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mTOR and Muscle Growth
by: Jay McCombs

Introduction

What does every pound you lift, every foul tasting concoction you drink and every horse pill you swallow have in common? Protein synthesis, or rephrased, getting ‘hyooge’. Every bodybuilder’s ultimate goal is to gain more muscle, and short of getting implants, that requires protein synthesis—the cogs and gears inside your muscles making themselves bigger.

So how’s it happen? More importantly, how can you make it happen at peak levels? The year of 2005 was a huge year for molecular research related to protein synthesis. The scientific community’s unraveling of the process advanced from roughly the Stone Age to around 1980 through the course of the year. There’s still a lot we don’t know, but with every passing month, more and more of the secrets fall beneath the heavy- handed fist of PhD’s relentlessly toiling away in labs all over the world. Ok, so maybe that’s a little dramatic, but the fact of the matter is, things have changed.

So unless you’re a science dork (like myself) how does this impact you, practically, day to day as a bodybuilder? Honestly, not a whole lot. It’s kind of like reading the last chapter of a book and then going back and reading the book through from the beginning – you know what’s going to happen, you’re just catching the details. Regardless of its practical application, it’s still good to understand things so you can be more adept in evaluating supplement makers’ claims. So, without further ado, let me tell you about protein synthesis.

Detailed Molecular Stuff

The gist of it is, you lift weights, you eat food, and you get bigger. The stuff between is a little more interesting (interesting being completely subjective). Central to the process is activating a set of enzymes and translation factors that eventually lead to increased protein synthesis. There are several pathways that end up in the same place, and they all probably overlap to some degree; but the way in which they are initiated is an important difference.

So now you should be asking, “How can I stimulate these pathways and thereby get even more muscular?” Well, the most established method involves insulin, the most anabolic of all the hormones – which involves eating carbs. Insulin activates a little ‘button’ named Akt which leads to protein synthesis via activating a protein named mTOR and a pathway independent of mTOR by the name of GSK-3 (don’t let the letters scare you, you can call them Bob and Tom if you want, just know what they do, which is stimulate protein synthesis). Everyone knows insulin rises proportionally to the rise in blood sugar. People have been drinking high carb beverages post workout for years, so this isn’t anything revolutionary.

The next way everyone already knows to stimulate protein synthesis is exercise. This is important because exercise activates protein synthesis via phosphorylating (a fancy way to say activating) certain portions of a protein named p70S6 kinase (p70S6k) in a pathway that is also apparently independent of mTOR. So p70S6k is just one more road that leads to increased protein synthesis. In rat models, exercise also activates mTOR directly and the Akt pathway mentioned above (remember, they also lead to increased protein synthesis). Once again, nothing revolutionary – everyone has been exercising as long as they’ve been bodybuilding.

The final piece of the puzzle is the involvement of amino acids. It has always made sense that in order to build muscle, you would need a steady supply of amino acids; however, the idea that amino acids themselves might be stimulating to protein synthesis hasn’t become tremendously popular until recently. Current research has focused on specific amino acids, called branch chain amino acids (BCAAs). BCAAs are essential amino acids (the body can’t produce them), and are uniquely metabolized (the liver lets the muscles have the first shot at using them). In the course of the last year, it became clear that BCAAs could stimulate mTOR – the tricky part would be, could they have enough of an effect on protein synthesis to affect the process above and beyond just by exercising? The answer, at least on a molecular level, is yes; however, on a ‘having bigger muscles’ level, probably not.

Remember what happens with exercise: p70S6k is activated and protein synthesis increases; however, intuitively, it doesn’t make sense that the body would increase protein synthesis without an ample source of amino acids. This is where BCAAs come in. What happens is exercise only partially activates p70S6k, rendering it active, but at about half its max activity. This mechanism that turns the second switch and makes it fully active, appears to come about by direct interaction with BCAAs. The end result is that protein synthesis occurs at a much higher rate post exercise.

Additionally, BCAAs directly stimulate the protein mTOR which, just to reiterate, leads to increased protein synthesis and increases the cellular machinery involved in protein synthesis. This means not only that you get the benefit of increased activity of p70S6k post workout; you also get the benefit of increased activation of eIF – two sets of signals that increase protein synthesis. So clearly, protein is an important part of the equation and something you definitely don’t want to miss post workout.

What to do? (the part you should have skipped to)

About now you might be ready to start eating a diet entirely of BCAAs. Well, that’s not such a good idea. There is a phenomenon called the muscle full effect , where continuously high levels of BCAAs seem to nullify their effects on protein synthesis. It’s like if someone poked you with a sharp stick all day, at some point, you would get used to the stick and it wouldn’t agitate you as much. This could be related to a lack of stimulation at other pathways such as from insulin or exercise. The theory is that the intake should mimic a normal meal schedule, and that a deficiency is much more detrimental than a mega dose is beneficial.

You might think you could benefit from extra BCAAs during your workout. Well, perhaps, but only in the sense that you could benefit from an increased supply of calories during your workout. While muscles are contracting, levels of calcium and calmodulin increase inside the cell. These guys directly inhibit the process of adding amino acids to a growing protein chain by inhibiting elongation factors. It’s like they take the battery out of the protein synthesis machinery.

So what about post workout? Aren’t there studies that show BCAAs can DOUBLE post workout protein synthesis? Yes, there are; however, you should first consider this. The bulk of post workout protein synthesis occurs from roughly 4-24 hours after the workout. BCAAs have their ‘doubling’ effect in the 1-3 hours window post exercise, when protein synthesis is very low to start with. So you double a really small number and you get a number not much bigger.

So, here’s the plan. Lift weights, eat a diet with adequate protein (15-25% of calories) and carbs, sleep, and then get big. That probably sounds a lot like what you’re already doing, but like I said, you already read the last chapter.

References

1. Norton LE, Layman DK. Leucine regulates translation initiation of protein synthesis in skeletal muscle after exercise. J Nutr. 2006 Feb;136(2):533S-7S. PMID: 16424142

2. Rennie MJ, Bohe J, Smith K, Wackerhage H, Greenhaff P. Branched-chain amino acids as fuels and anabolic signals in human muscle. J Nutr. 2006 Jan;136(1):264S-8S. PMID: 16365095

3. Blomstrand E, Eliasson J, Karlsson HK, Kohnke R. Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. J Nutr. 2006 Jan;136(1):269S-73S. PMID: 16365096

4. Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol. 2005 Oct;37(10):1974-84. PMID: 16087388

5. Rose AJ, Broholm C, Kiillerich K, Finn SG, Proud CG, Rider MH, Richter EA, Kiens B. Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men. J Physiol. 2005 Nov 15;569(Pt 1):223-8. Epub 2005 Oct 6. PMID: 16210351

6. Mechanical signal transduction in skeletal muscle growth and adaptation. J Appl Physiol. 2005 May;98(5):1900-8. PMID: 15829723

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