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Pre-workout Leucine Decreases Muscle Cell Energy


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  • Grand Poobah

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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.



1. Hawley JA, Gibala MJ and Bermon S. Innovations in athletic preparation: role of substrate availability to modify training adaptation and performance. J Sports Sci 2007; 25 Suppl 1, S115-124.
2. Pasiakos SM, McClung HL, et al. Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. Am J Clin Nutr 2011; 94, 809-818.
3. Saha AK, Xu XJ, et al. Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes 2010; 59, 2426-2434.
4. Blomstrand E, Eliasson J, et al. Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. J Nutr 2006; 136, 269S-273S.
5. Hillier TA, Fryburg DA, et al. Extreme hyperinsulinemia unmasks insulin's effect to stimulate protein synthesis in the human forearm. Am J Physiol 1998; 274, E1067-1074.
6. Guillet C, Prod'homme M, et al. Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. Faseb J 2004; 18, 1586-1587.
7. Biolo G, Declan Fleming RY and Wolfe RR. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest 1995; 95, 811-819.
8. Tremblay F, Lavigne C, et al. Role of dietary proteins and amino acids in the pathogenesis of insulin resistance. Annu Rev Nutr 2007; 27, 293-310.


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