COMMENTARY
Open Access
Ultramarathon is an outstanding model for the
study of adaptive responses to extreme load and
stress
Grégoire P Millet1* and Guillaume Y Millet2
Abstract
Ultramarathons comprise any sporting event involving running longer than the traditional marathon length of
42.195 km (26.2 miles). Studies on ultramarathon participants can investigate the acute consequences of ultra-
endurance exercise on inflammation and cardiovascular or renal consequences, as well as endocrine/energetic
aspects, and examine the tissue recovery process over several days of extreme physical load. In a study published
in BMC Medicine, Schütz et al. followed 44 ultramarathon runners over 4,487 km from South Italy to North Cape,
Norway (the Trans Europe Foot Race 2009) and recorded daily sets of data from magnetic resonance imaging,
psychometric, body composition and biological measurements. The findings will allow us to better understand the
timecourse of degeneration/regeneration of some lower leg tissues such as knee joint cartilage, to differentiate
running-induced from age-induced pathologies (for example, retropatelar arthritis) and finally to assess the
interindividual susceptibility to injuries. Moreover, it will also provide new information about the complex interplay
between cerebral adaptations/alterations and hormonal influences resulting from endurance exercise and provide
data on the dose-response relationship between exercise and brain structure/function. Overall, this study represents
a unique attempt to investigate the limits of the adaptive response of human bodies.
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Keywords: Cerebral adaptations, extreme environment, overload pathologies, ultra-endurance
Background
While the industrialized world adopts a sedentary life-
style, ultramarathon running races have become increas-
ingly popular in the last few years, notably in the US,
Europe, Japan, Korea, and South Africa. The ability to
run long distances is also considered to have played a
role in human evolution [1]. This makes the issue of
ultra-long distance physiology relevant. Ultramarathons
are basically either performed on mostly flat roads or
tracks, or run on varied terrain trails. They comprise
races that are completed over the space of multiple days
(for example, 6 days), with the winner being the one that
covers the most distance within this set period of time or
races that cover a specified distance during a single stage,
which normally range from 50 km to 160.9 km or over
several stages. The paper by Schütz et al. [2] explores the
physiological changes that occur in runners during this
latter type of events, probably one of the most demand-
ing physical exercise in humans, maybe only overpassed
by polar expeditions (for example, Scott’s party man-
hauling their sleds across the Antarctic for 159 days in
1911/1912, [3]) or other individual challenges such as the
run around Europe in 2009/2010, that is, 27,012 km in
1 year (74 km/day), by the Frenchman Serge Girard. We
recently reviewed the origin of muscle fatigue after pro-
longed exercises lasting from 30 minutes to several hours
[4] and found that the knee extensors isometric strength
loss increased in a non-linear way with exercise duration,
that is, there was a plateau after approximately 20 h of
running. Recent findings from our group confirm this
result for an even longer mountain ultramarathon (Tor
des Geants, 330 km; unpublished results). These fatigue
studies and other experiments conducted on inflamma-
tion [5], cardiovascular or renal consequences [6,7],
* Correspondence: gregoire.millet@unil.ch
1ISSUL Institute of Sport Sciences, Department of Physiology, Faculty of
Biology and Medicine, University of Lausanne, Switzerland
Full list of author information is available at the end of the article
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© 2012 Millet and Millet; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
endocrine/energetic aspects (see for example [8]) help to
understand acute consequences of an ultra-endurance
exercise (generally shorter than 24 h, more rarely 2 or
6 days) but do allow examining recovery process, that is,
tissue degeneration/regeneration over several days of
extreme physical load.
Trans Europe Foot Race: studying the limits of
human endurance
In an observational cohort study on 44 ultramarathon
runners over 4,487 km in 64 stages from South Italy to
North Cape, Norway (the Trans Europe Foot Race
2009), Schütz et al. [2] recorded daily sets of data from
magnetic resonance imaging (MRI), psychometric, body
composition and biological measurements. Beyond the
logistical achievement of following the runners and
moving a 30-m, 45-tonne 1.5 Tesla whole-body MRI
across Europe (!), they succeeded with a high rate of test
completion and data collection.
This ‘field’ experiment is unique since it is impossible
to expect subjects pushing to (and sometimes beyond)
their limits for 64 days without any day of rest in a
laboratory setting. Such commitment can be achieved
only in an official competition and is absolutely necessary
for exploring the adaptive responses in healthy subjects
at the limit of stress.
In our view, in the field of sports medicine, the longitu-
dinal design of this study will allow us to better under-
stand the time course of degeneration/regeneration of
some lower leg tissues as knee joint cartilage or ventral
tibial periosteum, to describe the adaptive responses (for
example, red bone marrow hyperplasia), to differentiate
running-induced from age-induced pathologies (for
example, retropatelar arthritis), to understand why some
painful reactions (for example, ‘shin splints’) can be
‘over-run’ whereas others lead to severe injuries (for
example, stress fracture) and finally to assess the interin-
dividual susceptibility to injuries.
This study will also bring new information about the
complex interplay between cerebral adaptations and hor-
monal influences resulting from endurance exercise. To
date, it is known that moderate exercise is beneficial to
brain heath (for example, increased perfusion or
increased brain-derived neurotrophic factor (BDNF))
[9,10]. But the potential deleterious effects (for example,
atrophy, ischemia, brain lesions) of extreme loads on
brain volume, plasticity and functionality are unknown.
In our opinion, these data are paramount for better
understanding the dose-response relationship between
exercise and brain structure/function. We have shown
that central fatigue was a major issue in long-distance
running exercise (see, for example, [11]) yet, to the best
of our knowledge, no studies have really assess cerebral
alteration related to this type of exercise. This is because
the observed decrease in voluntary activation does not
mean that cortical alterations really occur, since periph-
eral changes, that is, the combination of influences
including excitatory and inhibitory reflex inputs from
muscles, joints, tendons and cutaneous afferents, may
inhibit central drive at the spinal and supraspinal levels.
Also of interest is the investigation into pain perception
and the possibility to describe interindividual differences
in mechanisms of coping. Hormonal mechanisms (for
example, cortisol) and neurotransmitters (for example,
tryptophan, serotonin) are known to modulate the pain
perception [12]. But most previous studies were limited to
a single pain stimulus, whereas in the study of Schütz et
al. [2] the stimuli are different among subjects and also
fluctuating. The possibility of crossvalidation between the
MRI, the psychometric and the biological results is pro-
mising for better describing the time course of factors
influencing the fluctuation of pain throughout the race.
Future directions and conclusions
This study provides the opportunity to explore the
adaptive responses of humans submitted to the extreme
load and stress induced by a 4,487-km road race. The
methods used will allow investigation into various sub-
systems and their interaction in terms of tissue degen-
eration/regeneration,
pain
coping
or
cerebral
adaptations. Future research directions can combine
additional techniques such as transcranial magnetic sti-
mulation (to assess cortical excitability and inhibition
and supraspinal voluntary activation), cerebral multi-
channel near-infrared spectroscopy (to measure tissue
hemodynamics), and electroencephalography or cerebral
MRI, the latter in particular to assess long term cerebral
alterations as in Schütz et al. [2].
It is uncertain if/how the findings in Schütz et al.
paper can be translated to the fields of pathophysiology
or critical illness, since the stress induced by the run-
ning load is highly specific. However, one may assume
that some of the scientific knowledge accumulated will
help in better understanding of adaptive responses.
Since it is a road stage race, it is likely that the adap-
tive responses to fatigue would be largely different in
other environments/conditions such as high altitude,
heat, mountainous competition or sleep deprivation.
The exploration of exercising in such ‘extreme environ-
ments’ that often cannot be performed in a laboratory is
an extending field of sports physiology or sports medi-
cine. Together with large epidemiological surveys on
ultramarathon runners that still have to be conducted,
the amazing experiment of Schütz et al. [2] represents a
unique attempt to investigate the limits of adaptive
response of human bodies.
Millet and Millet BMC Medicine 2012, 10:77
http://www.biomedcentral.com/1741-7015/10/77
Page 2 of 3
Author details
1ISSUL Institute of Sport Sciences, Department of Physiology, Faculty of
Biology and Medicine, University of Lausanne, Switzerland. 2Université de
Lyon, F-42023, Saint Etienne, France.
Authors’ contributions
GPM and GYM drafted the manuscript and gave final approval for
publication.
Competing interests
The authors declare that they have no competing interests.
Received: 10 July 2012 Accepted: 19 July 2012 Published: 19 July 2012
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Pre-publication history
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Cite this article as: Millet and Millet: Ultramarathon is an outstanding
model for the study of adaptive responses to extreme load and stress.
BMC Medicine 2012 10:77.
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Ultramarathon is an outstanding model for the study of adaptive responses to extreme load and stress.
Millet, Grégoire P,Millet, Guillaume Y