Caffeine-Supplemented Diet Prevents Fatigue-Like Behavior in Tumor-Bearing Mice

Abstract

Caffeine is a widely consumed stimulant, known for its positive effects on physical and mental performance. These effects are potentially beneficial for ameliorating cancer-related fatigue, which affects the quality of life of patients with cancer. This study aimed to determine the anti-fatigue and antitumor effects of caffeine in tumor-bearing mice. BALB/c mice were intravenously injected with C26 colon carcinoma cells and fed with normal or 0.05% caffeine-supplemented diet. Fatigue-like behavior was assessed by running performance using a treadmill test. Lung, blood, liver, muscle, and epididymal adipose tissue samples were collected on day 13 and examined. The antitumor effect of caffeine was assessed using subcutaneous tumor-bearing mice fed with 0.05% caffeine-supplemented diet, and the tumor volume was measured. C26 tumor-bearing mice showed fatigue-like behavior associated with hypoglycemia, depleted liver glycogen and non-esterified fatty acid (NEFA) levels. C26 tumor-bearing mice fed with 0.05% caffeine-supplemented diet showed improved running performance associated with restored NEFA levels. However, exacerbated hypoglycemia and liver glycogen levels after caffeine consumption may be due to tumor-induced catabolic signals, as the tumor volume was not affected. Collectively, caffeine may exert anti-fatigue effects through enhanced lipolysis leading to restored NEFA levels, which can be used as an alternative energy source.

Authors Contribution

N.F. and A.H. designed the experiments and wrote the manuscript. E.M., and A.H. conducted some of the In Vivo studies. S.K., and T.H. provided scientific and technical advice. K.Y. has supervised the overall projects contributed on designed the protocol and story of the manuscript. All of the authors discussed the results and commented on the manuscript. All authors have critically reviewed content and approved final version submitted for publication.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by JSPS KAKENHI (grant number: 19K11800).