ArticleProceedings of the National Academy of Sciences of the United States of America2019
The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Does intermittent exposure to high altitude increase the risk of cardiovascular disease in workers? A systematic narrative review.BMJ open · 2020Pooled it
- Altitude thresholds for hemoglobin and plasma volume regulation in adult residents of different altitudes and their impact on hemoglobin concentration.Physiological reports · 2026Article
- Angiogenic Doping: Plausible Yet Difficult to Detect.Sports medicine (Auckland, N.Z.) · 2026Review
- Genomic Evidence for Natural Selection Underlying High-Altitude Adaptive Hemoglobin Levels Among Peruvian Andeans.Genome biology and evolution · 2026Article
- Hemoglobin mass and plasma volume responses are not different between lowlanders and Tibetan highlanders during early acclimatization to 4300 m.European journal of applied physiology · 2026Article
- Genetic analysis of cold tolerance and high-altitude adaptation in Gannan indigenous Tibetan sheep through genome-wide scans.BMC genomics · 2026Article
- Human adaptation to high-altitude: A contemporary comparison of the oxygen cascade in Andean, Tibetan and Ethiopian highlanders.Experimental physiology · 2026Review
- Excessive erythrocytosis and the hypertensive phenotype at high altitude: emerging evidence and unresolved questions.Frontiers in cardiovascular medicine · 2026Review
- Incomplete genetic compensation and countergradient variation of blood-oxygen transport in deer mice.Evolution; international journal of organic evolution · 2025Article
- Addressing Anemia in High-Altitude Populations: Global Impact, Prevalence, Challenges, and Potential Solutions.American journal of hematology · 2025Review
- Genetic adaptations shaping survival, pregnancy, and life at high altitude and sea level.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Tibetan PHD2D4E;C127S variant protects from viral diseases in hypoxia, but predispose to infections in normoxia via HIFα:IFN axis.PLoS pathogens · 2025Article
- Gas exchange, oxygen transport and metabolism in high-altitude waterfowl.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Alternatively spliced NFKB1 transcripts enriched in Andean Aymara modulate inflammation, HIF and hemoglobin.Nature communications · 2025Article
- Transcriptomic analysis of iPSC-derived endothelium reveals adaptations to high altitude hypoxia in energy metabolism and inflammation.PLoS genetics · 2025Article
- Life destiny of erythrocyte in high altitude erythrocytosis: mechanisms underlying the progression from physiological (moderate) to pathological (excessive) high-altitude erythrocytosis.Frontiers in genetics · 2025Review
- Marked hemoglobin mass expansion and plasma volume contraction in Sherpas acclimatizing to 5,400 m altitude.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Variations in HBA gene contribute to high-altitude hypoxia adaptation via affected OFrontiers in zoology · 2024Article
- Higher oxygen content and transport characterize high-altitude ethnic Tibetan women with the highest lifetime reproductive success.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Physiological and Genetic Basis of High-Altitude Indigenous Animals' Adaptation to Hypoxic Environments.Animals : an open access journal from MDPI · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In contrast to Andean natives, high-altitude Tibetans present with a lower hemoglobin concentration that correlates with reproductive success and exercise capacity. Decades of physiological and genomic research have assumed that the lower hemoglobin concentration in Himalayan natives results from a blunted erythropoietic response to hypoxia (i.e., no increase in total hemoglobin mass). In contrast, herein we test the hypothesis that the lower hemoglobin concentration is the result of greater plasma volume, rather than an absence of increased hemoglobin production. We assessed hemoglobin mass, plasma volume and blood volume in lowlanders at sea level, lowlanders acclimatized to high altitude, Himalayan Sherpa, and Andean Quechua, and explored the functional relevance of volumetric hematological measures to exercise capacity. Hemoglobin mass was highest in Andeans, but also was elevated in Sherpa compared with lowlanders. Sherpa demonstrated a larger plasma volume than Andeans, resulting in a comparable total blood volume at a lower hemoglobin concentration. Hemoglobin mass was positively related to exercise capacity in lowlanders at sea level and in Sherpa at high altitude, but not in Andean natives. Collectively, our findings demonstrate a unique adaptation in Sherpa that reorientates attention away from hemoglobin concentration and toward a paradigm where hemoglobin mass and plasma volume may represent phenotypes with adaptive significance at high altitude.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.