Safety of dietary guanidinoacetic acid: a villain of a good guy?

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 me-tabolism. GAA (also known as glycocyamine or betacyamine) has been investigated as an ener-gy-boosting dietary supplement in humans for more than 70 years. GAA is suggested to effective-ly increase low levels of tissue creatine and improve clinical features of cardiometabolic and neurological diseases, with GAA often outcompetes traditional bioenergetics agents in maintain-ing ATP status druing 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 appears 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 anal-ysis