Leucine is one of the nine essential amino acids (EAAs). EAAs must be consumed as part of the diet because the body cannot make them. Among the EAAs, leucine has received special attention for its role in muscle building, not only because it is the most abundant EAA in muscle protein, but also because of its nutraceutical role as a regulator of muscle protein synthesis. Are leucine muscle building benefits the “magic bullet,” or is leucine on an equal footing with the other EAAs? The truth is that it falls somewhere in between.
What Is Leucine?
Leucine is one of three branched-chain amino acids (BCAAs). The term branched-chain refers to the chemical structure of these EAAs. Isoleucine and valine are the other two BCAAs. Leucine is the best known of the BCAAs and it’s the most abundant EAA in muscle. In addition, leucine acts as a signal to activate various functions of the cells, including starting the process of protein synthesis.
How Muscle Protein Synthesis Works
Muscle protein is in a constant state of turnover. What this means is that muscle is being continuously broken down and resynthesized. Muscle building occurs over the course of the day when the rate of muscle protein synthesis exceeds the rate of breakdown. This can occur when there is a stimulated rate of muscle protein synthesis, a suppression of muscle protein breakdown, or a combination of the two.
Muscle protein synthesis involves the hooking together of a series of amino acids in a very specific sequence and amount. Under normal conditions, most of the amino acids that hook together to form new muscle protein are those released during protein breakdown. However, about 15-20% of the amino acids released during protein breakdown are not available to build new muscle protein. Some are irreversibly oxidized, while others are unleashed into the blood and taken up by other tissues and organs.
For this reason, an additional source of amino acids is needed so that the rate of protein synthesis can catch up with, or exceed, the rate of protein breakdown. Eleven of the amino acids in body protein are nonessential, which means the body produces them to meet the demands of any rate of protein synthesis. The essential amino acids such as leucine, on the other hand, must be consumed in the diet since they cannot be produced in the body. Consuming sufficient EAAs is mandatory for increasing the rate of muscle protein synthesis.
Leucine Muscle Building Nutraceutical
Muscle protein cannot be built on leucine alone. All of the EAAs must be available in proportion to their respective contributions to the composition of muscle protein for new protein to be produced.
Leucine comprises about 23% of the EAAs in muscle protein, and, as I’ve mentioned before, is the most abundant EAA in muscle protein. A high intake of leucine is therefore essential for muscle protein to be produced. As a result, the profile of EAAs consumed for the purpose of stimulating muscle protein synthesis, whether in a natural protein food source or an amino acid supplement, must contain a relatively high proportion of leucine.
There is no debate about the importance of leucine as an abundant constituent of muscle protein. Neither is there any controversy over the need for leucine to comprise at least 20-25% of consumed EAAs to maximally stimulate muscle protein synthesis. The question, rather, is whether leucine has such unique qualities that it should comprise a disproportionately greater amount compared to the other EAAs in a dietary amino acid supplement. Taken to the extreme, is a dietary supplement of leucine alone beneficial for building muscle?
Keep in mind…these questions are relevant only to amino acid supplements, as there is no natural protein food source made up of more than 23% leucine, and there is no natural protein food source that contains only leucine.
In order to answer these questions, we must first understand leucine’s role as a nutraceutical.
Leucine has been labeled a nutraceutical because it stimulates muscle protein synthesis beyond merely existing as a component of muscle protein.
Leucine can actually initiate the process of protein synthesis by activating a group of intracellular compounds collectively known as initiation factors. The key initiation factor activated by leucine is called mTOR. mTOR acts as a sensor in the cell. When leucine concentrations are low, mTOR receives the signal that there is not enough dietary protein present to build new skeletal muscle protein, and thus, mTOR is deactivated. When the leucine concentration in the cell increases after you consume leucine, mTOR is activated. Activation of mTOR can increase the amount of muscle protein that is produced, provided there are enough of the other EAAs in addition to leucine available to make complete proteins.
mTOR and Muscle Protein Synthesis
In normal, healthy adults mTOR can be activated and muscle protein synthesis stimulated with a balanced EAA supplement—there’s no need for extra leucine. However, in many clinical states, muscle protein synthesis is just not as responsive when EAAs are consumed, either as food or as supplements. This is called anabolic resistance and often occurs when battling cancer, severe trauma or illness, and regular old aging.
During anabolic resistance, an EAA supplement containing a disproportionately high leucine content (35-40% of EAAs) to activate mTOR may be needed to overcome the resistance. My team and I discovered this in 2006 when we studied the beneficial effects of an essential amino acid mixture with leucine on muscle protein metabolism in elderly and young individuals. You can read about the study, published in the American Journal of Physiology, Endocrinology, and Metabolism, here.
Leucine is not the only way to activate mTOR. Resistance exercise can further elevate mTOR, providing the potential for increased muscle protein synthesis. However, sufficient EAAs must be available for the further activation of mTOR to translate to increased protein synthesis. Put simply, you can’t make something out of nothing. A shortage of even just one EAA will limit the stimulation of muscle protein synthesis, even after a heavy resistance workout. While mTOR activation is not always linked with increased protein synthesis, it is an anabolic signal when all the necessary components are present.
Leucine Alone Is Not Enough
The best way to envision the role of leucine in protein synthesis is to consider the EAAs as a football team. Leucine is the quarterback, while the other positions are filled with other players, each with their specific roles. Just as a team of only quarterbacks would not have much success, neither does a nutritional supplement of only leucine.
There have been a number of studies examining the effectiveness of leucine as a nutritional supplement. As predicted from the analogy above, leucine alone has little effect on muscle building, according to a 2011 study published in the Journal of Nutrition. Compare these findings to a study we published in the journal Clinical Nutrition that showed how a formulation of EAAs with a high proportion of leucine (35-40%) helped overcome anabolic resistance and improve muscle mass, strength, and physical function in the elderly.
Leucine is important, but it can’t do the job alone!
Leucine and Muscle Protein Breakdown
The role of leucine in stimulating muscle protein synthesis has been studied extensively, but the building of muscle is determined not only by the rate of protein synthesis but also by the balance between the rates of synthesis and breakdown. In addition to stimulating muscle protein synthesis, leucine can reduce the rate of muscle protein breakdown.
Leucine consumption can stimulate the release of the hormone insulin, and the suppression of muscle protein breakdown by insulin is well known. As one of the BCAAs, leucine can also suppress protein breakdown directly. However, suppressing muscle protein breakdown only helps build new muscle if the rate of muscle protein synthesis is greater than the rate of breakdown, and this may not occur when just leucine or BCAAs are consumed. In fact, when muscle protein breakdown is reduced by leucine or the BCAAs alone, the rate of muscle protein synthesis is reduced correspondingly. This reflects the fact that the major source of EAAs for building new muscle protein is the EAAs that are released by protein breakdown…and if muscle protein breakdown is suppressed, the availability of EAAs for protein synthesis is also reduced.
As in the case of muscle protein synthesis, leucine can play a potentially important role in building muscle by inhibiting the rate of muscle protein breakdown, but to be anabolic (i.e., synthesis is greater than breakdown) all the EAAs must be consumed.
Leucine and Performance
Leucine is oxidized at an increased rate during endurance sports. This is evidenced in a study published in the Journal of Applied Physiology. Although not a large portion of total energy production is derived from leucine oxidation during exercise, the amount of leucine oxidized is significant in terms of the amount available for incorporation into protein. The increased oxidation of leucine during exercise can make its availability limiting for the production of new muscle protein. This is why it is necessary to consume EAAs in general, and leucine in particular, after exercise. Eating or supplementing with EAAs after exercise will not only prevent the loss in muscle protein that would occur otherwise (because of the oxidation of leucine) but also increase muscle protein synthesis and increase muscle strength and function.
Leucine and Type 2 Diabetes
We’ve known for 50 years that the blood concentration of leucine (and the other BCAAs) is elevated in individuals with type 2 diabetes. This knowledge has spurred theories that the BCAAs, and in particular leucine, are somehow involved in the development of insulin resistance and ultimately type 2 diabetes.
A recently-proposed theory gaining popularity is based on the premise that the activation of mTOR may be involved in causing insulin resistance. However, such theories are contradicted by studies that have shown that increasing leucine concentration with dietary supplements not only does not cause insulin resistance but also in some circumstances may improve control of the blood glucose concentration. In addition, supplementing with leucine, valine, and isoleucine can improve insulin sensitivity in a variety of insulin-resistant states according to other studies.
Leucine serves other functions as well:
- It promotes the growth and repair of bone tissue.
- It stimulates growth hormone production.
- It amplifies wound healing.
- It increases the number of mitochondria in muscle. (Mitochondria are the organelles in muscle where ATP is generated to fuel muscle contraction during exercise.)
Perhaps the most important takeaway is that leucine can’t do it solo. It needs the help of all the EAAs to be the magic bullet of muscle building the body needs.