The potential links between creatine and cancer are unclear. In general, evidence from in vitro studies and from studies conducted in animals suggests that creatine may have both cancer-suppressive and cancer-promoting properties.[1]
For example, in mouse models, both creatine and cyclocreatine (a synthetic analog of creatine) have been reported to slow down the rate of growth of subcutaneously implanted tumors.[2][3][4][5][6][7] The potential antitumor effects of cyclocreatine may require the presence of creatine kinase, through which cyclocreatine is converted to phosphocyclocreatine, which, in turn, potentially acts as an energy depleter by trapping ATP that has been released from the cell’s mitochondria or transported into the cell from outside, thereby limiting cancer cell proliferation.[4] However, because the expression of creatine kinase can vary widely depending on the type of tumor, the potential antitumor effects of cyclocreatine may also vary accordingly.[8] The potential antitumor properties of supplemental creatine may be related to its effects on cellular acidosis, inflammation, and oxidative stress,[5][7] as well as on the regulation of antitumor killer T cell immunity.[9]
On the other hand, findings from some studies suggest that creatine may promote invasion and metastasis of certain types of cancer — including colorectal cancer, breast cancer, and pancreatic cancer — through its energy-buffering properties and modulation of cell signaling.[10][11][12]
It’s important to highlight that the above findings are from in vitro and animal research, so their applicability to humans is currently unclear.
The limited available research in humans seems to suggest a potential protective role of creatine against cancer. Specifically, according to a 2023 cross-sectional study that was performed using data from 7,344 US adults who participated in the 2017–2020 National Health and Nutrition Examination Survey (NHANES), a higher intake of dietary creatine was associated with a lower risk of cancer or malignancy, with a 1% reduction in cancer risk for every additional milligram of creatine per kilogram of body mass consumed daily.[13] Moreover, in a 2006 randomized controlled trial, supplementation with creatine in people with colorectal cancer who were undergoing chemotherapy had no effect on muscle mass, muscle function, or quality of life, but improved biomarkers of nutritional status in a subsample of participants that were undergoing less aggressive chemotherapy.[14]
Overall, the available evidence from in vitro and animal studies suggests that creatine may suppress primary tumor growth, but promote invasion and metastasis of some types of tumor, with limited research in humans linking dietary creatine to a lower risk of cancer as well as to some minor protective effects in people undergoing mild chemotherapy for colorectal cancer.
References
- ^Zhang L, Bu PThe two sides of creatine in cancer.Trends Cell Biol.(2022-May)
- ^Kornacker M, Schlattner U, Wallimann T, Verneris MR, Negrin RS, Kornacker B, Staratschek-Jox A, Diehl V, Wolf JHodgkin disease-derived cell lines expressing ubiquitous mitochondrial creatine kinase show growth inhibition by cyclocreatine treatment independent of apoptosis.Int J Cancer.(2001-Nov)
- ^Schimmel L, Khandekar VS, Martin KJ, Riera T, Honan C, Shaw DG, Kaddurah-Daouk RThe synthetic phosphagen cyclocreatine phosphate inhibits the growth of a broad spectrum of solid tumors.Anticancer Res.(1996)
- ^Lillie JW, O'Keefe M, Valinski H, Hamlin HA, Varban ML, Kaddurah-Daouk RCyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors.Cancer Res.(1993-Jul-01)
- ^Kristensen CA, Askenasy N, Jain RK, Koretsky APCreatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies.Br J Cancer.(1999-Jan)
- ^Miller EE, Evans AE, Cohn MInhibition of rate of tumor growth by creatine and cyclocreatine.Proc Natl Acad Sci U S A.(1993-Apr-15)
- ^Campos-Ferraz PL, Gualano B, das Neves W, Andrade IT, Hangai I, Pereira RT, Bezerra RN, Deminice R, Seelaender M, Lancha AHExploratory studies of the potential anti-cancer effects of creatine.Amino Acids.(2016-Aug)
- ^Patra S, Ghosh A, Roy SS, Bera S, Das M, Talukdar D, Ray S, Wallimann T, Ray MA short review on creatine-creatine kinase system in relation to cancer and some experimental results on creatine as adjuvant in cancer therapy.Amino Acids.(2012-Jun)
- ^Di Biase S, Ma X, Wang X, Yu J, Wang YC, Smith DJ, Zhou Y, Li Z, Kim YJ, Clarke N, To A, Yang LCreatine uptake regulates CD8 T cell antitumor immunity.J Exp Med.(2019-Dec-02)
- ^Zhang L, Zhu Z, Yan H, Wang W, Wu Z, Zhang F, Zhang Q, Shi G, Du J, Cai H, Zhang X, Hsu D, Gao P, Piao HL, Chen G, Bu PCreatine promotes cancer metastasis through activation of Smad2/3.Cell Metab.(2021-Jun-01)
- ^Papalazarou V, Zhang T, Paul NR, Juin A, Cantini M, Maddocks ODK, Salmeron-Sanchez M, Machesky LMThe creatine-phosphagen system is mechanoresponsive in pancreatic adenocarcinoma and fuels invasion and metastasis.Nat Metab.(2020-Jan)
- ^Loo JM, Scherl A, Nguyen A, Man FY, Weinberg E, Zeng Z, Saltz L, Paty PB, Tavazoie SFExtracellular metabolic energetics can promote cancer progression.Cell.(2015-Jan-29)
- ^Ostojic SM, Grasaas E, Cvejic JDietary creatine and cancer risk in the U.S. population: NHANES 2017–2020Journal of Functional Foods.(2023 Sep)
- ^Norman K, Stübler D, Baier P, Schütz T, Ocran K, Holm E, Lochs H, Pirlich MEffects of creatine supplementation on nutritional status, muscle function and quality of life in patients with colorectal cancer--a double blind randomised controlled trialClin Nutr.(2006 Aug)