Inter-Effort Recovery Hypoxia Increases Peak Oxygen Consumption without Hematological Changes

Abstract

Intermittent hypoxia combined with physical training may enhance performance and health parameters but can impair session quality, limiting adaptations. To address these drawbacks, inter-effort recovery hypoxia has been proposed. This study investigated the effects of a 5-week inter-effort recovery hypoxia protocol followed by a 1-week tapering period in recreational runners. Twenty-four men were allocated to an inter-effort recovery hypoxia group (n = 11) or a normoxia group (n = 13) and assessed for body composition, hematological profile, running economy, maximum velocity, and peak oxygen uptake before training (W0), after training (W6), and after tapering (W8). Training consisted of 3 weekly sessions for 5 weeks: a 5-minute warm-up at 60% of maximum velocity, ten 1-minute effort at 120% (wk 1–3) or 130% (wk 4 and 5) of maximum velocity with 2-minute passive recovery, and 5-minute cool-down at 60% of maximum velocity. The inter-effort recovery hypoxia group inhaled hypoxic air (fraction of inspired oxygen=0.136) during warm-up, recovery bouts, and cool-down. Outcomes were analyzed using generalized linear mixed models. Peak oxygen uptake increased in the inter-effort recovery hypoxia group at W6 (+7%) and W8 (+10%), while the normoxia group improved at W8 (+7%), without group differences; running economy improved in the normoxia group at W8 (+10%). No significant changes occurred in erythropoietin, erythrocytes, hemoglobin, reticulocytes, or body composition. The 5-week inter-effort recovery hypoxia protocol enhanced peak oxygen uptake without hematological changes, indicating a feasible and non-erythropoietic strategy for improving aerobic fitness.

Keywords

Intermittent hypoxic training - hypoxia - erythropoietin - high intensity interval training - oxygen consumption

Publication History

Received: 23 September 2025

Accepted after revision: 23 December 2025

Article published online:
30 January 2026

• References

• 1 Girard O, Brocherie F, Goods PSR, Millet GP. An Updated Panorama of “Living Low-Training High” Altitude/Hypoxic Methods. Front Sports Act Living 2020; 2: 26
• 2 Millet GP, Roels B, Schmitt L, Woorons X, Richalet JP. Combining hypoxic Methods for peak performance. Sports Med 2010; 40: 1-25
• 3 Faiss R, Girard O, Millet GP. Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia. Br J Sports Med 2013; 47: i45-i50
• 4 Hoppeler H, Vogt M. Muscle tissue adaptations to hypoxia. J Exp Biol 2001; 204: 3133-3139
• 5 Li G, Zhao Y, Li Y, Lu J. Up-Regulation of Neuronal Nitric Oxide Synthase Expression by Cobalt Chloride Through a HIF-1α Mechanism in Neuroblastoma Cells. NeuroMol Med 2015; 17: 443-453
• 6 Zoll J, Ponsot E, Dufour S, Doutreleau S, Ventura-Clapier R, Vogt M. et al. Exercise training in normobaric hypoxia in endurance runners. III. Muscular adjustments of selected gene transcripts. J Appl Physiol 2006; 100: 1258-1266
• 7 Haase VH. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Reviews 2013; 27: 41-53
• 8 Girard O, Brocherie F, Millet GP. Effects of Altitude/Hypoxia on Single- and Multiple-Sprint Performance: A Comprehensive Review. Sports Med 2017; 47: 1931-1949
• 9 Noordhof DA, Schoots T, Hoekert DH, de Koning JJ. Is Gross Efficiency Lower at Acute Simulated Altitude Than at Sea Level?. Int J Sports Physiol Perform 2013; 8: 319-322
• 10 Feng X, Chen Y, Yan T, Lu H, Wang C, Zhao L. Effects of various living-low and training-high modes with distinct training prescriptions on sea-level performance: A network meta-analysis. PLoS One 2024; 19: e0297007
• 11 Westmacott A, Sanal-Hayes NEM, McLaughlin M, Mair JL, Hayes LD. High-Intensity Interval Training (HIIT) in Hypoxia Improves Maximal Aerobic Capacity More Than HIIT in Normoxia: A Systematic Review, Meta-Analysis, and Meta-Regression. Int J Environ Res Public Health 2022; 19: 14261
• 12 Afina AB, Oleg SG, Alexander AB, Ines D, Alexander Yu S, Nikita VV. et al. The Effects of Intermittent Hypoxic–Hyperoxic Exposures on Lipid Profile and Inflammation in Patients With Metabolic Syndrome. Front Cardiovasc Med 2021; 8: 700826
• 13 Burtscher J, Citherlet T, Camacho-Cardenosa A, Camacho-Cardenosa M, Raberin A, Krumm B. et al. Mechanisms underlying the health benefits of intermittent hypoxia conditioning. J Physiol 2023; 602: 5757-5783
• 14 Navarrete-Opazo A, Mitchell GS. Therapeutic potential of intermittent hypoxia: A matter of dose. Am J Physiol Regul, Integr Comp Physiol 2014; 307: R1181-R1197
• 15 Kelly LP, Basset FA. Acute Normobaric Hypoxia Increases Post-exercise Lipid Oxidation in Healthy Males. Front Physiol 2017; 8: 293
• 16 Billaut F, Buchheit M. Repeated-sprint performance and vastus lateralis oxygenation: Effect of limited O₂ availability. Scand J Med Sci Sports 2013; 23: e185-e193
• 17 McLean BD, Gore CJ, Kemp J. Application of ‘Live Low-Train High’ for Enhancing Normoxic Exercise Performance in Team Sport Athletes. Sports Med 2014; 44: 1275-1287
• 18 Papoti M, Manchado-Gobatto FB, Gobatto CA. Inter-effort recovery hypoxia: a new paradigm in sport science?. BMJ Open Sport Exerc Med 2023; 9: e001520
• 19 Carvalho CD, Ferronato GD, Coelho-Ruzzi VM, Papoti M. Standardization of evaluation and exercise prescription for deep water running with normobaric hypoxia exposure. Sci Sports 2024; 39: 607-617
• 20 Dellavechia de Carvalho C, Marcolino Putti G, Figueiredo Foresti Y, Alves Ribeiro F, Causin Andreossi J, Ferraz de Campos G. et al. Recovery in normobaric hypoxia as an additional stimulus for high-intensity intermittent training. Sci Sports 2023; 38: 189-196
• 21 Foresti YF, Carvalho CDD, Ribeiro FA, Andreossi JC, Luches-Pereira G, Bertucci DR. et al. Acute Physiological Responses to “Recovery Intermittent Hypoxia” in Hiit. Rev Bras Med Esporte 2024; 30: e2021_0499
• 22 Li SN, Anbalagan P, Pang J, Ihsan M, Girard O. Exercise responses to repeated cycle sprints with continuous and intermittent hypoxic exposure. Eur J Sport Sci 2024; 24: 1045-1055
• 23 de Arruda TB, Ribeiro FA, Putti GM, Papoti M. Inter-Effort Recovery Intermittent Hypoxia and Force Parameters in Sprint Interval Exercise. Int J Exerc Sci 2025; 18: 672-685
• 24 Roels B, Millet GP, Marcoux CJL, Coste O, Bentley DJ, Candau RB. Effects of hypoxic interval training on cycling performance. Med Sci Sports Exerc 2005; 37: 138-146
• 25 Putti GM, Costa GP, Norberto MS, De Carvalho CD, Bertuzzi RCDM, Papoti M. Use of Inter-Effort Recovery Hypoxia as a New Approach to Improve Anaerobic Capacity and Time to Exhaustion. High Alt Med Biol 2024; 25: 68-76
• 26 Morton JP, Cable NT. The effects of intermittent hypoxic training on aerobic and anaerobic performance. Ergonomics 2005; 48: 1535-1546
• 27 Takei N, Kakehata G, Inaba T, Morita Y, Sano H, Girard O. et al. Effect of hypoxic sprint interval exercise and normoxic recovery on performance and acute physiological responses. Eur J Sport Sci 2024; 24: 279-288
• 28 Humberstone-Gough CE, Saunders PU, Bonetti DL, Stephens S, Bullock N, Anson JM. et al. Comparison of live high: train low altitude and intermittent hypoxic exposure. J Sports Sci Med 2013; 12: 394-401
• 29 Mardyła M, Maciejczyk M, Pałka T, Więcek M, Kusmierczyk J, Szymura J. et al. Intermittent hypoxia training does not change erythrocyte aggregation indicators in young, healthy men. Front Physiol 2024; 15: 1386650
• 30 Gore CJ, Rodríguez FA, Truijens MJ, Townsend NE, Stray-Gundersen J, Levine BD. Increased serum erythropoietin but not red cell production after 4 wk of intermittent hypobaric hypoxia (4,000–5,500 m). J Appl Physiol 2006; 101: 1386-1393
• 31 Rodríguez FA, Ventura JL, Casas M, Casas H, Pagés T, Rama R. et al. Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia. Eur J Appl Physiol 2000; 82: 170-177
• 32 Wojan F, Stray-Gundersen S, Nagel MJ, Lalande S. Short exposure to intermittent hypoxia increases erythropoietin levels in healthy individuals. J Appl Physiol 2021; 130: 1955-1960
• 33 Nagel MJ, Jarrard CP, Lalande S. Effect of a Single Session of Intermittent Hypoxia on Erythropoietin and Oxygen-Carrying Capacity. IJERPH 2020; 17: 7257
• 34 Katuntsev V, Zakharov Sy, Sukhostavtseva T, Puchkova A. 2020; https://www.elibrary.ru/item.asp?id=45711377
• 35 Tobin B, Costalat G, Renshaw GMC. Intermittent not continuous hypoxia provoked haematological adaptations in healthy seniors: hypoxic pattern may hold the key. Eur J Appl Physiol 2020; 120: 707-718
• 36 Serebrovskaya TV. Intermittent Hypoxia Research in the Former Soviet Union and the Commonwealth of Independent States: History and Review of the Concept and Selected Applications. High Alt Med Biol 2002; 3: 205-221
• 37 McKay AKA, Stellingwerff T, Smith ES, Martin DT, Mujika I, Goosey-Tolfrey VL. et al. Defining Training and Performance Caliber: A Participant Classification Framework. Int J Sports Physiol Perform 2022; 17: 317-331
• 38 Borg G. Psychophysical basis of perceived exertion. Med Sci Sports Exerc 1982; 14: 377-381
• 39 Midgley AW, McNaughton LR, Polman R, Marchant D. Criteria for Determination of Maximal Oxygen Uptake. Sports Med 2007; 37: 1019-1028
• 40 Binder RK, Wonisch M, Corra U, Cohen-Solal A, Vanhees L, Saner H. et al. Methodological approach to the first and second lactate threshold in incremental cardiopulmonary exercise testing. Eur J Cardiovasc Prev Rehabil 2008; 15: 726-734
• 41 Saunders PU, Telford RD, Pyne DB, Cunningham RB, Gore CJ, Hahn AG. et al. Improved running economy in elite runners after 20 days of simulated moderate-altitude exposure. J Appl Physiol 2004; 96: 931-937
• 42 R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org 2024
• 43 Wickham H. ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag New York; 2016. Available from https://ggplot2.tidyverse.org
• 44 Bates D, Mächler M, Bolker B, Walker S. Fitting Linear Mixed-Effects Models Using lme4. J Stat Softw 2015; 67: 1-48
• 45 Kuznetsova A, Brockhoff PB, Christensen RHB. lmerTest Package: Tests in Linear Mixed Effects Models. J Stat Softw 2017; 82: 1-26
• 46 Good K, Rey K. ggResidpanel: Panels and Interactive Versions of Diagnostic Plots using 'ggplot2'. R package version 0.3.0. https://CRAN.R-project.org/package=ggResidpanel 2019;
• 47 Lenth Russel V, Piaskowski J. emmeans: Estimated Marginal Means, aka Least-Squares Means. R package version 1.10.3. https://CRAN.R-project.org/package=emmeans 2024
• 48 Sarkar D. Lattice: Multivariate Data Visualization with R. New York: Springer; 2008. http://lmdvr.r-forge.r-project.org
• 49 Müller K, Wickham H. tibble: Simple Data Frames. R package version 3.2.1. https://CRAN.R-project.org/package=tibble 2023
• 50 Geiser J, Vogt M, Billeter R, Zuleger C, Belforti F, Hoppeler H. Training High—Living Low: Changes of Aerobic Performance and Muscle Structure with Training at Simulated Altitude. Int J Sports Med 2001; 22: 579-585
• 51 Truijens MJ, Toussaint HM, Dow J, Levine BD. Effect of high-intensity hypoxic training on sea-level swimming performances. J Appl Physiol 2003; 94: 733-743
• 52 Nakamoto FP, Ivamoto RK, Andrade M dos S, de Lira CAB, Silva BM, da Silva AC. Effect of Intermittent Hypoxic Training Followed by Intermittent Hypoxic Exposure on Aerobic Capacity of Long Distance Runners. J Strength Cond Res 2016; 30: 1708-1720
• 53 Park H-Y, Shin C, Lim K. Intermittent hypoxic training for 6 weeks in 3,000 m hypobaric hypoxia conditions enhances exercise economy and aerobic exercise performance in moderately trained swimmers. Biol Sport 2017; 35: 49-56
• 54 Debevec T, Amon M, Keramidas ME, Kounalakis SN, Pišot R, Mekjavic IB. Normoxic and Hypoxic Performance Following 4 Weeks of Normobaric Hypoxic Training. Aviat, Space, Environ Med 2010; 81: 387-393
• 55 Arezzolo D, Coffey VG, Byrne NM, Doering TM. Effects of Eight Interval Training Sessions in Hypoxia on Anaerobic, Aerobic, and High Intensity Work Capacity in Endurance Cyclists. High Alt Med Biol 2020; 21: 370-377
• 56 Burtscher M, Gatterer H, Faulhaber M, Gerstgrasser W, Schenk K. Effects of Intermittent Hypoxia on Running Economy. Int J Sports Med 2010; 31: 644-650
• 57 Katayama K, Matsuo H, Ishida K, Mori S, Miyamura M. Intermittent Hypoxia Improves Endurance Performance and Submaximal Exercise Efficiency. High Alt Med Biol 2003; 4: 291-304
• 58 Saunders PU, Telford RD, Pyne DB, Hahn AG, Gore CJ. Improved running economy and increased hemoglobin mass in elite runners after extended moderate altitude exposure. J Sci Med Sport 2009; 12: 67-72
• 59 Miller GD, Husk J, Crouch AK, Eichner D. EPO and the athlete biological passport: Hematological results from a placebo-controlled, boosting and microdose EPO administration in male recreational athletes. Drug Test Anal 2022; 14: 1962-1973
• 60 Zembron-Lacny A, Tylutka A, Wacka E, Wawrzyniak-Gramacka E, Hiczkiewicz D, Kasperska A. et al. Intermittent Hypoxic Exposure Reduces Endothelial Dysfunction. BioMed Res Int 2020; 2020: 6479630
• 61 Camaschella C, Pagani A, Nai A, Silvestri L. The mutual control of iron and erythropoiesis. Int J Lab Hematol 2016; 38: 20-26
• 62 Wagner PD. Systemic oxygen transport and utilization. J Breath Res 2008; 2: 024001
• 63 Faiss R, Léger B, Vesin J-M, Fournier P-E, Eggel Y, Dériaz O. et al. Significant Molecular and Systemic Adaptations after Repeated Sprint Training in Hypoxia. PloS One 2013; 8: e56522
• 64 Ponsot E, Dufour SP, Zoll J, Doutrelau S, N’Guessan B, Geny B. et al. Exercise training in normobaric hypoxia in endurance runners. II. Improvement of mitochondrial properties in skeletal muscle. J Appl Physiol 2006; 100: 1249-1257
• 65 Bonne TC, Jeppesen JS, Bejder J, Breenfeldt Andersen A, Olsen NV, Huertas JR. et al. Moderate hypoxic exposure for 4 weeks reduces body fat percentage and increases fat-free mass in trained individuals: a randomized crossover study. Sleep and Breathing 2023; 27: 1611-1618
• 66 Morishima T, Kurihara T, Hamaoka T, Goto K. Whole body, regional fat accumulation, and appetite-related hormonal response after hypoxic training. Clin Physiol Funct Imaging 2014; 34: 90-97
• 67 Camacho-Cardenosa A, Camacho-Cardenosa M, Brooks D, Timón R, Olcina G, Brazo-Sayavera J. Effects training in hypoxia on cardiometabolic parameters in obese people: A systematic review of randomized controlled trial. Aten Prim 2019; 51: 397-405