Biomarkers predicting the effectiveness of normobaric altitude training

Simon Klügel; Svenja Nolte; Sebastian Hacker; Tom Kastner; Nico Walter; Daniel Fleckenstein; Celina Maier; Kristina Gebhardt; Angela Relogio; Deeksha Malhan; Anna Klemmer; Tobias Stauber; Karsten Hollander; Karsten Krüger

doi:10.1007/s00421-025-06088-3

Biomarkers predicting the effectiveness of normobaric altitude training

Eur J Appl Physiol. 2026 May;126(5):2553-2562. doi: 10.1007/s00421-025-06088-3. Epub 2025 Dec 6.

Authors

Simon Klügel^#¹, Svenja Nolte^#¹, Sebastian Hacker¹, Tom Kastner^{2

3}, Nico Walter³, Daniel Fleckenstein³, Celina Maier¹, Kristina Gebhardt¹, Angela Relogio⁴, Deeksha Malhan⁴, Anna Klemmer⁵, Tobias Stauber⁵, Karsten Hollander^#⁶, Karsten Krüger^#⁷

Affiliations

¹ Department of Exercise Physiology and Sports Therapy, Institute of Sport Science, Justus-Liebig-University Giessen, Kugelberg 62, 35394, Giessen, Germany.
² Department of Sports Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Institute for Applied Training Science, Leipzig, Germany.
⁴ Institute for Systems Medicine, Medical School Hamburg, Hamburg, Germany.
⁵ Institute for Molecular Medicine, Medical School Hamburg, Hamburg, Germany.
⁶ Institute of Interdisciplinary Exercise Science and Sports Medicine, Medical School Hamburg, Hamburg, Germany.
⁷ Department of Exercise Physiology and Sports Therapy, Institute of Sport Science, Justus-Liebig-University Giessen, Kugelberg 62, 35394, Giessen, Germany. karsten.krueger@sport.uni-giessen.de.

^# Contributed equally.

Abstract

Purpose: The aim of the present study was to identify blood-based biomarkers that could predict individual VO₂max improvement before the start of an artificial altitude training camp.

Methods: In an exploratory intervention study, 15 young highly trained athletes from the German Athletics Federation completed a 21-day Live High - Train Low program at an artificial altitude house, which simulated an altitude of 800 km·h (approximately 1.900-2.500 m) under normobaric hypoxia. V̇O₂max was measured pre- and post-intervention, and blood parameters were collected at six time points (pre, post and four times at altitude. The pre measurement functioned as baseline and was used for the predictive model.

Results: Altitude training led to a mean V̇O₂max increase of 2.1 mL · kg⁻¹ · min⁻¹ (+ 3.1%), with high interindividual variability (-1.7 to + 4.5 mL · kg⁻¹ · min⁻¹). Neither training load, sex, nor discipline explained these differences. Logistic regression analyses identified monocyte percentage (> 10%) and neutrophil percentage (> 50%) emerged as the strongest predictors of responder status (McFadden's R² = 0.61 and 0.65, respectively), while neutrophil-to-lymphocyte-ratio (NLR) and hematocrit also showed significant predictive value. Threshold analyses revealed that high-responders consistently displayed lower neutrophil activity (NLR < 1.5) and higher hematocrit levels (> 42.5%), in contrast to low-responders. Longitudinal biomarker trajectories further supported these distinctions, with high-responders maintaining adaptive immune and iron-related profiles, whereas low-responders exhibited persistent signs of innate immune activation and suboptimal erythropoietic status.

Conclusion: These results highlight the relevance of functional biomarker profiles for individualized training planning in elite sports. Practically, this opens new possibilities for the targeted use of altitude training while minimizing health risks.

Keywords: Athletes; Endurance performance; Hypoxia; Iron metabolism; Monocytes; NLR.