BEIDLEMAN, BETH A.; MUZA, STEPHEN R.; FULCO, CHARLES S.; JONES, JULI E.; LAMMI, ERIC; STAAB, JANET E.; CYMERMAN, ALLEN
Endurance performance decreases on initial exposure to altitude but improves after altitude acclimatization induced by 2-3 wk of continuous altitude residence (15,22). For low-altitude residents, acclimatization to a target altitude can be induced by slow progressive ascents or continuous sojourns at intermediate altitudes (14,23,28). These methods, however, may not be available or logistically practical for low-altitude residents needing to minimize their endurance performance decrement at high altitude after rapid ascent. An alternative method for inducing altitude acclimatization, termed intermittent hypoxic exposure (IHE), may reduce logistical problems and provide an acceptable alternative for minimizing endurance performance decrements at altitude after rapid ascent.
IHE typically consists of short (1-4 h·d−1) daily (5-7 d·wk−1) applications of hypoxia (3000-4500 m) for 1-4 wk combined with or without exercise training at sea level or altitude. The dose and duration of IHE as well as the environment used for exercise training are dependent on whether the primary outcome measure is sea-level or altitude endurance performance. If the goal is improved sea-level endurance performance, an exposure altitude ≥3000 m for at least 3 h·d−1 for 1-3 wk is needed to stimulate erythropoiesis and concomitant improvements in performance (8,17,29,31). However, if the goal is improved altitude endurance performance, an exposure altitude ≥4000 m for at least 1.5 h·d−1 repeated for 5-6 d is required to stimulate ventilatory acclimatization and concomitant improvements in performance (1,2,26). Ideally, exercise training should be incorporated into the IHE protocol in the same environment that is used for the primary outcome measure for optimal performance benefits (3,32,33).
Our laboratory has previously reported 16%-21% improvements in endurance performance at 4300-m altitude after 7-15 d of hypobaric IHE combined with exercise training at altitude due to ventilatory acclimatization (1,2). Whether the same magnitude of ventilatory acclimatization and concomitant endurance improvement can be induced at 4300-m altitude using 1 wk of normobaric IHE combined with exercise training at altitude is unknown. In addition, soldiers, mountaineers, rescue workers, and ultraendurance athletes may spend a couple of days at sea level after the last IHE before subsequent reexposure to altitude. Information regarding retention of ventilatory acclimatization and endurance performance on subsequent reexposure to altitude after a couple of days at sea level is limited.
The purpose of this study was to perform a single-blind sham-controlled study to investigate the effects of 1 wk of normobaric IHE combined with exercise training on endurance performance at a 4300-m altitude in healthy male lowlanders. We hypothesized that, in contrast to SHAM conditions, IHE would minimize endurance performance decrements at altitude after a 60-h delay at sea level as a result of retention of ventilatory acclimatization. Measurement of sea-level endurance performance was used solely as a control measure to determine whether any observed beneficial effect of IHE on endurance performance at altitude was due to an exercise training or altitude acclimatization effect.
Seventeen nonsmoking healthy male lowlanders completed this study. Eleven received IHE treatment and six received SHAM treatment. Each volunteer was blinded as to their group assignment. Baseline age, height, weight, peak oxygen consumption (V˙O2peak), and percent body fat were comparable in both groups (Table 1). Each was a lifelong low-altitude resident and had no exposure to altitudes greater than 1000 m for at least 6 months immediately preceding the study. All volunteers received medical examinations, and none had any condition warranting exclusion from the study. All tested within normal ranges for pulmonary function, hemoglobin concentration, and serum ferritin levels. To avoid iron depletion during the experiment, all volunteers consumed a One-a-Day Plus vitamin (Bayer Healthcare, Morristown, NJ) from their date of enrollment to their date of completion. Percent body fat was determined by dual-energy x-ray absorptiometry (DEXA; Lunar DPX, v6.3, Madison, WI). Each gave written and verbal acknowledgment of their informed consent and was made aware of their right to withdraw without prejudice at any time. The study was approved by the Institutional Review Board of the US Army Research Institute of Environmental Medicine in Natick, MA. The investigators adhered to the policies for the protection of human subjects as prescribed in Army Regulation 70-25, and the research was conducted in adherence with the provisions of 32 CFR Part 219.
The study was designed as a single-blind sham-controlled trial with one independent factor (IHE vs SHAM) and two repeated-measures factors (environment and test condition). An outline of the study design and testing schedule is shown in Figure 1. The groups were defined as IHE and SHAM. The environments were defined as sea level (SL) and high altitude (HA). The test conditions were defined as pretreatment (Pre-T) and posttreatment (Post-T). The IHE treatment consisted of a 2-h rest at a PO2 of 90 mm Hg (4500-m equivalent) followed by two 25-min bouts of cycle exercise at 80 ± 5% of peak HR (HRpeak) at a PO2 of 110 mm Hg (3000-m equivalent) in a hypoxia room (Colorado Altitude Training System, Boulder, CO). The SHAM treatment was identical except the PO2 was maintained at 148 mm Hg (610-m equivalent) for both rest and exercise. The mean CO2 levels in the hypoxia room were ≤0.05% during rest and ≤0.21% during exercise. Resting measurements of SaO2 were made within the last 20 min of the 4500-m exposure. During the two 25-min bouts of cycle exercise at 3000-m altitude-equivalent, HR (Model RS200; Polar Electro, Inc, Lake Success, NY), arterial oxygen saturation (SaO2; Model 8600; Nonin, Plymouth, MN), and RPE using the 6-20 Borg Scale (4) were recorded every 5 min. Power output was increased, if necessary, as exercise training progressed to ensure achievement of appropriate training HR. Six of the volunteers in the IHE group and six of the volunteers in the SHAM group completed 7 d of treatment and five volunteers in the IHE group completed 6 d of treatment. Volunteers were not allowed to exercise at SL during the week of treatment.
During the 2-wk SL baseline training, all volunteers performed two cycle endurance tests and four cycle exercise training sessions (consisting of two 25-min exercise bouts on a cycle ergometer at 80 ± 5% of HRpeak). Each volunteer also completed a V˙O2peak test at SL to set appropriate training workloads during treatment and during the cycle endurance test. After baseline training, each volunteer completed cycle endurance testing at SL and HA (Pre-T). Given that even one altitude exposure may partially acclimatize an individual on subsequent exposure to altitude (35), there was a 12-d washout period between the cycle endurance testing at Pre-T and the start of the IHE or SHAM treatment. During this washout period, both groups of volunteers participated in 3 d of cycle exercise training sessions, defined above, to maintain their fitness level.
All cycle endurance testing was performed in either a climatic (SL testing) or a hypobaric chamber (HA testing) maintained at a temperature and relative humidity of 21 ± 2°C and 45 ± 5%, respectively. The SL testing was performed at ambient barometric pressure (∼760 mm Hg), and HA testing was conducted at an altitude-equivalent of 4300 m (446 mm Hg).
Peak exercise testing.
V˙O2peak was measured during incremental cycling exercise to exhaustion on an electromagnetically braked cycle ergometer (Model Excalibur; Lode BV, Groningen, the Netherlands). After volunteers warmed up for 2 min at 50 W, the work rate was increased to 100 W for the next 2 min. Thereafter, the work rate was increased by 30 W every 2 min until the volunteer was unable to maintain a constant pedaling rate of 60 rpm. The highest V˙O2peak and peak work rate (Wpeak) during a 1-min period was used. Although V˙O2peak was not measured at HA, a 26% decrement from SL values was assumed (11) and used to set work rates approximating 40% and 60% of altitude V˙O2peak for the cycle endurance test at HA.
Cycle endurance testing.
Each cycle endurance test consisted of two consecutive 20-min SS exercise bouts (at 40% and 60% V˙O2peak) followed by a 10-min rest break and then a 720-kJ cycle time trial (i.e., time to complete a standardized amount of work on a cycle ergometer; Model Excalibur, Lode BV). Before the cycle endurance test, HR, SaO2, RPE, cardiac output (CO) by a finger blood pressure measurement system (Model Finometer; Finapress Measurement Systems, Arnhem, the Netherlands), and respiratory gas measurements (Model V˙max 229 (Sensormedics, Co, Yorba Linda, CA) or Model True Max 2400 (ParvoMedics, Inc., Sandy, UT)) were collected for 5 min, and the mean value was calculated. The HR, SaO2, RPE, CO, and respiratory gas measurements were also made from the 10th to the 15th minute during the two 20-min SS exercise bouts, and the mean values during this 5-min interval were calculated. A resting blood sample was analyzed for hemoglobin concentration [Hb] (i-Stat; Abbott Diagnostics, Abbot Park, IL) 5 min before the cycle endurance test and 2-3 min after finishing the 60% V˙O2peak SS exercise bout.
In the time trial test, volunteers were required to complete a fixed amount of work (720 kJ) on a cycle ergometer as quickly as possible. A shorter completion time from one testing condition to the next was considered an improvement in performance. During the cycle time trial performance test, volunteers were free to manually increase or decrease the work rate on the cycle ergometer by 5-W increments or decrements. There were no restrictions on the number of 5-W changes or their direction. This type of time trial test has been shown to have a high repeatability and low coefficient of variation for the outcome measure of time trial performance time (16). Respiratory gas and CO measurements were not made during the time trial portion of the cycle endurance test, but HR, SaO2, and RPE were collected every 5 min.
Volunteers consumed a standardized breakfast consisting of two to three Original Balance Bars (Balance Bar Food Company, Inc., East Hanover, NJ), two 8-oz orange juice boxes, and 5 mL of water·kg−1 body weight 1 h before beginning the cycle endurance test and were allowed to drink ad libitum during the cycle endurance test. Volunteers were required to abstain from caffeine, alcohol, tobacco, and exercise for at least 24 h before each cycle endurance test. Under all test conditions, cycle endurance testing was conducted at approximately the same time of day and same number of hours after eating.
For all measurements, a mixed-factorial ANOVA was used to analyze differences between the independent-group factor (IHE vs SHAM) and the two repeated-measures factors (environment and test condition). Pearson's product moment correlations were calculated for the relationships between changes in cycle time trial performance and changes in exercise HR, SaO2, and RPE during the cycle time trial. Significant main effects and interactions were analyzed using Tukey's least significant difference test. Statistical power calculations indicated that a sample of eight volunteers per group would provide a >80% chance of detecting a 6-min improvement in time trial performance in the IHE compared with the SHAM group given a reported 5-min SD for the identical time trial performance test (10). For all tests, statistical significance was set at P < 0.05. Data are presented as means ± SE.
Baseline endurance performance.
Seven volunteers in the IHE group could not finish the 720-kJ cycle time trial at HA at either Pre-T or Post-T. Time trial analysis was limited, therefore, to the time to reach 360 kJ (i.e., halfway point) at both SL and HA for all volunteers. One of the 11 volunteers in the IHE group only reached 210 and 240 kJ at Pre-T and Post-T, respectively. His data, therefore, were not included in the time trial analysis at SL or HA. From their first to their second time trial tests during the baseline phase, both the IHE (46.4 ± 2.5 to 38.9 ± 1.9min) and SHAM (43.5 ± 3.3 to 37.6 ± 2.4 min) groups demonstrated marked (P < 0.05) improvement in SL time trial performance, respectively. Time trial performance then plateaued from the second baseline time trial test to their first SL time trial test at Pre-T in both the IHE (38.9 ± 1.9 vs 38.0 ± 1.8 min) and SHAM (37.6 ± 2.5 vs 38.2 ± 2.4min) groups.
The IHE group demonstrated a 5% increase (P < 0.05) in resting SaO2 from day 1 (75 ± 1%) to day 6 (80 ± 1%) of the treatment but the SHAM group demonstrated no change in resting SaO2 from day 1 (98 ± 1%) to day 6 (98 ± 2%) of treatment. The IHE compared with the SHAM group trained at a slightly lower (P = 0.07) mean absolute (i.e., work rate) intensity (120 ± 5 vs 133 ± 6W) but the same mean relative (i.e., % HRpeak) intensity (79± 2 vs 80 ± 2%) during the first 6 d of treatment. The IHE compared with the SHAM group trained at a lower (P< 0.05) mean SaO2 (87 ± 1 vs 99 ± 1%) but similar mean RPE (10 ± 1 vs 10 ± 1) during the first 6 d of treatment.
High-altitude endurance performance.
There were no within- or between-group ventilatory, cardiovascular, perceived effort, or hematologic differences from Pre-T to Post-T during the cycle endurance test at HA except as indicated in Table 2. Resting SaO2 was increased (P < 0.05) in the IHE group but not in the SHAM group from Pre-T to Post-T. Individual (top) and group (bottom) time trial performance data at HA are presented in Figure 2. Five of the ten volunteers in the IHE group and three of the six volunteers in the SHAM group improved their time trial performance from Pre-T to Post-T. However, neither the IHE nor the SHAM group exhibited a change in time trial performance from Pre-T to Post-T. There were no within- or between-group differences in mean work rate, HR, SaO2, and RPE maintained during the time trial at Pre-T or Post-T (Table 3). There was no correlation between individual changes in time trial performance from Pre-T to Post-T, and individual changes in mean SaO2 and RPE maintained during the time trial from Pre-T to Post-T. There was a significant correlation (r = −0.82, P = 0.001) between the improvement in time trial performance and decrease in mean HR during the time trial from Pre-T to Post-T.
Sea-level endurance performance.
There were no within- or between-group ventilatory, cardiovascular, perceived effort, or hematologic differences from Pre-T to Post-T during the cycle endurance test at SL except as indicated in Table 4. Individual (top) and group (bottom) time trial performance data at SL are presented in Figure 3. Seven of the ten volunteers in the IHE group and four of the six volunteers in the SHAM group improved their time trial performance from Pre-T to Post-T. However, neither the IHE nor the SHAM group exhibited a change in time trial performance from Pre-T to Post-T. There were no within- or between-group differences in mean work rate, HR, SaO2, and RPE maintained during the time trial at Pre-T or Post-T (Table 3). There was no correlation between individual changes in time trial performance from Pre-T to Post-T, and individual changes in mean HR, SaO2, and RPE maintained during the time trial from Pre-T to Post-T.
The major finding of this investigation is that, contrary to our hypothesis, 1 wk of normobaric IHE combined with exercise training did not minimize the decrement in endurance performance at 4300 m during subsequent reexposure to high altitude. One week of IHE did induce ventilatory acclimatization as evidenced by the 5% increase in resting SaO2 from day 1 to day 6 of IHE. Although preexercise resting SaO2 was slightly elevated in the IHE group at Post-T, ventilatory acclimatization was not retained during SS exercise or the cycle time trial (Tables 3 and 4) on subsequent reexposure to HA after a 60-h delay at SL. The inability to retain ventilatory acclimatization during exercise likely explains our lack of improvement in endurance performance at HA in the IHE group. A secondary finding of this study was that as expected, 1 wk of normobaric IHE with exercise training did not improve endurance performance at SL. In addition, our lack of change in exercise HR, CO, and RPE during either of the two SS exercise bouts at SL or HA suggests a lack of training effect in either group from Pre-T to Post-T and further substantiates the absence of altitude acclimatization in the IHE group at Post-T.
Effects of IHE on high-altitude endurance performance.
We have previously reported 16%-21% improvements in endurance performance after 7-15 d of hypobaric IHE due to ventilatory acclimatization (1,2). Stimulation of the hypoxic ventilatory response, a key component of ventilatory acclimatization, has been previously demonstrated after short intermittent bouts of hypoxia (12,19,20). In this study, however, we found no evidence for any improvement in endurance performance after a week of normobaric IHE. Reasons for the discrepant findings between studies when using the same laboratory and techniques may be related to: 1) a previously undetected placebo or trial effect, 2) a previously undetected training effect, 3) the use of normobaric IHE versus hypobaric IHE, and/or 4) rapid ventilatory deacclimatization during the 60-h time lapse at SL before subsequent reexposure to high altitude.
A sham control group was included in this study to investigate the possibility of a placebo and/or trial effect given that each volunteer had two high-altitude exposures. The results of most IHE studies suffer from a lack of placebo control, and a placebo effect may have potent effects on endurance performance in and of itself (5). In this study, neither group improved endurance performance from Pre-T to Post-T. This finding suggests no placebo effect given that all of the test volunteers believed they were undergoing IHE, and no trial effect because of the Pre-T high-altitude exposure. Our lack of change in RPE during the two SS exercise bouts from Pre-T to Post-T in either group also suggests no placebo effect.
Sea-level endurance measurements before the subsequent reexposure to high altitude were made to determine whether any observed beneficial effect of IHE on endurance performance at altitude was due to an exercise training or altitude acclimatization effect. There was no change in ventilatory, cardiovascular, perceived effort, or hematologic responses during SS exercise or time trial performance at SL in either group from Pre-T to Post-T. It is clear that when a 2-wk baseline training period is used to bring fit but not elite volunteers up to a certain level of fitness, there is no additional training that occurs during 1 wk of normobaric IHE. This lack of training effect during a short period is in agreement with findings from other placebo-controlled IHE studies (13,25,30,33,36).
Given that the first two reasons do not seem to plausibly explain the discrepant results between studies, the mode of delivering the intermittent hypoxic stimulus must be considered. In our first two studies (1,2), we used hypobaric IHE, and in this study, we used normobaric IHE to deliver the hypoxic stimulus. When we compare the magnitude of ventilatory acclimatization (e.g., resting SaO2) induced using hypobaric IHE (e.g., 3% increase from day 1 to day7) with the magnitude of ventilatory acclimatization induced using normobaric IHE (e.g., 5% increase from day 1 to day6), we find no difference in the response outside the measurement error of the instrument. Both hypobaric and normobaric methods, therefore, seem to induce the same magnitude of ventilatory acclimatization, which suggests that normobaria was not the reason for discrepancy between studies.
The most likely reason for the discrepancy between studies is that in the two original studies (1,2), the subsequent reexposure to 4300 m was conducted <24 h after the last intermittent altitude exposure. The 3% increase in resting SaO2 induced during the 7-d hypobaric IHE study was retained during subsequent reexposure to 4300 m both at rest and during the cycle endurance test and time trial (2). In the present study, however, there was a 60-h delay at sea level before volunteers were reexposed to high altitude. Although resting SaO2 increased by 5% during the week of IHE treatment, on subsequent reexposure to 4300 m, the resting SaO2 was only increased by 1.5% and the exercise SaO2 during SS exercise and the cycle time trial was not increased at all (Tables 2 and 3). It is therefore likely that a significant degree of ventilatory acclimatization that developed during IHE in the present study was lost during the 60-h delay at sea level.
Although we have previously reported that ventilatory acclimatization (e.g., change in hypoxic ventilatory response and SaO2) obtained after 14 d of residence at 4300 m is retained ∼45% during subsequent reexposure to 4300 m in a hypobaric chamber after a 7-d delay at SL, this finding was observed after ventilatory acclimatization induced by altitude residence at 4300 m (27). In that study, resting SaO2 increased 10% after 14 d of altitude residence, whereas in the present study, resting SaO2 only increased 5% during the week of IHE. The loss of ventilatory acclimatization during subsequent reexposure in the present study is therefore not surprising given that the ventilatory acclimatization response after IHE was only half of that observed after altitude residence. Given our previous findings that ventilatory acclimatization was the main reason for the observed improvements in endurance performance at altitude, the loss of this effect helps to explain the lack of improvement in endurance performance at altitude in the present study.
Effects of IHE on sea-level endurance performance.
Unlike other studies that have used IHE to improve endurance performance at sea level (7,17,18,24), neither did we anticipate nor did we find improvements in sea-level endurance performance after 1 wk of IHE. Typical reasons cited for improvements in sea-level endurance performance after IHE include enhanced erythropoiesis, muscle oxidative capacity, and/or cycling efficiency (7,17,18). We did not find any differences in Hb values from Pre-T to Post-T, suggesting that erythropoiesis was unchanged after IHE treatment. Although we did not measure muscle oxidative capacity directly, resting and exercise RER values did not indicate any changes in substrate use from Pre-T to Post-T in the IHE group. Furthermore, we did not find any evidence for enhanced cycling efficiency, as measured by exercise O2 during either of the two SS exercise bouts, in the IHE group from Pre-T to Post-T. Given the short IHE treatment protocol used in this investigation, these results were not surprising. A recent double-blind investigation reported that even 4 wk of IHE at a similar altitude did not improve maximal or short-duration endurance performance at sea level in well-trained athletes (30).
Our finding contrasts with the results from a recent placebo-controlled study in which hypoxic compared with normoxic training was detrimental to sea-level short-term endurance performance in well-trained athletes (32). The authors attributed the results from that study to a decrease in absolute work rate developed during the hypoxic interval training sessions. Others have also suggested that when athletes return to sea level after altitude acclimatization, there is a detrimental effect on sea-level endurance performance during the first week of return to sea level (6). This finding has been attributed to training at a lower absolute work rate at altitude, which results in less ATP turnover and O2 flux in the working muscle (9,21). Those studies all performed hypoxic training for a minimum of 3-5 wk in elite athletes during which a reduction in absolute work rate for that length of time may have a negative impact on sea-level endurance performance. However, the results from this study suggest that 1 wk of IHE does not have any detrimental impact on endurance performance at sea level in healthy fit males. The practical implication is that military personnel, search and rescue teams, and mountaineers that train in hypoxia for up to a week to improve altitude performance (2,26,34) will not lose their sea-level endurance capacity. This is important information given that many of these groups of personnel routinely go from sea level to altitude and back to sea level.
This study has some limitations. First, the time trial analysis was cut off at the halfway point (i.e., 360 kJ) because of the number of nonfinishers in the IHE group. The volunteers may have gone faster or used a different pacing strategy during the time trial test if they knew a priori that the test was only 360 kJ. However, results from our previous research using the same 720-kJ time trial performance test demonstrate that volunteers work at ∼55% to 60% of their SL Wpeak at SL and ∼35% to 40% of their SL Wpeak at 4300 m throughout the entire cycle time trial (10). The mean work rate maintained during the cycle time trial, expressed as a percent of Wpeak, in this study is consistent with our previous research (Table 3). We do not feel, therefore, that the volunteers would have significantly increased their work rate if the time trial was set at 360 kJ from the start. Second, we did not measure oxygen consumption during the time trial, and as such, it is difficult to determine whether the volunteers pushed themselves to their limit. Although mean RPE was slightly low during the time trial because of the military psychological factor, mean HR was maintained at ∼85% to 90% of their SL HRpeak at SL and ∼75% to 80% of their SL HRpeak at HA (Table 3). The HR values during the time trial in this study are also in agreement with our previous research (10) and suggest that the volunteers were pushing themselves at a high intensity throughout the cycle time trial.
In conclusion, contrary to our hypothesis, 1 wk of normobaric IHE combined with exercise training did not minimize decrements in endurance performance during subsequent reexposure to high altitude. Although IHE induced ventilatory acclimatization, no ventilatory acclimatization benefits were present during exercise at 4300 m after a 60-h delay at sea level. This result is most likely due to a rapid loss of ventilatory acclimatization during the 60-h delay at sea level. Short-term normobaric IHE may be beneficial in minimizing endurance performance decrements at altitude if the subsequent altitude exposure occurs immediately, but further research is warranted. In addition, there was no improvement or decrement in sea-level endurance performance after 1 wk of normobaric IHE. The practical implication is that military personnel, search and rescue teams, and mountaineers that train in hypoxia for up to a week to improve altitude performance will not lose their sea-level endurance capacity.
The dedicated and professional efforts of Mr. Vinnie Forte, Ms. Ingrid Sils, Mr. Guy Tatum, Mr. Leonard Elliot, Mr. Rob Demes, Ms. Alison Money, Ms. Elizabeth Root, SSG Sarah Elliot, SSG Michael Cavallo, and SPC Miguel Fernandez supporting the collection and analysis of the data are acknowledged and greatly appreciated. The dedication and efforts of the test volunteers in completing this study are also acknowledged and appreciated.
Funding provided by US Army Medical Research Materiel Command ATO IV.MD.2006.01.
The results of the present study do not constitute endorsement by the American College of Sports Medicine. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, or decision, unless so designated by other official documentation. Approved for public release; distribution unlimited.
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