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placebo effect and physical fatigue are two fields of research that are of
great interest for the benefits they could provide to many different groups of
people.  These are two seemingly
unrelated fields, but there is value in studying them both.  They intersect where the placebo effect
begins to produce physiological changes and where fatigue is defined by the
limits of the brain.  Yet, research in
these subjects is scarce.

            Further investigation into these
topics would be critical for coaches, athletes, and anyone else who seek to
push their physical limits.  At a time
when athletes and other top performers are willing to utilize any method to
gain an edge, even ones that are harmful or ethically questionable, the
scientific community has a responsibility to investigate safer options.  Aside from athletes, many others could
benefit from such research.  Neuroscience
has never been more advanced and we learn more every day about the importance
of psychological factors in every field. 
It is vital that research on these topics be conducted and the
literature both reviewed and expanded.

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History of the Placebo Effect

            The placebo effect can be defined as
a beneficial effect, produced by a placebo drug or treatment, that cannot be
attributed to the properties of the placebo itself, and must therefore be due
to the patient’s belief in that treatment. 
Placebos are inert drugs or treatments that nevertheless result in a
tangible neurobiological effect.  Healers
and doctors have always used such remedies and sham treatments, long before the
existence of modern medicine.  Placebo as
a concept has existed in the medical literature for several centuries, but the
first experimental trial was conducted in 1799 (Price et al. 2008).  The placebo effect has always been of
interest, of course, but interest in it has dramatically increased in the last
40 years (Miller and Kaptchuk, 2008). 
There has been much debate over how the placebo can be called inert if
it elicits a physical response.  Despite
all the research and interest, it has had little practical application in the
real world and has not seen integration in modern medicine.  Rather it is relegated to the laboratory and
tested in clinical trials.

            Many experiments run such trials by
testing real drugs alongside placebos. 
This is done to isolate the real placebo effect and test the efficacy of
the drug.  These numerous trials have
raised interesting questions.  Recent
research on the placebo effect has been focused on investigating the psychosocial
context of the treatment, patient’s experience and beliefs, and the effect on
their brains (Price et al. 2008).

Environment, context, and method

            The recent research on psychosocial
context of placebos increasingly shows how the context and environment of the
treatment is even more important than the placebo itself. Fundamentally, it is subconscious
beliefs that invoke the placebo effect. 
There are many factors that influence these beliefs such as
communication, rituals, methods, conditioning, verbal suggestions and behaviors.
In one model, these cues affect expectancies, desires, and emotions, which in
turn trigger physiological mechanisms (Price et al. 2008).

            One particularly useful tool in this
line of research has been open and hidden paradigms (Price et al. 2008).  In an open paradigm, the treatment is
administered to the patient visibly by a healthcare professional who explains
the purpose of the treatment, as opposed to a hidden paradigm, in which
treatment is administered in secret.  The
results of such studies show that the open paradigms are significantly more
effective (Amanzio et al. 2001, Benedetti et al. 2003, Colloca et al. 2004). For
example, in one particular study (Benedetti et al. 2003) the open administration
of a drug by clinician was compared to hidden administration of the same drug
through infusion pump.  The results of
this experiment made it obvious that the clinician-patient relationship plays a
huge role in the placebo effect. 
Expounding on this theme will be the subject of future work in this

Placebo effect in athletics and

            The concept of the placebo effect in
athletics has only been studied recent years. 
There are so many ways the concept can be applied to physical performance
and this field is one of great growing interest.  The same problems that make the placebo
effect difficult to study apply even more so to physical performance.  The placebo effect has both subjective and
objective factors that are hard to separate and the effects vary greatly from
person to person.  In this field, the
most often used subjective effects of placebo are sedation and stimulation (Birdy
et al. 2011). The reduction of anxiety and stress are also of great interest,
as this plays a large role in sports. 
The body of literature on this topic is smaller, but still shows that
placebos do seem to be effective overall.

            One of the best ways to study this
subject is by using a stimulant drug alongside its placebo in a double
disassociation trial.  McClung and
colleagues conducted such a study, using runners in timed 1000 m trials
(McClung ET al.2007).  The drug
administered was sodium bicarbonate, a drug shown to improve performance and
decrease perceived exertion.  This
substance has been studied for decades and while the specifics are debatable,
the substance acts as a buffer to prevent pH levels from dropping below 7.4
into acidosis and causing fatigue.  More
importantly, this substance is known on the street to be effective, and is not
regulated by any international regulatory bodies. 

            The study used elite athletes and
separated into four groups: 1) a group that was told they would receive the
real drug and given the real drug, 2) a group that was told they would receive
the real drug and given a placebo, 3) a group was told they would receive
placebo and given the real drug, and 4) a group that was told they would
receive placebo and given placebo.  This
is the best possible way to test all aspects of the placebo effect.  This study is unique in its extreme attention
to detail and thoroughness.  The
researchers used standardized scripts, measured heart rate and lactate levels
in the blood, held a practice run, used trained track officials, ensured that
athletes ate the same food before the trials, and took trials separately to
remove competition bias.  Perhaps one
drawback of this setup was the low sample size, 16 athletes in total, 4 in each
group.  The study ultimately found that
the placebo groups saw almost as much improvement as the experimental group.

            Clark and colleagues conducted a
similar study, except using cyclists instead of runners (Clark et al.
2000).  The substance used was a
carbohydrate supplement.  The sample size
in this study was much larger, 43 athletes. 
They were split into two groups, one group given the carbohydrate
solution and the other given an inactive solution.  The groups were further randomized to three
subgroups: 1) group that was told the drink contained carbohydrate, 2) group
that was told it was a placebo 3) group that was told nothing at all.  The final results indicated that the placebo
effect conferred a small but worthwhile improvement.

            Similar to the last study, Beedie
and colleagues administered caffeine pills to cyclists alongside placebos
(Beedie et al. 2006).  As opposed to the
minor differences seen in other studies, this study demonstrated significant
improvements. In addition, the researchers discovered a couple of more
interesting revelations.  Their surveys
and questionnaires found that the subjects who experienced improvements did
believe they took a placebo during their trials and the remaining subjects did
not.  The researchers gave two groups an
inactive substance, while describing the substance to one group in positive
terms and to the other in negative terms (nocebo).  Accordingly, the first group improved and the
second group actually did worse.

            These findings were corroborated by
Duncan and colleagues (Duncan et al. 2009). 
In this study, 12 athletes were given caffeine alongside a placebo and
tested in anaerobic cycling to failure. 
The athletes were split into four groups again, in every combination: 1)
given caffeine and told it was caffeine 2) given caffeine and told it was
placebo 3) given placebo and told it was caffeine   4) given placebo and told it was placebo.  Participants were provided with literature
reviewing the published research on caffeine and high intensity exercise
performance and detailing anecdotal evidence relating to caffeine use among
elite team game performers.  This study
was also extremely thorough in regards to procedures, setups in timing so as
not to interfere with athletes’ circadian rhythms and measuring of blood
lactate levels.  In concluding this
study, peak power output, mean power output and rating of perceived exertion
were all significantly higher in the Caffeine trial, and significantly lower in
the placebo trials.

            All these studies and more were
summarized in a metanalysis (Bérdi et al. 2011) that concluded mixed results,
but an overall positive trend, finding that placebos have a small to moderate
effect on sports performance.  The
positive values in these studies would seem to indicate that there are some
practical values to be gained, but methodological problems in the studies
question their validity.  For example,
one problem is comparing the placebo group to its own baseline may lead to
overestimation.  Second, outside the laboratory
setting, with a host of other factors involved, equipment, opponents, pressure
and judges could influence the placebo effect. 
Third, the literature shows a high degree of variability showing the
effect varies widely from person to person. 
If the placebo effect can be thought of as a way to mobilize
psychophysiological reserves, these reserves could be different from one
individual to another.

            Aside from strictly athletics, the
placebo effect has been observed in all manner of outward physical changes
(Krum and Langer, 2007).  One study took
a number of female hotel cleaning staff and split them into two groups.  One group was told that their work meets the
required daily exercise guidelines set forth by the Surgeon General and the
other group was told that they do not. 
Over the next four weeks, without a change in behavior, a decrease of weight,
blood pressure, and body fat were observed in the first group.  The term placebo effect is typically used in
a medical context, but this phenomenon occurs when subconscious beliefs cause
physical changes in any situation. 
Subjects in contact with fake poison ivy developed rashes and people
undergoing fake knee operations experienced real swelling in the tendons and ligaments
(Krum and Langer, 2007).  It is quite
possible that the well-known benefits of exercise in addition to the actual
exercise itself can result in better health.

Physiological fatigue

            Fatigue can be defined as the fall
of force or power in response to contractile activity (Allen et al, 2008).  Fatigue is an incredibly complex concept with
both physical and mental components.  In
regards to the physical, it is an incredibly complex process.  On the cellular level, fatigue occurs when Adenosine
Triphosphate (ATP) consumption exceeds production, causing changes in certain
metabolites (Allen and Trajanovska, 2012). 
The concentration of inorganic phosphate increases, substantially
impairing myofibrillar performance.  But
fatigue also has a mental component.  It
could be argued that fatigue is a brain derived emotion (Noakes, 2012), though
ultimately the situation is more complicated and explained in more detail in
the following sections.

            There are four models of fatigue: 1)
the traditional model: the physical 2) the energy supply/energy depletion model
3) the
biomechanical model 4) the central governor model. The traditional
model is cardiovascular/anaerobic model that has been the standard model of
fatigue most widely accepted in the literature for the last 90 years.  Essentially, the model holds that fatigue
occurs when the cardiorespiratory system’s ability to pump oxygen to the
exercising muscles is exceeded by the demand for oxygen, prompting a shift into
anaerobic metabolism.  This model has
existed since the foundational paper of (Hill, 1925), where Hill proposed that
the three types of fatigue which were fatigue after quick explosiveness,
exhaustion after moderate intensity over a period of time, and general wear and
tear.  Since then, volumes of research
have been published on the factors that cause fatigue.  The three factors that cause fatigue are
maximal oxygen consumption (VO2 max), the lactate threshold’ and efficiency
(the speed at which one can use the consumed oxygen) (Joyner and Coyle, 2008).
This model has been challenged with the criticism that if this model is true,
then the heart would be the first to be affected by fatigue.  But it is not; that honor is reserved for the
muscles.  Opponents of this model also
argue that psychological factors play a role in fatigue.

            The biomechanical model supply is
also a cousin to the previous model and this model proposes that fatigue is not
caused by the failure to deliver oxygen, but rather the failure to deliver ATP
(Noakes, 2000).  It was Hill himself who
wrote that it was ultimately an inability to deliver energy to the muscles that
resulted in fatigue (Hill, 1927).  It is
generally agreed that middle and long distance running is dependent on this energy
delivery.  Therefore, according to this
model, the purpose of training should be to improve the energy systems and
their efficiency.  The criticism for this
model is that it is only hypothetical, and has not been proved enough.  Fatigue will physically always appear on the
surface to be an ATP problem.  To truly prove
this model, the other models need to be disproved.

            The central governor model is a
model involving muscles with respect to physics.  The model holds that muscles operate like
springs and produce torque (Noakes, 2000). 
The more efficient the muscle is, the more it behaves like a spring
producing less torque and being more elastic. 
This would slow down accumulation of the metabolites and the rise of
temperature, both of which cause fatigue.

            This particular model has become
popular and hotly debated in recent years. 
The thesis of this model is that there is a central subconscious
regulator that employs fatigue when the myriad systems of the body are in danger,
thereby protecting the whole body and maintaining homeostasis.  Thus, fatigue is a conscious sensation.  The mechanism through which the fatigue is
induced is because of the failure of the central nervous system.  Noakes’s (2000) study found the following:

model holds that the brain concentration of serotonin (and perhaps other
neurotransmitters, including dopamine and acetylcholine) alters the density of
the neural impulses reaching the exercising muscles, thereby influencing the
rate at which fatigue develops, especially during exercise. (p.15)

            An extension of this model is the
concept of teleoanticipation (Ulmer, 1996). 
The central governor attempts to judge the end time of the exercise
after gathering signals, and then perceived effort increases linearly until it
peaks at the completion of the exercise. 
As if forecasting, the brain calculates the exercise duration that can
be maintained without disrupting homeostasis, then produces a sensation of
exertion.  A study was conducted (Noakes
et al. (2004) that tested  Rating of Perceived
Exertion (RPE) as subjects engaged in timed trials.  The result showed that RPE linearly increased
until peaking at completion of the exercise. 
The results were verified with another study three years later (Eston et
al. 2007). Another study (Crew, 2008) substantiated this claim using timed
cycling trials.  Detractors of this model
point out that the model is internally inconsistent, unnecessarily complex, and
biologically implausible (Marcora, 2008). 
The extension of the model with the RPE is unnecessarily complex, as
well as the fact that the central governor would not need to induce a conscious
sensation of fatigue, seeing as it already has control over the nervous system
and muscle recruitment.  Critics also
attack the methodologies of the studies in support of this model.


            The two important concepts involved
in this study are the placebo effect and fatigue.  The placebo effect is largely the context and
environment of the treatment or drug being administered.  When used with athletes, the placebo effect
has been remarkably useful.  Fatigue has
both a physical and psychological component. 
The traditional model of fatigue is purely physical, but has been
recently challenged by the more psychological models.

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