Effects of Exercise on Iron Transfer in the Body
Main Article Content
Abstract
Although iron is found in trace amounts in the body, it plays an important role in oxygen transport and energy metabolism. Iron is therefore very important for athletes with high oxygen requirements, especially endurance athletes. Despite its importance, many athletes are diagnosed with iron deficiency. The relationship between iron regulation and exercise has been a focus of research, as it has been suggested that athletic performance is related to iron regulation. In particular, the discovery of hepcidin, an iron-regulating hormone synthesised in the liver, has received much attention. Hepcidin is known to inhibit iron absorption from the intestinal tract and promote iron excretion, and is closely related to iron nutritional status in vivo. In addition, the inflammatory cytokine interleukin-6 (IL-6) has been found to be an inducer of hepcidin expression. Much research has been conducted on the effects of training and diet (nutrients) on iron status in athletes. However, the detailed mechanisms of exercise-induced iron deficiency in athletes remain unclear. This paper summaries the less commonly reported effects of exercise on iron movement and diet on iron status.
In particular, we will focus on the impact of exercise on iron levels in the body, and the impact of meal timing and composition on iron levels.
Keywords:
Athlete, Exercise, Iron deficiency, Sports nutrition
Article Details
How to Cite
TAKAHASHI, Ryunosuke; FUJII, Takako.
Effects of Exercise on Iron Transfer in the Body.
Medical Research Archives, [S.l.], v. 13, n. 6, june 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6673>. Date accessed: 15 july 2025.
doi: https://doi.org/10.18103/mra.v13i6.6673.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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18. McKay AKA, Pyne DB, Burke LM, Peeling P. Iron Metabolism: Interactions with Energy and Carbohydrate Availability. Nutrients. 2020;12(12): 3692. Published 2020 Nov 30. doi:10.3390/nu121 23692
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21. Statuta SM, Asif IM, Drezner JA. Relative energy deficiency in sport (RED-S). Br J Sports Med. 2017;51 (21):1570-1571. doi:10.1136/bjsports-2017-097700
22. Marzuki MIH, Mohamad MI, Chai WJ, et al. Prevalence of Relative Energy Deficiency in Sport (RED-S) among National Athletes in Malaysia. Nutrients. 2023;15(7):1697. Published 2023 Mar 30. doi:10.3390/nu15071697
23. Loucks AB. Low energy availability in the marathon and other endurance sports. Sports Med. 2007;37(4-5):348-352. doi:10.2165/00007256-200 737040-00019
24. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101(7):2461-2463. doi:10.118 2/blood-2002-10-3235
25. Steensberg A, Febbraio MA, Osada T, et al. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. J Physiol. 2001;537(Pt 2):633-639. doi:10.1111/j.1469-7793.2001.00633.x
26. Solberg A, Reikvam H. Iron Status and Physical Performance in Athletes. Life (Basel). 2023;13(10): 2007. Published 2023 Oct 2. doi:10.3390/life13102007
27. Hennigar SR, McClung JP, Hatch-McChesney A, et al. Energy deficit increases hepcidin and exacerbates declines in dietary iron absorption following strenuous physical activity: a randomized-controlled cross-over trial. Am J Clin Nutr. 2021; 113(2):359-369. doi:10.1093/ajcn/nqaa289
28. Barney DE, Ippolito JR, Berryman CE, Hennigar SR. A Prolonged Bout of Running Increases Hepcidin and Decreases Dietary Iron Absorption in Trained Female and Male Runners. J Nutr. 2022; 152(9):2039-2047. doi:10.1093/jn/nxac129
29. Gagne, C.M.; Walberg-Rankin, J.L.; Ritchey, S.J. Effects of exercise on iron status in mature female rats. Nutr. Res. 1994 14:211-219. DOI:10.1016/S0271-5317(05)80380-X.
30. Ming Qian Z, Sheng Xiao D, Kui Liao Q, Ping Ho K. Effect of different durations of exercise on transferrin-bound iron uptake by rat erythroblast. J Nutr Biochem. 2002;13(1):47-54. doi:10.1016/s0955-2863(01)00194-2
31. Sawada T, Konomi A, Yokoi K. Iron deficiency without anemia is associated with anger and fatigue in young Japanese women [published correction appears in Biol Trace Elem Res. 2015 Dec;168(2): 520-1. doi: 10.1007/s12011-015-0531-0.]. Biol Trace Elem Res. 2014;159(1-3):22-31. doi:10.1007/s12011-014-9963-1
32. Sim M, Garvican-Lewis LA, Cox GR, et al. Iron considerations for the athlete: a narrative review. Eur J Appl Physiol. 2019;119(7):1463-1478. doi:10.1007/s00421-019-04157-y
33. Fujii T, Matsuo T, Okamura K. The effects of resistance exercise and post-exercise meal timing on the iron status in iron-deficient rats. Biol Trace Elem Res. 2012;147(1-3):200-205. doi:10.1007/s1 2011-011-9285-5
34. Fujii T, Matsuo T, Okamura K. Effects of resistance exercise on iron absorption and balance in iron-deficient rats. Biol Trace Elem Res. 2014;161 (1):101-106. doi:10.1007/s12011-014-0075-8
35. Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008;8(6):502-511. doi:10.1016/j.cmet.2008.09.012
36. Fujii T, Matsuo T, Okamura K. The effects of resistance exercise and post-exercise meal timing on the iron status in iron-deficient rats. Biol Trace Elem Res. 2012;147(1-3):200-205. doi:10.1007/s12 011-011-9285-5
37. Franzone PC, Paganuzzi A, Stefanelli M. A mathematical model of iron metabolism. J Math Biol. 1982;15(2):173-201. doi:10.1007/BF00275072
38. McCormick R, Moretti D, McKay AKA, et al. The Impact of Morning versus Afternoon Exercise on Iron Absorption in Athletes. Med Sci Sports Exerc. 2019;51(10):2147-2155. doi:10.1249/MSS.0 000000000002026
2. Deldicque L, Francaux M. Recommendations for Healthy Nutrition in Female Endurance Runners: An Update. Front Nutr. 2015;2:17. Published 2015 May 26. doi:10.3389/fnut.2015.00017
3. Ganz T, Nemeth E. Iron metabolism: interactions with normal and disordered erythropoiesis. Cold Spring Harb Perspect Med. 2012;2(5):a011668. doi:10.1101/cshperspect.a011668
4. Varga E, Pap R, Jánosa G, Sipos K, Pandur E. IL-6 Regulates Hepcidin Expression Via the BMP/SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia. Neurochem Res. 2021;46(5): 1224-1238. doi:10.1007/s11064-021-03322-0
5. Beard JL, Connor JR. Iron status and neural functioning. Annu Rev Nutr. 2003;23:41-58. doi:10.1146/annurev.nutr.23.020102.075739
6. Sawada T, Konomi A, Yokoi K. Iron deficiency without anemia is associated with anger and fatigue in young Japanese women [published correction appears in Biol Trace Elem Res. 2015 Dec;168(2): 520-1. doi: 10.1007/s12011-015-0531-0.]. Biol Trace Elem Res. 2014;159(1-3):22-31. doi:10.100 7/s12011-014-9963-1
7. Sim M, Garvican-Lewis LA, Cox GR, et al. Iron considerations for the athlete: a narrative review. Eur J Appl Physiol. 2019;119(7):1463-1478. doi:10.1007/s00421-019-04157-y
8. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102(3):783-788. doi:10.1182/blood-2003-03-0672
9. Lee PL, Beutler E. Regulation of hepcidin and iron-overload disease. Annu Rev Pathol. 2009;4:489-515. doi:10.1146/annurev.pathol.4.110807.092205
10. Nemeth E, Ganz T. Hepcidin and Iron in Health and Disease. Annu Rev Med. 2023;74:261-277. doi:10.1146/annurev-med-043021-032816
11. Fujii T, Kobayashi K, Kaneko M, Hata K. RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease. Immuno 20044(3):266-285. DOI: 10.3390/immuno4030017
12. Badenhorst CE, Dawson B, Cox GR, Laarakkers CM, Swinkels DW, Peeling P. Acute dietary carbohydrate manipulation and the subsequent inflammatory and hepcidin responses to exercise. Eur J Appl Physiol. 2015;115(12):2521-2530. doi:10.1007/s00421-015-3252-3
13. Varga E, Pap R, Jánosa G, Sipos K, Pandur E. IL-6 Regulates Hepcidin Expression Via the BMP/ SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia. Neurochem Res. 2021; 46(5):1224-1238. doi:10.1007/s11064-021-03322-0
14. Peeling P, Dawson B, Goodman C, et al. Effects of exercise on hepcidin response and iron metabolism during recovery. Int J Sport Nutr Exerc Metab. 2009;19(6):583-597. doi:10.1123/ijsnem.1 9.6.583.
15. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295. Published 2014 Sep 4. doi:10.1101/cshperspect.a016295
16. Solberg A, Reikvam H. Iron Status and Physical Performance in Athletes. Life (Basel). 2023;13(10): 2007. Published 2023 Oct 2. doi:10.3390/life13102007
17. Solberg A, Reikvam H. Iron Status and Physical Performance in Athletes. Life (Basel). 2023;13(10): 2007. Published 2023 Oct 2. doi:10.3390/life131 02007
18. McKay AKA, Pyne DB, Burke LM, Peeling P. Iron Metabolism: Interactions with Energy and Carbohydrate Availability. Nutrients. 2020;12(12): 3692. Published 2020 Nov 30. doi:10.3390/nu121 23692
19. Henderson SA, Dallman PR, Brooks GA. Glucose turnover and oxidation are increased in the iron-deficient anemic rat. Am J Physiol. 1986; 250(4 Pt 1):E414-E421. doi:10.1152/ajpendo.198 6.250.4.E414
20. Hayashi N, Ishibashi A, Iwata A, Yatsutani H, Badenhorst C, Goto K. Influence of an energy deficient and low carbohydrate acute dietary manipulation on iron regulation in young females. Physiol Rep. 2022;10(13):e15351. doi:10.14814/ph y2.15351
21. Statuta SM, Asif IM, Drezner JA. Relative energy deficiency in sport (RED-S). Br J Sports Med. 2017;51 (21):1570-1571. doi:10.1136/bjsports-2017-097700
22. Marzuki MIH, Mohamad MI, Chai WJ, et al. Prevalence of Relative Energy Deficiency in Sport (RED-S) among National Athletes in Malaysia. Nutrients. 2023;15(7):1697. Published 2023 Mar 30. doi:10.3390/nu15071697
23. Loucks AB. Low energy availability in the marathon and other endurance sports. Sports Med. 2007;37(4-5):348-352. doi:10.2165/00007256-200 737040-00019
24. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101(7):2461-2463. doi:10.118 2/blood-2002-10-3235
25. Steensberg A, Febbraio MA, Osada T, et al. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. J Physiol. 2001;537(Pt 2):633-639. doi:10.1111/j.1469-7793.2001.00633.x
26. Solberg A, Reikvam H. Iron Status and Physical Performance in Athletes. Life (Basel). 2023;13(10): 2007. Published 2023 Oct 2. doi:10.3390/life13102007
27. Hennigar SR, McClung JP, Hatch-McChesney A, et al. Energy deficit increases hepcidin and exacerbates declines in dietary iron absorption following strenuous physical activity: a randomized-controlled cross-over trial. Am J Clin Nutr. 2021; 113(2):359-369. doi:10.1093/ajcn/nqaa289
28. Barney DE, Ippolito JR, Berryman CE, Hennigar SR. A Prolonged Bout of Running Increases Hepcidin and Decreases Dietary Iron Absorption in Trained Female and Male Runners. J Nutr. 2022; 152(9):2039-2047. doi:10.1093/jn/nxac129
29. Gagne, C.M.; Walberg-Rankin, J.L.; Ritchey, S.J. Effects of exercise on iron status in mature female rats. Nutr. Res. 1994 14:211-219. DOI:10.1016/S0271-5317(05)80380-X.
30. Ming Qian Z, Sheng Xiao D, Kui Liao Q, Ping Ho K. Effect of different durations of exercise on transferrin-bound iron uptake by rat erythroblast. J Nutr Biochem. 2002;13(1):47-54. doi:10.1016/s0955-2863(01)00194-2
31. Sawada T, Konomi A, Yokoi K. Iron deficiency without anemia is associated with anger and fatigue in young Japanese women [published correction appears in Biol Trace Elem Res. 2015 Dec;168(2): 520-1. doi: 10.1007/s12011-015-0531-0.]. Biol Trace Elem Res. 2014;159(1-3):22-31. doi:10.1007/s12011-014-9963-1
32. Sim M, Garvican-Lewis LA, Cox GR, et al. Iron considerations for the athlete: a narrative review. Eur J Appl Physiol. 2019;119(7):1463-1478. doi:10.1007/s00421-019-04157-y
33. Fujii T, Matsuo T, Okamura K. The effects of resistance exercise and post-exercise meal timing on the iron status in iron-deficient rats. Biol Trace Elem Res. 2012;147(1-3):200-205. doi:10.1007/s1 2011-011-9285-5
34. Fujii T, Matsuo T, Okamura K. Effects of resistance exercise on iron absorption and balance in iron-deficient rats. Biol Trace Elem Res. 2014;161 (1):101-106. doi:10.1007/s12011-014-0075-8
35. Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008;8(6):502-511. doi:10.1016/j.cmet.2008.09.012
36. Fujii T, Matsuo T, Okamura K. The effects of resistance exercise and post-exercise meal timing on the iron status in iron-deficient rats. Biol Trace Elem Res. 2012;147(1-3):200-205. doi:10.1007/s12 011-011-9285-5
37. Franzone PC, Paganuzzi A, Stefanelli M. A mathematical model of iron metabolism. J Math Biol. 1982;15(2):173-201. doi:10.1007/BF00275072
38. McCormick R, Moretti D, McKay AKA, et al. The Impact of Morning versus Afternoon Exercise on Iron Absorption in Athletes. Med Sci Sports Exerc. 2019;51(10):2147-2155. doi:10.1249/MSS.0 000000000002026