Combination Effect of Caffeine Intake and Thermotherapy on the Blood Levels of Human Irisin and Fibroblast Growth Factor 21 in Healthy Males

J Physiol Investig. 2025 Jul 9. doi: 10.4103/ejpi.EJPI-D-25-00003. Online ahead of print.

Abstract

Caffeine is a widely consumed psychoactive substance known to influence physiological processes such as heat generation and autonomic nervous system activity. Fibroblast growth factor 21 (FGF-21) and irisin are the biomarkers associated with thermogenesis and metabolic regulation. The study aimed to determine whether thermotherapy along with caffeine intake could increase the blood levels of FGF-21 and irisin. A total of 87 healthy male subjects were randomly divided into a control group and a caffeine intake group. For heat loading, an experiment was performed in which each subject was given a 30-min half-body bath in hot water (42°C ± 0.5°C), and their tympanic temperature (Tty), mean skin temperature (mTs), and serum FGF-21 and irisin levels were measured. Compared to the control group, the caffeine intake group showed significantly increased Tty, mTs, serum FGF-21, and irisin after thermotherapy. Especially, administration of caffeine led to a significantly amplified response in circulating FGF-21 and irisin levels, showing an additional 22.93% and 28.70% increase, respectively, compared to the control group (P < 0.001). The results suggest that as a new form of synergy, the combination of caffeine intake and thermotherapy could potentially be applied to broader clinical and physiological settings.

Keywords: Brown adipose tissue; caffeine; fibroblast growth factor 21; irisin; thermogenesis; thermotherapy.