To our knowledge, the efficacy of BCAA has not been firmly established for hormonal response and fatigue. Therefore, this systematic review and meta-analysis has sought to provide insight into the potential advantages conferred by such supplementation to enable trainers to make informed decisions as to their efficacy and usage. The results of the current meta-analysis, performed in 20 randomized controlled trials, revealed no noticeable effects of BCAA supplementation in decreasing fatigue substances and hormone levels during training protocols of different durations. The major finding of this study was the observation of significantly lower values of cortisol concentration during 2 hours and more post exercise with BCAA. Thus, our findings support those of previous investigators, namely, that amino acid ingestion is capable of attenuating exercise-induced increases in cortisol .
Cortisol is a catabolic hormone and the main glucocorticoid hormone in humans, secreted from the adrenal cortex in response to psychological and physical stress . While cortisol increases during exercise, most of the changes and effects of this hormone occur after exercise during early recovery. Short-term elevation in plasma cortisol concentration, within the physiological range, stimulates proteolysis and elevates plasma leucine concentration and utilization. A fraction of plasma BCAA would seem to be utilized for protein synthesis, in contradiction to the cortisol protein synthesis inhibitory mechanism . BCAAs slow the release of essential amino acids from active muscles, prevent exercise-induced muscle proteolysis, reduce muscle damage, and increase muscle protein synthesis during the recovery period [12, 39]. It can hence be concluded that part of the anticatabolic effect of BCAAs is related to lower values of cortisol concentration.
A review paper by Hormoznejad et al.  reported that, in order to assess fatigue, plasma ammonia activity and plasma lactate concentration are widely used as markers. However, the above meta-analysis was performed based on ammonia and lactate. These factors are not only the most used outcomes: they are the best markers of muscle fatigue [28, 33, 35]. Data for ammonia was heterogenic and a meta-analysis was not undertaken. Despite the high heterogeneity of the data, a meta-analysis was conducted previously without any subgroup for follow-up time , and in our opinion, these results should not be considered reliable. Moreover, intake of BCAA for any duration had no significant effect on lowering lactate concentration in the follow-up times post exercise, compared to a placebo. Nevertheless, without considering follow-up times, with an overall analysis BCAA was effective in lactate reduction for subgroups of aerobic exercise and trained status of athletes (Table 3).
The rate of lactate production exceeds the rate of removal during high-intensive exercise. The excess lactate facilitates acidosis and suppresses the enzymatic activation related to glycolysis, which impedes ATP synthesis and finally leads to fatigue. McLean et al.  suggested that a 77 mg/kg dose of BCAA does not significantly alter the overall distribution of pyruvate into lactate and alanine, compared with placebo. Matsumoto et al.  reported an increase in circulatory BCAA levels and suggested that BCAA supplementation induced an increase in BCAA oxidation during the exercise test. It was thus speculated that an increase in acetyl-CoA and succinyl-CoA supply to the TCA cycle via the BCAA catabolic pathway suppressed lactate production during the exercise test. In a study by Kim et al. , lactate concentrations of the two groups of BCAA and controls, respectively, showed a statistically significant increase at 30 min into exercise. Lactate concentrations in the BCAA intake group indicated a statistically meaningful decrease immediately after exercise and returned to a stable level at 30 min after exercise. However, in the present meta-analysis, we could not analyze immediately post-exercise follow-up due to the high heterogeneity of the data.
Several factors can affect the high heterogeneity and the inconclusive findings that have been reported. Some of these are: the percentage of leucine, isoleucine, and valine; different manufacturers of BCAA; and variations in BCAA classifications between countries. All these factors may contribute to the inconsistencies in results. Moreover, the studies included in this review reported different dosages, ranging from 1.5 g/day  to 64 g/day .