One of the more well-characterized muscle-building supplements is the branched-chain amino acid leucine, which has clearly been shown to inhibit muscle protein breakdown while simultaneously increasing the rate of muscle protein synthesis, ultimately promoting substantial muscle growth.1 Leucine consumption promotes muscle protein accumulation and muscle growth by activating the extremely important nutrient-sensing molecule mTOR, which directly turns off muscle protein degradation while activating muscle protein synthesis. Several studies have shown mTOR activation by leucine intake specifically during and after resistance exercise.2,3

Although it has been well established that leucine consumption during and after resistance exercise promotes muscle growth, the verdict is still out regarding the performance-enhancing effect from leucine consumption before training. Some of the uncertainty about leucine's pre-workout consumption stems from the fact that leucine consumption decreases energy production within the muscle cell, potentially diminishing muscle performance during exercise. Another concern about pre-workout leucine consumption involves the likely desensitization of the potent muscle-building hormone insulin, resulting from additional leucine consumed before working out. The final concern involves the negative influence that leucine consumption may have on the central nervous system (CNS) where pre-workout leucine consumption might increase the rate of CNS fatigue, promoting overall sluggishness that decreases exercise performance.

Pre-workout Leucine Decreases Muscle Cell Energy

In order to build muscle, you'd think that you need to be in an anabolic state at all times— which might also make you believe that the ubiquitous consumption of muscle-building compounds, like leucine, should enhance muscle growth. Yet the reality is being constantly in an anabolic state is not optimal for muscle size and strength. This is mainly because maximal muscle growth requires the perfect blend of muscle-building anabolism combined with energy-producing catabolism. In other words, if you want to build muscle, something has to supply them with energy to function. Well, that's where catabolic processes like glycogenolysis, the breakdown of glycogen into glucose for energy, play a huge role mainly because intense weightlifting requires glucose for energy. So, although leucine potently stimulates muscle growth, it also prevents the breakdown of glycogen into glucose4, reducing available energy that is necessary for muscle contraction. Of course, reduced muscular contraction decreases strength output— which likely compromises the ability to get huge.

Too Much Leucine Diminishes Muscle Growth

Insulin is the most potent muscle-building hormone produced in the human body, possessing the ability to drastically increase muscle protein synthesis and enhance muscle growth.5 Insulin achieves this muscle-building effect by binding to the insulin receptor and setting off a cascade of signaling events that eventually activates the enzyme mTOR, triggering muscle growth.6,7 However, insulin signaling is very sensitive to overstimulation— where too much insulin signaling can rapidly trigger negative feedback mechanisms that turn down insulin-driven muscle growth. In addition to the well-known influence that glucose has on insulin secretion and activity, one of the more potent insulin activators is leucine. Interestingly, several studies have shown that insulin resistance can occur with increased amino acid consumption, especially the branched-chain amino acid leucine.8,9 The exact mechanism by which leucine modulates insulin sensitivity is currently unclear. Although the decreased insulin sensitivity may be associated with greater insulin secretion induced by leucine10,11, potentially inducing insulin resistance. Of course, insulin resistance from too much leucine consumption would reduce all of insulin’s anabolic properties, meaning a decrease in muscle protein accumulation and therefore muscle growth.

Leucine Consumption Before Your Workout Promotes Sluggishness and Fatigue

The CNS, composed of the brain and spinal cord, serves as the main “processing center” for the entire nervous system that controls all the workings of your body. Neurons, or nerve cells, are the core components of the CNS that function to receive and confer all of this body-regulating information by electrical and chemical signaling. Neuronal electrical signaling is ultimately converted at the nerve ending or synapse into chemical signaling utilizing neurotransmitters that diffuse across the synapse to adjacent neurons, triggering further electrical signaling down those neurons, which eventually control numerous processes in the body.
Serotonin is a neurotransmitter secreted within the neuronal synapse that induces sleep and drowsiness. Intense exercise has been shown to increase the release of serotonin in the brain, putatively contributing to exercise-induced fatigue. Initially, it was thought that the increase in serotonin alone triggered fatigue. However, it turns out that greater fatigue from exercise is influenced more specifically by an increase in the ratio of serotonin to another neurotransmitter known as dopamine.12
The neurotransmitter dopamine has well-defined roles including increased mental arousal, improved motor control and greater levels of motivation, which all tend to improve exercise performance. Therefore, a lower serotonin to dopamine ratio, by either decreasing performance-inhibiting serotonin or increasing performance-enhancing dopamine, should improve exercise capacity. Interestingly, leucine consumption has been shown to inhibit serotonin production by preventing transport of the serotonin-precursor tryptophan into the brain.13 Because tryptophan is a building block for serotonin, lower tryptophan in the brain reduces serotonin production— suggesting that leucine consumption before exercise could actually mitigate exercise-induced fatigue.
On the other hand, a recent study by Choi et al.14 showed that leucine also competitively inhibits dopamine production by preventing the uptake of the dopamine-precursor tyrosine into the brain. Since greater brain dopamine function improves physical performance, the finding that leucine reduces dopamine levels in the brain highlights why leucine consumption, especially before exercise when motivation and energy levels are paramount, may have a detrimental influence on physical performance despite leucine’s ability to also reduce serotonin levels.
In conclusion, leucine’s capacity to trigger anabolic processes, such as muscle growth and glycogen production, makes the timing of leucine consumption very important. While leucine consumption during and after lifting weights effectively prevents muscle breakdown while enhancing muscle growth, consuming leucine before your workout appears to have several drawbacks that negatively influence exercise performance— suggesting that pre-workout leucine consumption is not best for optimal muscular performance.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

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