Individualized Intermittent Hypoxia Training: Principles and Practices

  • Tatiana V. SerebrovskayaEmail author
  • Lei Xi


Individual variation of homeostatic response to hypoxia has been recognized by investigators from the former Soviet Union as well as Western countries. The proven influence of both hereditary and environmental parameters on physiological responses must drive the selection of individual regimes for athletic training, disease treatment, and outcome prognostication. Our longitudinal examinations of identical twins both at sea level and altitudes have shown that the ventilatory response to hypoxic stimulus is a rigid, genetically determined, physiological characteristic reflecting an organism’s overall nonspecific reactivity. On the basis of our twin investigations, we have designed a nomogram to estimate individual nonspecific reactivity and functional reserves for prognosis of subject adaptation to hypoxia. Various strategies of adaptation were identified for persons with differing hypoxic ventilatory sensitivity. Intermittent hypoxic training (IHT) regimes can be customized to match this known individual reactivity. Mechanisms that mediate interindividual variation of adaptation to hypoxia were primarily determined by making measurements in animals with high (HR) and low (LR) resistance to acute hypoxia. Although there are several possible causes for such variation, much of the interest in Russian/Ukraine has focused on mitochondria. The researchers found that, when compared to LR rats, HR rats had: (1) greater mitochondrial enzyme complex I activity, (2) increased nitric oxide inhibition of Ca2+-ATPase activity with concomitant decreased intracellular Ca2+, (3) enhanced antioxidant activity, and (4) increased gene expression. Differential selective oxidation of two Krebs cycle substrates, alpha-ketoglutarate versus succinate, acts more intensively in HR animals, thereby enhancing cholinergic status. Our investigations have shown that l-arginine injections as well as IHT increase mitochondrial calcium capacity in LR rats to the same level as HR rats. Mitochondrial ATP-dependent potassium channel openers affected mitochondrial respiration differently in HR and LR rats. These differences were similar to the IHT effects. Nevertheless, there is a continued search for potential universal marker(s) for individual prognosis of adaptation to hypoxia. Future investigations will shed light on this very important question. Collectively, we can envisage a bright future for individualized IHT, which may play a significant role in the fast-developing field of personalized preventive medicine against various human diseases.


Acute Hypoxia Intermittent Hypoxia Training Reveal Risk Factor Mitochondrial Enzyme Complex mKATP Channel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Commonwealth of Independent States




Hypercapnic ventilatory sensitivity


Hypoxia-inducible factor 1


High resistant


Hypoxic ventilatory response


Intermittent hypoxic training


Live high-train low


Low resistant


Mitochondrial ATP-dependent potassium channels


Medium resistant


Nitric oxide


Maximal oxygen uptake


  1. 1.
    Abrahams E, Silver M. The case for personalized medicine. J Diabetes Sci Technol. 2009;3:680–4.PubMedGoogle Scholar
  2. 2.
    Agadzhanyan NA, Mirrakhimov MM. Mountains and resistance. Moscow: Nauka Publishers; 1970 [In Russian].Google Scholar
  3. 3.
    Agadzhanyan NA. Adaptation and an organism’s reserves. Moscow: Fizkultura i Sport; 1983 [In Russian].Google Scholar
  4. 4.
    Aidaraliev AA, Maksimov AL. Human adaptation to extreme conditions. The experience of prognosis. Leningrad: Nauka; 1988 [In Russian].Google Scholar
  5. 5.
    Aidaraliev AA, Maksimov AL, Chernook TB. Adaptation capabilities of polar explorers in Antarctic mountains. Kosm Biol Aviakosm Med. 1987;21(6):62–6 [In Russian].PubMedGoogle Scholar
  6. 6.
    Aydaraliev AA, Maksimov AL. Physical capacity estimation in the mountains. Methodical recommendations. Moscow: Nauka; 1980 [In Russian].Google Scholar
  7. 7.
    Aydaraliev A, Baevsky R, Berseneva T, et al. A framework for evaluating an organism’s functional reserves. Frunze: Ilim; 1988. 195 pp [In Russian].Google Scholar
  8. 8.
    Baevsky RM. Prognosis of the body’s position between normal and pathological condition. Moscow: Meditsina; 1979 [In Russian].Google Scholar
  9. 9.
    Baevsky RM. Principals of astronauts’ health predictions and results of prognostic examinations during prolonged space expeditions. In: Physiological investigations of imponderability. Moscow: Nauka; 1983. p. 200–28 [In Russian].Google Scholar
  10. 10.
    Berezovski VA, Boyko КA, Klimenko КC, et al. Hypoxia and individual peculiarities of reactivity. Kiev: Nfukova Dumka; 1978 [In Russian].Google Scholar
  11. 11.
    Berezovski VA, Serebrovskaia TV. Ventilatory response to a hypercapnic stimulus as an index of the reactivity of the human respiratory system. Fiziol Zh. 1987;33(3):12–8 [In Ukrainian].PubMedGoogle Scholar
  12. 12.
    Berezovskii VA, Levashov MI. The build-up of human reserve potential by exposure to intermittent normobaric hypoxia. Aviakosm Ekolog Med. 2000;34(2):39–43 [In Russian].PubMedGoogle Scholar
  13. 13.
    Berezovskii VA, Serebrovskaia TV. Individual reactivity of the human respiratory system and its evaluation. Fiziol Zh. 1988; 34(6):3–7 [In Russian].PubMedGoogle Scholar
  14. 14.
    Berezovskii VA, Serebrovskaia TV, Ivashkevich AA. Various individual features of human adaptation to altitude. Kosm Biol Aviakosm Med. 1987;21(1):34–7 [In Russian].PubMedGoogle Scholar
  15. 15.
    Berezovskii VA, Serebrovskaia TV, Lipskii PI. Respiratory function in twins under different gas mixtures. Fiziol Zh. 1981;27(1):20–5 [In Russian].PubMedGoogle Scholar
  16. 16.
    Berezovsky VA, editor. Hypoxia: individual sensitivity and reactivity. Kiev: Naukova Dumka; 1978 [In Russian].Google Scholar
  17. 17.
    Bernardi L, Passino C, Serebrovskaya Z, Serebrovskaya T, Appenzeller O. Respiratory and cardiovascular adaptations to progressive hypoxia. Effect of interval hypoxic training. Eur Heart J. 2001;22:879–86.PubMedCrossRefGoogle Scholar
  18. 18.
    Bhaumik G, Sharma RP, Dass D, et al. Changing hypoxic ventilatory responses of men and women 6 to 7 days after climbing from 2100 m to 4350 m altitude and after descent. High Alt Med Biol. 2003;4:341–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Bolmont B, Bouquet C, Thullier F. Relationships of personality traits with performance in reaction time, psychomotor ability, and mental efficiency during a 31-day simulated climb of Mount Everest in a hypobaric chamber. Percept Mot Skills. 2001;92:1022–30.PubMedGoogle Scholar
  20. 20.
    Burov A. System for valuation of the operators professional aging rates. Human factors in organizational design and management-VI. In: Proceedings of the sixth international symposium on human factors in organizational design and management. Hague, Netherlands; 19–22 Aug 1998.Google Scholar
  21. 21.
    Burtscher M, Bachmann O, Hatzl T, et al. Cardiopulmonary and metabolic responses in healthy elderly humans during a 1-week hiking programme at high altitude. Eur J Appl Physiol. 2001;84:379–86.PubMedCrossRefGoogle Scholar
  22. 22.
    Bushov IuV, Makhnach AV, Protasov KT. Analysis of individual differences of psychological reactions to combined hypoxic exposure. Fiziol Cheloveka. 1993;19:97–103 [In Russian].PubMedGoogle Scholar
  23. 23.
    Chan IS, Ginsburg GS. Personalized medicine: progress and promise. Annu Rev Genomics Hum Genet. 2011;12:217–44.PubMedCrossRefGoogle Scholar
  24. 24.
    Chapman RF, Stray-Gundersen J, Levine BD. Individual variation in response to altitude training. J Appl Physiol. 1998;85:1448–56.PubMedGoogle Scholar
  25. 25.
    Chapman RF, Stray-Gundersen J, Levine BD. Epo production at altitude in elite endurance athletes is not associated with the sea level hypoxic ventilatory response. J Sci Med Sport. 2010;13:624–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Collins DD, Scoggin CH, Zwillich CW, et al. Hereditary aspects of decreased hypoxic response. J Clin Invest. 1978;62:105–10.PubMedCrossRefGoogle Scholar
  27. 27.
    Deindl E, Kolar F, Neubauer E, et al. Effect of intermittent high altitude hypoxia on gene expression in rat heart and lung. Physiol Res. 2003;52:147–57.PubMedGoogle Scholar
  28. 28.
    Dembo AR, Zemtsovski EV, Frolov BA. Echocardiogram and ­correlative rhythmography in sport. Leningrad: Nauka; 1979 [In Russian].Google Scholar
  29. 29.
    Eckes L. Altitude adaptation. Part III. Altitude acclimatization as a problem of human biology. Gegenbaurs Morphol Jahrb. 1976; 122:535–69 [In German].PubMedGoogle Scholar
  30. 30.
    Edmunds NJ, Moncada S, Marshall JM. Does nitric oxide allow endothelial cells to sense hypoxia and mediate hypoxic vasodilatation? in vivo and in vitro studies. J Physiol. 2003;546:521–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Egorov PI. Effect of high altitude flight on a pilot’s body systems. Moscow: Medgiz; 1937 [In Russian].Google Scholar
  32. 32.
    Gurvich HE. Influence of high-altitudes on an organism. In: Krotkov FG, editor. Physiology and hygiene of high-altitude flights. Moscow-Leningrad: State Publishing House of the Biological and Medical Literature; 1938. p. 17–24 [In Russian].Google Scholar
  33. 33.
    Henry Y, Guissani A. Interactions of nitric oxide with hemoproteins: roles of nitric oxide in mitochondria. Cell Mol Life Sci. 1999;55:1003–14.PubMedCrossRefGoogle Scholar
  34. 34.
    Hochachka PW, Rupert JL. Fine tuning the HIF-1 ‘global’ O2 sensor for hypobaric hypoxia in Andean high-altitude natives. Bioessays. 2003;25:515–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Hopfl G, Ogunshola O, Gassmann M. Hypoxia and high altitude. The molecular response. Adv Exp Med Biol. 2003;543:89–115.PubMedCrossRefGoogle Scholar
  36. 36.
    Kawakami Y, Yamamoto H, Yoshikawa T, et al. Chemical and behavioral control of breathing in adult twins. Am Rev Respir Dis. 1984;129:703–7.PubMedGoogle Scholar
  37. 37.
    Kaznacheev VP, Baevsky RM, Berseneva AP. Prenosological diagnostics during screening tests of a specific human population. Leningrad: Nauka; 1980 [In Russian].Google Scholar
  38. 38.
    Kolchinskaya AZ. Mechanisms of interval hypoxic training effects. Hypoxia Med J. 1993;1:5–7.Google Scholar
  39. 39.
    Kolchinskaya AZ, Hatsukov BH, Zakusilo MP. Oxygen insufficiency: destructive and constructive actions. Nalchik: Kabardino-Balkaria Scientific Center; 1999 [In Russian].Google Scholar
  40. 40.
    Kurhaliuk NM. State of mitochondrial respiration and calcium capacity in livers of rats with different resistance to hypoxia after injections of L-arginine. Fiziol Zh. 2001;47:64–72 [In Ukrainian].PubMedGoogle Scholar
  41. 41.
    Kurhalyuk NM, Serebrovskaya TV, Kolesnikova EE. Role of cholino- and adrenoreceptors in regulation of rat antioxidant defense system and lipid peroxidation during adaptation to intermittent hypoxia. Probl Ecol Med Genet Cell Immunol, Kiev-Lugansk-Kharkiv. 2001;7(39):126–37 [In Ukrainian].Google Scholar
  42. 42.
    Kurhalyuk NM. Role of L-arginine on guinea pigs mitochondrial respiration in myocardium under acute hypoxia. Bull L’viv Univ ser Biol. 2002;29:177–86 [In Ukrainian].Google Scholar
  43. 43.
    Lapshin AV, Manukhina EB, Meerson FZ. Adaptation to short stress exposures prevents the enhancement of the endothelium-dependent reactions of the aorta in myocardial infarct. Fiziol Zh SSSR Im I M Sechenova. 1991;77(3):70–8 [In Russian].PubMedGoogle Scholar
  44. 44.
    Levine BD, Stray-Gundersen J. Dose-response of altitude training: how much altitude is enough? Adv Exp Med Biol. 2006;588:233–47.PubMedCrossRefGoogle Scholar
  45. 45.
    Luk’ianova LD. Molecular mechanisms of tissue hypoxia and organism adaptation. Fiziol Zh. 2003;49(3):17–35 [In Russian].PubMedGoogle Scholar
  46. 46.
    Lukyanova LD. Molecular, metabolic and functional mechanisms of individual resistance to hypoxia. In: Sharma BK, Takeda N, Ganguly NK, et al., editors. Adaptation biology and medicine. New Dehli: Narosa Publishing House; 1997. p. 236–50.Google Scholar
  47. 47.
    Lukyanova LD, Korablev AV. Some physiological and metabolic characteristics of an animal’s individual resistance to hypoxia. In: Proceedings of the third Soviet Union conference of adaptation. Moscow; 1982. p. 73–6.Google Scholar
  48. 48.
    Lukyanova LD, Dudchenko AV, Germanova EL, et al. Mitochondrial signaling in formation of body resistance to hypoxia. In: Xi L, Serebrovskaya TV, editors. Intermittent hypoxia: from molecular mechanisms to clinical applications. New York: Nova; 2009. p. 391–417.Google Scholar
  49. 49.
    Lysenko GI, Serebrovskaya TV, Karaban IN, et al. Use of the method of gradually increasing normobaric hypoxia in medical practice. Methodical recommendations. Kiev: Ukrainian Ministry of Healthcare; 1998 [In Ukrainian].Google Scholar
  50. 50.
    Maidikov YL, Makarenko NV, Serebrovskaya TV. Human mental activity during high altitude adaptation. Pavlov’s J Higher Nerv Act (USSR). 1986;36(1):12–9.Google Scholar
  51. 51.
    Makarenko NV. Psychophysiological human functions and operator’s work. Kiev: Naukova Dumka; 1991 [In Russian].Google Scholar
  52. 52.
    Malkin VB, Gora EP. Participation of respiration in rhythmic interactions in the body. Usp Fiziol Nauk. 1996;27(2):61–77 [In Russian].PubMedGoogle Scholar
  53. 53.
    Mankovska I, Bakunovsky O, Vargatiy C. Oxygen-transport systems in humans at rest and during physical work after a long-term wintering sojourn at Ukrainian Antarctic station “Academician Vernadsky”. In: Proceeding of the 2nd Ukrainian Antarctic conference. Kiev; 22–24 June 2004. p. 11 [In Ukrainian].Google Scholar
  54. 54.
    Medvedev VI. Constancy of human physiological and pathological functions under extreme conditions. Leningrad: Nauka; 1982 [In Russian].Google Scholar
  55. 55.
    Mirrakhimov MM, Khamzamulin RO, Ragozin ON. Features of the ECG in acute altitude sickness. Kardiologiia. 1986;26(2):32–4 [In Russian].PubMedGoogle Scholar
  56. 56.
    Mirrakhimov MM, Aidaraliev AA, Maksimov AL. Prognostic aspects of physical activity at high altitudes. Frunze: Ilim; 1983 [In Russian].Google Scholar
  57. 57.
    Moore LG. Comparative human ventilatory adaptation to high altitude. Respir Physiol. 2000;121:257–76.PubMedCrossRefGoogle Scholar
  58. 58.
    Navakatikyan AO, Kapshuk AP. Mathematical analysis of heart rhythm during work of different intensity. In: Mathematical methods of research planning, data analysis and prognosis in hygiene. Kiev: Zdorov’e; 1977. p. 34–41 [In Russian].Google Scholar
  59. 59.
    Negoescu R, Filcescu V, Boanta F, et al. Hypobaric hypoxia: dual sympathetic control in the light of RR and QT spectra. Rom J Physiol. 1994;31:47–53.PubMedGoogle Scholar
  60. 60.
    Nicolas M, Thullier-Lestienne F, Bouquet C, et al. A study of mood changes and personality during a 31-day period of chronic hypoxia in a hypobaric chamber (Everest-Comex 97). Psychol Rep. 2000;86:119–26.PubMedCrossRefGoogle Scholar
  61. 61.
    Noel-Jorand MC, Joulia F, Braggard D. Personality factors, stoicism and motivation in subjects under hypoxic stress in extreme environments. Aviat Space Environ Med. 2001;72:391–9.PubMedGoogle Scholar
  62. 62.
    Rozenblyum DE. Adaptation to oxygen deficiency in short-term, repetitive exposure to low barometric pressure. Bull Exp Biol Med. 1943;21(7–8):6–9 [In Russian].Google Scholar
  63. 63.
    Semenza GL. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol. 2000;88:1474–80.PubMedGoogle Scholar
  64. 64.
    Serebrovskaia TV. Hereditary defect of sensitivity to hypoxia in normal sensitivity to hypercapnia. Patol Fiziol Eksp Ter. 1982;4:80–3 [In Russian].PubMedGoogle Scholar
  65. 65.
    Serebrovskaia TV, Ivashkevich AA, Maidikov IL. The relation of the reactivity of the human respiratory system, mental and physical work capacity and metabolic characteristics during a 1-year stay in the mountains. Fiziol Zh. 1989;35(4):61–9 [In Russian].PubMedGoogle Scholar
  66. 66.
    Serebrovskaia TV, Lipskii PI. Levels of hereditary determination of human cardiorespiratory system functional indices. Fiziol Zh. 1982;28(3):267–73 [In Russian].PubMedGoogle Scholar
  67. 67.
    Serebrovskaya TV, Kurhalyuk NM, Nosar VI, et al. Combination of intermittent hypoxic training with exogenous nitric oxide treatment improves rat liver mitochondrial oxidation and phosphorilation under acute hypoxia. Fiziol Zh. 2001;47(1):85–92 [In Ukrainian].Google Scholar
  68. 68.
    Serebrovskaya TV. Intermittent hypoxia research in the former Soviet Union and the Commonwealth of Independent States (CIS): history and review of the concept and selected applications. High Alt Med Biol. 2002;3:205–21.PubMedCrossRefGoogle Scholar
  69. 69.
    Serebrovskaya TV, Kurhalyuk NM, Moibenko AA et al. Effects of mitochondrial KATP stimulation on myocardial energy supply in rats with different resistance to hypoxia. In: Proceedings of the 5th international conference “Hypoxia in Medicine”, Innsbruk; 2003. Hypoxia Medical J. 2003; 3:36.Google Scholar
  70. 70.
    Shakhtarin VV, Kiriachkov IuIu, IaM K, et al. The autonomic reaction of the body to stress and its prognostic value. Vestn Akad Med Nauk SSSR. 1990;3:33–7 [In Russian].PubMedGoogle Scholar
  71. 71.
    Shen C, Powell-Coffman JA. Genetic analysis of hypoxia signaling and response in C. elegans. Ann N Y Acad Sci. 2003;995:191–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Sirotinin NN. Effect of acclimatization to high mountain climate on adaptation to decreased atmospheric pressure using a decompression chamber. Arkh Pat Anat Pat Physiol. 1940;6:35–42 [In Russian].Google Scholar
  73. 73.
    Streltsov VV. Physiological validation of decompression chamber training for high altitude flights. Abstract of report at the All-Union conference on aerospace medicine. Leningrad; 1939. p. 18 [In Russian].Google Scholar
  74. 74.
    Tsvetkova AM, Tkatchouk EN. “Hypoxia user”: the opportunity of individual programming of interval hypoxic training. In: Hypoxia: mechanisms, adaptation, correction. Moscow: BEBIM; 1999. p. 83–4.Google Scholar
  75. 75.
    Vasin MV, Petrova TV, Bobrovnitskii IP, et al. Human biochemical status and its relation to body resistance when exposed to acute hypoxic hypoxia. Aviakosm Ekolog Med. 1992;26(5–6):43–9 [In Russian].PubMedGoogle Scholar
  76. 76.
    Vogt M, Billeter R, Hoppeler H. Effect of hypoxia on muscular performance capacity: “living low-training high”. Ther Umsch. 2003;60:419–24 [In German].PubMedCrossRefGoogle Scholar
  77. 77.
    Waters KA, Gozal D. Responses to hypoxia during early development. Respir Physiol Neurobiol. 2003;136:115–29.PubMedCrossRefGoogle Scholar
  78. 78.
    Weil JV. Variation in human ventilatory control: genetic influence on the hypoxic ventilatory response. Respir Physiol Neurobiol. 2003;135:239–46.PubMedCrossRefGoogle Scholar
  79. 79.
    Zagryadsky VP. Selected lectures on physiology during military labor. Leningrad: Nauka; 1972 [In Russian].Google Scholar

Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  1. 1.Department of HypoxiaBogomoletz Institute of Physiology, National Academy of Sciences of UkraineKievUkraine
  2. 2.Division of Cardiology, Department of Internal MedicineVirginia Commonwealth UniversityRichmondUSA

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