A Prolonged Bout of Running Increases Hepcidin and Decreases Dietary Iron Absorption in Trained Female and Male Runners

Abstract

Background: Declines in iron status are frequently reported in those who regularly engage in strenuous physical activity. A possible reason is increases in the iron regulatory hormone hepcidin, which functions to inhibit dietary iron absorption and can be induced by the inflammatory cytokine interleukin-6 (IL-6).

Objectives: The current study aimed to determine the impact of a prolonged bout of running on hepcidin and dietary iron absorption in trained female and male runners.

Methods: Trained female and male collegiate cross country runners (n = 28, age: 19.7 ± 1.2 y, maximal oxygen uptake: 66.1 ± 6.1 mL $\cdot$ kg -1$\cdot$ min-2, serum ferritin: 21.9 ± 13.3 ng/mL) performed a prolonged run (98.8 ± 14.7 min, 21.2 ± 3.8 km, 4.7 ± 0.3 min/km) during a team practice. Participants consumed a stable iron isotope with a standardized meal 2 h postrun and blood was collected 1 h later. The protocol was repeated 2 wk later except participants abstained from exercise (rest). RBCs were collected 15 d after exercise and rest to determine isotope enrichment. Differences between exercise and rest were assessed by paired t tests and Wilcoxon matched-pairs signed rank tests. Data are means ± SDs.

Results: Plasma hepcidin increased 51% after exercise (45.8 ± 34.4 ng/mL) compared with rest (30.3 ± 27.2 ng/mL, P = 0.0010). Fractional iron absorption was reduced by 36% after exercise (11.8 ± 14.6 %) compared with rest (18.5 ± 14.4 %, P = 0.025). Plasma IL-6 was greater after exercise (0.660 ± 0.354 pg/mL) than after rest (0.457 ± 0.212 pg/mL, P < 0.0001). Exploratory analyses revealed that the increase in hepcidin with exercise may be driven by a response in males but not females.

Conclusions: A prolonged bout of running increases hepcidin and decreases dietary iron absorption compared with rest in trained runners with low iron stores. The current study supports that IL-6 contributes to the increase in hepcidin with prolonged physical activity, although future studies should explore potential sex differences in the hepcidin response.This trial was registered at Clinicaltrials.gov as NCT04079322.

Keywords: dietary iron absorption; endurance athletes; hepcidin; inflammation; interleukin-6; iron deficiency; low energy availability; physical activity; trained runners.