Forum : “Living high-training low”

10-08-09, 12:58
“Living high-training low” altitude training improves
sea level performance in male and female elite runners

1Norwegian University of Sport and Physical Education, 0806 Oslo, Norway;
2Indiana University, Bloomington, Indiana 47405; and 3The Institute of Exercise
and Environmental Medicine, Presbyterian Hospital of Dallas, and the
University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75231
Received 20 July 2000; accepted in final form 17 May 2001

Stray-Gundersen, James, Robert F. Chapman, and
Benjamin D. Levine. “Living high-training low” altitude
training improves sea level performance in male and female
elite runners. J Appl Physiol 91: 1113–1120, 2001.—
Acclimatization to moderate high altitude accompanied by
training at low altitude (living high-training low) has been
shown to improve sea level endurance performance in accomplished,
but not elite, runners. Whether elite athletes, who
may be closer to the maximal structural and functional
adaptive capacity of the respiratory (i.e., oxygen transport
from environment to mitochondria) system, may achieve similar
performance gains is unclear. To answer this question,
we studied 14 elite men and 8 elite women before and after 27
days of living at 2,500 m while performing high-intensity
training at 1,250 m. The altitude sojourn began 1 wk after
the USA Track and Field National Championships, when the
athletes were close to their seasons fitness peak. Sea level
3,000-m time trial performance was significantly improved
by 1.1% (95% confidence limits 0.3–1.9%). One-third of the
athletes achieved personal best times for the distance after
the altitude training camp. The improvement in running
performance was accompanied by a 3% improvement in maximal
oxygen uptake (72.1 6 1.5 to 74.4 6 1.5 mlzkg21 z
min21). Circulating erythropoietin levels were near double
initial sea level values 20 h after ascent (8.5 6 0.5 to 16.2 6
1.0 IU/ml). Soluble transferrin receptor levels were significantly
elevated on the 19th day at altitude, confirming a
stimulation of erythropoiesis (2.1 6 0.7 to 2.5 6 0.6 mg/ml).
Hb concentration measured at sea level increased 1 g/dl over
the course of the camp (13.3 6 0.2 to 14.3 6 0.2 g/dl). We
conclude that 4 wk of acclimatization to moderate altitude,
accompanied by high-intensity training at low altitude, improves
sea level endurance performance even in elite runners.
Both the mechanism and magnitude of the effect appear
similar to that observed in less accomplished runners,
even for athletes who may have achieved near maximal
oxygen transport capacity for humans.
endurance performance; hypoxia; erythropoietin; symmorphosis;
maximal oxygen uptake; running; athletics
WE HAVE PREVIOUSLY SHOWN that 4 wk of acclimatization
to moderate altitude (2,500 m) combined with training
at low altitude (1,250 m) (HiLo) is superior to an
equivalent training camp at sea level (24). This form of
altitude training produced a 1.4% improvement in
group sea level endurance performance in collegiate
and recent postcollegiate runners (age 20 6 2 yr). The
mechanism for the improvement in performance with
this approach appears to be twofold: an increase in red
cell mass as a function of the hematological adaptation
to moderate altitude, which produces an increase in
maximal oxygen uptake (V˙ O2 max), plus the maintenance
of sea level oxygen flux during low-altitude
training, which preserves skeletal muscle structure
and function and facilitates an improvement in sea
level running performance.
However, despite numerous anecdotal reports of the
success of altitude training for world class athletes,
some recent reports have suggested that HiLo, or any
form of altitude training, may not be advantageous for
elite compared with collegiate level athletes (1, 2, 14).
The concept of symmorphosis, as elaborated by Hoppeler
and Weibel (17), argues that, for any system,
such as the respiratory chain for oxygen transport, the
maximal capacity of each parameter is adjusted quantitatively
to match the structural and functional limits
of the demands placed on the system as a whole. Thus,
for the “elite athletes” of the animal kingdom, each step
of the pathway of oxygen from the atmosphere to the
mitochondria has evolved toward optimal function and
maximal aerobic power, allowing little room for further
adaptive improvement. Therefore, for elite human athletes,
small, short-term improvements in one step of
the oxygen cascade may be met by functional limits in
other steps, minimizing the potential performance benefit
of altitude training. However, elite human athletes
living and training at sea level are unable to develop
similar levels of circulating hemoglobin/red cell mass
as “high-endurance” animal species who have the ability
to autotransfuse by splenic contraction (23, 25).
Thus raising circulating hemoglobin levels conceivably
has the greatest potential for improving elite endurance
performance in humans. In addition, the interaction
between convective and diffusive components of
Address for reprint requests and other correspondence: B. D.
Levine, Institute for Exercise and Environmental Medicine, 7232
Greenville Ave., Suite 435, Dallas, TX 75231 (E-mail: benjaminlevine
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J Appl Physiol
91: 1113–1120, 2001.
http://www.jap.org 8750-7587/01 $5.00 Copyright 2001 the American Physiological Society 1113
oxygen transport, as described by Wagner (35), would
predict an increase inV˙ O2 max with increasing circulating
hemoglobin and red cell mass. In support of these
concepts, transfusion studies (5, 10, 37) and those
administering recombinant erythropoietin (3, 4) suggest
that an increase in red cell mass by itself will
increase theV˙ O2 max for all endurance athletes, regardless
of performance level.
Thus the present study was designed to investigate
the effect of the HiLo paradigm on elite runners who
were likely to be much closer to their ultimate performance
potential than the athletes previously studied
with this approach. The study was timed such that the
athletes would be in the best shape of the year [i.e.,
after they had just completed the spring track season
culminating with the National Collegiate Athletic Association
(NCAA) championships and the USA Track
and Field National Championships]. We hypothesized
that the combination of acclimatization to 2,500 m and
high-intensity training at 1,250 m would improve sea
level performance in elite middle- and long-distance
Twenty-six distance runners (17 men and 9 women) were
recruited. Athletes were required to be competitive at a
national level in an event from the 1,500 m to the marathon.
Twenty-four of the 26 athletes were ranked in the US top 50
for their event in 1997. The athletes included two 1996
Olympians, and 50% of the athletes had competed in the
1996 US Olympic Trials. All but four athletes competed in
the 1997 NCAA Championships or the 1997 USA Track and
Field Championships or both. Three of those four athletes
were attempting to run qualifying times up to the day of the
meet. Exclusion criteria included altitude residence (.1,000
m) or recent illness or injuries preventing normal training
and racing. The subjects gave their written consent to the
study, which had received approval from the Institutional
Review Board of the University of Texas Southwestern Medical
The study protocol was a modification of one previously
developed by the authors for collegiate runners (24). Briefly,
the athletes were assessed at sea level in the week before and
the week after 27 days of living at 2,500 m (see Fig. 1). The
NCAA Championships were held at sea level 3 wk before the
altitude sojourn, and the USA Track and Field Championships
ended 1 wk before the altitude sojourn. Individualized
training plans were developed by the athlete and his or her
coach. Plans were discussed with the investigators and conformed
to a training template presented by the investigators
(24). Athletes were required to perform high-intensity, highvelocity
training at 1,250 m. All other training took place
between 1,250 and 3,000 m with most of the training occurring
between 2,000 and 2,800 m. This modification of the
HiLo model, termed “HiHiLo,” (living at moderate altitude,
low-intensity base training at moderate altitude, high-intensity
interval training at low altitude), has been demonstrated
in pilot work to provide identical improvement inV˙ O2 max and
5,000-m time as the original HiLo model (34). All athletes
received oral liquid iron supplementation (Feo-Sol, 9 mg
elemental iron/ml) with dose adjusted on the basis of plasma
ferritin concentration (range: 5–45 ml/day).
Performance. Sea level performance was assessed by
3,000-m time trial races on a 400-m all-weather track (Indiana
University, Bloomington, IN) the day before and 3 days
after the altitude sojourn. The time trials were run in mens
and womens heats in the early evening (1900 to 2000).
Athletes were instructed to achieve the best time possible on
each time trial. Experienced pace setters (athletes not otherwise
involved in the project) were utilized to set a fast,
competitive pace for the first 1,600 m of the 3,000 m race to
ensure physiological rather than tactical performance. The
pace setter or “rabbit” ran the same preselected race pace in
both the prealtitude and postaltitude time trials. Temperatures
ranged from 25 to 27C, relative humidity ranged
between 50 and 75%, and there was no wind. Time was
recorded for each subject to the nearest 0.1 s.
Treadmill assessment. After a 15-min warm-up, the athlete
ran to volitional exhaustion performing a protocol with
constant velocity and increase in grade of 2% every 2 min.
Inspired ventilation was measured by a dual-thermistor flow
probe (Torrent 1200, Hector Engineering), and expired gas
concentrations were measured in a 5-liter mixing chamber by
mass spectrometer (Marquette RMS M-100, Milwaukee, WI).
Heart rate was recorded at the end of each minute by telemetry
(Polar). Percent arterial oxyhemoglobin saturation was
measured by ear oximetry (Hewlett-Packard 47201A). Data
were collected and displayed with the use of a data acquisition
control system (Workbench for Windows 2.0, Strawberry
Tree) sampling at 40 Hz. Values for arterial oxygen saturation,
oxygen uptake, and minute ventilation were averaged
over each minute of exercise.
Hematology assessment. Venous blood was drawn into
tubes containing EDTA, with the subject in the supine position,
between 0600 and 0700 on four occasions: 3 days before
the altitude sojourn, after the first night at altitude (20 h),
after 19 days at altitude, and 20 h after return to sea level.
Whole blood was assayed in duplicate for hemoglobin concentration
(Radiometer OSM-3) and hematocrit (spun capillary
tubes). Plasma was then obtained by centrifugation and
stored frozen (280C) until assayed. Plasma was assayed by
RIA with commercial kits and a gamma counter (ISODATA
20–20) for ferritin (DSL, Webster, TX), erythropoietin (DSL),
and soluble transferrin receptor concentrations (Orion).
Fig. 1. Timetable for the experiment. NCAA, National Collegiate
Athletic Association; USATF, USA Track and Field; Hi, high altitude;
Lo, low altitude.
J Appl Physiol • VOL 91 • SEPTEMBER 2001 • www.jap.org (http://www.jap.org)
Data are presented in the tables as means 6 SD. SPSS 6.1
was utilized for statistical calculations. Performance and

O2 max were compared by paired t-test. The hematologic
data were compared by one-way ANOVA. Gender differences
were tested by using a two-way ANOVA (altitude 3 gender).
Significance was set at P # 0.05. When a significant effect
was obtained, post hoc analysis was performed with the
Student-Newman-Keuls test to identify differences.
Fourteen men (25 6 3 yr, 179 6 5 cm, 63.6 6 5.2 kg)
and eight women (24 6 3 yr, 168 6 5 cm, 53.3 6 4.9 kg)
successfully completed the protocol for a total of 22
complete subjects. Four subjects (three men and one
woman) suffered injury (n 5 2) or illness (n 5 2) during
the sojourn that prevented normal training or racing
and were not included in the analysis. There were no
gender differences with respect to the response to the
altitude sojourn; therefore, data for men and women
are considered together.
Group 3,000-m performance at sea level was significantly
improved after the HiLo treatment (Table 1 and
Fig. 2). Men and women improved to similar extents,
reducing time trial time by 5.8 s (95% confidence limits
1.8–9.8 s) or 1.1% (95% confidence limits 0.3–1.9%).
Three athletes improved their sea level 3,000-m time
by as much as 23 s, whereas one athlete ran 18 s
Maximal Exercise

O2 max was significantly increased by 3% after the
altitude camp (see Fig. 3). Maximal ventilation was
also significantly increased after the altitude camp
(Table 2). There was a significant relationship between
the change in V˙ O2 max and the change in maximal
minute ventilation (r 5 0.67, P 5 0.0006). Moreover,
there was a less robust but still statistically significant
relationship between the change in V˙ O2 max and the
change in 3,000-m running time (r520.48, P 5 0.02).
Maximal heart rate was unchanged. Arterial oxygen
saturation was reduced to 89 6 4% during maximal
exercise but was unaffected by the altitude camp. Time
to exhaustion on the treadmill was not significantly
Hematology Assessments
Hemoglobin concentration increased on acute ascent
to altitude, remained elevated during the camp, and
was significantly elevated on return to sea level (see
Table 3). Hematocrit was significantly elevated when
measured on the 19th day at altitude and remained
significantly elevated on return to sea level. Plasma
ferritin concentrations were not significantly altered
from the initial value. However, despite oral iron supplementation,
there was a trend (P 5 0.07) for subsequent
values to be lower than the initial value. Plasma
erythropoietin concentration doubled after one night at
Table 1. Sea level performance
Pre-HiLo Post-HiLo
3,000 m time, min:s
Group (n 5 22) 8:45.460:39 8:39.660:39*
Women (n 5 8) 9:32.460:11.1 9:26.960:11.3*
Men (n 5 14) 8:18.460:14.0 8:12.660:10.8†
Values are means 6 SD. HiLo, living high-training low. *P #
0.05; †P , 0.10 pre vs. post.
Fig. 2. Change in 3,000-m performance in elite male (A) and female
(B) runners to a 4-wk living high-training low-altitude sojourn. *P ,
0.05; &P , 0.10 compared with prealtitude.
Fig. 3. Change in maximal oxygen uptake (V˙ O2max) in elite male (A)
runners and elite female (B) runners to a 4-wk living high-training
low- altitude sojourn. *P , 0.05 compared with prealtitude.
Table 2. V˙ O2max
Pre-HiLo Post-HiLo
Time to exhaustion, min 8.861.1 9.061.0

E, l/min 152631 163634*
HR, beats/min 19267 19168
%Arterial saturation 8964 8964

O2max, mlzkg21 zmin21 72.166.9 74.466.8*
Values are means 6 SD; n 5 22 (18 men, 8 women). V˙ O2max,
maximal oxygen uptake; V˙ E, minute ventilation; HR, heart rate.
*P # 0.05 pre- vs. post-HiLo.
J Appl Physiol • VOL 91 • SEPTEMBER 2001 • www.jap.org (http://www.jap.org)
2,500 m and was not different from baseline after 19
days at the camp. Then plasma erythropoietin levels
decreased significantly on return to sea level. Soluble
transferrin receptor concentrations were significantly
elevated (25%) after 19 days at altitude, consistent
with active erythropoiesis (3, 5), and returned to baseline
on return to sea level.
The major finding of this study is that, in this group
of elite runners, sea level 3,000-m running performance
improved significantly in response to a 27-day
camp utilizing the HiLo paradigm. In fact, nine athletes
recorded personal records at the distance after
the HiLo camp, despite having prepared for and competed
in national championship events just before the
sojourn. The mechanism of the improvement appears
to be similar to that previously described in carefully
controlled studies of collegiate-level athletes (24) with
a stimulation of erythropoiesis leading to an apparent
increase in oxygen delivery to peripheral tissues as
evidenced by 1) a near doubling of plasma erythropoietin
concentration and a 43% reduction in serum ferritin
concentration despite oral iron supplementation
on acute exposure to altitude, 2) a rise in soluble
transferrin receptor concentration with chronic exposure
to altitude, and 3) an increase in hemoglobin
concentration and hematocrit on return to sea level
with a decrease in plasma erythropoietin concentration
below original sea level baseline.
We must acknowledge that our study suffers from a
major limitation shared by most research conducted in
elite athletes: namely, the absence of a concurrent
control group performing a similar training camp at
sea level. Such a control group would be optimal to
ensure that the athletes did not improve merely from
the result of a training camp per se, rather than living
high-training low. A number of lines of evidence, however,
suggest that the study design employed in this
experiment was sufficient to account for most of this
effect. First, in our previous studies (24), which included
many years of piloting work, we determined
that for collegiate athletes at least 2 wk of controlled
training were necessary to overcome the “training
camp effect.” For example, in one preliminary study of
a sea level training camp, six male runners increased
theirV˙ O2 max from 68 6 1.5 to 70 6 1.4 mlzkg21 zmin21
after 2 wk of supervised training, but did not increase
further after an additional 2 wk of training (70 6 1.8
mlzkg21 zmin21) (Levine and Stray-Gundersen, unpublished
observations). Thus, for all the 52 male and
female athletes studied in our previously published
reports (24, 34), after a 2-wk “lead-in” phase of supervised
training there was no significant increase in

O2 max with an additional 4 wk of structured training
at sea level (64 6 0.8 to 64 6 0.8 mlzkg21 zmin21).
Moreover, after these 6 wk of sea level training by
collegiate athletes in these studies, there was no further
improvement obtained even by an outstanding
training camp environment at sea level for an additional
4 wk (24). In the present study, we considered
that the months of preparation by these elite athletes
for their national championships were at least equivalent
to the 2 wk of training applied to collegiate athletes
a number of weeks after their competitive season
for the purpose of minimizing the training camp effect.
Additionally, on review of each athletes training program
leading up to the championships, all had peaked
appropriately for this event. As far as could be determined
from inspection of training logs and individual
meetings with each athlete over the course of the
study, no one had a change in training that could
explain an improved performance.
We suspect, but cannot prove, that the athletes were
equally motivated to give their best performance in
precamp as well as postcamp time performance tests.
We can say, however, that these athletes were all
extremely competitive, and it was our clinical impression
that motivation was high during all study races.
Moreover, all the time trials were paced by an experienced
pace setter who maintained the same running
speed for 4 of 7.5 laps in both the pre- and postcamp
trials. Finally, athletes were pushed to exhaustion in
all treadmill tests, and there was no evidence from
respiratory exchange ratio or heart rate that the athletes
gave a better effort on the second test than the
first (for example, maximal heart rate was 192 on the
first test and 191 on the second test).
We also cannot exclude the possibility that the use of
iron supplements to ensure adequate iron availability
for erythropoiesis with altitude exposure (24) could
have resulted in an increase in hemoglobin concentration
independent of an altitude effect. We suspect this
possibility is unlikely, however, for the following reasons.
1) None of the athletes in this study was anemic
or had small red blood cells typical of iron deficiency
Table 3. Hematologic assessments
Sea Level Pre-HiLo Acute HiLo Chronic HiLo Sea Level Post-HiLo F
Hemoglobin, g/dl 13.361.1 14.361.2* 15.161.2* 14.361.1* †
Hematocrit, % 41.062.5 40.662.5 42.562.6* 42.862.8* †
Ferritin, mg/ml 69679 39641 37633 34622 0.07
Erythropoietin, ng/ml 8.562.5 16.264.6* 9.762.0 7.462.1* †
Soluble transferrin receptor, mg/ml 2.160.7 2.060.6 2.560.6* 2.060.5 †
Values are means 6 SD. *P , 0.05 different from initial sea level value (Student-Newman-Keuls post hoc tests); †significant F statistic
(P#0.05) (1-way ANOVA).
J Appl Physiol • VOL 91 • SEPTEMBER 2001 • www.jap.org (http://www.jap.org)
anemia. All had normal hemoglobin concentration and
hematocrit, and all had normal red cell size and distribution.
2) Despite oral iron supplementation, the iron
requirements of altitude exposure were such that bone
marrow iron stores as measured by serum ferritin did
not increase over the course of the training camp. In
fact, ferritin decreased with each longitudinal measurement
(Table 3), suggesting that bone marrow iron
stores were more rather than less depleted at the end
of the altitude camp. 3) The baseline erythropoietin
concentrations were normal and low, arguing against a
physiologically significant anemia; anemia is the most
potent stimulus to synthesis of erythropoietin (20).
Thus the available evidence would argue against simple
treatment of iron deficiency as the mechanism of
the increase in hemoglobin and hematocrit in this
Finally, because of time constraints associated with
performing the study in elite athletes during peak
competition periods, the subjects were not as completely
characterized, nor were the details of the training
program as rigorously controlled to the same extent
as in previous work (24). However, the same basic
training template was used for the protocol, and key
parameters were measured in both populations, including
erythropoietin and hemoglobin concentrations,

O2 max, and time trial performance, that allowed comparison
to our previous studies.
When the results from carefully controlled, comprehensively
assessed studies on collegiate runners are
compared with the results of the present study (see
Table 4), the results are remarkably similar in both
direction and magnitude of the effect. In addition,
when similar parameters were measured, the results
suggest that the same mechanism produced the effect,
i.e., an increase in erythropoietin leading to an increase
in hemoglobin concentration, increasedV˙ O2 max,
and increased performance. Therefore, we believe that
the compromises made in this study to evaluate elite
athletes during a time of peak fitness did not compromise
the validity of the results.
The Unique Model of Elite Athletes
Elite athletes of the animal kingdom provide a
unique model of the concept of symmorphosis, whereby
the structural design of all components comprising a
system is matched quantitatively to functional demand
(17). For example, foxes, dogs, and horses have ;2.5
times the mass-specific rate of oxygen consumption
compared with sedentary species of the same body size,
such as the agouti, goat, or steer. For such animals, the
mechanism of this large adaptive range of oxygen consumption
appears due to a large mitochondrial volume,
matched by a large muscle capillary volume and vascular
conductance in skeletal muscle; a higher hemoglobin
concentration; and a large maximal stroke volume.
The redundancy in the pulmonary system of
nonathletic species, manifested by excess ventilatory
and diffusing capacity, is nearly eliminated in the
athletic species, confirming the principle of symmorphosis.
In other words, comparative studies suggest
that such “athletes” are operating at or close to the
upper limit of their structural capacity for convective
transport of oxygen at V˙ O2 max.
If this analysis is also relevant for humans, it could
be argued that elite human athletes would have a
smaller adaptive capacity for increasing oxygen transport
than less accomplished athletes, such as those
originally reported using the HiLo approach. Although
the amount of published data examining truly elite
athletes undergoing altitude training is limited, at
least one small study of world-class Australian cyclists,
before and after a 31-day altitude camp (2,690 m),
recently reported no changes in hemoglobin mass nor
sea level V˙ O2 max despite an improvement in performance
(14). The authors suggested that the outcome
was, at least in part, due to limited adaptive reserve in
such athletes (14), particularly in the lung, which is
essentially static to training. For example, elite endurance
athletes display pulmonary gas-exchange limitations
at sea level of a greater magnitude and prevalence
than lesser trained individuals, part of which is
accounted for by limitations in ventilation (8). However,
in the present study, we observed an increase in
maximal ventilation that was commensurate with the
increase in V˙ O2 max. We cannot determine from the
data in this experiment whether the increase in maximal
ventilation was simply a consequence of the increased

O2 max or rather the cause of the increased

O2 max as a function of increased ventilatory work. An
increase in ventilation during exercise that persists for
a period of time after return to sea level would be an
expected result of ventilatory acclimatization to high
altitude and suggests that, at least in these athletes,
flow limitation did not restrict maximal ventilation to a
major degree. We speculate that if the initial increase
inV˙ O2 max was, at least in part, required to support an
increase in ventilatory work from altitude acclimatization,
then the restoration of normal respiratory control
over time after return to sea level would allow the
increased oxygen transport capacity to be directed to
working skeletal muscle, thus providing an explanation
for the oft-cited observation (9) that many athletes
achieve their best performances after a period of reac-
Table 4. Comparison of elite and collegiate athletes for changes in selected hematologic and performance variables
DEpo, % DHb, g/dl DV˙ O2max, mlzkg21 zmin21 DPerformance, %
Elite runners (n 5 22; 14 M, 8 F) 103674% 1.061.1 2.362.6 1.1
College runners (n 5 26; 18 M, 8 F) 59640% 1.160.7 2.562.4 1.4
Values are means 6 SD. D, change in; Epo, erythropoietin; M, men; F, women. Performance refers to 3,000-m racing time (elite runners)
or 5,000-m racing time (college runners).
J Appl Physiol • VOL 91 • SEPTEMBER 2001 • www.jap.org (http://www.jap.org)
climatization to sea level. Further study will be necessary
to confirm or exclude this hypothesis.
A more detailed analysis of human vs. nonhuman
athletes suggests, in fact, that the most likely avenue
for elite human athletes to improve oxygen transport
would be to raise their red cell mass and circulating
hemoglobin concentration. In human athletes, red cell
mass is the one component of the oxygen cascade that
does not increase to the level observed in “elite athletes”
of the animal kingdom. Humans do not clearly
autotransfuse by splenic contraction at the onset of
exercise like horses (25) and dogs (23). This effect
raises exercise hematocrit well into the 50s in those
species. Thus, when the oxygen-carrying capacity of
the blood is increased in elite athletes, either by acute
red blood cell infusion (5, 10, 37) or by chronic administration
of recombinant human erythropoietin (3, 4),

O2 max increases. The results shown in the present
study are in the same direction as and half the magnitude
of the results obtained by either an acute (transfusion)
or chronic increase in red cell mass (exogenous
rhEPO administration). At least one uncontrolled
study has suggested altitude-induced improvements in

O2 max in undeniably elite athletes (7). One of these
subjects (JR) went on to set a world record after living
at altitude and training intermittently at sea level.
Some investigators, failing to observe an increase in
hemoglobin/myoglobin mass after brief periods of time
in normobaric hypoxic environments (8–10 h/night for
10 days to 3 wk), have questioned the erythropoietic
effect of moderate altitude exposure (1, 2). However,
the evidence in favor of such an altitude-mediated
erythropoiesis is quite compelling. Cross-sectional
studies in the Peruvian Andes (19, 28, 32) as well as in
the Colorado Rockies (36) have demonstrated clearly
that there is an elevated red cell mass in natives of
high altitude that is proportional to the oxyhemoglobin
saturation (19, 36).
Moreover, when sea level natives ascend acutely to
altitude, there is an increase in iron turnover by more
than twofold that begins within the first few hours of
exposure and peaks by ;2–3 wk (12, 18, 28). Direct
examination of the bone marrow during acute highaltitude
exposure has documented a dramatic increase
in nucleated red blood cells, virtually doubling by 7
days, indicative of accelerated erythropoiesis (18, 28).
Although most of these data are from altitudes higher
than the 2,500 m studied in the present experiment,
our elite endurance athletes spent significant time
exercising at low-moderate altitudes, which causes further
arterial desaturation (8), suggesting that athletes
may have a greater stimulation of erythropoiesis for
the same altitude than a more sedentary population.
As in the present study with elite athletes, previous
studies have also shown that both iron turnover (18,
28) as well as erythropoietin concentrations (6, 15, 20,
24, 30) return to sea level values relatively rapidly
during chronic altitude exposure. Nevertheless, the red
cell mass continues to increase for up to 8 mo of chronic
altitude exposure, at least at altitudes above 4,000 m
(28), suggesting that this level of stimulated erythropoiesis
is elevated for the absolute level of the arterial
oxygen content. Thus when altitude natives or altitude
sojourners return to sea level, there is a suppression of
erythropoietin (6, 12, 15, 20, 24, 30), a reduction in iron
turnover and bone marrow production of erythroid cell
lines (18, 28), and a decrease in red cell survival time
(28, 29). The change in the ratio of hemoglobin concentration
to erythropoietin concentration over the time
course of the present study (decrease with acute exposure,
increase during chronic exposure, and further
increase on return to sea level) is further evidence for
the stimulation of erythropoiesis on ascent and deceleration
of the erythropoiesis on return to sea level in
these athletes following the living high-training low
model of altitude training.
Many other factors exist, however, that may compromise
the ability of small studies to document clearly an
increase in red cell mass with moderate altitude exposure,
and that may have led to divergent results with
different groups of elite athletes. Duration of altitude
exposure, in terms of both time/day at altitude and
number of weeks, may play an important effect: studies
employing 8–10 h hypoxia/day have not been effective
(1, 2), whereas those employing 16 h hypoxia/day have
shown an increased in hemoglobin/myoglobin mass using
the same methods (31). Inflammatory cytokines
(e.g., IL-1) also may limit the increase in erythropoietin
in response to hypoxia (11, 13, 21), suggesting that the
presence of injury or infection could impair the erythropoietic
response to altitude.
There is also a marked individual variability in the
response to altitude training. We have previously reported
that, even with the optimal method of HiLo or
HiHiLo training, only slightly more than 50% of athletes
will be robust responders (i.e., improvement by
more than the group mean) to altitude, in part because
Fig. 4. Comparison of athletes of various performance levels and the
change in performance from a 4-wk living high-training low altitude
sojourn. Race time represents the initial time trial presented as a
percent of the American record (AR) in the event at the time. The
change in performance is the percent change from the precamp time
trial to the postcamp time trial.
J Appl Physiol • VOL 91 • SEPTEMBER 2001 • www.jap.org (http://www.jap.org)
of a prominent and sustained increase in erythropoietin
at altitude leading to an increase in red cell mass
(6). Although the genetic mechanisms responsible for
determining the erythropoietic response to hypoxia in
humans have not been entirely worked out, animal
models suggest that this response may be transcriptionally
regulated (26). Moreover, at least some individuals
have genetic polymorphisms in the erythropoietin
gene (33) or the erythropoietin receptor (27) that
may profoundly influence the erythropoietic response
to hypoxia (22). It is possible, therefore, particularly in
studies with relatively small sample sizes, that the
presence of significant numbers of nonresponders could
bias the study outcome in favor of no detectable response.
Practical Implications for Performance
of Elite Athletes
In previous work examining collegiate athletes (6,
24), we identified a 1.4% improvement in 5,000-m performance,
a 2.5 6 2.4 mlzkg21 zmin21 improvement in

O2 max, and a 1.1 6 0.7 g/dl increase in hemoglobin
concentration after 4 wk at 2,500 m. In this study, we
obtained a 1.1% improvement in 3,000 m performance,
a 2.3 6 2.6 mlzkg21 zmin21 improvement in V˙ O2 max,
and a 1.0 6 1.1 g/dl in hemoglobin concentration in elite
runners. When all the athletes who have completed a
HiLo or HiHiLo camp in our studies are examined
together, there is no influence of performance ability on
the response to such altitude training (Fig. 4).
Figure 4 also demonstrates that, although substantial
individual variability remains within all athletes,
the variation is smaller for the elite subjects. Thus the
coefficient of variation for the collegiate athletes was
3.3%, whereas that for the elite athletes was just over
half as great, or 1.9%. Because of this reduced variability,
the percent improvement, expressed as a fraction
of the variation within the elite population, is 0.58, well
within the criteria of 0.5–0.7 recently recommended for
the identification of a “worthwhile” enhancement of
performance for elite athletes (16). Although a 1.1%
improvement in performance may not seem like a large
effect, at an elite level in sports, races are won or lost
by small fractions of a percent. Thus the benefit of a
HiLo or HiHiLo altitude training camp has the potential
to substantially improve race outcome for individual
elite athletes.
In conclusion, despite having prepared for and competed
in national championship events, elite runners
improved sea level running performance by 1.1% (95%
confidence limits 0.3–1.9%) after 27 days of living at
moderate altitude (2,500 m) and performing high-intensity
training at low altitude (1,250 m). Data collected
indicate that the magnitude and mechanism of
the effect are similar to those obtained in collegiate
runners undergoing the same experimental paradigm.
The mechanism involves expansion of the red cell mass
and an increase in circulating hemoglobin levels, accompanied
by maintenance of oxygen flux to working
muscle. Thus the HiLo training approach is effective in
improving sea level running performance ranging from
50 to 90% of the world record in events lasting from ;7
to 20 min. We believe that this paradigm can be used to
enhance sea level performances that are dependent on
high levels of oxygen transport.
This project involved the coordinated support and effort of many
people and several organizations. We thank the athletes who participated
in the project. We also thank all the people who helped to
bring about this experiment, including the speakers, the Department
of Health Science, Indiana University, the track coaching staff at
Indiana University, and the staff and volunteers of USA Track and
Field and the US Olympic Committee. Particular thanks go to Drs.
Harmon Brown, David Martin, Jay T. Kearney, and Martha Ludwig
for tireless support and perseverance. A special note of gratitude and
appreciation goes to Greg Harger for all of his work on this project.