Caffeine, skeletal muscle signalling, and exercise adaptation: a narrative review separating acute ergogenic effects from chronic remodelling.

Caffeine is one of the most widely used and extensively studied ergogenic aids in sport, yet whether its well-established acute benefits extend to the chronic remodelling of skeletal muscle remains unresolved. In this narrative review, we distinguish the acute ergogenic effects of caffeine from its potential influence on chronic skeletal muscle remodelling, because the mechanisms that improve acute performance need not be those that govern repeated tissue adaptation. The evidence for acute ergogenicity rests on a large human literature, in which adenosine receptor antagonism is the probable dominant mediator, with additional contributions from potassium handling, ryanodine receptor 1 (RyR1) sensitisation, altered contractile behaviour, and reduced perceived effort. Evidence that repeated caffeine exposure around exercise modifies chronic skeletal muscle adaptation in humans remains limited; available training trials are short, narrow in modality, and lack muscle biopsy endpoints, and several acute endurance studies under substrate restriction are better interpreted as training quality mediator evidence. Preclinical work is more mechanistic but directionally mixed, supporting Ca²