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

Introduction

Iron deficiency is a common nutrient disorder in athletes, which left untreated, can have significant impacts on training consistency and athletic performance. Currently, there are a variety of methods that practitioners can use to address an iron deficiency [1], with the appropriate approach taken usually determined by the severity of the issue. Such approaches include dietary assessment and food modulation (lowest severity), oral iron supplementation, or parenteral iron delivery (highest severity). To determine the best approach, a standardised process for establishing the severity of the issues must be first considered.

Currently, there are numerous biological markers available to establish the iron status of an athlete [2]; however, many of these markers are acutely influenced by exercise, and a true gold standard of measuring/reporting iron status in athlete populations is yet to be clearly determined. Despite these issues, typical current practice sees iron status commonly determined via the presenting iron stores (serum ferritin; sFer), transferrin saturation (Tsat), and haemoglobin concentration (Hb). In combination, these three blood markers are then typically used to categorise the significance/severity of disrupted iron stores into three stages, as shown in [Table 1], which provides a collective summary of several published sources as a guide to help categorise an athlete’s iron status [3] [4] [5] [6]. Of note, the interpretation of iron status from a single marker (i. e. only sFer) is not recommended [7], and the impact of exercise/training on these blood markers should be minimised using the pre-blood screening guidelines established by Sim et al. [8].

Table 1 Classification, description, and common treatment approach to various levels of iron status based on the presenting serum ferritin (sFer), transferrin saturation (Tsat), and haemoglobin (Hb).

Classification	Serum Ferritin	Transferrin Saturation	Haemoglobin	Description	Common treatment approach
Healthy iron status	>50 µg.L− 1	>16%	F:>120 g.L− 1 M:>130 g.L− 1	Iron stores and blood parameters are healthy	NA
Sub-optimal iron stores	35–50 µg.L− 1			Ferritin threshold of 50 µg.L− 1 is associated with a hepcidin threshold for increased iron absorption, signalling the onset of early ID	Nutritional assessment
Iron depletion (ID)	25–35 µg.L− 1			Iron stores in the bone marrow, liver, and spleen are depleted	Nutritional assessment and potential oral iron supplement
Iron deficiency non-anaemia (IDNA)	15–25 µg.L− 1	<16%		Iron supply to the erythroid marrow is reduced	Nutritional assessment and oral iron supplement
Iron deficiency anaemia (IDA)	<15 µg.L− 1		F: <120 g.L− 1 M: <130 g.L− 1	Haemoglobin concentration and oxygen-carrying capacity is decreased	Parenteral iron

Note: F=female; M=male. Table created based on combined data and explanations from [3] [4] [5] [6].

Within athlete populations, it is commonly reported that the prevalence of iron deficiency (anaemia (IDA) and non-anaemia (IDNA)) is 15–35% in females and ~3–11% in males [8] [9] [10]. However, specific athlete cohort studies report>50% of a study population can present with compromised iron stores [11] [12]. Regarding the more severe stages of iron deficiency (IDA), various studies inform a prevalence of 2–5% in females and 1–2% in males [13] [14]. Across both IDNA and IDA, the higher prevalence in females is generally attributed to the impact of the menstrual cycle.

Given the high prevalence of iron deficiency in athlete populations, it is important to understand the mechanisms of relevance that can collectively impact iron stores. Currently, we understand that there are several mechanisms of iron loss during exercise. These include processes such as haemolysis, sweating, haematuria, and gastrointestinal blood loss [15]. Further, it is also evident that athletes commonly battle energy deficit (through lack of time for adequate recovery nutrition or through purposeful calorie restriction in weight-sensitive sports), which can be associated with low nutrient quality and inadequate iron intake from the diet [16]. Finally, we also know that exercise results in a transient increase to the body’s iron regulatory hormone, hepcidin [17], which results in a temporary reduction in the absorption of iron from the gut, especially in foods consumed 2 h post-exercise [18], where absorption seems to coincide with the peak post-exercise elevations in hepcidin levels at 3–6 h [17].

Although the iron loss from any single mechanism above might be small, it is their combined effect over multiple training sessions that may accrue and present as a burden on an athlete’s iron stores over time. Clearly, these mechanisms present a case for iron loss during exercise, but equally, a period of reduced iron absorption in the post-exercise period. Impacting the mechanisms of iron loss during exercise is challenging, since there is limited ability for a practitioner, coach, or athlete to control these factors when a certain type, duration, or intensity of training is required for appropriate physical adaptation. However, our ability to impact iron provision and uptake from the diet and/or from various methods of supplementation, are very good. Therefore, a focus on timing iron intake to coincide with peak periods of absorption (or to avoid peak periods of malabsorption) from the gut becomes important, since it is the gut propensity for iron uptake that limits our ability to effectively treat iron deficiency through food and oral iron supplements.

Recent work from our group [1] [12] [19] [20] [21] and others [18], have been exploring factors that impact dietary iron absorption from the gut in relation to exercise. Collectively, this work informs us that there appears to be a peak period for iron absorption within the 30 min either side of exercise [19] [21], which is lost if the food/supplement is consumed≥2 h post-exercise [18]. Further, this propensity for increased absorption appears better in the morning as compared to the afternoon [19], likely due to the natural diurnal increase in hepcidin levels that marginally negates afternoon iron absorption from a one-off meal [22]. Collectively, this work provides us with significant strategic approaches to timing iron intake for optimised iron absorption at the gut. However, if we are using these strategies to correct an iron deficiency, it should be considered that the time duration to have a significant impact is relatively long (i. e. 8–12 weeks of oral supplementation to improve iron status by 40–80% [12] [23] [24]. Although this result is positive and appropriate for individuals who are IDNA or better, an 80% improvement in iron stores for an IDA athlete with sFer <10 µg.L^− 1 and compromised Hb concentrations would likely still not shift them into the IDNA classification. Accordingly, contemporary approaches to iron replenishment in these specific IDA athlete populations are focussed on parenteral iron provision, which has the benefit of by-passing the gut (where our key limitations exist) and supplying iron direct to circulation. Regardless, the use case for such approaches should be well considered by the practitioner and athlete, and therefore, the remainder of this review will focus on parenteral iron delivery in athletes.

Parenteral iron approaches to treating anaemia

Parenteral treatment of iron deficiency is particularly warranted in the presence of severe IDA, or when there are ongoing and significant iron losses (e. g. heavy menstrual bleeding) [25]. Of note, thorough investigation of the underlying cause and exclusion of medical conditions such as occult gastrointestinal (GI) blood loss (e. g., from non-steroidal anti-inflammatory use, carcinoma), malabsorption (e. g. coeliac disease), and non-GI blood loss (e. g. abnormal uterine bleeding), should be considered by the treating physician [26]. Unsurprisingly, in clinical populations with chronically elevated hepcidin levels (e. g. cancer, inflammatory conditions), parenteral iron administration is recommended as it overcomes the negative effect of hepcidin on GI absorption [27]. In athletes, where repeated exercise-induced elevations of hepcidin occur daily [17] [28], the limitations to gut absorption of oral iron intake may be substantial. Interestingly, the amount of hepcidin required to block iron absorption from the gut is lower than that required to block iron recycling from macrophages, where intravenous (IV) iron is taken up [29]. Therefore, parenteral iron therapy becomes a viable treatment option for athletes presenting with IDA, or in those presenting with an inadequate response, intolerable side-effects, or poor adherence to oral iron therapy [25].

Intravenous iron: formulations and safety

Intravenous (IV) iron consists of an iron core within a carbohydrate shell [29]. The stability of the shell dictates the maximum dose that can be given in a single infusion: iron sucrose is less stable, allowing for only 200 mg to be administered per infusion [29], whereas the newer formulations of ferric carboxymaltose, ferric derisomaltose, low molecular weight iron dextran, and ferumoxytol have stable shells, permitting larger doses and fewer total infusions [25] [30]. Ferric derisomaltose and ferumoxytol, for example, are typically provided in a single infusion of up to 1000 mg over 15 min, in contrast to the multiple infusions required with iron sucrose [31]. Iron polymaltose is a cheaper preparation, which is also approved for total dose infusion, although over a longer period by slow infusion (~ 5 h) [32] [33]; more rapid infusion (~ 1 h) of iron polymaltose, however, may be safe and well-tolerated [33] [34]. The cumulative dose required is based on the individual’s Hb, target Hb, and body weight [32], although some centres adopt a ‘standard’ 1-g dose protocol [35].

While serious adverse events and infusion reactions (e. g. anaphylaxis) were previously a concern with early IV preparations, primarily due to high molecular weight iron dextran formulations that are no longer available [36] [37], the newer formulations appear to have a similar safety profile to oral iron [31]. In fact, a meta-analysis from 2015 (n=103 randomised controlled trials) reported no increased risk of serious adverse events (relative risk 1.04 95%CI 0.93–1.17), compared to oral iron or placebo [38]. Milder reactions, such as headache, fever, joint pain, and urticaria, however, might be expected [25] [39]. Nevertheless, monitoring for 30 min after infusion by appropriately qualified staff is still advised [25] to monitor for and manage severe reactions (e. g. loss of consciousness, cardiac arrest, wheezing/stridor, hypotension) [39]. Iron-induced hypophosphatemia can occur following IV iron, particularly with ferric carboxymaltose, however is usually transient and frequently asymptomatic [31]. Nevertheless, phosphate measurement and replacement must be considered in individuals presenting with symptoms, such as muscle weakness and mental state changes, following parenteral iron treatment [25]. In the case of repeated administration, bone pain and fractures may also alert the clinician to possible hypophosphatemia [25] a risk that should also be considered and discussed prior to administration in athletes.

Intramuscular iron

Intramuscular (IM) iron, while effective, has shown to be no safer than intravenous (IV) iron, can be more painful, and is associated with permanent skin staining and possibly sarcomas [26] [27] [32] [33]. For athletes, this would be especially problematic as it has the potential to negatively impact training or competition in the immediate days post-treatment. Notably, current best practice guidelines from the Australian Institute of Sport (AIS) indicate a preference for IV iron infusion (preferably ferric carboxymaltose) only in athletes presenting with severe IDA, ineffective oral supplementation, or compromised Hb_mass in close proximity to a major sporting event [40]. Most importantly, both IV and IM iron therapy must be guided by sports physicians in-conjunction with a particular organisations policy (e. g. no needle).

Efficacy of IV formulations on haematological variables

Advantageously, newer IV formulations allow for complete, or almost complete, iron repletion to occur with a single dose (~1000 mg) administered over 15–60 min [31]. With these total dose protocols, peak ferritin concentrations are achieved in 7–9 days [41] with pharmacokinetic studies (using lower doses of 200 mg) demonstrating persistent elevations compared to baseline at 2 weeks [42]. The incremental increase in Hb varies depending on the initial Hb and the dose given [43]. Current evidence in clinical populations suggests that Hb increases by 2 g.dL^− 1 per week; plateauing around 5–14 days [44] [45]. Here, the significant advantage of IV formulations is highlighted by the rapid normalisation of haematological parameters when compared to oral therapy. Indeed, in IDA pregnant women (mean sFer: 13 μg.L^− 1, Hb 11.4 g.dL^− 1), IV iron (1000 mg of ferric carboxymaltose or iron polymaltose) resulted in larger sFer and Hb increases at 4 weeks post infusion when compared to oral supplementation (325 mg daily ferrous sulphate) [46]. Similarly, a study in IDA postpartum women (sFer<15 μg.L^− 1, Hb<9 g.dL^− 1) also demonstrated that those treated with IV iron (iron sucrose 200 mg x 2) had more rapid increases in Hb in the first 2 weeks than those receiving oral supplementation (ferrous sulphate 200 mg twice daily) [45]. However, there was no significant difference between groups in Hb concentration at 6 weeks [45], emphasising that, where GI absorption is not impaired, similar longer-term outcomes can be achieved with oral and IV routes. Nevertheless, the rapidity of repletion and the ability to circumvent the gut is particularly attractive in certain clinical populations, including IDA athletes.

A target increase in Hb of ~ 2 g.dL^− 1 at 2–4 weeks is recommended in medical guidelines [47], with subsequent measurement of Hb at 4 weeks (or earlier if symptomatic), to evaluate treatment response and decide on subsequent doses [47]. Here, it is worth noting that, in athletes, the measurement of Hb to monitor the response to iron therapy in anaemia may be misleading. Haemoglobin concentration is dependent upon both the absolute mass of haemoglobin (i. e. Hb_mass) and blood volume (plasma and red cells) [48]. In athletes, Hb may be falsely low due to increased plasma volume or falsely high in the setting of dehydration. Therefore, the use of Hb_mass (through carbon monoxide rebreathing technique [49]) may be more precise and provide better information about oxygen carrying capacity. Nevertheless, this measurement is generally confined to research situations and is difficult for clinical practice. Accordingly, practitioners and clinicians are advised to employ current best practice standardisation protocols (e. g. well-hydrated state, morning sample, body position, rested and limited exercise in the 12 h prior to sampling) to maximise the validity and reliability of venous blood measurements [8].

Impact of parenteral iron approaches in athletes

Efficacy of parenteral iron on performance outcomes in non-anaemic athletes

While studies in athletes are limited, the effect of IV iron on haematological and performance indices appears to be dependent on the severity of iron deficiency pre-infusion. Burden and colleagues [50] examined the short- and medium-term effects of a 500 mg IV iron infusion in highly trained IDNA female (sFer <30 μg.L^− 1, Hb>12 g.dL^− 1) and male (sFer <40 μg.L^− 1, Hb>12 g.dL^− 1) marathon runners (Tsat 33.1±12.0%). Twenty-four hours after the infusion, mean sFer concentrations increased and remained elevated 4 weeks later. However, no differences in Hb concentrations, running economy, time to exhaustion, or VO_2max were reported at either 24 h or 4 weeks post-infusion. Further, a randomized controlled trial by Woods and colleagues [51] recruited 14 distance runners without iron deficiency anaemia (sFer: 30–100 μg.L^− 1, Hb>12.0 g.dL^− 1), and examined the impact of three 100-mg IV iron (or placebo) treatments, each separated by 2 weeks, on performance, fatigue, and haematological indices. After 6 weeks, improvements in fatigue (Cohen’s effect size –1.54, p=0.05) and mood scores (Cohen’s effect size –1.58, p=0.02) were reported in the group receiving IV iron, in contrast to the group receiving a saline placebo injection. Unsurprisingly, no improvement in 3000-m time-trial performance was seen at week 4 nor was there any increase in Hb_mass at week 6 post-infusion [51], outcomes likely explained by the relatively high iron stores of the athletes (sFer>30 μg.L^− 1) prior to infusion.

In addition to these findings, Garvican and colleagues [24] examined the efficacy of IV ferric carboxymaltose in highly trained distance runners with low (sFer≤35 μg.L^− 1 and Tsat<20%, or sFer≤15 μg.L^− 1) or sub-optimal iron stores (sFer <65 μg.L^− 1). After a series of IV injections over a 6-week period, Hbmass (4.9%) increased only in the low iron stores group, which was accompanied by an increase in VO_2max (3.3%) and run time to exhaustion (9.3%). Conversely, no change reported in the suboptimal group, suggesting that supplementation is more effective when iron stores are compromised. Of interest, an oral iron supplement group in the same study showed no increase in Hb_mass or VO_2max after 6 weeks, regardless of initial sFer status (low or suboptimal).

To summarise, it appears that iron supplementation in non-iron-deficient athletes does not improve performance, and therefore, indiscriminate use of IV iron is not recommended. However, greater efficacy of IV iron supplementation is observed in athletes with lower sFer concentrations, suggesting the practice should be reserved for cases where iron stores are significantly compromised, such as IDA.

Efficacy of parenteral iron on performance outcomes in anaemic athletes

Few studies have investigated the effect of parenteral iron on haematological and performance variables in IDA athletes. A single case report has been published on a female athlete with IDA and represents the only ‘longitudinal’ (15 weeks) evidence for parenteral approaches to be used with anaemic athletes. Here, a female middle-distance runner (sFer 9.9 μg.L^− 1, Hb 8.8 g.L^− 1) received an IM iron injection (100 mg Fe), which was followed by 15 weeks of oral iron supplementation [52]. After 2 weeks, initial improvements in haematological variables were rapid, where the authors describe a 136% increase in sFer (to 23.4 μg.L^− 1), 36% increase in Hb (to 12 g.dL^− 1) and a 49% increase in Hb_mass (389 g to 580 g). These outcomes were maintained, if not improved, at 15 weeks post-injection (sFer 27.0 μg.L^− 1, Hb 13 g.dL^− 1 and Hbmass 710 g). Alongside the haematological improvements, the athlete ran a personal best time over 3,000 m ~70 days post-infusion. Although this case study showed a rapid and prolonged effectiveness of parental treatment in a single athlete, it should be noted that this approach was combined with oral iron supplementation, making it difficult to distinguish the sole efficacy of IM injections. Similarly, Pedlar et al., [7] showed IM iron injections given to a female Olympic Games 1500-m runner increased sFer levels more than four-fold (from 11 μg.L^− 1 to 47 μg.L^− 1; extrapolated from Figure 1 in Pedlar et al. [7]) prior to a major event. However, these improved iron stores were back down to similar pre-IM injection levels within 6 months, despite oral iron supplements being used to support the increase. Of note, the athlete presented in the study by Pedlar and colleagues was not considered to have IDA (with Hb levels>120 g.L^− 1), and therefore, no study has to date examined the long-term effects of parenteral iron treatments in elite athletes with IDA, and the impact this may have on performance. Accordingly, much needed research in this space is required to better inform practitioners of the potential benefits of parenteral iron treatment.

Long-term impacts and decay

In a retrospective examination of a highly trained female athlete cohort with IDNA, McKay et al. [53] modelled the rate of decay in sFer following an IV infusion. These authors reported that sFer takes 499 days [range: 212–776 days] and 647 days [361–925 days] post-infusion to fall to 50 μg.L^− 1and 35 μg.L^− 1, respectively. Importantly, each individual athlete responded differently, with a random intercept for “subject” accounting for the majority of model variance, and factors such as the athletes’ sport, age, or pre-infusion ferritin concentrations deemed less important. Noteworthily, potential confounding factors such as training load, menstrual cycle status, and dietary intake were not considered and may significantly contribute to the rate of sFer decay. Nevertheless, current recommendations suggest that athletes undergoing an IV iron infusion should assess iron status 1 month post-infusion to determine treatment efficacy, with a repeat assessment at 6 months post-infusion to determine iron retention [53]. If further follow-up treatment is required, this should be developed on an individual basis and may include a combination of dietary, oral, and parenteral strategies; although, as noted above, sFer levels still decayed to baseline by 6 months post-IM injection in the case study presented by Pedlar et al., [7] despite being supported with oral iron supplements during this period, which further highlights the individual response to treatment. Accordingly, future research should examine the rate of decay in sFer and Hb prospectively, considering differences between IDA and IDNA athletes, as well as the potential influence of individual factors which may affect the rate of decay.

Special considerations of parenteral iron use in athletes

World Anti-Doping Code Considerations

For athletes engaging in international competition, consideration must be given to the regulations governing the use of IV infusions. The World Anti-Doping Agency (WADA) defines an IV infusion as ‘the supply of fluid and/or prescribed medication by drip or push directly into a vein’ and states that they are ‘prohibited both in-competition and out-of-competition if the volume delivered exceeds 100 ml within a 12-h period’ [54]. However, if the infusion is received in the course of hospital treatment, a surgical procedure, or clinical diagnostic investigations, a therapeutic use exemption (TUE) may be necessary [54]. Although formulations vary in how they are administered (injection versus infusion, volume of solution), iron polymaltose, given as a slow infusion, typically exceeds this volume, and therefore, preference may be given to formulations such as ferric carboxymaltose. As such, consideration must be given to the need for IV therapy, the formulation used, and in some cases, potential application for a TUE prior to administration of IV iron in athlete populations.

Altitude

Unique to athletes is the need to consider iron supplementation prospectively to defend against the anticipated increased iron demand for physiological adaptation. Altitude training is frequently utilized by endurance athletes with the aim of inducing hypoxia-mediated adaptations to erythropoiesis. Supplementary iron is recommended when sFer is less than 35 μg.L^− 1 at 4–6 weeks prior, or<130 μg.L^− 1 at 2 weeks prior to altitude, in an attempt to optimize increases in Hb_mass [55]. Unless sFer is less than 15 μg.L^− 1, oral iron is preferred to align with the “no needle” policies of many sporting organizations [55]. Indeed, a study in non-anaemic endurance-trained athletes (Hb ~ 14 g.dL^− 1; mean sFer ~ 71.2–88.1 μg.L^− 1 with 4 of 34 subjects with sFer<20 ug.L^− 1), demonstrated a similar increase in Hb_mass after 21 days of simulated altitude exposure in both oral (3.7%) and IV (3.2%) iron-supplemented groups, in contrast to a lack of Hb_mass response in the placebo group (0.1%) [56]. This was associated with a larger increase in sFer in the 2 weeks prior to altitude exposure in the IV group, compared to the oral and placebo groups (IV 47% and 92% larger, respectively), and an increase in VO_2peak after altitude in the IV supplemented group only. Of note, a decrease in VO_2peak was seen in individuals across all groups, leading the authors to postulate that the results may have been confounded by residual fatigue after altitude training [56]. This study, combined with the guidelines presented above, suggest that iron supplementation might be necessary for hypoxia-mediated erythropoietic adaptation even in non-iron deficient athletes. Further, IV supplementation does not provide additional benefit to Hb_mass over oral therapy in non-iron deficient athletes [56]. However, considering the time required for IV iron to impact ferritin and Hb over oral iron supplementation in the short term (1–4 weeks), IV iron may be necessary in an IDA or IDNA athlete where a rapid rate of increase is required due to a limited lead-up time to altitude exposure.

Pregnancy

Pregnant women are a special population requiring consideration, with the increased numbers of athletes continuing sport throughout pregnancy. Indeed, IDA affects ~37% of pregnant women (aged 15–49 years) worldwide [57], and when considering the increased iron requirements needed to simultaneously support both foetal development and high training loads, it is unsurprising that pregnant athletes are an extremely high risk group for iron deficiency. Pregnant athletes are a severely under-researched population, and so, current guidance is limited. Iron deficiency in pregnancy is known to have potential adverse maternal and foetal outcomes, such as premature birth, low birth weight, maternal infections, and increased maternal mortality [57]. Where treatment is required, oral iron is the first line approach, with IV iron indicated only if the response to oral therapy is inadequate and only in the second and third trimesters [31] [58]. However, given the adverse GI side-effects from oral therapy, there is increased interest in newer IV preparations. Indeed, a recent meta-analysis suggested an increased rate of target Hb achievement (OR=2.66), increased Hb after 4 weeks (WMD=0.84 g.dL^− 1), and decreased adverse reactions (OR=0.35) in pregnant women receiving IV compared to oral iron supplementation [59]. Additionally, ferric carboxymaltose may have fewer side-effects while also being more convenient and less costly than iron sucrose [60]. In pregnant athletes, where the risk of iron deficiency may be amplified, the use of IV iron could be preferable; however, further research, particularly on long-term outcomes, is warranted.

Summary and conclusions

The high prevalence of iron deficiency in athletes is attributed to a combination of increased losses, inadequate dietary intake, and exercise-induced increases in hepcidin. While oral iron supplementation is considered first-line treatment, the significant adverse GI side effects and the need to optimally time consumption around exercise pose potential challenges in the adherence and absorption of iron orally administered in athletes. On the other hand, parenteral iron, specifically IV, offers the advantage of circumventing hepcidin inhibition in the GI tract, while achieving more rapid increases in sFer and Hb. Of note, newer IV formulations allow for single total dose administration within an hour with a similar safety profile to that of oral iron. Current evidence suggests notable improvements with IV iron therapy in haematological and performance variables in IDA, and in IDNA where sFer is<15 μg.L^− 1. However, it is understandable that various sporting organisations have a cautious approach to the use of needles for treating nutrient deficiencies, confining IV iron therapy to IDA, ineffective long-term oral supplementation, or compromised haematological status in close proximity to a major sporting event [40]. In addition, parenteral iron should only be administered in consultation with a sports medicine physician, where consideration must be given to the need for a TUE in accordance with WADA regulations. Finally, future studies investigating parenteral iron approaches in athletes are warranted to assess the longer-term impacts on haematological and performance variables, in addition to exploring the individual factors (e. g. training load, dietary intake, menstrual cycle status) that affect the rate of decay.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

The salary of MS is supported by a Royal Perth Hospital Research Foundation Fellowship (RPHRF CAF 00/21) and an Emerging Leader Fellowship from the Western Australian Future Health Research and Innovation Fund.

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Publication History

Received: 31 August 2023

Accepted: 13 November 2023

Accepted Manuscript online:
14 November 2023

Article published online:
22 December 2023