**1. Introduction**

Strategies that support athlete health and training availability are integral to the optimization of training outcomes and competition preparation. Nutrition has been recognized as an important contributor to these goals, with the provision of energy, macronutrients and micronutrients underpinning both health and performance. Energy supply is a basic consideration in sports nutrition, with athletes experiencing both deliberate and unintentional changes to the balance between intake and expenditure as they manipulate body composition and training loads. Although energy balance is the traditional metric by which such changes have been evaluated, the newer concept of energy availability [1] has become a major topic in considerations of athlete health, training consistency and competition performance. Energy availability (EA), calculated by removing the energy cost of an athlete's exercise program from their dietary energy intake, represents the energy that is remaining to support the body's normal physiological functioning (e.g., reproductive system, bone metabolism, and endocrine function) [2]. Low energy availability (LEA), arising from reduction in an athlete's energy intake and/or an increase in exercise load, is associated with downregulation and impairment of key physiological processes due to the lack of adequate energy support [3]. LEA underpins the clinical sequalae associated with the syndromes known as the Female Athlete Triad [4] and Relative Energy Deficiency in Sport (RED-S) [5,6]. While the former focused on disruption to the menstrual

cycle and bone health in female athletes, these models now acknowledge that LEA is also an important issue in male athletes [7].

Carbohydrate (CHO) availability has emerged as another key theme of interest, with this term describing the balance between CHO requirements of the muscle and central nervous system (and potentially other organs and body systems) around an exercise session relative to the endogenous and/or endogenous CHO supply [8]. There is plentiful evidence that strategies which achieve high CHO availability (i.e., to balance supply to the demand) are associated with enhancement of exercise capacity and sports performance, particularly during prolonged endurance events requiring high intensity e fforts [9,10]. These outcomes have led to recommendations that when optimal performance is desired, endurance athletes adopt strategies of daily CHO intake and/or high CHO availability around key exercise sessions to meet the session fuel demands [8]. However, the application of advanced analytical techniques to investigate exercise–nutrient interactions has shown strategies that achieve low CHO availability (i.e., acute CHO restriction around an exercise session) can amplify cellular adaptations within skeletal muscle during and after exercise [11]. If manipulation of CHO availability could be integrated into the training cycle, matching availability to the demands and goals of each session, a strategic blend of augmented adaptation workouts and targeted quality sessions could lead to enhanced performance outcomes [8,12]. Meanwhile, an alternative approach to metabolic preparation for endurance exercise is to chronically restrict dietary CHO, allowing the muscle to achieve a 2–3 fold increase in fat oxidation, coupled with a simultaneous decrease in CHO utilization, thus shifting its fuel reliance from finite CHO stores to the relatively unlimited body fat reserves [13–15]. The overall favorability of these strategies should be considered in the context of an athlete's performance goals and their requirement for metabolic flexibility [8,16,17]. Furthermore, they should be carefully integrated into the athlete's periodized training program to meet specific training goals and performance outcomes [8].

Although the main concerns around LEA have targeted reproductive and bone health, there is now greater awareness of the potential for wider disruption to body systems [5,6]. In parallel, there is growing interest in the e ffects of manipulating CHO availability beyond impacting metabolic changes in the muscle or performance outcomes, to the downstream targets of inter-organ cross-talk. Iron metabolism is emerging as a system that can be influenced by both factors. Poor iron status is often associated with LEA [6], with recent study of 1000 female athletes reporting an odds ratio of 1.64 for a history of anemia, low hemoglobin or low iron stores in those identified with LEA [18]. In addition, there are mechanisms by which exercising under low CHO availability can impair iron regulation [19,20]. Therefore, the purpose of this review is to synthesize the current information on the impact of manipulating energy and CHO availability on iron metabolism, with consideration to current dietary practices adopted by elite endurance athletes. This paper was prepared as a narrative review in recognition of the complexity and the early stage of development of these themes. Our intention is to draw on observations from our own extensive research on each of the separate topics, as well as the work of others, to focus attention on issues that should be further addressed by a systematic series of observational and intervention studies.

#### **2. Why Are Adequate Iron Stores Necessary for Athletes?**

Iron is fundamentally important to the optimal function of endurance athletes, given the mineral's role in athlete-relevant processes such as oxygen transport, cellular energy production, cognitive processing, and immune function [21,22]. Compromised iron stores can impair critical physiological processes, with significant negative e ffects on athlete health and performance. For example, high levels of aerobic fitness, a common prerequisite for elite endurance performance, can be limited by the oxygen-delivery capacity to the muscle [23]. In iron-compromised individuals with anemia, the impairment of hemoglobin production results in decrements to aerobic performance [24]. However, in such cases, once iron stores are restored via oral or intravenous supplementation, increases in VO2max [25], exercise time-trial performance [26] and exercise e fficiency [27,28] have been reported.

Despite research and clinical knowledge, iron deficiency in athlete populations remains a common issue. To understand the prevalence, various thresholds used to classify the severity of iron deficiency must be established. Accordingly, three stages of iron deficiency have been proposed: (1) Iron depletion, where iron stores are depleted without hematological consequences; (2) Iron deficiency non-anemia, where erythropoiesis diminishes as the iron supply to the erythroid marrow is reduced; and (3) Iron deficiency anemia, where hemoglobin production falls, resulting in anemia [29]. At a minimum, quantification of serum ferritin, hemoglobin and transferrin concentrations are required to diagnose an iron deficiency, with additional variables such as serum soluble transferrin receptor, hemoglobin mass, or C-reactive protein presenting as potential beneficial adjunct markers of detection [20]. While there is general agreemen<sup>t</sup> that iron deficiency can negatively impact performance, there is less conformity surrounding the classification criteria of these categories. Iron deficiency non-anemia has been commonly defined in athletic populations as a serum ferritin of <20 <sup>μ</sup>g·L−<sup>1</sup> and transferrin <16% [20,29]; however, variations in the literature range from serum ferritin values of <12 <sup>μ</sup>g·L−<sup>1</sup> through to <40 <sup>μ</sup>g·L−<sup>1</sup> [29–31]. Iron deficiency anemia is thought to be apparent once hemoglobin concentrations become compromised, with diagnostic thresholds below 11.5–12 <sup>g</sup>·dL−<sup>1</sup> commonly used. The incidence of iron deficiency non-anemia is reported as 24–47% of female and 0–17% of male athletes [32]; however, rates as high as 86% of female youth athletes from a mixed-sport cohort have been reported [33]. The higher incidence of iron deficiency observed in females has been attributed to the increased iron losses associated with menstruation [34]. However, the high prevalence of low iron stores commonly seen in athletes can also be partially explained by incorporation of iron into new tissues and cells induced by adaptation to training, as well as exercise-associated iron losses via exercise-induced mechanisms such as hemolysis, hematuria, sweating, gastrointestinal bleeding, and acute transient increases in the iron regulatory hormone, hepcidin [35].
