Guanidinoacetic acid in human nutrition: Beyond creatine synthesis

Abstract

Guanidinoacetic acid (GAA) is a nutrient that has been used in human nutrition since the early 1950s. Recommended for its role in creatine biosynthesis, GAA demonstrated beneficial energy‐boosting effects in various clinical conditions. Dietary GAA has also been suggested to trigger several creatine‐independent mechanisms. Besides acting as a direct precursor of high‐energy phosphagen creatine, dietary GAA is suggested to reduce blood glucose concentration by acting as an insulinotropic food compound, spare amino acid arginine for other metabolic purposes (including protein synthesis), modulate taste, and perhaps alter methylation and fat deposition in various organs including the liver. GAA as a food component can have several important metabolic roles beyond creatine biosynthesis; future studies are highly warranted to address GAA overall role in human nutrition.

Guanidinoacetic acid ameliorates hepatic steatosis and inflammation and promotes white adipose tissue browning in middle-aged mice with high-fat-diet-induced obesity

“…Additionally, several studies have assessed the metabolic and clinical effects of GAA and found that supplemental GAA does not significantly affect biomarkers of liver damage. 27,43,44 Therefore, further investigations are needed to explain the relationship between GAA and hepatic steatosis. Apart from that, here, it was found that the HFD disrupted lipid and cholesterol metabolism in mice.…”

“…These sources include red meat, poultry, milk, and a few plant-based foods. 27 Therefore, dietary supplementation of GAA may influence the hepatic metabolic process via creatine. Previous studies have demonstrated that creatine exerts a negative regulatory effect on adipogenesis during early differentiation by inhibiting the phosphatidylinositol 3-kinase (PI3K) signaling pathway.…”

Dietary Methionine Enhances Portal Appearance of Guanidinoacetate and Synthesis of Creatine in Yucatan Miniature Piglets

“…Guanidinoacetic acid (GAA) is an amino acid derivative and endogenous substance in body tissues [ 1 , 2 ]. GAA acts as an immediate precursor for creatine, which plays a key role in energy metabolism, especially in muscle [ 3 ] and brain [ 4 ].…”

Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature

“…Guanidinoacetate N-methyltransferase (GAMT) is an enzyme that functions to create creatine (Cr), a substance used in the body to transfer and contain energy in the form of phosphate [1] . The process of creatine generation begins with the amino acids glycine and L-arginine.…”

“…The process of creatine generation begins with the amino acids glycine and L-arginine. These substrates are trans-aminated to create guanidinoacetic acid (GAA) using the enzyme L-arginine:glycine amidinotransferase (AGAT), after which GAA is transported to the liver or other tissues where GAMT uses S-adenosyl-L-methionine to add a methyl group to form creatine [ 1 , 2 ]. Creatine Kinase (CK) is then used to create phosphocreatine (PCr) which functions as an excellent energy storage source for the formation of adenosine triphosphate (ATP), both of which are used in muscle activity and exercise [3] , [4] , [5] , [6] .…”