The following article is borrowed from Paul Cribb and should serve as a kickoff to the discussion. I invite all informed, intelligent opinions on the matter. Glycocyamine – Is it a "Creatine-Enhancer?" by Paul Cribb, B.H.Sci HMS AST Director of Research You many have read about a new compound called glycocyamine in the muscle magazines. Some supplement marketers are selling this product as a creatine enhancer. What is Glycocyamine? Glycocyamine is the intermediate step of creatine synthesis in the liver. It is often called guanidinoacetate. The first step in creatine synthesis occurs with the transfer of the amidino group of arginine to glycine to yield ornithine and guanidinoacetate via L-arginine:glycine amidinotransferase. Because of this, glycocyamine (guanidinoacetate) is often used in medical research as a marker for alterations in creatine metabolism and an indicator of conditions such as arginine-glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) deficiencies.[2,3] A reduction of guanidinoacetic acid in body fluids is desired for GAMT deficiency (an inborn error of creatine biosynthesis). These diseases are characterized by creatine depletion and accumulation of guanidinoacetate in the brain. Glycocyamine as a Supplement. There are no direct studies on glycocyamine as a performance enhancing supplement or a creatine enhancer. Even more important to athletes, there is no theoretical research that even remotely suggests glycocyamine might enhance muscle growth or the effectiveness of creatine supplementation. One study has examined the effects of supplementing with glycocyamine and creatine on physiological plasma homocysteine levels in rats. It’s from this research that marketers of glycocyamine supplements seem to be drawing their “science-based” sales pitch on glycocyamine. A number of studies have confirmed a relationship between an increased plasma concentration of homocysteine and the development of cardiovascular disease. Even a small increase in circulating homocysteine increases coronary artery disease risk by 60% for men and 80% for women. Supplementation with creatine is suspected to decrease homocysteine levels. Because the methylation of guanidinoacetate to creatine via consumes more S-adenosylmethionine than all other methylation reactions combined, the researchers behind the rat study hypothesized that guanidinoacetate and creatine supplementation may have opposite effects on homocysteine levels. Results showed they did. Creatine supplementation was shown to decrease liver homocysteine levels, thus substantiating the possibility of creatine as a supplement that may help people avoid cardiovascular disease. However, guanidinoacetate supplementation was shown to increase homocysteine levels. This is not a good thing if you want to reduce your risk of cardiovascular disease. Would glycocyamine be effective for bodybuilders? To provide a theoretical answer this question, we must look at glycocyamine’s role in metabolism and the role of creatine supplementation. Firstly, remember that glycocyamine is an intermediate involved in creatine synthesis within the liver. Without the presence of supplementation the body only synthesizes a small amount of creatine (less than 2-grams) per day. However, from the research it is clear that creatine supplementation reduces the body’s need to synthesize creatine, therefore the role of glycocyamine would be virtually eliminated. Secondly, compare this to regular doses that bodybuilders supplement (5-20-grams per day). Glycocyamine has no biochemical role what so ever in creatine supplementation and accumulation in muscle. Therefore you can start to understand why glycocyamine would be fairly useless supplement for bodybuilders. Finally, as muscle cells cannot manufacture creatine, any attempt to increase muscle glycocyamine content via supplementation in an effort to help increase creatine stores would obviously be useless. Also, creatine relies on a highly selective cell transporter, I can’t see how a non-insulin-stimulating compound like glycocyamine could enhance creatine uptake in muscle. The bottom line . . . Guanidinoacetate/glycocyamine’s role in the small amount of creatine synthesized by the body has nothing to do with creatine supplementation. Promoting glycocyamine as a supplement that enhances the effects of creatine supplementation is completely without practical or theoretical biological evidence.