Intravenous Iron Does Not Augment the Hemoglobin Mass Response to Simulated Hypoxia.

PURPOSE: Iron is integral for erythropoietic adaptation to hypoxia, yet the importance of supplementary iron compared with existing stores is poorly understood. The aim of the present study was to compare the magnitude of the hemoglobin mass (Hbmass) in response to altitude in athletes with intravenous (IV), oral, or placebo iron supplementation. METHODS: Thirty-four, nonanemic, endurance-trained athletes completed 3 wk of simulated altitude (3000 m, 14 h·d), receiving two to three bolus iron injections (ferric carboxymaltose), daily oral iron supplementation (ferrous sulfate), or a placebo, commencing 2 wk before and throughout altitude exposure. Hbmass and markers of iron regulation were assessed at baseline (day -14), immediately before (day 0), weekly during (days 8 and 15), and immediately, 1, 3, and 6 wk after (days 22, 28, 42, and 63) the completion of altitude exposure. RESULTS: Hbmass significantly increased after altitude exposure in athletes with IV (mean % [90% confidence interval (CI)], 3.7% [2.8-4.7]) and oral (3.2% [2.2-4.2]) supplementation and remained elevated at 7 d postaltitude in oral (2.9% [1.5-4.3]) and 21 d after in IV (3.0% [1.5-4.6]) supplementation. Hbmass was not significantly higher than baseline at any time point in placebo. CONCLUSIONS: Iron supplementation appears necessary for optimal erythropoietic adaptation to altitude exposure. IV iron supplementation during 3 wk of simulated live high-train low altitude training offered no additional benefit in terms of the magnitude of the erythropoietic response for nonanemic endurance athletes compared with oral supplementation.

Validation of a blood marker for plasma volume in endurance athletes during a live-high train-low altitude training camp.

Altitude is a confounding factor within the Athlete Biological Passport (ABP) due, in part, to the plasma volume (PV) response to hypoxia. Here, a newly developed PV blood test is applied to assess the possible efficacy of reducing the influence of PV on the volumetric ABP markers; haemoglobin concentration ([Hb]) and the OFF-score. Endurance athletes (n=34) completed a 21-night simulated live-high train-low (LHTL) protocol (14 h.d-1 at 3000 m). Bloods were collected twice pre-altitude; at days 3, 8, and 15 at altitude; and 1, 7, 21, and 42 days post-altitude. A full blood count was performed on the whole blood sample. Serum was analysed for transferrin, albumin, calcium, creatinine, total protein, and low-density lipoprotein. The PV blood test (consisting of the serum markers, [Hb] and platelets) was applied to the ABP adaptive model and new reference predictions were calculated for [Hb] and the OFF-score, thereby reducing the PV variance component. The PV correction refined the ABP reference predictions. The number of atypical passport findings (ATPFs) for [Hb] was reduced from 7 of 5 subjects to 6 of 3 subjects. The OFF-score ATPFs increased with the PV correction (from 9 to 13, 99% specificity); most likely the result of more specific reference limit predictions combined with the altitude-induced increase in red cell production. Importantly, all abnormal biomarker values were identified by a low confidence value. Although the multifaceted, individual physiological response to altitude confounded some results, the PV model appears capable of reducing the impact of PV fluctuations on [Hb].

Influence of combined iron supplementation and simulated hypoxia on the haematological module of the athlete biological passport.

The integrity of the athlete biological passport (ABP) is underpinned by understanding normal fluctuations of its biomarkers to environmental or medical conditions, for example, altitude training or iron deficiency. The combined impact of altitude and iron supplementation on the ABP was evaluated in endurance-trained athletes (n = 34) undertaking 3 weeks of simulated live-high: train-low (14 h.d-1 , 3000 m). Athletes received either oral, intravenous (IV) or placebo iron supplementation, commencing 2 weeks prior and continuing throughout hypoxic exposure. Venous blood was sampled twice prior, weekly during, and up to 6 weeks after altitude. Individual ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (%retic), and OFF score were calculated using the adaptive model and assessed at 99% and 99.9% specificity. Eleven athletes returned values outside of the calculated reference ranges at 99%, with 8 at 99.9%. The percentage of athletes exceeding the thresholds in each group was similar, but IV returned the most individual occurrences. A similar frequency of abnormalities occurred across the 3 biomarkers, with abnormal [Hb] and OFF score values arising mainly during-, and %retic values mainly post- altitude. Removing samples collected during altitude from the model resulted in 10 athletes returning abnormal values at 99% specificity, 2 of whom had not triggered the model previously. In summary, the abnormalities observed in response to iron supplementation and hypoxia were not systematic and mostly in line with expected physiological adaptations. They do not represent a uniform weakness in the ABP. Nevertheless, altitude training and iron supplementation should be carefully considered by experts evaluating abnormal ABP profiles.