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| Alanine is the liver's favorite gluconeogenic amino acid and leucine appears to increase its usage. |
So what did the Brazilian researchers do?
Basically, the idea Campos-Ferraz et al. had in mind, when they came up with their 8 week exercise + 2 week supplementation protocol (see Table 1) was to ...
In other words: The researchers wanted to find out whether or not leucine would exert identical, less or more pronounced effects on muscle glycogen use and endurance performance in rodents that the full spectrum of branch-chained amino acids, i.e. leucine, valine and isoleucine."evaluate effects of the use of supplementation with leucine or a mixture of BCAAs in trained rats submitted to an exercise-induced protocol of glycogen depletion.
Table 1: Exercise progression; suppl. was initiated in w7 after lactate test
Furthermore, we attempted to investigate muscle and liver biochemical parameters that were not performed in the previous study in order to elucidate the role of BCAAs in glycogen depletion. " (Campos-Ferraz. 2013)
Contrary to what bro-science and the shiny ads of the supplement industry are suggesting, the scientists' fundamental hypothesis was that the BCAAs supplementation would impair the rodents endurance capacity, because the branched-chain amino acids would be used in muscle to yield acetyl-CoA. This, in turn could reduce the activity of the glucose-alanine cycle, by which the muscles are supplied with alanine-derived glucose from the liver and (once the BCAAs got burne) result in an earlier onset of fatigue.
BCAAs are "glycogen depleters"?!
If you take a look at the data Campos Ferraz et al. gathered in the testing sessions at the end of the supplementation period, in the course of which the rats received an oral gavage of 166mg/kg per day (in human terms this would be ca. 3-3.5g per day) of BCAAs or leucine, it is quite obvious that the the leucine group had a significantly lower muscle and liver glycogen degradation ratios than the BCAA group.
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| Figure 1: Liver & mucle glycogen degradation and time to exhaustion (expressed relative to placebo); muscle TCA intermediate content and enzyme activity / concentration (Campos-Ferraz. 2013) |
As the researchers point out, these observations stand in line with their original hypothesis: Leucine can spare a significant amount of muscle and liver glycogen and thus produce a highly significant increase in resistance to exhaustion compared to the mixture of BCAAs (P<0.001).
If you take another look at the data in Figure 1 you will probably notice the significant increase in TCA cycle intermediates (citrate and malate) in the BCAA group. These changes provide further evidence that the provision of all three branch-chain amino acid emphasized the use of glucose as a main substrate to sustain the endurance activity.
"Mouse vs. man": Can we ignore the differences in BCAA metabolism?
At this point, it may however be about time to point out that the activity of the BCAA catabolizing enzyme branched-chain keto acids dehydrogenase complex (BCKD) in humans is quite different from that in rats.
"In the latter [the rat], liver BCKD is almost completely unphosphorylated (activated) in basal state, making it possible to metabolize more rapidly BCKA from the portal blood; in humans, BCKD in liver is normally phosphorylated (inactivated) in order to spare BCAAs for protein synthesis." (Campos-Ferraz. 2013)In other words: While rodents use BCAAs mostly as an energy source, the human body spares them as a potential protein anabolic.
In view of the fact that the BCAAs are not used to the same degree as an alternative substrate in the human vs. the rodent liver, it is actually not very surprising that the results of the study at hand appear to conflict with data from a previous study by the same laboratory (Gualano. 2011). In the corresponding experiment, Gualano et al observed measurable increases in exercise capacity and lipid oxidation in human subjects during endurance exercise after muscle glycogen depletion in response to the provision of 300mg/kg BCAAs per day.
So, the study is totally irrelevant, right? Not really, no. The fact that we are not able to use BCAAs as a readily available energy source like rodents does after all not mean that they must necessarily have the opposite effects on us. In fact, you all know that the vast majority of studies investigating the beneficial effects of BCAAs on endurance performance in humans yielded a null-result (!) - despite the fact fact that generations of researchers have been convinced that the inhibition of tryptophan uptake must blunt the exercise induced onset of fatigue (learn more in the articles cited in the red box).
The actual new information this study brings to the table is thus not that BCAAs are not ergogenic. It's rather the previously overlooked leucine induced acceleration of the glucose alanine cycle in liver. It is the activation of this (catabolic!) powerhouse by the means of which leucine "might have an interesting use in physical performance in prolonged or submaximal exercise, where muscle glycogen stores are more likely to be depleted" (Campos-Ferraz. 2013). It should be noted, though, that these effects are probably only observed after the glycogen levels are fully depleted - after an intense workout, towards the end of a race or after an fasted training - in those situations, the performance benefits may even be more more significant than in the study at hand.
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| Don't forget the endurance reducing increase in glucose usage that appears to be caused by isoleucine (and maybe valine) can also be beneficial: "The Glucose Repartioning Effects of Isoleucine" | read more. |
Reference:
- Campos-Ferraz PL, Bozza T, Nicastro H, Lancha AH Jr. Distinct effects of leucine or a mixture of the branched-chain amino acids (leucine, isoleucine, and valine) supplementation on resistance to fatigue, and muscle and liver-glycogen degradation, in trained rats. Nutrition. 2013 Nov-Dec;29(11-12):1388-94.
- Gualano AB, Bozza T, Lopes De Campos P, Roschel H, Dos Santos Costa A, Luiz Marquezi M, et al. Branched-chain amino acids supplementation enhances exercise capacity and lipid oxidation during endurance exercise after muscle glycogen depletion. J Sports Med Phys Fitness 2011;51:82–8