Hypoxia is used in various ways to improve sea-level performance. Because classical high-altitude training may not improve sea-level performance in elite athletes, because of lower training intensities in hypoxia (17), the paradigm has shifted to living high and training low (11,12). Altitude acclimatization, predominantly through increases in red blood cell mass, accounts for performance improvement, whereas negative effects of reduced training intensity can be prevented by training at low altitudes. Because this concept is dependent on a particular topographical setting that is not present in most areas where athletes train, exposure to artificial hypoxic environments at low altitudes (usually at an inspiratory PO2 equivalent to altitudes of approximately 2500 m) during sleep is used (6,18). Nitrogen concentrators, which generate a hypoxic environment in tents that can be set up easily in bedrooms, are commercially available at a fairly low cost. However, the modalities of exposure for improving sea-level performance and the underlying mechanisms are still highly controversial, as demonstrated by a recent public debate (5,9,13,15).
The most recent development led to smaller, cheap devices supplying hypoxic gas mixtures of a very low inspiratory PO2 (corresponding to altitudes of 5000-6000 m) to which athletes are exposed at rest repetitively for a few minutes for approximately 1 h. Manufacturers have claimed, on the basis of anecdotal reports on the Internet, to improve aerobic or anaerobic sea-level performance through the use of this so-called short-term intermittent hypoxic exposure (IHE). However, a placebo-controlled, double-blind study has revealed no effect of IHE on aerobic performance or on markers of erythropoiesis (8).
Because classical high-altitude training (14,19,22) and the training modality of sleep high/train low (4,16) has been reported to improve anaerobic performance and/or buffer capacity, and because beneficial effects of some studies using IHE might be attributed to increased anaerobic performance, we examined this hypothesis in a placebo-controlled, double-blind trial. In addition, we examined whether IHE had any beneficial effect on plasma levels of lactate, V˙O2, HR, or V˙E at the submaximal workloads during the ergometer test, because the latter two parameters have been reported to decrease in a preliminary publication of a controlled trial (2).
Twenty endurance-trained men participated in this study. They were nonsmoking sea-level dwellers who had engaged in two to four aerobic exercise sessions per week for at least 1 yr before the study. Subjects were instructed to maintain their normal training program throughout the study period, and they completed a training log that recorded the exercise duration of each workout from 4 wk before until the end of the experiments. All subjects gave written informed consent to the study, which had been approved by the ethics committee of the medical faculty of the University of Heidelberg.
Study design and exercise testing.
This is a placebo-controlled, randomized, double-blind trial that was performed in six blocks during a period of 7 months. All tests and treatment took place in the division of sports medicine at the medical clinic of the University of Heidelberg, at an altitude of approximately 100 m above sea level. Before the study, subjects completed a medical examination and an incremental cycle ergometer test to exhaustion with electrocardiography and blood pressure control to exclude individuals with cardiovascular disease and to familiarize the subjects with the incremental exercise test. On two additional days, subjects had to undergo a Wingate anaerobic test each day for familiarization. Two days after the last familiarization tests, that is, 4 and 3 d before and on the 2 d after the intervention, a Wingate anaerobic test and then an incremental exercise test on the next day were performed. For the exercise testing, subjects came to the laboratory in the afternoon between 2:00 p.m. and 5:00 p.m. Each subject was always tested at the same hour of the day in the same order. All exercise tests were performed on an electromagnetically braked cycle ergometer (Lode Excalibur sport, Groningen, the Netherlands). Horizontal and vertical positions of the handlebar and saddle unit, preferred by each subject as determined on the first visit, were used in each test. The person who ran the IHE sessions was not involved in pre- and post-IHE exercise testing.
Hypoxic treatment consisted of 15 consecutive days in which subjects came to the laboratory each day between 8:00 a.m. and 9:00 a.m. and rested in a seated position, breathing through a mouthpiece attached to a two-way valve, for six consecutive cycles of 6 min, followed by 4 min breathing ambient air. The inspiratory side of the two-way valve was connected to 150-L Douglas bags, and the expiratory side was free. For the hypoxia group, the Douglas bags were connected to cylinders that contained 11% O2 from day 1 to day 7 and 10% O2 from day 8 to day 15 (equivalent to an ambient PO2 at altitudes of approximately 5200 and 5900 m). An identical bag system was used for the control group, but the Douglas bags were fed by compressed ambient air. When breathing through the mouthpiece, subjects wore a nose clip. The level of hypoxia was consistent with the studies done in this field (2,8). The time of exposure to hypoxia and normoxia (6 and 4 min, respectively) was chosen to evaluate a protocol that had been reported to increase repeated-sprint performance (www.pharmapacific.com/results.html). Values of the arterial oxygen saturation (SpO2) were monitored throughout the hypoxic treatment via fingertip pulse oximetry (Datex-Ohmeda 3900, Louisville, KY), and these values were noted for each subject within the last 30 s of the 6-min exposure episodes. The bag systems and the pulse oximeters were placed behind the seated subjects and were hidden by a screen. Four subjects (two from the hypoxia group) missed one session of the intervention during the first week.
The Wingate anaerobic test.
The Wingate anaerobic test consisted of a 30-s all-out cycling bout on the Lode cycle ergometer against a high constant resistance (braking torque), which was set at 0.75 N·m·kg−1 body mass. The Wingate protocol was controlled via a personal computer running the Lode Wingate software (version 1.00.10, Groningen, the Netherlands) interfaced to the Lode ergometer. After a warm-up period of 5 min of pedaling and then 2 min of recovery, subjects pedaled as fast as possible to achieve maximal pedaling frequency during a 5-s unloaded countdown. Immediately thereafter, the resistance was applied to the flywheel and remained constant during the 30-s all-out cycling. The Lode Wingate software measured peak power as the highest mechanical power achieved at any stage of the 30-s all-out cycling, and mean power was calculated as the average mechanical power sustained throughout the 30 s. Subjects had to stay seated on the saddle throughout the test, and their feet were fixed to the pedals with toe clips to prevent them from slipping. Strong verbal encouragement was provided during the all-out cycling. To get the highest possible peak power, subjects were asked to pedal as fast as possible right from the start and not to preserve energy for the last part of the test. Before the warm-up, and at 1, 3, 5, 7, and 10 min after the Wingate anaerobic test, 20 μL of blood was collected from the earlobe for lactate measurement by an enzymatic method (Super GL ambulance; Dr. Müller Gerätebau GmbH, Germany).
The incremental cycle ergometer test.
The incremental cycle ergometer test was conducted to assess aerobic performance. The test was begun at an initial workload of 50 W on the Lode cycle ergometer with increments of 50 W at every 3 min. Subjects were encouraged to pedal as long as possible until exhaustion. The test was terminated if the subjects were unable to continue pedaling at a rate above 60 rpm despite verbal encouragement. V˙E, V˙O2, and CO2 output were measured breath-by-breath and were averaged for 30-s periods with a ZAN 680 computerized cardiopulmonary exercise test system (ZAN, Oberthulba, Germany). V˙O2max and V˙E max were determined as the highest average values measured for the V˙E and V˙O2. Before each test, O2 and CO2 analyzers of the spirometry system were calibrated with calibration gas containing 16% O2 and 6% CO2, and the flow sensor for measuring ventilation was calibrated with a 1-L appropriate calibration syringe according to the manufacturer's instructions. Electrocardiography was recorded continuously during the test with a ZAN 800 ECG. Before the test, during the last 20 s of each step, and at 1, 3, 5, and 10 min after the test, 20 μL of capillary blood was collected from the earlobe for measurement of plasma lactate.
Although the aim of this study was primarily to investigate the effects of IHE on athletic performance, we also examined the effects of intervention on erythropoietin (EPO), red blood cell (RBC) count, hemoglobin concentration ([Hb]), and hematocrit (Hct). Pre- and posttreatment blood samples for detection of [Hb], RBC count, and Hct were taken directly before the first hypoxic treatment session and a day after the last session before the cycle ergometer test. Venous blood samples (5 mL) were drawn into an EDTA tube from the antecubital vein in the sitting position, and [Hb], Hct, and RBC counts were taken using a Coulter T 840 counter (Coulter Electronics, Krefeld, Germany). Blood samples for determining EPO concentration in serum were drawn from an antecupital vein before the first, the eighth, and the last treatment sessions. EPO was measured by a chemiluminescent immunoassay method (Immulite, DPC Biermann, Bad Nauheim, Germany). One subject in the control group was excluded from the analysis of EPO measurements because of a missing value on day 8.
Results are expressed as mean ± standard deviation (SD). Normal distributions of data were confirmed by the Kolmogorov-Smirnov test. The two-way repeated-measures ANOVA was used to test for interaction and main effects (between and within subjects). The repeated-measures one-way ANOVA was performed for analysis of changes in SpO2 levels in the hypoxia group. The independent-samples t-test was used to find out whether there was a significant difference between groups at baseline for any of the subjects' characteristics. All statistical analyses were done using SPSS for Windows, version 11.5.0 (SPSS, Chicago, IL). Statistical significance was accepted at P < 0.05.
There were no significant differences in age, body mass, BMI, V˙O2max, or Pmax between the groups at baseline (Table 1). The group means for the weekly training volume before and during the study were 4.0 ± 1.9 versus 4.4 ± 2.0 h·wk−1 and 4.3 ± 1.6 versus 4.0±1.6h·wk−1 for the hypoxia and control groups, respectively. Differences between and within subjects, as well as the interaction, were not significant.
All subjects in the hypoxia group tolerated the hypoxic treatment without any reported adverse effects. After completion of the posttests, subjects were asked whether they thought they had been in the hypoxia or the control group. Of the 10 subjects in the IHE group, one assumed he had been exposed to hypoxia, one assumed normoxia exposure, and eight could not decide. Of the 10 subjects in the normoxic group, two assumed they had been exposed to IHE, five assumed normoxia exposure, and three were undecided.
The level of SpO2 in the control group during the hypoxic treatment was 98.2 ± 0.3%. In the hypoxia group, it dropped to 81.9 ± 2.1 and 77.0 ± 2.9% for days 1-7 and days 8-15, respectively. There was an overall significant increase for the level of SpO2 in the hypoxia group from day 1 (80.6 ± 1.8%) to day 7 (83.1 ± 2.4%) (P < 0.001) and from day 8 (76.2 ± 3.2%) to day 15 (77.7 ± 2.7%) (P < 0.05).
The Wingate anaerobic test.
The values of the peak power from pre- to posttest in the hypoxia group (1132.9 ± 102.1 vs 1150.6 ± 109.3 W) and the control group (1124.9 ± 107.1 vs 1126.2 ± 128.5 W) did not differ significantly. The same was true for the values of the mean power in the hypoxia group (626.0 ± 48.0 vs 623.5 ± 42.4W) and the control group (583.2 ± 30.7 vs 602.1 ± 40.3 W) (individual values are shown in Fig. 1). Lamax after the Wingate anaerobic test was not different before and after the treatment in the hypoxia group (12.2 ± 1.6 vs 12.6±1.7 mM) or control group (11.4 ± 2.9 vs 11.4 ± 3.0 mM). There also was no significant between-group or interaction effect for these values.
FIGURE 1-Individual ...Image Tools
The incremental cycle ergometer test.
The hypoxic treatment had no significant effect on any of the parameters measured during the cycle ergometer test. Time effects, group effects, and time × group interaction were not significant for V˙O2max, Pmax, V˙E max, power output at the 4-mmol lactate threshold (P4 mmol), or HR at the 4-mmol lactate threshold (HR4 mmol) (Table 2). In addition, the levels of RERmax, HRmax, and Lamax were not significantly different between or within groups at any time (Table 2 and Fig. 2). There also were no significant between-group, within-group, or time × group interaction effects at any submaximal level for V˙O2, V˙E, HR, or lactate concentration during the incremental cycle ergometer test (Fig. 3).
[Hb] did not change significantly before or after the intervention in the hypoxia group (14.7 ± 0.9 vs 15.0 ± 0.7 g·dL−1) or in the control group (14.8 ± 0.6 vs 14.8 ± 0.8 g·dL−1). There also was no significant between-group difference or interaction effect for these values. The same is true for RBC count and Hct (data not shown). EPO concentration in serum remained unchanged on the first day (9.9 ± 1.9 mU·mL−1), the eighth day (12.0 ± 4.7 mU·mL−1), and the last day (10.9 ±3.8 mU·mL−1) of treatment in the hypoxia group. The same was true for the control group (data not shown).
The aim of this study was to determine whether short-term IHE would enhance anaerobic or aerobic performance at sea level. The results indicate that 15 consecutive days of IHE (6 min of hypoxia and then 4 min of normoxia for 1 h) does not increase anaerobic performance in a Wingate anaerobic test, nor can it improve maximal or submaximal aerobic exercise performance during a cycle ergometer test in endurance-trained men. This study is the first to report the effects of IHE on aerobic and anaerobic performance, using a randomized double-blind placebo-controlled design.
In the present study, 15 consecutive days of IHE did not affect peak power or mean power as determined by the Wingate anaerobic test. Furthermore, there was no increase in maximal lactate accumulation after the Wingate anaerobic test or after the cycle ergometer test compared with baseline and with values obtained in the control group.
This study does not support claims made by the providers of devices for IHE nor by a controlled study published on the Internet (www.pharmapacific.com/results.html) that has reported increased repeated-sprint performance after IHE. In that study, the number and duration of hypoxic episodes in each session, the number of sessions, and the maximum dose of hypoxia (SpO2 of 77%) were similar to those used in our study. The possible explanation for the positive results of that work could involve the limitations of the experimental design: 15 subjects in the treatment group breathed through silos containing an absorbent for CO2 to prevent the accumulation of CO2, and 14 subjects in the control group breathed through silos without such an absorbent. As a result, control subjects most likely hyperventilated because of partial rebreathing and subsequent increases in PCO2. Therefore, they cannot be considered an adequate control group. In addition, the result of the shuttle run test in that study may have been affected by the possible effect of variability in the turning points.
By choosing a rigorously double-blind, controlled design, and performing two familiarization tests, we eliminated confounding factors that might have influenced the outcome of an all-out test, such as differences in the subjects' motivation, biased encouragement by examiners, and improvement from better familiarity with the test procedure. Interestingly, subjects were not able to reliably recognize short-term exposure to severe hypoxia.
Our data are in agreement with the findings of Julian et al. (8), who have reported no effect of IHE on running performance for 3000 m, which, to some extent, also depends on the anaerobic component. Because the aerobic performance (V˙O2max) in that study did not change, anaerobic performance must have remained unchanged as well. Interestingly, the group of researchers who reported on the Internet the beneficial effects of IHE on repeated-sprint performance could not confirm their previous finding; in agreement with the present study, they report no significant improvement of anaerobic performance after 9-14 sessions of IHE between 15 and 10% O2 (7), suggesting that the results of the first study were more likely attributable to play of chance than to a real effect of IHE.
This study demonstrates no effect of IHE on sea-level aerobic performance. This result is in agreement with the findings of another study that used a double-blind design (8), where seven highly trained distance runners could not improve their maximal or submaximal aerobic performance on the treadmill or improve their 3000-m running performance after a 20-d IHE regimen during a 4-wk period (5 min breathing hypoxic air with 12-10% O2, and then 5 min of recovery in normoxia, for 70 min).
IHE has no effect on submaximal performance, as shown by unchanged relationships of power output to lactate, heart rate, and ventilation at submaximal levels (Fig. 3). Furthermore, the unchanged relationship between power output and oxygen consumption (Fig. 3) demonstrates that IHE does not affect mechanical efficiency. These findings do not support the results of two preliminary reports: Burtscher et al. (2) report reductions in HR and V˙E at one submaximal exercise level of 150 W during incremental exercise cycle ergometry in a controlled, double-blind study after 20 sessions of IHE (9-11% O2), and Stuke et al. (21) show a 20% increase in exercise time for cycling at an intensity corresponding to 80% of maximal power output, accompanied by a significant decrease in V˙E during exercise after only 10 d of IHE with 9% O2 during a 2-wk period. It appears that the latter study was neither randomized nor blinded. Although more detailed information is necessary to reliably identify factors that account for the discrepancies between studies, it should be pointed out again that maximal exercise performance is highly dependent on motivation. It has been shown that frequent verbal encouragement increases maximal effort of healthy students during a Bruce treadmill test and leads to improvement in maximal exercise time, V˙O2max, RERmax, Lamax, and ratings of perceived exertion, whereas no encouragement or infrequent encouragement could not lead to such improvements (1). Thus, a bias of the examiner favoring the study hypothesis has to be considered as an important confounder in studies without double-blind design. Interestingly, identical maximum values for plasma levels of lactate and heart rate of our subjects in the cycle ergometer test demonstrate that the efforts in this all-out test were identical before and after IHE for both groups (Table 2).
The only significant effect of IHE in our study was an SpO2 increase in the hypoxia group during the days of exposure to the same level of hypoxia. This increase of SpO2 is most likely attributable to the ventilatory acclimatization to hypoxia that leads to an increase in ventilation; however, this was not measured. Our conclusion is supported by studies of IHE conducted in the former Soviet Union (20) that report that IHE led to ventilatory acclimatization to hypoxia. Thus, 15 sessions of brief, intermittent exposures to severe hypoxia seem to be sufficient to trigger some degree of ventilatory acclimatization, which may be beneficial for athletes performing at high altitude-a hypothesis that needs to be tested.
IHE did not lead to a persistent increase in plasma levels of EPO. Although we did not measure plasma levels of EPO several hours after IHE, it is unlikely that they significantly increased, because the shortest hypoxic exposure time that has been reported to increase the serum level of EPO is 84 min of continuous exposure to a simulated altitude of 4000 m (3), or 4 h of intermittent exposure to air with 10.5% O2 (~5500) (2.5 min of hypoxia and 1.5 min of recovery in normoxia) (10). Our assumption is supported by unchanged levels for Hct and [Hb] and by identical findings from a comparable study that also included measurements of reticlocytes (8). In summary, the IHE used in this study did not lead to a substantial increase in erythropoiesis. Accordingly, we did not find any increase in V˙O2max.
In summary, this placebo-controlled, double-blind study demonstrates that 15 consecutive daily sessions of six intermittent exposures to 10-11% O2 lasting 6 min did not increase anaerobic or aerobic performance in endurance-trained athletes.
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