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Continuous and intermittent exposure to the hypoxia of altitude: implications for glutamine metabolism and exercise performance
  1. D M Bailey1,
  2. L M Castell2,
  3. E A Newsholme2,
  4. B Davies1
  1. 1Hypoxia Research Unit, Health and Exercise Sciences Research Laboratory, University of Glamorgan, Pontypridd CF37 1DL, United Kingdom
  2. 2Cellular Nutrition Research Group, University Department of Biochemistry, Oxford OX1 3QU, United Kingdom
  1. Correspondence to: Dr D M Bailey, Hypoxia Research Unit, Health and Exercise Sciences Research Laboratory, School of Applied Sciences, University of Glamorgan, Pontypridd CF37 1DL, United Kingdom

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Take home message

The duration of exposure to environmental hypoxia during physical exercise is a potential mediator of immune function and athletic performance. Continuous hypoxic training resulted in overt immunodepression whereas intermittent hypoxic training increased physical exercise performance considerably.

Although most elite athletes invest a considerable amount of time and resources training at altitude, the practical benefits gained remain to be clearly established despite almost half a century of investigation. Elucidating the potential factors that affect physical performance after return to sea level has been the subject of much interest and controversy.

The time spent exposed to the hypoxia of altitude would appear to be an important mediator of sea level performance. A combination of physical exercise and intermittent hypoxia (defined as an exposure time of 30 minutes to 12 hours a day) has been shown to accelerate the normal adaptations invoked by a comparable programme of normoxic training with cardioprotective and performance enhancing benefits.1 In contrast, increased free radical mediated oxidative stress,2 decreased cell mediated immunity,3 and increased incidence of infectious episodes4 have been reported in continuous hypoxia (defined as an exposure time of 24 hours a day). We have previously reported two cases of infectious mononucleosis following chronic exposure to 1500–2000 m.5

Glutamine has been identified as a conditionally essential amino acid required for lymphocyte proliferation and macrophage phagocytosis, and it has been suggested that any physiological decrease in plasma glutamine may impair the host's defence against opportunistic infections.6 In the light of these findings, we examined changes in plasma glutamine, the incidence of overt physical illness, and maximal exercise performance as a function of continuous and intermittent hypoxic training at comparable inspiratory partial pressures of oxygen (Pio2) or simulated altitudes.

Methods

SUBJECTS

After ethical approval, volunteers were solicited from two separate cohorts of international standard endurance runners (continuous group, n = 22) and endurance trained university students (intermittent group, n = 32).

EXPERIMENTAL DESIGN

In study 1 (continuous group), 22 elite distance runners had the option of spending four weeks at an altitude training camp based at 1640 m in Johannesburg, South Africa (Pio2 = 122 (1) mm Hg). Of these, 10 volunteers travelled to altitude (continuousEXP) and 12 trained at sea level in the United Kingdom (Pio2 = 151 (3) mm Hg; continuousCON). Although it was not possible to randomly assign volunteers to the altitude or sea level training camps, retrospective analysis identified that the two subgroups drawn from a homogeneous group of distance runners had comparable performance capabilities.

In study 2 (intermittent group), 18 volunteers were randomly assigned in a double blind manner to train for four weeks in a laboratory inspiring a medical grade normobaric hypoxic gas (Pio2 = 115 (2) mm Hg; intermittentEXP), and 14 performance matched volunteers trained while exposed to normobaric normoxia (Pio2 = 150 (2) mm Hg; intermittentCON). These gases were designed to approximate the Pio2 experienced in study 1.

All volunteers performed a standardised exercise test in normobaric normoxia before and after training for the determination of maximal aerobic capacity (V̇o2max). The incidence of physical symptoms associated with an upper respiratory tract or gastrointestinal tract illness was assessed, and resting venous blood samples were analysed for a differential white blood cell count and plasma glutamine.

HYPOXIC/NORMOXIC TRAINING PROGRAMMES

Both the normoxic and hypoxically trained subgroups performed the same volume of physical training at the same percentage of heart rate maximum, which was enforced using electrocardiograph calibrated bipolar telemetry (Vantage, Polar Electro, Oy, Finland).

STATISTICAL ANALYSIS

Changes in selected dependent variables as a function of timing (before v altitude v after) and group (exposure to hypoxia (EXP) v controls (CON)) were analysed using a two factor mixed analysis of variance. After a significant interaction and simple main effects, a posteriori comparisons within groups were analysed using Bonferroni paired samples t tests. Simple effects between groups were assessed using a one way analysis of variance and a Tukey honestly significant test. The α level was set at p<0.05 for all two tailed tests, and values are reported as means (SD).

Results

A considerable increase in the incidence of respiratory tract or gastrointestinal tract illness was observed during continuous exposure to the hypoxia of terrestrial altitude (fig 1). This was accompanied by a decrease in plasma glutamine (fig 2), which was more pronounced in those volunteers presenting with an illness than in those who remained apparently healthy (−182 (38) μmol/l v −92 (32) μmol/l; p<0.05). Plasma glutamine concentration remained depressed and total white blood cell count decreased after return to sea level (table 1), whereas no changes were observed for (V̇o2max. In contrast, fig 3 illustrates the increase in plasma glutamine (+78 (109) μmol/l, p<0.05) and o2max (+0.47 (0.77) litres/min, p<0.05) invoked by intermittent hypoxia, whereas changes in the differential white blood cell count (table 1) and the incidence of illness were unremarkable.

Table 1

Differential white blood cell count before, during, and after continuous/intermittent hypoxic training

Figure 1

Incidence and duration (in days) of illnesses encountered at sea level and during continuous exposure to 1640 m. Any respiratory problems indicates any two of the following symptoms: sore throat, cough, runny nose, sinusitis, earache.

Figure 2

Changes (values found at altitude or after return to sea level minus the value found before) in the resting concentration of plasma glutamine during and after continuous hypoxic training. Pre, altitude, and post indicate values obtained before, during (day 19 at 1640 m), and after continuous hypoxic (exp)/normoxic (con) training. *Significant difference from within subgroup value (p<0.05). †Significant difference between groups (p<0.05).

Figure 3

Changes ((before/after) × 100%) in the resting concentration of plasma glutamine and V̇o2max after intermittent normoxic (CON) and hypoxic (EXP) training. †Significant difference between groups (p<0.05).

Discussion

While we acknowledge the limitations imposed by two separate cohorts with different exercise capabilities and the logistical idiosyncrasies of field research, our observations suggest that the duration of the hypoxic stimulus is an important modulator of immune function and physical exercise performance. The appreciable increase in overt physical illness at altitude, either due to the chronicity of hypoxia per se and/or contact with novel infectious pathogens, may suggest possible immunodepression, an observation previously linked to depression of cell mediated immunity.7, 8 The decrease in plasma glutamine, which has been shown to decrease both lymphocyte proliferation and response time in vitro,9 may be a contributory factor implicated in such a response. However, whether the decrease in glutamine was a cause or a consequence of illness remains to be established.

In contrast, physical illness was not prevalent during intermittent hypoxic training despite a similar Pio2. The increase in (V̇o2max appeared to be independent of changes in arterial oxygen content (data not shown) and possibly due to other unquantified central and/or peripheral factors. The increase in plasma glutamine was intriguing and to our knowledge has only previously been anecdotally reported in a review.10

In conclusion, a combination of physical exercise and repeated bouts of intermittent hypoxia appears to initiate a disruption in systemic homoeostasis which is followed by an adaptive phase which, in general terms, appears to be beneficial. Adaptation appears to be inadequate during continuous hypoxia, which could have potentially deleterious consequences.

Acknowledgments

This research was supported by the British Olympic Association, British Athletics Federation, and British Oxygen Company.

Take home message

The duration of exposure to environmental hypoxia during physical exercise is a potential mediator of immune function and athletic performance. Continuous hypoxic training resulted in overt immunodepression whereas intermittent hypoxic training increased physical exercise performance considerably.

References

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