We have talked a lot about the benefits of BCAAs.  I mentioned that Leucine is the most important of the BCAAs.  When it comes to signaling muscle building (protein synthesis), Leucine is king.  It has been shown to increase protein synthesis by up to 145%. In terms of direct effect it may be the single most important amino acid for hypertrophy.

Leucine is one of the branched chain amino acids (BCAA).  Exercise leads to the oxidation of BCAA’s as a primary source of fuel as well as signaling pathways for recovery.  BCAA’s are unique in that they can lead to increased insulin and cortisol depending on the situation. Leucine is the most important of the 3 BCAAs for signaling muscle growth.  Leucine leads to the signaling of a pathway called mTOR, which is the same signaling pathway that is activated by growth factors like IGF-I. In fact Leucine acts in a more direct way on the mTOR pathway than growth factors because it does not require as many intermediate steps.

Pathway of Protein Synthesis Activation

The mTOR pathway activity increases in response to muscle activity during hypertrophy and decreases in activity during atrophy.  IGF-1 activates AKT, GSK-3beta and mTOR to promote hypertrophy. The mTOR pathway leads to regulation of protein translation, with increased translation acting as a key regulatory point in skeletal muscle hypertrophy.

The activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, are directly involved in regulating skeletal muscle fiber size.  So if your goal is to grow muscle, you have to activate this pathway, and often.

Keep It Balanced

Leucine works synergistically with the other BCAAs enhancing its effects, but it needs to be within a certain ratio. BCAAs with leucine in a ratio of about 4 to 1 with valine and isoleucine have been shown to be most effective for muscle building. When leucine intake is too far out of balance with the other BCAAs, it can lead to an imbalance in the blood amino acid levels, reducing the anabolic signaling of leucine.

Benefits & Uses

The benefits of higher leucine BCAA formulas include less muscle damage, less pain from training, increased performance, decreased fatigue, and greater muscle growth. Leucine enriched BCAAs are especially valuable for older trainees (35+) who have a harder time activating mTOR to build muscle.  

When restricting calories, you may also use it with meals to maximize the benefits of food protein.  Leucine is most effective when taken with other BCAA’s, essential amino acids or protein, or with elevated insulin levels.  In each of these cases there is an exponential benefit to using higher levels of leucine.

Timing

Post-training the mTOR pathway should be well unregulated and adding leucine can help facilitate a little better recovery. The following meals in the upcoming hours post training you can add as little as 2 grams of leucine to help promote the use of amino acids already in your system to be used for growth and repair by reactivating the mTOR pathway.  The mTOR pathway is also partly dependent on insulin for maximal stimulus, so it is less effective in a low carb or low calorie state.

That isn’t to say that leucine is not beneficial in absence of carbohydrates, but it work synergistically with insulin for maximum anabolic effects.  Leucine itself will still increase your uptake and use of plasma amino acids for protein synthesis, just not to the same magnitude, and it will have less of a glycogen rebuilding effect.  

Leucine can be used effectively at almost any time.  It does however need to work in somewhat of a pulse. The mTOR pathway can only be stimulated every 3-4 hours.  This is one of the reasons that eating higher protein meals every 3-4 hours tends to be more beneficial for hypertrophy.

Protein synthesis comes in pulses.  When looking at the comparison of increased protein synthesis by amino acid rich meals from 4oz of meat over 3 meals vs 1 meal of 12 oz, the pulsing of the amino acids every 3 hours resulted in greater overall protein synthesis.  Protein synthesis declines between 90 to 120 minutes after eating a high-protein meal, even though the blood still contains elevated levels of amino acids. At this point the pathway had become saturated and actually shuts down, and there is not activating it any further.   After 3-4 hours however, ingesting leucine (or leucine and carbs) is all you need to do to re-stimulate protein synthesis and take advantage of the leftover amino acids still circulating in your system. Insulin also stimulates the mTOR pathway, but if your goal is to stay lean, leucine is the better choice to make more use out of your protein.

A key time of course to take leucine is around training time.  For maximal hypertrophy benefits you want the mTOR pathway to be stimulated immediately after training.  Peri workout, post workout, leucine supplementation are probably the most important. To be safe the meals after training could also contain some leucine.  The effects of training can throw off the time table of signaling, so having all your bases covered gives you the best chance to maximize protein synthesis. Most BCAA supplements will have a higher amount of leucine than the other BCAAs.  But when using BCAA’s pre and intra workout, you must remember that you oxidize BCAA’s for training fuel as well. So not all the leucine ingested will be used for anabolic signaling. This function of BCAA’s is part of their muscle sparing benefits, that helps decrease the damage to your muscles during training.

Combining with EAAs

As I mentioned earlier you can take leucine two hours after training to extend muscle protein synthesis, but leucine is just the signaling agent for the protein synthesis. You still need building blocks for protein synthesis to occur. This is where Essential Amino Acids (EAAs) come in.   We know leucine works better with the other BCAAs which are essential amino acids, but it actually works better when you have more of the EAAs.

You should take leucine in a stack with all of the EAAs  immediately after training, and then again two hours later. You can take high leucine BCAA’s pre, and intra training, or add them to food meals where the food is providing the other EAAs.  If you’re serious about building muscle, research shows it’s beneficial to take leucine two hours after each meal as well to further support protein synthesis. This is especially important for hard gainer types or people that tend to run very high metabolisms.

EAAs provide the building blocks for protein synthesis but they also activate the mTORC1 signaling pathway that is also essential for muscle building.  The most effective way to use leucine for increased workout recovery and protein synthesis is to have your large protein post workout, followed by an EAAs mix that contains at least 40% leucine according to one study.  Other research suggest that as long as you have at least 3-4g of free l-leucine with the amino acids, you will get the benefit of the leucine.

I tend to suggest the latter for simplicity sake, and it seems to be well supported.