Creatine Biology in the Context of Cancer
Creatine monohydrate has been used in recreational physical activity, competitive sports and has seen emerging utility in rehabilitation settings. With over four decades of research, creatine monohydrate has one of the most robust long-term safety datasets among dietary supplements across a broad array of populations, and continued support for its efficacy in improving muscular performance.
Beyond skeletal muscle metabolism and functioning, creatine plays a central role in cellular bioenergetics via the creatine–phosphocreatine shuttle, buffering ATP availability in tissues with fluctuating energy demands. Given that cancer is ultimately a disease of metabolic reprogramming, interest has grown in whether manipulating creatine availability could influence the various hallmarks of cancer.
Creatine kinase (CK) catalyzes the reversible conversion of creatine (Cr) to phosphocreatine (PCr), maintaining intracellular ATP homeostasis via the ATP-PCr cycle. While classically associated with skeletal muscle, the ATP-PCr cycle is also active in T cells, macrophages, CNS and peripheral nervous tissues, and rapidly proliferating cells.
Cancer cells exhibit metabolic plasticity. Some tumors upregulate creatine transporters (SLC6A8) and CK isoforms, potentially leveraging phosphocreatine buffering under hypoxic or nutrient-stressed conditions. Conversely, in certain contexts, creatine pathway manipulation appears to impair tumor growth. Further investigation is needed to tease out the mechanisms of long-term durability of creatine modulation within the cancer treatment setting.
Creatine may preserve lean muscle mass in patients with cancer.
Cancer-associated sarcopenia is independently associated with poorer treatment tolerance, increased toxicity, and reduced survival. Creatine supplementation (3–5 g/day) reliably increases intramuscular phosphocreatine stores and improves strength in non-cancer populations, particularly when combined with resistance training. Mechanistically, creatine could support ATP buffering in muscle during systemic inflammation and reduced caloric intake, but this remains insufficiently studied.
In oncology, data are limited, To date, no large RCTs have demonstrated survival or treatment/tolerance benefits.
The role of creatine in cancer immunometabolism and immunotherapy is still in early investigation.
Preclinical models have demonstrated that increasing creatine availability enhances CD8+ T-cell effector function by supporting ATP-dependent activation pathways. In murine systems, creatine transporter expression increases upon T-cell activation, creatine supplementation improves tumor control in some models, and synergy with immune checkpoint inhibition has been observed experimentally. These findings position creatine within the broader field of immunological and metabolic modulation; however, translation to human oncology remains speculative.
Creatine has not been evidenced to promote tumor growth.
A recurring concern is whether enhanced energy buffering could facilitate tumor proliferation. Current human data have not demonstrated that creatine supplementation accelerates tumor growth or increases cancer incidence. However, clinical oncology trials evaluating tumor endpoints are lacking, tumor-specific metabolic dependencies may vary, and some malignancies appear to utilize extracellular creatine.
Creatine has not been found to increase the risk of kidney damage in healthy populations.
Creatine naturally converts to creatinine in vivo; thus, creatine supplementation increases serum creatinine, without necessarily affecting GFR. In oncology practice, this could confound the interpretation of renal function, complicate dosing decisions for nephrotoxic agents, and trigger unnecessary imaging or referrals.
In non-cancer populations, creatine monohydrate at 3–5 g/day has demonstrated:
No consistent evidence of renal injury in individuals with normal baseline function.
No significant hepatic toxicity.
Good long-term tolerability.
Creatine should not be framed as an anticancer therapy, but as a supportive measure.
Data in advanced cancer populations, particularly those receiving cytotoxic or targeted therapies, are sparse. At present, its role would be more supportive, primarily in muscle preservation and slowing the decline in quality of life. Creatine monohydrate and other formulations of creatine could provide a mechanistically sound, safe, and cost-effective option for helping patients slow their decline. As oncology increasingly incorporates metabolic and host-directed strategies, even simple molecules like creatine warrant thoughtful, mechanistic scrutiny
Abbreviations: ATP, adenosine triphosphate; CNS, central nervous system; Cr, creatine; GFR, glomerular filtration rate; PCr, phosphocreatine; RCT, randomized, controlled trial.
Keep an eye out for data updates from completed and ongoing trials of creatine in oncology, such as the following:
Phase III CREATIVE-52 study of creatine with or without exercise in metastatic prostate cancer to preserve muscle mass (NCT06112990; Estimated completion, November 2028)
Phase I/II THRIVE study of breast cancer survivors receiving creatine and structured exercise intervention (NCT04207359; Completed March 2023)
CaRTiC study of creatine and resistance training in preservation of muscle mass and physical function in patients with breast cancer (NCT05878106; Completed December 2025)
We all rise together,
Blaise Collins, PhD, ACSM-EP-C | Monthly Blog Contributor, Jenerise | Medical & Scientific Director | Neurology, Oncology, Hematology | Exercise Physiologist
References
Del Arco A, et al. Effect of creatine supplementation on body composition in cancer patients: A systematic review. Nutrition and Cancer, 2025.
Geng Y, et al. It is not just about storing energy: The multifaceted role of creatine metabolism on cancer biology and immunology. International Journal of Molecular Sciences, 2024.
Peng & Saito, Creatine supplementation enhances anti-tumor immunity by promoting ATP production in macrophages. Frontiers in Immunology, 2023.
Memorial Sloan Kettering Cancer Center, Creatine: Purported benefits, side effects & more. MSKCC Integrative Medicine, 2026.
