Time-Release Leucine Science Page

Active TR TM



What is Leucine?


Leucine is a hydrophobic amino acid.  It is categorized as one of the branched chain amino acids due to its side chain structure (the other amino acids with branched chain structures are isoleucine and valine).  It is also an essential amino acid (EAA) because the human body cannot synthesize it from other amino acids.  Leucine must therefore be attained from the diet and ingested from specific foods.  



What does it do?


Leucine is the most important amino acid involved in any training-dependent change or adaptation in muscular tissue. Simply put, without Leucine, you would not be able to see any significant improvements in muscle strength, power, size, or repair and recovery.  Leucine is a very important regulator of skeletal muscle protein synthesis, and thus muscle adaptation and growth.  In order for maximal stimulation of the production of new skeletal muscle proteins, blood levels of amino acids (specifically Leucine) must reach a threshold level.  This can be done by eating a specific amount of protein rich foods (based on their Leucine content) or by taking a Leucine supplement.        



How does it regulate Muscle Protein Synthesis?


Leucine regulates muscle protein synthesis by activating the main pathway of muscle protein synthesis, mTOR, which stands for mammalian target of rapamycin.  Leucine does this by increasing the calcium concentration within muscles similarly to the action of muscle contraction. This increase in intramuscular calcium has the effect of activating mTOR, which then starts the cascade of processes that results in an increase in the synthesis of new muscle protein within muscle cells. It is this increase in new muscle protein that allows for muscle repair, muscle growth, and potential for the greatest muscular adaptations to training.  When mTOR, the “gatekeeper” for muscle protein synthesis, senses that levels of both energy and specific nutrients are adequate, it triggers the process and synthesis of new skeletal muscle proteins within activated muscle cells.  If energy levels (availability of ATP) or amino acid (specifically leucine) levels are not enough to reach a specific threshold, then mTOR and muscle protein synthesis is not activated and therefore the production of new muscle proteins does not occur.  The general consensus among researchers and scientists in this field is that if ATP levels are too low, then an increase in muscle protein synthesis or other skeletal muscle adaptation is not a primary priority.  At this point, an increase in muscle protein synthesis would be a luxury, and not a necessity.  In short, muscle repair, significant adaptation, or growth can only occur if the body recognizes there is enough energy to fuel the process without putting any other bodily system in energy debt.  If an increase in muscle size is the adaptive response to training, then there must be ample stored energy to maintain the life of the new tissue.  Similarly, if the levels of Leucine and other amino acids are not high enough to reach the mTOR threshold, then the body assumes there exists an inadequate amount of dietary protein, and thus an inadequate amino acid pool to be the building blocks of the new skeletal muscle protein. 


In order to maximize training and recovery, the goal is to stimulate mTOR and muscle protein synthesis as often as possible. This can be an issue since Leucine concentrations spike very quickly after supplementation, and then drop very quickly. 



How does exercise fit in?


In general, the type of exercise you participate in will play a role in determining the level and extent of mTOR activation and muscle protein synthesis.  Aerobic exercise affects skeletal muscle protein synthesis differently when compared to anaerobic exercise.   Anaerobic exercise, such as weight lifting or other forms of resistance training, leads to an increase in mTOR and muscle protein synthesis while simultaneously increasing the catabolic pathways that break down muscle protein.  Aerobic exercise, such as endurance running or cycling, leads to a decrease in mTOR and muscle protein synthesis while increasing catabolic processes, which are processes that break down skeletal muscle protein.  In short, endurance exercise not only leads to a potential reduction in skeletal muscle, but also in a reduction in the body’s ability to synthesize new skeletal muscle proteins.  A commonly used example of this is to visually compare the physique of a world-class marathoner and a world-class 100-meter sprinter.  It is quite obvious that the nature of endurance exercise results in a very dramatic reduction in available ATP (blocking mTOR), as well as inadequate levels of the specific amino acids necessary to stimulate muscle repair, adaptation, and growth.  Due to this, many researchers and scientists believe Leucine is not only important for anaerobic (power, strength, and speed dependent sports), but is also extremely important for individuals participating and competing in endurance-type exercise.  In the end, adaptation, muscle repair, and muscle growth cannot occur until protein balance swings back into the positive side of the equation.  The end result of both types of exercise is a net negative protein balance, which is where dietary Leucine comes into play. 



How much do you need?


Ingesting Leucine results in an increase in the positive side of the protein balance equation, and thus is necessary to stimulate mTOR.  How much Leucine is enough to “tip the scale” and stimulate muscle protein synthesis?  Research shows that ingesting 2.0-2.5 grams of Leucine is enough to stimulate muscle protein synthesis, though taking 3+ grams may stimulate muscle protein synthesis to a greater extent. 



Where do you get it?


Achieving the minimum necessary level in the bloodstream can be done by ingesting a leucine-only supplement, a branched chain amino acid supplement, a protein supplement, or by eating protein dense foods.  In order to ensure you are getting enough of the specific supplement or food, you must figure out the Leucine content.  Whey protein, for example, has a Leucine content of about 10-12%.  This means that if you ingest 25-30 grams of high quality whey protein, you will get about 3 grams of Leucine.  Beef, eggs, poulty, and fish are also good sources of essential amino acids, and thus Leucine; however, the amount of each differs to reach the 2.5-3.0 grams of Leucine threshold necessary for mTOR activation and muscle protein synthesis.



What is Time-Release Leucine?


            Since blood levels of amino acids, specifically Leucine, spike and then drop back to baseline in a 4-6 hour window, athletes are somewhat limited to the number of times within a day they can maximally stimulate recovery and repair.  Recently, however, Time-Release Leucine has been made available to the market.  This specific type of Leucine does not become active in the blood stream until approximately 2 hours after ingestion.  It also maintains the elevated level of Leucine in the blood for much longer than Leucine by itself.  Due to this specific characteristic, Time-Release Leucine has potential application and benefit for enhancing and expediting night-time recovery, as well as providing significant benefit for individuals who train and compete in endurance and aerobic activities, train in a fasted state, or for those who go long periods of time between meals.  By providing a Leucine spike in the blood right around the time plasma concentrations of Leucine drop significantly (approximately 2 hours after ingestion), athletes can decrease the amount of time their body is in a catabolic state (breakdown), and maximize the amount of time their body is repairing from training-induced muscle damage.  In this way, Time-Release Leucine is setting you up for your next training session and getting you closer and closer to your long-term performance goals.


Research shows that even a large meal prior to bed cannot fully maintain glycogen stores throughout the sleeping period, and thus everyone has some degree to amino acid breakdown from skeletal muscle upon waking and before nutrients are ingested.  Due to this, Time-Release Leucine can have a dramatic impact on shortening the time the body is in a catabolic state during sleep and thus greatly enhance neuromuscular adaptations to training as well as maximizing recovery from training and injury.







Leucine and TR Leucine Sources:



Norton LE, Layman DK. Leucine regulates translation initiation of protein synthesis in skeletal muscle after exercise. J Nutr. 2006;136(2):533S-537S.




Greiwe JS, Kwon G, Mcdaniel ML, Semenkovich CF. Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle. Am J Physiol Endocrinol Metab. 2001;281(3):E466-71.



Rieu I, Balage M, Sornet C, et al. Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol (Lond). 2006;575(Pt 1):305-15.



Du M, Shen QW, Zhu MJ, Ford SP. Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase. J Anim Sci. 2007;85(4):919-27.



Nair KS, Schwartz RG, Welle S. Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. Am J Physiol. 1992;263(5 Pt 1):E928-34.



Tipton KD, Elliott TA, Ferrando AA, Aarsland AA, Wolfe RR. Stimulation of muscle anabolism by resistance exercise and ingestion of leucine plus protein. Appl Physiol Nutr Metab. 2009;34(2):151-61.



Anthony JC, Anthony TG, Layman DK. Leucine supplementation enhances skeletal muscle recovery in rats following exercise. J Nutr. 1999;129(6):1102-6.



Katsanos CS, Kobayashi H, Sheffield-moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006;291(2):E381-7.



Ispoglou T, King RF, Polman RC, Zanker C. Daily L-leucine supplementation in novice trainees during a 12-week weight training program. Int J Sports Physiol Perform. 2011;6(1):38-50.