Plasma Hepcidin Increases with Prolonged Running in Male, but Not Female, Collegiate Distance Runners with Low Iron Stores

Abstract

Objectives Hepcidin is a negative regulator of extracellular iron availability and dietary iron absorption. Previous studies have shown that hepcidin increases with prolonged endurance exercise, but not in those with low iron stores (serum ferritin <30 ng/mL). The objective of this study was to determine the plasma hepcidin response to exercise, compared to rest, in highly trained male and female collegiate distance runners. Methods In a cross-over design, healthy male (n = 14; age 20.2 ± 1.4 y; BMI 20.4 ± 1.6 kg/m2; VO2 max 69.8 ± 5.6 mL/kg/min) and female (n = 14; age 20.1 ± 1.4 y, P = 0.79; BMI 18.1 ± 1.6 kg/m2, P < 0.001; VO2 max 62.5 ± 4.2 mL/kg/min, P < 0.001) collegiate distance runners performed a bout of running (males: 109.8 ± 8.7 min, 15.0 ± 1.3 miles; females: 87.7 ± 10.4 min, P < 0.0001, 11.3 ± 1.5 miles, P < 0.0001) or no activity (rest) separated by 2 weeks. Indicators of iron status and plasma hepcidin were determined at baseline and three hours after exercise or rest. Dietary iron and total iron intake (dietary iron + iron from supplements) were determined by Food Frequency Questionnaires. Results Serum ferritin (males: 24.0 ± 15.9 ng/mL, females: 19.4 ± 9.5 ng/mL, P = 0.39) and plasma hepcidin (males: 22.3 ± 20.6 ng/mL, females: 24.6 ± 19.6 ng/mL, P = 0.77) did not differ between males and females at baseline. Baseline hemoglobin (males: 14.5 ± 0.8 g/dL, females: 13.4 ± 1.0 g/dL, P < 0.01) and hematocrit (males: 45.3 ± 2.2%, females: 42.1 ± 2.6%, P < 0.01) were greater in males compared to females. Dietary iron intake (males: 18.6 ± 6.3 mg/d, females: 17.1 ± 6.4 mg/d, P = 0.55) and total iron intake (males: 48.7 ± 32.9 mg/d, females: 64.6 ± 32.3 mg/d, P = 0.22) did not differ between males and females. Plasma hepcidin increased with exercise compared to rest in males (change from rest: 30.3 ± 42.0 ng/mL, P = 0.02) but not in females (change from rest: 0.8 ± 32.0 ng/mL, P = 0.93). Change in plasma hepcidin with exercise was correlated with sex (R = 0.380, P = 0.05) and BMI (R = 0.383, P = 0.04), but not baseline ferritin, run time, run distance, hemoglobin, hematocrit, dietary iron, or total iron intake (P > 0.05 for all). Conclusions The post-exercise hepcidin response occurs in male, but not female, collegiate distance runners with low iron stores. These findings indicate that declines in iron status in female distance runners are independent of exercise-induced hepcidin. Funding Sources Intramural funds to S.R.H.