012) Effects of guanidinoacetic acid on growth performance, meat quality and antioxidation in growing-finishing pigs. J Anim Vet Adv 11(5):631–636

    Article  CAS  Google Scholar 

  31. Hiramatsu M (2003) A role of guanidino compounds in the brain. Mol Cell Biochem 244(1–2):57–62

    Article  CAS  Google Scholar 

  32. Major RH, Weber CJ (1928) The effects of glycocyamine and glyocyamidine on the blood pressure. Johns Hopkins Med J 42:207

    CAS  Google Scholar 

  33. Major RH (1929) Observations on the effects of certain guanidine compounds upon the blood pressure. Tr A Am Physician 44:332

    Google Scholar 

  34. Major RH (1930) Some observations upon the physiologic and therapeutic action of glycocyamine. J Clin Investig 9(1):24

    Google Scholar 

  35. Ginsberg AM, Stoland OO (1931) The effect of glycocyamine on the coronary circulation. Pharmacol Exp Ther 41(2):195–208

    CAS  Google Scholar 

  36. Udenfriend S, Creveling CR, Ozaki M, Daly JW, Witkop B (1959) Inhibitors of norepinephrine metabolism in vivo. Arch Biochem Biophys 84:249–251

    Article  CAS  Google Scholar 

  37. Charlier R (1961) Coronary vasodilators: international series of monographs on pure and applied biology division: modern trends in physiological sciences, vol 10. Pergamon Press, Oxford

    Google Scholar 

  38. Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N, Stefanadis C (2012) The role of nitric oxide on endothelial function. Curr Vasc Pharmacol 10(1):4–18

    Article  CAS  Google Scholar 

  39. Stockler S, Schutz PW, Salomons GS (2007) Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. Subcell Biochem 46:149–166

    Article  Google Scholar 

  40. Schulze A (2003) Creatine deficiency syndromes. Mol Cell Biochem 244(1–2):143–150

    Article  CAS  Google Scholar 

  41. Braisant O (2012) Creatine and guanidionoacetate transport at blood-brain and blood-cerebrospinal fluid barriers. J Inherit Metab Dis 35(4):655–664

    Article  Google Scholar 

Download references

Acknowledgments

Supported by the Serbian Ministry of Science (Grant No. 175037).

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Correspondence to Sergej M. Ostojic.

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Ostojic, S.M. Advanced physiological roles of guanidinoacetic acid. Eur J Nutr 54, 1211–1215 (2015). https://doi.org/10.1007/s00394-015-1050-7

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