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08.12.2016

The unsuspected anabolic effect of AKG (in massively high doses)

Athletes who take supplements will be familiar with alpha-ketoglutarate, aka AKG [structural formula shown here]. Supplements manufacturers often attach it to amino acids in the hope that this will boost their functioning. The same AKG, according to a study published by Chinese researchers in Scientific Reports, has an anabolic effect. As long as you're not scared of hefty doses...

Study
The researchers gave young mice drinking water that contained 0, 1 or 2 percent AKG for nine weeks. The human equivalent of these doses, for an adult weighing 80 kg, would be about 12 and 24 g per day.

Results
The lowest dose had little effect on AKG concentrations in the blood of the lab animals, but the highest dose did have an effect: it increased the mice's bodyweight.

AKG had no effect on the weight of the liver. So it doesn't look like AKG in these doses causes liver damage. At the same time, the supplementation resulted in an increase in muscle mass and a reduction in fat mass.

The figures above show that the increase in muscle mass was a consequence of hypertrophy. AKG resulted in a big increase in the dimensions of the muscle fibres. The figure below shows that AKG activates the classic anabolic signal molecules like mTOR and Akt in the muscle cells.

How AKG activates the anabolic signal route is shown in the figure above. In-vitro studies show that the effects of AKG on the anabolic signal molecules partially disappeared when the researchers deactivated the gene for the GPR91 receptor [GPR91 siRNA].

So AKG works through this receptor. The receptor family that GPR91 belongs to 'sees' metabolites that are released during the citric acid cycle - like AKG. The GPR99 receptor, which bears a striking resemblance to GPR91, 'sees'... AKG. [Nature. 2004 May 13;429(6988):188-93.] So GPR91 would seem to do the same.

Conclusion
"AKG promotes skeletal muscle protein synthesis and inhibits the degradation mediated by the Akt/mTOR pathway", the researchers wrote. "These data suggest the promising application of AKG in maintaining protein turnover balance in skeletal muscle and treating muscle atrophy."

Two slight grumbles in our concluding remarks. Uno: muscle cells of mice contain many GPR91-receptors, but whether that's also the case for human muscle cells? We have no idea. Duo: In the doses we're talking about here, AKG probably raises blood pressure, and has other side effects too. So make sure you read up properly before starting to experiment with high doses of AKG. A suggestion: [Cell Commun Signal. 2016 Jan 12;14:3.]

Source:
Sci Rep. 2016 May 26;6:26802.

More:
Alpha-keto acids (like AKG) give athletes more energy 02.10.2012

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