A communicational link between skeletal muscle, brain, and cells of the immune system

The present paper reviews evidence for the role of specific amino acids in the etiology of fatigue and the overtraining syndrome in athletes. An increase in the plasma concentration ratio of free tryptophan: branched-chain amino acids may mediate an increase in 5-HT synthesis in the brain and thus induce fatigue during exercise. Glutamine is essential for the proper functioning of cells of the immune system and a decrease in plasma glutamine concentration post-exercise and in overtraining may induce an impairment in immune function. Branched-chain amino acids may play a central role in both these processes. Thus, they compete with free tryptophan for entry into the brain. Branched-chain amino acids may also be important precursors of nitrogen for the synthesis of glutamine in skeletal muscle or important in the control of glutamine release from muscle. Consequently, the metabolism of glutamine, tryptophan, and branched-chain amino acids may be the key to understanding some aspects of central fatigue and some aspects of immunosuppression that are very relevant to athletic endeavor. They may be also relevant to other physiological and pathological conditions.