Abstract
Guanidinoacetic acid (GAA) is a natural amino acid derivative that is well-recognized for its central role in the biosynthesis of creatine, an essential compound involved in cellular energy metabolism. GAA (also known as glycocyamine or betacyamine) has been investigated as an energy-boosting dietary supplement in humans for more than 70 years. GAA is suggested to effectively increase low levels of tissue creatine and improve clinical features of cardiometabolic and neurological diseases, with GAA often outcompeting traditional bioenergetics agents in maintaining ATP status during stress. This perhaps happens due to a favorable delivery of GAA through specific membrane transporters (such as SLC6A6 and SLC6A13), previously dismissed as un-targetable carriers by other therapeutics, including creatine. The promising effects of dietary GAA might be countered by side-effects and possible toxicity. Animal studies reported neurotoxic and pro-oxidant effects of GAA accumulation, with exogenous GAA also appearing to increase methylation demand and circulating homocysteine, implying a possible metabolic burden of GAA intervention. This mini-review summarizes GAA toxicity evidence in human nutrition and outlines functional GAA safety through benefit-risk assessment and multi-criteria decision analysis.
Highlights
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Guanidinoacetic acid (GAA, known as glycocyamine, betacyamine or Namidinoglycine) belongs to the class of organic compounds known as alpha amino acids and derivatives
GAA is combined with S-adenosyl-L-methionine, a reaction catalyzed by guanidinoacetate N-methyltransferase (GAMT), to produce creatine and Sadenosyl-L-homocysteine
Summary
The first documented report of GAA utilization as an experimental nutritional intervention in humans arguaby dates back approximately 70 years ago. We found that serum concentrations of folic acid, vitamin B6, B12, and holo-transcobalamin (carrier protein which binds the active form of vitamin B12) were not affected by the placebo or GAA intervention, implying that GAA dosages administered in this trial are probably insufficient to significantly impact circulating biomarkers of methyl donor micronutrients. Another trial evaluated the effects of supplemental GAA on DNA methylation [41], a critical epigenetic process for genome regulation. Might be caused by dietary GAA affects other biological methylation pathways, including amino acid and protein methylations or polysaccharide methylation
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