Leucine Does Not Have Anti-Fatigue Effects During Exercise to Exhaustion, BCAAs Even Reduce Maximal Endurance

If your are competing in endurance sports BCAA supplements may be more than useless, they may be detrimental.

I have to admit that the results of a recent study from the University of Sao Paulo came as a surprise to me. It would be negligent, however, to ignore that the results Patricia L. Campos-Ferraz and her colleagues present in their latest paper in Nutrition, because I personally don't believe in the use of isolated leucine supplementation.

In the corresponding experiment, the scientists from Sao Paulo aimed to 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.
Furthermore, Campos-Ferraz et al. attempted to investigate muscle and liver biochemical parameters that were not performed in the studies in order to elucidate the role of BCAAs in glycogen depletion. In that, the scientists' hypothesis was "that the mixture of BCAAs supplementation would impair performance because they would be used mostly in muscle to yield acetyl-CoA, reducing the activity
of the glucose-alanine cycle and thus gluconeogenesis in liver from amino acids, whereas leucine alone could feature the opposite effect in this experimental model" (Campos-Ferraz. 2013).

Obviously, this hypothesis did already imply that the lack of hepatic neogenesis in response to BCAA supplementation may blunt the endurance performance of the 8 wk old rodents that were used as "subjects" in the study at hand.

Table 1: Swimming training protocol | BW = body weight (Campos-Ferraz. 2013).

As the overview of the study design in Table 1 tells you, the rodents underwent a 7-week adaptation phase over the course of which the the exercise intensity was progressively increased until the rodents were finally exposed to an intermittent, progressive swimming test until exhaustion and sacrificed.

Figure 1: Leucine is transaminated to alanine in skeletal muscle. Alanine reaches the liver where it can be reconverted to glucose. Unlike alanine, leucine can also be converted to ketones in the liver. Simultaneously, leucine can augment translocation of GLUT-4 and stimulate glucose uptake and protein synthesis when EAA & energy supply is adequate (Campos-Ferraz. 2013).

"One day after the lactate threshold test and still during week 7 of the experiment, the supplementation protocol began. Animals were supplemented orally by intragastric gavage throughout the following 7 d with either the mixture of BCAAs, leucine, or placebo, 166 mg of the corresponding amino acids/kg daily diluted in 2 mL distilled water. This dose has been determined based on the calculations of leucine flux in humans as 88 mg/g daily (Young. 1998) and BCAAs oxidation as 144 mg/kg daily (Elango. 2008). In order to make an isonitrogenous supplementation between the LEU and BCAAs groups, the amount of 166 kg LEU/ kg, which corresponded to two times the determined LEU flux dose, as described above, was applied and equalized in the BCAAs group. All amino acids were provided by Ajinomoto (Tokyo, Japan)" (Campos-Ferraz. 2013).

In human terms the 166mg/kg would be approximately 2.0-2.5g depending on the individuals body weight. Significantly less than many people consume before and after their workouts, but enough to elucidate significant performance relevant effects. With differences between the placebo and supplementation arms and differences between the BCAA and leucine arms of the study.

Figure 2: Liver glycogen degradation (A); liver glycogen content (B); muscle glycogen degradation (C); muscle glycogen content (D) in placebo (PLA), the mixture of BCAAs, and leucine (LEU) groups (Campos-Ferraz. 2013).

More specifically, both, the muscle and liver glycogen degradation ratio were significantly higher in the mixture of BCAAs group compared to the PLA group (P < 0.05). In comparison to the BCAA group, the LEU group presented decreased liver glycogen degradation ratio compared with the mixture of BCAAs group (P < 0.05). Both muscle and liver glycogen content were significantly spared in the mixture of BCAAs and LEU groups compared to the PLA group (P < 0.01). More importantly, however, the performance test demonstrated that LEU supplementation enhanced resistance to exhaustion compared to the mixture of BCAAs (P < 0.001). Compared to the PLA trial, however, no difference was found when LEU supplementation.

At first this may be surprising, but eventually the data in Figure 2 explains it all. The inhibition of muscle glycogen degradation by BCAAs that is often advertised as one of the most significant benefits of BCAA supplements will turn against you, when you work out to exhaustion, because it reduces availability of glucose and thus increases the dependence on alternative fuel sources from the TCA cycle - a fact that is evidenced by the increases in muscle citrate content and malate content, the scientists observed in the BCAA group.
References:

• Campos-Ferraz, Patricia L., et al. "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 29.11 (2013): 1388-1394.
• Elango, Rajavel, Ronald O. Ball, and Paul B. Pencharz. "Indicator amino acid oxidation: concept and application." The Journal of nutrition 138.2 (2008): 243-246.
• Young, Vernon R., Dennis M. Bier, and Peter L. Pellett. "A theoretical basis for increasing current estimates of the amino acid requirements in adult man, with experimental support." The American journal of clinical nutrition 50.1 (1989): 80-92.