Exercise combined with creatine supplementation for skeletal muscle hypertrophy: mechanistic basis, nutritional context, and applications.

Creatine supplementation is one of the most widely studied nutritional strategies for enhancing resistance-training adaptations and skeletal muscle development. This narrative review evaluates the evidence linking creatine supplementation with skeletal muscle hypertrophy, integrating mechanistic insights, nutritional considerations, and practical applications. Current evidence indicates that creatine primarily supports hypertrophic adaptation by increasing phosphocreatine availability and enhancing the capacity to perform high-intensity training, thereby increasing the mechanical stimulus for muscle growth. Creatine-associated increases in lean mass should, however, be interpreted cautiously because changes may reflect a combination of intracellular water expansion, glycogen-associated water storage, and genuine increases in contractile tissue. Proposed molecular mechanisms, including anabolic signaling, myogenic regulation, myostatin modulation, and satellite-cell-related responses, remain biologically plausible but vary considerably in evidential strength and require further validation in contemporary human trials. Individual responses may be influenced by age, sex, baseline creatine status, dietary patterns, and training characteristics. From a nutritional perspective, creatine-fortified foods represent a promising application area, although formulation stability, processing challenges, and consumer acceptance require further investigation. Future research should prioritize standardized hypertrophy assessments and longer-duration interventions to clarify the direct and indirect contributions of creatine to skeletal muscle adaptation.