Bioscience of Microbiota, Food and Health
Online ISSN : 2186-3342
ISSN-L : 2186-3342
Full Paper
Creatine supplementation enhances immunological function of neutrophils by increasing cellular adenosine triphosphate
Suguru SAITODuo-Yao CAOAlato OKUNOXiaomo LIZhenzi PENGMusin KELELNoriko M TSUJI
Author information
Supplementary material

2022 Volume 41 Issue 4 Pages 185-194


Creatine is an organic compound which is utilized in biological activities, especially for adenosine triphosphate (ATP) production in the phosphocreatine system. This is a well-known biochemical reaction that is generally recognized as being mainly driven in specific parts of the body, such as the skeletal muscle and brain. However, our report shows a novel aspect of creatine utilization and ATP synthesis in innate immune cells. Creatine supplementation enhanced immune responses in neutrophils, such as cytokine production, reactive oxygen species (ROS) production, phagocytosis, and NETosis, which were characterized as antibacterial activities. This creatine-induced functional upregulation of neutrophils provided a protective effect in a murine bacterial sepsis model. The mortality rate in mice challenged with Escherichia coli K-12 was decreased by creatine supplementation compared with the control treatment. Corresponding to this decrease in mortality, we found that creatine supplementation decreased blood pro-inflammatory cytokine levels and bacterial colonization in organs. Creatine supplementation significantly increased the cellular ATP level in neutrophils compared with the control treatment. This ATP increase was due to the phosphocreatine system in the creatine-treated neutrophils. In addition, extracellular creatine was used in this ATP synthesis, as inhibition of creatine uptake abolished the increase in ATP in the creatine-treated neutrophils. Thus, creatine is an effective nutrient for modifying the immunological function of neutrophils, which contributes to enhancement of antibacterial immunity.

Content from these authors
© 2022 by BMFH Press

This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license.
Previous article Next article