Effects of Acute Exercise on Hepcidin in Women

Purpose: The purpose of this study was to investigate whether acute exercise will affect serum hepcidin levels and iron status in active women. Additionally, two different exercise durations were compared to determine if there is a minimum duration of exercise required to induce changes in the inflammatory markers C-Reactive Protein (CRP) and Interluekin-6 (IL-6) and the iron regulatory peptide hepcidin, as well as changes in ferritin and serum iron. Methods: Twelve active women ages 19-32 participated in this study. Subjects performed an incremental treadmill test to exhaustion to determine VO2max. Subjects were then required to perform two different submaximal treadmill runs (60 minutes and 120 minutes in duration) at a pace that elicited 65% of their pre-determined VO2max. The order of the two submaximal trials was randomized and counterbalanced, and all exercise sessions were completed before noon. Blood samples were obtained immediately prior to, immediately following, and 3, 6, 9 and 24 hours following each of the submaximal runs, for the determination of hemoglobin (Hb), hematocrit (Hct), hepcidin, ferritin, serum iron, CRP and IL-6. Post-exercise measures were corrected for plasma volume shifts. A two-way repeated measures ANOVA (trials X time, 2 X 6) was conducted to examine changes in the measured variables, and differences between the trials and sampling time points. Results: No significant time X trial interactions were observed for any of the measured variables. Significant main effects for time and trial were observed for hepcidin. The mean hepcidin concentration was higher for the 120 minute trial. The results of a one-way ANOVA for each of the trials revealed a significantly increased concentration of hepcidin at 3 hours post-exercise for both trials (60 min (nmol/L): pre – 0.73 ± 0.56, post – 0.96 ± 0.69, 3h – 1.99 ± 2.00, 6h– 1.40 ± 1.20, 9h – 1.06 ± 0.75, 24h – 0.76 ± 0.52; 120 min (nmol/L): pre – 1.07 ± 0.99, post – 1.29 ± 1.00, 3h – 4.60 ± 4.61, 6h – 3.47 ± 4.11, 9h – 1.92 ± 1.74, 24h – 1.33 ± 1.61). This value was significantly different than baseline, post, and 24 hours post-exercise means, in both trials. Significant main effects for time were observed for serum iron, ferritin, CRP, IL-6, Hb and Hct. When data for the trials were combined, serum iron was significantly decreased at 9 hours post-exercise, compared to the 3 hours post- and 24 hours post-exercise concentrations. A significant increase in IL-6 was observed immediately post exercise (pre: 1.5 ± 1.92 pg/ml, post: 3.5 ± 2.40 pg/ml), and gradually decreased to return to baseline at 24 hours post-exercise. Serum ferritin concentrations were increased immediately following exercise, however this was only significantly different from the 24 hours post-exercise mean, which was slightly lower than baseline. CRP was slightly elevated following exercise with the highest levels observed 24 hours following exercise, however, these values were not significantly different from baseline. Conclusions: Both submaximal runs resulted in significant increases in serum concentrations of hepcidin three hours after exercise. The increase in hepcidin was preceded by a significant increase in IL-6 observed immediately after exercise, and was followed by a significant decrease in serum iron observed nine hours after exercise. It was concluded that participation in endurance exercise causes increases in the production of hepcidin which will subsequently influence concentrations of serum iron, via hepcidin's affects on the iron exporter ferroportin. Additionally, increases in serum ferritin following exercise may have clinical implications for the timing of blood sampling for the measurement of ferritin, as false elevations due to exercise may mask iron deficiency, especially in active women.