Mechanisms underlying the health benefits of intermittent hypoxia conditioning

Johannes Burtscher; Tom Citherlet; Alba Camacho-Cardenosa; Marta Camacho-Cardenosa; Antoine Raberin; Bastien Krumm; Erich Hohenauer; Margit Egg; Mona Lichtblau; Julian Müller; Elena A Rybnikova; Hannes Gatterer; Tadej Debevec; Sebastien Baillieul; Giorgio Manferdelli; Tom Behrendt; Lutz Schega; Hannelore Ehrenreich; Grégoire P Millet; Max Gassmann; Christoph Schwarzer; Oleg Glazachev; Olivier Girard; Sophie Lalande; Michael Hamlin; Michele Samaja; Katharina Hüfner; Martin Burtscher; Gino Panza; Robert T Mallet

doi:10.1113/JP285230

Mechanisms underlying the health benefits of intermittent hypoxia conditioning

J Physiol. 2023 Oct 20. doi: 10.1113/JP285230. Online ahead of print.

Authors

Johannes Burtscher¹, Tom Citherlet¹, Alba Camacho-Cardenosa², Marta Camacho-Cardenosa³, Antoine Raberin¹, Bastien Krumm¹, Erich Hohenauer^{4

5

6}, Margit Egg⁷, Mona Lichtblau^{8

9}, Julian Müller^{8

9}, Elena A Rybnikova¹⁰, Hannes Gatterer^{11

12}, Tadej Debevec^{13

14}, Sebastien Baillieul¹⁵, Giorgio Manferdelli¹, Tom Behrendt¹⁶, Lutz Schega¹⁶, Hannelore Ehrenreich¹⁷, Grégoire P Millet¹, Max Gassmann^{18

19

20}, Christoph Schwarzer²¹, Oleg Glazachev²², Olivier Girard²³, Sophie Lalande²⁴, Michael Hamlin²⁵, Michele Samaja²⁶, Katharina Hüfner²⁷, Martin Burtscher²⁸, Gino Panza^{29

30}, Robert T Mallet³¹

Affiliations

¹ Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland.
² Department of Physical Education and Sports, Faculty of Sports Science, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.
³ Clinical Management Unit of Endocrinology and Nutrition - GC17, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain.
⁴ Rehabilitation and Exercise Science Laboratory (RES lab), Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Landquart, Switzerland.
⁵ International University of Applied Sciences THIM, Landquart, Switzerland.
⁶ Department of Neurosciences and Movement Science, University of Fribourg, Fribourg, Switzerland.
⁷ Institute of Zoology, University of Innsbruck, Innsbruck, Austria.
⁸ Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
⁹ University of Zurich, Zurich, Switzerland.
¹⁰ Pavlov Institute of Physiology, Russian Academy of Sciences, St Petersburg, Russia.
¹¹ Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy.
¹² Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL-Private University for Health Sciences and Health Technology, Hall in Tirol, Austria.
¹³ Faculty of Sport, University of Ljubljana, Ljubljana, Slovenia.
¹⁴ Department of Automatics, Biocybernetics and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia.
¹⁵ Service Universitaire de Pneumologie Physiologie, University of Grenoble Alpes, Inserm, Grenoble, France.
¹⁶ Chair Health and Physical Activity, Department of Sport Science, Institute III, Otto von Guericke University Magdeburg, Magdeburg, Germany.
¹⁷ Clinical Neuroscience, University Medical Center and Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
¹⁸ Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zurich, Switzerland.
¹⁹ Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
²⁰ Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.
²¹ Institute of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
²² Department of Normal Physiology, N.V. Sklifosovsky Institute of Clinical Medicine, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.
²³ School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Crawley, Western Australia, Australia.
²⁴ Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, USA.
²⁵ Department of Tourism, Sport and Society, Lincoln University, Christchurch, New Zealand.
²⁶ Department of Health Science, University of Milan, Milan, Italy.
²⁷ Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, University Hospital for Psychiatry II, Medical University of Innsbruck, Innsbruck, Austria.
²⁸ Department of Sport Science, University of Innsbruck, Innsbruck, Austria.
²⁹ The Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI, USA.
³⁰ John D. Dingell VA Medical Center Detroit, Detroit, MI, USA.
³¹ Department of Physiology & Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA.

PMID: 37860950
DOI: 10.1113/JP285230

Abstract

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure.

Keywords: cardiovascular diseases; cellular stress responses; intermittent hypoxia conditioning; mitochondria; neurological disorders; oxygen sensing.

Abstract

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