The athlete's hematological response to hypoxia: A meta‐analysis on the influence of altitude exposure on key biomarkers of erythropoiesis

Lobigs, Louisa M.; Sharpe, Ken; Garvican-Lewis, Laura A; Gore, Christopher J.; Peeling, Peter; Dawson, Brian; Schumacher, Yorck Olaf

doi:10.1002/ajh.24941

Cited by 31 publications

(45 citation statements)

References 48 publications

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“…However, experts in the field and the authors themselves concur that this model is limited by the small number of data points at the lower end of the kilometer hour range and may furthermore overestimate the effect of low hypoxic doses because of an “altitude threshold” related to the s‐shape of the oxyhemoglobin saturation curve. Finally, a recent meta‐analysis highlights the complexity of the hematological response associated with altitude, even using the km.h model . Second, we cannot exclude that using a daily hypoxic exposure of 16.7 hours instead of 20‐22 hours as in the protocol of Levine and Stray‐Gundersen 1997 may have played some role in preventing the adaptive response; however, we could not find evidence supporting this contention.…”

Section: Discussionmentioning

confidence: 76%

“…Finally, a recent meta-analysis highlights the complexity of the hematological response associated with altitude, even using the km.h model. 49 Second, we cannot exclude that using a daily hypoxic exposure of 16.7 hours instead of 20-22 hours as in the protocol of Levine and Stray-Gundersen 1997 may have played some role in preventing the adaptive response; however, we could not find evidence supporting this contention. The daily hypoxic exposure of 16.7 hours used in the present study was based on previous work showing positive results with quite similar daily exposure (17.4 hours) 6 and recommendations indicating that daily hypoxic exposure of at least 16 hours appears long enough to elicit sustained adaptive response.…”

Section: Study Limitationsmentioning

confidence: 80%

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Hypobaric live high‐train low does not improve aerobic performance more than live low‐train low in cross‐country skiers

Robach

Hansen

Pichon

et al. 2018

Scandinavian Med Sci Sports

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Live high-train low (LHTL) using hypobaric hypoxia was previously found to improve sea-level endurance performance in well-trained individuals; however, confirmatory controlled data in athletes are lacking. Here, we test the hypothesis that natural-altitude LHTL improves aerobic performance in cross-country skiers, in conjunction with expansion of total hemoglobin mass (Hb , carbon monoxide rebreathing technique) promoted by accelerated erythropoiesis. Following duplicate baseline measurements at sea level over the course of 2 weeks, nineteen Norwegian cross-country skiers (three women, sixteen men, age 20 ± 2 year, maximal oxygen uptake (VO max) 69 ± 5 mL/min/kg) were assigned to 26 consecutive nights spent at either low (1035 m, control, n = 8) or moderate altitude (2207 m, daily exposure 16.7 ± 0.5 hours, LHTL, n = 11). All athletes trained together daily at a common location ranging from 550 to 1500 m (21.2% of training time at 550 m, 44.2% at 550-800 m, 16.6% at 800-1100 m, 18.0% at 1100-1500 m). Three test sessions at sea level were performed over the first 3 weeks after intervention. Despite the demonstration of nocturnal hypoxemia at moderate altitude (pulse oximetry), LHTL had no specific effect on serum erythropoietin, reticulocytes, Hb , VO max, or 3000-m running performance. Also, LHTL had no specific effect on (a) running economy (VO assessed during steady-state submaximal exercise), (b) respiratory capacities or efficiency of the skeletal muscle (biopsy), and (c) diffusing capacity of the lung. This study, showing similar physiological responses and performance improvements in the two groups following intervention, suggests that in young cross-country skiers, improvements in sea-level aerobic performance associated with LHTL may not be due to moderate-altitude acclimatization.

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Section: Discussionmentioning

confidence: 76%

Section: Study Limitationsmentioning

confidence: 80%

Hypobaric live high‐train low does not improve aerobic performance more than live low‐train low in cross‐country skiers

Robach

Hansen

Pichon

et al. 2018

Scandinavian Med Sci Sports

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“…Exposure to hypoxia results in a number of inherent physiological adaptations, which alter an athlete's haematological profile . The volumetric response to altitude is of interest here, and specifically, the influence of the initial haemoconcentration on the ABP markers, [Hb] and the OFF‐score.…”

Section: Discussionmentioning

confidence: 99%

“…Beidleman et al also described variability in the individual response, where the reported standard error for [Hb] is large for the impact of the time spent at altitude (Table 3 of Beidleman et al), suggesting considerable inter‐individual variability at altitude. Additionally, the intermittent nature of the LHTL protocol, differences in training load, and the non‐standardisation of blood collection times may have impacted the variable volumetric response reported here. Due to scheduling restrictions in the current study, the timing of the blood withdrawals and training programmes were not standardised.…”

Section: Discussionmentioning

confidence: 99%

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

Lobigs

Garvican-Lewis

Vuong

et al. 2018

Drug Testing and Analysis

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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 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].

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“…Consequently, parameters of the ABP can be affected either acutely, as a result of hemoconcentration arising from acute plasma volume reduction within the first 1–3 days of exposure to hypoxia, or as a function of accelerated erythropoiesis per se. Recently, Lobigs et al, published a meta‐analysis on the effect of hypoxic exposure on hematological parameters comprising the ABP. Data were included from a total of 17 studies which measured [Hb], square‐root transformed reticulocyte percentage (sqrt (retic%)), and the OFF‐score, during or after hypoxic exposure.…”

Section: Introductionmentioning

confidence: 99%

A novel mixed living high training low intervention and the hematological module of the athlete biological passport

Voss

Al-Hamad

Samsam

et al. 2019

Drug Testing and Analysis

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Exposure to either natural or simulated hypoxia induces hematological adaptations that may affect the parameters of the Athlete Biological Passport (ABP). The aim of the present study was to examine the effect of a novel, mixed hypoxic dose protocol on the likelihood of producing an atypical ABP finding. Ten well‐trained middle‐distance runners participated in a “live high, train low and high” (LHTLH) altitude training camp for 14 days. The participants spent ˜6 hr.d‐1 at 3000–5400 m during waking hours and ˜10 h.d‐1 overnight at 2400–3000 m simulated altitude. Venous blood samples were collected before (B0), and after 1 (D1), 4 (D4), 7 (D7), and 14 (D14) days of hypoxic exposure, and again 14 days post exposure (P14). Samples were analyzed for key parameters of the ABP including reticulocyte percentage (Ret%), hemoglobin concentration ([Hb]), and the OFF‐score. The ABP adaptive model was administered at a specificity of 99% to test for atypical findings. We found significant changes in [Hb] and Ret% during the hypoxic intervention. Consequently, this led to ABP threshold deviations at 99% specificity in three participants. Only one of these was flagged as an “atypical passport finding” (ATPF) due to deviation of the OFF‐score. When this sample was evaluated by ABP experts it was considered “normal”. In conclusion, it is highly unlikely that the present hypoxic exposure protocol would have led to a citation for a doping violation according to WADA guidelines.

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The athlete's hematological response to hypoxia: A meta‐analysis on the influence of altitude exposure on key biomarkers of erythropoiesis

Cited by 31 publications

References 48 publications

Hypobaric live high‐train low does not improve aerobic performance more than live low‐train low in cross‐country skiers

Hypobaric live high‐train low does not improve aerobic performance more than live low‐train low in cross‐country skiers

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

A novel mixed living high training low intervention and the hematological module of the athlete biological passport

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