Lactate Is Not a Cause of Fatigue

Abstract

For many years, it has generally been believed that the accumulations of lactate (lactic acid) in muscles and in the central nervous system are associated with peripheral and central nervous system fatigue, respectively. We conducted an overview of the roles of lactate, which have recently been clarified, under the condition of fatigue. First, the intra-cellular acidification of muscle caused by an accumulation of lactate has protective effects during muscle fatigue. The excitation-induced accumulation of extracellular K⁺ leads action potentials to be a less effective trigger of Ca²⁺ release in working muscles, and acidification by the accumulation of lactate reduces this effect by decreasing the contribution of Cl⁻ channels, which act to keep the membrane potential near the Cl⁻ reversal potential. Since the Cl⁻ reversal potential is near the resting membrane potential, the effect of Cl⁻ channel activity is to increase the Na⁺ current necessary to generate an action potential, which triggers Ca²⁺ release. Second, in the central nervous system, lactate generated in astrocytes contributes to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission, and administered lactate can also be utilized as energy substrates. Finally, an increased blood lactate level during muscle fatigue is not associated with central fatigue. From these results, we can conclude that lactate is a favorable substrate rather than the cause of fatigue.