Altitude Acclimatization, Training and Performance

Howard J Green
Department of Kinesiology, University of Waterloo, Waterloo, Ontario

Green, H.J. (2000). Altitude acclimatization, training and performance. Journal of Science and
Medicine in Sport 3 (3): 299-312.
Exposure to altitude results in a reduction in partial pressure of oxygen in the arterial
blood and a reduction in oxygen content. In an attempt to maintain aerobic metabolism
during increased effort, a series of acclimatization responses occur. Among the most
conspicuous of these responses is an increase in hemoglobin (Hb) concentration. The
increase in Hb has been construed as the fundamental adaptation enabling increases in
aerobic power and performance to occur on return to sea-level. However, the use of
altitude to boost training adaptations and improve elite sea-level performance, although
tantalizing, is largely unproven. The reasons appear to be many, ranging from the poor
experimental designs employed, to the numerous strategies designed to manipulate the
altitude experience and the large inter-individual differences in response patterns.
However, other factors may also be important. Acclimatization has also been shown to
induce alteration in selected properties of the muscle cell, some of which may be
counterproductive. The processes involved ill cation cycling, as an example, appear to be
down-regulated. Changes in these processes could impair certain types of performance.

Introduction
The p r a c t i c e of u s i n g a l t i t u d e a s a n a i d to i m p r o v i n g sea-level e n d u r a n c e
p e r f o r m a n c e in a t h l e t e s r e m a i n s e x t r e m e l y p o p u l a r . F o r some, it is r e g a r d e d b y
m a n y a s i n d i s p e n s a b l e to s u c c e s s a t t h e elite level (Levine & S t r a y - G u n d e r s o n ,
1992; R u s k o , 1996). The r a t i o n a l e for t h i s p r a c t i c e is b a s e d on t h e belief t h a t t h e
u s e of a l t i t u d e p r o m o t e s selected a c c l i m a t i z a t i o n effects w h i c h c a n n o t b e realized
d u r i n g sea-level a n d w h i c h a r e integral to t h e r e q u i r e m e n t s of t h e event.
Identifying. t h e a c c l i m a t i z a t i o n effects h a s p r o v e d elusive. Indeed, s u s p i c i o n
c o n t i n u e s to exist a s to w h e t h e r a l t i t u d e a c c l i m a t i z a t i o n h a s a n y r e d e e m i n g
p o s i t i v e b e n e f i t s to s e a - l e v e l p e r f o r m a n c e (Bailey & Davies, 1998). T h e
f u n d a m e n t a l r e a s o n u n d e r l y i n g this d i l e m m a a p p e a r s simple. No clear c u t a n d
c o n s i s t e n t a d v a n t a g e to p e r f o r m a n c e h a s b e e n d e m o n s t r a t e d d u r i n g sea-level
c o m p e t i t i o n s following a l t i t u d e m a n i p u l a t i o n . Moreover, science h a s p r o v e d
woefully i n a d e q u a t e in g e n e r a t i n g e x p e r i m e n t a l p a r a d i g m s t h a t allow b o t h for t h e
d e m o n s t r a t i o n of t h e a l t i t u d e effect a n d i n s i g h t into t h e u n d e r l y i n g m e c h a n i s m s .
R e c e n t a d v a n c e s in a l t i t u d e physiology a p p e a r to offer i m p o r t a n t c l u e s t h a t c o u l d
b e u s e f u l in resolving t h e controversy. T h e s e a d v a n c e s a r e t h e s u b j e c t of t h e
p r e s e n t paper.

Science and Acclimatization

In spite of a l m o s t 50 y e a r s of r e s e a r c h , d i r e c t e d a t defining t h e role of a l t i t u d e
a c c l i m a t i z a t i o n o n sea-level p e r f o r m a n c e , t h e i s s u e r e m a i n s controversial. T h e r e
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are a n u m b e r of reasons for this. The most conspicuous is the lack of

reproducibility, defined as a general inability to generate the same results with
repeated experiments. This problem is compounded by the n u m e r o u s variables
that can be manipulated in the "altitude experience", all potentially capable of
modifying the conclusions. Another fundamental problem with many studies is
the failure to include an appropriate control group, which, with exception of the
hypoxic stimulus, should be similar in every respect to the experimental group.
Without a control group, it is impossible to conclude, particularly where a positive
outcome has been observed, that the effect is due specifically to altitude
acclimatization. Moreover, when it is realized that the primary objective of the
altitude training is to promote adaptations in excess of what can be realized by
sea-level training alone, this is a particularly important design flaw. Subject
n u m b e r represents another major limitation. At the elite level, it is clear that the
greatest adaptative effect that can be expected from altitude represents only a few
percent. Moreover, the response appears to be highly variable among athletes
(Rusko, 1996; Bailey & Davies, 1997). With a small subject n u m b e r (typically
under 10), the probability of Finding a significant effect when one exists is very low.
By using conventional probability levels (i.e. p<0.05), under such circumstances,
it is possible that valuable information has been misinterpreted.
Another compounding problem is the large n u m b e r of potential strategies that
can be used to exploit the altitude effect. Conventionally, the altitude experience
has been practised by residing and training at moderate heights (high-high) for
periods of 3 to 4 weeks. Additional strategies that are becoming increasingly

Categories
Low-Low Low-High High-High High-Low
live low live low live high live high
train low train high train high train low

Table 1: Potential altitude manipulation strategies used to alter sea.level performance compared to sea.level.

inviting include living at moderate altitudes and training at sea-level (high-low)

and living at sea-level and training at altitude (low-high). The high - low approach
may be accomplished by actually living at altitude and descending to lower
elevations to train (Levine & Stray-Gunderson, 1992) or by living at sea-level but
sleeping in hypoxic environments induced either with nitrogen dilution
(normobaric hypoxia) or by valying the atmospheric pressure (hypobaric hypoxia)
(Rusko, 1996). The low - high approach can also be practiced by either going to
altitude on a daily basis or by training at sea-level in hypoxic environments. It is
important to realize ttl3t the acclimatization approach, conducted in the natural
altitude environment, attendant with a variety of other influences (cold, dietary,
etc.), may produce results different that acclimation when only a single variable
(hypoxia) is manipulated.
Even within a simple paradigm, numerous variables and possibilities exist. The
actual height and length of residence at altitude needed to induce the desired
acclimatization effects remain questionable. To a large degree, the appeal of the
altitude experience is due to the phenomenal success of native high-landers in

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middle and long distance events (Bailey & Davies, 1997). These athletes may
derive the benefits that can only be realized by residence at altitude for
generations. Other unsolved issues include the specifics of the training needed to
induce the appropriate adaptations and the time following the return to sea-level
for the benefits to be fully realized in competition. Given the highly individualized
acclimatization and deacclimatization response patterns which appear to exist,
these factors will not be easily resolved.
A final issue relates both to the isolation of the properties that are induced by
acclimatization and which are responsible for the performance improvement and
the mechanisms whereby these properties are induced by acclimatization.
Resolving these scientific issues creates the possibility of increasing the efficiency
and success of programs aimed at using altitude as an adjunct to training or
perhaps, more importantly, in replacing the altitude exercise with other less costly
manipulations shown to induce the same adaptations. However, identifying the
adaptations fundamental to performance improvement is not without com-
plication. Success in middle distance and distance events, as examples, depends
on a complex and integrated response involving multiple systems, tissues, organs
and cells. To search for a single underlying factor, either at the cellular a n d / o r
molecular level, which can account for small improvements in performance, may
be naive at best.
Sea-Level Training
Insight into the potential ways in which acclimatization may benefit sea-level
performance can be provided by examining the specific adaptations that occur
with altitude residence and relating them to the properties identified as being
important in specific athletic events. In general, the use of supplemental
acclimatization techniques has been rationalized to events of middle and long
distance where the peak amount of energy that can be generated by aerobic
metabolism ~O2max) is deemed critical. Accordingly, processes that regulate
V O2max, which are involved in promoting delivery of 02 to the working muscles
(central), or in the utilization of 02 by the working muscles (peripheral), appear
relevant.
It is generally agreed that a high VO2max is dependent on both high blood flows
and arterial 02 delivery rates to the working muscles and high 02 extraction rates
(Wagner, 2000). High arterial 02 delivery rates are dependent, or least in part, on
large cardiac outputs. Several studies have now demonstrated that these high
cardiac outputs are critically dependent on large total blood volumes (TBV),
involving both higher plasma volumes (PV) and red cell volumes (RCV) (Green et
al., 1995; Sawka et al., 1992). According to current theory, at maximal exercise,
the higher TBV allows less peripheral vasoconstriction (increased blood flow) and
increased cardiac output (increased stroke volume) while allowing blood pressure
to be appropriately regulated (Wagner, 2000). Interestingly, to-date there is little
evidence to demonstrate that sea-level training can induce increases in TBV
mediated by increases in both PV and RCV, necessary to realize a high VO2max
(Green et al., 1991). Increases in PV with training are readily observable with
increases in excess of 20% reported (Convertino et al., 1980). Increases in PV of
this magnitude do not negatively impact on VO2max, at least in the untrained,
since PV can be artificially expanded by this amount without any effect (Grant et
al., 1997). However, for VO2max to be increased significantly, increases in RCV
are also needed to maintain hemoglobin concentration relatively constant and
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 Altitude Acclimatization, Training and Performance

consequently, with the increases in muscle blood flow that occurs, to enhance
arterial 02 delivery. The benefit of increasing RCV to VO2max and performance
comes from experiments in which RCV has been ~tificially increased by re-
infusion of stored red cells or by injections of recombinant h u m a n erythropoietin
(EPO). Increases in VO2max, ranging between 5 and 13% have been commonly
reported (for review see Bailey & Davies, 1997). It is for this reason that RCV has
been the most common property examined in studies investigating altitude
acclimatization and performance.
Athletes displaying a high VO2max also display a n u m b e r of peripheral features
that can appear important in being able to generate large amounts of energy
aerobically. Typically, muscle fibre composition (vastus lateralis) consists almost
exclusively of Type 1 (slow-twitch) and Type 11A (fast-twitch) fibres (Saltin &
Gollnick, 1983). The percentage of the very fast, Type 11B (11A, which normally
represents 10 to 15% in the untrained), are generally low. There is also evidence
to indicate the athlete with a high VO2max, particularly those involved in distance
events, display a pre-dominance of Type 1 fibres (Coyle et al., 1991; Saltin &
Gollnick, 1983), which may have important implications to work efficiency (Coyle
et al., 1991). Another distinguishing feature of the muscle in the elite is the high
mitochondrial content that is observed (Saltin & Gollnick, 1983). The high
mitochondrial content is consistent with a high potential for flux through the citric
acid cycle and electron transport chain, both of which are critical for high-rates of
02 utilization. The high mitochondrial potential is accompanied by either an
unchanged potential for high-energy phosphate transfer, glycogenolysis and
glycolysis, or a down-regnlation in these metabolic pathways (Saltin & Gollnick,
1983). Muscles most highly specialized for aerobic metabolism characteristically
display high aerobic to anaerobic enzyme ratios, making them even more superbly
equipped to combust substrates aerobically (Pette & Staron, 1990). The aerobic
based metabolic organization in trained muscle cells is also accompanied by a
large n u m b e r of capillaries and high capillary to fibre area rates (Saltin & Gollnick,
1983). This provides for an interface with the circulation, allowing the high
cardiac outputs to be accommodated with minimal increases in flow velocity and
allowing for increased conductance of 02 from the red cell to the mitochondria, as
a result of increased cross sectional and decreased diffusion distance (Wagner,
2000). Collectively, these properties promote increased 02 extraction by the
working muscle.
Trained endurance athletes exhibiting a high VO2max also m u s t be able to
access substrates for the generation of reducing equivalents by mitochondria. For
realization of VO2max or for middle distance events which are conducted near
VO2max, the substrate used is essentially stored carbohydrates in the form of
glycogen, in the muscle (Brooks, 1998). However, for distance events, not only is
a sufficient endogenous supply of muscle glycogen and triglycerides important
b u t substrates in the form of glucose and fatty acids must be supplied from the
liver and adipose tissue, respectively (Brooks, 1998). For this to occur, high
concentrations of proteins involved is both the facilitated transport of glucose (i.e.
Glut 4) and fatty acid (i.e. fatty acid binding proteins, FABP) across the
sarcolemma into the interior of the cell are required (Turcotte, 2000). Moreover,
high oxidative flux rates, necessary to achieve VO2max, will also result in
activation of glycolysis, leading to the production of lactic acid. Diffusion of lactate
from the cell or into the mitochondria where it can be used as a substrate is to

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some degree dependent on a family of proteins called lactate transporters (Juel &
Halestrap, 1999). Interestingly, these transport proteins are high in muscle ceils
with a pronounced aerobic metabolism (Turcotte, 2000).
Other processes, not generally acknowledged, may also regulate the VO2max
that can be achieved or sustained. Those processes represent the excitation-con-
traction processes which allows for the neural signal to be conducted to the
interior of the fibre, ultimately resulting in weak to strong actomyosin binding and
force development. The processes involved in excitation and contraction can be
subdivided into two categories, namely those involved in producing an increase in
intracellular free Ca 2+ (Ca2+f) and these involved in translating the Ca 2+ signal into
activation of the myofibrillar apparatus. The former category involves trans-
mission of the neural signal as an action potential in the sarcolemma and T-
tubule, formation of a mechanical link (dihydropyridine receptors) between the T-
tubules and the Ca 2+ release channel (ryanodine receptor) of the sarcoplasmic
reticulum (SR) and release of stored Ca 2+ from the SR into the cytoplasm. The
latter category involves a sequence of steps beginning with the sensing of the Ca 2+
by the regulatory protein, troponin, movement of a second regulatory protein,
tropomyosin and ultimately aUosteric co-operative regulation of actin and myosin
into strong binding and cycling (Gordon et al., 2000). During contraction, these
processes utilize the majority of the ATP produced by the metabolic pathways. In
the case of the processes involved in the generation of a Ca2+f transient, ionic
balance (Na+, K+) must be restored across the sarcolemma and T-tubule and Ca 2+
must be sequestered back into the SR. These functions are provided by two
integral membrane proteins, the Na+K+ -ATPase and the Ca2-ATPase, which can
use the energy provided by the hydrolysis of ATP to transport these cations
against a concentration gradient (Green, 2000; Green, 1998). Actomyosin cycling
depends on another ATPase, the acto-myosin ATPase, which utilizes the energy
provided by ATP-hydrolysis to induce weak to strong cross bridge formation,
cycling and dissociation of the cross bridges (Gordon et al., 2000). To be able to
generate the forces and velocities required to achieve a VO2max, these processes
must be able to respond to high-activation frequencies as dictated by the neural
command. This means that the ATPases m u s t be in sufficient concentration to
hydrolyze available ATP for performance of their specific fimction. Fibre type
contraction velocity is intimately dependent on the myosin heavy chain and light
chain isoform composition. The heavy chains in which the myosin ATPase is
located, and in which determines the histochemical basis for fibre type
identification, is high in fast fibres and low in slow fibres as might be expected
(Schiaffmo and Reggiani, 1996). Similarly, the SR including the Ca2+-ATPase and
the Ca2+-release channel exists in higher density in fast-contracting fibres
(Green,1998). Collectively, the properties of the SR and the myofibrillar proteins
provide both for rapid Ca2+-transients, rapid development of force and rapid
relaxation rates.
In contrast, the Na ÷, K+-ATPase appears not to be regulated by the speed of
contraction but by the oxidative potential of the fibre (Green, 2000). As with the
aerobic potential of the muscle cell, physical activity represents a potent stimulus
for up-regulation of the Na+-K+-ATPase (Green, 2000), suggesting that changes in
this protein might be important in protecting membrane excitability during
progressive exercise leading to VO2max. It is also becoming increasingly clear that
during progressive and prolonged activity, one or more of the cellular ATPases

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m a y become partially inhibited (Green, 1998). In vivo, this appears to be due to

changes in the intracellular environment such as an accumulation of selected
metabolic by-products (Cooke & Pate, 1990). A similar effect m a y also occur with
the Ca2-release channel (Favero, 1999). Moreover, structural abnormalities m a y
also occur, particularly to the cation cycling ATPases (Green, 1998), effects that
m a y be explained by free radical damage (Kourie, 1998) or proteolysis (Belcastro
et al., 1996). As a consequence, it is possible that an inability to achieve a high
VO2max or an inability to sustain a high power output m a y be mechanistically
linked to failure of one or more of the excitation-contraction processes.
A major goal of training, at least for middle and long distance events, is to be
able to increase the peak a m o u n t of energy that can be generated by aerobic
processes ~ O 2 m a x ) and to increase the ability to sustain performance at
increasingly higher levels of VO2max. From a peripheral perspective, this comes
from integration of both the metabolic pathways that supply ATP and the
excitation-contraction processes utilizing ATP. A fundamental priority is being
able to minimize the disruption to ATP homeostasis in the cell at increasing levels
of effort (Hochachka & Matheson, 1992). Excessive decreases in the high-energy
phosphate potential of the cell as a result of inadequate re-generation of ATP
aerobically, will result in a n a b n o r m a l accumulation of metabolic by-products,
mediated both by high-energy p h o s p h a t e hydrolysis and activation of glycolysis.
Under such circumstances, cellular ATPases are inhibited in order to preserve
ATP balance. The consequence is fatigue, defined as an inability to sustain
performance. Inadequate activities of one or more of the cellular ATPases, on the
other hand, could result in an inability to appropriately respond to the neural
command, resulting in an inability to realize the full mechanical abilities of the
muscle as defmed by the muscle mass. Under such circumstances, the
development of high metabolic capacities, both oxidative and glycolytic, m a y have
limited usefulness. It also appears t h a t the location of the energy metabolic
pathways within the cell are important. Compartmentalization occurs s u c h that
the ATP producing metabolic machinery is located in proximity to the cellular
ATPases, the enzymes utilizing the ATP (Green, 1998).
All of the properties of the cell alluded to are highly adaptable. However, some
are m u c h more resistant to change t h a n others. Aerobic related properties which
include the mitochondria, capillaries and the Na+-K+ ATPase a p p e a r readily
adaptable. In contrast, the sarcoplasmic reticulum, the myofibrfllar a p p a r a t u s
and the potential of the metabolic pathways involved in high-energy p h o s p h a t e
transfer and glycolysis, although capable of extensive re-organization, are more
resistant to rapid alteration (Pette & Staron, 1997). How might these properties be
adapted during chronic hypoxia to increase VO2max or to enhance performance
in middle and long distance events?
Altitude Acclimatization
The use of altitude as supplement to training is based on the rationale t h a t one
or more of the acclimatization effects, which are not or minimally expressed
through sea-level training, can be exploited to boost sea-level performance.
Although the rationale is not without a teleological basis, it m a y be considerably
more complicated t h a n first appears. Ascent to altitude results in a reduction in
the partial pressure of 02, which in the absence of respiratory compensation, is
directly reflected in arterial 02 (paO2) a n d arterial O 2 content (CaO2). Under s u c h
circumstances, the adaptative challenge is to restore the work that can be
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accomplished aerobically to sea-level values a n d / o r depending on the exercise

intensity, to reduce the strain associated with generating the same oxidative flux
rates. Three primary acclimatization strategies have been proposed (Hochachka et
al., 1991). These include 1) restore the contribution of aerobic based ATP
production by restoring CaO2; 2) increase the a m o u n t of energy that can be
generated b y a given VO 2 by shifting to carbohydrate based metabolism; 3)
increase mechanical efficiency, defined as the work that can be performed at a
given level of VO 2. At sea-level, at least in athletes not experiencing exercise-
induced hypoxemia (EIH), the fundamental factor triggering the acclimatization
responses, namely a low Pa02 and CaO2, is absent. Consequently, although it
m a y be desirable to increase ATP yield per unit 02 combusted by shifting towards
CHO based metabolism, j u s t the opposite occurs, namely an increase in fat
metabolism (Brooks, 1998). In addition, there is little evidence to indicate that
training at sea level altars mechanical efficiency. However, perhaps an even more
fundamental question is the degree to which the acclimatization strategies are
expressed in the altitude resident and u n d e r what environmental conditions.
To assess the potential benefits of short-term residence of altitude, typical of
that used by athletes, on sea-level performance, it is important to characterize the
actual acclimatization effects under carefully controlled conditions. Such a series
of studies h a s been performed on Pike's Peak (4,300 In) in the United States.
These studies, although conducted at altitudes considerably in excess of those
typically used by athletes, have greatly increased our understanding of the
changes that occur. After three weeks of acclimatization, TBV was unchanged
while RCV was increased and PV decreased (Wolfel et al., 1991). The increase in
Hb concentration in conjunction with a n increase in arterial 02 saturation helped
to restore CaO2. During submaximal, exercise performed at altitude following
acclimatization, V02 was unchanged from sea-level (SL). However, fundamental
different m e c h a n i s m s were used to maintain VO2. Following acclimatization,
cardiac output and stroke volume were decreased along with muscle blood flow.
These changes necessitated an increase in extraction of 02 by the working
muscles to maintain V02 constant. Moreover, systemic arterial pressure and leg
vascular resistance were all increased, probably as a result of increased
sympathetic activation (Wolfel et al., 1991). Other adaptations were also observed.

Sea-Level Altitudes
Hematology
Red Cell Volumes
Plasma Volume 1-
Total Blood Volume
Submaxlmal Exercise
Cardiac Output $
Heart Rate $ T
Stroke Volume t $
Leg Blood Flow $
Arterial-venous 0 2 diff. T

Note: Altitude representsacclimatizationwithout training.

Table 2: Comparisonsbetween sea-levelendurancetraining and acclimatization on hematology and cardiovascular

function during submaximalexercise.
3O5
Altitude Acclimatization, Training and Performance

Acclimatization also induced a n increased reliance on blood glucose during

exercise (Brooks et al., 1991a) a n d a decrease in fat utilization (Roberts et al.,
1996). At the muscle level, fibre type composition, fibre area, the n u m b e r of
capillaries per fibre and capillary to fibre areas were also unaltered by
acclimatization (Green et al., 1992). Similarly, with the exception of hexokinase
and phosphofructokinase, which were increased and decreased respectively, no
other changes in metabolic potential was observed (Green et al., 1992). The
muscle metabolic response, although disturbed to a greater extent during exercise
with acute hypoxia, as indicated by the higher accumulation of by-products such
as lactate, was generally restored to sea-level with acclimatization. Interestingly,
lactate clearance was also increased, approaching the sea-level response (Brooks
et al., 1991b). Collectively, these responses clearly demonstrate the benefits of
acclimatization in neutralizing the impact of an 02 deficient environment, allowing
VO 2 to remain undisturbed with less of a strain on the peripheral elements. Such
m a y also be the case with the cardiovascular system. The decrease of cardiac
output observed following acclimatization (Wolfel et al., 1991) m a y mirn'mize the
work of the heart, given the increase in blood viscosity that would be expected
with elevations in RCV and decreases in PV.
Unclear from these studies, however, is the exercise response on return to sea-
level after acclimatization. This issue h a s been studied using essentially the s a m e
acclimatization protocol (Bender et al., 1988; Bender et al., 1989). Exercise
performed under sea level conditions, both before and after acclimatization,
indicated essentially the s a m e responses as observed as altitude (Wolfel et al.,
1991), namely that VO 2 was maintained by a widened a-VO 2 difference to
compensate for the reduction in muscle blood flow that occurs in association with
the elevated Hb concentration. These investigators (Bender et al., 1989) also found
a reduction in net lactate release, a finding that could be explained either by a
decreased production a n d / o r increased removal, possibility within the muscle
itself. At present, it is unclear whether the shift towards CHO oxidation and
tighter metabolic control, as occurs during exercise at altitude following
acclimatization, also is expressed at sea-level.
A series of studies conducted at sea-level both prior to and 3 to 4 days following
a 21 day mountaineering expedition to Mount Denali (6184 m) m a y also have
relevance to the potential effect of altitude on performance. As with the Pike's
Peak study (Green et al., 1992), we could find little evidence of changes in fibre
type composition, fibre area, capfllarization or in the potential of the various
metabolic pathways and segments (Green et al., 2000a). However, during exercise,
clear adaptive effects were evident. Acclimatization resulted in an improved energy
state in the working muscle as indicated by the more protected high-energy
phosphate potential and reduced accumulation of metabolic by-products s u c h as
lactate (Green et al., 2000b). These responses are typical of the sea-level training
response. However, unlike training at sea-level, we also found reductions in
exercise V02, indicating a n increase in mechanical efficiency (Green et al., 2000c).
The increase in mechanical efficiency could not be solely explained by an
increased CHO utilization b u t rather appeared to represent an actual increase in
efficiency in the excitation-contraction processes involved in contraction.
Interestingly, both Na+K+-ATPase (Green et al., 2000a) and SR Ca2-ATPase (Green
et al., 2000d), the two enzymes involved in ATP hydrolysis and cation transport
were reduced. The down-regulation observed m a y be involved in the improved

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 Altitude Acclimatization, Training and Performance

Sea-Level Altitudes
Excitation
Na+ -K+ -ATPase T $
Ca2+ -ATPase $
Contractile
Fibre Type (1 vs 2)
Subtypes (Type liB) $
MetabOliC
Oxidative T -$
High-energy phosphate transfer
Glycolysis -$
MOrphologic
Area T -$
Capillaries ]"
Capillary/Fibre Area ]" -T
Transporters
Glut-4 $ ?
FABP T ?
Lactate T ?
MyOglObin
Note: Altitude representsacclimatizationwithout training.

Table3: Comparisons between sea.level endurance training and acclimatization muscle structure and
composition.

efficiency. Of particular concern, however, is the significance of the reductions in

cation cycling potential in performance. The Na+K÷-ATPase, as an example,
appears to be particularly affected by hypoxia, not only in muscle b u t in a variety
of ceils (Kourie, 1998; Clerici and Matthay, 2000). It is possible that reductions in
Na+-K+-ATPase could impair m e m b r a n e excitability and the VO 2 m a x observed
(Clausen, 1998) or promote early fatigue by compounding the inactivation o f N a +-
K+-ATPase activity that normally occurs with prolonged exercise (Verburg et al,,
1999). Moreover, the Na+-K÷-ATPase in addition to the controlling m e m b r a n e
excitability, is also involved in regulating osmolality and cell volume, both of
which have important implications to metabolism and protein turnover (Green,
2000). Indeed, the fluid and electrolyte disturbances observed with altitude m a y
be associated with inhibition of the Na÷-K+-ATPase in a variety of cells.
Although these studies suggest possible transfer benefits to sea-level
performance, the effects of more intense exposure to altitude clearly have negative
consequences. Analyses of tissue obtained from the vastus lateralis of alpinists
before and after expeditions to Mount Everest indicated a reduction in fibre area
and decreases in the fractional volume of mitochondria, a disproportionate
a m o u n t of which was lost from the s u b s a r c o l e m m a region (Hoppeler &
Desplanches, 1992). Although muscle capillary to fibre area ratios were
increased, this was not due to capillary neoformation b u t to a loss of fibre area
(Hoppeler and Desplanches, 1992). Biochemical analyses of the tissue indicated
that while the potential for high-energy phosphate transfer and glycolysis was

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Altitude Acclimatization, Training and Performance

preserved, reductions of approximately 25% were evident in the mitochondrial

enzymes involved in oxidative phosphorylation, ~-oxidation and ketone body
oxidation (Howald et al., 1990). "Operation Everest", an experiment designed to
examine the adaptations to progressive hypobaria indicated essentially the s a m e
effects (Green, 1992). In general, the acclimatization responses observed in these
extreme environments are in contradiction to the adaptations desired for middle
and long distance runners.
The intrigue with the use of altitude for performance e n h a n c e m e n t h a s also
been fuelled by reports of prodigious exercise capacities of indigenous high
landers who have been resident in hypoxic environments for generations. These
natives have been reported to display m u c h less of a decrease in VO2max t h a n
newcomers to altitude or to those acclimatized over several weeks (Hochachka,
1996). As expected, high-altitude natives display elevated Hb concentrations and
elevated blood volumes and possibly mutations in structure of the Hb molecule
itself which permits a higher 02 saturation (Ramirez et al., 1999). However,
additional adaptive effects appear m u c h less defined. The functional impact of the
adaptations that have been observed in native high landers h a s been dramatically
demonstrated during exercise at sea-level (Hochachka et al., 1991; Matheson et
al., 1991). It h a s been reported t h a t during exercise long time residents to altitude
(4,200 m), as compared to sea-level residents, display features normally
associated with the endurance trained state, namely a reduced perturbation of
the muscle phosphorylation potential and lower lactate accumulation (Hochachka
et al., 1991; Matheson et al., 1991). Interestingly, VO2max volumes remain
substantially below aerobic trained athletes (Matheson et al., 1991). The
impressive work capacity has been suggested to occur as a result of improved
coupling between processes involved in ATP supply and utilization, providing for
a better protection of the energy state of the muscle (Matheson et al., 1991). It h a s
also been reported that the high-altitude natives display a great mechanical
efficiency during work (Hochachka et al., 1991). As with the increased efficiency
reported on mountaineers (Green et al., 2000c), the increase in efficiency would
have to involve more t h a n j u s t a shift towards increased CHO utilization, b u t also
involve a reduction in the energy expenditure associate with the excitation and
contraction processes. These metabolic and efficiency effects observed in high
altitude do not appear to be explained by a metabolic re-organization since
mitochondrial potential appears lower t h a n the sea-level residents (Kayser et al.,
1991). Although, there is some suggestion of an increased capfllarization, muscle
fibre areas do not appear different (Kayser et al., 1991).
These studies, although invaluable in describing the acclimatization effects of
altitude, m a y be of limited application for athletes since the studies generally did
not involve training and since they were conducted at altitudes considerably more
extreme t h a n used by athletes. However, they do suggest that sea-level benefits
m a y result as indical;ed b y the training-like responses to exercise. Although m a n y
studies have been conducted on athletes, few have examined the cellular
responses that occur with altitude training. One exception was a study performed
by Mizuno et al (1990). These authors found that training at 2,700 m increased
m u s c l e mitochondrial a n d / o r capillarization, depending on the m u s c l e
(gastrocnemius vs triceps brachii) and buffer capacity. Although, the design of the
study did not enable conclusions to be drawn regarding the effects of altitude per
se, I,he findings do indicate that aerobic based adaptations can occur at altitude.

308
 Altitude Acclimatization, Training and Performance

The suggestion that significant cellular adaptations can be induced by training at

altitude, has also been shown in high altitude residents (3,600 m) (Desplanches
et al., 1996). In this study, it was demonstrated that endurance training increased
muscle capillary-to-fibre ratio, capillary density as well as the volume density of
mitochondria. These changes were accompanied by increases in VO2max.
Optimal Use of AltitUde
Recently, the need to both live and train at altitude has been questioned. Levine
and Stray-Gundersen (1997), in perhaps the most rigorous scientific study
conducted to-date, have provided evidence that living at altitude (2,500 m) while
training low (1,250 m) (high-low), improves sea-level performance (5,000 m) more
than living and training at sea-level (low-low) or living and training at altitude
(high-low). While both groups responded to altitude with increased VO 2 max (5%)
and RCV (9%), only the high-low group increased performance, an effect they
attribute not only to the changes in RCV and VO2max but to the ability to
maintain sea-level training velocities. In a subsequent paper (Chapman et al.,
1998), addressing the factors underlying the large inter-individual variation in
response patterns, the authors found that those benefiting from the altitude
experience responded with greater increases in RCV (secondary to increases in
EPO) and VO2max. These conclusions, although providing the first substantive
evidence of a strategy to improve performance, are in need of qualification.
Particularly questionable was the response of the low-low group which,
surprisingly, displayed evidence of impaired performance. Moreover, the high-low
group was not without an hypoxic stimulus, since training was conducted at
1,250 m. The mechanisms, ostensibly involved in the increase in VO2max and
performance, namely RCV, was increased in the high-low group at the expense of
decreases in PV. This effect is consistent with the effects observed during
acclimatization to 4,300 m which appears to be compensated for by reductions in
blood flow and increases in 02 extraction by the working muscles during
submaximal exercise (Wolfel et al., 1991; Bender et al., 1988). Since VO 2 max was
increased, it would appear that cardiac output and muscle blood flow were not
compromised at maximal effort. It is of interest that the high-high group
demonstrated the response typical of the observed with infusion of RBC, and
which has been demonstrated to improve V_O2max and performance (Bailey &
Davies, 1997), namely an increase in RCM, no change in PV and an apparent
increase in TBV. The improvements demonstrated by the high-low group (Levine
and Stray-Gunderson, 1997) have been instrumental in promoting the use of
"nitrogen houses" where athletes sleep in normobaric hypoxic environments
(2650-3000 m) while training normally at sea-level (Rusko, 1996). The results of
these experiments remain equivocal. Recent studies, using this approach over a
12 to 23 day period, have not been able to document any effect on reticulocyte
production or Hb mass (Ashenden et al., 1999a; Ashenden et al., 1999b).
Another hypoxic based strategy that shows promise for enhancing performance
is to live low and train high (low-high). This strategy, used primarily in highly-
controlled experimental settings because of practical limitations, has been
accomplished by having individuals breath an hypoxic gas mixture while training
(Melissa et al., 1997; Green et al., 1999; Terrados et al., 1988; TelTados et al.,
1990). When training at equivalent submaximal power outputs as in normoxia,
the low-high strategy has been shown to potentiate the increases ill mitochondrial
capacity (TelTados et al., 1990; Melissa et al., 1997) in conjunction with small but
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 Altitude Acclimatization, Training and Performance

significant i n c r e a s e s i n myoglobin (Terrados et al., 1990). These a d a p t a t i o n s do

n o t a p p e a r to alter the n o r m a l t r a i n i n g increase i n VO2max or tilne to fatigue
d u r i n g h i g h - i n t e n s i t y exercise (Melissa et al., 1997). As h a s b e e n n o t e d with a n
altitude expedition, (Green et al., 2000a), the Na+-K+-ATPase p u m p w a s down-
regulated i n the hypoxic leg a n d i n c r e a s e d i n the n o r m o x i c t r a i n e d leg (Green et
al., 1999). The f u n c t i o n a l significance of this effect r e m a i n s to be d e t e r m i n e d .

Summary
The u s e of altitude (or hypoxia) to promote acclimatization r e s p o n s e s , n o t
n o r m a l l y realized d u r i n g sea-level training, to improve sea-level p e r f o r m a n c e ,
r e m a i n s popular. However, scientific evidence s u p p o r t i n g this practice r e m a i n s
controversial. Recent evidence s u g g e s t s t h a t a n effective strategy is to live at
m o d e r a t e altitudes a n d t r a i n at low altitudes. The altitude r e s i d e n c e p r o m o t e s
i n c r e a s e d RCV a n d VO2max, while the low altitude p e r m i t s h i g h - q u a l i t y t r a i n i n g
sessions. However, residence a t altitude also p r o m o t e s other acclimatization
effects, m a n y of w h i c h could b e deleterious to p e r f o r m a n c e . C o n t i n u e d
investigation will u n d o u b t e d l y lead to m a n y more i n s i g h t s regarding b o t h the
effects of v a r i o u s altitude strategies o n p e r f o r m a n c e a n d the m e c h a n i s m s w h i c h
are involved.

References
Ashenden, M.J., Gore, C.J., Dobson, G.P., & Hahn, A. (1999a). "Live high, train low" does not
change the total haemoglobin mass of male endurance athletes sleeping at a simulated
altitude of 3000m for 23 nights. European Journal of Applled Physiology, 80: 479-484.
Ashenden, M.J., Gore, C.J., Martin, D.T., Dobson, G.P., & Hahn, A.G. (1999b). Effects of a 12-
day "live high, train low" camp on reticulocyte production and haemoglobin mass in elite
female road cyclists. European Journal of Applied Physiology, 80: 472-478.
Barley, D.M., & Davies, B. (1997). Physiological implications of altitude training for endurance
performance at sea level. British Journal of Sports Medicine, 31: 183-190.
Barley, D.M., & Davies, B. (1998). Implications of moderate altitude training for sea-level
endurance in elite distance runners. European Journal of Applied Physiology, 78: 360-
368.
Belcastro, A.N., Gflchrist, .S., & Scrubb, J. (1996). Role of calcium-activated neutral protease
(calpain) with diet and exercise. Canadian Journal of Applied Physiology, 21: 328-346.
Bender, P.R., Groves, B.M., McCullough, R.E., McCuUough, R.G., Huang,S .-Y., Hamilton, A.J.,
Wagner, P.D., Cymerman, A., & Reeves,J .T. (1988). Oxygen transport to exercising leg in
chronic hypoxia. Journal of Applied Physiology, 65: 2592-2597.
Bender, P.R., Groves, B.M., McCullough, R.E., McCullough, R.G., Trad, L., Young, A.J.,
Cymerman, A., & Reeves, J.T. (1989). Decreased exercise muscle lactate release after high
altitude acclimatization. Journal of Applied Physiology, 67: 1456-1462.
Brooks, G.A. (1998). Mammalian fuel utilization during sustained exercise. Comparative
Biochemistry and Physiology: Part B, 120: 89-107.
Brooks, G.A., Butterfield, G.E., WoKe,R.R., Groves, B.M., Mazzeo, R.S., Sutton, J.R., Wolfel, E.E.,
& Reeves, J.T. (199 I b). Decreased reliance on lactate during exercise after acclimatization to
4,300 m exercise. Journal of Applied Physiology, 71: 333-341.
Brooks, G.A., Butterfield, G.E., WoKe, R.R., Groves, B.M., Mazzeo, R.S., Sutton, J.R., Wolfel, .E.,
& Reeves, J.T. (1991a). Increased dependence on blood glucose after acclimatization to 4,300
m. Journal of Applied Physiology, 70: 919-927.
Chapman, R.F., Stray-Gtmderson, J., & Levine, B.D. (1998). Individual variation in respect to
altitude training. Journal of Applied Physiology, 85: 1448-1456.
Clausen, T. (1998). Clinical and therapeutic significance of the Na+, K+ pump. Clin.Sci., 95: 1-17.
Clerici, C., & Matthay, M. (2000). Hypoxia regulated gene expression of alveolar epithelial
transport proteins. Journal of Applied Physiology, 88: 1890-1896.
Convertino, V.A., Greenleaf, J.E., & Bernhauer, E.M. (1980). Role of thermal and exercise factors
in the mechanism of hypervolemia. Journal of Applied Physiology, 48: 657-664.
Cooke,~R., & Pate, E. (1990). The inhibition of muscle contraction by the by-products of ATP
hydrolysis. In: Biochemistry of Exercise VII, B.Taylor (Ed.), pp.59-72. Human Kinetics,
110
 Altitude Acclimatization, Training and Performance

Champaign, Ill.
Coyle, E.F., Feltner, M.E., Kautz, S.A., Hamilton, M.T., Montain, S.J., Baylor, A.M., Abraham,
L.D., & Petrek, G.W. (1991). Physiological and biochemical factors associated with elite
endurance cycling performance. Medicine and Science in Sports and Exercise, 23: 93-
107.
Desplanches, D., Hoppeler, H., Ttischer, L, Mayet, M.H., Spielvogel, H., Ferretti, G., Kayser, B.,
Leuenberger, M., Grfinenfelder, A., & Favier, R. (1996). Muscle tissue adaptations of high-
altitude natives to training in chronic hypoxia or acute normoxia. J o u r n a l of Applied
Physiology, 81: 1946-1951.
Favero, T.G. (1999). Sarcoplasmic reticulum Ca2+-release a n d muscle fatigue. J o u r n a l of
Applied Physiology, 87: 471-483.
Gordon, A.M., Homsher, E., & Regnier, M. (2000). Regulation of contraction in skeletal muscle.
Physiol Reviews, 80: 853-924.
Grant, S., Green, H., Phillips, S., Erms, D., & Sutton, J. (1997). Effects of acute expansion of
plasma volume on cardiovascular and thermal function during prolonged exercise.
European J o u r n a l of Applied Physiology, 76: 356-362.
Green, H., MacDougall, J., Tarnopolsky, M., & Melissa, N.L (1999). Downregulation of Na+-K+-
ATPase p u m p s in skeletal muscle with training in normobaric hypoxia. J o u r n a l of Applied
Physiology, 86:1745-1748.
Green, H., Roy, B., Grant, S., Hughson, R., Burnett, M., Otto, C., Pipe, A., Mckenzie, D.M., &
Johnson, M. (2000c). Increases in submaximal cycling efficiency mediated by altitude
acclimatization. J o u r n a l of Applied Physiology, 89: 000-000.
Green, H., Roy, B., Grant, S., Otto, C., Pipe, A., McKenzie, D., & Johnson, M. (2000b). H u m a n
skeletal muscle exercise metabolism following a n expedition to Mount Denali. American
Journal of Physiology, (in press).
Green, H., Roy, B., Grant, S., Tupling, R., Otto, C., Pipe, A., McKerLzie, D., & Ouyang, J. (2000d).
Effects of a 21 day expedition to 6194 m on h u m a n skeletal muscle SR Ca 2+-ATPase. High
Altitude Medicine and Biology, (in press).
Green, H.J. (1992). Muscular adaptations at extreme altitude. Metabolic implications during
exercise. International Journal of Sports Medicine, 13 (Suppl. 1): St63-S165.
Green, H.J. (1998). Cation p u m p s in skeletal muscle: Potential role in muscle fatigue. Acta
Physiologica Scandinavica, 162:201-213.
Green, H.J. (2000). Adaptations of the muscle cell to training. Role of the Na+-K+-ATPase.
Canadian J o u r n a l of Applied Physiology, 25:204-216.
Green, H.J., Carter, S., Grant, S., Tupling, R., Coates, G., & All, M. (1995). Vascular volumes and
hematology in specifically trained athletes. J o u r n a l of Applied Physiology, (submitted).
Green, H.J., Roy, B., Grant, S., Burnett, M., Tupling, R., Otto, C., Pipe, A., & McKenzie, D.
(2000a). Down-regulation in muscle Na + -K+-ATPase following a 21 day expedition to 6,194m.
J o u r n a l of Applied Physiology: 88, 634-640.
Green, H.J., Sutton, J.R., Coates, G., All, M., & Jones, S. (1991). Response of red cell volume and
plasma volume to prolonged training in humans. J o u r n a l of Applied Physiology, 70:1810-
1815.
Green, H.J., Sutton, J.R., Wolfel, E.E., Reeves, J.T., Butterfield, G.E., & Brooks, G.A. (1992).
Altitude acclimatization and energy metabolic adaptations in skeletal muscle during exercise.
Journal of Applied Physiology, 73: 2701-2708.
Hochachka, P.W. (1996). Metabolic defense adaptations to hypobaric hy-poxia in man. In:
Handbook of Physiology: Environmental Physiology, M.J.Fregly & C.M.Blatteis (Eds.), pp.
1115-1122. Oxford University Press, New York.
Hochachka, P.W. & Matheson, G.O. (1992). Regulating ATP turnover over broad dynamic work
ranges in skeletal muscles. J o u r n a l of Applied Physiology, 73: 1697-1703.
Hochachka, P.W., Stanley, C., Mathewson, G.O., McKenzie, D.C., Allen, P.S., & Parkhouse, W.S.
(1991). Metabolic and work efficiencies during exercise in Andean natives. J o u r n a l of
Applied Physiology, 70:1720-1730.
Hoppeler, H., & Desplanches, D. (1992). Muscle structural modifications in hypoxia.
International Journal of Sports Medicine, 13 (Suppl i): S166-S168.
Howald, H., Pette, D., Simoneau, J.A., Uber, A., Hoppeler, H., & Ceretelli, P.I. (1990). Effect of
chronic hypoxia on muscle enzyme activities. International Journal of Sports Medicine,
11 (Suppl. 1): 510-514.
Juel, C., & Halestrap, A.P. (1999). Lactate transport in skeletal muscle-rate of regulation of
monocarboxylate transporter. J o u r n a l of Applied Physiology, 517: 633-642.

311
 Altitude Acclimatization, Training and Performance

Kayser, B., Hoppeler, H., Claasen, H., & Ceretelli, P. (1991). Muscle structure and performance
capacity of Himalayan Sherpas. Journal of Applied Physiology, 70: 1938-1942.
Kourie, J.I. (1998). Interaction of reactive oxygen species with ion transport mechanisms.
American Journal of Physiology, 275: C 1-C24.
Levine, B.D., & Stray-Gunderson, J. (1992). A practical approach to altitude training: where to
live and train for optimal performance enhancement. International Journal of Sports
Medicine, 13 (Suppl. 1): 5209-5212.
Levine, B.D., & Stray-Gunderson, J. (1997}. "Living high-training low": effect of moderate altitude
acclimatization with low-altitude training on performance. Journal of Applied Physiology,
63: 102-112.
Matheson, G.O., Allen, P.S., Ellinger, D.C., Hanstock, C.C., Gheorghiu, D., McKenzie, D.C.,
Stanley, C., Park_house, W.S., & Hochachka, P.W. {1991). Skeletal muscle metabolism and
work capacity - a 31p-NMR study of Andean natives and lowlanders. Journal of Applied
Physiology, 70: 1963-1976.
Melissa, L., MacDougall, J.D., Tarnopolsky, M.A., Cipriano, N., & Green, H.J. (1997). Skeletal
muscle adaptations to training under normobaric hypoxic versus normoxic conditions.
Medicine and Science in Sports and Exercise, 29: 238-243.
Mizuno, M., Juel, C., Bro-Rasmussen, T., Mygind, E., Schibye, B., Rasmussen, B., & Saltin, B.
(1990). Limb skeletal muscle adaptation in athletes after training at altitude. Journal of
Applied Physiology, 68: 496-502.
Pette, D., & Staron, R.S. (1990). Cellular and molecular diversities of mammalian skeletal muscle
fbers. Reviews of Physiology, Biochemistry and Pharmacology, 116: 1-75.
Pette, D., & Staron, R.S. (1997). Mammalian skeletal muscle fiber type transitions. International
Review of Cytology, 170: 143-223.
Ramirez, G., Brittle, P.A., Rosen, R., Rabb, H., & Pineda, D. (1999). High altitude living. Genetic
and environmental adaptation. Aviation,Space and Environmental Medicine, 70:73-81.
Roberts, A.C., Butterfield, G.E., Cymerman, A., Reeves, J.T., Wolfel, E.E., & Brooks, G.A. (1996).
Acclimatization to 4,300m altitude decreases reliance of fat as a substrate. Journal of
Applied Physiology, 81: 1762-1771.
Rusko, H.R. (1996). New aspects of altitude training. American Journal of Sports Medicine 24:
$48-52.
Saltin, B., & Gollnick, P.D. (1983). Skeletal muscle adaptability: Significance for metabolism and
performance. In: Handbook of Physiology, Skeletal Muscle, L.D. Peachy, R.H. Adrian, &
S.R.Geiger (Eds.), pp.551-631. Williams and Wllkins, Baltimore.
Sawka, M.N., Young, A.J., Pandolf, K.B., Dennis, R.C., & Valeri, C.R. (1992). Erythrocyte, plasma,
and blood volume of healthy young men. Medicine and Science in Sports and Exercise,
24: 447-453.
Schiaffino, S., & Reggiani, C. (1996). Molecular diversity of myoflbrillar proteins: gene regulation
and functional significance. Physiological Reviews, 76: 371-423.
Terrados, N., Jansson, E., Sylvan, C., & Kaijser, L. (1990). Is hypoxia a stimulus for synthesis of
oxidative enzymes and myoglobin? Journal of Applied Physiology, 68: 2369-2372.
Terrados, N., McLichna, J., Sylven, C., Jansson, E., & Kaijser, L. (1988). Effect of training at
simulated altitude on performance and metabolic capacity in competitive road cyclists.
European Journal of Applied Physiology, 57: 203-209.
Turcotte, L. (2000). Muscle fatty acid uptake during exercise: Possible mechanisms. Exercise and
Sports Science Reviews, 28: 4-9.
Verburg, E., Hallen, J., Sejersted, O.M., & Vollestad, N.K. (1999). Loss of potassium from muscle
during moderate exercise in human: a result of insufficient activation of the Na+-K+-pump.
Acta Physiologica Scandinavica, 165: 357-367.
Wagner, P. {2000). New ideas on limitations to VO2-max. Exercise and Sport Science Reviews,
28: 10-14.
Wolfel, E.E., Groves, B.M.~, Brooks, G.A., Butterfield, G.E., Mazzeo, R.S., Moore, L.G., Sutton,
J.R., Bender, P.R., Dahms, T.E., McCullough, R.E., Huang, S.-Y., Sun, S.F., Grover, R.F.,
Hultgren, H.N., & Reeves, J.T. (1991). Oxygen transport during steady state, submaximal
exercise in chronic hypoxia. Journal of Applied Physiology, 70:1129-1136.

312