Muscle Sport Magazine

Leucine: The Dietary Anabolic Trigger

By Layne Norton, BS Biochemistry – Protein synthesis is a term you may see often when you read articles dealing with building muscle. But what is it? Quite simply, it is the synthesis of new skeletal muscle proteins. When this occurs on a large scale it is known as skeletal muscle hypertrophy (growth) and it is the process by which our muscles get bigger. Anyone who has ever read a muscle magazine or talked to a meathead long enough knows that consuming a diet high in protein is one of the major ways to maximize muscle gain. Protein is made up of amino acids, which have been shown to stimulate muscle protein synthesis. There are over 20 amino acids that occur in the dietary protein we eat, but do they all have the same impact on muscle growth? The answer is no. An amino acid called Leucine is the king of stimulating muscle protein synthesis.


Different forms of exercise affect muscle in different ways. Endurance exercise affects skeletal muscle protein turnover by decreasing the rate of skeletal muscle protein synthesis and increasing the rate of protein degradation (muscle breakdown) (1). Resistance exercise is unique in comparison to other forms of exercise as an acute bout of resistance exercise actually elevates skeletal muscle protein synthesis in addition to increasing the rate of skeletal muscle protein degradation. The overall effect in both cases is a negative net protein balance (2). In the short term therefore, exercise results in a catabolic condition. Long-term exercise however, causes increases in muscle mass. It has been shown that in order for protein balance to become positive post workout, dietary protein, specifically the amino acid leucine, must be consumed and protein balance will remain negative until it is consumed (3,4). Leucine is one of the three branched chain amino acids and is unique in its ability to stimulate skeletal muscle protein synthesis. In fact, leucine has a several fold greater impact on protein synthesis than any other amino acid!


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So how does leucine stimulate skeletal muscle protein synthesis? First we need to understand more about the pathway that leucine activates. It has been shown that leucine activates a major complex in the anabolic pathway called mTOR (5-7). Think of mTOR as the amino acid sensor of the cell. mTOR is sensitive to leucine concentrations. Decreasing leucine concentrations signal to mTOR that there is not enough dietary protein present to synthesize new skeletal muscle protein and it is deactivated. As leucine concentrations increase, it signals to mTOR that there is sufficient dietary protein to synthesize new skeletal muscle protein and mTOR is activated. Though researchers are not sure exactly how leucine activates mTOR, it has been shown that mTOR is sensitive to leucine concentrations and activation of mTOR is strongly associated with increased protein synthesis. mTOR increases protein synthesis through two different mechanisms (8). It increases the rate the skeletal muscle proteins are translated (process by which genetic information is converted into protein) and mTOR also increases the production of different complexes in the protein synthetic pathway, thereby increasing the body’s capacity to stimulate skeletal muscle protein. So not only does mTOR stimulation cause the body to create new muscle tissue faster, it also increases the amount that can be produced in a period of time. I could go into more detail but I would most likely lose most of my audience and the current level of discussion is fine for understanding the pathway. An analogy to help you understand this would be a contractor building a new skyscraper. The contracting company is mTOR, the skyscraper is the protein you are trying to synthesize, the machines (bulldozers, cranes, etc.) you use to make the building are the protein synthesis pathway components, and leucine is the cash needed to make the project work. When enough cash is available (increasing leucine concentrations), the contracting company cannot only start building the skyscraper (synthesizing muscle protein), they can also purchase more machines (increased synthetic components) to increase the capacity and speed at which they construct the skyscraper (the muscle protein being synthesized).


Now that the thick science is out of the way, what does this tell us? Is it beneficial to supplement with extra leucine, or do we get enough from a high protein diet? There is some evidence that supplemental leucine may be beneficial even if one supplies ample protein. Recently researchers conducted an experiment where subjects resistance trained for 45 minutes and then supplemented with carbohydrate alone, carbohydrate plus protein (approximately 30g) or carbohydrate plus protein and leucine. They found that the carbohydrate/protein/leucine supplement reduced muscle protein breakdown and increased muscle protein synthesis to a greater degree than the carbohydrate/protein supplement and to a much greater degree than the carbohydrate only supplement (9). A possible explanation for these results could be due to the rapid spike in blood leucine concentrations that a free form leucine supplement could achieve. Whole proteins take long periods of time to be digested and enter into circulation. Thus, blood concentrations of leucine increase slowly and plateau at a lower level when a whole protein source is consumed. Even with a fast digesting protein such as whey, it can take hours for the leucine in whey to be liberated from the protein and enter circulation; therefore leucine concentrations in the blood never spike to high levels. An isolated leucine supplement however, would be quickly absorbed into circulation, thus spiking blood leucine levels & drastically increasing intracellular leucine concentrations and activating the aforementioned anabolic pathways.




Leucine may also be of great assistance to those who are looking to maintain maximum muscle mass while dieting. We know that dieting is inherently catabolic and is the time period during which you are most likely to lose muscle. So how can leucine help one get shredded but still maintain maximum muscle mass? Recall from our earlier discussion that leucine is more anabolic than the other amino acids. It may therefore be possible to substitute say, 5g of leucine for 30-40g of dietary protein and still have the same or greater stimulatory effect on muscle protein synthesis. You still maintain high levels of protein synthesis…but you’ve managed to knock an extra 100 kcals off of your diet, helping you to get even more shredded.

In conclusion, it is clear that leucine increases protein synthesis by increasing the activity of mTOR. Leucine has a far greater stimulatory effect on protein synthesis than any other amino acid and it has been shown that protein synthesis increases similarly in response to a relatively small dose of leucine compared to a whole food meal. It has also been demonstrated that adding leucine to a protein rich meal further increases the rate of skeletal muscle protein synthesis. One might consider leucine the anabolic component of protein and one of the most promising supplements in years!




Layne Norton received his BS in Biochemistry from Eckerd College and is a PhD candidate in nutritional sciences at the University of Illinois.  His research focuses on optimal protein intake and muscle protein metabolism.  Layne is a natural pro bodybuilder with the IFPA and NGA and is also an accomplished powerlifter.  Layne is the owner of BioLayne LLC, a consulting business for contest prep coaching and general nutrition and training consultations.  He also recently released a DVD entitled “Layne Norton Unleashed” which focuses on his training and nutrition practices and theories.  Please visit for more information about Layne, his services, or purchasing his DVD.






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  1. Koopman R, Wagenmakers AJ, Manders RJ, Zorenc AH, Senden JM, Gorselink M, Keizer HA, van Loon LJ. (2005) Combined ingestion of protein and free leucine with carbohydrate increases post exercise muscle protein synthesis in vivo in male subjects. Am. J. Physiol. Endocrinol. Metab. 288(4): E645-653.


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