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      Comparison of the Effectiveness of High-Intensity Interval Training in Hypoxia and Normoxia in Healthy Male Volunteers: A Pilot Study

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          Abstract

          Aims

          The study investigated the effect of high-intensity interval training in hypoxia and normoxia on serum concentrations of proangiogenic factors, nitric oxide, and inflammatory responses in healthy male volunteers.

          Methods

          Twelve physically active male subjects completed a high-intensity interval training (HIIT) in normoxia (NorTr) and in normobaric hypoxia (HypTr) (FiO 2 = 15.2%). The effects of HIIT in hypoxia and normoxia on maximal oxygen uptake, hypoxia-inducible factor-1-alpha, vascular endothelial growth factor, nitric oxide, and cytokines were analyzed.

          Results

          HIIT in hypoxia significantly increases maximal oxygen uptake ( p=0.01) levels compared to pretraining levels. Serum hypoxia-inducible factor-1 ( p=0.01) and nitric oxide levels ( p=0.05), vascular endothelial growth factor ( p=0.04), and transforming growth factor- β ( p=0.01) levels were increased in response to exercise test after hypoxic training. There was no effect of training conditions for serum baseline angiogenic factors and cytokines ( p > 0.05) with higher HIF-1 α and NO levels after hypoxic training compared to normoxic training ( F = 9.1; p < 0.01 and F = 5.7; p < 0.05, respectively).

          Conclusions

          High-intensity interval training in hypoxia seems to induce beneficial adaptations to exercise mediated via a significant increase in the serum concentrations of proangiogenic factors and serum nitric oxide levels compared to the same training regimen in normoxia.

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          Most cited references61

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          Combining hypoxic methods for peak performance.

          Gregoire P Millet, B. Roels, L. Schmitt … (2010)
          New methods and devices for pursuing performance enhancement through altitude training were developed in Scandinavia and the USA in the early 1990s. At present, several forms of hypoxic training and/or altitude exposure exist: traditional 'live high-train high' (LHTH), contemporary 'live high-train low' (LHTL), intermittent hypoxic exposure during rest (IHE) and intermittent hypoxic exposure during continuous session (IHT). Although substantial differences exist between these methods of hypoxic training and/or exposure, all have the same goal: to induce an improvement in athletic performance at sea level. They are also used for preparation for competition at altitude and/or for the acclimatization of mountaineers. The underlying mechanisms behind the effects of hypoxic training are widely debated. Although the popular view is that altitude training may lead to an increase in haematological capacity, this may not be the main, or the only, factor involved in the improvement of performance. Other central (such as ventilatory, haemodynamic or neural adaptation) or peripheral (such as muscle buffering capacity or economy) factors play an important role. LHTL was shown to be an efficient method. The optimal altitude for living high has been defined as being 2200-2500 m to provide an optimal erythropoietic effect and up to 3100 m for non-haematological parameters. The optimal duration at altitude appears to be 4 weeks for inducing accelerated erythropoiesis whereas <3 weeks (i.e. 18 days) are long enough for beneficial changes in economy, muscle buffering capacity, the hypoxic ventilatory response or Na(+)/K(+)-ATPase activity. One critical point is the daily dose of altitude. A natural altitude of 2500 m for 20-22 h/day (in fact, travelling down to the valley only for training) appears sufficient to increase erythropoiesis and improve sea-level performance. 'Longer is better' as regards haematological changes since additional benefits have been shown as hypoxic exposure increases beyond 16 h/day. The minimum daily dose for stimulating erythropoiesis seems to be 12 h/day. For non-haematological changes, the implementation of a much shorter duration of exposure seems possible. Athletes could take advantage of IHT, which seems more beneficial than IHE in performance enhancement. The intensity of hypoxic exercise might play a role on adaptations at the molecular level in skeletal muscle tissue. There is clear evidence that intense exercise at high altitude stimulates to a greater extent muscle adaptations for both aerobic and anaerobic exercises and limits the decrease in power. So although IHT induces no increase in VO(2max) due to the low 'altitude dose', improvement in athletic performance is likely to happen with high-intensity exercise (i.e. above the ventilatory threshold) due to an increase in mitochondrial efficiency and pH/lactate regulation. We propose a new combination of hypoxic method (which we suggest naming Living High-Training Low and High, interspersed; LHTLHi) combining LHTL (five nights at 3000 m and two nights at sea level) with training at sea level except for a few (2.3 per week) IHT sessions of supra-threshold training. This review also provides a rationale on how to combine the different hypoxic methods and suggests advances in both their implementation and their periodization during the yearly training programme of athletes competing in endurance, glycolytic or intermittent sports.
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            Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions.

            R. Billeter, Hans Hoppeler, A Puntschart … (2001)
            This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O(2) uptake (8.3-13.1%) and maximal power output (11.4-20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the alpha-subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1alpha(736), a splice variant of HIF-1alpha newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1alpha. Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in hypoxia. Augmented mRNA levels of oxidative enzymes, phosphofructokinase, and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions. Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training. Fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O(2) uptake or maximal power output.
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              Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression.

              L Attisano, C Bernabeu, A Corbí … (2001)
              Signaling by transforming growth factor (TGF)-beta family members is mediated by Smad proteins that regulate gene transcription through functional cooperativity and association with other DNA-binding proteins. The hypoxia-inducible factor (HIF)-1 is a transcriptional complex that plays a key role in oxygen-regulated gene expression. We demonstrate that hypoxia and TGF-beta cooperate in the induction of the promoter activity of vascular endothelial growth factor (VEGF), which is a major stimulus in the promotion of angiogenesis. This cooperation has been mapped on the human VEGF promoter within a region at -1006 to -954 that contains functional DNA-binding sequences for HIF-1 and Smads. Optimal HIF-1alpha-dependent induction of the VEGF promoter was obtained in the presence of Smad3, suggesting an interaction between these proteins. Consistent with this, co-immunoprecipitation experiments revealed that HIF-1alpha physically associates with Smad3. These results demonstrate that both TGF-beta and hypoxia signaling pathways can synergize in the regulation of VEGF gene expression at the transcriptional level.
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                Author and article information

                Contributors
                Aleksandra Żebrowska:
                ORCID: https://orcid.org/0000-0001-7446-528X
                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date Collection: 2019
                Publication date (Electronic): 22 September 2019
                Volume: 2019
                Electronic Location Identifier: 7315714
                Affiliations
                1Department of Physiology, Academy of Physical Education in Katowice, Katowice, Poland
                2School of Medicine with the Division of Dentistry, Department of Lung Disease and Tuberculosis, Medical University of Silesia, 1 Koziołka St. 41-803 Zabrze, Katowice, Poland
                3Department of Neuroscience and Imaging, Dipartimento, University di Madonna delle Piane, Via dei Vestini 31, 66100 Chieti, Italy
                Author notes

                Academic Editor: Toshiyuki Sawaguchi

                Author information
                https://orcid.org/0000-0001-7446-528X
                https://orcid.org/0000-0002-9374-8071
                Article
                DOI: 10.1155/2019/7315714
                PMC ID: 6778879
                PubMed ID: 31662994
                SO-VID: 562a9267-f3a6-4950-80f4-07ffe6aaf4ac
                Copyright © Copyright © 2019 Aleksandra Żebrowska et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 2 June 2019
                Date revision received : 7 August 2019
                Date accepted : 5 September 2019
                Funding
                Funded by: Ministerstwo Nauki i Szkolnictwa Wyzszego
                Award ID: 0029/RS4/2016/54
                Categories
                Subject: Research Article

                Data availability:

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