Branched-Chain Amino Acids and Central Fatigue: Implications for Diet and Behavior

Abstract

The branched-chain amino acids (BCAA) leucine, isoleucine, and valine can influence metabolism in the brain in several ways, including an effect on the synthesis of the monoamines dopamine, norepinephrine, and 5-hydroxytryptamine (5-HT). These monoamines are synthesized from the aromatic amino acids tyrosine and tryptophan, the latter being the precursor for 5-HT. The rate-limiting step in the synthesis of 5-HT is the transport of tryptophan across the blood–brain barrier, a process that is influenced not only by the plasma concentration of tryptophan, but also by the plasma levels of the other large neutral amino acids, including the BCAA, which compete with tryptophan for entry into the brain. Changes in the release of 5-HT in the brain are known to be involved in the control of arousal, sleepiness, and changes in mood and have also been suggested to play a role in the fatigue that occurs during and after physical exercise. In agreement with this proposal, the synthesis and release of 5-HT in experimental animals is enhanced during sustained exercise. Moreover, studies on human subjects reveal that the ratio of free tryptophan (i.e., unbound to albumin)/BCAA in plasma increases during endurance exercise and, furthermore, that tryptophan is taken up by the brain in this situation. Ingestion of BCAA leads to elevation in their plasma concentrations and should consequently decrease uptake of tryptophan into the brain, thereby attenuating the rate of synthesis and release of 5-HT and reducing central fatigue. When this hypothesis was tested in human subjects in connection with different types of physical exertion, positive effects on mental performance and perceived effort were reported in both field studies and under controlled laboratory conditions. Under certain conditions, BCAA can also improve physical performance, but this is dependent on the type of exercise, the amount and composition of the supplement administered, and the physical condition of the subjects. Finally, although exercise also increases uptake of BCAA by the brain, the significance of this effect remains unclear. Perhaps BCAA play some additional role in connection with central neurotransmission during sustained exercise.