International Journal of Sport Nutrition and Exercise Metabolism, 2019, 29, 181-188
https://doi.org/10.1123/ijsnem.2018-0288© 2019 Human Kinetics, Inc.

SCHOLARLY REVIEWExercise-Induced Illness and Inﬂammation: Can Immunonutrition
and Iron Help?
Lindy M. Castell
University of Oxford

David C. Nieman
Appalachian State University

Stéphane Bermon
International Association of Athletics FederationsPeter Peeling
The University of Western Australia
The main focus of this review is illness among elite athletes, how and why it occurs, and whether any measures can be taken tocombat it or to prevent its onset. In particular, there is particular interest in exercise-induced immunodepression, which is a resultof the immune system regarding exercise (e.g., prolonged, exhaustive exercise) as a challenge to its function. This promotes theinﬂammatory response. There is often a high incidence of illness in athletes after undertaking strenuous exercise, particularly
among those competing in endurance events, not only mainly in terms of upper respiratory tract illness, but also involving
gastrointestinal problems. It may well be that this high incidence is largely due to insufﬁcient recovery time being allowed after,
for example, a marathon, a triathlon, or other endurance events. Two examples of the incidence of upper respiratory tract illness inmoderate versus endurance exercise are provided. In recent years, increasing numbers of research studies have investigated theorigins, symptoms, and incidence of these bouts of illness and have attempted to alleviate the symptoms with supplements, sports
foods, or immunonutrition. One aspect of the present review discusses iron deﬁciency, which has been primarily suggested tohave an impact upon cell-mediated immunity. Immunonutrition is also discussed, as are new techniques for investigating links
between metabolism and immune function.
Keywords: exercise-induced immunodepression, immunity, metabolism, nutrients

Immunodepression and Immunonutrition
Investigation of exercise-induced effects on the immune system began
more than 100 years ago, when Larrabee (1902) observed a marked
leukocytosis after violent exercise, including a large number ofpolymorphonuclear neutrophils. Since then, many scientists havestudied the effects of strenuous and/or prolonged exercise on different
aspects of immune function and have generally concluded that exercise
can lead to immunodepression. Immunodepression is a more accurate
term than immunosuppression, which implies a speciﬁc manipulationof the immune system, for example, as with cyclosporine.
High-performance athletes undertake high-intensity training
and competition. Additional stresses such as long-haul ﬂights,

Castell is with Green Templeton College, University of Oxford, Oxford, United
Kingdom. Nieman is with the Human Performance Lab, Appalachian State
University, Kannapolis, NC. Bermon is with the International Association of
Athletics Federations, Health & Science Department, Monaco. Peeling is with
the School of Human Sciences (Exercise and Sport Science), The University ofWestern Australia, Crawley, Western Australia. Address author correspondence to
Lindy M. Castell at lindy.castell@gtc.ox.ac.uk.

sleep disruption, and environmental change, encompassed within
physiological, metabolic, and psychological stress, are linked toimmune dysfunction, inﬂammation, oxidative stress, and muscle
damage. White blood cell numbers and function, salivary IgA
output, skin delayed-type hypersensitivity response, major histocompatibility complex II expression, and other biomarkers of
immune function are altered for several hours, sometimes days,
during the recovery from prolonged, exhaustive exercise. These
immune changes occur in several compartments of the immune
system and body, including the skin, upper respiratory tract
mucosal tissue, lung, blood, muscle, and peritoneal cavity(Bermon et al., 2017; Peake et al., 2017; Walsh et al., 2011).
In relation to exercise, interest in immunonutrition is relatively
new. Only in the last few years have a considerable number of
papers on immunonutrition and exercise-induced immunodepression been published. Nevertheless, it is still necessary to investigate
further whether immunonutrition can help to combat exerciseinduced immunodepression effectively. Nutrients that have arole in immunonutrition are glucose, amino acids (for protein
synthesis), and fatty acids, which act as fuels for energy generationin immune system cells and, importantly, enable the ability of cells
to proliferate; micronutrients (e.g., iron, zinc, and magnesium) are181

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important for competent immune function, as are vitamins A and D.
Some nutrients must be provided in the diet, as they cannot be
synthesized in mammalian cells (Calder, 2013).
Improved techniques such as metabolomics, proteomics, andlipidomics have revealed that metabolism and immunity are inextricably interwoven. This has led to a new area of research termed
immunometabolism (Nieman et al., 2018a). Studies on humanathletes exercising intensely for >2 hr showed that signiﬁcant
increases in at least 300 identiﬁed metabolites can be measured,
while body glycogen stores are depleted and increases occur in avariety of lipid super-pathway metabolites, including oxidized derivatives called oxylipins (Nieman et al., 2018b). Oxylipins are
involved in initiating, mediating, and resolving the innate immune
response (Markworth et al., 2016; Nieman et al., 2018b).
Small, immune-related proteins (e.g., cytokines) are involved
with pathogen defense and immune cell chemotaxis and locomotion. The most studied cytokine in exercise immunology isInterleukin-6, which increases markedly after strenuous exercise(Febbraio & Pedersen, 2002). Other proteins increase chronicallyduring recovery and are involved in the inﬂammatory acute phase
response. In response to an acute immunological challenge, such as
exercise stress, cells of the immune system must be able to growand proliferate to generate effector cells producing speciﬁc molecules. Activation of the immune system is associated with oxygenand biosynthetic demands. However, the metabolic capacity of
immune cells is reduced during recovery from physiologicallydemanding bouts of intensive exercise, resulting in transient immunodepression. The circulating numbers of most immune cells
return to normal within 5–6 hr postexercise: an exception is naturalkiller cells, the numbers and function of which can remain depressed for up to 48 hr during the recovery period.

Illness Risk
Subclinical and Clinical Illness
As a consequence of exercise-induced immunodepression, resistanceto pathogens is lowered, increasing the risk of subclinical and clinicalinfection and illness (Schwellnus et al., 2016; Walsh et al., 2011). In
some of the earliest studies on this topic, marathon and ultramarathon
runners have been shown to be at an increased risk of upper respiratory
tract illness (URTI) (Nieman et al., 1990; Peters & Bateman, 1983).
Out of 2,311 endurance runners, nearly 13% reported URTI during theweek after the Los Angeles Marathon race, compared with 2.2% of
the control runners (Nieman et al., 1990). Those running >96 km/
week versus <32 km/week doubled their odds for illness. A one-year
retrospective study of 852 German athletes showed that the URTI
risk was highest in endurance athletes who also reported signiﬁcantstress and sleep deprivation (Konig et al., 2000). Timpka et al.
(2017) recently reported that endurance athletes were ca. 10-foldmore likely to have an illness during the World Championships thanspeed/power athletes. In an early study, among nonelite athletes, thelevels of illness were monitored in more than 200 runners androwers; the incidence of URTI was lowest in the middle-distancerunners and highest in runners after a full or ultramarathon and inelite rowers after prolonged, intensive training (Castell et al., 1996).
Nieman (1994) used the economists’ J-curve in a novel approach todescribe the incidence of URTI in athletes (Figure 1).
Spence et al. (2007) provided an interesting slant on the wholeaspect of exercise-induced immunodepression by reporting nonspeciﬁc URTIs as opposed to URT infections (Figure 2). They saw
a higher rate of URT illness among elite athletes than in

Figure 1 — The incidence of illness in sedentary controls and athletes:
This is reduced (i.e., improved) by moderate, regular exercise; however, it
increases sharply with prolonged, exhaustive exercise or with overtraining.
URTI = upper respiratory tract illness. Modiﬁed from “Infectious Episodes in
Runners Before and After the Los Angeles Marathon,” by D.C. Nieman, L.M.
Johansen, J.W. Lee, J. Cermak, and K. Arabatzis, 1990, Journal of Sports
Medicine and Physical Fitness, 30, pp. 316–328. Copyright 1990 by Elsevier.

recreationally competitive athletes. However, pathogens were
only isolated in <30% of URI cases. The authors recommended
that physicians consider both infectious and noninfectious causes
in athletes presenting with symptoms. It is interesting to compare
their curve with Nieman’s J-curve from 1994.
As illness data have increased (Hellard et al., 2015; Svendsen
et al., 2015), organizations, including the International Olympic
Committee and the International Associations of Athletics Federations, have initiated acute illness surveillance systems to improve
both prevention and treatment procedures (Schwellnus et al., 2016;
Timpka et al., 2017). Engebretsen et al. (2013) undertook a survey
on the 2012 London Olympics; they reported a high rate of illness
among competitors in six sports including athletics, with the mostcommon cause of URTI being infection. The International Olympic
Committee has focused on the inappropriate management of bothFigure 2 — Episodes of U-URI and URTI during 5 months’ surveillanceof recreational versus elite athletes compared with sedentary controls.
n = number of subjects in each cohort. U-URI = unidentiﬁed upper
respiratory illnesses; URTI = upper respiratory tract illness. Reproduced
from “Incidence, Etiology, and Symptomatology of Upper Respiratory
Illness in Elite Athletes,” by L. Spence, W.J. Brown, D.B. Pyne, M.D.
Nissen, T.P. Sloots, J.G. McCormack, . . . P.A. Fricker, 2007, Medicine &Science in Sports & Exercise, 39, pp. 577–586. Copyright 2007 by Wolters
Kluwer Health, Inc.

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183

Figure 3 — Percentage of modiﬁed training weeks (due to injury/illness across 5 years) by monitoring a 6-month preparation period for participants
who failed or succeeded in reaching their key performance goal. n = 33 track and ﬁeld athletes. From “Performance Success or Failure Is Inﬂuenced by
Weeks Lost to Injury and Illness in Elite Australian Track and Field Athletes: A 5-Year Prospective Study,” by B.P. Raysmith and M.K. Drew, 2016,
Journal of Science and Medicine in Sport, 19, pp. 778–783. Copyright 2016 by Elsevier.

internal (e.g., psychological responses) and external (e.g., training
and competition workloads) loads. According to the International
Olympic Committee, load management is a key strategy for reducing illness incidence and associated downturns in exercise
performance, interruptions in training, missed competitive events,
and the risk of serious medical complications. Clarsen et al. (2014)
undertook a questionnaire study for athletes preparing for the
Olympic Games; of the 36% of athletes with health problems,
15% had problems leading to reductions in sports performance orparticipation. Raysmith and Drew (2016) produced a ﬁgure that
demonstrated the risk of failure in a variety of international competitions, which was attributed to the weeks of modiﬁed training
due to illness or injury (Figure 3). Epidemiological data from international competition events show that 5–21% of elite athletes
experience illness episodes, with higher proportions in females
and in endurance events (Alonso et al., 2010; Drew et al., 2018;
Schwellnus et al., 2016; Timpka et al., 2017). The recorded incidences of URTI in these elite athletes ranged from 18% to 50%,
with several studies reporting infection as the most frequent cause.
An important aspect of prolonged, exhaustive exercise and/or competition can, therefore, be exercise-induced immunodepression. Also
affected are the digestive tract, skin tissues, and the genitourinary
tract. The signiﬁcant risk factors include high levels of depression
or anxiety, unusually intensive training periods with large ﬂuctuations, frequent long-haul ﬂights, competitive events in the winter,lack of sleep, and a low energy diet intake. The decrease in exercise
performance after URTI can last 2–4 days. Runners who start an
endurance race with systemic symptoms of an acute illness are
2–3 times less likely to complete the race.

Gastrointestinal Illnesses From Infectious Origins
Traveler’s Diarrhea. Epidemiology Elite athletes are often
required to travel across multiple time zones and continents to train

or compete. These travels and sojourns in foreign and remote countries can represent a dietary challenge and expose athletes to travelrelated illnesses. The most frequently reported illness reported hereis traveler’s diarrhea (TD). The TD is deﬁned as three or moreunformed stools occurring within a day, associated with a symptom
like vomiting, abdominal pain, nausea, or fever. Although recovery
usually occurs within a couple of days, such an infectious episodemay seriously impair the athlete’s capacity to train or compete during
this period. The incidence of TD largely depends on the destination.
High-risk areas comprise a large part of Asia, the Middle-East,
Africa, and Central and South America, whereas Eastern Europe,
South Africa, and the Caribbean are considered to be intermediaterisk areas (CDC Health Information, 2013). TD pathogens mayvary from one country to the other, but food or water contaminatedby Escherichia Coli is the most frequent cause (Patel et al., 2018).
Viruses account for approximately 10% of TD cases, and norovirus and rotavirus are the most frequently reported (Widdowson
et al., 2005). These viruses are a real threat for athletes, teams, andcompetition organizers since they are very contagious and can leadto outbreaks that are difﬁcult to contain (Six et al., 2016).
Prevention of TD Considering these risks of gastrointestinal
infection and their potentially negative impacts on athletic performance, it is very tempting to keep some antibiotic prophylaxis instock for elite athletes traveling to high-risk destinations. However,this should be considered on a case-by-case basis, since the actual
guidelines on this issue do not recommend that antimicrobial prophylaxis be used routinely by travelers (Riddle et al., 2017). Shoulda prophylactic treatment be prescribed, bismuth subsalicylate (twotablets, four times daily; 2.1 g/day) may be considered as a ﬁrstline treatment for an athlete who has a good compliance proﬁleand is not taking doxycycline for the prevention of malaria (toavoid the possible reduction of doxycycline absorption). Whenan antibiotic prophylaxis is indicated, rifaximin is recommended.
Neither the antibiotic quinolones nor the association trimethoprim–

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sulfamethoxazole are recommended because of the possibility ofdrug-resistant strains. Moreover, quinolones carry a risk of serious
side effects on tendons and muscles and should always be used withextreme caution in elite athletes (Arabyat et al., 2015).
Although there is little evidence that food and water precautions signiﬁcantly reduce the risk of TD (Shlim, 2005), athletes andtheir staff should always try to minimize risks by drinking fromsealed bottles and avoiding high-risk foods such as unpeeled fresh
fruits and vegetables, open buffets, undercooked meats, and foodsfrom street vendors.
Probiotics have been tested as possible nutritional options toprevent TD. Although two meta-analyses suggest a marginal beneﬁt of probiotics, both suggest there is insufﬁcient evidence forextrapolation to global recommendations for their use (McFarland,
2007; Sazawal et al., 2006). This is mainly explained by a variability in the age groups, setting, microbial agents involved, formulations, dose, and regimens in the different studies (see also Peeling
et al., 2018).

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Runner’s Diarrhea. Although runners may experience abdomi-

nal cramps, nausea, vomiting, and bloating during competition, themain gastrointestinal complaint is diarrhea (also called runner’s
trots). This is an exercise-induced diarrhea without pain, but sometimes associated with blood in the feces. The prevalence of Runner’s
Diarrhea (RD) is not clear since it varies greatly between studies(De Oliviera, 2017). This is probably explained by a lack of uniformity in the deﬁnition of RD. Runner’s Diarrhea is twice as
frequent in running as in cycling or swimming and is positively
associated with the duration and intensity of running.
Although the pathophysiology is not fully understood, RD iscaused by ischemic, mechanical or nutritional factors (De Oliviera,2017). During running, the autonomous nervous system operates a
blood shift from the splanchnic bed to the skeletal muscles, heart, andbrain areas. Hence, the splanchnic ﬂow has been shown to be reduced
by up to 80% in individuals running at a pace representing 70% of the
maximal oxygen uptake. This ischemia is sometimes associated withreperfusion, which creates intestinal barrier function loss, increased
permeability, and bacterial translocation. This phenomenon is aggravated by heat and the consumption of nonsteroidal anti-inﬂammatory
medicines. An increase of gut and organ mobility inside the abdomen
submitted to the running-induced impacts and vibrations is anotherproposed causative factor for RD but has been poorly documented sofar. Finally, inappropriate nutritional strategies or behaviors also
contribute to RD. For instance, a high intake of ﬁbers; high-fat andhigh-protein diets; and fructose (alone), caffeine, and bicarbonate(used as a buffering agent) consumption have been identiﬁed as
promoters of RD. The concentration and nature of carbohydrates(CHO) and electrolytes also play an important role in the genesis of
RD. Indeed, drinks with a high concentration of CHOs and increased
osmolality delay gastric emptying and may cause a shift of water in the
gut lumen, favoring the onset of diarrhea. Conversely, the addition of amoderate amount of sodium (0.4–0.8 g/L) increases glucose uptake
and enhances water absorption. As the normal glucose and multiple
transportable CHOs’ (glucose plus fructose plus maltodextrin) absorption rates by the intestine are 1.2 g/min and 1.8 g/min, respectively, therecommended CHO content in sports drinks is from 6% to 8% tominimize the risk of RD. This ensures reduced drink osmolality,
which enhances water and solute intakes and, therefore, limits the riskof gastrointestinal distress in some athletes (Jeukendrup, 2014). In
runners with irritable bowel syndrome, prior to running, the consumption of fermentable oligosaccharide, disaccharide, monosaccharide,and polyols (FODMAP), found in wheat, onions, some fruits andvegetables, and some dairy products, can favor RD. There is only very

limited evidence for suggesting that athletes with a normal bowel
function should avoid FODMAP.
Training the gut. During recent years, some promising research
has also shown that the stomach and the gut can be trained to
improve tolerance and gastric emptying during exercise (seeJeukendrup, 2017 for a more detailed description). For instance,
Lambert et al. (2008) showed that trained runners were able tocomfortably tolerate ingestion of a CHO-electrolyte solution at a
rate similar to their sweat rate during 90 min of moderate-intensity
running. This was achieved without any noticeable change in thegastric emptying rate. Moreover, it seems that gastric emptying
can be speciﬁcally adapted to the type of nutrient, as a few days of
increased dietary glucose intake increases the gastric emptying of
glucose. Similarly, an increased fat intake for the same duration
results in faster gastric emptying of fats, but not CHO.

Immunonutrition
Increasing numbers of studies involving elite athletes and immunonutrition have been reported. In 2017, the consensus statementof Bermon et al., 2017 focused on topics that have generated
immunonutrition research data. These include antioxidants, bovine
colostrum, CHOs, fatty acids, herbal supplements, minerals, prebiotics, probiotics, proteins, and vitamin D, some of which are also
discussed in Peeling et al. (2018). Space constraints do not permit alengthy discussion of all of these topics here, so the reader isdirected to Bermon et al. (2017) for an in-depth evaluation of therole these compounds have in immunonutrition. CHO and ironare discussed in this context in the present review, and CHO is
discussed in connection with gastrointestinal problems (see “Gastrointestinal Illnesses From Infectious Origins” section).
The most widely used supplement in sports is CHO, recognizedsince the 1960s as an ergogenic aid. Khansari et al. (1990) ﬁrst
suggested that increased CHO availability might combat exerciseinduced immunodepression via the stress hormone (cortisol)
response to exercise. The effects of an increased consumption of
CHO (60 g/hr) include the attenuated trafﬁcking of some leukocyte
subsets; a decrease in neutrophil degranulation was prevented; anincreased neutrophil respiratory burst; decreased numbers and percentages of antiviral Type 1 helper T-cells; decreased IFN-γ production; and positive lymphocyte responses to inﬂuenza, tetanus, andrhinovirus during exercise (Bermon et al., 2017). However, there iscurrently insufﬁcient evidence to suggest that CHO has a positiveeffect on URTI (Bermon et al., 2017). High CHO availability isimportant for elite endurance athletes in training and competition.
However, glycogen regulates the molecular cell signaling pathways
and hence the oxidative phenotype; thus, training with low CHO has
recently become popular with athletes (Hearris et al., 2018).

Iron
Iron is a trace mineral of signiﬁcant importance in the athlete’s
diet due to its key roles in oxygen transport, energy metabolism,
and immune function (since adequate iron supply is required by
the host for mounting an effective immune response, with iron deﬁciency primarily suggested to impact upon cell-mediated immunity; Beard, 2001). As a result of such processes, iron is important
to athlete performances that stress the aerobic energy system(i.e., middle-distance track running events and beyond). However,the symptoms of an iron deﬁciency include feelings of lethargy andfatigue (Nielsen & Nachtigall, 1998) and, consequently, there is

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clear merit in ensuring adequate iron stores across all athlete populations to mitigate any negative effects from the issues resulting
from a compromised iron status.
Compromised iron stores present as a common issue in athlete populations, with collective assessments of athlete cohorts
published by practitioners from the Australian Institute of Sportsuggesting an incidence rate of ∼15–20% in females and 3–4% in
males (Fallon, 2004, 2008); however, much higher rates in female
athletes (>30%) have also been observed (Beard & Tobin, 2000).
Currently, some debate exists as to the best approach and hematological measures for deﬁning an iron deﬁciency. However, current
routine assessment includes (at minimum) an analysis of the blood
markers serum ferritin, hemoglobin, and transferrin saturation,with the generally accepted hematological thresholds for detecting
an iron deﬁciency recently detailed by Clénin et al. (2015). It is
important that all hematological markers be analyzed from a blooddraw consistently collected at the same time point, that is, in themorning before the day’s training sessions begin; the athlete should
be in a rested state (no physical activity prior to collection) after anovernight 10-hr fast.
The increased incidence of iron deﬁciency in athlete populations may result from a number of exercise- and nonexercisedependent factors (for a review, see Peeling et al., 2008). Thesemay include considerations such as an inadequate dietary ironintake (possibly a result of an inadequate overall energy intake);being a vegetarian athlete (since nonheme [vegetable] iron sources
are absorbed less efﬁciently than heme [meat] iron sources) (Beard& Tobin, 2000); heavy, menstrual blood loss in female athletes(Pedlar et al., 2018); exercise-induced hemolysis, hematuria, or
gastrointestinal bleeding (for a review, see Peeling et al., 2008); andﬁnally, altered postexercise iron absorption and recycling as a resultof elevations to the iron regulatory hormone, hepcidin (Peeling
et al., 2009). No doubt, these issues are hard to avoid due to theirinnate association to athletic training, and as a result, iron supplementation protocols are generally required to treat this problem.
Currently, there appear to be several means of correcting aniron deﬁciency through supplementation. The ﬁrst, and most basic,
is to increase dietary intake of high iron-containing foods such as
red meat, leafy green vegetables, lentils, beans, nuts, seeds, andfortiﬁed cereals. When considering the dietary intake of iron, it isimportant to note that a higher bioavailability can be achieved byincreasing the concurrent consumption of food components thatenhance iron absorption (such as ascorbic acid—vitamin C) or bydecreasing the content of inhibitors such as phytates and tannins(Hallberg et al., 1989). Since the recommended daily iron intake is
8 mg for males and up to 18 mg for menstruating females (Food andNutrition Board, 2001), an athlete presenting with an iron deﬁciency should, in the ﬁrst instance, work with a trained sports
dietitian to ensure the whole food composition of the diet contains
sufﬁcient amounts of iron to meet the demands of training. The
second and most widely used approach to iron supplementation
involves the use of oral iron supplements. In general, these come in
the ferrous (ferrous fumarate, ferrous sulfate, and ferrous gluconate),or ferric form; the latter is less well tolerated (Brittenham, 2000).
Athlete cohort studies show generally positive responses (40–80%
increase) to long-term oral iron supplementation (8+ weeks) provided at a rate of ∼100 mg per day (Dawson et al., 2006; Garvican
et al., 2014). Of interest, recent research has shown that alternate
day supplementation (rather than every day), can result in a greater
fractional and cumulative total iron absorption, when the same
absolute dose (i.e., 60 mg of iron for 14 days consecutively vs.
28 days alternating) is provided (Stoffel et al., 2017). As a result,

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alternate day supplementation (over a longer time period) may
prove to be a more efﬁcacious approach to supplementation andshould be considered by the athlete’s nutrition team. Despite thegenerally positive responses to oral iron supplementation, it should
be noted that a high incidence of gastrointestinal disturbance fromoral iron supplementation is commonly reported (Tolkien et al.,2015); however, supplement forms provided as iron polymaltose or
using enteric tablet coating may help reduce any gastrointestinal upset.
Indeed, it is evident from the above information that a signiﬁcant length of time is needed to realize a positive outcome withthe use of oral iron supplements. In situations where time may beof the essence (i.e., rapidly improving iron stores before starting at
an altitude camp to optimize hematological adaptation; GarvicanLewis et al., 2018), faster approaches to correcting an iron deﬁciency might be considered. Such a prospect leads us to the more
contemporary methods of correcting an individual’s iron stores,
such as intramuscular or intravenous (IV) iron supplementation.
Both processes have been shown to have extremely positive andfast-acting impacts on an athlete’s iron status (Dawson et al., 2006;
Garvican et al., 2011; Garvican et al., 2014), likely as a result of
bypassing the gut, where many known issues of iron absorption
exist. Although the speed of effect is a key positive outcome ofthese alternative iron supplementation methods, such protocols
should be reserved for athletes in desperate need of iron therapy,
who appear unresponsive to more traditional approaches of dietaryintervention or oral iron supplementation. Any such decision toundertake these alternative supplement approaches should only becontemplated under the supervision of a sports physician sincerisks of anaphylaxis with the parenteral iron administration havebeen reported (Rampton et al., 2014). Administration methods
must be acceptable and consistent with the rules of the sport’s
highest governing body and the antidoping authorities.
In summary, iron plays an essential role in the body of an
athlete, and there are both performance and health implications
related to compromised iron stores. As such, annual athlete screening for iron status should be a routine practice, with three monthly
follow-ups provided to those with known issues in maintaining ahealthy iron store. When identiﬁed, iron-deﬁcient athletes should,
in the ﬁrst instance, have a full dietary assessment under the instruction of a qualiﬁed sports dietitian. Once the dietary component is optimized, unresponsive athletes might consider a daily
oral iron supplement provided for an 8–12 week period, before
a reassessment of the iron stores is conducted. In extreme andpersistent unresponsive cases, the athlete and his or her support
team (dietitian and sports physician) might consider the use of
intramuscular or intravenous supplementation. However, checksof protocol legality and athlete safety must be thoroughly considered prior to such action.
This review has focused on illnesses and possible nutritional
aids to combat them; nevertheless, it seems appropriate to add some
additional helpful and practical suggestions. Readers should bearin mind that other reviews in this Special Issue will also be giving
practical advice from different sports perspectives.

Practical Recommendations
1. Training and Competition Load Managementa. Develop a detailed, individualized training and competition
plan that also provides for sufﬁcient recovery using sleep,
nutrition, hydration, and psychological strategies.

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b. Use small increments when changing training loads (typically<10% weekly).
c. Develop a competition event calendar based on the health ofindividual athletes.
d. Monitor for early signs and symptoms of overreaching, overtraining, and illness.
e. Avoid intensive training when ill or experiencing early signs
and symptoms of illness.
f. Participate in current illness surveillance systems by sport
agencies.
2. Hygienic, Lifestyle, Nutritional, and Behavioral Strategies
a. Minimize pathogen exposure by avoiding close contact with
infected individuals in crowded, enclosed spaces and not
sharing drinking or eating implements. Medical staff should
isolate infected athletes.
b. Limit hand-to-face contact (i.e., self-inoculation), and wash
hands regularly and effectively. Medical staff should educate
athletes to minimize pathogen spread to others (e.g., sneezing
and coughing into the crook of the elbow).
c. Follow other hygienic practices to limit all types of infections, including safe sex and the use of condoms. Wear open
footwear when using public facilities, to limit skin infections. Use insect repellent and cover the arms and legs withclothing at dawn or dusk.
d. Maintain vaccines needed for home and foreign travel; focus
on annual inﬂuenza vaccination.
e. As advised in the section on gastrointestinal illness, during
foreign travel, all team members should minimize risks bydrinking from sealed bottles. They should also avoid foods
such as unpeeled fresh fruits and vegetables, open buffets,
undercooked meats, and foods from street vendors.
f. Follow strategies that facilitate regular, high-quality sleep.
g. Avoid excessive alcohol intake.
h. Consume a well-balanced diet with sufﬁcient energy to maintain a healthy weight; focus on grains, fruits, and vegetables
to provide sufﬁcient CHO and polyphenols that reduce
exercise-induced inﬂammation and improve viral protection(see Bermon et al., 2017; Castell, Stear & Burke, 2015
Peeling et al., 2018, for further information on nutritional
supplements).
3. Psychological Load Managementa. Follow stress management techniques that reduce the extraneous load of life hassles and stresses.
b. Develop coping strategies that minimize the internalized
impact of negative life events and emotions.
c. Periodically monitor psychological stresses using available
instruments.

Conclusion
Athletes must train hard for competition, and they are interested instrategies to keep their immune systems robust and illness rates
low despite the physiological stress experienced. The ultimate
objective is to achieve performance goals with little interruption
from illness and fatigue due to exercise-induced immunodepression. Several training, hygienic, nutritional, and psychologicalstrategies are recommended, requiring the coordinated involvement of medical staff, coaches, sports nutritionists, and athletes.
An illness prevention program should be developed and implemented, focusing on full preventative precautions for high-risk
individuals.

References
Alonso, J.M., Tscholl, P.M., Engebretsen, L., Mountjoy, M., Dvorak, J., &Junge, A. (2010). Occurrence of injuries and illnesses during the 2009
IAAF World Athletics Championships. British Journal of Sports
Medicine, 44, 1100–1105. PubMed ID: 21106775 doi:10.1136/bjsm.
2010.078030
Arabyat, R.M., Raisch, D.W., McKoy, J.M., & Bennett, C.L. (2015).
Fluoroquinolone-associated tendon-rupture: A summary of reports in
the Food and Drug Administration’s adverse event reporting system.
Expert Opinion on Drug Safety, 14, 1653–1660. PubMed ID:
26393387 doi:10.1517/14740338.2015.1085968
Beard, J., & Tobin, B. (2000). Iron status and exercise. American Journalof Clinical Nutrition, 72(Suppl. 2), 594S–597S. PubMed ID:
10919965 doi:10.1093/ajcn/72.2.594S
Beard, J.L. (2001). Iron biology in immune function, muscle metabolism
and neuronal functioning. Journal of Nutrition, 131(2S-2), 568S–
579S; discussion 580S. PubMed ID: 11160590 doi:10.1093/jn/
131.2.568S
Bermon, S., Castell, L.M., Calder, P.C., Bishop, N.C., Blomstrand, E.,
Mooren, F.C., : : : Nagatomi, R. (2017). Consensus statement: Immunonutrition and exercise. Exercise Immunology Reviews, 23, 8–50.
Brittenham, G.M. (2018). Disorders of iron metabolism: Iron deﬁciency
and overload. In R. Hoffman, E. Benz, L. Silberstein, H. Heslop, J.
Weitz, & J. Anastasi Hematology: Basic principles and practice (7thed, pp. 478–490). Philadelphia, PA: Elsevier.
Calder, P.C. (2013). Feeding the immune system. Proceedings of the
Nutrition Society, 72, 299–309. PubMed ID: 23688939 doi:10.1017/
S0029665113001286
Castell, L.M., Poortmans, J., & Newsholme, E.A. (1996). Does glutamine
have a role in reducing infections in athletes? European Journal ofApplied Physiology, 73, 488–490. doi:10.1007/BF00334429
Castell, L.M., Stear, S., & Burke, L.M. (Eds.). (2015). Nutritional
supplements in sport, exercise and health: An A-Z guide. Oxfordshire,
UK: Routledge.
Centers for Disease Control and Prevention. (2013). CDC health information for international travel 2014: The yellow book. New York,
NY: Oxford University Press.
Clarsen, B., Ronsen, O., Myklebust, G., Florenes, T.W., & Bahr, R.
(2014). The Oslo Sports Trauma Research Center questionnaire
on health problems: A new approach to prospective monitoring of
illness and injury in elite athletes. British Journal of Sports Medicine,
48(9), 754–760. PubMed ID: 23429267 doi:10.1136/bjsports-2012092087
Clénin, G., Cordes, M., Huber, A., Schumacher, Y.O., Noack, P., Scales,J., & Kriemler, S. (2015). Iron deﬁciency in sports—deﬁnition,
inﬂuence on performance and therapy. Swiss Medical Weekly, 145,
w14196. doi:10.4414/smw.2015.14196
Dawson, B., Goodman, C., Blee, T., Claydon, G., Peeling, P., Beilby, J., &Prins, A. (2006). Iron supplementation: Oral tablets versus intramuscular injection. International Journal of Sport Nutrition and Exercise
Metabolism, 16(2), 180–186. PubMed ID: 16779924 doi:10.1123/
ijsnem.16.2.180
De Oliveira, E.P. (2017). Runner’s diarrhea: What is it, what causes it, andhow can it be prevented? Current Opinion in Gastroenterology, 33,
41–46. doi:10.1097/MOG.0000000000000322

IJSNEM Vol. 29, No. 2, 2019

Downloaded by on 04/17/19

Exercise-induced Illness and Inﬂammation

Drew, M., Vlahovich, N., Hughes, D., Appaneal, R., Burke, L.M.,
Lundy, B., : : : Waddington, G. (2018). Prevalence of illness, poor
mental health and sleep quality and low energy availability prior to the2016 Summer Olympic Games. British Journal of Sports Medicine,52, 47–53. PubMed ID: 29056598 doi:10.1136/bjsports-2017-098208
Engebretsen, L., Soligard, T., Steffen, K., Alonso, J.M., Aubry, M.,
Budgett, R., : : : Renstrom, P.A. (2013). Sports injuries and illnesses
during the London Summer Olympic Games 2012. British Journal ofSports Medicine, 47, 407–414. PubMed ID: 23515712 doi:10.1136/
bjsports-2013-092380
Fallon, K.E. (2004). Utility of hematological and iron-related screening inelite athletes. Clinical Journal of Sports Medicine, 14(3), 145–152.
doi:10.1097/00042752-200405000-00007
Fallon, K.E. (2008). Screening for haematological and iron-related abnormalities in elite athletes-analysis of 576 cases. Journal of Science andMedicine in Sport, 11(3), 329–336. PubMed ID: 17543581 doi:10.
1016/j.jsams.2007.02.017
Febbraio, M.A., & Pedersen, B.K. (2002). Muscle-derived interleukin-6:
Mechanisms for activation and possible biological roles. FASEBJournal, 16(11), 1335–1347. PubMed ID: 12205025 doi:10.1096/
fj.01-0876rev
Food and Nutrition Board. (2001). Institute of Medicine (US) Panel on
Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K,
Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese,
Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington(DC): National Academies Press (US). https://www.ncbi.nlm.nih.
gov/books/NBK222307/
Garvican, L.A., Lobigs, L., Telford, R., Fallon, K., & Gore, C.J. (2011).
Haemoglobin mass in an anaemic female endurance runner before
and after iron supplementation. International Journal of Sports,
Physiology and Performance, 6(1), 137–140. doi:10.1123/ijspp.
6.1.137
Garvican, L.A., Saunders, P.U., Cardoso, T., Macdougall, I.C., Lobigs, L.M.,
Fazakerley, R., : : : Gore, C.J. (2014). Intravenous iron supplementation in distance runners with low or suboptimal ferritin. Medicine &Science in Sports & Exercise, 46(2), 376–385. PubMed ID: 23872938
doi:10.1249/MSS.0b013e3182a53594
Garvican-Lewis, L.A., Vuong, V.L., Govus, A.D., Peeling, P., Jung, G.,
Nemeth, E., : : : Gore, C.J. (2018). Intravenous iron does not augment
the hemoglobin mass response to simulated hypoxia. Medicine &Science in Sports & Exercise, 50(8), 1669–1678. PubMed ID:
29538179 doi:10.1249/MSS.0000000000001608
Hallberg, L., Brune, M., & Rossander, L. (1989). The role of vitamin C iniron absorption. International Journal of Vitamin and Nutrition
Research Supplements, 30, 103–108.
Hearris, M.A., Hammond, K.M., Fell, J.M., & Morton, J.P. (2018).
Regulation of muscle glycogen metabolism during exercise: Implications for endurance performance and training adaptations. Nutrients,
10(3), 298. PubMed ID: 29498691 doi:10.3390/nu10030298
Hellard, P., Avalos, M., Guimaraes, F., Toussaint, J.F., & Pyne, D.B.
(2015). Training-related risk of common illnesses in elite swimmers
over a 4-yr period. Medicine & Science in Sports & Exercise, 47, 698–
707. PubMed ID: 25100341 doi:10.1249/MSS.0000000000000461
Jeukendrup, A.E. (2014). A step towards personalized sports nutrition:
Carbohydrate intake during exercise. Sports Medicine, 44(Suppl. 1),
S25–S33. doi:10.1007/s40279-014-0148-z
Jeukendrup, A.E. (2017). Training the gut for athletes. Sports Medicine,
47(Suppl. 1), 101–110. PubMed ID: 28332114 doi:10.1007/s40279017-0690-6
Khansari, D.N., Murgo, A.J., & Faith, R.E. (1990). Effects of stress on the
immune system. Immunology Today, 11, 170–175. PubMed ID:
2186751 doi:10.1016/0167-5699(90)90069-L

187

Konig, D., Grathwohl, D., Weinstock, C., Northoff, H., & Berg, A. (2000).
Upper respiratory tract infection in athletes: Inﬂuence of lifestyle,
type of sport, training effort, and immunostimulant intake. Exercise
Immunology Reviews, 6, 102–120.
Lambert, G.P., Lang, J., Bull, A., Eckerson, J., Lanspa, S., & O’Brien, J.
(2008). Fluid tolerance while running: Effect of repeated trials.
International Journal of Sports Medicine, 29, 878–882. PubMed
ID: 18512180 doi:10.1055/s-2008-1038620
Larrabee, R.C. (1902). Leucocytosis after violent exercise. Journal of
Medical Research, 7, 76–82. PubMed ID: 19971455
Markworth, J.F., Maddipati, K.R., & Cameron-Smith, D. (2016). Emerging roles of pro-resolving lipid mediators in immunological andadaptive responses to exercise-induced muscle injury. Exercise
Immunology Reviews, 22, 110–134.
McFarland, L.V. (2007). Meta-analysis of probiotics for the preventionof traveler’s diarrhea. Travel Medicine and Infectious Disease, 5,
97–105. PubMed ID: 17298915 doi:10.1016/j.tmaid.2005.10.003
Nielsen, P., & Nachtigall, D. (1998). Iron supplementation in athletes.
Current recommendations. Sports Medicine, 26(4), 207–216.
PubMed ID: 9820921 doi:10.2165/00007256-199826040-00001
Nieman, D.C. (1994). Physical activity, ﬁtness and infection. In: C.
Bouchard, R.J. Shephard, & T. Stephens (Eds.), Physical activity,ﬁtness, and health: International Proceedings and Consensus Statement (pp. 796–813). Champaign, IL: Human Kinetics Books.
Nieman, D.C., Groen, A., Pugachev, A., & Vacca, G. (2018a). Detection of functional overreaching in endurance athletes using proteomics. Journal of Proteome Research, 6(3), 33. doi:10.3390/
proteomes6030033
Nieman, D.C., Johansen, L.M., Lee, J.W., Cermak, J., & Arabatzis, K.
(1990). Infectious episodes in runners before and after the Los
Angeles Marathon. Journal of Sports Medicine and Physical Fitness,
30, 316–328. PubMed ID: 2266764
Nieman, D.C., Lila, M.A., & Gillitt, N.D. (2018b). Immunometabolism: A
multi-omics approach to interpreting the inﬂuence of exercise and dieton the immune system. Annual Review of Food Science Technology.
Patel, A.R., Oheb, D., & Zaslow, T.L. (2018). Gastrointestinal prophylaxis
in sports medicine. Sports Health, 10(2), 152–155. PubMed ID:
28952896 doi:10.1177/1941738117732733
Peake, J.M., Neubauer, O., Della Gatta, P.A., & Nosaka, K. (2017).
Muscle damage and inﬂammation during recovery from exercise.
Journal of Applied Physiology, 122, 559–570. PubMed ID: 28035017
doi:10.1152/japplphysiol.00971.2016
Pedlar, C.R., Brugnara, C., Bruinvels, G., & Burden, R. (2018). Ironbalance and iron supplementation for the female athlete: A practical
approach. European Journal of Sports Science, 18(2), 295–305.
doi:10.1080/17461391.2017.1416178
Peeling, P., Castell, L.M., Derave, W., de Hon, O., & Burke, L. (2019).
Sports foods and dietary supplements for optimal function andperformance enhancement in track and ﬁeld athletes. International
Journal of Sport Nutrition and Exercise Metabolism, 29(2). doi:10.
1123/ijsnem.2018-0271.
Peeling, P., Dawson, B., Goodman, C., Landers, G., & Trinder, D. (2008).
Athletic induced iron deﬁciency: New insights into the role ofinﬂammation, cytokines and hormones. European Journal of Applied
Physiology, 103(4), 381–391. PubMed ID: 18365240 doi:10.1007/
s00421-008-0726-6
Peeling, P., Dawson, B., Goodman, C., Landers, G., Wiegerinck, E.T.,
Swinkels, D.W., & Trinder, D. (2009). Effects of exercise on
hepcidin response and iron metabolism during recovery. International Journal of Sport Nutrition and Exercise Metabolism,
19(6), 583–597. PubMed ID: 20175428 doi:10.1123/ijsnem.19.
6.583

IJSNEM Vol. 29, No. 2, 2019

Downloaded by on 04/17/19

188

Castell et al.

Peters, E.M., & Bateman, E.D. (1983). Ultramarathon running and upper
respiratory tract infections. An epidemiological survey. South African
Medical Journal, 64, 582–584. PubMed ID: 6623247
Rampton, D., Folkersen, J., Fishbane, S., Hedenus, M., Howaldt, S.,
Locatelli, F., : : : Weiss, G. (2014). Hypersensitivity reactions to
intravenous iron: Guidance for risk minimization and management.
Haematologica, 99(11), 1671–1676. PubMed ID: 25420283 doi:10.
3324/haematol.2014.111492
Raysmith, B.P., & Drew, M.K. (2016). Performance success or failure isinﬂuenced by weeks lost to injury and illness in elite Australian track
and ﬁeld athletes: A 5-year prospective study. Journal of Science andMedicine in Sport, 19, 778–783. PubMed ID: 26839047 doi:10.1016/
j.jsams.2015.12.515
Riddle, M.S., Connor, B.A., Beeching, N.J., DuPont, H.L., Hamer, D.H.,
Kozarsky, P., : : : Ericsson, C.D. (2017). Guidelines for the prevention and treatment of travelers’ diarrhea: A graded expert panel report.
Journal of Travel Medicine, 24(Suppl. 1), S57–S74. PubMed ID:
28521004 doi:10.1093/jtm/tax026
Sazawal, S., Hiremath, G., Dhingra, U., Malik, P., Deb, S., & Black, R.E.
(2006). Efﬁcacy of probiotics in prevention of acute diarrhoea:
A meta-analysis of masked, randomised, placebo-controlled trials.
The Lancet Infectious Diseases, 6, 374–382. PubMed ID: 16728323
doi:10.1016/S1473-3099(06)70495-9
Schwellnus, M., Soligard, T., Alonso, J.M., Bahr, R., Clarsen, B., Dijkstra,
H.P., : : : Engebretsen, L. (2016). How much is too much? (Part 2)
International Olympic Committee consensus statement on load in sportand risk of illness. British Journal of Sports Medicine, 50, 1043–1052.
PubMed ID: 27535991 doi:10.1136/bjsports-2016-096572
Shlim, D.R. (2005). Looking for evidence that personal hygiene precautions prevent traveler’s diarrhea. Clinical Infectious Diseases,
41(Suppl. 8), S531–S535. doi:10.1086/432947
Six, C., Aboukais, S., Giron, S., D’Oliveira, J.C., Peloux-Petiot, F.,
Franke, F., : : : Malfait, P. (2016). Outbreak of diarrhoeal illness
in participants in an obstacle adventure race, Alpes-Maritimes,
France, June 2015. Eurosurveillance, 21(23), 30253. doi:10.
2807/1560-7917.ES.2016.21.23.30253

Spence, L., Brown, W.J., Pyne, D.B., Nissen, M.D., Sloots, T.P.,
McCormack, J.G., : : : Fricker, P.A. (2007). Incidence, etiology,
and symptomatology of upper respiratory illness in elite athletes.
Medicine & Science in Sports & Exercise, 39, 577–586. PubMed ID:
17414793 doi:10.1249/mss.0b013e31802e851a
Stoffel, N.U., Cercamondi, C.I., Brittenham, G., Zeder, C., GeurtsMoespot, A.J., Swinkels, D.W., : : : Zimmermann, M.B. (2017).
Iron absorption from oral iron supplements given on consecutive
versus alternate days and as single morning doses versus twicedaily split dosing in iron-depleted women: Two open-label,randomised controlled trials. The Lancet Haematology, 4(11),e524–e533. PubMed ID: 29032957 doi:10.1016/S2352-3026(17)30182-5
Svendsen, I.S., Gleeson, M., Haugen, T.A., & Tønnessen, E. (2015). Effectof an intense period of competition on race performance and selfreported illness in elite cross-country skiers. Scandinavian Journal of
Medicine & Science in Sports, 25, 846–853. PubMed ID: 25818900
doi:10.1111/sms.12452
Timpka, T., Jacobsson, J., Bargoria, V., Périard, J.D., Racinais, S., Ronsen, O.,: : : Alonso, J.M. (2017). Preparticipation predictors for championshipinjury and illness: Cohort study at the Beijing 2015 International
Association of Athletics Federations World Championships. British
Journal of Sports Medicine, 51, 271–276. PubMed ID: 27827793
doi:10.1136/bjsports-2016-096580
Tolkien, Z., Stecher, L., Mander, A.P., Pereira, D.I., & Powell, J.J. (2015).
Ferrous sulfate supplementation causes signiﬁcant gastrointestinal
side-effects in adults: A systematic review and meta-analysis. PLoS
ONE, 10(2), e0117383. PubMed ID: 25700159 doi:10.1371/journal.
pone.0117383
Walsh, N.P., Gleeson, M., Shephard, R.J., Gleeson, M., Woods, J.A.,
Bishop, N.C., : : : Simon, P. (2011). Position statement. Part one:
Immune function and exercise. Exercise Immunology Reviews,
17, 6–63.
Widdowson, M.A., Monroe, S.S., & Glass, R.I. (2005). Are noroviruses
emerging? Emerging Infectious Diseases, 11, 735–737. PubMed ID:
15898170 doi:10.3201/eid1105.041090

IJSNEM Vol. 29, No. 2, 2019