science nutrition blog

Leucine is a well-characterized branched-chain amino acid known for its muscle-building properties. It inhibits 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 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. This raises the question of whether leucine should be taken before or after workout sessions to maximize its benefits.2,3

When considering leucine before or after workout, it's important to weigh the benefits and drawbacks of each timing. Although leucine consumption during and after resistance exercise promotes muscle growth, the performance-enhancing effect from leucine pre workout is still under scrutiny. Some concerns about leucine's pre-workout consumption include:

• Decreased energy production within the muscle cell, potentially diminishing muscle performance during exercise.
• Potential desensitization of the potent muscle-building hormone insulin, resulting from additional leucine consumed before working out.
• Negative influence on the central nervous system (CNS) where leucine pre workout consumption might increase the rate of CNS fatigue, promoting overall sluggishness that decreases exercise performance.

Pre-workout Leucine and Muscle Energy Dynamics

In order to build muscle, you'd think that you need to be in an anabolic state at all times. However, maximal muscle growth requires a balance of muscle-building anabolism and energy-producing catabolism. Intense weightlifting requires glucose for energy, and catabolic processes like glycogenolysis, the breakdown of glycogen into glucose, play a crucial role. While leucine stimulates muscle growth, it also prevents the breakdown of glycogen into glucose, reducing available energy necessary for muscle contraction. This reduction in muscular contraction can decrease strength output, which likely compromises the ability to achieve muscle size and strength. Understanding these dynamics is crucial when deciding on leucine consumption timing.

Insulin Sensitivity and Leucine Consumption

Insulin is a potent muscle-building hormone, drastically increasing muscle protein synthesis and enhancing muscle growth.5 It achieves this by binding to the insulin receptor and activating the enzyme mTOR, which triggers muscle growth. However, insulin signaling is sensitive to overstimulation, where excessive signaling can trigger negative feedback mechanisms that reduce insulin-driven muscle growth. Leucine is a potent insulin activator, and studies have shown that increased amino acid consumption, especially leucine, can lead to insulin resistance. This insulin resistance would reduce insulin’s anabolic properties, decreasing muscle protein accumulation and growth.6,7,8,9,10,11

Leucine Influence on Central Nervous System Fatigue

The CNS, composed of the brain and spinal cord, serves as the main processing center for the nervous system. Neurons, or nerve cells, receive and transmit body-regulating information through electrical and chemical signaling. Serotonin, a neurotransmitter secreted within the neuronal synapse, induces sleep and drowsiness. Intense exercise increases serotonin release in the brain, contributing to exercise-induced fatigue. Fatigue is influenced by the serotonin to dopamine ratio, with dopamine improving mental arousal, motor control, and motivation. Leucine consumption inhibits serotonin production by preventing tryptophan transport into the brain, suggesting that leucine consumption before exercise could mitigate exercise-induced fatigue.
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. 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. 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 and enhances muscle growth, consuming leucine before your workout appears to have several drawbacks that negatively influence exercise performance. This suggests that leucine pre workout consumption is not optimal for 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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