Guanidinoacetic acid more effective than creatine

Supplementation with guanidinoacetic acid [first formula on the right] boosts the creatine concentration in cells even more than supplementation with creatine [second formula] itself does, a discovery made by Serbian researchers at the University of Novi Sad. But although supplements containing guanidinoacetic acid can be bought off the shelf, the Serbs don’t think athletes should drop creatine for guanidinoacetic acid.

The researchers got five students to take 3.4 g creatine every day for four weeks, and on another occasion to take 3 g guanidinoacetic acid for the same amount of time. There was a wash-out period of four weeks between the trials. The researchers did MRI scans to determine the concentration of creatine in the participants’ brain and muscle cells, before and after the supplementation periods.

After supplementation with guanidinoacetic acid the researchers found about three times more creatine in the participants’ cells than after the creatine supplementation.

The researchers are enthusiastic about their discovery: “Here we demonstrated for the first time that dietary guanidinoacetic acid is better than creatine to improve brain and muscle creatine availability in humans,” they wrote. “Four-week supplementation with guanidinoacetic acid was superior in tissues evaluated, with 3.3-fold higher tissue creatine levels as compared with creatine itself.”

The researchers suspect that cells are absorb guanidinoacetic acid better than creatine. “While creatine is mainly transported via specific transporter (SLC6A8; also used for guanidinoacetic acid transport), dietary guanidinoacetic acid could be imported through additional delivery channels (SLC6A6, GAT2, passive diffusion),” thinking out loud. After guanidinoacetic acid has been absorbed by the cells, the enzyme guanidinoacetate N-methyltransferase [usually shortened to GAMT] can convert it into creatine.

Supplementation with guanidinoacetic acid also led to a greater increase in the amino acid homocysteine in the blood than creatine supplementation did. That’s to be expected. For guanidinoacetic acid to be converted into creatine methyl groups are needed. These detach the GAMT enzyme from S-adenosylmethionine, as a result of which the latter becomes homocysteine.

Second thoughts
“Our study provided preliminary evidence that 4 weeks of supplementation with 3.0 g/day of guanidinoacetic acid is superior to creatine in facilitating cellular bioenergetics, as evaluated by the skeletal muscle and brain creatine levels,” the researchers summarised.

But that doesn’t mean that the researchers think athletes should start taking guanidinoacetic acid instead of their creatine supplements. The rise in homocysteine levels is too high for that in their view. It came perilously close to the 15 micromoles per litre that doctors regard as just still acceptable.

“Guanidinoacetic acid loading should be considered as a controversial dietary routine since elevated homocysteine has been implicated as a risk factor for cardiovascular disease, renal dysfunction, and orosteoporotic fractures. Therefore, long-term safety studies evaluating different biomarkers of cardiometabolic health during guanidinoacetic acid loading are warranted before recommending it as a novel dietary supplement.”

Some supplements companies have chosen to disregard these studies – a wide range of products containing guanidinoacetic acid are already available online and in sports shops.

Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men


In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues. Source: