Iron deficiency of Sports Nutrition
Main Article Content
Abstract
Anemia resulting from iron deficiency is recognized as one of the most prevalent forms of malnutrition on a global scale. Iron is an essential metal that plays a key role in various biological processes, including the formation of hemoglobin, deoxyribonucleic acid synthesis, and mitochondrial respiration. However, mounting evidence indicates that excess iron in the body can generate reactive oxygen species (ROS), which have been demonstrated to inflict harm on cells, tissues, and organs, resulting in deleterious effects. Consequently, merely augmenting iron intake does not invariably result in enhanced well-being. Therefore, it is imperative to maintain iron concentrations within a precise physiological range. In recent years, the relationship between hepcidin, which regulates iron content in the body, and inflammation, particularly the inflammatory cytokine interleukin-6, has become the focus of significant research. However, a significant proportion of athletes manifest symptoms consistent with chronic inflammation rather than episodic inflammation. This paper provides a comprehensive overview of iron deficiency and iron deficiency anemia in athletes and identifies research directions that may lead to new therapeutic possibilities.
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How to Cite
TAKAHASHI, Ryunosuke; FUJII, Takako.
Iron deficiency of Sports Nutrition.
Medical Research Archives, [S.l.], v. 13, n. 10, oct. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7039>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i10.7039.
Section
Review 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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3. Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nat Rev Immunol. 2015;15(8): 500-510. doi:10.1038/nri3863
4. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46(7): 678-684. doi:10.1038/ng.2996
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6. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93(4):1721-1741. doi:10.1152/physrev.00008.2013
7. Brune M, Magnusson B, Persson H, Hallberg L. Iron losses in sweat. Am J Clin Nutr. 1986;43(3):438-443. doi:10.1093/ajcn/43.3.438
8. Scrimshaw NS. Functional consequences of iron deficiency in human populations. J Nutr Sci Vitaminol (Tokyo). 1984;30(1):47-63. doi:10.3177/jnsv.30.47
9. Scrimshaw NS. Functional consequences of iron deficiency in human populations. J Nutr Sci Vitaminol (Tokyo). 1984;30(1):47-63. doi:10.3177/jnsv.30.47
10. 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
11. 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
12. 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.19.6.583
13. 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
14. Sawada T, Konomi A, Yokoi K. Erratum to: Iron Deficiency Without Anemia Is Associated with Anger and Fatigue in Young Japanese Women. Biol Trace Elem Res. 2015;168(2):520-521. doi:10.1007/s12011-015-0531-0
15. 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
16. WHO. Prevalence of anemia in women of reproductive age (aged 15–49) (%). Retrieved from: https://www.who.int/data/gho/data/indicators/indicator
17. Stewart JG, Ahlquist DA, McGill DB, Ilstrup DM, Schwartz S, Owen RA. Gastrointestinal blood loss and anemia in runners. Ann Intern Med. 1984;100(6):843-845. doi:10.7326/0003-4819-100-6-843
18. Tobin BW, Beard JL. Interactions of iron deficiency and exercise training in male Sprague-Dawley rats: ferrokinetics and hematology. J Nutr. 1989;119(9): 1340-1347. doi:10.1093/jn/119.9.1340
19. Ehn L, Carlmark B, Höglund S. Iron status in athletes involved in intense physical activity. Med Sci Sports Exerc. 1980;12(1):61-64.
20. Sacks D, Baxter B, Campbell BCV, et al. Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke: From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World Stroke Organization (WSO). J Vasc Interv Radiol. 2018;29(4):441-453. doi:10.1016/j.jvir.2017.11.026
21. Iancu TC. Ferritin and hemosiderin in pathological tissues. Electron Microsc Rev. 1992;5(2):209-229. doi:10.1016/0892-0354(92)90011-e
22. Galetti V, Stoffel NU, Sieber C, Zeder C, Moretti D, Zimmermann MB. Threshold ferritin and hepcidin concentrations indicating early iron deficiency in young women based on upregulation of iron absorption. EClinicalMedicine. 2021;39:101052. Published 2021 Jul 31. doi:10.1016/j.eclinm.2021.101052
23. Nachtigall D, Nielsen P, Fischer R, Engelhardt R, Gabbe EE. Iron deficiency in distance runners. A reinvestigation using Fe-labelling and non-invasive liver iron quantification. Int J Sports Med. 1996;17(7): 473-479. doi:10.1055/s-2007-972881
24. Reinke S, Taylor WR, Duda GN, et al. Absolute and functional iron deficiency in professional athletes during training and recovery. Int J Cardiol. 2012;156(2):186-191. doi:10.1016/j.ijcard.2010.10.139
25. Hinton PS. Iron and the endurance athlete. Appl Physiol Nutr Metab. 2014;39(9):1012-1018. doi:10.1139/apnm-2014-0147
26. Mielgo-Ayuso J, Zourdos MC, Calleja-González J, Córdova A, Fernandez-Lázaro D, Caballero-García A. Eleven Weeks of Iron Supplementation Does Not Maintain Iron Status for an Entire Competitive Season in Elite Female Volleyball Players: A Follow-Up Study. Nutrients. 2018;10(10):1526. Published 2018 Oct 17. doi:10.3390/nu10101526
27. Matsuo, T.S., H. Suzuki, M., Dubbell exercise improves non-anemic iron deficiency in young women without iron supplementation. Journal of nutritional science and vitaminology 2002. 48(2): p. 161–164.
28. 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
29. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276(11):7806-7810. doi:10.1074/jbc.M008922200
30. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090-2093. doi:10.1126/science.1104742
31. Ganz T. Iron homeostasis: fitting the puzzle pieces together. Cell Metab. 2008;7(4):288-290. doi:10.1016/j.cmet.2008.03.008
32. McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009;12(4):444-454. doi:10.1017/S1368980008002401
33. Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287(2):153-170. doi:10.1111/joim.13004
34. Paul BT, Manz DH, Torti FM, Torti SV. Mitochondria and Iron: current questions. Expert Rev Hematol. 2017;10(1):65-79. doi:10.1080/17474086.2016.1268047
35. Merler E. L'incidenza del mesotelioma diminuisce parallelamente alla diminuzione o interruzione dell'esposizione ad amianto: una conferma della relazione dose-risposta, non priva di implicazioni preventive [Mesothelioma incidence decreases parallel to asbestos exposure decrement or interruption: a confirmation of a dose-response relationship, with implications in public health]. Epidemiol Prev. 2007;31(4 Suppl 1):46-52.
36. Lakhal-Littleton S, Wolna M, Chung YJ, et al. An essential cell-autonomous role for hepcidin in cardiac iron homeostasis. Elife. 2016;5:e19804. Published 2016 Nov 29. doi:10.7554/eLife.19804
37. Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117(17):4425-4433. doi:10.1182/blood-2011-01-258467
38. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113(9):1271-1276. doi:10.1172/JCI20945
39. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38(5):531-539. doi:10.1038/ng1777
40. Corradini E, Babitt JL, Lin HY. The RGM/DRAGON family of BMP co-receptors. Cytokine Growth Factor Rev. 2009;20(5-6):389-398. doi:10.1016/j.cytogfr.2009.10.008
41. Andriopoulos B Jr, Corradini E, Xia Y, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet. 2009;41(4):482-487. doi:10.1038/ng.335
42. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet. 2009;41(4):478-481. doi:10.1038/ng.320
43. Monnier PP, Sierra A, Macchi P, et al. RGM is a repulsive guidance molecule for retinal axons. Nature. 2002;419(6905):392-395. doi:10.1038/nature01041
44. Hata K, Fujitani M, Yasuda Y, et al. RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J Cell Biol. 2006;173(1):47-58. doi:10.1083/jcb.200508143
45. Samad TA, Srinivasan A, Karchewski LA, et al. DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J Neurosci. 2004;24(8):2027-2036. doi:10.1523/JNEUROSCI.4115-03.2004
46. Fujii, T. Kobayashi, K. Kaneko, M. Osana, S. Tsai, CT. Ito, S. Hata, K. RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease. Immuno, 2024. 4(3): p. 266–285. https://doi.org/10.3390/immuno4030017
2. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell. 2010;142(1):24-38. doi:10.1016/j.cell.2010.06.028
3. Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nat Rev Immunol. 2015;15(8): 500-510. doi:10.1038/nri3863
4. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46(7): 678-684. doi:10.1038/ng.2996
5. Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J. Body iron metabolism and pathophysiology of iron overload. Int J Hematol. 2008;88(1):7-15. doi:10. 1007/s12185-008-0120-5
6. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93(4):1721-1741. doi:10.1152/physrev.00008.2013
7. Brune M, Magnusson B, Persson H, Hallberg L. Iron losses in sweat. Am J Clin Nutr. 1986;43(3):438-443. doi:10.1093/ajcn/43.3.438
8. Scrimshaw NS. Functional consequences of iron deficiency in human populations. J Nutr Sci Vitaminol (Tokyo). 1984;30(1):47-63. doi:10.3177/jnsv.30.47
9. Scrimshaw NS. Functional consequences of iron deficiency in human populations. J Nutr Sci Vitaminol (Tokyo). 1984;30(1):47-63. doi:10.3177/jnsv.30.47
10. 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
11. 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
12. 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.19.6.583
13. 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
14. Sawada T, Konomi A, Yokoi K. Erratum to: Iron Deficiency Without Anemia Is Associated with Anger and Fatigue in Young Japanese Women. Biol Trace Elem Res. 2015;168(2):520-521. doi:10.1007/s12011-015-0531-0
15. 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
16. WHO. Prevalence of anemia in women of reproductive age (aged 15–49) (%). Retrieved from: https://www.who.int/data/gho/data/indicators/indicator
17. Stewart JG, Ahlquist DA, McGill DB, Ilstrup DM, Schwartz S, Owen RA. Gastrointestinal blood loss and anemia in runners. Ann Intern Med. 1984;100(6):843-845. doi:10.7326/0003-4819-100-6-843
18. Tobin BW, Beard JL. Interactions of iron deficiency and exercise training in male Sprague-Dawley rats: ferrokinetics and hematology. J Nutr. 1989;119(9): 1340-1347. doi:10.1093/jn/119.9.1340
19. Ehn L, Carlmark B, Höglund S. Iron status in athletes involved in intense physical activity. Med Sci Sports Exerc. 1980;12(1):61-64.
20. Sacks D, Baxter B, Campbell BCV, et al. Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke: From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World Stroke Organization (WSO). J Vasc Interv Radiol. 2018;29(4):441-453. doi:10.1016/j.jvir.2017.11.026
21. Iancu TC. Ferritin and hemosiderin in pathological tissues. Electron Microsc Rev. 1992;5(2):209-229. doi:10.1016/0892-0354(92)90011-e
22. Galetti V, Stoffel NU, Sieber C, Zeder C, Moretti D, Zimmermann MB. Threshold ferritin and hepcidin concentrations indicating early iron deficiency in young women based on upregulation of iron absorption. EClinicalMedicine. 2021;39:101052. Published 2021 Jul 31. doi:10.1016/j.eclinm.2021.101052
23. Nachtigall D, Nielsen P, Fischer R, Engelhardt R, Gabbe EE. Iron deficiency in distance runners. A reinvestigation using Fe-labelling and non-invasive liver iron quantification. Int J Sports Med. 1996;17(7): 473-479. doi:10.1055/s-2007-972881
24. Reinke S, Taylor WR, Duda GN, et al. Absolute and functional iron deficiency in professional athletes during training and recovery. Int J Cardiol. 2012;156(2):186-191. doi:10.1016/j.ijcard.2010.10.139
25. Hinton PS. Iron and the endurance athlete. Appl Physiol Nutr Metab. 2014;39(9):1012-1018. doi:10.1139/apnm-2014-0147
26. Mielgo-Ayuso J, Zourdos MC, Calleja-González J, Córdova A, Fernandez-Lázaro D, Caballero-García A. Eleven Weeks of Iron Supplementation Does Not Maintain Iron Status for an Entire Competitive Season in Elite Female Volleyball Players: A Follow-Up Study. Nutrients. 2018;10(10):1526. Published 2018 Oct 17. doi:10.3390/nu10101526
27. Matsuo, T.S., H. Suzuki, M., Dubbell exercise improves non-anemic iron deficiency in young women without iron supplementation. Journal of nutritional science and vitaminology 2002. 48(2): p. 161–164.
28. 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
29. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276(11):7806-7810. doi:10.1074/jbc.M008922200
30. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090-2093. doi:10.1126/science.1104742
31. Ganz T. Iron homeostasis: fitting the puzzle pieces together. Cell Metab. 2008;7(4):288-290. doi:10.1016/j.cmet.2008.03.008
32. McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009;12(4):444-454. doi:10.1017/S1368980008002401
33. Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287(2):153-170. doi:10.1111/joim.13004
34. Paul BT, Manz DH, Torti FM, Torti SV. Mitochondria and Iron: current questions. Expert Rev Hematol. 2017;10(1):65-79. doi:10.1080/17474086.2016.1268047
35. Merler E. L'incidenza del mesotelioma diminuisce parallelamente alla diminuzione o interruzione dell'esposizione ad amianto: una conferma della relazione dose-risposta, non priva di implicazioni preventive [Mesothelioma incidence decreases parallel to asbestos exposure decrement or interruption: a confirmation of a dose-response relationship, with implications in public health]. Epidemiol Prev. 2007;31(4 Suppl 1):46-52.
36. Lakhal-Littleton S, Wolna M, Chung YJ, et al. An essential cell-autonomous role for hepcidin in cardiac iron homeostasis. Elife. 2016;5:e19804. Published 2016 Nov 29. doi:10.7554/eLife.19804
37. Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117(17):4425-4433. doi:10.1182/blood-2011-01-258467
38. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113(9):1271-1276. doi:10.1172/JCI20945
39. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38(5):531-539. doi:10.1038/ng1777
40. Corradini E, Babitt JL, Lin HY. The RGM/DRAGON family of BMP co-receptors. Cytokine Growth Factor Rev. 2009;20(5-6):389-398. doi:10.1016/j.cytogfr.2009.10.008
41. Andriopoulos B Jr, Corradini E, Xia Y, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet. 2009;41(4):482-487. doi:10.1038/ng.335
42. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet. 2009;41(4):478-481. doi:10.1038/ng.320
43. Monnier PP, Sierra A, Macchi P, et al. RGM is a repulsive guidance molecule for retinal axons. Nature. 2002;419(6905):392-395. doi:10.1038/nature01041
44. Hata K, Fujitani M, Yasuda Y, et al. RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J Cell Biol. 2006;173(1):47-58. doi:10.1083/jcb.200508143
45. Samad TA, Srinivasan A, Karchewski LA, et al. DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J Neurosci. 2004;24(8):2027-2036. doi:10.1523/JNEUROSCI.4115-03.2004
46. Fujii, T. Kobayashi, K. Kaneko, M. Osana, S. Tsai, CT. Ito, S. Hata, K. RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease. Immuno, 2024. 4(3): p. 266–285. https://doi.org/10.3390/immuno4030017