Amino Acids

, Volume 48, Issue 8, pp 1993–2001 | Cite as

Exploratory studies of the potential anti-cancer effects of creatine

  • P. L. Campos-Ferraz
  • B. Gualano
  • W. das Neves
  • I. T. Andrade
  • I. Hangai
  • R. T. S. Pereira
  • R. N. Bezerra
  • R. Deminice
  • M. Seelaender
  • A. H. Lancha
Original Article
Part of the following topical collections:
  1. Creatine


Two experiments were performed, in which male Wistar Walker 256 tumor-bearing rats were inoculated with 4 × 107 tumor cells subcutaneously and received either creatine (300 mg/kg body weight/day; CR) or placebo (water; PL) supplementation via intragastric gavage. In experiment 1, 50 rats were given PL (n = 22) or CR (n = 22) and a non-supplemented, non-inoculated group served as control CT (n = 6), for 40 days, and the survival rate and tumor mass were assessed. In experiment 2, 25 rats were given CR or PL for 15 days and sacrificed for biochemical analysis. Again, a non-supplemented, non-inoculated group served as control (CT; n = 6). Tumor and muscle creatine kinase (CK) activity and total creatine content, acidosis, inflammatory cytokines, and antioxidant capacity were assessed. Tumor growth was significantly reduced by approximately 30 % in CR when compared with PL (p = 0.03), although the survival rate was not significantly different between CR and PL (p = 0.65). Tumor creatine content tended to be higher in CR than PL (p = 0.096). Tumor CK activity in the cytosolic fraction was higher in CR than PL (p < 0.0001). Blood pCO2 was higher in CT and CR than PL (p = 0.0007 and p = 0.004, respectively). HCO3 was augmented in CT compared to PL (p = 0.03) and CR (p = 0.001). Plasma IL-6 was lower and IL-10 level was higher in CR than PL (p = 0.03 and p = 0.0007, respectively) and TNF-alpha featured a tendency of decrease in CR compared to PL (p = 0.08). Additionally, total antioxidant capacity tended to be lower in CT than PL (p = 0.07). Creatine supplementation was able to slow tumor growth without affecting the overall survival rate, probably due to the re-establishment of the CK-creatine system in cancer cells, leading to attenuation in acidosis, inflammation, and oxidative stress. These findings support the role of creatine as a putative anti-cancer agent as well as help in expanding our knowledge on its potential mechanisms of action in malignancies.


Diet Supplementation Tumor Malignancy 



Creatine kinase


CO2 partial pressure


Interleukin 6




Interleukin 10



The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 12/02682-9;12/50079-0).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Research involving animals

Our experimental protocol has been approved by the local Ethics Committee on Research (Of. CEP/03511/EEFE/30.05.2011). This study was conducted under the standards of the Brazilian College of Animal Experimentation (COBEA).


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • P. L. Campos-Ferraz
    • 1
    • 2
  • B. Gualano
    • 1
  • W. das Neves
    • 1
  • I. T. Andrade
    • 1
    • 2
  • I. Hangai
    • 1
    • 3
  • R. T. S. Pereira
    • 1
  • R. N. Bezerra
    • 2
  • R. Deminice
    • 5
  • M. Seelaender
    • 4
    • 6
  • A. H. Lancha
    • 1
  1. 1.School of Physical Education and Sport, Department of BiodynamicsUniversity of São PauloSão PauloBrazil
  2. 2.Faculty of Applied SciencesState University of CampinasLimeiraBrazil
  3. 3.Faculty of Public HealthUniversity of Sao PauloSão PauloBrazil
  4. 4.Institute of Biomedical SciencesUniversity of Sao PauloSão PauloBrazil
  5. 5.Department of Physical EducationState University of LondrinaLondrinaBrazil
  6. 6.Faculty of MedicineUniversity of Sao PauloSão PauloBrazil

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