-regulatory hormone, hepcidin. This hormone regulates iron metabolism by internalizing ferroportin ( Nemeth et al., 2004b ), which impedes the absorption of iron from the gut and recycling of iron by macrophages. Hepcidin activity can be directly upregulated by the inflammatory cytokine interleukin-6 (IL-6; Nemeth
Alannah K.A. McKay, Peter Peeling, David B. Pyne, Nicolin Tee, Marijke Welveart, Ida A. Heikura, Avish P. Sharma, Jamie Whitfield, Megan L. Ross, Rachel P.L. van Swelm, Coby M. Laarakkers, and Louise M. Burke
Alannah K. A. McKay, Ida A. Heikura, Louise M. Burke, Peter Peeling, David B. Pyne, Rachel P.L. van Swelm, Coby M. Laarakkers, and Gregory R. Cox
concentrations of the inflammatory cytokine interleukin-6 (IL-6) ( Hennigar et al., 2017 ), which may have downstream implications for the iron-regulatory hormone hepcidin ( Badenhorst et al., 2015 ). Adherence to a low-CHO diet (3 g/kg) for 24 hr can amplify the immediate postexercise IL-6 and the 3-hr
Claire E. Badenhorst, Katherine E. Black, and Wendy J. O’Brien
in isolation to diagnose LEA and that support from a biological marker may be beneficial in monitoring and detecting early changes to EA at an individual level ( Burke et al., 2018c ). One such potential marker is hepcidin, a 25 amino acid peptide hormone commonly recognized as the primary regulator
Mia K. Newlin, Sara Williams, Tim McNamara, Harold Tjalsma, Dorine W. Swinkels, and Emily M. Haymes
To investigate the effects of acute exercise on serum hepcidin and iron (sFe) in active women. Changes in interleukin-6 (IL-6), hepcidin, ferritin, and sFe in response to 2 different exercise durations were compared.
Twelve women age 19–32 yr performed 2 treadmill runs (60 and 120 min) at 65% of VO2max. Blood samples were obtained before, immediately after, and 3, 6, 9, and 24 hr after exercise. Two-way repeatedmeasures ANOVA was conducted to examine changes in measured variables. Significance was accepted at p < .05.
Significant effects for trial were observed for hepcidin (60 min: 1.15 ± 0.48 nmol/L; 120 min: 2.28 ± 1.44 nmol/L) and for time, with hepcidin significantly increased 3 hr postexercise in both trials (60 min: 3 hr – 1.99 ± 2.00 nmol/L; 120 min: 3 hr – 4.60 ± 4.61 nmol/L). Significant main effects for time occurred for sFe, ferritin, and IL-6. sFe was significantly decreased 9 hr postexercise compared with 3 and 24 hr postexercise. IL-6 was significantly increased immediately postexercise.
Both runs resulted in significant increases in hepcidin 3 hr after exercise. Increases in hepcidin were preceded by significant increases in IL-6 immediately postexercise and followed by significant decreases in sFe 9 hr postexercise. It was concluded that endurance exercise increases the production of hepcidin, which affects sFe. The 2-hr exercise bout stimulated greater changes in serum hepcidin than the 1-hr bout.
Xiaoya Ma, Kaitlyn J. Patterson, Kayla M. Gieschen, and Peter F. Bodary
The prevalence of iron deficiency tends to be higher in athletic populations, especially among endurancetrained females. Recent studies have provided evidence that the iron-regulating hormone hepcidin is transiently increased with acute exercise and suggest that this may contribute to iron deficiency anemia in athletes. The purpose of this study was to determine whether resting serum hepcidin is significantly elevated in highly trained female distance runners compared with a low exercise control group. Due to the importance of the monocyte in the process of iron recycling, monocyte expression of hepcidin was also measured. A single fasted blood sample was collected midseason from twenty female distance runners averaging 81.9 ± 14.2 km of running per week. Ten age-, gender-, and BMI-matched low-exercise control subjects provided samples during the same period using identical collection procedures. There was no difference between the runners (RUN) and control subjects (CON) for serum hepcidin levels (p = .159). In addition, monocyte hepcidin gene expression was not different between the two groups (p = .635). Furthermore, no relationship between weekly training volume and serum hepcidin concentration was evident among the trained runners. The results suggest that hepcidin is not chronically elevated with sustained training in competitive collegiate runners. This is an important finding because the current clinical conditions that link hepcidin to anemia include a sustained elevation in serum hepcidin. Nevertheless, additional studies are needed to determine the clinical relevance of the well-documented, transient rise in hepcidin that follows acute sessions of exercise.
Peter Peeling, Brian Dawson, Carmel Goodman, Grant Landers, Erwin T. Wiegerinck, Dorine W. Swinkels, and Debbie Trinder
Urinary hepcidin, inflammation, and iron metabolism were examined during the 24 hr after exercise. Eight moderately trained athletes (6 men, 2 women) completed a 60-min running trial (15-min warm-up at 75–80% HRpeak + 45 min at 85–90% HRpeak) and a 60-min trial of seated rest in a randomized, crossover design. Venous blood and urine samples were collected pretrial, immediately posttrial, and at 3, 6, and 24 hr posttrial. Samples were analyzed for interleukin-6 (IL-6), C-reactive protein (CRP), serum iron, serum ferritin, and urinary hepcidin. The immediate postrun levels of IL-6 and 24-hr postrun levels of CRP were significantly increased from baseline (6.9 and 2.6 times greater, respectively) and when compared with the rest trial (p ≤ .05). Hepcidin levels in the run trial after 3, 6, and 24 hr of recovery were significantly greater (1.7–3.1 times) than the pre- and immediate postrun levels (p ≤ .05). This outcome was consistent in all participants, despite marked variation in the magnitude of rise. In addition, the 3-hr postrun levels of hepcidin were significantly greater than at 3 hr in the rest trial (3.0 times greater, p ≤ .05). Hepcidin levels continued to increase at 6 hr postrun but failed to significantly differ from the rest trial (p = .071), possibly because of diurnal influence. Finally, serum iron levels were significantly increased immediately postrun (1.3 times, p ≤ .05). The authors concluded that high-intensity exercise was responsible for a significant increase in hepcidin levels subsequent to a significant increase in IL-6 and serum iron.
Yu-Qian Liu, Yan-Zhong Chang, Bin Zhao, Hai-Tao Wang, and Xiang-Lin Duan
Some athletes are diagnosed as suffering from sports anemia because of iron deficiency, but the regulatory mechanism remains poorly understood. It is reported that hepcidin may provide a way to illuminate the regulatory mechanism of exercise-associated anemia. Here the authors investigate the hepcidin-involved iron absorption in exercise-associated anemia. Twelve male Wistar rats (300 ± 10 g) were randomly divided into 2 groups, 6 in a control group (CG) and 6 in an exercise group (EG, 5 wk treadmill exercise of different intensities with progressive loading). Serum samples were analyzed for circulating levels of IL-6 by means of enzyme-linked immunosorbent assay (ELISA). The expression of hepatic hepcidin mRNA was examined by real-time polymerase chain reaction analysis. The protein levels of divalent metal transporter 1 (DMT1), ferroportin1 (FPN1), and heme-carrier protein 1 (HCP1) of duodenum epithelium were examined by Western blot. The results showed that the amount of iron and ferritin in serum were lower in EG than in CG (p < .05). The levels of IL-6 and white blood cells were greater in EG than in CG (p < .01). The expression of DMT1, HCP1, and FPN1 was significantly lower in EG than in CG (p < .01). The mRNA expressions of hepatic hepcidin and hemojuvelin in skeletal muscle were remarkably higher in EG than in CG. The data indicated that inflammation was induced by strenuous exercise, and as a result, the transcriptional level of the hepatic hepcidin gene was increased, which further inhibited the expression of iron-absorption proteins and led to exercise-associated anemia.
Marc Sim, Brian Dawson, Grant Landers, Debbie Trinder, and Peter Peeling
The trace element iron plays a number of crucial physiological roles within the body. Despite its importance, iron deficiency remains a common problem among athletes. As an individual’s iron stores become depleted, it can affect their well-being and athletic capacity. Recently, altered iron metabolism in athletes has been attributed to postexercise increases in the iron regulatory hormone hepcidin, which has been reported to be upregulated by exercise-induced increases in the inflammatory cytokine interleukin-6. As such, when hepcidin levels are elevated, iron absorption and recycling may be compromised. To date, however, most studies have explored the acute postexercise hepcidin response, with limited research seeking to minimize/attenuate these increases. This review summarizes the current knowledge regarding the postexercise hepcidin response under a variety of exercise scenarios and highlights potential areas for future research—such as: a) the use of hormones though the female oral contraceptive pill to manipulate the postexercise hepcidin response, b) comparing the use of different exercise modes (e.g., cycling vs. running) on hepcidin regulation.
Marc Sim, Brian Dawson, Grant Landers, Dorine W. Swinkels, Harold Tjalsma, Debbie Trinder, and Peter Peeling
The effect of exercise modality and intensity on Interleukin-6 (IL-6), iron status, and hepcidin levels was investigated. Ten trained male triathletes performed 4 exercise trials including low-intensity continuous running (L-R), low-intensity continuous cycling (L-C), high-intensity interval running (H-R), and high-intensity interval cycling (H-C). Both L-R and L-C consisted of 40 min continuous exercise performed at 65% of peak running velocity (vVO2peak) and cycling power output (pVO2peak), while H-R and H-C consisted of 8 × 3-min intervals performed at 85% vVO2peak and pVO2peak. Venous blood samples were drawn pre-, post-, and 3 hr postexercise. Significant increases in postexercise IL-6 were seen within each trial (p < .05) and were significantly greater in H-R than L-R (p < .05). Hepcidin levels were significantly elevated at 3 hr postexercise within each trial (p < .05). Serum iron levels were significantly elevated (p < .05) immediately postexercise in all trials except L-C. These results suggest that, regardless of exercise mode or intensity, postexercise increases in IL-6 may be expected, likely influencing a subsequent elevation in hepcidin. Regardless, the lack of change in postexercise serum iron levels in L-C may indicate that reduced hemolysis occurs during weight-supported, low-intensity activity.
Irena Auersperger, Bojan Knap, Ales Jerin, Rok Blagus, Mitja Lainscak, Milan Skitek, and Branko Skof
Exercise-associated iron deficiency is a common disorder in endurance athletes. The authors investigated the effects of long-term endurance exercise on hepcidin concentrations, inflammatory parameters, and iron status in moderately trained female long-distance runners. Eighteen runners were assigned to either an interval- or a continuous-training exercise group. The physical training consisted of two 3-week progressive overload periods, each followed by a week’s recovery, and concluded with a 10- or 21-km competitive run. Samples were taken 6 times during the 8-wk training program, first at baseline (BPre), then after the first and second 3-wk training loads (TPost1, TPost2), after each recovery week (Recovery1 and Recovery2), and poststudy (BPost). Soluble transferrin receptor (sTfR) concentrations were increased in Recovery2 and BPost compared with BPre (p = .02), hemoglobin decreased in TPost1 and TPost2 (p < .001), and red blood cells decreased in TPost2 (p = .01). Hepcidin decreased with time in TPost1 and in BPost compared with BPre (p < .001) and increased in TPost2 compared with TPost1 (p < .001). No differences over time were found for high-sensitivity C-reactive protein. The main findings of the current study indicate that serum hepcidin and sTfR were affected after 8 weeks of endurance running in women. No positive relation was found with inflammation.