Creatine Beyond Muscle: Pleiotropic Effects with and Without Exercise—A Critical Narrative Review

Creatine is an established ergogenic aid, but its benefits beyond its effects in muscles remain uncertain. This critical narrative review examines cognitive, neurological, psychiatric, metabolic, vascular, skeletal, inflammatory, and rehabilitation outcomes. Targeted searches and citation tracing included publications available on 30 October 2026. We distinguished effects without prescribed exercise, incremental benefits within a common programme, interaction, intervention packages, and mediation. Small studies under sleep loss or hypoxia reported selected cognitive signals; findings in rested adults were inconsistent and benefits in the neurodegenerative conditions examined remained unestablished. Psychiatric findings remained heterogeneous and did not establish clinically important average efficacy. A potentially clinically important glycated haemoglobin reduction in one small exercise-add-on trial in type 2 diabetes remains unreplicated and at a high risk of bias. Vascular findings concerned short-term surrogates; bone-density outcomes were largely null, chronic anti-inflammatory efficacy unestablished, and rehabilitation findings inconsistent. Creatine modestly increased lean mass during resistance training, but downstream clinical mediation was unproven. Sparse evidence on randomised creatine-by-exercise interaction and mediation limits causal attribution without invalidating incremental effects estimated in suitable two-arm trials. Heterogeneous regimens preclude a generalisable dose recommendation. Clinical interpretation should remain indication-specific, prioritising the replication of relevant effects and testing interactions or mediations when those are the research questions.