Creatine Supplementation in Patients With Cancer: A Systematic Review and Meta‐Analysis

Background Creatine supplementation (CrSUPP) has demonstrated benefits in improving body composition, muscle strength and physical function in healthy older adults. However, preclinical studies have raised concerns about the potential for CrSUPP to negatively impact cancer outcomes. This systematic review and meta‐analysis aimed to evaluate the efficacy and safety of CrSUPP in patients with cancer. Methods PubMed, Embase and Cochrane databases were systematically searched for randomized controlled trials (RCTs) comparing CrSUPP to placebo (PBO) in cancer patients. Outcomes included changes in body composition (lean mass [LM] and fat mass [FM]), muscle strength, physical function, quality of life (QoL), safety and survival. Standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the I 2 statistic (significance: p < 0.1, I 2 > 25%). Random‐effects models were applied. The protocol was registered in PROSPERO (CRD42025634948). Results Five RCTs including 373 patients (190 CrSUPP, 183 PBO) were analysed. Three studies included patients with non‐metastatic disease, whereas two included predominantly advanced cancer cases. Most patients were receiving active oncologic treatment. CrSUPP regimens varied, with three trials using a loading dose (20 g/day for 5–7 days), followed by maintenance (2–5 g/day), and two trials using either a loading or maintenance dosing strategy. Intervention duration ranged from 1 to 12 weeks, combined with resistance training in two studies. There were no significant differences between CrSUPP and PBO for LM (MD 0.55 kg [95% CI, −3.96, 5.07], p = 0.81, I 2 = 0%) or muscle strength (SMD −0.05 [95% CI, −0.29, 0.18], p = 0.65, I 2 = 0%). FM was significantly reduced in the CrSUPP group (MD −2.81 kg [95% CI, −4.21, −1.41], p < 0.001, I 2 = 0.9%). Physical function showed no significant changes (SMD −0.20 [95% CI, −0.68, 0.28], p = 0.41, I 2 = 0%). QoL was assessed in three studies, with data available from two, showing no CrSUPP effect. Safety data from three studies revealed no differences in adverse events between groups; renal function was assessed in one trial and showed non‐clinically relevant creatinine elevations. Overall survival was reported in one trial, showing no impact of CrSUPP. Conclusions CrSUPP did not significantly affect muscle strength, physical function or lean mass in cancer patients and may be associated with a reduction in fat mass; however, this finding should be interpreted with caution given the limited number of studies, heterogeneity of patient populations, interventions and outcome measures.