A history of research on hypoxic adaptation, its physiological mechanisms, and training approaches in medicine and sport. A review of different types of hypoxia.
Editorial note. Published in 2021, this material describes different forms of hypoxic exposure, including altitude and athletic training. These should not automatically be equated with IHHT. This is a review of a method, not a study of an OXYTERRA device and not instructions for self-administration. The original bibliography contains two different entries numbered 40; both have been retained under their original numbers, without deletion or merging.
Abstract
This review addresses the phenomena of hypoxic adaptation and training. It briefly outlines the historical stages in the study of human adaptation to hypoxia and the use of hypoxic training in medicine and sport. It describes the contribution of Russian science to the development of this field and summarizes the literature on the mechanisms of hypoxic adaptation, hypoxic training models, and their effectiveness. The review concludes by discussing the considerable potential of hypoxic training in elite sport.
Keywords: hypoxia, adaptation, hypoxic training, hypoxytherapy, sport.
Introduction
Adaptation to hypoxia is extremely widespread among living organisms and appears to be one of the most evolutionarily ancient forms of adaptation [1]. Hypoxia, defined as an inadequate supply of oxygen to tissues and cells or impaired oxygen utilization, was initially associated only with pathological conditions [2, 3]. These views changed substantially when, in the late 19th century, hypoxia was shown to occur during the ‘natural functioning of the body’ [4].
A conceptual shift gradually took place: interest in hypoxia came to be seen as physiologically important for understanding adaptive changes in response to an external hypoxic factor, and clinically important for studying various pathophysiological conditions, especially cardiovascular and cerebrovascular diseases. The adaptive potential of hypoxia can also be used successfully in therapeutic strategies for prevention, rehabilitation, and treatment [5, 6].
A brief history of the subject
One of the earliest written references to hypoxytherapy is attributed to Hippocrates, who advised the sick to move to a moderate altitude. The traveler Marco Polo, describing the people of Asia, also noted that when ill they went to the mountains to recover [7]. Moving to the mountains can be considered a specific case of adaptation called acclimatization, meaning an individual adaptive response of the body to prolonged residence in particular natural and climatic conditions. The duration of acclimatization depends on the altitude, temperature conditions, and individual characteristics, and may range from 7 to 25 days. Shorter periods of hypoxia (minutes to hours), alternating with periods of normoxia, are called intermittent hypoxia. This type of hypoxia became more common with industrial development and the exploration of the Earth. Advances in ballooning, aviation, and the space industry, as well as the development of high-altitude areas for economic activity, made it necessary to study carefully the effects of intermittent hypoxia on humans.
From 1870 to 1878, French zoologist and physiologist Paul Bert (1833–1886) conducted 670 experiments on the physiological consequences of changes in atmospheric pressure, studying balloonists flying at different altitudes [8]. Following a 1911 mountain expedition and chamber studies by John Scott Haldane (1892–1964), who had initially studied decompression sickness in deep-sea divers, suits for pilots and recommendations for improving adaptation to hypoxia were developed [9]. In 1919, chemical engineer Harold Pierce developed a pressure chamber equipped with a refrigeration unit, enabling researchers to study human responses to the combination of cold and reduced atmospheric pressure [10].
Research on hypoxia in Russia
One of the earliest recorded uses of pressure chambers in Russia dates to 1869, when A. N. Simonov established a ‘pneumatic clinic’ on Vasilievsky Island in St. Petersburg. It consisted of two iron pressure chambers for four people and one ‘stone’ chamber comprising two rooms for ten people [11].
In the USSR, hypoxia research developed extensively. A major breakthrough in understanding the physiological mechanisms by which hypoxia affects animals and humans was made by G. E. Vladimirov [12], P. I. Egorov [13], V. V. Streltsov [14], N. N. Sirotinin [15], and D. E. Rosenblum [16].
Interest in hypoxia, initially driven by the needs of military pilots, expanded into medical and fundamental research. From the 1970s onward, a substantial body of research was published by N. A. Agadzhanyan [17], V. A. Berezovsky [18], A. Z. Kolchinskaya [19], L. D. Lukyanova [20], T. V. Serebrovskaya [21, 22] and many other researchers. High-altitude expeditions to Altai, the Caucasus, the Pamirs, and the Tien Shan investigated the effects of chronic hypoxia on local residents. In 1973, N. N. Sirotinin founded the Elbrus Medical and Biological Station [3, 17, 18, 20], where intensive research, including by our group, continues to examine the effects of hypobaric hypoxia on the body’s physiological systems and resistance [6, 23].
A substantial body of clinical and experimental evidence has now accumulated in Russian and international literature describing hypoxic adaptation and indicating that hypoxic training can be highly effective in medicine. Unfortunately, Russian research in this area consists mainly of studies from the second half of the 20th century; interest in the subject has waned somewhat in Russia, and many outstanding achievements by Russian specialists have been forgotten. This is particularly true of protocols developed for hypoxic training using intermittent hypoxia, whose efficacy has been demonstrated in treating cardiovascular, metabolic, and neurological disorders, allergies, bronchial asthma, diabetes, and many other common diseases [21, 24].
Intermittent hypoxia
Intermittent hypoxia consists of repeated episodes of hypoxia alternating with episodes of normoxia, less severe hypoxia, or hyperoxia. Intermittent or interval hypoxic training (IHT) protocols used in experiments vary considerably in cycle duration, the number of hypoxic episodes, and the number of training days. They range from relatively short hypoxic episodes (1–10 min), alternating with 1–20-minute episodes of normoxia within a day [25], to longer daily exposures (1–12 h) over periods of 2 to 90 days [26].
The relationship between hypoxia level and training regimen is an important factor in balancing efficacy and safety. Training with moderate hypoxia (9–16% O2) and a low cycle frequency (3–15 episodes per day) most often produced beneficial effects without pathology, whereas severe hypoxia (2–8% O2) and a larger number of daily episodes (48–2.400 per day) more often led to pathological conditions [27]. Thus, the accumulated evidence suggests that a ‘low dose’ of hypoxic training (moderate hypoxia and a small number of episodes) may be a simple, safe, and effective method with considerable therapeutic potential in clinical practice.
Key mechanisms of the adaptive response to hypoxia
Resistance to hypoxia in animals and humans is determined by genetic and phenotypic characteristics. Oxygen homeostasis is maintained through the coordinated function of the respiratory system, circulation, hematopoiesis, and tissue respiration; oxygen partial pressure is a universal indicator of tissue oxygenation [2, 18, 19].
Adaptive responses to physiological and exogenous hypoxia are similar and share many features with compensatory adaptive mechanisms in diseases that ultimately involve tissue hypoxia; thus, responses to hypoxia remain nonspecific up to a point. The nonspecific stress response to hypoxia is accompanied by increased glucocorticoid levels, leading to activation of gluconeogenesis in the liver and skeletal muscles. As a systemic structural trace of disturbed homeostasis develops, the factors driving the stress response disappear, and the stress response itself subsides after playing its role in establishing adaptation [2].
Classical specific systemic mechanisms of adaptation to hypoxia include changes in pulmonary ventilation [21, 28], changes in cardiovascular function that increase oxygen delivery to tissues in need, and tissue-level changes that enable more efficient use of oxygen in metabolic processes [2].
Cellular regulation and HIF-1
Regulation of the adaptive response to hypoxia at the cellular level is largely driven by activation of the hypoxia-sensitive transcription factor hypoxia-inducible factor 1 (HIF-1) [29]. HIF-1 is a heterodimer of HIF-1α and HIF-1β. Oxygen levels regulate HIF-1α in a dose-dependent manner: its level gradually rises as the oxygen content of air falls from 20% to 5%, with a particularly pronounced increase below 5% O2 [30]. More than 60 direct target genes have been identified for HIF-1, covering erythropoiesis, angiogenesis, glucose transporters, and other functions. HIF-1α levels change rapidly in both directions: for example, signs of HIF-1α degradation in lung tissue appear less than 1 min after reoxygenation [31]. This rapid dynamics enables a timely adaptive response to brief hypoxic episodes, which is particularly important in intermittent hypoxia; HIF-1 appears to be a critical factor in initiating and reversing adaptive responses to intermittent hypoxia.
However, there are important differences between the adaptive responses to prolonged and intermittent hypoxia. One is their differential effect on the biphasic respiratory response [32]. Unlike prolonged hypoxia, which markedly reduces the initial increase in ventilation and increases the magnitude of its subsequent decline, intermittent hypoxia does not cause a secondary decrease in ventilation in humans [33], or in experimental animals [25]. This may be related to the specific ability of intermittent hypoxia to alter neuronal respiratory activity: it produces a sustained increase in normoxic ventilation [25] by inducing serotonin-dependent long-term facilitation of respiratory activity [34], whereas prolonged hypoxia does not produce this effect [35]. Finally, differences in the adaptive response to intermittent hypoxia may also be determined by genetic variation: intermittent hypoxia was shown to increase the blood-pressure response to hypoxia, heart size, and atrial natriuretic peptide mRNA levels in spontaneously hypertensive rats (SHR), but not in normotensive Wistar–Kyoto rats [36].
Use of hypoxic training in medicine and sport
Repeated hypoxic episodes are a powerful stressor and cause significant cumulative changes in the body’s physiological responses. In addition to improving survival under severe hypoxia [37] interval hypoxic training (IHT) can increase the body’s overall nonspecific resistance [2, 5, 28].
Cross-adaptation is the phenomenon whereby adaptation to one stressor confers resistance to another [2, 6], leaving a molecular imprint in protein expression and antioxidant-system activity. For example, intermittent hypoxic training has been shown to have a pronounced antiarrhythmic effect during acute myocardial ischemia in animals [2] and to prevent experimental atherosclerosis in rabbits [38]. The cardioprotective effect of IHT correlates with the ability of intermittent hypoxia to increase coronary blood flow and angiogenesis, as well as the expression of antioxidant enzymes [39].
Interval hypoxic training has gained wide acceptance in civilian and sports medicine [40]. In addition to conditions directly associated with hypoxia (lung and cardiovascular diseases) [3], IHT has demonstrated efficacy in treating diseases of the central nervous system and gastrointestinal tract, and in dermatology, hematology, and diabetes [3, 22]. Normobaric intermittent hypoxic training has a thymoleptic effect, but does not lead to significant improvement in anxiety-depressive conditions [41].
Hypoxic training in sport
Hypoxic training can also be used successfully as a strategy to improve performance in athletes, especially those in cyclic endurance sports [3, 19, 40]. The 1968 Summer Olympic Games were held in Mexico City, more than 2 km above sea level. To address hypoxic adaptation among USSR national-team athletes, mandatory training camps in mountainous conditions were proposed [4], and hypoxic training became a required part of preparation for elite athletes in the USSR.
Decades of Russian research have demonstrated the high efficacy of hypoxic training: 10–30 IHT sessions (300–420 min of hypoxia) have an effect equivalent to a month at moderate altitude [42]. Five weeks of IHT in athletes increased maximal oxygen uptake by 3.4 mL/min·kg, alongside a 6% improvement in running performance over distances of varying duration and a 5% increase in maximal exercise time on a cycle ergometer. Male athletes typically achieve comparable results after more than 9 months of intensive training [43]. In mountaineers, IHT increased physical work capacity and endurance in an exercise cardiorespiratory test and according to heart-rate variability assessment [44], while in rowers it increased hemoglobin content by 6.8% and red blood cell count by 5.1% [45].
Unfortunately, in recent years, foreign colleagues have taken the lead in research on this topic.
Hypoxic training before the 2002 Winter Olympics in Salt Lake City enabled the British national biathlon team to compete with optimal physiological indicators without an acclimatization period: resting blood pressure and heart rate decreased, hemoglobin increased, and blood lactic acid levels during submaximal exercise normalized [46].
Altitude-training models
There are three main models of altitude training for athletes: live high + train high; live low + train high; and live high + train low. Altitude training or residence, as well as normobaria, can be simulated using a pressure chamber, breathing gas mixtures, or a combination of these approaches with high-altitude exposure [47].
The ‘live high, train low’ strategy has been shown to improve athletes’ hematological and ventilatory parameters and increase erythropoietin synthesis [48].
With the reverse approach, in which athletic exercise is performed under hypoxic conditions, performance may remain unchanged or, conversely, decline substantially [49], although it was initially assumed that training under such hypoxic conditions, accompanied by a particularly pronounced reduction in oxygen partial pressure in muscle tissue, would simulate more strenuous training and therefore produce a greater training response.
Living and training at altitude combine the increase in red blood cell volume resulting from acclimatization with an additional training stimulus caused by tissue hypoxia during exercise. The high red blood cell levels in athletes using this model are well documented and correlate with overall training indicators in highly qualified athletes [50].
Prospects for use in sport
The large number of international publications on hypoxic training in athletes in recent years confirms the growing global relevance of this issue and the widely recognized practical potential of hypoxic training in elite sport. In contrast, insufficient attention from Russian sports medicine to hypoxic training as a means of improving athletic performance and health is, in our view, one factor contributing to the declining competitiveness of Russian sport internationally.
It can be considered established that the skilled use of different hypoxic-training regimens, without doping substances, increases athletes’ resistance to physical and psychoemotional stress by stimulating nonspecific and specific physiological adaptation mechanisms. This increases the intensity and effectiveness of training and can substantially improve athletic performance without risking adverse health effects.
Conclusions
Long-term research has shown that hypoxic training substantially increases the body’s resistance to physical and psychoemotional stress by activating cross-adaptation mechanisms. Despite the pioneering contribution of Russian researchers, the considerable practical potential of this phenomenon is currently realized only to a limited extent in Russia. Greater attention should clearly be paid to incorporating different types of hypoxic training into the training programs of athletes at various levels, which would undoubtedly help improve athletic performance.
In addition, hypoxic training has emerged as a promising non-pharmacological approach to treatment and rehabilitation for patients with a wide range of conditions, as well as for prevention and training in healthy people.
This work was supported by Russian Foundation for Basic Research grant No. 19-015-00336.
Related material
Physiological mechanisms of intermittent normobaric hypoxia
Hypoxic protocols and physical performance: an umbrella review
References
References 1–8
1. Bickler P.E., Buck L.T. Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen availability // Ann. Rev. Physiol. 2007. V. 69. P. 145–170.
2. F. Z. Meerson, V. P. Tverdokhlib, V. M. Boyev et al. Adaptation to periodic hypoxia in therapy and prevention. Moscow, 1989. Meerson F.Z., Tverdokhlib V.P., Boyev V.M. et al. Adaptation to periodic hypoxia in therapy and prevention. Moscow, 1989.
3. V. V. Goranchuk, N. I. Sapova, A. O. Ivanov. Hypoxytherapy. St. Petersburg, 2003. Goranchuk V.V., Sapova N.I., Ivanov A.O. Hypoxytherapy. St. Petersburg, 2003.
4. A. G. Nikolaeva. Using adaptation to hypoxia in medicine and sport. Vitsebsk, 2015. Nikolaeva A.G. Using adaptation to hypoxia in medicine and sport. Vitsebsk, 2015.
5. R. B. Strelkov, A. Ya. Chizhov. Intermittent normobaric hypoxia in prevention, treatment, and rehabilitation. Yekaterinburg, 2001. Strelkov R.B., Chizhov A.Y. Intermittent normobaric hypoxia in the prevention, treatment and rehabilitation. Yekaterinburg, 2001.
6. M. Yu. Zenko, E. A. Rybnikova. Cross-adaptation: from F. Z. Meerson to the present day. Part 1. Adaptation, cross-adaptation, and cross-sensitization // Uspekhi fiziologicheskikh nauk. 2019. Vol. 50, no. 4, pp. 3–13. Zenko M.Y., Rybnikova E.A. Cross adaptation: from F.Z. Meerson to our days. P. 1. Adaptation, cross adaptation and cross-sensitization // Uspekhi fiziologicheskikh nauk. 2019. V. 50. № 4. P. 3–13.
7. V. A. Berezovsky, M. I. Levashov. Introduction to orotherapy. Kyiv, 2000. Berezovsky V.A., Levashov M.I. Introduction to orotherapy. Kiev, 2000.
8. Bert P. La pression barométrique: recherches de physiologie expérimentale. Paris, 1878.
References 9–14
9. Haldane J.S., Kellas A.M., Kennaway E.L. Experiments on acclimatization to reduced atmospheric pressure // J. Physiol. 1919. V. 53. P. 181–206.
10. Jenkins D.R. Dressing for altitude: US aviation pressure suits, Wiley post to space shuttle. Washington, NASA SP. 2012.
11. V. V. Smolin, G. M. Sokolov, B. N. Pavlov. Diving and its medical support. Moscow, 2001. Smolin V.V., Sokolov G.M., Pavlov B.N. Diving and its medical support. Moscow, 2001.
12. Vladimirov G.E., Galvyalo M.Ya., Goryukhina T.A. et al. Use of stays in a high-altitude climate for pilot altitude training // Oxygen deprivation and combating it. 1939. pp. 43–104.
13. Egorov P.I. The effect of high-altitude flights on the pilot’s body. Moscow, 1937.
14. Streltsov V.V. The effect of reduced barometric pressure on the body // Issues in Aviation Medicine. 1939. Vol. 5–6, No. 1, pp. 60–81.
References 15–19
15. Sirotinin N.N. The effect of acclimatization to a high-altitude climate on adaptation to reduced atmospheric pressure in a barometric chamber // Archive of Pathological Anatomy and Pathological Physiology. 1940. Vol. 6, Nos. 1–2, pp. 35–42.
16. Rozenblyum D.E. Some conclusions from observations of the effect of rarefied air on the body // Military Medical Journal. 1948. No. 1, p. 36.
17. Agadzhanyan N.A., Mirrakhimov M.M. Mountains and the body’s resistance. Moscow, 1970.
18. Berezovsky V.A., Levashov M.I. Increasing human reserve capacity through training with intermittent normobaric hypoxia // Aerospace and Environmental Medicine. 2000. Vol. 34, No. 2, pp. 39–43.
19. Kolchinskaya A.Z., Abazova Z.Kh., Kumykov V.K. et al. Key milestones in the development of hypoxia science // Problems of Social Hygiene, Public Health and the History of Medicine. 2002. No. 2, pp. 52–54.
References 20–26
20. Lukyanova L.D. Bioenergetic hypoxia: concept, mechanisms, and methods of correction // Bulletin of Experimental Biology and Medicine. 1997. Vol. 124, No. 9, pp. 244–254.
21. Serebrovskaya T.V., Karaban I.N., Kolesnikova E.E. et al. Human hypoxic ventilatory response with blood dopamine content under intermittent hypoxic training // Can. J. Physiol. Pharmacol. 1999. V. 77. P. 967–973.
22. Serebrovska T.V., Portnychenko A.G., Portnichenko V. I. et al. Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients // Eur. J. of Appl. Physiol. 2019. V. 119. № 3. P. 813–823.
23. Rybnikova E.A., Baranova K.A., Gluschenko T.S. et al. Role of HIF-1 in neuronal mechanisms of adaptation to psychoemotional and hypoxic stress // Int. J. of Physiol. and Pathophysiol. 2015. V. 6. № 1. P. 1–11.
24. Karash Yu.M., Strelkov R.B., Chizhov A.Ya. Normobaric hypoxia in treatment, prevention, and rehabilitation. Moscow, 1988.
25. Cao K.Y., Zwillich C.W., Berthon-Jones M. et al. Increased normoxic ventilation induced by repetitive hypoxia in conscious dogs // J. Appl. Physiol. 1992. V. 73. P. 2083–2088.
26. Rodriguez F.A., Casas H., Casas M. et al. Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity // Med. Sci. Sports Exerc. 1999. V. 31. P. 264–268.
References 27–35
27. Navarrete-Opazo A., Mitchell G.S. Therapeutic potential of intermittent hypoxia: a matter of dose // Am. J. of Physiol.-Regulatory, Integrative and Comparative Physiol. 2014. V. 307. № 10. P. R1181–R1197.
28. Ragozin O.N., Pashchenko I.G., Balykin M.V. Normobaric hypoxia in the chronotherapy of bronchial asthma. Ulyanovsk, 2001.
29. Semenza G.L. HIF-1: mediator of physiological and pathophysiological responses to hypoxia // J. Appl. Physiol. 2000. V. 88. P. 1474–1480.
30. Jiang B.H., Semenza G.L., Bauer C. et al. Hypoxia-inducible factor-1 levels vary exponentially over a physiologically relevant range of O2 tension // Am. J. Physiol. Cell Physiol. 1996. V. 271. P. C1172–C1180.
31. Yu A.Y., Frid M.G., Shimoda L.A. et al. Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung // Am. J. Physiol. Lung Cell Mol. Physiol. 1998. V. 275. P. L818–L826.
32. Easton P.A., Slykerman L.J., Anthonisen N.R. Ventilatory response to sustained hypoxia in normal adults // J. Appl. Physiol. 1986. V. 61. P. 906–911.
33. Nieuwenhuijs D., Sarton E., Teppema L. et al. Propofol for monitored anesthesia care: implications on hypoxic control of cardiorespiratory responses // Anesthesiol. 2000. V. 92. P. 46–54.
34. Turner D.L., Mitchell G.S. Long-term facilitation of ventilation following repeated hypoxic episodes in awake goats // J. Physiol. 1997. V. 499. P. 543–550.
35. Dwinell M.R., Janssen P.L., Bisgard G.E. Lack of longterm facilitation of ventilation after exposure to hypoxia in goats // Respir. Physiol. 1997. V. 108. P. 1–9.
References 36–42
36. Kraiczi H., Magga J., Sun X.Y. et al. Hypoxic pressor response, cardiac size, and natriuretic peptides are modified by long-term intermittent hypoxia // J. Appl. Physiol. 1999. V. 87. P. 2025–2031.
37. Mayfield K.P., Hong E.J., Carney K.M. et al. Potential adaptations to acute hypoxia: Hct, stress proteins, and set point for temperature regulation // Am. J. Physiol. Regulatory Integrative Comp. Physiol. 1994. V. 266. P. R1615–R1622.
38. Kitaev M.I., Aitbaev K.A., Lyamtsev V.T. The effect of hypoxic hypoxia on the development of atherosclerosis in rabbits // Aerospace and Environmental Medicine. 1999. Vol. 33, No. 5, pp. 54–57.
39. Zhuang J., Zhou Z. Protective effects of intermittent hypoxic adaptation on myocardium and its mechanisms // Biol. Sig. Recep. 1999. V. 8. P. 316–322.
40. Volkov N.I. Interval training in sports. Moscow, 2000.
40. Atamanov A.A., Buikov V.A. Hypobaric therapy for anxiety disorders in neuroses and psychosomatic diseases. Chelyabinsk, 1999.
42. Kogan O.G., Naydin B.L. Medical rehabilitation in neurology and neurosurgery. Moscow, 1988.
References 43–48
43. Dardouri U. Interval hypoxic training in the preparation of highly qualified football players: Abstract of a candidate’s dissertation. Moscow, 1997.
44. Ganapolsky V.P., Avdyushenko S.A., Grinchuk S.S. et al. The effect of hypoxic training and pharmacological correction on physical work capacity and autonomic regulation in mountaineers // Aerospace and Environmental Medicine. 2019. Vol. 53, No. 5, pp. 77–84.
45. Hamlin M.J., Hellemans J. Effect of intermittent normobaric hypoxic exposure at rest on haematological, physiological, and performance parameters in multi-sport athletes // J. Sports Sci. 2007. V. 25. № 4. P. 431–441.
46. Whyte P.G., Lane A., Pedlar C. et al. Intermittent hypoxic training in process of pre-acclimation among GB biathlon team preparing for the 2002 Olympic Games // 12th Commonwealth International Sport Conference. Abst. of reports. 2002. P. 19–23.
47. Adhikari S., Sreeman R., Saraswat S. et al. Does ‘live high-train low’ hypoxic training really improves endurance capacity of long distance runners? // Eur. Respiratory J. 2017. V. 50. Suppl. 61. P. PA2269.
48. Knaupp W., Khilnani S., Sherwood J. et al. Erythropoietin response to acute normobaric hypoxia in humans // J. Appl. Physiol. 1992. V. 73. P. 837–840.
References 49–50
49. Truijens M.J., Toussaint H.M., Dow J. et al. Effect of high-intensity hypoxic training on sea-level swimming performances // J. Appl. Physiol. 2003. V. 94. P. 733–43.
50. Jacobs R.A., Rasmussen P., Siebenmann C. et al. Determinants of time trial performance and maximal incremental exercise in highly trained endurance athletes // J. Appl. Physiol. 2011. V. 111. P. 1422–1430.
Technology and practice
To compare the parameters of the training protocols, see the section “IHHT Technology”: breathing-mixture protocols and session monitoring.
Applications of IHHT in sports and recovery is presented in a separate section of the website.