The Muscle Building Magic of Additional(!) Leucine: 1.68g Leucine in Your Intra-Workout EAA Mixture is Good, Twice the Amount is 33% Better, Though!

Image 1:  Buying L-Leucine in bulk
can save a lot of money; plus, it
gives you the advantage of being
able to adapt the leucine to EAA ratio,
whenever you read about new study
results on the SuppVersity ;-)
I don't know if I can actually call it 'news', when I tell you that intra-workout consumption of the branched-chain amino acid leucine will help you build muscle, but I am pretty sure that you, just like me, have always been wondering whether the provision of leucine in a more 'natural' EAA composition would produce the same, or even better results.

Although a number of leucine-enhanced products, i.e. EAA or BCAA products which contain more leucine than the standard 2:1:1 formulas, have been hitting the market, lately, Pasiakos et al. are the first who put the (acknowledgedly plausible) hypothesis that BCAA, or, in this case, EAA formulas with a higher than normal leucine content would elicit greater protein-anabolic effects (Pasiakos. 2011).

Before the eight healthy volunteers who participated in Pasiakos' study began their 60 minute moderate endurance-type exercise (60% VO2Max) on a cycle ergometer they were infused with radioactive tracer isotopes of leucine and phenylalanine (see figure 1 for exact quantities) to track muscle protein synthesis and whole-body protein turnover in response to the exercise. Throughout the exercise bout, the volunteers consumed 125 mL of either the leucine enriched (L-EAA) or an isonitrogeneous EAA control supplement in 20-min intervals "beginning immediately after exercise initiation and ending at the completion of the exercise bout".
Figure 1: Composition of the isonitrogenous EAA control (EAA) and the leucine enriched variety (L-EAA); both with added tracers (data adapted from Pasiakos. 2011)
What Pasiakos et al. found, a +33% greater increase in post-workout muscle protein synthesis, a -13.3% decrease in whole body protein synthesis and roughly -20% less protein breakdown, speaks for the muscle building magic of the primary of the four isomeric amino acids that is so heavily advertised in supplement stores, online shops and muscle magazines, lately.  Despite its profound effect on muscle protein metabolism, the additional +1.63g of leucine in the leucine-enriched EAA formula did not increase the mTOR response over exercise and standard EAA, alone - there was however a trend towards longer lasting yet less pronounced elevations in both mTOR and Akt phosphorylation in the L-EAA group, which could partly explain the overall increase in the protein anabolic response to exercise and (re-)feeding.
Note: The decrease in whole-body protein synthesis (-13.3%, cf. figure 2) which occurred in the study at hand appears to be something you would want to avoid. If, however, you remember what you have learned in the Amino Acids for Super Humans Series, a possible mechanism to explain this observation would be related to a decreased synthesis and usage of the intra-organ nitrogen carriers alanine, glutamine and aspartate, which would then be (ab-)used by your liver and other organs as an alternative fuel source. The 33% increase in muscle protein synthesis, on the other hand, underlines that the provision of additional leucine in the course of a strenous workout does not compromise your ability to build muscles, but, on the contrary, enhances the accrual of 'new muscle mass'.
In essence, this increase is not really surprising, as it only confirms what bros and pros, alike, have been suspecting, all along: more leucine = more anticatabolic, muscle proteinogenic signalling.
Figure 2: Effects of EAA with different leucine content (3.5 g vs. 1.87 g leucine) on protein metabolism in 8 healthy subjects after cycle ergometer exercise (data calculated base on Pasiakos. 2011)
In view of the "more is more"-mentality that is readily and willingly fostered by the producers of respective supplements, it should be mentioned that the "addition" of leucine (=reduction of other amino acids, cf. figure 1) to an otherwise standardized EAA mixture only brought the leucine level up to those roughly 4g you would get from two servings of your favorite whey protein shake, anyway.
Illustration 1: Hypothetical linear ("more-is-more") and more realistic, but probably still overpronounced dose-response relation between added leucine [in g] and x-fold  increase in muscle protein synthesis over isonitrogenous EAA control.
It is also worth mentioning that even with only 3.5 of leucine, the 90% increase in supplemental leucine does not result in an equipotent 90% increase in the muscle anabolic response. It is also unrealistic to assume that the does-response relationship would be linear (cf. illustration 1, green line), so that +20g of leucine would illicit a 4.68x increase in muscle protein synthesis over EAA alone. Rather, it is much more likely that we will see some sort of logarithmic dose response curve, as I sketched it in figure 2 (red line; the real dose response curve is probably less steep, though) response, where additional +20g of leucine would increase muscle protein synthesis by no more than 2.25x (again, the sketched graph in illustration 1 probably overestimates the effect size) over a standard EAA supplement.
Always keep in mind: Leucine's role in muscle protein turnover is both that of a substrate, as well as that of a signal / switch. Since leucine is not found in isolation in any naturally occurring protein source, your body interprets its availability as a sign that there are plenty of other amino acids (BCAAs and EAAs, in particular) available and shifts muscular protein metabolism towards synthesis. Yet human as your body is, it also starts to be lavish with its amino acids and ramps up nitrogen oxidation (+69.7% in the study at hand), as well. Consequently, the ratio of amino acids that are actually used to 'build muscle' to those that are burned to fuel your energy demands plummets - in commercial terms the marginal benefit diminishes... keep that in mind when you try to swallow your 500g pot of l-leucine with 1l of water in the course of a 45min workout - it may not be worth the agony ;-)
So I guess, the take home message of this study, which by the way was not financed by one of the major supplement companies but by the US military, is that, in the case of leucine, the otherwise illusive concept of "more is more" actually applies - at least as long as we are talking about quantities that would be achievable by nutrition alone (~1-5g). With higher amounts of leucine enrichment and thus lower amounts of EAA in the mixture, the lack of available EAAs could abolish any additional increases in muscle protein synthesis. In view of the increases in protein oxidation (+69.7%, cf. figure 2), it is in fact much more likely that the ingestion of 20g of additional leucine in isolation or in combination with only 10g of essential amino, i.e. at a 2:1 leucine to EAA ratio (in the study the ratios were about 1.87:8.23 and 3.5:6.5), would lead to a marginal increase in muscle protein synthesis (over isonitrogenous EAA) and a major increase in amino acid oxidation. In other words the leucine would be (ab-)used as fuel.

In comparison to the aforementioned high leucine low/normal EAA scenario, the use of 20g instead of 10g of the leucine-enriched amino acid formula (exact composition see figure 1), and thus 7g of leucine + 13g of EAAs seems to be a more reasonable approach. After all, we can only hope that the US Army Research Institute of Environmental Medicine is similarly interested in the optimal leucine to EAA ratio or the effects on strength training and finances a follow up study, about the results of which - you know it - you will read at the SuppVersity, first!
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