Caffeine as an Ergogenic Aid for Neuromuscular Performance: Mechanisms of Action from Brain to Motor Units

Ergogenic aids have long attracted scientific interest for their potential to enhance neuromuscular performance, with caffeine being among the most extensively studied. While traditionally attributed to peripheral actions on skeletal muscle, accumulating evidence indicates that, at physiological doses, caffeine's ergogenic effects are predominantly mediated by antagonism of central adenosine receptors. This antagonism leads to increased arousal, reduced inhibitory neuromodulation, enhanced corticospinal excitability, and altered motor unit recruitment and firing behavior. Importantly, the concentrations required to elicit direct effects on excitation-contraction coupling via ryanodine receptors exceed those compatible with human safety, rendering such mechanisms unlikely in vivo. This narrative review synthesizes contemporary neurophysiological evidence to propose that caffeine acts primarily by "tuning" motor system gain through central neurotransmitter modulation, rather than by directly augmenting muscle contractile properties. Additionally, we highlight unresolved questions regarding persistent inward currents, sex-dependent neuromodulatory influences-including the potential role of estrogen in regulating adenosine receptor expression-and the implications of repeated caffeine use during training for neural adaptation and motor control. Finally, we outline key methodological and conceptual directions for future research aimed at refining our understanding of caffeine's neuromuscular effects in both acute and chronic contexts.