The Powerful Role mTOR Plays in Muscle Hypertrophy

November 6, 2022

by Cathe Friedrich

If you’re trying to optimize muscle growth, you should be familiar with the concept of mTOR. This acronym stands for Mammalian Target of Rapamycin, mTOR is a protein that regulates cell growth in response to nutritional cues like amino acids from food sources like meat and fish. If you’re trying to hypertrophy your muscles through resistance training, you should understand the importance of mTOR.

mTOR, found in all animal cells, is an essential regulator of protein synthesis. It acts as a critical factor in controlling the cell cycle and cell proliferation and survival. In terms of muscle hypertrophy, mTOR is a master regulator of cell growth and metabolism. It exists in two states, active and inactive. When activated, mTOR stimulates protein synthesis and growth by allowing nutrients to enter cells more easily.

When mTOR is “turned on,” studies show it increases protein synthesis by as much as two times. This boost in protein synthesis stimulates muscle hypertrophy. Along with its role in cellular growth and proliferation, mTOR plays a role in muscle tissue repair. When mTOR is active, muscle cells take up amino acids faster, so muscle tissue repair and muscle hypertrophy take place. Therefore, mTOR turns on anabolic pathways that build muscle.

Dietary Protein Activates mTOR

One factor that activates and deactivates mTOR is the amount of protein in your diet. Consuming a moderate to high protein diet turns on mTOR while calorie restriction and a low-protein diet reduce the activity of mTOR.

There’s no way around it. Of all the nutrients required for muscle building, protein is arguably the most essential. Protein is the building block of muscle. Your muscles are made up of protein, and amino acids are the building blocks of protein. And when you exercise, your body needs more amino acids to build and repair muscle tissue. A physically active person needs more protein than a sedentary person. Depending on the intensity, duration, and frequency of workouts, protein needs may double.

When you eat a high-protein meal or snack after working out, the amino acids from that protein snack are more available for muscle repair and rebuilding—helping you recover faster and help your muscle fiber repair. It also helps turn on mTOR to support muscle repair and growth. So, protein has a dual purpose. It supplies the building blocks for muscle gains and turns on anabolic pathways due to its effect on mTOR.

You Also Need Protein for Muscle Maintenance

When you do not consume enough protein regularly, especially if you’re calorie-restricting, your body will break down its own proteins to maintain muscle integrity which can lead to muscle loss. Therefore consuming sufficient amounts of high-quality proteins is important for maintaining lean mass during times of calorie restriction too. So, you need enough protein in your diet to turn on mTOR and supply your muscle cells with the amino acids they need to rebuild and repair.

Certain Amino Acids Activate mTOR More

Not all amino acids are equally adept at turning on mTOR. The branched-chain amino acids, leucine, isoleucine, and valine are the most powerful mTOR activators, and of these, leucine is the most powerful activator of mTOR. The amino acid leucine has been shown to activate mTOR to a greater degree than other amino acids.

Therefore, consuming foods high in leucine will boost mTOR the most. Some of the best sources of leucine include:

Beef
Chicken
Pork
Tofu
Tuna
Soy protein isolate
Whey protein isolate
Soybeans
Whole eggs
Beans
Seeds
Cheese
Cottage Cheese

As you can see, many are animal products, but you can also get leucine from soy-based foods, beans, and seeds. The Journal of the International Society of Sports Nutrition says that adults need up to 3 grams of leucine every 3 to 4 hours throughout the day to maximize muscle hypertrophy. This assumes you’re lifting weights to build muscle. Otherwise, this is higher than the recommended daily intake. The higher quantity of leucine helps turn on the mTOR pathway.

Are There Downsides to Activating mTOR?

Inhibition of mTORC1 increases lifespan in mice suggesting that this pathway may have an important role in regulating aging. For example, mTOR also turns on cell autophagy, the process by which cells eliminate damaged proteins and “junk” that builds up inside cells. Autophagy is a kind of “clean up’ and “detox” for cells. Without sufficient autophagy, undesirable metabolic products can build up inside a cell and contribute to health issues and aging.

For example, some animal studies link greater mTOR activation with a higher risk of some cancers. When the mTOR pathway is active, it encourages new blood vessel formation to tumors, thereby feeding their growth. So, people with cancer may theoretically be better to avoid eating large quantities of leucine-rich foods and avoid a high-protein diet. It’s unclear whether this is the case with humans and is an area that needs more research.

Ideally, you want mTR activity to be high in muscle tissue and, possibly, in the brain, but lower elsewhere. Unfortunately, there’s no easy way to control that. One solution might be to cycle a high protein, leucine-rich diet, so you get the benefits for muscle growth but also don’t interfere with cellular clean-up or autophagy.

Conclusion

mTOR turns on muscle protein synthesis, making it important for muscle repair and hypertrophy. Protein and resistance training help to activate it. So, mTOR plays a key role in muscle repair and growth, yet it still has some potential downsides for cellular health if it’s consistently high. As with everything, moderation may be key. If you’re not working out on a particular day, you don’t need to eat a high-protein diet. Adjust your protein intake based on your workouts.

References:

von Walden F, Liu C, Aurigemma N, Nader GA. mTOR signaling regulates myotube hypertrophy by modulating protein synthesis, rDNA transcription, and chromatin remodeling. Am J Physiol Cell Physiol. 2016 Oct 1;311(4):C663-C672. doi: 10.1152/ajpcell.00144.2016. Epub 2016 Aug 31. PMID: 27581648.
Atherton PJ, Smith K. Muscle protein synthesis in response to nutrition and exercise. J Physiol. 2012 Mar 1;590(5):1049-57. doi: 10.1113/jphysiol.2011.225003. Epub 2012 Jan 30. PMID: 22289911; PMCID: PMC3381813.
Stipanuk MH. Leucine and protein synthesis: mTOR and beyond. Nutr Rev. 2007 Mar;65(3):122-9. doi: 10.1111/j.1753-4887.2007.tb00289.x. PMID: 17425063.”Does Leucine Lessen Longevity? Unraveling Mysterious mTor.” 13 Oct. 2021, https://archive.nfpt.com/blog/does-leucine-lessen-longevity-unraveling-mysterious-mtor.
Jäger, R., Kerksick, C.M., Campbell, B.I. et al. International Society of Sports Nutrition Position Stand: protein and exercise. J Int Soc Sports Nutr 14, 20 (2017). https://doi.org/10.1186/s12970-017-0177-8.
Resistance training increases the rate of muscle-protein synthesis. Human Kinetics. Published 2018. Accessed October 29, 2022. https://us.humankinetics.com/blogs/excerpt/resistance-training-increases-the-rate-of-muscle-protein-synthesis