Parenteral Iron Therapy: Examining Current Evidence for Use in Athletes.

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.

Factors Influencing the Hepcidin Response to Exercise: An Individual Participant Data Meta-analysis.

BACKGROUND: Hepcidin, the master iron regulatory hormone, has been shown to peak 3-6 h postexercise, and is likely a major contributor to the prevalence of iron deficiency in athletes. Although multiple studies have investigated the hepcidin response to exercise, small sample sizes preclude the generalizability of current research findings. OBJECTIVE: The aim of this individual participant data meta-analysis was to identify key factors influencing the hepcidin-exercise response. METHODS: Following a systematic review of the literature, a one-stage meta-analysis with mixed-effects linear regression, using a stepwise approach to select the best-fit model, was employed. RESULTS: We show that exercise is associated with a 1.5-2.5-fold increase in hepcidin concentrations, with pre-exercise hepcidin concentration accounting for ~ 44% of the variance in 3 h postexercise hepcidin concentration. Although collectively accounting for only a further ~ 3% of the variance, absolute 3 h postexercise hepcidin concentrations appear higher in males with lower cardiorespiratory fitness and higher pre-exercise ferritin levels. On the other hand, a greater magnitude of change between the pre- and 3 h postexercise hepcidin concentration was largely attributable to exercise duration (~ 44% variance) with a much smaller contribution from VO2max, pre-exercise ferritin, sex, and postexercise interleukin-6 (~ 6% combined). Although females tended to have a lower absolute 3 h postexercise hepcidin concentration [1.4 nmol·L-1, (95% CI [- 2.6, - 0.3]), p = 0.02] and 30% less change (95% CI [-54.4, - 5.1]), p = 0.02) than males, with different explanatory variables being significant between sexes, sample size discrepancies and individual study design biases preclude definitive conclusions. CONCLUSION: Our analysis reveals the complex interplay of characteristics of both athlete and exercise session in the hepcidin response to exercise and highlights the need for further investigation into unaccounted-for mediating factors.

The Impact of Acute Calcium Intake on Bone Turnover Markers during a Training Day in Elite Male Rowers.

INTRODUCTION: Although an acute exercise session typically increases bone turnover markers (BTM), the impact of subsequent sessions and the interaction with preexercise calcium intake remain unclear despite the application to the "real-life" training of many competitive athletes. METHODS: Using a randomized crossover design, elite male rowers ( n = 16) completed two trials, a week apart, consisting of two 90-min rowing ergometer sessions (EX1, EX2) separated by 150 min. Before each trial, participants consumed a high (CAL; ~1000 mg) or isocaloric low (CON; <10 mg) calcium meal. Biochemical markers including parathyroid hormone (PTH), serum ionized calcium (iCa) and BTMs (C-terminal telopeptide of type I collagen, osteocalcin) were monitored from baseline to 3 h after EX2. RESULTS: Although each session caused perturbances of serum iCa, CAL maintained calcium concentrations above those of CON for most time points, 4.5% and 2.4% higher after EX1 and EX2, respectively. The decrease in iCa in CON was associated with an elevation of blood PTH ( P < 0.05) and C-terminal telopeptide of type I collagen ( P < 0.0001) over this period of repeated training sessions and their recovery, particularly during and after EX2. Preexercise intake of calcium-rich foods lowered BTM over the course of a day with several training sessions. CONCLUSIONS: Preexercise intake of a calcium-rich meal before training sessions undertaken within the same day had a cumulative and prolonged effect on the stabilization of blood iCa during exercise. In turn, this reduced the postexercise PTH response, potentially attenuating the increase in markers of bone resorption. Such practical strategies may be integrated into the athlete's overall sports nutrition plan, with the potential to safeguard long-term bone health and reduce the risk of bone stress injuries.

Short-Term Carbohydrate Restriction Impairs Bone Formation at Rest and During Prolonged Exercise to a Greater Degree than Low Energy Availability.

Bone stress injuries are common in athletes, resulting in time lost from training and competition. Diets that are low in energy availability have been associated with increased circulating bone resorption and reduced bone formation markers, particularly in response to prolonged exercise. However, studies have not separated the effects of low energy availability per se from the associated reduction in carbohydrate availability. The current study aimed to compare the effects of these two restricted states directly. In a parallel group design, 28 elite racewalkers completed two 6-day phases. In the Baseline phase, all athletes adhered to a high carbohydrate/high energy availability diet (CON). During the Adaptation phase, athletes were allocated to one of three dietary groups: CON, low carbohydrate/high fat with high energy availability (LCHF), or low energy availability (LEA). At the end of each phase, a 25-km racewalk was completed, with venous blood taken fasted, pre-exercise, and 0, 1, 3 hours postexercise to measure carboxyterminal telopeptide (CTX), procollagen-1 N-terminal peptide (P1NP), and osteocalcin (carboxylated, gla-OC; undercarboxylated, glu-OC). Following Adaptation, LCHF showed decreased fasted P1NP (~26%; p < 0.0001, d = 3.6), gla-OC (~22%; p = 0.01, d = 1.8), and glu-OC (~41%; p = 0.004, d = 2.1), which were all significantly different from CON (p < 0.01), whereas LEA demonstrated significant, but smaller, reductions in fasted P1NP (~14%; p = 0.02, d = 1.7) and glu-OC (~24%; p = 0.049, d = 1.4). Both LCHF (p = 0.008, d = 1.9) and LEA (p = 0.01, d = 1.7) had significantly higher CTX pre-exercise to 3 hours post-exercise but only LCHF showed lower P1NP concentrations (p < 0.0001, d = 3.2). All markers remained unchanged from Baseline in CON. Short-term carbohydrate restriction appears to result in reduced bone formation markers at rest and during exercise with further exercise-related increases in a marker of bone resorption. Bone formation markers during exercise seem to be maintained with LEA although resorption increased. In contrast, nutritional support with adequate energy and carbohydrate appears to reduce unfavorable bone turnover responses to exercise in elite endurance athletes. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Sequential Submaximal Training in Elite Male Rowers Does Not Result in Amplified Increases in Interleukin-6 or Hepcidin.

Previous research investigating single bouts of exercise have identified baseline iron status and circulating concentrations of interleukin-6 (IL-6) as contributors to the magnitude of postexercise hepcidin increase. The current study examined the effects of repeated training bouts in close succession on IL-6 and hepcidin responses. In a randomized, crossover design, 16 elite male rowers completed two trials, a week apart, with either high (1,000 mg) or low (<50 mg) calcium pre-exercise meals. Each trial involved two, submaximal 90-min rowing ergometer sessions, 2.5 hr apart, with venous blood sampled at baseline; pre-exercise; and 0, 1, 2, and 3 hr after each session. Peak elevations in IL-6 (approximately 7.5-fold, p < .0001) and hepcidin (approximately threefold, p < .0001) concentrations relative to baseline were seen at 2 and 3 hr after the first session, respectively. Following the second session, concentrations of both IL-6 and hepcidin remained elevated above baseline, exhibiting a plateau rather than an additive increase (2 hr post first session vs. 2 hr post second session, p = 1.00). Pre-exercise calcium resulted in a slightly greater elevation in hepcidin across all time points compared with control (p = .0005); however, no effect on IL-6 was evident (p = .27). Performing multiple submaximal training sessions in close succession with adequate nutritional support does not result in an amplified increase in IL-6 or hepcidin concentrations following the second session in male elite rowers. Although effects of calcium intake require further investigation, athletes should continue to prioritize iron consumption around morning exercise prior to exercise-induced hepcidin elevations to maximize absorption.

Acute Ketogenic Diet and Ketone Ester Supplementation Impairs Race Walk Performance.

PURPOSE: This study aimed to determine if LCHF and ketone ester (KE) supplementation can synergistically alter exercise metabolism and improve performance. METHODS: Elite race walkers (n = 18, 15 males and 3 females; V˙O2peak, 62 ± 6 mL·min-1·kg-1) undertook a four-stage exercise economy test and real-life 10,000-m race before and after a 5-d isoenergetic high-CHO (HCHO, ~60%-65% fat; CHO, 20% fat; n = 9) or LCHF (75%-80% fat, <50 g·d-1 CHO, n = 9) diet. The LCHF group performed additional economy tests before and after diet after supplementation with 573 mg·kg-1 body mass KE (HVMN; HVMN Inc., San Francisco, CA), which was also consumed for race 2. RESULTS: The oxygen cost of exercise (relative V˙O2, mL·min-1·kg-1) increased across all four stages after LCHF (P < 0.005). This occurred in association with increased fat oxidation rates, with a reciprocal decrease in CHO oxidation (P < 0.001). Substrate utilization in the HCHO group remained unaltered. The consumption of KE before the LCHF diet increased circulating KB (P < 0.05), peaking at 3.2 ± 0.6 mM, but did not alter V˙O2 or RER. LCHF diet elevated resting circulating KB (0.3 ± 0.1 vs 0.1 ± 0.1 mM), but concentrations after supplementation did not differ from the earlier ketone trial. Critically, race performance was impaired by ~6% (P < 0.0001) relative to baseline in the LCHF group but was unaltered in HCHO. CONCLUSION: Despite elevating endogenous KB production, an LCHF diet does not augment the metabolic responses to KE supplementation and negatively affects race performance.