Leucine is one of the nine essential amino acids (EAAs). EAAs are considered “essential” because the body can’t make them, and they must be consumed as part of the diet. Among the EAAs, leucine has received special attention for its role in muscle building, not only because it’s the most abundant EAA in muscle protein, but also because of its nutraceutical role as a regulator of muscle protein synthesis—the process of muscle building. But are these leucine muscle building benefits the “magic bullet,” or is leucine no more or less important than any of the other EAAs? The truth is that it falls somewhere in between.
What Is Leucine?
Leucine is one of the three branched-chain amino acids (BCAAs), the other two being isoleucine and valine. The term branched-chain refers to the chemical structure of these EAAs, which consists of branched side chains—the shorter chains of atoms attached to the main chain, or backbone, of the molecule.
Leucine is the best known of the BCAAs and is, as already mentioned, the most abundant EAA in muscle tissue. In addition, leucine acts as a signal to activate various cellular functions, including the process of protein synthesis.
How Muscle Protein Synthesis Works
Muscle protein is in a constant state of turnover, being continuously broken down and resynthesized. Muscle building takes place when the rate of muscle protein synthesis exceeds the rate of muscle protein breakdown. This can occur when there’s a stimulated rate of muscle protein synthesis, a suppression of muscle protein breakdown, or a combination of the two.
The process of muscle protein synthesis itself 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% to 20% of the amino acids released during protein breakdown are not available to build new muscle protein. Some are irreversibly oxidized, while others are released into the bloodstream 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 on its own to meet the demands of protein synthesis rates. By contrast, EAAs such as leucine must be consumed in the diet since they can’t be produced in the body. For this reason, consuming sufficient EAAs is mandatory for increasing the rate of muscle protein synthesis.
Leucine Muscle Building Supplements
Muscle protein can’t be built with leucine alone. In fact, for new muscle protein to be produced, all of the EAAs must be available in proportion to their respective contributions to the composition of that protein.
Since leucine is the most abundant EAA in muscle protein, comprising about 23% of the total EAAs, high leucine intake is essential for the production of muscle protein. Consequently, 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’s no debate about the importance of leucine as a building block of muscle protein. Neither is there any controversy regarding the need for leucine to make up at least 20% to 25% of consumed EAAs to maximally stimulate muscle protein synthesis.
The question is, rather, whether the effects of leucine are so unique that this one substance should constitute a disproportionately greater amount of a dietary amino acid supplement compared with the other EAAs. In other words, is leucine supplementation alone beneficial for building muscle?
Keep in mind that this question is relevant only to amino acid supplements, as there is no natural protein source made up of more than 23% leucine, and there is no natural protein source that contains only leucine. So, in order to answer this, we must first understand leucine’s role as a nutraceutical.
Leucine has been called a nutraceutical because it has the ability to stimulate muscle protein synthesis on its own and is more than just one of the components of muscle protein. In fact, leucine can actually initiate the process of protein synthesis by activating a group of intracellular compounds known collectively as initiation factors.
The key initiation factor activated by leucine is a protein called mammalian target of rapamycin (mTOR), which acts as a sensor within the cell. When leucine concentrations are low, mTOR receives the signal that there’s not enough dietary protein present to build new skeletal muscle protein and is deactivated. But when the concentration of leucine within the cell increases, mTOR is activated.
Activation of mTOR can increase the amount of muscle protein produced, provided there are enough of the other EAAs (in addition to leucine) available to make complete proteins.
Muscle Protein Synthesis and mTOR
In normal, healthy adults, mTOR can be activated and muscle protein synthesis stimulated with a balanced EAA supplement, so 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.
When this happens, it’s referred to as anabolic resistance—the reduced stimulation of muscle protein synthesis in response to protein intake. Anabolic resistance often occurs alongside conditions such as cancer or severe trauma or illness or during the regular process of aging.
During a state of anabolic resistance, an EAA supplement containing a disproportionately high amount of leucine (35% to 40%) may be needed to activate mTOR and overcome the resistance.
My team and I actually discovered this in 2006, when we studied the beneficial effects of an EAA 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.
But leucine is not the only way to activate mTOR. Resistance exercise can also further elevate mTOR, providing the potential for increased muscle protein synthesis. However, when engaged in resistance training, sufficient EAAs must be available for the further activation of mTOR to translate into increased protein synthesis.
Put simply, you can’t make something out of nothing. And that’s because a shortage of even one EAA will limit the stimulation of muscle protein synthesis, even after a heavy resistance workout. So while mTOR activation isn’t always linked to increased protein synthesis, it is an anabolic signal when all the necessary components are present.
Leucine Alone Isn’t Enough
The best way to envision the role of leucine in protein synthesis is to think of the EAAs as a football team, where leucine is the quarterback and the other positions are filled with other EAAs, each with their own specific role. Just as a team of only quarterbacks wouldn’t have much success in a game, a nutritional supplement wouldn’t have much success if it contained only leucine.
There have been a number of studies examining the effectiveness of leucine as a nutritional supplement. And as predicted by the analogy above, leucine alone has been shown to have little effect on muscle building—according to a 2011 study published in the Journal of Nutrition.
Compare these findings with a study we published in the journal Clinical Nutrition that showed how a formulation of EAAs with a high proportion of leucine (35% to 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.
With this in mind, it’s interesting to note that leucine also has the ability to reduce the rate of muscle protein breakdown and, thus, muscle loss. One reason for this is that leucine 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 consuming just leucine or BCAAs.
In fact, a reduction in muscle protein breakdown caused by leucine or BCAAs alone is accompanied by a corresponding reduction in the rate of muscle protein synthesis. This reflects the fact that the major source of EAAs for building new muscle protein is the EAAs that are released by protein breakdown. Therefore, 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 increase the anabolic response—meaning 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: Respiratory, Environmental and Exercise Physiology. Although a large portion of total energy production isn’t derived from leucine oxidation during exercise, the amount of leucine oxidized is significant in terms of the amount available for incorporation into protein.
In other words, the increased oxidation of leucine during exercise can make its availability—or lack thereof—limiting for the production of new muscle protein.
This is why it’s necessary to consume EAAs in general, and leucine in particular, post exercise. Consuming protein shakes, whey protein, or EAAs after exercise will not only prevent the loss in muscle protein that would occur otherwise (because of the oxidation of leucine) but will also increase muscle protein synthesis and increase muscle strength and function.
Leucine and Type 2 Diabetes
We’ve known for 50 years that blood concentrations of leucine (and the other BCAAs) are elevated in individuals with type 2 diabetes. This knowledge has spurred theories that the BCAAs, and leucine in particular, are somehow involved in the development of insulin resistance and, ultimately, type 2 diabetes.
A recently proposed theory that’s been gaining popularity is based on the premise that the activation of mTOR may be involved in causing insulin resistance. However, this theory is contradicted by studies that have shown that increasing leucine concentrations in dietary supplements not only doesn’t cause insulin resistance but may also, in some circumstances, actually improve blood sugar control.
Studies have also shown that supplementing with all the BCAAs can improve insulin sensitivity in a variety of insulin-resistant states.
Additional Benefits of Leucine
Leucine serves other functions as well. For example, it:
- Increases the number of muscle mitochondria—the organelles where adenosine triphosphate (ATP) is generated to fuel muscle contraction during exercise
- Promotes the growth and repair of bone tissue
- Stimulates growth hormone production
- Speeds wound healing
Perhaps the most important takeaway here is that leucine—like most things in life—can’t do what it does alone. It needs the help of all the EAAs to be the magic bullet of muscle building the body needs.