AltitudeOmics: Rapid Hemoglobin Mass Alterations with Early Acclimatization to and De-Acclimatization from 5260 m in Healthy Humans

Abstract

It is classically thought that increases in hemoglobin mass (Hbmass) take several weeks to develop upon ascent to high altitude and are lost gradually following descent. However, the early time course of these erythropoietic adaptations has not been thoroughly investigated and data are lacking at elevations greater than 5000 m, where the hypoxic stimulus is dramatically increased. As part of the AltitudeOmics project, we examined Hbmass in healthy men and women at sea level (SL) and 5260 m following 1, 7, and 16 days of high altitude exposure (ALT1/ALT7/ALT16). Subjects were also studied upon return to 5260 m following descent to 1525 m for either 7 or 21 days. Compared to SL, absolute Hbmass was not different at ALT1 but increased by 3.7±5.8% (mean ± SD; n = 20; p<0.01) at ALT7 and 7.6±6.6% (n = 21; p<0.001) at ALT16. Following descent to 1525 m, Hbmass was reduced compared to ALT16 (−6.0±3.7%; n = 20; p = 0.001) and not different compared to SL, with no difference in the loss in Hbmass between groups that descended for 7 (−6.3±3.0%; n = 13) versus 21 days (−5.7±5.0; n = 7). The loss in Hbmass following 7 days at 1525 m was correlated with an increase in serum ferritin (r = −0.64; n = 13; p<0.05), suggesting increased red blood cell destruction. Our novel findings demonstrate that Hbmass increases within 7 days of ascent to 5260 m but that the altitude-induced Hbmass adaptation is lost within 7 days of descent to 1525 m. The rapid time course of these adaptations contrasts with the classical dogma, suggesting the need to further examine mechanisms responsible for Hbmass adaptations in response to severe hypoxia.

AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia

“…15,33–39 Here we correlated raw metabolomics data for each metabolite in each biological replicate at SL, ALT1 and 16 to other data available for each subject (Supplementary Table S3). Linear correlation values (r) were used to perform HCA (Supplementary Figure S2) with the goal of highlighting a core set of metabolites and physiological/athletic parameters that show strong correlations (> |0.6|).…”

“…The study was performed as part of the AltitudeOmics research program, as previously reported 15,33–39 . Twenty-one healthy volounteers (12 males and nine females, 19–23 years - Supplementary Table 1) were enrolled upon written consent, in agreement with the Declaration of Helsinki.…”

“…8–14 Increases in red cell volume (RCV) and total hemoglobin mass (Hbmass) are observed as early as one or two weeks after exposure to high altitude, even though these adaptations are eventually lost following descent to low altitude. 14,15 Besides, while hypoxia can induce systemic increase of erythropoietin (EPO) levels within hours of hypobaric hypoxia 16 , EPO-stimulated production of mature RBCs from the bone marrow can take days to occur. 17 …”

UBC‐Nepal expedition: phenotypical evidence for evolutionary adaptation in the control of cerebral blood flow and oxygen delivery at high altitude

“…In lowlanders returning from altitude, [Hb] has been shown to return to sea‐level values within 1–2 weeks (Ryan et al . ; Siebenmann et al . ) although this did not appear to be the case for the Sherpa population we tested.…”

Sightings edited by Erik Swenson and Peter Bärtsch

“…The AltitudeOmics group (Ryan et al, 2014) demonstrates how by measuring total hemoglobin with a CO-rebreathing method that hemoglobin mass at 5260 m increases significantly within 7 days, continues to increase over the next 10 days, and is back to pre-exposure values after return from 5260 m to 1525 m within 7 days. Increase in serum ferritin after return is compatible with increased destruction of erythrocytes.…”