Scand J Med Sci Sports 2008: 18 (Suppl.
1): 57–69
Printed in Singapore . All rights reserved
DOI: 10.1111/j.1600-0838.2008.00833.x
Effects of various training modalities on blood volume
W. Schmidt, N. Prommer
Department of Sports Medicine/Sports Physiology, University of Bayreuth, Bayreuth, Germany
Corresponding author: W. Schmidt, Department of Sports Medicine/Sports Physiology, University of Bayreuth, 95440
Bayreuth, Germany. Tel: 149 921 55 3464, Fax: 149 921 55 3468, E-mail: walter.schmidt@uni-bayreuth.de
Accepted for publication 30 April 2008
It is controversially discussed whether soccer games should
be played at moderate (2001–3000 m) and high altitudes
(3001–5500 m) or should be restricted to near sea level and
low altitude (501–2000 m) conditions. Athletes living at
altitude are assumed to have a performance advantage
compared with lowlanders. One advantage of altitude
adaptation concerns the expansion of total hemoglobin
mass (tHb-mass), which is strongly related to endurance
performance at sea level. Cross-sectional studies show that
elite athletes posses  35% higher tHb-mass than the
normal population, which is further elevated by 14% in
athletes native to altitude of 2600 m. Although the impact of
Hypotheses
Altitude residents are characterized by higher oxygen
transport capacity of the blood than non-adapted
subjects from lowlands. This improved oxygen capa-
city is due to the adaptation of the erythropoietic
system which compensates reduced oxygen availabil-
ity by increasing total hemoglobin mass (tHb-mass).
It, therefore, is assumed that this adaptation process is
one main cause for the higher endurance performance
of altitude natives in hypoxia. In athletic competitions
(e.g., soccer games) conducted at altitude it is assumed
that this fact may put lowlanders which do not have
sufficient time to adapt their erythropoietic system at
a disadvantage. However, the differences in endurance
performance at altitude due the advantage of im-
proved oxygen capacity have not yet been quantified.
This fact is of special importance regarding the
current discussion whether soccer games should be
played at moderate (2001–3000 m) and high altitude
(3001–5500 m). To answer this question the present
review addresses the following hypotheses:
1. Maximal endurance performance directly de-
pends on the oxygen transport capacity and
therefore on tHb-mass
2. Athletes living at altitude posses more tHb-mass
and do therefore perform better at altitude than
non-adapted sea-level subjects
Copyright & 2008 The Authors
Journal compilation & 2008 Blackwell Munksgaard
this huge tHb-mass expansion on performance is not yet
investigated for altitude conditions, lowland athletes seek for
possibilities to increase tHb-mass to similar levels. At sea
level tHb-mass is only moderately influenced by training and
depends more on genetic predisposition. Altitude training in
contrast, using either the conventional altitude training or the
live high–train low (414 h/day in hypoxia) protocol for 3–4
weeks above 2500 m leads to mean increases in tHb-mass of
6.5%. This increase is, however, not sufficient to close the gap
in tHb-mass to elite athletes native to altitude, which may be
in advantage when tHb-mass has the same strong influence on
aerobic performance at altitude as it has on sea level.
3. Training at sea level of professional athletes does
not increase tHb-mass to the same level as it
occurs in athletes native to altitude.
4. Altitude training of athletes from lowlands may
close the gap in tHb-mass between sea level and
altitude athletes and may therefore lead to equal
chances regarding aerobic performance.
In addition, this review addresses (i) the hypoxic
threshold to elevate tHb-mass in a sea-level athlete
and (ii) the magnitude of tHb-mass expansion which
can be expected by different hypoxic measures.
Overview
Influence of tHb-mass on endurance performance
Maximal endurance performance expressed as VO2max
depends on muscular oxygen consumption and oxy-
gen transport of the blood. In elite endurance athletes
muscular oxidative capacity is well adapted whereas
oxygen transport is the main limiting factor (Wagner,
2000). The impact of blood on VO2max is demon-
strated in studies describing the effect of phlebotomy,
of blood re-transfusion, and of erythropoietin (EPO)
application. One day after drawing 550 mL of blood
VO2max decreased by 255 mL/min in moderately
trained subjects (Prommer et al., 2007b). After phle-
botomy and subsequent re-transfusion of 1800 mL
57
Schmidt and Prommer
blood VO2max differed by 740 mL/min (Celsing et al.,
1987), and in case of a 4-week lasting EPO applica-
tion, a raise in VO2max by 307 mL/min is reported
(Parisotto et al., 2000). Best correlations between
changes in VO2max and blood constituents were
found for tHb-mass and red cell mass (RCM). The
change of 1 g of hemoglobin, either by reduction or
by expansion, is associated with a change in VO2max
by  3 mL/min (Parisotto et al., 2000; Prommer
et al., 2007b). This review, therefore, focuses on
tHb-mass/RCM rather than on blood or plasma
volume although both are the main performance
limiting factors for elite athletes under physiological
conditions.
Measurement of tHb-mass
Until 1990 only few data on tHb-mass and RCM for
training and altitude conditions were available be-
cause the prevailing direct determination methods at
that time were based on radioactive markers and
were, therefore, associated with considerable side
effects. The CO re-breathing method first described
by Grehant and Quinquard (1882) and modified by
Thomsen et al. (1991), Burge and Skinner (1995) and
Schmidt and Prommer (2005) provided the possibi-
lity of collecting substantial amounts of data. It was,
however, at first criticized by, e.g., Sawka et al.
(2000) as to overestimate tHb-mass by about 20%
due to the assumption that CO diffuses to myoglobin
and muscular cytocromes. This argument was re-
cently rebutted by Prommer and Schmidt (2007)
demonstrating that this effect is negligible because
the duration of the test (7 min) is too short for large
diffusion rates. Complete mixing of CO in the blood
including also those red cells being located in the
spleen (Prommer et al., 2007a) is guaranteed 7 min
after inhalation of the CO bolus. In an extensive
meta-analysis Gore et al. (2005) demonstrated the
CO-re-breathing method as the superior technique
[coefficient of variance (CV) 2.2%] compared with
the hitherto gold standard using radioactive markers
(51chromium labeled red cells, CV 2.8%) and to
Evans Blue dilution (CV 6.7%). The actual opti-
mized CO-re-breathing technique with a typical error
between 1.1% (Gore et al., 2006) and 1.7% (Schmidt
& Prommer, 2005) allows the identification of even
small changes in tHb-mass (95% confidence limit:
between  2.2% and  3.3%, respectively) occur-
ring with endurance training and adaptation to
hypoxia.
tHb-mass at altitude
It is a well-known fact since decades that altitude
hypoxia stimulates erythropoiesis and increases tHb-
mass and blood volume (BV). Weil et al. (1968)
58
described a threshold at an arterial PO2 of
70 mmHg (1600 m) corresponding to an oxygen sa-
turation of 95%, below which RCM continuously
increases with declining SaO2. Residents from
2600 m (Bogota, Colombia; Böning et al., 2001)
and 3550 m (Putre, Chile; Heinicke et al., 2003) are
therefore characterized by 11% and 14% higher tHb-
mass values, respectively. In subjects from 4390 m
even 83% elevated values were found (Sánchez et al.,
1970). It has, however, to be noted that all of these
data were collected from South and North American
inhabitants. Whether this polycythemia is also pre-
valent in residents from the Himalayas is question-
able because they possess much lower [Hb] (Beall,
2000) than the Andean population residing at similar
altitudes, indicating either higher plasma volume or
lower hemoglobin mass.
In this context, data are not only rare for chronic
hypoxia but also for transient stays at altitude. No
changes in tHb-mass are reported for up to 3-week
periods below 4000 m (Sawka et al., 2000) while
modest increases were described after 6 months
long-term intermittent hypoxia at 3550 m (11%;
Heinicke et al., 2003; Prommer et al., 2007c), and
after a 6-week Himalaya expedition at a mean
altitude of 5000 m (14%; Böning et al., 1997). Strong
changes by more than 40% were shown by Pugh
(1964) after 126 days above 5500 m and by Reyna-
farje et al. (1959) after 1 year at 4550 m. Available
data, therefore, clearly demonstrate that hypoxia
improves oxygen transport capacity in case time of
exposure and altitude pass a certain threshold.
tHb-mass and performance – cross-sectional studies in
normoxia
Beside altitude exposure the state of endurance
performance is the main factor associated with
tHb-mass and RCM. Kjellberg et al. (1949) were
the first investigators describing the relationship
between BV, tHb-mass, and aerobic performance.
They reported a training-dependent level of BV and
tHb-mass of 75.0 mL/kg and of 11.5 g/kg for un-
trained male subjects, 90.1 mL/kg (120%) and
13.6 g/kg (118%) for moderately trained athletes,
as well as 103.4 mL/kg (138%) and 15.7 g/kg
(137%) for elite athletes, respectively. A similar
picture on a 10% lower absolute level was demon-
strated for females. In a second pioneer study,
Åstrand (1952) confirmed this close relationship
between tHb-mass and VO2max (r 5 0.97) for a broad
range of tHb-mass (between 100 and 900 g) for all
age groups between 7 and 30 years. The differences in
BV between trained and untrained subjects were
confirmed later by Dill et al. (1974) and Brotherhood
et al. (1975), while other investigators (e.g., Green
et al., 1999) showed only marginal differences in both,

tHb-mass and BV. In 2001 Heinicke et al. differen-
tiated BV and tHb-mass in male elite athletes of
different disciplines and reported about 40% higher
values in endurance athletes (running, cycling, triath-
lon, and cross country skiing) than in untrained
subjects, but only moderately elevated values in
athletes practicing anaerobic disciplines (112%,
down hill skiers) and in swimmers (120%). In the
latter group, the supine position during training
and the immersion effects may counteract the BV
and tHb-mass expansion. Data from football players
are not yet available. From the results of Gore
et al. (1997)) and Heinicke et al. (2001), however,
we may assume a BV of about 100 mL/kg and tHb-
mass of 14.0 g/kg in elite football players (VO2max
65 mL/kg).
The strong positive relationship between VO2max,
BV, and tHb-mass for absolute and relative values
was proved in several cross-sectional studies with
small numbers of subjects (Åstrand, 1952; Conver-
tino, 1991; Gore et al., 1997; Schmidt et al., 1999;
Heinicke et al., 2001).
To obtain a generally accepted base for the depen-
dency of VO2max on tHb-mass and BV, we performed
the following meta-analysis: In total 611 subjects, 393
males and 218 females, living at sea level (n 5 490),
2600 m (n 5 82), or 3500 m (n 5 39) were included.
The studies were carried out by two laboratories
[Berlin (n 5 212) and Bayreuth (n 5 399)] and most of
the data are published in peer-reviewed journals
(Schmidt, 1999, 2002; Heinicke et al., 2001; Böning
et al., 2001; Schmidt et al., 2002; Prommer et al.,
2007c).
All subjects performed a vita maxima test on a
treadmill or on a cycle ergometer with a similar
protocol (for detailed description see original pub-
lications). In order to obtain comparable VO2max for
the cycle ergometer and the treadmill, values
achieved with the latter test were reduced by 7%
(e.g. Dill et al., 1974). VO2max which was examined at
altitude was calculated to sea-level conditions
according to Fulco et al. (1998). In all subjects tHb-
mass and BV were determined by the CO re-breathing
technique as described by Heinicke et al. (2001,
n 5 507) or by Schmidt and Prommer (2005,
n 5 104). Both methods yielded identical results
(Schmidt & Prommer, 2005). Furthermore, hemoglo-
bin concentration and hematocrit (n 5 593) as well as
serum concentrations of EPO (n 5 496) and transfer-
rin receptor (n 5 370) were included into the meta-
analysis. All of the data, except for EPO, were
normally distributed and showed no systematic dif-
ference between the two laboratories. No dependen-
cies on age were observed. The athletes were
classified into four performance categories according
to their relative sea-level VO2max values (for classifi-
cation see Table 1).
Total hemoglobin mass and altitude training
The results of this meta-analysis are in accordance
with the tHb-mass and BV data of Kjellberg et al.
(1949) showing the lowest values for non-exercising
subjects (NP) and about 30% higher values for elite
athletes (EP, Fig. 1, Table 1). It has to be noted that
the NP-group was not completely sedentary. In all of
the athletic performance groups, plasma volume was
likewise expanded as red cell volume leading to
similar hemoglobin concentrations in all subgroups
of the same altitude.
Despite a broad scattering of VO2max (e.g., with a
prevailing tHb-mass of 12.0 g/kg VO2max values
between  40 and  60 mL/kg/min can be at-
tained), there is a close relationship between these
two parameters (r 5 0.79, Fig. 2). The slope of the
regression line (at 0 m: 4.4), which is similar for males
(4.2) and females (4.6) indicates that a change in tHb-
mass by 1 g/kg is associated with a change in VO2max
by 4.4 mL/kg/min. A similar close dependency is
obtained between BV and VO2max (r 5 0.762) where
a change in 1 mL blood/kg is related to a change in
VO2max by 0.7 mL/kg/min.
These data are well in accordance with the results
of previous studies involving smaller sample size.
Gore et al. (1997) described a slope of 4.4 for relative
tHb-mass and Convertino (1991) 0.66 for relative BV
and VO2max.
While the effects of tHb-mass and BV on perfor-
mance can be precisely quantified by all these cross-
sectional studies, we did not find any significant
dependency of VO2max on hemoglobin concentration
(males r 5 0.03, females r 5 0.12) or hematocrit
(males r 5 0.08, females r 5 0.11). We, therefore,
conclude that under physiological, non-anemic con-
ditions at sea level the oxygen transport to the muscle
tissue is regulated by changes in BV with normal
hemoglobin concentration rather than by changes in
hemoglobin concentration, itself.
tHb-mass and performance – cross-sectional studies in
hypoxia
There is no doubt that altitude residents posses
higher tHb-mass than comparable inhabitants from
lowlands (see ‘‘tHb-mass at altitude’’). If tHb mass is
the major determinant of performance, one could
assume that endurance performance is also increased
which would give this population an advantage in
competitions at altitude (e.g., soccer games).
Whether the strong relationship between the oxygen
transport system and VO2max is also true for natives
to altitude, however, still has to be evaluated.
To address this question, we also included subjects
from altitude (2600 m, n 5 82; 3500 m, n 5 39) into
the meta-analysis and classified them according to
the criteria for lowlanders (see Table 1). Their
VO2max determined at altitude was, therefore, cor-
59
Schmidt and Prommer
Table 1. VO2max, blood volumes, and hematological indices of subjects from lowlands and altitude classified according to their aerobic performance

NP MP HP EP

VO2max (mL/kg/min)
< 0m 41.9  3.9 53.4  2.7 61.9  2.3 72.2  5.9
, 0m 33.1  4.7 43.4  2.9 52.4  2.1 62.7  4.0
BV (mL/kg)
< 0m 82.1  7.3 89.9  7.8 97.7  8.6 105.4  10.0
2600 m 82.0  9.6 91.5  7.4 99.5  6.7 115.7  10.8**
, 0m 75.6  7.6 84.0  7.0 91.5  8.5 99.8  7.5
2600 m 72.0  9.0 88.0  9.4 92.1  7.2 105.9  4.1
PV (mL/kg)
< 0m 49.0  5.4 54.2  5.6 59.0  6.2 63.1  7.1
2600 m 45.7  6.1* 51.0  6.0* 55.3  4.6 65.2  7.3
, 0m 48.9  5.4 55.2  5.6 59.0  6.4 64.3  6.0
2600 m 43.5  6.1*** 54.2  6.3 56.1  4.7 65.6  4.8
EV (mL/kg)
< 0m 33.3  2.7 36.7  3.6 40.9  3.8 43.3  4.0
2600 m 36.2  4.2** 40.5  3.6*** 44.2  3.1* 50.5  4.3***
, 0m 27.2  3.4 30.2  3.0 33.3  3.2 36.2  3.3
2600 m - - - 40.8
Hb (g dL)
< 0m 15.0  0.9 14.8  1.0 14.9  0.9 15.0  1.0
2600 m 16.6  0.9*** 16.4  1.1*** 16.3  0.9*** 15.9  0.7***
, 0m 13.2  0.8 12.8  1.1 13.1  0.8 13.4  0.8
2600 m 14.4  1.0*** 13.8  0.7*** 13.9  0.6* 13.8  0.8
<
n 5 314 0m 34 104 103 73
n 5 79 2600 m 36 17 7 19
,
n 5 176 0m 30 72 38 36
n 5 42 2600 m 22 11 7 2

The subjects were divided into four groups according to their VO2max at sea level. Males: normal performance (NP, n 5 70)o48 mL/kg/min, moderate
performance (MP, n 5 121) 48–57 mL/kg/min, high performance (HP, n 5 110) 58–67 mL/kg/min, and elite performance (EP, n 5 92)467 mL/kg/min.
Females: NP (n 5 52)o37 mL/kg/min, MP (n 5 83) 38–47 mL/kg/min, HP (n 5 45) 48–57 mL/kg/min, and EP (n 5 38)457 mL/kg/min.
0 m indicates near sea level condition, 2600 m combines data from natives to 2600 m and 3550 m as well as long-term intermittently adapted subjects to
3550 m (adaptation period between 6 months and 22 years). Differences between altitudes:
*Po0.05,
**Po0.01,
***Po0.001.
Except for haemoglobin concentration all differences between MP, HP, and EP to NP are highly significant.

rected to sea-level conditions (see Fulco et al., 1998).
Because the relationship between tHb-mass and
VO2max was not different in both altitude groups
(Fig. 2) they were combined to one group (2600 m) in
order to increase statistical power.
In all male performance groups tHb-mass was
between 9% and 14% higher in the altitude than in
the sea-level groups (Fig. 1). A similar picture with
slightly lower differences was found for the female
groups. This higher RCM was compensated by
reduced plasma volume leading in turn to a similar
BV as in lowlanders (Table 1). Only in the elite
athletes from altitude tHb-mass and BV were dis-
proportionately high which explains their very high
VO2max values. Also hemoglobin concentration of
the altitude subgroups was considerably increased
due to lower plasma volume and elevated tHb-mass.
The regression line demonstrating the relationship
between tHb-mass and VO2max is displaced to the
right for the altitude residents indicating the need of
higher tHb-mass for a similar aerobic performance as
achieved by lowlanders. From these data, we con-
clude that increased tHb-mass in altitude residents
does not result in higher VO2max values at sea level.
This is supported by Prommer et al. (2007c) describ-
ing even lower VO2max at sea level for well-adapted
subjects to 3550 m with markedly increased tHb-
mass compared with lowlanders.
Hence, the question is whether altitude residents
and hypoxia-adapted subjects can at least benefit
from their hematological adaptation in hypoxia.
Again Prommer et al. (2007c) found no differences
in VO2max obtained at 3550 m in altitude-adapted
soldiers and newcomers being the first day at that
altitude despite a difference in tHb-mass of 11%.
Furthermore, data of Heinicke et al. (2003) indicate
lower VO2max in residents living permanently at
altitude compared with newcomers.

60

Fig. 1. Total hemoglobin mass in male and female subjects
from lowland and altitude with different state of perfor-
mance. The group ‘‘2600 m’’ combines subjects from 2600 to
3550 m. Definitions of performance states see Table 1.
Fig. 2. Total hemoglobin mass (tHb-mass) vs VO2max. Pre-
sented are relative values of 611 subjects native to lowland
and to 2600 m, as well as natives and adapted subjects to
3550 m.
To evaluate the effect of tHb-mass on performance
at altitude directly Young et al. (1996) infused
700 mL autologous erythrocytes in saline (  97 g
hemoglobin) before ascending to 4300 m. VO2max
measured the day before re-infusion, and on day 1,
and day 9 at altitude did not differ from the values of
a control group. At altitude it dropped by 26% and
remained on the same low level in both groups. These
results were confirmed by Pandolf et al. (1998)
showing no significant differences in 3.2 km race
time at 4300 m when 700 mL autologous erythrocytes
were re-transfused.
All these studies clearly state that increased tHb-
mass does not necessarily lead to higher aerobic
performance at altitude. It has, however, to be noted
that all studies were conducted with relatively un-
Total hemoglobin mass and altitude training
trained subjects and that the results may not mirror
the behavior of elite athletes. According to Wagner
(2000), the oxygen transport system gains impor-
tance with increasing training state whereas in un-
trained subjects the metabolic capacity of the muscle
is the performance-limiting factor. We, therefore,
cannot exclude that like at sea level the erythrocytic
system is the determining factor for endurance per-
formance in elite athletes. To answer this question
more data are necessary.
Strategies to increase tHb-mass
Effect of training in normoxia on tHb-mass
High tHb-mass and BV in elite endurance athletes
are frequently assumed to be due to an erythropoietic
adaptation to the training process. Sawka et al.
(2000) postulated no effect on RCM in case the
training period is o11 days, but showed a marked
increase by about 8% when 21 days are exceeded.
Original data from the literature are, however, in-
consistent. In most training studies lasting 4–12
weeks on untrained or trained subjects no effect on
tHb-mass or RCM was found using direct methods
for determination like radioactive labeling (Ray et
al., 1990; Green et al., 1991; Shoemaker et al., 1996)
or CO re-breathing (Gore et al., 1997). Only Remes
(1979) described a small increase by 4.1% in RCM in
a group of 30 soldiers after 6 months of military
training. Two other studies, however, using the
indirect determination by Evans Blue dilution and
subsequent calculation of RCM reported an increase
by  8% after 3 weeks (Schmidt et al., 1988) and by
 12% after 12 weeks of endurance training (War-
burton et al., 2004). Because it cannot be excluded
that the cell factor (ratio body Hct/venous Hct) used
in these studies for calculation of tHb-mass changes
during the training period as it occurs e.g., at altitude
(Sánchez et al., 1970) the positive erythropoietic
response to training has to be confirmed by direct
measurements.
We, therefore, documented the effect of a 9 months
lasting (December–September) endurance training
for a marathon competition on tHb-mass and VO2max
in 16 leisure sportsmen (six without marathon ex-
perience). As demonstrated in Table 2, tHb-mass
significantly increased by 6.4% (60 g) and BV by
10.3% (690 mL) the latter being mostly due to the
well-known plasma volume expansion (111.6%,
470 mL). As a consequence [Hb] significantly de-
creased by 0.5 g/dL. VO2max continuously increased
during the training period by 5.9% (250  213 mL/
min) and was closely related to the increase in tHb-
mass. The slope of the regression line is equal to that
after phlebotomy and blood re-transfusion confirm-
ing again that the change in tHb-mass by 1 g is
61
Schmidt and Prommer
correlated with a change in VO2max by  3 mL/min subsequently for their high endurance performance.
(Fig. 3). Whenever the impact of special genetic alterations, as
It has to be noted that this moderate increase in e.g., ACE gene polymorphism (e.g. Joyner, 2001) is
tHb-mass by 6.4% was observed in relatively un- still unclear, our opinion is supported by Martino et
trained subjects. In highly trained athletes, Prommer al. (2002) describing high BV (92.3 mL/kg) and high
et al. (2005) showed in contrast no systematic tHb-mass (13.8 g/min) in subjects with high VO2max
changes in five repetitive measurements over a whole (65.0 mL/kg/min) without any training history. Also
training year. The mean individual oscillation (dif- our results from a longitudinal study determining
ference between the lowest and highest value) during tHb-mass twice with an interval of 9 years (1998–
the year was 4.6%, which is just slightly above the 2007, n 5 11) showed unchanged values (tHb-mass in
noise of the applied CO-re-breathing method. From 1998: 1028  184 g, in 2007: 1023  196.3 g,
all available data, we may therefore conclude that TEM 5 4.0%) despite most of the previously compe-
training has only small effects on tHb-mass and that titive athletes had quit their carrier or markedly
genetic predisposition should be considered to be reduced their training volume (unpublished results).
responsible for high tHb-mass in elite athletes and
Effect of training in hypoxia on tHb-mass (Table 3)
The effect of conventional altitude training (Live
Table 2. VO2max, blood volumes, and hematological indices during a High–Train High, LH–TH) on tHb-mass or RCM
9-month lasting endurance training of 16 male leisure sportsmen is still discussed controversially. Some authors are of
December/ March/April August/
the opinion that the erythropoietic capacity of elite
January September endurance athletes has already reached an upper
limit which cannot be exceeded by using physiologi-
Body mass (kg) 80.0  9.5 80.2  9.2 79.1  9.3 cal measures (see Gore et al., 1998). On the other
[Hb] (g dL) 15.2  0.8 15.1  0.7 14.7  0.5**
Hematocrit (%) 43.9  1.7 44.1  1.9 43.1  1.5
hand the very high tHb-mass values of elite athletes
tHb-mass (g) 932  112 967  110* 992  103*** native to altitude (114%, Fig. 1) let us assume that
Red cell mass (mL) 2683  299 2823  313** 2906  273*** the erythropoietic capacity has not reached its max-
Blood volume (mL) 6720  705 7027  684* 7410  627*** imum in lowlanders. Altitude training or hypoxic
Plasma volume (mL) 4037  439 4204  413 4504  392***
VO2max (mL/min) 4250  381 4426  480** 4500  444***
training may, therefore, serve as an additional sti-
mulus to increase tHb-mass. The literature, however,
The initial anthropometric and performance data are: age provides inconsistent results. No effects were found
41.2  5.9 years, body mass 80.0  9.5 kg, height 177.3  5.9 cm, after training camps performed below 2000 m
VO2max 53.5  4.5 mL/kg/min. Mean training volume from December to (1760 m, Friedmann et al., 1999; 1900 m, Svedenhag
April: 320  98 min/week, from April to September 410  119 min/week. et al., 1997) and also at 2690 m when athletes fell ill
Difference from baseline:
(Gore et al., 1998). An alternative explanation is that
*Po0.05,
the accuracy of the method used in these studies was
**P40.01,
***Po0.001.
not high enough to detect small changes. The ma-
jority of studies, however, found an increase in tHb-
mass. Substantial increases after a 3- or 4-week
lasting training camp at altitudes between 2100 and
2500 m are shown by Rusko et al. (200416%),
Friedmann et al. (200516.3%), Heinicke et al.
(200519.3%), and Levine and Stray-Gunderson
(1997110.5%).
During the last years the concept ‘‘LH–TL’’ in-
troduced by Drs. Levine and Stray-Gunderson
(1992) and by Finnish scientists of Dr. Rusko’s group
(Laitinen et al., 1995), became more and more
popular. Most investigators affirm that this form of
training achieves positive effects on aerobic perfor-
mance even though the mechanisms involved are not
clear yet. Some attribute increased performance after
a LH–TL protocol mainly to augmented RCM
(Levine & Stray-Gundersen, 2005), while the others
Fig. 3. Relationship between changes in tHb-mass and consider increased efficiency and buffer capacity
VO2max after a 9-month lasting marathon training. THb- most relevant mechanisms because they did not
mass, Total hemoglobin mass. find substantial increases in tHb-mass (Gore &

62
 Table 3. Changes in tHb-mass or red cell mass after conventional altitude training and after Live High–Train Low (LH–TL) protocols

Author Year of Athletic Number of Sex Mode of Days/nights Altitude/artificial Daily exposure Total hours Change in Signi- Control
publication discipline athletes hypoxia in hypoxia altitude in meters to hypoxia in hypoxia tHb-mass/ ficance group
(h/day) RCM (%)

Conventional altitude training

No significant effect
Dill et al. 1974 Runners 12 m Natural 20 2300 24 480 0.5 1
Telford et al. 1996 Runners 9 m Natural 28 1760 24 672 0 1
Svedenhag et al. 1997 Cross country skiers 7 m1f Natural 30 1900 24 720 3.1
Friedmann et al. 1999 Boxers 16 m Natural 18 1800 24 432 5 1
Gore et al. 1998 Cyclists 8 m Natural 31 2690 24 744 1
Mean 25.4 2090 24 610 0.2
 SD 6.0 398 0.0 144 3.4

Significant effect
Levine and 1997 College runners 13 m1f Natural 28 2500–2700 24 672 10.5 1 1
Sray-Gunderson
Rusko 1996 Runners 14 m1f Natural 28 2200 24 672 6 1
Friedmann et al. 2005 Junior swimmers 16 m1f Natural 21 2100–2300 24 504 6.3 1
Heinicke et al. 2005 Biathletes 10 m1f Natural 21 2050 24 504 9.3 1
Mean 24.5 2263 24 588 8.0
 SD 4.0 234 0.0 97 2.2

LH–TL
Daily exposure to hypoxia:414 h/day
Laitinen et al. 1995 Runners 7 m Artificial 20–28 2500 16–18 408 7.3 1 1
Levine and 1997 College runners 13 m1f Natural 28 2500–2700 17 476 5.3 1
Sray-Gundersen
Rusko et al. 1999 Cross country 12 m1f Artificial 25 2500 14 350 5 1 1
skiers, triathletes
Wehrlin et al. 2006 Runners, 10 m1f Artificial 24 2500 18 504 5.3 1 1
Robach et al. 2006 Swimmers 9 m1f Artificial 13 2500 16 208 7.5 1 1
3000
Wehrlin and Marti 2006 Runners 2 m Natural 26 2456 18 468 5.75 1
Brugniaux et al. 2006 Runners 5 m Artificial 18 3000 14 252 10.4 1 1
Schmidt et al. Unpublished Cyclists 6 m Natural 19 2100 19 361 5.4 1
Mean 23.7 2556 16.7 398 6.5
 SD 5.3 265 1.6 103 1.8

LH–TL
Daily exposure to hypoxia:o14 h/day
Ashenden et al. 1999a Triathletes 6 m Natural 23 3000 8–10 207 1.8 1
Ashenden et al. 1999b Cyclists 6 f Artificial 12 2650 8–10 108 2.7 1
Dehnert et al. 2002 Triathletes 11 m1f Natural 14 1956 13 156 2.4 1
Saunders et al. 2004 Runners 10 m Artificial 20 2000–3100 9–12 210 1.6 1
Robach et al. 2006 Cross country skiers 6 m1f Artificial 18 2500–3500 11 198 1.5 1
Niess et al. Unpublished Runners 8 m1f Artificial 20 3400 8 160 1.2 1
Neya et al. 2007 Runners 10 m Artificial 29 3000 10–12 319 1.4 1
Mean 19.1 2787 10.4 198 0.7
 SD 6.0 466 1.8 75 1.8
Total hemoglobin mass and altitude training

63
Schmidt and Prommer
Fig. 4. Percentage changes in mean tHb-mass or red cell
mass during LH–TL protocols in relation to the hours of
daily exposure to hypoxia. For more information see Table
3. The horizontal lines indicate the mean change in tHb-mass
for daily hypoxic exposures of less (left side) and of more
(right side) than 14 h/day. tHb-mass, total hemoglobin mass;
LH–TL, live high–train low.
Hopkins, 2005). At the first glance, the effect of LH–
TL on tHb-mass is confusing (Table 3) reaching from
no effect (e.g., Ashenden et al., 1999a, b) to increases
by 10.1% (Brugniaux et al., 2006). When, however,
the changes in tHb-mass are analyzed precisely
according to the daily time of hypoxic exposure a
clear statement is possible (Fig. 4): In case of 3–4
weeks lasting LH–TL protocols above 2100 m there
is no substantial effect on tHb-mass when daily
hypoxic exposure is o14 h (10.5 
1.9%). Once this threshold is exceeded similar ery-
thropoietic effects as described for continuous alti-
tude training are achieved (16.5  1.8%). These
results agree with recommendations of Rusko et al.
(2004) of spending more than 12 h/day above a
natural or simulated altitude of 2000 m for 3 weeks
and the findings of Wilber et al. (2007) that more
than 22 h/day at 2000–2500 m or 12–16 h/day at
higher altitude (2500–3000 m) serve as potent ery-
thropoietic stimuli.
To test the conclusions of Wilber, we performed an
analysis of variance including the variables ‘‘daily
time of hypoxic exposure (h/day),’’ ‘‘altitude/degree
of hypoxia’’ (in meters), ‘‘type of hypoxia’’ (altitude
or artificial hypoxia), and ‘‘total days of LH–TL
protocol’’ of all the studies having performed LH–
TL protocol of 12–29 days above 2100 m. We found
a strong effect on tHb-mass of daily time of hypoxic
exposure (Po0.001), a small effect of ‘‘total days of
LH–TL protocol’’ (Po0.05), and no significant ef-
fects of altitude or the type of exposure. Including all
these four variables into a multiple linear regression
analysis a strong relationship to tHb-mass was found
(r 5 0.864, Po0.001) allowing to anticipate the effect
of LH–TL on the erythropoietic response.
64
Concerning short-term hypoxic exposure, there is
no evidence that normoxic/hypoxic intervals (e.g.,
5 min/5 min; Julian et al., 2004) or longer regular
(training) sessions in hypoxia for 1–3 h have any
positive effect on tHb-mass (Rodriguez et al., 2007).
We conclude that training at altitude either con-
ventional or LH–TL can increase tHb-mass in the
mean as long as certain requirements, i.e. more than
14 h/day above 2100 m for at least 3 weeks are
complied. However, the effects of chronic hypoxia
on tHb-mass as demonstrated for athletes native to
altitude cannot be achieved by the usually performed
altitude/hypoxic training measures.
Mechanisms of regulation of tHb-mass
The regulation of tHb-mass is mainly under control
of the hormone EPO, which is produced in peritub-
ular cells of the kidney. Serum EPO concentration is
regulated by the HIF-1 system mediating the signal
of reduced renal PO2 (for detailed descriptions see
e.g. Caro, 2001). When analyzing the resting EPO
concentration of the cross-sectionals studies de-
scribed above only small influence of altitude and
training status occur. Serum transferrin receptor
concentration, in contrast, was positively influenced
by altitude and training status proving the induction
of an accelerated erythropoiesis.
During acute exercise one may assume reduced
systemic PO2 and therefore the induction of the HIF-
1a cascade. Data concerning the intra-renal PO2
during exercise are, however, not yet available. Ex-
ercise induced lower renal perfusion and reduced
oxygen transport to the kidney may be compensated
by decreased sodium re-absorption and therefore
lower oxygen consumption as well as by enhanced
oxygen delivery due to a right shifted oxygen dis-
sociation curve. It is, therefore, no surprise that
plasma EPO concentration does not increase during
and some hours after exercise (e.g. Schmidt et al.,
1991), while it increases some days after long-lasting
exercise (Schwandt et al., 1991) probably as a result
of hemodilution and lower hemoglobin concentra-
tion. For training at sea level, we therefore state no
direct influence on the erythropoietic system but an
indirect adaptation of tHb-mass by regulating hemo-
globin concentration up to individually normal va-
lues after plasma volume expansion. In contrast to
exercise at sea level renal pO2 decreases in hypoxia
resulting in an inversely proportional increase of
plasma EPO concentration (Ge et al., 2002).
When adapting to altitude EPO initially increases
for about 2 days depending primarily on the decline
in hemoglobin–oxygen saturation, which is asso-
ciated with the degree of altitude. After staying
some days at altitude, EPO again decreases reaching
a constant level slightly above the original base line.

It is not known, whether this decline reflects
enhanced EPO-binding to its receptor (Rusko et al.,
2004) or a decrease in EPO production due to
a functional feedback loop limiting the hypoxic
response by a HIF-regulated expression of
prolyl-4-hydroxylase (PHD2 and PHD3) (Stiehl
et al., 2006).
Interestingly, the EPO-system completely recovers
within 2 or 3 days after returning to sea level.
Subjects commuting weekly between altitudes show
oscillations in plasma-EPO for more than 20 years
(Heinicke et al., 2003). Daily changes of altitudes
may increase the sensitivity of the EPO system
and may therefore explain higher morning plasma
EPO concentration when applying the LH–TL
compared with the LH–TH protocol (Rusko et al.,
2004).
When exercise is performed under acute hypoxia,
EPO increases in a similar magnitude as under
resting hypoxic conditions. Exercise in chronic hy-
poxia (natives to 3500 m) even results in a significant
decrease in plasma EPO (Schmidt et al., 1993). We,
therefore, conclude that exercise under hypoxic con-
ditions has no direct effect on red cell production.
Originally, RCM was assumed to be exclusively
regulated by the erythropoietic activity of the bone
marrow and the red cell survival time to be relatively
constant (  100 days) in healthy subjects. This
dogma was disproved by Alfrey et al. (1997) and
Rice et al. (2001) showing a selective destruction of
young red cells (age lower than 12 days) in cases of
plethora induced by space flight or descend from
high altitude. Changing the altitude from 4380 m to
sea level resulted in a decrease of RCM by about
10% within 7 days in well-acclimatized subjects (Rice
et al., 2001). This reaction called neocytolysis is
triggered by a strongly reduced plasma EPO concen-
tration whereas daily administration of a small dose
of rhEPO completely prevents the hemolysis. Neo-
cytolysis probably occurs within the spleen, where
endothelial cells respond to the withdrawal of EPO
by influencing the interaction of phagocytes with
young red cells which are targeted by surface adhe-
sion molecules (Trial et al., 2001; Rice & Alfrey,
2005; Risso et al., 2007).
This mechanism can also be considered as cause of
the above-described missing response of tHb-mass to
LH–TL protocols with o14 h/day in hypoxia. In
these cases, the daily occurring increase of EPO
may induce a high production of reticulocytes,
which, however, do not survive due to the strong
oscillating EPO-levels (Schmidt, 2006).
Also the effects of conventional altitude training
may be modified by neocytolytic processes. That is
that under practical aspects a longer stay at altitude
may be more efficient, because more of the red cells
produced at altitude exceed the critical age of  10
Total hemoglobin mass and altitude training
days and will therefore not be subject to neocytolytic
processes after the athletes return to sea level.
The different individual responses to altitude
(Chapman et al., 1998) have been discussed on a
genetic and physiological background. In a first
study, Witkowski et al. (2002) showed a specific allele
of the EPO gene (D7S477 allele) discriminating
between subjects reacting with high or low erythro-
poietin response to 2800 m altitude. This result,
however, was not confirmed in follow-up studies.
One theory for the existence of responders and non-
responders is based on the individual hypoxic venti-
latory response influencing arterial Hb–O2-satura-
tion and subsequently renal EPO production. In
the study of Heinicke et al. (2005) an example for a
responder is provided. His increase in tHb-mass by
18.3% within 3 weeks at 2100 m (mean of the
group17.2%) was accompanied by lower Hb–O2-
saturation, right shifted oxygen dissociation curve,
and higher EPO concentration. Reasons for a miss-
ing response to altitude may be a high hypoxic
ventilatory response (HVR) as it is typical for
females rather than for males (Böning et al., 2004)
as well as the inhibition of erythropoiesis due to
inflammatory diseases or a lack of iron availability.
Conclusions
VO2max directly depends on tHb-mass under nor-
moxic conditions. Hence, a change in tHb-mass of
1 g results in a change of VO2max of  3 mL/min.
Elite endurance athletes show in the mean 35%
higher values than the normal population, whereas
athletes native to altitude posses even 14% more. The
altitude induced higher O2-transport capacity does
neither augment VO2max at sea level nor at altitude in
relatively untrained subjects. Whether it increases
endurance performance in elite athletes native to
altitude still remains questionable.
Training at sea level has only small direct impact
on the erythropoetic system. Genetic predisposition
seems to be a prerequisite for high tHb-mass and high
endurance performance. Conventional altitude train-
ing as well as the concept LH–TL similarly increases
tHb-mass as long as the following guidelines are
followed: altitude above 2100 m, duration about 3–4
weeks, daily time of hypoxic exposure not o14 h/day
(414 h/day – tHb-mass16.5%; o14 h/day – tHb-
mass10.7%). The mean level of tHb-mass in elite
athletes native to altitude (114%) can, however, not
be achieved by these altitude training measures.
Recommendations
1. Organizers of athletic competitions should be
aware that athletes of endurance disciplines
from lowlands may be discriminated due to
65
Schmidt and Prommer
insufficient time for hematological adaptation
and ventilatory acclimatization.
2. Regarding the general strong relationship be-
tween tHb-mass and VO2max athletes from low-
lands may improve their aerobic capacity at
altitude by increasing their tHb-mass. tHb-
mass in highly trained athletes can be augmented
by either conventional altitude training and/or
LH–TL at altitudes above 2100 m. Both mod-
alities of altitude training should be performed
for at least 3 weeks and in case of LH–TL
procedures the daily hypoxic exposure should
not be o14 h/day at natural altitude or corre-
sponding normobaric or hypobaric hypoxia.
3. Whether an athlete can increase his tHb-mass by
altitude or hypoxia and to which extent this may
occur is individually different. In case various
stays at altitude or various hypoxic measures are
scheduled the erythropoietic response has to be
evaluated to distinguish responders from non-
responders.
4. Athletes of endurance disciplines are advised to
make use of the hematological adaptation pro-
cess and arrive at least 1 week at moderate and 2
weeks at high altitude before the start.
5. Since 3 weeks after an altitude training tHb-
mass is reduced again by 50% the time lag
between descent from altitude training and
competition should be o20 days.
6. Filled iron stores (we recommend Ferritin levels
of 435 ng/mL) are necessary to obtain the
optimal effect of altitude or hypoxia exposure
on erythropoiesis.
Further investigation
1. Further investigations are needed to clarify the
role tHb-mass is playing for maximum perfor-
mance at altitude. It has to be investigated
whether the strong relationship between tHb-
mass and VO2max at sea level is also true for
hypoxic conditions.
2. tHb-mass and BV of football players native to
different altitudes should be compared placing
special emphasis on ethnic origin since the form
of adaptation to hypoxia may be different.
3. The effects of neocytolysis on RCM have to be
evaluated when well-adapted athletes descend
from altitude and when sea-level athletes live
high and train low.
Key words: VO2max, total hemoglobin mass, red cell
mass, altitude, live high–train low.
Acknowledgement
We thank Prof. Dr. Böning for providing us with tHb-mass
data.
Conflict of interest: The author has declared that they
have no conflict of interests.

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