Abstract / Summary
Background: Fatigue in high-intensity exercise is often attributed to a defended ceiling of peripheral fatigue; evidence is mixed. Objectives: We aimed to assess whether the end-exercise potentiated-twitch decrement behaves as a regulated variable across candidate mechanisms. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched to 12 August 2026. Evidence came from controlled studies in adults, with permeabilized-fiber, rodent, and isolated-actomyosin experiments only where human measurement is impossible. Results: Nine mechanisms met the criteria. Inorganic phosphate and hydrogen ions impair the cross-bridge cycle; reduced sarcolemmal excitability (K+) and reduced sarcoplasmic reticulum Ca2+ release reverse over minutes and days, respectively. Only the cross-bridge effects are driven by metabolites (protons, ATP, lactate) that are agonists of group III/IV afferents; the afferents do not sense contractile impairment itself. Oxygen delivery, respiratory-muscle work, substrate availability, and perceptual load altered fatigue rate more than the end-exercise value, which varied with duration, prior exercise, muscle mass, and mode. Conclusions: Evidence fits a threshold in the phosphate–force relationship, though this does not demonstrate a defended limit. The decrement is not constant across tasks; we propose, as a testable hypothesis, that the regulated quantity is the summed afferent and effort signal. Selection was purposive, without formal risk-of-bias appraisal.