Is there such a thing as a “muscle full” effect ?

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Is there such a thing as a “muscle full” effect ?

Published on April 27, 2013 in Nutrition
03242010-protein-power-story

The muscle full hypothesis was proposed by Atherton et al. based on their research from 2010 with an oral dose of 48g of whey protein (1) and older research by their group using continuous infusion of amino acids (2) and suggests that muscle protein synthesis is attenuated after time, and eventually returns to baseline, despite continuous availability of amino acids in circulation. It seems to concur with other research demonstrating a cap on muscle protein synthesis at a dose of around 20g of a fast digesting high quality protein, orally ingested (3,4). The Atherton study was a milestone, but it has since led to rather poorly designed research (5) claiming that eating too frequently would impede muscular gains, which is simply not the case. We will discuss that study at length toward the end of the article. First I think it is perhaps important to discuss the biochemical basis for the muscle full effect and the Atherton study itself.
The biochemistry of nutrient driven muscle protein synthesis

You can find more detailed descriptions of the process of mTORC1 activation, its upstream regulators and its downstream effectors, in this article. We will only briefly re-iterate the relevant topics here. Suffice it to say that when sufficient insulin or growth factor signaling is present (insulin levels of 20-30 mU/L or higher, or exercise induced IGF-1 signaling) amino acids, with a key role for leucine, stimulate the activity of the mTOR complex 1 (mTORC1), the cells key anabolic signal integrator, which is considered both necessary and sufficient for muscular hypertrophy. That implies that overexpression of mTORC1 in an otherwise normal cell leads to anabolic events, and that blocking of mTORC1 leads to attenuation of growth. How amino acids achieve this is a complex and (despite making a lot of headway in recent years) still not completely understood process, but it begins with the entry of leucine and other amino acids into the cell. Leucine is taken up by the SLC7A5/SLC3A2 (which I have affectionately dubbed the “leucine pump” for easy reference) transmembrane protein, but the process requires the expulsion of glutamine from the cell. Indeed, research has demonstrated that in cells that cannot manufacture glutamine readily that glutamine deprivation blocks mTORC1 signaling because the cell cannot absorb leucine (6). When leucine concentrations in the extracellular space rise, glutamine is pumped out the cell and exchanged for leucine, which is taken up into the cell. Once in the cell, leucine stimulates glutaminolysis, the two-step process of turning glutamine into alpha-ketoglutarate (alphaKG). AlphaKG may actually play a direct role in mTORC1 activation (7), although that hasn’t been fully confirmed. In any case it forms the substrate for at least two other non-essential amino acids (proline and arginine) that will likely be required for muscle protein synthesis. At the same time the high nitrogenous medium, due to the presence of a lot of amino acids, inhibits Glutamine synthesis, the reverse process of making glutamine out of alphaKG (8). Through this three pronged approach, and the lowering of extracellular leucine, leucine uptake depletes the cell of glutamine which forms a negative feedback on its own absorption. Since the amino acids stimulate muscle protein synthesis, which incorporates them into proteins, their level inside the cell drops, which then takes the brakes off glutamine synthesis increasing intracellular glutamine, provided energy is still high enough. This is a key factor because extra alpha-KG is obtained as a sub step of the Krebs cycle, but only if the cycle is halted at that phase, and high levels of ATP are a requirement for that inhibition.

full article at ...... http://muscleandsportsscience.com/is-there-such-a-thing-as-muscle-full-effect/