Association of Serum Hepcidin Levels with Aerobic and Resistance Exercise: A Systematic Review

Abstract

Background: Prevalence of iron deficiency is commonly reported among athletic population groups. It impairs physical performance due to insufficient oxygen delivery to target organs and low energy production. This is due to the high demand of exercise on oxygen delivery for systemic metabolism by the erythrocytes in the blood. Hepcidin, the key regulator of iron homeostasis, decreases to facilitate iron efflux into the circulation during enhanced erythropoiesis. However, acute anaemia of exercise is caused by increased hepcidin expression that is induced by stress and inflammatory signal. The study aimed to systematically review changes in serum hepcidin levels during resistance and aerobic exercise programmes. Methods: A systemic literature search from 2010 to April 2020 across seven databases comprised of Cochrane library, PubMed, Web of Science, Scopus, Embase, MEDLINE, and OpenGrey. The primary outcome was increased or decreased serum hepcidin from baseline after the exercise activity. Risks of bias were evaluated by using the National Institutes of Health (NIH) for quality assessment of before and after different exercise programmes. Results: Overall, twenty-three studies met the inclusion criteria. Out of the 23 studies, 16 studies reported significantly exercise-induced serum hepcidin elevation. Of the 17 studies that evaluated serum interleukin (IL)-6 levels, 14 studies showed significant exercise-induced serum IL-6 elevation. Changes in exercise-induced serum hepcidin and IL-6 levels were similar in both resistance and endurance exercise. Significant correlations were observed between post-exercise hepcidin and baseline ferritin levels (r = 0.69, p < 0.05) and between post-exercise hepcidin and post-exercise IL-6 (r = 0.625, p < 0.05). Conclusion: Resistance and endurance training showed significant increase in serum hepcidin and IL-6 levels in response to exercise. Baseline ferritin and post-exercise IL-6 elevation are key determining factors in the augmentation of hepcidin response to exercise.

Anemia in Sports: A Narrative Review

“…Iron deficiency is associated with an alteration of the transport and delivery of oxygen to the tissues, and therefore may affect athletic performance. Iron is also involved in energy metabolism within the electron transport chain, DNA synthesis, oxidative phosphorylation in mitochondria, and ATP production [ 17 , 18 ]. Iron deficiency affects up to 52% of female adolescent athletes [ 6 ] and 30–50% of athletes participating in endurance sports [ 19 ].…”

“…The iron metabolism involves absorption from the duodenal enterocytes, usage in the erythroid precursors, and storage and reutilization in the hepatocytes and tissue macrophages ( Figure 1 ) [ 19 ]. Hepcidin is the key regulator of iron homeostasis, as its synthesis is inhibited to facilitate iron efflux in the circulation during increased erythropoiesis [ 17 ]. Hepcidin is produced in the liver and degrades the ferroportin transport channel, reducing the ability of macrophages to recycle the iron and thus iron availability [ 22 ].…”

The Hepcidin-25/Ferritin Ratio Is Increased in University Rugby Players with Lower Fat Mass

“…Recently, many researchers have attempted to find a biomarker for exercise-induced anemia, and the hepcidin level was suggested as a potential biomarker for lower energy availability [ 8 , 13 , 16 , 17 ]. It is well known that the hepcidin level is positively correlated with the ferritin level [ 13 , 14 , 15 , 16 ]. In the present study, we confirmed this relationship in male university rugby players.…”

“…However, normal hepcidin levels among athletes remain a topic of debate [ 11 , 12 ]; while one study shows that the levels are higher in athletes [ 11 ], another reports that the levels are not elevated [ 12 ]. This discrepancy is partly ascribed to the fact that lean athletes have low ferritin levels, and resting hepcidin levels are generally regulated by the ferritin level [ 13 , 14 , 15 , 16 ]; however, in some cases, the hepcidin level is independent of the ferritin level. For instance, acute exercise increases the hepcidin level without changing the ferritin level due to exercise-induced inflammation caused by elevated interleukin-6 (IL-6) levels [ 14 , 15 , 16 ].…”

“…This discrepancy is partly ascribed to the fact that lean athletes have low ferritin levels, and resting hepcidin levels are generally regulated by the ferritin level [ 13 , 14 , 15 , 16 ]; however, in some cases, the hepcidin level is independent of the ferritin level. For instance, acute exercise increases the hepcidin level without changing the ferritin level due to exercise-induced inflammation caused by elevated interleukin-6 (IL-6) levels [ 14 , 15 , 16 ]. This higher hepcidin level can remain sustained for 2–3 days while the IL-6 level is in the normal range soon after the exercise [ 16 , 17 , 18 ].…”