Delimaris,Ι.(2014). Potential Adverse Biological Effects of Excessive Exercise and Overtraining Among Healthy Individuals. Αcta Medica Martiniana, 14 (3):5-12

Abstract

A growing body of research has investigated the potential health risks of excessive exercise on human health. There is now a clear need for an up-to-date, critical synthesis of reliable findings on this topic. Objective. To determine the potential adverse biological effects of excessive exercise and overtraining among - initially - healthy men and women. Design. Brief review. Material and method. In order to identify relevant studies, the electronic database Medline was searched using the following terms/key words: “excessive exercise” OR “overtraining”” AND “adverse effects”. Studies had to: a) be written in English, b) published from January 1980- March 2014, and c) involve healthy men and women (individuals with no pre-existing medical conditions). Results and discussion. The main adverse effects associated with excessive exercise and overtraining among healthy individuals were musculoskeletal injuries, adverse cardiovascular effects, exercise-induced muscle damage, exerciserelated alterations of immunity, exercise-related reproductive dysfunction, chronic negative energy balance, osteoporosis, and sleep disorders. Conclusions. The findings of the present study suggest that excessive exercise and overtraining can have serious health consequences. Sports physicians, trainers and health educators should be aware of these risks and advise the people accordingly. Further research needs to be carried out in this area, including high quality trials.

Full text

POT ENTIAL ADVERSE BIOLOGICAL EFFECTS OF EXCESSIVE
EXERCISE AND OVERT RAINING AMONG HEALTHY INDIVIDUALS
Ioannis Delimaris
Department of Dietetics and Nutrition, Harokopio University of Athens, Athens, Greece
A b s t ract
Background. A growing body of research has investigated the potential health risks of excessive exercise on
human health. There is now a clear need for an up-to-date, critical synthesis of reliable findings on this topic.
Objectiv e. T o determine the potential adverse biological effects of excessive exercise and overtraining among – ini-
tially - healthy men and women. Desi gn. Brief review. Material and method. In order to identify relevant studies,
the electronic database Medline was searched using the following terms/key words: “excessive exercise” OR “over-
training” AND “adverse effects”. Studies had to: a) be written in English, b) published from January 1980- March
2014, and c) involve healthy men and women (individuals with no pre-existing medical conditions). Results and
discussion. The main adverse effects associated with excessive exercise and overtraining among healthy individ-
uals were musculoskeletal injuries, adverse cardiovascular effects, exercise-induced muscle damage, exercise-
related alterations of immunity, exercise-related reproductive dysfunction, chronic negative energy balance, osteo-
porosis, and sleep disorders. Conc lusions.The findings of the present study suggest that excessive exercise and
overtraining can have serious health consequences. Sports physicians, trainers and health educators should be
aware of these risks and advise the people accordingly. Further research needs to be carried out in this area,
including high quality trials.
Keywords: adverse effects; excessive exercise; overtraining.
INTRODUCTION
Regular physical exercise is related with significant beneficial biological effects: it could
reduce the risk of coronary heart disease , diabetes, hypertension, colon cancer, breast can-
cer, depression and obesity [1]. Nevertheless, if exercise becomes excessive, it could be
related with serious medical complications [2]. According to the 4th edition of the Diagnostic
and Statistical Manual (DSM-IV) «
exercise becomes „excessi ve“ when it significantly inter-
feres w ith important activities, or occurs at inappropriate times or in inappropriate settings, or
when the athlete keeps exercising in spite of injury or other medical complications»
[2].
Excessive exercise usually results in „overtraining“ , which is a maladapted response to
excessive exercise without adequate rest (when either training volume or intensity is exces-
sive for prolonged periods); however, excessive exercise does not lead to overtraining in all
cases [3]. It has been estimated that the prevalence of excessive exercise in the general pop-
ulation is close to 3%, but among certain groups (such as ultra-marathon runners and
sport science students) the prevalence might be higher [4]. With regard to the possible
adverse biological effects of excessive exercise and overtraining the available literature is
still lacking conclusive information, while there is a large heterogeneity in the reported sci-
entific evidence. To our knowledge no single review study exists which adequately covers the
topic. The aim of the present study was to determine the potential adverse biological effects
of excessive exercise and overtraining among healthy men and women so as to add to exist-
ing knowledge by providing an up-to-date synthesis of recent evidence.
ACTA MEDICA MARTINIANA 2014 14/3 DOI: 10.1515/acm-2015-0001
5
Corresponding author:
Ioannis Delimaris, Dr.Med.Sci., Department of Dietetics and Nutrition, Harokopio University of Athens,70 El.
Venizelou Str, 17671 Athens,Greece; e-mail: dr.i.delimaris@gmail.com

Fig. 1 : Flow chart demonstrating search strategy
.
6ACTA MEDICA MARTINIANA 2014 14/3
MATERIAL AND METHODS
Desi g n
A brief review was performed based on a narrative synthesis of previously published lit-
erature.
Criteria for inclusion of studies
• Literature written in English.
• Literature published from January 1980 to March 2014.
• Studies that involved healthy men and women with no pre-existing medical conditions.
• Studies that had keywords in the title and/or abstract.
Search methods for identification of studies
The material of the present study was exclusively Internet-based. A comprehensive elec-
tronic literature search in the database PubMed was performed (from 10 April 2014 to 30
May 2014) using the following terms/key words: “excessive exercise” OR “overtraining” AND
“adverse effects”. In addition, a search in the reference lists was carried out. The search
process is shown in Figure 1.
Selection of studies
All obtained references from the search were organized and duplicates were excluded. The
titles and abstracts were screened for content and relevance to the topic with focus on the
inclusion criteria. The integral text of selected titles was read and the reference list of select-
ed articles was consulted in order to find out other relevant publications. Additionally, stud-
ies which failed to adequately describe the potential biological adverse effects of excessive
exercise and overtraining were excluded. In total 45 studies were included in the brief review
(Fig. 1).

Fig. 2 Potential adverse biological effects of excessive exercise and overtraining.
Musculoskeletal Injuries
Overtraining places a demand on the musculoskeletal system that may lead to its injuries.
The types of injuries that have been identified range from overt, which are obvious injuries
that will usually prevent athletic performance for some period of time, to subclinical, which
decrease performance, but may be seldom recognized [5]. At the subclinical level it has been
suggested that excessive training could cause repetitive tissue microtrauma (the repeated
exposure of the musculoskeletal tissue to low-magnitude forces results in injury at the
microscopic level), either to muscle and/or connective tissue and/or to bony structures,
and that this could result in chronic inflammation [6,7]. A prospective study investigating
the influence of physical activity on health outcomes among healthy adults showed that the
risk of sustaining an activity-related injury (any self-reported muscle, tendon, bone, liga-
ment, or joint injury) increased with higher duration and/or higher intensity of physical
activity [8]. Moreover, a controlled epidemiological investigation indicated that high total vol-
ume of vigorous physical training could be an etiologic factor for exercise-related injuries
(ankle sprains, iliotibial band syndrome, and stress fractures were the most common diag-
noses) [9].
Adverse cardiovascular effects
It has been suggested that long-term excessive endurance exercise training may cause
adverse structural and electrical cardiac remodeling, including fibrosis and stiffening of the
atria, right ventricular, and large arteries. This theoretically might provide a substrate for
atrial and ventricular arrhythmias and increase cardiovascular risk [10]. Chronically train-
ing for and participating in extreme endurance competitions such as marathons, very long
distance bicycle racing, etc., can cause transient acute volume overload of the atria and
right ventricle, with transient reductions in right ventricular ejection fraction. In veteran
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Data extraction and analysis
The essential data from each published study were extracted and synthesized. The results
are presented in a narrative form.
RESULTS AND DISCUSSION
The most common potential adverse biological effects of excessive exercise and overtrain-
ing for – initially - healthy men and women (with no pre-existing medical conditions) are
summarized in Figure 2 and described in narrative form below.

8ACTA MEDICA MARTINIANA 2014 14/3
extreme endurance athletes, excessive, high-intensity endurance exercise may be associat-
ed with diastolic dysfunction, large-artery wall stiffening and coronary artery calcification
[11]. Some arrhythmias appear to be more prevalent amongst endurance athletes.
Furthermore, excessive exercise has been associated with clinico-biochemical evidence of
acute damage (elevation of cardiac biomarkers), and some recent imaging techniques raise
the possibility of small areas of myocardial scar [12]. However, it has to be mentioned that
not all veteran extreme endurance athletes develop pathological cardiac remodeling, and
indeed lifelong exercisers generally have low mortality rates and excellent functional capac-
ity [11].
Exercise-induced muscle damage
Imbalance in the training load-recovery relationship is the primary factor contributing to
exercise-induced muscle damage. Muscle damage results in an immediate and prolonged
reduction in muscle function, most notably a reduction in force-generating capacity [13]. At
the ultrastructural level of skeletal muscle it has been shown that exercise myopathy (due
to the destruction of myofibrils and atrophy of muscle fibers) depends on the muscle fiber
type. The most sensitive to the long-lasting exhaustive endurance exercise are fast-twitch
muscle fibers [14]. Direct measures of exercise-induced muscle damage include cellular and
subcellular disturbances, particularly Z-line streaming. Several indirectly assessed markers
of muscle damage after exercise include increases in T2signal intensity, prolonged decreas-
es in force production, increases in inflammatory markers both within the injured muscle
and in the blood, increased appearance of muscle proteins in the blood, and muscular sore-
ness [15]. Moreover, exhaustive exercise of even short duration could lead to glycogen
depletion in human muscle fibres [16].
Exercise-related alterations of immunity
An increased incidence of upper respiratory tract infections has been associated with
excessive exercise, such as a marathon, manifesting between 3–72 hours post-race [17].
Although high-performance athletes are generally not clinically immune deficient, there is
evidence that several immune parameters are suppressed during prolonged periods of
intensive exercise training. These could include decreases in neutrophil function, serum or
salivary immunoglobulin concentrations, natural killer cell number and possibly cytotoxic
activity in peripheral blood [18]. Exercise-related alterations of immune function could exist
due to : a) tissue trauma sustained during intense exercise, producing cytokines and a TH2
cell response which results in simultaneous suppression of cell-mediated immunity, and b)
elevated levels of circulating cortisol and catecholamines, as well as prostaglandin E2 [17].
Exercise-related male reproductive dysfunction
It has been proposed that the hypothalamic-pituitary-testicular axis can be altered due to
excessive exercise in men [19]. The hypothesis of impaired hypothalamic regulation due to
excessive exercise has been supported by data that indicate a decreased maximum rise of
pituitary hormones (corticotrophin, growth hormone), cortisol and insulin after a stan-
dardised exhaustive exercise test [20], and a negative relationship between testosterone lev-
els and training volume in men participating in chronic endurance training [21]; however,
limited information is available due to lack of relevant human studies. This alteration could
lead to a decrease of testosterone levels in blood [19]. Again the mechanisms are not clear:
a variety of systems could influence the decrease of testosterone production, including
decreased gonadotrophin, increased cortisol, catecholamine or prolactin levels, or perhaps
even an accumulation of metabolic waste materials [22]. Low testosterone levels could cause
the development of hypogonadotropic hypogonadism characteristics, and oligo-spermatoge-
nesis [23], and in this sense long-term strenuous exercise could have a deleterious effect on
reproduction [24]. Moreover, a positive relationship between strenuous bicycle riding and
erectile dysfunction has been reported; the underlying causative pathophysiological mech-

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anism has been linked with chronic perineal vascular trauma, rather than a direct asso -
ciation with training volume or energy deficit [25].
Exercise-related female reproductive dysf unction
Excessive exercise by females may be associated with reduced gonadal function probably
due to alterations of the hypothalamic-pituitary axis (neuroendocrine abnormalities, hypoe-
strogenemia) and/or a negative calorie balance [26, 27]. This exercise-related female repro-
ductive dysfunction is frequent in an abnormally high percentage of female runners, bal-
let dancers, and in participants in a variety of other vigorous sports. The menstrual dys-
function described in these girls and women includes delayed puberty, luteal phase defi-
ciency, secondary oligomenorrhea-amenorrhea or anovulation [27, 28, 29]. Regarding
women of normal body weight it has been hypothesized that the reproductive system is
disrupted by a chronic negative energy balance, and not by the exercise itself; however, fur-
ther research evidence is needed [25].
Chronic negative energy balance
Acute negative energy balance is associated with body weight loss while chronic negative
energy balance is an inadequacy in food to which individuals adapt, and it is defined as
a weight-stable energy balance state (low body weight and fat store) in the presence of lower
than normal energy intakes [30]. Many athletes, especially female athletes, are chronically
energy deficient [31]. Due to the fact that the energy cost of high volume/ high intensity
prolonged exercising is significant it has been proposed that excessive exercise and over-
training could result in (intentional or unintentional) chronic negative energy balance [25].
When this chronic energy deficit is intentional it is usually related with anorexia nervosa
which is more frequent among female athletes [32]. The prevalence of hyperactivity (exces-
sive exercise) in anorexia nervosa lies between 31 and 80%, depending on the study and its
criteria for hyperactivity [33]. Nevertheless, chronic negative energy balance is usually
unintentional because appetite and body weight are not reliable indicators of energy and
macronutrient needs [31]. High dose exercise does not seem to increase hunger or energy
intake in humans [34].On the contrary, the existence of exercise-induced suppression of
appetite (resistance to begin eating) has been indicated, although more research in this
area is warranted [35].
Osteoporosis
Moderate exercise protects against osteoporosis, but excessive exercise and overtraining
could increase the risk for premature osteoporosis [36, 37]. Excessive exercise could cause
alterations in the hypothalamic-pituary-gonadal axis resulting in relatively low production
of sex hormones among otherwise healthy individuals. Decreased estrogen levels in females
and reduced testosterone levels in males are consider to accelerate bone loss [26]. Moreover,
excessive exercise and overtraining have been associated with a long-term increase of cor-
tisol secretion due to chronic (physical and/or psychological) stress [38]. Elevated cortisol
levels -if prolonged- could affect calcium and bone metabolism by increasing bone resorp-
tion, and decreasing bone formation or the intestinal absorption of calcium [39].
Furthermore, a negative energy balance due to excessive exercise and overtraining could be
the cause of protein and/or calcium undernutrition that could result in osteopenia or pre-
mature osteoporosis [40]. This phenomenon has been described as a part of the «Female
Athletic Triad», which consists of an eating disorder (usually anorexia nervosa), osteoporo-
sis and amenorrhea [40].
Sleep Disorders
Mild physical exercise is a modality of non-pharmacological treatment for sleep disorders
(sleep-enhancing effect of exercise), but excessive exercise and overtraining have been asso-
ciated with insufficient or poor sleep [41, 42]. Sleep disorders could occur due to a distur-

10 ACTA MEDICA MARTINIANA 2014 14/3
bance of circadian rythms, an imbalance in the neuroendocrine axis or psychobehavioral
(mood, behavior, and cognitive) changes accompanying overtraining [43]. In particular it
has been hypothesized that excessive exercise could result in elevated blood levels of cate-
cholamines (by the sympathetic nervous system) and increased cortisol secretion (by the
adrenal cortex glands) [43]. Sleep disturbances are associated with aberrant patterns of cat-
echolamines and cortisol secretion, such as those found in insomnia [44].
Limitations of the literature review
The present study synthesized narratively the current scientific literature data so as to
determine the potential adverse biological effects associated with excessive exercise and
overtraining in (initially) healthy men and women. Nevertheless, this brief review has some
methodological limitations: several relevant papers might have not been identified because
they were not available electronically, while unpublished reports, doctoral theses and stud-
ies that are not written in English were not included. This review is restricted to literature
written in English found in databases and reference lists.
Moreover, limited information is available due to lack of relevant human studies, so the
number of articles reviewed in this study cannot lead to conclusive evidence regarding the
potential severity of adverse effects of excessive exercise in healthy individuals. There are
also additional non-biological (e.g. psychological, social) adverse effects of excessive exercise
activities; however, their investigation was outside of the scope of this study.
Strengths of the literature review
This is, as far as we know, the first literature review which includes the potential adverse
biological effects associated with excessive exercise and overtraining in one single study.
Therefore, the review provides an updated overview of the subject area.
Future perspectives
The data from this study reveal several recommendations worthy of future study. High
quality trials should clarify the probability of a significant adverse biological effect occur-
ring given exposure to a particular exercise/training scheme (volume, intensity etc). The
identification of risk factors for excessive exercise could be an important part of its clinical
management or health education programs that are implemented with adolescent athletes
and their families (or coaches) before adolescents begin to experience the onset of over-
training. Furthermore, meta-analyses of large numbers of studies are needed to validate the
results and outcomes. Parameters evaluated are affected by age, group, endurance, strength
activities, timing of excessive exercise, training and recovery method etc. Physicians, coach-
es, health educators, and parents need to be educated and should: a) inform athletes or
students regarding the negative effects of overtraining, and the biological benefits of adopt-
ing a healthy way of physical activity, b) suggest athletes or students to keep a real-time
monitoring record of the frequency, duration, and type of exercise they are engaged in [45].
According to WHO guidelines (for the general population) adults (18-64 years old) should
adopt a moderate-intensity aerobic physical activity to 300 minutes/week, while muscle-
strengthening activities should be done involving major muscle groups on 2 days/week [1].
However, the ideal exercise scheme is different among well-trained or recreational athletes
or untrained adults, so an exercise training program should be personalized (according age,
sex, medical history etc.) and always performed upon the recommendation of a physician.
CONCLUSIONS
This brief review has examined the potential adverse biological effects of excessive exer-
cise and overtraining among (initially) healthy men and women. The results of this investi-
gation show that excessive exercise and overtraining could lead to musculoskeletal injuries,

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adverse cardiovascular effects, exercise-induced muscle damage, exercise-related alter-
ations of immunity, exercise-related reproductive dysfunction, chronic negative energy bal-
ance, osteoporosis, and sleep disorders. The recognition of potential adverse biological
effects of excessive exercise and overtraining is important for implementing prevention pro-
grams (via proper interventions) and could be promoted by an increased awareness both of
relevant scientific information and of its limitations.
Con f lict of Interests
The author declares that there is no conflict of interests regarding the publication of this
paper.
Funding statement
This study received no grant from any funding agency in the public, commercial or not-
for-profit sectors.
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Received: July, 5, 2014
Accepted: August, 23, 2014