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Weight, muscle and bone loss during space flight: Another perspective

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Space flight is a new experience for humans. Humans adapt if not perfectly, rather well to life without gravity. There is a reductive remodeling of the musculo-skeletal system. Protein is lost from muscles and calcium from bones with anti-gravity functions. The observed biochemical and physiological changes reflect this accommodative process. The two major direct effects of the muscle loss are weakness post-flight and the increased incidence of low back ache pre- and post-flight. The muscle protein losses are compromised by the inability to maintain energy balance inflight. Voluntary dietary intake is reduced during space flight by ~20 %. These adaptations to weightlessness leave astronauts ill-equipped for life with gravity. Exercise, the obvious counter-measure has been repeatedly tried and since the muscle and bone losses persist it is not unreasonable to assume that success has been limited at best. Nevertheless, more than 500 people have now flown in space for up to 1 year and have done remarkably well. This review addresses the question of whether enough is now known about these three problems (negative energy balance, muscle loss and bone loss) for to the risks to be considered either acceptable or correctible enough to meet the requirements for a Mars mission.
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INVITED REVIEW
Weight, muscle and bone loss during space flight:
another perspective
T. P. Stein
Received: 11 July 2012 / Accepted: 5 November 2012
Ó Springer-Verlag Berlin Heidelberg 2012
Abstract Space flight is a new experience for humans.
Humans adapt if not perfectly, rather well to life without
gravity. There is a reductive remodeling o f the musculo-
skeletal system. Protein is lost from muscles and calcium
from bones with anti-gravity functions. The observed bio-
chemical and physiological changes reflect this accommo-
dative process. The two major direct effects of the muscle
loss are weakness post-flight and the increased incidence of
low back ache pre- and post-flight. The muscle protein
losses are compromised by the inability to maintain energy
balance inflight. Voluntary dietary intake is reduced during
space flight by *20 %. These adaptations to weightlessness
leave astronauts ill-equipped for life with gravity. Exercise,
the obvious counter-measure has been repeatedly tried and
since the muscle and bone losses persist it is not unrea-
sonable to assume that success has been limited at best.
Nevertheless, more than 500 people have now flown in
space for up to 1 year and have done remarkably well. This
review addresses the question of whether enough is now
known about these three problems (negative ener gy bal-
ance, muscle loss and bone loss) for to the risks to be
considered either acceptable or correctible enough to meet
the requirements for a Mars mission.
Keywords Space flight Weight loss Exercise
Muscle loss Bone loss Energy balance
Background
Space flight is a new experience for humans. Lack of
gravity rem oves the force that causes water to gravitate
toward the lower body; hence there are fluid shifts from the
lower body to the upper body and accompanying cardio-
vascular changes. Tension on the weight bearing compo-
nents of the musculo-skeletal system is greatly reduced, as
is the work required for movement. The body responds by a
reductive remodeling of the musculo-skeletal system. This
has been a constant finding with space flight and ground-
based models (bed rest and rodent hind limb unloading).
The human space flight response is more complex than
that found with ground-based models. Observations from
space flight missions not only reflect the response to micro-
gravity; there are other contributing factors to the overall
response, specifically the constraints imposed by the com-
plex environment needed to support life. Envir onmental
factors are multiple and varied. They include cabin tem-
perature, air composition, lighting, noise, food supply and
the work goals of the mission. With increasing flight
duration, other factors such as radiation exposure, social
factors such as isolation effects and inter-personal dynamics
are likely to become progressively more important.
Many of these factors are difficult or impossible to
control during space missions. Some are likely to vary from
person to person, others are mission-dependent. An
example of mission dependence is dietary intake. Figure
1
compares energy intake during the first 2 weeks of space
flight for the three Skylab missi ons, and three shuttle
missions. For the three Skylab missions the astronauts ate a
required diet, for the three shuttle missions diet was ad-lib
(Leach and Rambaut
1977; Stein 2000, 2001; Whedon
et al.
1977). The Spacelab Life Sciences 2 (SLS2) shuttle
mission was a repeat of the Spacelab Life Sciences 1
Communicated by Nigel A.S. Taylor.
T. P. Stein (&)
Department of Surgery, University of Medicine
and Dentistry of New Jersey, SOM,
2 Medical Center Drive, Stratford, NJ 08084, USA
e-mail: tpstein@umdnj.edu
123
Eur J Appl Physiol
DOI 10.1007/s00421-012-2548-9
(SLS1) mission so as to provide enough subjects for sta-
tistical analyses. The Life and Microgravity Sciences
(LMS) shuttle mission had a very high inflight exercise
requirement; much less exercise was done on the SLS1/2
missions. Figure
1 shows that astronauts on the same
mission appear to eat about the same amount of food. The
observation suggests that mission specifics rather than
subject-related factors affect dietary intake (Stein
2000,
2001).
Objectives of this review
There have been many reviews over the last 30 years of the
human metabolic response to space flight. For the most part,
the reviews focused on the biochemical/physiological
aspects of the muscle and bone losses, assessing their
potential for adverse effects on crew health and performance
and the ‘limited’ success of various propos ed counter-mea-
sures for the muscle and bone losses. Some of the reviews
have been commissioned by government agencies to assist in
program development. There is a potential conflict of interest
in these reviews because often the reviewers are content
experts, tend to emphasize the importance of their areas of
interest and sometimes are the beneficiary of future grants.
(The same might be said of this review).
That said, this review will argue that there is a lack of
balance in the literature; the published reviews are unduly
pessimistic. They focus almost exclusively on the numer-
ous biochemical changes and physiological decrements
found with the musculo-skeletal system found during space
flight and its ground-based analogs. Even though the
problems have been known for many years, progress over
the last 40 years is questionable. Are some of the problems
manageable with current protocols? Which problems
require further work before humans can safely venture into
space long-term? Reviewing a problem from a different
perspective might provide new insight s. In an era of limited
resources, prioritization is necessary.
Identifying a problem provides the rationale for further
research. But to get a funding agency to pay for the research
requires making a convincing case that there is a serious risk
to the astronauts if the problem is not better understood and
a counter-measure developed. There is a natural tendency
by investigators to over-exaggerate the importance of their
particular area of research. Thus, the literature is replete
with warnings about the dire consequences of allowing
‘problems’ to continue unresolved. These concerns might
have been justified 40 years ago, but are they today? An
unintended consequence has been to delay further human
exploration of space beyond the Space Statio n era. Planning
for new manned missions have moved ever further into the
future for both financial and ‘physiological’ reasons. Are
the ‘physiological concerns reall y valid?
The basic fact is that more than 500 people have now
flown in space for up to 1 year and have done remarkably
well. Humans adapt if not perfectly, rather well to life
without gravity. The observed biochemical and physio-
logical changes reflect this accommodative process. There
have been no life-threatening events. (In contrast there
have been catastrophic engineering failures with both the
US and Russian programs resulting in the death of 14 US
and 4 Russian astronauts).
Traditionally, there have been two ways of studying the
human response to space flight. (i) From actual measure-
ments, preferably inflight but for relatively invariant
parameters such as body composition, immediately post-
flight data are acceptable. (ii) By the use of ground-based
models, principally bed rest for humans and hind limb
unloading for rats. There is now a third. The use of
NASA’s longitudinal study of astrona ut health (LSAH)
data base. The LSAH includes data from the earliest space
missions (Apollo, Skylab) through the latest ISS missions.
It is likely that use of the LSAH will assume increasing
prominence as the data base increases and interest focuses
on long-duration missions.
The longitudinal study of astronaut health (LSAH) data
base
Nearly all reported studies on the human response to space
flight, especially those pertaining to the muscle loss
DAYS
ENERGY INTAKE (kcal. kg
-
1
.d
-1
)
0
10
20
30
40
50
LMS
SLS1/2
SKYLAB 2
SKYLAB 3
SKYLAB 4
5
10
15
Fig. 1 Comparison of energy intake during the first 2 weeks of space
flight for the three Skylab missions (Whedon et al.
1977), SLS1/2
(Stein et al.
1996) and the LMS shuttle mission (Stein et al. 1999b)
Eur J Appl Physiol
123
problem have been based on measurements made on a few
astronauts on one mission. Because no two missi ons are
alike, extrapolating the results of one mission to space
flight in general is problem atic. The ever-expanding LSAH
data base makes comprehensive meta-analyses feasible and
a better assessment of long-term risks as more data are
accumulated on the ISS. Few measurements of changes in
lean body mass or body protein content with space flight
are available, so body weight is often used as a proxy for
lean body mass.
A number of investigators have used this data base and
important findings have resulted. Three analyses are rele-
vant to the topic of this review. (1) Factors associated with
weight loss. Weight loss is highly variable. Figure
2 shows
recent data from the ISS (Matsumoto et al.
2011; Smith
et al.
2004). Does analysis of the LSAH contribute new
information? (2) The type, incidence and severity of inju-
ries to the musculoskeletal system incurred during space
flight and (3) Are there long-term health-related problems
post-flight?
Risk from the weight/muscles loss
The two major direct effects of the muscle loss that have
been observed are weakness post-flight and the increased
incidence of low back pain during and after flight. Most of
the muscle loss occurs early in flight but continues at a
lower rate, once the initial response is over (Matsumoto
et al.
2011; Smith et al. 2004, 2005). After several months
in space, the loss of muscle (and bone) can be substantial.
The rate of body weight loss has been estimated as 2.4 %/
100 days in space (Matsumoto et al.
2011). Details of how
much of this weight loss is body fat and how much lean
body mass are not known.
Inflight, the most serious problem reported with the
musculo-skeletal system is an increased risk of minor
injuries secondary to muscle strain, usually manifesting as
low back pain early in flight (Wing et al.
1991). A recent
analysis of the available data in the LSAH data base by
Scheuring gave quantitative data on the frequency, severity
and possible causes of muscle injury during and after
spaceflight (Scheuring et al.
2009). 219 injuries were
attributed to the musculo-skeletal system (Table
1).
Figures 3 and 4 show the location of the injuries and type
of injury. None of the injuries can be considered to be
serious for the inflight phase of mission. Hand injuries,
abrasions and small lacerations were the most common
injuries. Crew activity in the space-craft, such as moving
between modules, exercise and EVA suit injuries were the
most common causes. The rate of exercise-related muscle
injuries was estimated to be 0.003 per flight day (Scheuring
et al.
2009). The rate did not increase with increased flight
duration. For a 1-year mission with six astronauts, this
translates into a probability of *7 injuries (Scheuring et al.
2009).
The adaptation to weightlessness leaves astronauts ill-
equipped for life with gravity when they return to earth.
Astronauts returning from even short duration space flights
of 1–2 weeks often experience muscle fatigue, weakness, a
lack of coordination in movement and muscle soreness
(Edgerton and Roy
1994; Riley et al. 1995; Stauber et al.
1990). Isometric, concentric and eccentric force develop-
ment declines by as much as 30 %. The loss of muscle
mass is responsible at least in part for the decrease in
muscle strength and increased fatigability observed after
space flight (Fitts et al.
2000; Grigorev et al. 1996; Leonard
et al.
1983; Nicogossian 1994; Vor obyov et al. 1981). The
post-flight muscle weakness has been a major focus of
counter-measure programs. The available flight data show
DAYS IN ORBIT
0 50 100 150 200
% BODY WT LOSS
-14
-12
-10
-8
-6
-4
-2
0
2
4
6
Fig. 2 Variability of weight loss on the ISS (Matsumoto et al. 2011;
Smith et al.
2005)
Table 1 The frequency of inflight injury has declined with space
vehicle development (Scheuring et al.
2009)
Program Total flight hours Incidence
Mercury 6 3.005
Gemini 1,940 0.049
Apollo 7,506 0.010
Skylab 12,352 0.002
Shuttle 1299,467 0.033
Apollo/Soyuz 652 0
NASA/MIR 22,693 0.004
ISS 56,581 0.008
Eur J Appl Physiol
123
that these problems do not seem to impair inflight perfor-
mance or post-flight health status for missions lasting up to
1 year (Smith et al.
2005; Zwart et al. 2009).
Three factors have been identified as contributing to the
inflight muscle loss. Firstly, the reductive remodeli ng,
secondly the level of pre-flight physical fitness and thirdly
an inability to maintain energy balance inflight.
The reductive remodeling
The reductive remodeling of the musculo-skeletal system is
an inevitable consequence of space flight. It has been found
on all missions with humans and rodents and all ground-
based models. Bed rest studies on subjects in energy bal-
ance have shown that the reduction in muscle size and
strength is due to the decreased work load on the muscle.
The major sites of the losses are the muscles and bones
with anti-gravity functions that are located in the trunk and
legs (Grigoriev and Egorov
1992; LeBlanc et al. 1995,
1996; Thornton and Rummel 1977; Whedon et al. 1977).
These losses have occurred on both US and Russian mis-
sions despite attempts to ensure an adequate diet and a
vigorous exercise regimen (Fitts et al.
2010; Koz lovskaya
et al. 1990; LeBlanc et al. 1996; Leonard et al. 1983).
In addition to a net loss of protein, there is a shift in
myosin isoforms from slow to fast isoforms (Fitts et al.
2000, 2010; Trappe et al. 2009). Fast twitch fibers are
primarily glycolytic and prone to fatigue with endurance.
This metabolic shift toward increased reliance on glycol-
ysis is found with space flight (Baldwin and Haddad
2001;
Fitts et al.
2001), the rat hind limb suspension model (Fitts
et al. 2000; Henriksen and Tischler 1988; Langfort et al.
1997) and bed rest (Acheson et al. 1995). Glycolysis is
very effective for high intensity short d uration acute
activities, but if sustained output is needed, an energy
profile where fat use is favored is desirable. And, as stated
above, this adaptive response leaves the astronauts ill-sui-
ted for the return to earth.
How serious a problem is this reduced capacity for
work? A recent Soyuz landing illustrates the worst case
scenario observed to date. After a 5-month flight, the
Soyuz re-entry vehicle landed somewhere in Kazakhstan. It
took more than 5 h to recover the crew. For safety reasons,
the crew had to get out of the landing capsu le unassisted. It
took them 5 h to accomplish what should have been a half-
hour task. The misadventure provides strong evidence for
impaired muscle functionality after Mars-like transit,
demonstrating serious weaknesses in crew performance.
All three crew members exhibited reduced capability, up to
voluntary immobility. Nevertheless, the inconvenience was
only temporary; the crew were rescued and transported to a
state-of-the-art rehabilitation facility.
Counter-measures for the reductive remodeling
Exercise
If a resistive exercise program is incorporated into the bed rest
protocol, the muscle loss can be prevented (Bamman et al.
1998; Ferrando et al. 1997; Loehr et al. 2011). This does not
appear to be the case with space flight. Exercise, the obvious
counter-measure has been repeatedly tried and since the
problem persists it is not unreasonable to assume that success
has been limited at best (Fitts
1996; Trappe et al. 2009).
Current counter-measures have focused on exercise.
Defining ‘success ’ depends on wha t the designated end-
point is. What should the end-point be? The question is
important. Much money, valuable crew time and resources
have been spent on trying to develop ‘effective’ counter-
Number of Injuries
0
20
40
60
80
100
Crew Activity
EVASuit
Exercise
Unknown
LES/ACES
Experiment
EVA
Egress
Fig. 3 Injury sites during space flight (Scheuring et al. 2009)
Number of Injuries
0
5
10
15
20
25
Hand
Foot
Shoulder
Arm
Wrist
Leg
Back
Neck
Trunk
Fig. 4 Injury frequency during space flight (Scheuring et al. 2009)
Eur J Appl Physiol
123
measures. Is the target set unrealistically high for the over-
compensated astronaut? Pre-flight astronauts are at peak
physical fitness, many engage in strenuous exercise regi-
mens preflight and so may have more to lose during a
period favoring deconditioning.
Data from the LSAH show that this does in fact occur.
Matsumoto et al. used the LSAH data base to investigate
which covariates predicted weight loss during spaceflight
(Matsumoto et al.
2011). The data base used involved 246
astronauts from Skylab to Shuttle to ISS with a total of 514
missions (some astronauts flew more than one mission).
The mean rate of weight loss was -2.4 % per 100 days
in space (Matsumoto et al.
2011). As previously men-
tioned, the weight loss is highly variable (Fig.
3). Type and
amount of pre-flight exercise were predictors of inflight
weight loss. Astronauts who reported walking, the least
stressful exercise as part of their pre-flight exercise pro-
gram lost less body weight than those who engaged in more
aggressive exercise regimens (body weight change:
-1.85 ± 0.19 %/100 days for exercise walkers, (n = 132)
vs. -2.33 ± 0.14 %/100 days for other exercise modalities
(n = 265, p = 0.05). Furthermore, pre-flight exercise ses-
sions of greater than 1 h predicted greater weight loss
during spaceflight (body weight change: -2.70 ± 0.30 %/
100 days for C1 h, n = 82 vs. -2.03 ± 0.12 %/100 days
for \1 h, n = 315, p = 0.02) (Matsumoto et al.
2011).
These findings are consistent with most astrona uts being in
an over-compensated state pre-flight; the nearer they are to
a normal baseline, the less the weight loss. If an astronaut
has more to lose to start with, should it be of concern if he
or she lose more protein inflight and shows a degree of
deconditioning?
The human species is very adaptable. While the com-
bination of adaptation and accommodation may not be
perfect, modern humans thrive in just about every eco-
logical niche available, including space flight. Adaptive
mechanisms are numerous ranging from darker skin color
in the tropics to increased oxygen carrying capacity at high
altitude. Two adaptations are particularly relevan t to space
flight. The first is a decreased reliance on muscle power.
The second pertains to energy balance. Acute minor defects
in the adaptation/accommodation process can have serious
chronic consequences. Does this also apply to space flight?
Adaptation to decreased work requirement from the
musculo-skeletal system is not a totally novel experience
for humans. Over the last *200 years, humans have
adopted from the lifestyle of our ancestral ‘hunter-gather-
ers relying on ’muscle power’ to one where the work is
done by machines and there has been a profound shift to a
much more sedentary lifestyle. Space flight is further along
this continuum than modern humans who drive to work at a
desk job to be followed by an evening of watching tele-
vision. How much is an open question. Humans seem to
have adapted rather well to a decreased need for skeletal
muscle by the millions on the ground and by the hundreds
in space. The only major adverse performance-related
consequences are an increased incidence of low back pain
and a decreased capacity to perform physical work. Low
back pain affects one in ever y three adults over the age of
50 (Manek and MacGregor
2005).
For the general population, a sedentary lifestyle is also
strongly associated with a pre-disposition toward devel-
oping obesity and hence metabolic syndrome. In turn
metabolic syndrome is a major contributing factor to the
chronic metabolic diseases such as type II diabetes, car-
diovascular disease and some cancers. Nevertheless, met-
abolic syndrome is not likely to be a serious health risk
factor for astronauts because once a mission is over,
astronauts resume their normally active lives.
For ground-based humans, decreased work capacity
need not be a problem. Not so for astronauts where there is
a requirement to maintain a certain level of physical fitness.
An unanswer ed question here is, what is the level of fitness
required to support the mission? For sure it should be
sufficient to enable astronauts to complete extra-vehicular
activities (EVA) and emergency egress with a margin of
safety. Should it go beyond the need to minimize the
inflight losses to facilitate recovery post-flight? Or should
post-flight problems be treated after return to earth as part
of the rehabilitation program? The answer to these ques-
tions should define the objectives and type of the inflight
exercise program.
Targeted dietary interventions
Exercise is anabolic leading to an increase in protein mass.
There is ample ground-based data showing that protein
accretion with exercise can benefit from additional amino
acids being available. During the past few years, there has
been much interest in the use of dietary amino acids sup-
plements to exercise to decrease the losses in muscle mass
and strength observed after space flight.
The published bed rest study results do not make a
convincing case for amino acid/protein supplementation as
countermeasure for lessening loss in protein mass during
space flight (Blanc and Stein
2011). A single amino acid
supplementation study with women showed no benefit
from leucine supplementation (Trappe et al.
2007). Of the
six published bed rest protein supplementation studies,
three showed benefit, three did not. A recent development
in evaluating protein requirements in humans may explain
the discrepancy in the results. The current official RDA/
DRI (0.8 g/kg/d) could under-estimate requirements by as
much as 40 % (Elango et al.
2008; Humayun et al. 2007).
Interestingly, the three supplementation studies that
showed benefits fed their test subjects a baseline protein
Eur J Appl Physiol
123
levels around the old RDA/DRI for protein i.e. 0.6–0.8 g/
kg/d. The three that did not show benefit gave the subjects
a baseline protein intake of 1.0 or more g/kg/d of protein.
Thus, the positive effects from protein supplementation
observed in some of the studies might just reflect the
benefits of supplementing a marginally adequate baseline
protein intake during bed rest because of under-estimation
of the actual RDA/RDI rather than a protective effect
against bed rest-induced disuse (Blanc and Stein
2011).
Although the precise protein requirements for long-dura-
tion space flight are not known, it is not likely to be sub-
stantially different from ground-based needs (Lane et al.
2007). The available dietary prot ein intake of astronauts is
usually well above the current RDA/DRI (Table
2). Minor
adjustments in amino acid/protein intakes are unlikely to
significantly affect crew health.
Endocrine interventions
Endocrine factors are ob viously involved in the regulation
of muscle mass and power. Three of the major hormones
known to regulate muscle mass are testosterone, cortisone
and insulin. Insulin and testosterone are anabolic; cortisol
is catabolic and usually associated with a stress response.
Short term shuttle data suggest that testosterone is
decreased, cortisol either increased or unchanged and
insulin resistance increased. In the case of cortisol, if there
is an increase, it does not seem to apply to all astronauts
and in the case of insulin, the measurements are indirect
being based on urinary C-peptide excretion (Ferrando et al.
1999, 2002; Stein 2001). However, data from short term
missions are likely to be complicated by the acute adaptive
changes that occur as the body adjusts to fluid shifts, dis-
turbed circadian rhythms, loss of tension on the weight
bearing muscles, the novel diet and the emotional response
to an exhilarating experience. Data from long-duration
missions are more informative about adaptation/accom-
modation to space flight.
The primary questions here are: (i) what are the changes
with long-duration space flight (ii) what would the inter-
ventions be to reduce the rate of muscle deconditioning? A
recent study by Smith and colleagues reviewed all the data
for testosterone and cortisol from the early long-duration
Skylab flights through the shuttle missions to the more
recent ISS missions resolves the question for testosterone
and cortisol. Essentially, they found no change with either
testosterone or cortisol with long-duration space flight
(Smith et al.
2012). ‘No matter what form of testosterone
(total, free, or bioavailable) was measured, or with which
method, there was clearly no change during long-duration
space flight (Smith et al.
2012). Although there was much
scatter in the serum cortisol data, it too did not change with
long-duration space flight.
The phrase ‘no change implies that there were ‘no
detectable change within the limits of measurement’. There
is ‘noise’ in the measurement because of limiting sampling
(maximum of only five inflight data points) and inadequate
dietary intake inflight which could complicate data inter-
pretation. The implication is that failure to detect any
change precludes developing an endocrine-based inter-
vention to attenuate the muscle loss because the experi-
mental data indicate no change. In fact there might be
change, either too small to detect, or the changes occurring
at different times during the day from when the samples
were collected. Much more data would be required to test
for this and there is no guarantee that anything useful
would be found. The default position is that the body has
adapted very well to life without gravity.
Either way, the Smi th data strongly suggest that when
compared to other approaches for maintaining health dur-
ing long-duration space flight, endocrine studies are not
likely to be as productive as investigating exercise
modalities, nutrition etc. An interesting point from the
Smith study was the discrepancy with bed rest and animal
models. Long-duration space flight showed no change in
cortisol, whereas there was an increase with bed rest (Smith
Table 2 Energy and protein intake during space flight
Mission Protein intake
G protein kg
-1
d
-1
Adequate? Energy intake
Kcal kg
-1
d
-1
Adequate? Reference
Apollo 1.09 ± 0.05 Adequate 24.9 ± 1.0 Inadequate Lane and Rambaut (
1994)
Skylab 2 1.37 ± 0.02 Adequate 39.2 ± 0.7 Adequate Leach and Rambaut (
1977)
Skylab 3 1.49 ± 0.12 Adequate 43.3 ± 4.8 Adequate Leach and Rambaut (
1977)
Skylab 4 1.62 ± 0.02 Adequate 43.5 ± 0.7 Adequate Leach and Rambaut (
1977)
Shuttle, early 1.01 ± 0.10 Marginal 27.0 ± 1.9 Inadequate Lane and Rambaut (
1994)
SLS1/2 1.11 ± 0.06 Adequate 34.4 ± 3.1 Adequate Stein (
2001)
LMS 0.81 ± 0.08 Inadequate 24.4 ± 2.4 Inadequate Stein et al. (
1999b)
MIR 1.13 ± 0.19 Adequate 26.1 ± 2.4 Inadequate Stein et al. (
1999a)
ISS 1.37 ± 0.12 Adequate 30.7 ± 2.5 Inadequate Smith et al. (2005)
Eur J Appl Physiol
123
et al. 2012). Apparently, space flight is a more comfortable
situation than lying in bed with a downward tilt for weeks
at a time. Results from ground-based models are data from
model systems that have to be verified by flight
experiments.
Low back pain
The other major effect on skeletal muscle is an increased
susceptibility to transient low back pain (Scheuring et al.
2009). At the worst, low back pain will compromise
mobility and at best subject the individual to discomfort.
Three approaches are actively being pursued for the inflight
situation.
Counter measures—low back pain
1. Engineering modification to the design of the space
vehicle. There has been success here. Analysis of the
LSAH data base shows a progressive reduction in the
incidence of low back pain from Skylab to the ISS.
Scheuring attributed this trend to improvements in
cabin design (Scheuring et al.
2009).
2. Exercise paradigms based on the results of bed rest
studies. Aerobic or low load exercise is not as effective
in maintaining muscle size during bed rest as high load
exercise (Suzuki et al.
1994; Zange et al. 2009). Low
load exercise (1 9 body weight) does not prevent the
atrophy of the spinal extensors during long-term bed
rest but higher loads (1.5 9 body weight) do. Com-
plicating result interpretation is variability with type of
exercise (Akima et al.
2003; Alkner and Tesch 2004;
Armbrecht et al. 2010; Belavy et al. 2009; Shackelford
et al.
2004).
3. Supplementing exercise with vibration. Whole body
vibration increases muscle activation (Cochrane et al.
2009; Roelants et al. 2006), so it is possible that this
might be additive to exercise. Indeed, structural studies
have shown that high load resistive exercise with
whole body vibration reduces the changes in the cross
sectional areas of extensor and psoas muscles (Belavy
et al.
2008). A recent bed rest study addressed the
question whether high load resistive exercise plus
vibration was better than resistive exercis e alone in
reducing the lumbar muscle CSA changes and the
incidence of lower back pain after 60 days of bed rest
(Armbrecht et al.
2010; Belavy et al. 2010). The
exercise counter-measure was succe ssful in reducing
the muscle cross sectional area losses, but there was no
extra benefit from vibration. Rather disconcertingly,
exercise subjects reported an increased incidence of
low back pain during the first week of bed rest (Belavy
et al.
2010).
4. A caveat. The number of subjects was small, the
instrumentation for testing vibration (and exercise)
cumbersome and these might have contributed to the
null result. The other point to be aware of is that the
lower back pain is transitor y, and only seems to be a
minor inconvenience. Is development of a counter-
measure for something that is transitory, manageable
and not as health threatening as some of the other
adverse effects of long-duration flight might be (e.g.
radiation, social factors) cost effective? On the ground,
non-prescription drugs are often helpful!
The energy deficit
The energy requirements for space flight are *1.7 9 RMR
(Lane
1992; Smith et al. 2005; Stein et al. 1999b; Zwart
et al. 2009). A consistent finding with space flight has been
that astronauts fall short of this goal. Smith reported that
the average intake on the ISS was
*80 % of recommended
(Smith et al.
2005; Zwart et al. 2009). For small (\*10 %)
energy intake deficits the body adapts by reducing prot ein
turnover, substrate cycling, involuntary physical activity
etc. (Stein
2001). For larger energy deficits such as those
found with the ISS, adaptation is not possible. The weight
loss is chronic, in the long-term incompatible with health
and eventually life-threatening.
From a meta-analysis of data in the LSAH data base,
Matsumoto et al. concluded that if weight loss continued at
the rate currently observed on the ISS, clinically significant
weight loss (10 % or more) would occur in the second year
of a future long-term missions (Matsumoto et al.
2011). A
loss of *30 % is life-threatening.
The inflight energy deficit is enough to negatively impact
protein metabo lism, both from the ability to maintain pro-
tein turnover and to minimize the protein losses from the
reductive remodeling. With bed rest, a 15–20 % decrease in
the whole body protein turnover rate is found and is due to a
*50 % decrease in muscle protein synthesis (Ferrando
et al.
1996; Gibson et al. 1987). A much greater decrease
*50 % was found with long-duration space flight on the
Russian Space Station, MIR. The reason was that energy
intake was 25 % lower inflight (Stein et al.
1999a).
Increasing inflight exercise without a corresponding
increase in intake appears to exacerbate the negative protein
balance. Figure
5 compares energy intake, expenditure,
balance and nitrogen balance for the two very similar shuttle
missions, SLS1/2 and LMS. The periods of comparison are
the first 9/12 days on SLS1/2 (Stein et al.
1996) and the first
12 days for LMS (Stein
2001; Stein et al. 1999b). The same
Eur J Appl Physiol
123
orbiter (Columbia) in the same configuration (with the Space
Lab module) was used for both missions. Both missions were
very busy missions with science as the primary mission
objective. Crew members were very active moving about the
cabin throughout the day doing investigator originated
experiments. The principal difference was that LMS had
extensive exercise requireme nts as part of the scientific
program. Dietary intake was not regulated on either mission.
The SLS1/2 astronauts did not exercise, ate more and were in
approximate energy balance. On LMS, energy intake failed
to meet extra energy needs of the exercise program and the
protein loss was much greater (Fig.
5) (Stein 2000). A high
rate of aerobic exercising is extremely costly in energy needs
(Convertino
1990).
Interestingly, a recent 60-day bed rest study on two
groups of women replicated the flight observations (Berg-
ouignan et al.
2010). One group followed a rigorous
exercise regimen during bed rest; the other (control) group
did not. The control group was in slight negative energy
balance, the exercised group was in marked negative
energy balance during bed rest. They concluded that
humans can adjust energy intake to meet needs in the
absence of exercise but not with exercise.
Testing exercise modalities and equipment is a very high
priority on the ISS. But testing an exercise program when
energy balance is negative does not provide a valid
assessment of the effectiveness of the exercise program in
preventing mus cle loss and weakness because of com plex
interactions between the anabolic effects of exercise and
the limited availability of energy to support it. This cannot
be done unless the negative energy balance problem is
corrected. Thus, we really do not know how successful the
inflight exercise programs are. They might be very effec-
tive if the astronauts were in energy balance.
Energy deficits—counter measures
Is it reasonable to expect human physiology to fully adapt?
Based on ground-based population observations, it seems
highly improbable that the inability to maintain energy bal-
ance will self-correct. The food supply has changed dramati-
cally over the last 50 years and there have been clinically
significant effects. Recent epidemics of a number of otherwise
unrelated diseases are now attributed to a consequence of a
mismatch between the world we live in today and the Paleo-
lithic bodies we have inherited. With the combination of
lifestyle and diet changes, for many people there is an inability
to regulate energy balance. The hypothesis provides a rational
explanation for such well-known diseases as cardiovascular
disease, diabetes and obesity. The central problem is obesity.
Obesity is the end result of an inability to maintain energy
balance. The prevalence of obesity in the US, as defined by
proportion of adults with BMI’s greater than 30 has increased
from less than 20 % in 1980 to more than 30 % by 2010. This
time period is far too short for genotypic changes; the changes
are phenotypic.
Normally dietary intake fluctuates around energy
requirements; long-term bala nce is effected by a complex
and incompletely understood combination of effects on the
intake side, (appetite regulation) and the energy expendi-
ture side (substrate cycling, brown adipose tissue thermo-
genesis, non-exercise-induced thermogenesis, physical
activity etc.). In contrast to the elegant reductive remod-
eling of the anti-gravity muscles, metabolism has not
accommodated as well. Energy intake during space flight
fails to balance expenditure.
To this author, this does not seem like an insurmount-
able problem even though the underlying mechanisms are
poorly understood (Bergouignan et al.
2010; Westerterp
2010). The energy costs of spaceflight are reasonably well
known, 1.7 9 RMR (Lane 1992; Smith et al. 2005; Stein
et al.
1999b; Zwart et al. 2009) as are the overall nutritional
requirements (Lane et al.
2007). Some adjustment on an
individual basis might be required for astronauts involved
in extensive extr a-vehicular activities (EVA). On the ISS
daily dietary intake is routinely monitored so it should not
be too difficult to estimate an astronauts energy balance on
a weekly basis and require supplementary energy intake on
an as needed basis.
Bone: counter-measur es
Like muscle, the inflight losses of bone occur in spite of
aggressive exercise regimens with a variety of very
expensive devices (Cavanagh et al.
2005; Keyak et al.
2009; Lang et al. 2004). There are two conclusions that can
be drawn. (1) Further development of exercise regimens
Fig. 5 Comparison of energy intake, expenditure and balance and
nitrogen balance during space flight on the SLS1/2 and LMS shuttle
missions (Stein et al.
1996, 1999b). Data are mean ± SEM
Eur J Appl Physiol
123
and equipment is not likely to be very productive and cost
effective. (2) As discussed above for the muscle problem
and below for the bone problem, they are manageable.
For bone, there are options other than ‘more’ or ‘dif-
ferent’ exercise. On the ground, much success with mil-
lions of women has been obtained by giving a
bisphosphonate to reduce the post-menopausal resorption
of bone. Bisphosphonates have also been successful with
bed rest (LeBlanc et al.
2007). There is currently a bis-
phosphonate treatment study on the ISS. This is a crucial
experiment. If even partial success is achieved, the already
low inflight risks from the bone loss would be further
reduced. The level of risk from the reductive remodeling of
the musculo-skeletal system could be man aged by a com-
bination of bisphosphonates, some exercise, an adequate
diet and care to avoid ‘heavy lifting’.
Bone loss will be a problem after return to 1 g from very
long missions. Recovery is a very slow process; it takes
much longer than the actual duration of the mission (Sib-
onga et al.; Loehr et al.; Sibonga et al.
2007). But, however
slow the recovery of lost bone is in a rehabilitation center
after a mission it will not impact the actual mission. After
return to earth, extensive rehabilitation facilities are
available. So, it might be a much more practical option to
focus on limiting the inflight bone loss enough to minimize
any inflight risk rather than try to prevent the inflight bone
loss (Payne et al.
2007).
Osteoporosis is a formidable problem affecting millions
of women (and some men). It is the obje ctive of major
research efforts by government health agencies. The rela-
tively small amounts of money spent looking at disuse
bone loss in a very small number of subjects (astronauts)
should not be sold to the public as a promis e by the space
program to advance the treatme nt of osteoporosis.
Targeting counter-measures to the mission
Counter-measures are designed to keep the astronauts as
close as possible to their pre-flight status. How would the
inflight weight loss look if it were expressed as percentage
of body weight 6 or 12 months post-flight? As previously
discussed, analysis of data in the LSAH suggests it would
be smaller (Matsumoto et al.
2011).
Rather than aim for maintaining pre-flight status, inflight
counter-measures shoul d be targeted at maintaining a level
of fitness to: (i) support EVA activity and (ii) meet the
requirements of the post-flight phase. The former does not
appear to be a problem. An important factor here has been
progressively decreasing the work load required for EVA
activity by improvements in suit design. While some
exercise should be done throughout the mission, limiting an
aggressive exercise program to the last couple of months of
a long-duration mission might lessen the impact of exercise
on energy balance inflight and strengthen the muscles
before landing.
For the post-flight period, there are four scenarios
depending on the mission involved. (1) Return to earth, (2)
a Mars landing (1/3 g), (3) a return to the Moon and (4) an
asteroid landing.
(1) Return to earth is not a problem; there are already
excellent and well -tested facilities in place for astronaut
rehabilitation. (2) Current Space Agency plans propose a
Mars landing far into the future—2040 or even later. Who
knows how far science will have progressed in the inter-
vening years? There is no urgency to continue to evaluate
late 20th technology for an event that is not likel y to occur
until the mid 21st century. (3) For a moon landing with an
extended stay, there is effectively no gravity. Humans have
already have had experience with the problems encoun-
tered on the moon nearly half a century ago. The space
suits were very cumbersome and restricted mobility and
flexibility. Much improvement has been made with EVA
space suits in the intervening half century so this should
improve both comfort and the ability to work (Scheuring
et al.
2009). (4), Likewise for an asteroid landing—at the
time of writing, NASA’s preferred immediate short term
(*2020–2025) objective because there is no gravity.
Conclusions
1. A case can be made for down-grading the inflight
exercise program relative to the other problems for
long-duration space flight. Some exercise is needed,
but maybe not so much as currently planned? How
much is the question? Counter-measures are designed
to keep the astronauts as close as possible to their pre-
flight status. Are we over-estimating the inflight mus-
cle losses? If the inflight weight loss was expressed as
percentage of the body weight 6 or 12 months pre- or
post-flight it would probably be smaller than when it is
compared to the immediate pre-flight period (Mat-
sumoto et al.
2011).
2. An increase in the incidence of low back pain occurs.
Given that ground treatments are not very successful,
the problem is not disabling, is transient and self-
resolving the problem is manageable. Attempts to
develop a counter-measure are not likely to be cheap
or productive, but success could have considerable
benefits to society!
3. Because of the underlying energy deficits, inflight
exercise regimens have not been properly tested.
4. As missions become longer, the inability to maintain
energy balance will become progressively more
important. Solving it is not a sophisticated technical
Eur J Appl Physiol
123
problem; a combination of dietary record keeping and
monitoring body weight—procedures already avail-
able and commercially available energy bars should
suffice.
5. Exaggerating the potential negative consequences of
space flight-induced changes in the skeletal muscle has
been counter-productive. It has raised concerns with
legislators that may be unnecessary about the safety of
the human space program and has led governments to
delay into the far future the mission that is of real
interest to the public, a Mars landing. If the mission is
not going to be for another 30–50 years, why spend
money now? The net result has been a loss interest in
the human space program.
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... Thus, the increased energy expenditure associated with exercise countermeasures appears not to be accompanied by increased energy intake, resulting in a negative energy balance. In fact, a negative nitrogen balance-suggesting loss of muscle mass-was also reported in-flight-despite performing exercise countermeasures (Stein, 2000;Stein, 2013). However, interestingly during the first 2 weeks of the Space Life Sciences (SLS) 1 and 2 Shuttle missions (Stein et al., 1996) where no exercise countermeasures were performed, energy and nitrogen balance were stable, suggesting a muscle mass preservation (Stein, 2000). ...
... In space, as with the skeletal system, the muscles most affected are those with a prime 'anti-gravitational' function such as those in the trunk and lower limbs (Stein, 2013;Winnard et al., 2019). Based on the data presented in the review of Winnard et al. (2019) moderate effects (Hedges g ≥ 0.6) occur within seven to 14 days of HDTBR, while large effects (Hedges g ≥ 1.2) occur after 28-35 days. ...
... Restoration of muscle mass and strength of crewmembers during the post-flight rehabilitation period seems to occur at the same rate, or even at a faster rate, of the initial atrophy (Leblanc et al., 1990;Tesch et al., 2005;Petersen et al., 2017). Thus, definition of the imposition of an exercise holiday should consider the high degree of inter-individual variability expressed in muscle outcomes (Gernand, 2004;Stein, 2013;Winnard et al., 2019). Consideration of relative effects should be made as 'stronger' crewmembers may be able to retain operational functionality whilst experiencing greater absolute and relative decrements of their pre-flight muscle mass and strength compared to those with lower pre-flight levels. ...
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In an attempt to counteract microgravity-induced deconditioning during spaceflight, exercise has been performed in various forms on the International Space Station (ISS). Despite significant consumption of time and resources by daily exercise, including around one third of astronauts’ energy expenditure, deconditioning—to variable extents—are observed. However, in future Artemis/Lunar Gateway missions, greater constraints will mean that the current high volume and diversity of ISS in-flight exercise will be impractical. Thus, investigating both more effective and efficient multi-systems countermeasure approaches taking into account the novel mission profiles and the associated health and safety risks will be required, while also reducing resource requirements. One potential approach is to reduce mission exercise volume by the introduction of exercise-free periods, or “ exercise holidays ”. Thus, we hypothesise that by evaluating the ‘recovery’ of the no-intervention control group of head-down-tilt bed rest (HDTBR) campaigns of differing durations, we may be able to define the relationship between unloading duration and the dynamics of functional recovery—of interest to future spaceflight operations within and beyond Low Earth Orbit (LEO)—including preliminary evaluation of the concept of exercise holidays. Hence, the aim of this literature study is to collect and investigate the post-HDTBR recovery dynamics of current operationally relevant anthropometric outcomes and physiological systems (skeletal, muscular, and cardiovascular) of the passive control groups of HDTBR campaigns, mimicking a period of ‘exercise holidays’, thereby providing a preliminary evaluation of the concept of ‘exercise holidays’ for spaceflight, within and beyond LEO. The main findings were that, although a high degree of paucity and inconsistency of reported recovery data is present within the 18 included studies, data suggests that recovery of current operationally relevant outcomes following HDTBR without exercise—and even without targeted rehabilitation during the recovery period—could be timely and does not lead to persistent decrements differing from those experienced following spaceflight. Thus, evaluation of potential exercise holidays concepts within future HDTBR campaigns is warranted, filling current knowledge gaps prior to its potential implementation in human spaceflight exploration missions.
... This need for exploration has increased with the imminent return to the Moon and the potential for exploration of Mars (NASA 2014(NASA , 2020. Current research findings indicate that nearly all systems in the human body will be adversely affected by the altered gravity in extraterrestrial environments; these adverse effects include bone injury (Stein, 2012;Shiba et al., 2017), heart rate alterations (Liu et al., 2015), intracranial hypertension and visual impairment (Zhang and Hargens, 2018), and increased urinary stone risk (Liakopoulos et al., 2012). However, most research has focused on the musculoskeletal system because of its close relationship with gravity (Morey-Holton et al., 2005). ...
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... A large challenge to developing machine learning applications for human spaceflight is the severe limitation in data for training and validating machine learning models. Less than 600 individuals have flow to space across a period of multiple decades 36 . In-flight ophthalmic imaging modalities have also differed over these decades which adds another layer of dataset insufficiency. ...
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Long-duration spaceflight introduces the human body to various risks and physiological changes, including increased radiation exposure, bone density loss, skeletal muscle atrophy, and vision changes. The field of space medicine seeks to further understand and potentially mitigate these risks to protect astronaut health during spaceflight. Protection and mitigation of these consequences on the human body may also help to uphold mission performance for prolonged space missions. In this chapter, we discuss some of the various hazards that have been identified in the spaceflight environment, as well as several countermeasure strategies that have been tested. This chapter serves as an introduction to the field of space medicine and a primer for the following textbook chapters on Spaceflight Associated Neuro-Ocular Syndrome.
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Summary During and after prolonged bed rest, changes in bone metabolic markers occur within 3 days. Resistive vibration exercise during bed rest impedes bone loss and restricts increases in bone resorption markers whilst increasing bone formation. Introduction To investigate the effectiveness of a resistive vibration exercise (RVE) countermeasure during prolonged bed rest using serum markers of bone metabolism and whole-body dual X-ray absorptiometry (DXA) as endpoints. Methods Twenty healthy male subjects underwent 8 weeks of bed rest with 12 months follow-up. Ten subjects performed RVE. Blood drawings and DXA measures were conducted regularly during and after bed rest. Results Bone resorption increased in the CTRL group with a less severe increase in the RVE group (p = 0.0004). Bone formation markers increased in the RVE group but decreased marginally in the CTRL group (p < 0.0001). At the end of bed rest, the CTRL group showed significant loss in leg bone mass (−1.8(0.9)%, p = 0.042) whereas the RVE group did not (−0.7(0.8)%, p = 0.405) although the difference between the groups was not significant (p = 0.12). Conclusions The results suggest the countermeasure restricts increases in bone resorption, increased bone formation, and reduced bone loss during bed rest.
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Objectives: The current study aimed to examine the effectiveness of a resistive vibration exercise countermeasure during prolonged bed-rest in preventing lower-limb muscle atrophy. Methods: 20 male subjects underwent 56-days of bed-rest and were assigned to either an inactive control, or a countermeasure group which performed high-load resistive exercises (including squats, heel raises and toe raises) with whole-body vibration. Magnetic resonance imaging of the lower-limbs was performed at twoweekly intervals. Volume of individual muscles was calculated. Results: Countermeasure exercise reduced atrophy in the triceps surae and the vastii muscles (F>3.0, p<.025). Atrophy of the peroneals, tibialis posterior and toe flexors was less in the countermeasure- subjects, though statistical evidence for this was weak (F≤2.3, p≥.071). Atrophy in the hamstring muscles was similar in both groups (F<1.1, p>.38). The adductor longus, sartiorius and rectus femoris muscles showed little loss of muscle volume during bed-rest (F<1.7, p>.15). Conclusions: The countermeasure exercise programme was effective in reducing atrophy in the extensors of the knee and ankle but not the hamstrings.