Effects of creatine supplementation on lean mass, muscle size and muscle performance during immobilisation and rehabilitation: A systematic review

Abstract

Creatine monohydrate (CrM) supplementation has established benefits in exercising populations; however, its efficacy during disuse and subsequent rehabilitation remains unclear. This systematic review assessed the effects of CrM supplementation on muscle size, lean mass and muscle performance (strength, power, endurance) during periods of disuse and rehabilitation. PubMed, Scopus, Web of Science and Cochrane Library were searched from inception to March 2026 following PRISMA guidelines. Six randomised placebo‐controlled trials were included ( n  = 118, mean ages: 15–24 years, disuse model: 1–2 weeks limb‐immobilisation). Two studies reported comparable reductions in quadriceps cross‐sectional area (CSA; assessed via CT or NMR imaging) between CrM and placebo during disuse (−5.6% vs. −5.5%; −11.0% vs. −9.4%), whereas two reported smaller reductions from CrM supplementation in lower‐limb lean mass (−5.6% vs. −8.9%) or preserved upper‐limb lean mass (0.9% vs. −3.7%) (assessed via bioelectrical impedance analysis (BIA) or dual energy X‐ray absorptiometry (DXA)). These contrasting findings may reflect limitations of BIA/DXA, including hydration effects, rather than preservation of muscle tissue. Effects on muscle performance were inconsistent, with favourable findings from CrM supplementation in upper‐ but not lower‐limb models. Four studies included recovery, three of which used resistance‐based rehabilitation. Two reported greater increases with CrM supplementation across quadriceps CSA (21.3% vs. 14.3%), lower‐limb lean mass (5.6% vs. 3.8%), power (52.2% vs. 35.2%) and strength (28.7% vs. 22.8%). Current evidence does not unanimously support CrM supplementation as an effective countermeasure to mitigate disuse‐induced muscle atrophy, lean mass loss or declines in muscle performance. Whether CrM supplementation meaningfully influences rehabilitation following disuse, particularly in older adults and clinical populations at greater risk of disuse atrophy and incomplete recovery, warrants further investigation.