Long-distance trail running induces functional iron deficiency driven by inflammation

Area of Science:

• Exercise Physiology
• Nutritional Biochemistry
• Cellular Metabolism

Background:

• Iron is vital for cellular energy production, especially mitochondrial respiration.
• Functional iron deficiency can occur during inflammation, limiting iron access to tissues.
• The effects of extreme endurance exercise on systemic iron metabolism and cellular iron sensing are not well understood.

Purpose of the Study:

• To investigate systemic iron trafficking and cellular iron sensing adaptations in elite athletes after extreme endurance exercise.
• To characterize the molecular response of peripheral blood mononuclear cells (PBMCs) to exercise-induced iron dysregulation.

Main Methods:

• Analysis of serum iron markers and PBMC gene expression in seven elite athletes before and after an 86.9 km trail run.
• Measurement of inflammatory markers (interleukin-6), iron regulatory proteins (hepcidin, ferritin), and hemolysis indicators.
• Assessment of PBMC transcriptional changes related to iron uptake, storage, and hypoxia.

Main Results:

• The extreme exercise induced inflammation (increased IL-6), leading to elevated hepcidin and ferritin, and decreased serum iron and transferrin saturation.
• Evidence of intravascular hemolysis was observed.
• PBMCs showed increased expression of iron uptake and hypoxia-related genes, and decreased expression of iron storage and export genes, indicating cellular adaptation to low iron availability.

Conclusions:

• Long-distance trail running induces functional iron deficiency via inflammatory and hemolytic pathways.
• PBMC gene expression adapts to restricted iron availability by upregulating iron import and hypoxia-response genes.
• These iron homeostasis alterations during intense exercise may affect mitochondrial function and cellular metabolism.