Parenteral Iron Therapy: Examining Current Evidence for Use in Athletes

Abstract

A high prevalence of iron deficiency exists in athlete populations. Various mechanisms, including increased losses through sweat, haemolysis, haematuria, and gastrointestinal micro-ischemia; inadequate dietary intake; and transient exercise-induced increases in the regulatory hormone, hepcidin, contribute to the increased prevalence in athletes. Indeed, hepcidin has been shown to peak around 3–6 hours post-exercise, limiting iron absorption from the gut. As the practitioner’s ability to control losses is limited, the key to treatment of iron deficiency in athletes is optimal timing of dietary and oral iron supplementation around these periods of reduced gut absorption. While timing and dosing schedule strategies might be sufficient to treat iron deficiency non-anaemia, the significant lag to impact iron status is relatively long. Therefore, in iron deficiency anaemia, the use of parenteral iron has the benefit of rapid repletion of iron stores and normalisation of haemoglobin status, while bypassing the action of hepcidin at the gut. Furthermore, newer intravenous formulations can be administered as a single total dose over 15–60 min and have a similar safety profile to oral treatment. This review discusses the existing evidence for parenteral iron use in athletes and the unique context for consideration when choosing the parenteral route in this population.

Key words

iron supplement - intravenous iron - athlete - nutrient deficiency

Publication History

Received: 31 August 2023

Accepted: 13 November 2023

Accepted Manuscript online:
14 November 2023

Article published online:
22 December 2023

• References

• 1 McCormick R, Sim M, Dawson B. et al. Refining treatment strategies for iron deficient athletes. Sports Med 2020; 50: 2111-2123
• 2 Clénin G, Cordes M, Huber A. et al. Iron deficiency in sports – definition, influence on performance and therapy. Swiss Med Wkly 2015; 145: w14196
• 3 World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. 2011 Available from https://www.who.int/publications/i/item/WHO-NMH-NHD-MNM-11.1 Accessed: 10 November 2023
• 4 Peeling P, Blee T, Goodman C. et al. Effect of iron injections on aerobic-exercise performance of iron-depleted female athletes. Int J Sport Nutr Exerc Metab 2007; 17: 221-231
• 5 Galetti V, Stoffel NU, Sieber C. et al. Threshold ferritin and hepcidin concentrations indicating early iron deficiency in young women based on upregulation of iron absorption. eClin Med 2021; 39: 101052
• 6 World Health Organization. WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. 2020 Available from https://www.who.int/publications/i/item/9789240000124. Accessed: 10 November 2023
• 7 Pedlar CR, Whyte GP, Burden R. et al. A case study of an iron-deficient female Olympic 1500-m runner. Int J Sports Physiol Perform 2013; 8: 695-698
• 8 Sim M, Garvican-Lewis LA, Cox GR. et al. Iron considerations for the athlete: a narrative review. Eur J Appl Physiol 2019; 119: 1463-1478
• 9 Sims ST, Mackay K, Leabeater A. et al. High prevalence of iron deficiency exhibited in internationally competitive, non-professional female endurance athletes–a case study. Int J Environ Res Public Health 2022; 19
• 10 Sim M, Garvican-Lewis LA, Cox GR. et al. Iron considerations for the athlete: a narrative review. Eur J Appl Physiol 2019; 119: 1463-1478
• 11 Tan D, Dawson B, Peeling P. Hemolytic effects of a football-specific training session in elite female players. Int J Sports Physiol Perform 2012; 7: 271-276
• 12 Attwell C, McKay A, Sim M. et al. Timing is everything, but does it really matter? Impact of 8-weeks morning versus evening iron supplementation in ballet and contemporary dancers. Eur J Sport Sci 2023; 23: 2275-2282
• 13 Parks RB, Hetzel SJ, Brooks MA. Iron deficiency and anemia among collegiate athletes: a retrospective chart review. Med Sci Sports Exerc 2017; 49: 1711-1715
• 14 Nicotra D, Arieli R, Redlich N. et al. Iron deficiency and anemia in male and female adolescent athletes who engage in ball games. J Clin Med 2023; 12: 970
• 15 Peeling P, Dawson B, Goodman C. et al. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol 2008; 103: 381-391
• 16 Peeling P, Sim M, McKay AKA. Considerations for the consumption of vitamin and mineral supplements in athlete populations. Sports Med 2023;
• 17 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: 583-597
• 18 Barney DE, Ippolito JR, Berryman CE. et al. A prolonged bout of running increases hepcidin and decreases dietary iron absorption in trained female and male runners. J Nutr 2022; 152: 2039-2047
• 19 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: 2147-2155
• 20 McCormick R, Dreyer A, Dawson B. et al. The effectiveness of daily and alternate day oral iron supplementation in athletes with suboptimal iron status (Part 2). Int J Sport Nutr Exerc Metab 2020; 30: 191-196
• 21 McKay AKA, Anderson B, Peeling P. et al. Iron absorption in highly-trained runners: Does it matter when and where you eat your iron?. Med Sci Sports Exerc 2023; 55: 916-916
• 22 Schaap CC, Hendriks JC, Kortman GA. et al. Diurnal rhythm rather than dietary iron mediates daily hepcidin variations. Clin Chem 2013; 59: 527-535
• 23 Dawson B, Goodman C, Blee T. et al. Iron supplementation: oral tablets versus intramuscular injection. Int J Sport Nutr Exerc Metab 2006; 16: 180-186
• 24 Garvican LA, Saunders PU, Cardoso T. et al. Intravenous iron supplementation in distance runners with low or suboptimal ferritin. Med Sci Sports Exerc 2014; 46: 376-385
• 25 Pasricha SR, Tye-Din J, Muckenthaler MU. et al. Iron deficiency. Lancet 2021; 397: 233-248
• 26 Snook J, Bhala N, Beales ILP. et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut 2021; 70: 2030-2051
• 27 Auerbach M, Ballard H, Glaspy J. Clinical update: intravenous iron for anaemia. Lancet 2007; 369: 1502-1504
• 28 Fensham NC, McKay AKA, Tee N. et al. Sequential submaximal training in elite male rowers does not result in amplified increases in interleukin-6 or hepcidin. Int J Sport Nutr Exerc Metab 2022; 32: 177-185
• 29 Girelli D, Ugolini S, Busti F. et al. Modern iron replacement therapy: clinical and pathophysiological insights. Int J Hematol 2018; 107: 16-30
• 30 Nikravesh N, Borchard G, Hofmann H. et al. Factors influencing safety and efficacy of intravenous iron-carbohydrate nanomedicines: from production to clinical practice. Nanomedicine: NBM 2020; 26: 102178
• 31 Auerbach M, Gafter-Gvili A, Macdougall I. Intravenous iron: a framework for changing the management of iron deficiency. Lancet Haematol 2020; 7: e342-e350
• 32 National Blood Authority Australia. Iron product choice and dose calculation for adults (2016); Available from: https://blood.gov.au/iron-product-choice-and-dose-calculation-guide-adults Accessed: 10 November 2023
• 33 Garg M, Morrison G, Friedman A. et al. A rapid infusion protocol is safe for total dose iron polymaltose: time for change. Int Med J 2011; 41: 548-554
• 34 Newnham E, Ahmad I, Thornton A. et al. Safety of iron polymaltose given as a total dose iron infusion. Int Med J 2006; 36: 672-674
• 35 Karim S, Butler JM, Barclay ML. A 1 g dose of intravenous iron is sufficient to treat iron deficiency anaemia. Int Med J 2020; 50: 1563-1566
• 36 Wang C, Graham DJ, Kane RC. et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA 2015; 314: 2062-2068
• 37 Bannow BS. In older adults, iron dextran and ferumoxytol each had higher anaphylaxis risk at≤1 d than iron sucrose. Annals Internal Med 2022; 175: JC95
• 38 Avni T, Bieber A, Grossman A. et al. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc 2015; 90: 12-23
• 39 DeLoughery TG. Safety of oral and intravenous iron. Acta Haematol 2019; 142: 8-12
• 40 Australian Institute of Sport. Iron deficiency best practice guidelines (2022). Available from: https://www.ais.gov.au/__data/assets/pdf_file/0014/1000490/Sport-supplement-fact-sheets-Iron-v4.pdf Accessed: 10 November 2023
• 41 Blunden RW, Lloyd JV, Rudzki Z. et al. Changes in serum ferritin levels after intravenous iron. Ann Clin Biochem 1981; 18: 215-217
• 42 Garbowski MW, Bansal S, Porter JB. et al. Intravenous iron preparations transiently generate non-transferrin-bound iron from two proposed pathways. Haematologica 2021; 106: 2885-2896
• 43 Neef V, Baumgarten P, Noone S. et al. The impact of timing of intravenous iron supplementation on preoperative haemoglobin in patients scheduled for major surgery. Blood Transfus 2022; 20: 188-197
• 44 Klein AA, Chau M, Yeates JA. et al. Preoperative intravenous iron before cardiac surgery: a prospective multicentre feasibility study. Br J Anaesth 2020; 124: 243-250
• 45 Bhandal N, Russell R. Intravenous versus oral iron therapy for postpartum anaemia. BJOG 2006; 113: 1248-1252
• 46 Khalafallah AA, Hyppa A, Chuang A. et al. A prospective randomised controlled trial of a single intravenous infusion of ferric carboxymaltose vs single intravenous iron polymaltose or daily oral ferrous sulphate in the treatment of iron deficiency anaemia in pregnancy. Semin Hematol 2018; 55: 223-234
• 47 Gasche C, Berstad A, Befrits R. et al. Guidelines on the diagnosis and management of iron deficiency and anemia in. inflammatory bowel diseases. Inflam Bowel Dis 2007; 13: 1545-1553
• 48 Otto JM, Montgomery HE, Richards T. Haemoglobin concentration and mass as determinants of exercise performance and of surgical outcome. Extrem Physiol Med 2013; 2: 33
• 49 Schmidt W, Prommer N. The optimised CO-rebreathing method: a new tool to determine total haemoglobin mass routinely. Eur J Appl Physiol 2005; 95: 486-495
• 50 Burden RJ, Pollock N, Whyte GP. et al. Effect of intravenous iron on aerobic capacity and iron metabolism in elite athletes. Med Sci Sports Exerc 2015; 47: 1399-1407
• 51 Woods A, Garvican-Lewis LA, Saunders PU. et al. Four weeks of IV iron supplementation reduces perceived fatigue and mood disturbance in distance runners. PLoS One 2014; 9: e108042
• 52 Garvican LA, Lobigs L, Telford R. et al. Haemoglobin mass in an anaemic female endurance runner before and after iron supplementation. Int J Sports Physiol Perform 2011; 6: 137-140
• 53 McKay AKA, Goods PSR, Binnie MJ. et al. Examining the decay in serum ferritin following intravenous iron infusion: a retrospective cohort analysis of Olympic sport female athletes. Appl Physiol Nutr Metab 2020; 45: 1174-1177
• 54 World Anti-Doping Agency. Intravenous infusions and/or injections (2023). Available from: https://www.wada-ama.org/sites/default/files/2023-10/tue_physician_guidelines_iv_infusion_october_2023.pdf Accessed: 10 November 2023
• 55 Stellingwerff T, Peeling P, Garvican-Lewis LA. et al. Nutrition and altitude: strategies to enhance adaptation, improve performance and maintain health: a narrative review. Sports Med 2019; 49: 169-184
• 56 Garvican-Lewis LA, Vuong VL, Govus AD. et al. Intravenous iron does not augment the hemoglobin mass response to simulated hypoxia. Med Sci Sports Exerc 2018; 50: 1669-1678
• 57 World Health Organization. Anaemia (2023); Available from: https://www.who.int/health-topics/anaemia#tab=tab_1 Accessed: 10 November 2023
• 58 Tran K, McCormack S. Screening and treatment of obstetric anemia: a review of clinical effectiveness, cost-effectiveness, and guidelines. In: Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. 2019
• 59 Govindappagari S, Burwick RM. Treatment of iron deficiency anemia in pregnancy with intravenous versus oral iron: systematic review and meta-analysis. Am J Perinatol 2019; 36: 366-376
• 60 Christoph P, Schuller C, Studer H. et al. Intravenous iron treatment in pregnancy: comparison of high-dose ferric carboxymaltose vs. iron sucrose. J Perinat Med 2012; 40: 469-474