Biochemically, α-keto acids are endogenous intermediate metabolites, analogs to amino acids and may affect the cellular and blood level of ammonia [
33‐
36]. Therefore, it is likely that supplementation with α-keto acids has an impact on physical training. We have therefore hypothesized that supplementation with α-keto acids improves exercise tolerance and training effects. In this study, we found that by supplementing the subjects with KAS, their training volume, maximum power output and maximum muscle torque, as well as their performance, were all significantly increased, which was associated with a better recovery-stress state. Therefore, KAS can indeed improve training tolerance.
KAS effects on physical training
A number of studies of nutritional intervention during physical training have been published. A recent study reported that acute supplementation of cyclists with keto analogs and amino acids during exercise attenuated exercise-induced hyperammonemia [
22]. However, the effects of KAS alone during prolonged physical training have not been reported. In the present study, we have adopted the double blind, randomized and placebo-controlled trial design, so that the subjective component affecting exercise tolerance could be precluded from the effects of KAS. To provoke the metabolic challenge, a cohort of untrained subjects was recruited and a very strenuous training program was undertaken to achieve an “over-reaching” status. The training was highly demanding; the subjects in the control group could not maintain their assigned training volume during the second half of the program (Table
2, Figure
23 and
4). The training data also showed a typical training effect at the stage of over-reaching; i.e., a significant improvement in maximum power output after recovery but only slightly in aerobic exercise capacity, as previously reported [
37]. The subjects underwent an endurance-training bout first so that the energy reserve was exhausted, and the subsequent sprint running would then draw energy partly from protein metabolism. This training strategy constitutes a valid metabolic challenge [
6]. To exclude the influence of components other than α-keto acids, the intake of energy and minerals was carefully matched in the placebo preparation. There were no side effects or difficulties in compliance, suggesting that the supplementation was safe.
Despite the hard training, over-training did not occur because there were no clinical complaints and no decrease in the maximum performance and maximum blood lactate concentration (10.7 ± 2.4 mM). The training, however, improved VO
2max (average 14%, P<0.01) in all three groups (Table
2). This result is in accord with those of other studies [
38]. The training effect on VO
2max was comparable among the three groups, although the training volume was quite different at the second half of the training phase. This finding may be explained by the fact that the oxygen delivery determined principally by the cardiorespiratory system is the primary limiting factor for VO
2max[
39]. The maximum power output did not change in the control group after the training phase and recovery (NS). There was a similar increase in maximum power output in both study groups after the training and more so after recovery, indicating a “super-compensation” effect from training (Table
2). These results are in good accord with those of previous studies [
40], and suggest a significant training effect in both groups supplemented with KAS. Similarly, the muscle function, both maximum torque on isometric measurement and maximum performance on isokinetic measurement, increased significantly after recovery in both groups supplemented with KAS. The maximum muscle torque was higher in the AKG group than in the BCKA group (Figure
3), mainly due to the different baseline levels but not changes in training (NS). In the present study, the endurance capacity (P
LAT in Table
2) was improved in all three groups with no significant difference among the groups, which could be attributed to the concurrent training program executed with combined training components [
41].
It is also interesting to observe the relative changes in VO2max and Pmax.. There was a similar increase in VO2max in all three groups, but the Pmax was much higher in the two groups with KAS than in the control group, suggesting that there was either a higher work efficiency or a higher quotient of anaerobic energy metabolism associated with KAS. Because the maximum blood lactate concentration was comparable among the groups (data not shown), the higher relation of Pmax to VO2max for both groups with KAS can be considered as reflecting improved work efficiency.
VO
2max was determined on a cycle-ergometer instead of using a treadmill test since this method was established in our laboratory and a rapid linear increment of the workload was better to achieve. Determination of VO
2max on a cycle-ergometer is well established and widespread in the routine practice of sports medicine. Yet it remains unclear whether a lack of statistically significant difference in this parameter among the groups could be attributed to the known fact that VO
2max determined on a cycle-ergometer is generally lower than that determined on a treadmill [
42,
43].
In summary, the training program performed in this study produced distinct training effects in the control group. However, KAS supplementation was associated with additional improvements in Pmax and maximum muscular torque and performance. Together with the data from training volume, it can be concluded that KAS improves training tolerance and has beneficial effects on physical training.
KAS effects on stress-recovery state
The state of stress-recovery during and after a training phase can be assessed using the questionnaire RESTQ-sport [
28]. In general, the profiles of the RESTQ scores were quite different among the three groups (Figure
5A-D). The term general stress reached its highest level in the control group after the third training week (Figure
5A). Emotional exhaustion (Figure
5C) and a slight increase in somatic complaints (Figure
5B) followed the same pattern but with distinct disturbed breaks as a sign of poor recovery (Figure
5D). A decrease in the general stress parameters at the end of the 4
th training week and after recovery was associated with a reduction in training volume (Figure
2). This finding is in agreement with those of Kellmann and Gunther, who concluded that the general stress and somatic complaints were correlated with the duration of intense training [
28]. In contrast with the results for the control group, the RESTQ scores for the terms general stress (Figure
5A) and emotional exhaustion (Figure
5C) in the BCKA group did not change significantly and remained at a lower level, but the somatic complaints increased during the training period (Figure
5B). These data suggest that BCKA supplements can relieve general stress and emotional exhaustion and better preserve the recovery after high-level exercise. With the AKG supplement, the RESTQ profile was comparable to that of the control group, although the training volume was higher in the 3
rd and 4
th training weeks. Considering the relationship between the amount of training and RESTQ scores in general stress and somatic complaints reported by Kellmann and Gunther [
28], our data suggest that supplementation with AKG helps maintain the level of general stress, somatic complaints and emotional exhaustion during high-intensity training.
To the best of our knowledge, there are no previous studies investigating the effects of KAS supplementation on physical training. However, two relevant studies have been reported [
8,
22]. In a study of adult rats, De Almeida et al. have shown that exercise increased ammonia levels twofold with respect to the control and significantly increased blood urea levels (17%). Those authors also report that acute supplementation with keto acid-associated amino acids (KAAA) clearly reduced exercise-induced hyperammonemia [
8]. This result was supported by a study of male cyclists, where it was observed that short-term supplementation with KAAA blunted exercise-induced hyperammonemia [
22]. However, in these two acute studies, the effect of KAAA on exercise tolerance was not investigated. Thus, whether the inhibition of exercise-induced hyperammonemia by supplementation with KAAA leads to an improvement in training tolerance remains unclear. Although the underlying mechanism of the effects of the supplementation of α-keto acids on physical exercise remains unclear, we have shown the beneficial impact of the supplementation with KAS on physical training in untrained individuals. Further studies are needed to clarify whether KAS supplementation affects amino acid homeostasis and ammonia metabolism during and after physical exercise.