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What causes muscle fatigue during strenuous exercise?

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Illustration of the human muscular system from a side view, showing detailed muscles throughout the body with labels identifying major muscles in the head, torso, arms, and legs. — human muscle system Lateral view of the human muscular system.

Muscle fatigue during strenuous exercise can result from the depletion of energy stores and the accumulation of metabolic byproducts. Prolonged exercise, like marathon running, is associated with glycogen depletion, which is crucial for energy production through oxidative glycolysis. Intense exercise lasting only a few minutes can lead to the buildup of lactate, causing intracellular acidosis due to anaerobic glycolysis. Additionally, a reduction in phosphocreatine levels occurs during both types of strenuous exercise, although adenosine triphosphate (ATP) levels remain relatively stable. These physiological changes contribute to the muscle's inability to sustain force or recover adequately between contractions.1