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Acta Clin Croat, Vol. 51, No. 4, 2012 633
Acta Clin Croat 2012; 51:633-641 Review
THE IMMUNE SYSTEM AND OVERTRAINING IN
ATHLETES: CLINICAL IMPLICATIONS
Anthony C. Hackney1,2 and Kristen J. Koltun1
1Applied Physiology Laboratory, Department of Exercise & Sports Science; 2Department of Nutrition, School of
Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
SUMMARY – e primary objective of this review is to provide an overview of how overtra-
ining and the overtraining syndrome (OTS) affect the immune system of athletes. A secondary
objective is to provide sports medicine clinicians with guidance as to how best to prevent and/or
treat some of the health consequences of overtraining and the OTS as related to the development
of a compromised immune system associated with exercise training. e OTS is a physically debili-
tating condition that results in athletes being totally compromised in their capacity to perform and
compete. Many physiological systems are affected by the process of overtraining and the OTS; but
one system in particular, the immune, is highly susceptible to degradation resulting in a reduction
in overall health and performance. Monitoring of an athlete’s exercise training load and other life
stresses is critical to the determination of when their training regimen may be excessive, thereby
increasing the risk of OTS developing. Taking steps to mitigate prolonged exposure to extreme
stress (training + life or otherwise) in athletes as well as promoting a healthy immune system can si-
gnificantly aid in the advancement of an athlete’s training regimen progression and ultimate physical
performance and overall health. In this light, this review provides approaches to aid sports medicine
clinicians in promoting a healthy immune system in athletes.
Key words: Cytokines; Athletes; Stress; Hormones; Sports performance; Overtraining
Correspondence to: Dr. Anthony C. Hackney, University of North
Carolina, CB # 8700 – Fetzer Hall, Chapel Hill, North Carolina,
27599, USA
E-mail: ach@email.unc.edu
Received February 23, 2012, accepted July 20, 2012
Introduction
e intent of an exercise training program for ath-
letes is to improve their physical performance capac-
ity. In attempting to enhance physical performance
and cause positive physiological adaptations, competi-
tive athletes must perform a tremendous amount of
exercise on a regular basis. If training regimen stresses
are excessive (involving working at too great an inten-
sity, and/or containing too great a volume of work), or
an athlete has too many additional life stresses during
training, it is possible for physiological mal-adapta-
tions to occur. Such mal-adaptations can lead to phys-
ical performance declines. In the field of exercise and
sports physiology, this process of applying excessive
training stress is referred to as overtraining (see Table
1 for a detailed operational definition)1-3. If overtrain-
ing is persistently applied, then there is the potential
for the medical condition called the overtraining syn-
drome (OTS) to develop in the athlete4-6. e OTS
has been referred to in the past as burnout or staleness
and recently it has been proposed that the term unex-
plained underperformance syndrome be used1,7,8.
e OTS is a physically debilitating condition
that results in an athlete being totally compromised in
their capacity to perform and compete. Table 2 pres-
ents some of the signs and symptoms associated with
overtraining and OTS development. e information
in Table 2 indicates that many physiological systems
are affected by the OTS. e primary intent of this
paper is to provide an overview on how overtrain-
634 Acta Clin Croat, Vol. 51, No. 4, 2012
Anthony C. Hackney and Kristen J. Koltun Overtraining and the immune system
ing and the OTS affect one system in particular, the
immune system. e focus is on the immune system
because of new research linking this system to the
development of OTS in athletes and due to its over-
arching impact on so many aspects of human health.
To this end, steps toward management and care that
sports medicine clinicians can take to prevent and/or
treat some of the health consequences of overtraining
and OTS as related to the immune system are also
presented.
Background
Currently, it is unclear as to the exact physiological
mechanism responsible for inducing the OTS state;
however, there are several prevailing theories. ese
consist primarily of the muscle glycogen hypothesis,
central fatigue hypothesis, glutamine hypothesis,
sympathetic-parasympathetic hypothesis, hypotha-
lamic-pituitary hypothesis and the cytokine-tissue
trauma hypothesis. e latter one, cytokine-tissue
trauma, is currently recognized by many scientists as
the prevailing hypothesis in the contemporary under-
standing of the overtraining phenomenon6,8.
Cytokine hypothesis
Dr. Lucille Lakier Smith of South Africa has de-
veloped the main concepts of this hypothesis in which
it is proposed that with excessive exercise training (i.e.
overtraining) there is a high level of musculoskeletal
loading from the exercise which results in tissue dam-
age9. is tissue damage in turn results in local and
systemic inflammation and the activation of immune
system responses. If the athlete is not provided with
adequate rest and recovery in the training regimen
these responses become disproportionately greater
because of subsequent repetitive exercise training ses-
sions. Consequently, inflammatory chemical signaling
agents of the immune system (i.e. cytokines [which
act to facilitate immune cell components such as lym-
phocytes, neutrophils and monocytes]) act directly
and indirectly upon multiple physiological systems to
promote alterations in metabolism, behavior, sexual
function, endocrine functions, protein synthesis rates,
and other immune functions (see Table 2), which ul-
timately culminates in the OTS symptoms and com-
promised physical performance4, 10 -16.
Immune response overview
A key element in Dr. Lakier Smith’s hypothesis is
the type and pattern of the cytokine response, which
leads eventually to a form of immune system suppres-
Table 1. Operational definition of overtraining as applied
to the exercise training of athletes1-3
Overtraining – a mal-adaptive state related to the physi-
cal, behavioral and/or emotional condition of an athlete
that occurs when the volume and intensity of his exercise
training load becomes excessive and exceeds the indi-
vidual’s ability to recover. It results in a consistent and
persistent decline in the physical performance capacity
of the athlete relative to their ability to perform train-
ing and/or compete in sporting events. e level of de-
cline in physical performance that marks overtraining is
highly individualized and dependent upon the observa-
tion and interpretation of the athlete, his coach and his
athletic trainer.
Table 2. Some of the major signs and symptoms of over-
training and the overtraining syndrome
Physiological function:
Decreased competitive performance
Decreased muscular strength
Increased muscular soreness
Chronic fatigue
Reduced tolerance to training overload
Sleep-wake cycle abnormalities
Gastrointestinal disturbances
Reduced testosterone levels
Reduced thyroid hormone levels
Elevated cortisol levels
Elevated creatine kinase
Altered lactate responses to exercise
Reduced sexual drive and libido
Altered heart rate responses to exercise
Suppressed immune function
Psychological function:
Increased feelings of depression
Lethargy and apathy
Emotional abnormalities
Loss of appetite
Lack of competitive drive
Restlessness
Difficulty in concentrating
Acta Clin Croat, Vol. 51, No. 4, 2012 635
Anthony C. Hackney and Kristen J. Koltun Overtraining and the immune system
sion (i.e. immuno-suppression). A highly detailed,
in-depth presentation of the immune basis for the
development of this immuno-suppression is beyond
the scope of this discussion, mainly because the im-
mune system is a highly complex, integral physiologi-
cal system. Nevertheless, a brief explanatory overview
is warranted and presented here. e human immune
system is composed of many interdependent cell types
that respond collectively to protect the body from
pathogenic (i.e. bacterial, parasitic, fungal, viral) in-
fections and from the growth of tumor cells, as well
as to manage tissue inflammation responses. Inflam-
mation is one of the first responses of the immune
system to infections17. e symptoms of inflammation
are redness, swelling, heat, and pain in an area, which
are caused in part by increased blood flow into a tis-
sue17,18 . Inflammation is produced by the eicosanoids
and cytokines (see following discussion) which are
released by injured or infected cells. Eicosanoids in-
clude prostaglandins that produce fever and dilation
of blood vessels associated with the inflammation,
and the leukotrienes that attract certain white blood
cells (leukocytes), specifically neutrophils which are
associated with tissue repair18.
e actions of the immune system can be divided
into what are referred to as the innate and adaptive
immune responses. e innate responses are the first
line of immune defense and are viewed as indiscrimi-
nately attacking pathogens, while the adaptive re-
sponses (which typically follow those of the innate)
tend to target specific pathogens and have an antigen-
specific memory of such pathogens18. Figure 1 gives
a schematic overview of the general aspects of these
components to the immune system. Both the innate
and adaptive immune responses are associated with
the production of cytokines. ere are a multitude of
cytokines that can be produced, and they are typically
classified as either proinflammatory or anti-inflamma-
tory in function, although some cytokines have both
pro- and anti-inflammatory actions18. In Dr. Lakier
Smith’s theory, the tissue trauma of excessive exercise
results in the production of an abundance of proin-
flammatory cytokines, which then leads to the devel-
opment of a sickness response or a chronic fatigue-like
behavior in an athlete19-21. e key proinflammatory
cytokines most associated with the theory are inter-
leukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor
necrosis factor-alpha (TNF-α)9. Research by several
investigators, especially Dr. Paula Robson-Ansley of
the United Kingdom, has produced findings that sub-
stantiate the role of proinflammatory cytokines, espe-
cially IL-6, as being the key physiological mediators
Fig. 1. Schematic overview of the basic components of the immune system (IgA = im-
munoglobulin A; IgM = immunoglobulin M).
Othe r compo nents: e.g.; acu te phase proteins, cy tokines, epithelial barriers
636 Acta Clin Croat, Vol. 51, No. 4, 2012
Anthony C. Hackney and Kristen J. Koltun Overtraining and the immune system
for the development of many of the symptoms associ-
ated with OTS20,21.
Immuno-suppression
e production of proinflammatory cytokines also
leads to an up-regulation of humoral immunity and
suppression of the cell-mediated immunity compo-
nents of the adaptive immune responses18. Because of
its immune system role, development of cell-mediated
immuno-suppression increases the risk of illness or
illness-like symptoms such as upper respiratory symp-
toms (URS) and infections (URI). e development
of such an illness or illness-like symptoms is further
associated with compromises in physical performance
capacity as athletes find exercise training or competi-
tion difficult or impossible under such conditions22,23.
is phenomenon of cell-mediated immuno-
suppression and increased URS-URI risk is in line
with what are referred to as the Open Window and
J-Curve response concepts, which are related to exer-
cise training and illness status as proposed by several
eminent health researchers2 4-26. e Open Window
concept entails that after an intensive exercise session
there is a period of time (3-72 hours) in which there
is an increased susceptibility to illnesses, such as URI.
With insufficient rest there can be a cumulative ef-
fect of consecutive days of intensive training (i.e. the
“window” staying open for a longer period of time).
is concept of a period of increased susceptibility to
illness following exercise has been linked to the oc-
currence of natural killer (NK) cell inhibition (part of
the innate immune responses) that can happen after
an exercise session brought on by the increased levels
of cortisol, catecholamines, proinflammatory cytok-
ines, and increased prostaglandins (from monocytes)
in response to the exercise session25,27-29. e NK cell
suppression in turn seems to assist in the aspects of
the greater adaptive immune responses and the up-
regulation of humoral immunity9,19. Interestingly,
NK cell suppression is especially associated with and
found following prolonged-duration aerobic forms of
exercise (e.g., marathon training), which have some of
the highest incidences of OTS development5,30,31. In
a similar fashion, the J-Curve response concept states
that the risk of URI development initially goes down
as a sedentary individual gets involved with light to
moderate exercise training for health and fitness, but
substantially increases as they move their training to
higher levels of volume and/or intensity such as occurs
in individuals wanting to compete in sporting activi-
ties. Diagrammatic depictions of these concepts are
shown in Figures 2 and 3.
An additional final point to consider is “the chick-
en or the egg” argument about the development of the
OTS and immuno-suppression. at is, does the im-
mune system become suppressed and this leads to the
OTS, or does an athlete develop the OTS and it results
in immuno-suppression? Dr. Lakier Smith’s hypoth-
esis most certainly proposes it is the former scenario
and not the latter. However, not all researchers who
study overtraining in athletes are in total agreement
on this point and further research is needed to rectify
this question and devise an answer5,6,12,22,23.
e proposed cytokine-tissue trauma theory by
Dr. Lakier Smith, while not perfect, does reconcile
and connect many of the major pathogenic and clini-
Fig. 2. Open Window theoretical concept associated with
immune responses to acute exercise (h = hours).
Open Window Theory: Af ter intense exercise increased
susceptibility to lines
Intense
Exercis e
“Open W indow ”
3-72 h
Baseline
Fig. 3. J-Curve response concept associated with the im-
mune responses to exercise training (URI = upper respira-
tory infections).
J – Curve Response
Above
Averag e
Averag e
Below
Averag e
URI R ISK
AMOU NT – IN TENS ITY OF T RAI NIN G EXER CISE
S edent ary Mode rate High
Acta Clin Croat, Vol. 51, No. 4, 2012 637
Anthony C. Hackney and Kristen J. Koltun Overtraining and the immune system
cal manifestations typically seen in athletes who have
been diagnosed with the OTS. It is important to
recognize, however, that this entire line of research
is hampered because the systematic research on over-
training, for ethical reasons, is very limited and in
many situations findings consist of case study-like re-
ports. at is, it would be ethically inappropriate to
take an athlete who perhaps makes their livelihood
through sports participation and intentionally over-
train them and compromise their ability to compete
and raise financial sponsorship.
Training Load: Overload – Over-Reaching –
Overtraining
In the last few years, there has been a re-defining
of some of the terminology associated with training
and the development of OTS. In particular, it is im-
portant to this discussion that the reader recognizes
the distinctions between the different terms used for
the types of training loads. e concept of overload
in exercise training progression is typically well un-
derstood – i.e. the principle of overload states that a
greater than normal exercise load on the body is re-
quired for training adaptations to take place and as
one adapts to this exercise load it must be progressed
to a greater load in order to continually stimulate and
induce physical improvement32,33. What is typically
less clear is the distinction between over-reaching
training and overtraining. Over-reaching training is
considered a short-term excessive training overload
that can actually result in a short-term transient de-
cline in physical performance. However, over-reach-
ing is usually administered for a very short period of
time, its training intensity is only slightly excessive,
and it is followed by a period of reduced training (~2
weeks) and is done in an attempt to achieve a great-
er adaptive compensation. Some coaches and sports
physiologists feel that cycles of over-reaching are nec-
essary in a training program to produce a super-com-
pensation, which allows the athlete to reach higher
levels of competitive performance8, 31. A task force of
the leading scientists from the European Congress of
Sports Science (ECSS) have termed this scenario as
functional over-reaching. In contrast, overtraining is
viewed as an exercise training load that is extremely
excessive and results in large, more long-lasting per-
formance declines, even when periods of rest and
recovery are allowed, and culminates in persistent
declines in physical performance and the potential
development of OTS. is scenario has been termed
a form of non-functional over-reaching by the ECSS
task force31. According to the task force, if the OTS
stage is allowed to be developed in an athlete, the
only known course of treatment action appears to be a
substantial-extended period of rest for the athlete and
removal from the training and competitive environ-
ments4,5,12,34.
However, it is also critical to recognize that other
life stresses encountered by the athletes, besides that
of training load alone, have influences on their adap-
tive responses. Athletes may experience many psy-
chosocial stresses within their educational, personal,
occupational, and financial situations5,7,31. ere is
also the stress of traveling to sporting competitions,
as well as different cultural settings, competing too
frequently, ambient environmental factors, medical/
medication conditions or treatments, and poor dietary
practices that can all influence how a training load is
perceived and tolerated by the athlete8,22,30,31. Relative
to this last point (diet), it is especially important for
the athlete to maintain an adequate daily carbohy-
drate intake, as insufficient carbohydrate intake will
exacerbate the risk of immuno-suppression develop-
ment35-38. All of these aforementioned factors combine
to add to the total stress placed upon the athlete and,
in doing so, can impact the effectiveness of a training
plan to ensure the desired overall performance out-
comes are reached. us, what may be an appropriate
overload or functional over-reaching training dosage
could become excessive and inappropriate when com-
bined with the influence of other daily life stresses be-
ing placed upon the athlete’s physiology. is makes
it critical for the coach and athletic trainer to under-
stand and appreciate what are the “events happening”
in the life of the athlete besides just what is occurring
on the practice field.
Practical Aspects of Dealing with Immuno-
Suppression
Evidence demonstrates that development of ex-
ercise training induced immuno-suppression is asso-
ciated with compromised physical performance22,25.
But, development of an infection of any type, for any
reason, in an athlete can lead to inability to train or
638 Acta Clin Croat, Vol. 51, No. 4, 2012
Anthony C. Hackney and Kristen J. Koltun Overtraining and the immune system
compete at an optimal level22,26. Hence, it is impor-
tant for sports medicine clinicians to recognize pre-
ventative and treatment steps and actions to allow
for maintenance of appropriate immune function and
health in athletes39.
Prevention
As with nearly all medical and health conditions,
prevention is far superior to treatment in providing for
a more successful overall maintenance of the athlete’s
training regimen and physical performance capac-
ity. Research supports that there are several proactive
steps and actions that athletes and sports medicine
clinicians can take to reduce the risk of development
of an infection or a compromised immune system22,40.
ese include such items as the athletes should:
• keep vaccine(s) administration updated
• attempttominimizecontactwithknowninfected
or sick people
• washhandsfrequentlythroughouttheday
• limitmouth/nosecontactwhenwithinfection
symptoms (i.e. URS)
• donotsharedrinkswithotherathletes
• donotsharetowelsorwashclothswithother
athletes
• isolateteammembersfromothersifdisplaying
infection symptoms
• protectairwayfromverycoldordryairwhen
performing strenuous exercise
• maintainadequatedailydietarycarbohydrate
intake (~60% daily caloric intake)
• wearproperclothingforweatherconditionsand
avoid getting cold-wet after exercise
• attempttogetaminimumof7-hourssleepanight
• avoidrapidweightlossand“crash”dieting
approaches to weight loss
• wearclothingtopreventunnecessaryhazardous
dermatological exposures (e.g., shower shoes)
• wheneverpossibleminimizeotherlifestressors
Evidence-based findings support that following
these steps can significantly decrease the risk of infec-
tions developing in athletes18,22 . Obviously, it may not
be completely realistic to incorporate all of the above
into daily behaviors and lifestyles of every athlete.
Treatment
Even with compliance to all of the abovemen-
tioned preventative steps and actions there is always
the likelihood that an athlete will develop an infec-
tion of some type. is condition would be apparent
if they display symptoms such as sore throat, cough-
ing, runny/congested nose, muscle/joint pain-edema,
headache, fever, malaise, diarrhea and vomiting18. Re-
cently, a group of leading exercise immunologists have
recommended the following course of action when
clinicians are dealing with an athlete displaying overt
signs of an infection and/or inflammation22,40.
• day 1 of illness – no strenuous exercise or compe-
tition; they should drink plenty fluids; keep from
getting wet/cold; minimize life stress. If feverish
– induce nasal drainage, and use decongestants-
analgesics;
• day2ofillness–ifsymptomsworsen–noexercise,
rest. If no fever or worsening of symptoms, then
light-easy exercise (30-45 minutes) allowed;
• day3ofillness–iffever,symptomspersist,consult
physician. If no fever or worsening of symptoms,
then light-moderate exercise (45-60 minutes) al-
lowed; and
• day4ofillness–ifnosymptomrelief,noexercise–
continued rest; have an office visit with a physician.
If relief (1st day of improved symptoms) and no fe-
ver, then light-easy exercise (as noted above). Use
the same number days as off to return and step up
to normal training; monitor tolerance to gradually
increasing exercise intensity, take additional days
off if poor tolerance (if necessary).
Finally, in order to optimize treatment, it is critical
that all members of the healthcare team treating the
athlete have good communication with one another
concerning the progression and responses of the ath-
lete if symptoms develop and persist41-43.
Conclusions
In conclusion, competitive athletes subject them-
selves to a high level of exercise training stress in or-
der to enhance their physical performance capacity.
is training stress, as well as the other stresses of life
these athletes encounter, places them at a great risk
of developing the OTS. e physiological cause(s) of
the OTS is presently uncertain, but one of the leading
Acta Clin Croat, Vol. 51, No. 4, 2012 639
Anthony C. Hackney and Kristen J. Koltun Overtraining and the immune system
theories is the “cytokine tissue-trauma” hypothesis.
is hypothesis proposes that undue proinflamma-
tory cytokine responses to excessive exercise training
(overtraining) creates a “sickness behavior” response,
development of immuno-suppression, and ultimately
leads to a decline in physical performance capacity of
the athlete. is hypothesis presents one of the most
encompassing and complete perspectives on how exer-
cise training and development of the OTS are explic-
itly linked mechanistically to a compromised physi-
ological system – i.e. the immune system. Additional
future research, however, is necessary and warranted
to collect further evidence to substantiate or refute
this hypothesis.
Steps to prevent and reduce the risk of infection
involve sports medicine clinicians helping foster and
develop appropriate behaviors and actions in athletes
(as noted above). Likewise, once an infection-inflam-
mation response is manifested in the athlete, it is criti-
cal for clinicians to take the actions to mitigate the se-
verity and impact of the illness development through
the recommended intervention steps. By doing so, the
clinician can promote a more rapid return to normal
health and exercise training level in the athlete.
Acknowledgments
Aspects of this paper were presented at the 2011
American College of Sports Medicine national meet-
ing in Denver, Colorado, at the Symposium on Over-
training-Overreaching in Elite Athletes and Military
Personnel.
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Acta Clin Croat, Vol. 51, No. 4, 2012 6 41
Anthony C. Hackney and Kristen J. Koltun Overtraining and the immune system
Sažetak
IMUNI SUSTAV I PREKOMJERAN TRENING KOD ŠPORTAŠA: KLINIČKE IMPLIKACIJE
A.C. Hackney i K.J. Koltun
Primarni cilj ovoga rada je dati pregled načina na koje prekomjeran trening i sindrom prekomjernog treninga utječu na
imuni sustav športaša. Sekundarni cilj je pružiti kliničarima koji se bave športskom medicinom smjernice kako najučin-
kovitije spriječiti i/ili liječiti neke od zdravstvenih posljedica prekomjernog treninga i sindroma prekomjernog treninga u
odnosu na razvoj poremećaja imunog sustava udruženih s treningom. Sindrom prekomjernog treninga je stanje onemoća-
losti koje kod športaša potpuno onemogućava športske aktivnosti i natjecanje. Proces prekomjernog treninga i sindroma
prekomjernog treninga utječe na mnoge fiziološke sustave, no jedan od tih sustava, tj. imuni sustav, osobito je osjetljiv na
te utjecaje, što dovodi do poremećaja općeg zdravstvenog stanja i smanjene sposobnosti za športske aktivnosti. Ključno je
pratiti opterećenje treningom i drugim životnim stresnim situacijama kod pojedinog športaša kako bi se utvrdilo kad je
režim treniranja možda pretjeran pa postoji opasnost od razvoja sindroma prekomjernog treninga. Poduzimanjem mjera
za ublažavanje izloženosti krajnjem stresu (trening + životne situacije ili drugo) kod športaša te podržavanjem zdravog
imunog sustava može se značajno pomoći u promicanju progresivnog režima treniranja i krajnje fizičke učinkovitosti,
kao i zdravlja općenito. U tom smislu ovaj pregled upućuje kako pomoći kliničarima koji se bave športskom medicinom u
promicanju zdravog imunog sustava kod športaša.
Ključne riječi: Citokini; Športaši; Stres; Hormoni; Uspjeh u športu; Prekomjeran trening