Review

Exercise-Induced Gastrointestinal Symptoms in Endurance

Sports: A Review of Pathophysiology, Symptoms, and
Nutritional Management
Emanuela Ribichini 1, * , Giulia Scalese 1, * , Alessandra Cesarini 1 , Chiara Mocci 1 , Nadia Pallotta 1 ,
Carola Severi 1 and Enrico Stefano Corazziari 2

1 Gastroenterology, Department of Translational and Precision Medicine, Sapienza University of Rome,

00186 Rome, Italy; [email protected] (A.C.); [email protected] (C.M.);
[email protected] (N.P.); [email protected] (C.S.)
2 Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy;
[email protected]
* Correspondence: [email protected] (E.R.); [email protected] (G.S.)

Abstract: Strenuous exercise can be associated with “Exercise Induced Gastrointestinal Syndrome”
(Ex-GIS), a clinical condition characterized by a series of gastrointestinal (GI) disturbances that may
impact the physical and psychological performance of athletes. The pathophysiology comprises
multi-factorial interactions between the GI tract and the circulatory, immune, enteric, and central
nervous systems. There is considerable evidence for increases in the indices of intestinal damage,
permeability, and endotoxemia associated with impaired gastric emptying, slowing of small intestinal
transit, and malabsorption of nutrients. Heat stress and racing mode seem to exacerbate these GI
disturbances. GI symptomatology that derives from strenuous exercise is similar to that of IBS
and other GI functional disorders defined in the Rome IV Criteria. To manage Ex-GIS, the exercise
modality, state of dehydration, environmental temperature, concomitant therapies, and self-managed
Citation: Ribichini, E.; Scalese, G.; diet should be evaluated, and if risk elements are present, an attempt should be made to modify
Cesarini, A.; Mocci, C.; Pallotta, N.; them. Multiple strategies can be successively adopted to manage Ex-GIS. Nutritional and behavioral
Severi, C.; Corazziari, E.S. interventions appear to be the principal ones to avoid symptoms during the exercise. The aim of this
Exercise-Induced Gastrointestinal
review will be to explore the pathophysiology, clinical aspect, and current literature on behavioral
Symptoms in Endurance Sports: A
and nutritional strategies to manage Ex-GIS, regarding a gluten-free diet and low-fermentable oligo-,
Review of Pathophysiology,
di-, and mono-saccharides and polyols (FODMAP) diet.
Symptoms, and Nutritional
Management. Dietetics 2023, 2,
Keywords: gastrointestinal symptoms; endurance sport; diet; IBS
289–307. https://doi.org/10.3390/
dietetics2030021

Academic Editor: Bahram H.

Arjmandi 1. Introduction
Received: 26 July 2023 Physical activity has many positive effects on health, especially on the musculoskeletal,
Revised: 30 August 2023 cardiovascular, and gastrointestinal (GI) systems. Its effect depends on the intensity, dura-
Accepted: 12 September 2023 tion, and modality of physical activity. Mild- to moderate-intensity exercise with a regular
Published: 19 September 2023 duration (e.g., between 3.5 and 4 h per week) plays a protective role against colon cancer,
diverticular disease, gallstones, and constipation [1,2]. On the other hand, strenuous exer-
cise and endurance sports may cause exercise-induced gastrointestinal symptoms (Ex-GISs)
in up to 70% of athletes, and they can manifest as upper symptoms (e.g., regurgitation,
Copyright: © 2023 by the authors.
upper abdominal bloating, belching, epigastric pain, and heartburn) and lower symptoms
Licensee MDPI, Basel, Switzerland.
(e.g., flatulence, urge to defecate, lower abdominal bloating, abdominal pain, abnormal
This article is an open access article
defecation including loose water stools, diarrhea, and fecal blood loss) [3]. Endurance exer-
distributed under the terms and
conditions of the Creative Commons
cise is considered a sport aimed at improving the ability to sustain intense physical activity
Attribution (CC BY) license (https://
over time, without significant loss of performance. Endurance includes different physical
creativecommons.org/licenses/by/ activities with different levels of intensity and thus workouts can differ greatly according
4.0/). to the disciplines practiced. Cycling, swimming, marathons, triathlons, running, mountain

Dietetics 2023, 2, 289–307. https://doi.org/10.3390/dietetics2030021 https://www.mdpi.com/journal/dietetics

Dietetics 2023, 2 290

biking, and climbing are some of those considered endurance sports simply because they
require an expenditure of energy for a long time [4]. Ex-GIS might result from responses to
exercise that compromise gastrointestinal integrity and function and may even be the reason
why some stop sports participation [3]. The mechanisms leading to GI discomfort during
exercise are not yet fully understood [5]. Exercise responses may involve two different path-
ways: a circulatory–gastrointestinal pathway [6] and a neuroendocrine–gastrointestinal
pathway [7]. The combination of splanchnic hypoperfusion and altered enteric nervous
system activity may result in a compromised GI system. The loss of epithelial integrity
observed during strenuous physical exercise leads to increased intestinal permeability with
bacterial translocation and inflammation. This alteration may negatively impact exercise
performance and post-exercise recovery due to abdominal distress and impairment in the
uptake of fluid, electrolytes, and nutrients. Exercise may also have a substantial impact on
gut microbiota (GM) composition and structure, but the role of the microbiota in exercise
adaptation remains unknown [8]. Notable differences have been described between com-
peting athletes and inactive people. Zhao et al. [9] examined the GM and fecal metabolites
of amateur runners before and after a half marathon, and they showed shifts in the relative
abundance of the GM at several different taxonomic levels [9]. Therefore, there is a need
to integrate the evidence more comprehensively for all elements of exercise-associated GI
disturbances. In this light, the purpose of this article is firstly, to review the physiological
and pathophysiological changes of the GI tract during endurance exercise, exploring the
pathophysiology of Ex-GIS; secondly, to describe the clinical aspects of the syndrome
and its effect on athletes’ performances; and thirdly, to review the current literature on
behavioral and nutritional strategies to manage the condition, with particular regard to
dietetic regimens adopted by athletes to reduce symptoms.

2. Methods
Three databases (PubMed, MEDLINE, Cochrane, Canada) were searched for relevant
publications. The search was performed up to March 2023. The search strings utilized for
the chapter’s introduction and pathophysiology of Ex-GIS, proposed mechanisms for GI
distress, and gastrointestinal symptoms during exercise were “endurance”, “endurance
sports”, “endurance activity”, “gastrointestinal symptoms”, and “exercise-induced gas-
trointestinal symptoms”. We identified studies published from 1965 to 2023. The search
performed in PubMed returned 290 results, in MEDLINE 216 results, and in the Cochrane
library 97 trials. The search strings utilized for the chapters nutritional and behavior strate-
gies to reduce Ex-GIS and efficacy of specific diets applied by endurance athletes to avoid
Ex-GIS were “endurance”, “endurance sports”, “endurance activity”, “diet”, and “nutri-
tion”. We identified studies published from 1972 to 2023. The search performed in PubMed
returned 2663 results, in MEDLINE 2197 results, and in the Cochrane library 1038 trials.
The selection process began with the evaluation of the title and the abstract of the works.
All the works in which the keywords and the purposes of the review were not present were
excluded. In terms of inclusion criteria, only studies in the English language were selected.
Studies that did not address the impact of diet on endurance performance or health-related
parameters were excluded. Finally, the authors discussed the research findings and selected
the studies that were clinically and practically relevant for the purposes of this review.
Based on our inclusion and exclusion criteria, we identified 142 research articles.

3. Pathophysiology of Ex-GIS: Proposed Mechanisms for GI Distress

The pathophysiology of Ex-GIS includes two primary pathways: (I) the
neuroendocrine–gastrointestinal pathway, involving an increase in sympathetic activa-
tion, reducing overall GI functional capacity [3] and (II) the circulatory–gastrointestinal
pathway, involving the redistribution of blood flow to working muscles and periph-
eral circulation, subsequently reducing total splanchnic perfusion and nutrient absorp-
tion [10,11]. It is still under debate whether the neuroendocrine pathway may affect the
circulatory–gastrointestinal one and, in cascade, reduce the total splanchnic perfusion, or
 activation, reducing overall GI functional capacity [3] and (II) the circulatory–
gastrointestinal pathway, involving the redistribution of blood flow to working muscles
Dietetics 2023, 2 and peripheral circulation, subsequently reducing total splanchnic perfusion and nutrient 291
absorption [10,11]. It is still under debate whether the neuroendocrine pathway may affect
the circulatory–gastrointestinal one and, in cascade, reduce the total splanchnic perfusion,
or whether
whether thethe splanchnic
splanchnic hypoperfusion
hypoperfusion in in response
response to to the
the intensity/durationof
intensity/duration ofmuscle
muscle
activity may influence the neuroendocrine activation. It is plausible that the combination
activity may influence the neuroendocrine activation. It is plausible that the combination
ofthe
of thealtered
alteredenteric
entericnervous
nervoussystem
system activity
activity andand
thethe splanchnic
splanchnic hypoperfusion
hypoperfusion maymay
re-
result
sult in in
GIGI symptoms
symptoms and/orininacute
and/or acuteororchronic
chronichealth
healthcomplications
complications[5].
[5].The
Theproposed
proposed
mechanismsfor
mechanisms forgastrointestinal
gastrointestinaldiscomfort
discomfortarearesummarized
summarizedininFigure
Figure1.1.

Figure 1.
Figure 1. Proposed
Proposedmechanisms
mechanismsfor forEx-GIS
Ex-GISpathophysiology. Abbreviations:
pathophysiology. Ex-GIS:
Abbreviations: exercise-
Ex-GIS: exercise-
induced gastrointestinal symptoms; VO2max: maximal oxygen consumption; SNS: sympathetic
induced gastrointestinal symptoms; VO2max: maximal oxygen consumption; SNS: sympathetic
nervoussystem;
nervous system;ENS:
ENS:enteric
entericnervous
nervoussystem.
system.

3.1.
3.1. Neuroendocrine–Gastrointestinal
Neuroendocrine–GastrointestinalPathway
Pathway
The
The alteration
alteration of of the
the enteric
enteric nervous
nervous system
system (ENS)
(ENS) activity,
activity, through
through aa cascade
cascade of of
events,
events, results
resultsininclinical
clinicalcomplications
complicationsand andGIGI symptoms
symptoms known
known as Ex-GIS.
as Ex-GIS. Physical ac-
Physical
tivity induces
activity induces sympathetic
sympathetic activation,
activation,which is considered
which is consideredthe main causecause
the main of altered ENS
of altered
activity [12,13]. The digestive system is controlled by the bidirectional activity
ENS activity [12,13]. The digestive system is controlled by the bidirectional activity of the of the central
nervous system system
central nervous (CNS) and (CNS) theand
ENS,
theboth
ENS,ofbothwhich participate
of which in theinregulation
participate the regulation of the
of
various functions
the various of theof
functions intestines. ENS can
the intestines. independently
ENS regulateregulate
can independently GI functions without
GI functions
central
withoutinput.
central Indeed,
input. the ENS the
Indeed, is considered a quasi-autonomous
ENS is considered part of the
a quasi-autonomous nervous
part of the
system including several neural circuits that control motor functions,
nervous system including several neural circuits that control motor functions, local blood local blood flow, and
mucosal transport and secretions and modulate immune
flow, and mucosal transport and secretions and modulate immune and endocrine and endocrine functions [14].
Enteroendocrine cells (EECs), which
functions [14]. Enteroendocrine cellsare basal-granulated
(EECs), cells dispersed in cells
which are basal-granulated the gut epithe-
dispersed
lium, represent the endocrine elements of the intestine and release
in the gut epithelium, represent the endocrine elements of the intestine and release gut gut peptides, such as
cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide
peptides, such as cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY), all having
an
YYanorectic
(PYY), all effect. Ghrelin,
having on the other
an anorectic effect. hand, is an on
Ghrelin, orexigenic
the other peptide
hand,produced by the
is an orexigenic
enteroendocrine cells in the oxyntic glands of the stomach and
peptide produced by the enteroendocrine cells in the oxyntic glands of the stomach andupper intestine; thus, its
plasma levels are high before meals and are suppressed in response
upper intestine; thus, its plasma levels are high before meals and are suppressed in to food intake [15].
These neuropeptides
response to food intake act[15].
either in aneuropeptides
These paracrine fashion on both
act either in aintestinal
paracrineand neural
fashion oncells
both
in proximity or enter the bloodstream and can have peripheral effects, such as change in
intestinal and neural cells in proximity or enter the bloodstream and can have peripheral
gastric emptying and gut motility [16]. Briefly, CCK is synthesized and released from I
effects, such as change in gastric emptying and gut motility [16]. Briefly, CCK is
cells of the upper intestine in response to food intake. It slows down gastric emptying and
synthesized and released from I cells of the upper intestine in response to food intake. It
stimulates pancreatic and gallbladder secretions. CCK exerts its satiety action primarily
slows down gastric emptying and stimulates pancreatic and gallbladder secretions. CCK
through the activation of vagal afferent fibers innervating both the stomach and the upper
exerts its satiety action primarily through the activation of vagal afferent fibers innervating
intestine [17,18]. CCK levels rapidly increase after food ingestion, present a peak a few
minutes after meal initiation, and decline to baseline levels with meal termination [19]. In
contrast, the other gut peptides have patterns of release and actions that are consistent
with effects beyond the meal. Indeed, plasma levels of both PYY and GLP-1, which are
synthesized and released from L cells located primarily in the distal intestine, occur more
slowly, not peaking until after meal termination and remaining high for several hours after
Dietetics 2023, 2 292

a meal [20,21]. Both PYY and GLP-1 inhibit food intake. Few data are currently available
regarding the modification of gut peptide levels in response to physical activity. Various
animal and cell models have demonstrated that the activation of adenosine receptors in-
duces the release of GLP-1 and PYY from EECs [22,23], and concentrations of both are
increased during moderate- and high-intensity exercise. Moreover, exercise induces the
vago-vagal reflex from the brain back to the gut [24], which plays a role in the ability of CCK
to regulate gastric emptying and intestinal motility [25]. Some studies have evaluated the
modifications of gut peptide levels in response to different kinds of exercise. Halliday TM
and colleagues demonstrated that circulating concentrations of the anorexic gut peptides,
namely PYY and GLP-1, are increased following aerobic exercise as compared to resistance
exercise and that circulating concentrations of the orexigenic gut peptide, namely ghrelin,
are also higher following aerobic exercise and sedentary control vs. resistance exercise [26].
Other similar results were reported by Broom et al. [27] and Balaguera-Cortes et al. [28];
they both found blunted ghrelin responses to resistance exercise as compared to aero-
bic exercise. Furthermore, enteric neurons contain receptors for GABA, serotonin, and
dopamine, neuropeptides that have been found to be influenced by exercise [29]. In detail,
high-intensity exercise causes an increase in GABA concentrations in the sensorimotor
cortex, while acute exercise increases plasma dopamine levels [30]. Although exercise
induces changes in neuropeptides and may affect enteric neuron activation and function, it
is not fully known whether exercise directly affects local levels of enteric neuropeptides. It
is plausible that alterations in gastric emptying and gut motility during exercise are due, at
least in part, to increased gut peptide secretion and action. Among the neurotransmitters,
catecholamines and serotonin have recently been a topic of interest because of their roles in
gut physiology and their potential roles in GI and CNS pathophysiology. There are three
main catecholamines: norepinephrine (noradrenaline) and epinephrine (adrenaline), which
are peripheral catecholamines, and dopamine, which is a central-acting catecholamine. As
mentioned above, endurance exercise increases sympathetic nervous system (SNS) activity,
increasing the circulating concentrations of norepinephrine and epinephrine [31]. The main
function of norepinephrine is in vascular smooth muscle; indeed, it mainly acts on the
alpha receptors at all concentration ranges, and causes vasoconstriction, increased vascular
resistance, and decreased overall blood flow to the intestine. Epinephrine instead acts in a
dual way; at low doses, it stimulates the beta receptors, leading to vasodilation, meanwhile
at high doses, it acts similarly to norepinephrine and causes vasoconstriction. Finally,
dopamine receptor affinity is also concentration-dependent and, indeed, low dopamine
levels cause vasodilation and increased splanchnic blood flow through interaction with
D1 receptors, meanwhile at high doses, it acts like the other catecholamines and can be
classified as a vasoconstrictor, decreasing splanchnic blood flow [29]. Serotonin exerts a
wide range of actions on the GI tract by binding to seven classes of specific receptors (5-HT1
to 5-HT7), each of which produces its own response. For instance, 5-HT4 agonists relieve
visceral pain and increase intestinal motility [32], while the activation of 5-HT3 receptors
following the ingestion of irritants causes a rise in serotonin release by EECs, which in turn
increases peristalsis and causes diarrhea. Regarding exercise-induced motility changes,
data available to date are not unique, and many variables need to be considered. The
duration and intensity of exercise, for example, may have different effects on the ENS,
and while a short duration (i.e., <60 min) appears to promote GI motility, more prolonged
(i.e., up to 90 min) exercise may cause inhibition [5]. Likewise, low-intensity exercise
has little effect on GI motility, meanwhile in more vigorous exercise, ESN and relative
GI functions become progressively inhibited [5]. Therefore, it can be assumed that most
changes occurring in the intestinal tract are intensity- and duration-dependent and that
exercise stress of ≥2 h at 60% VO2max may represent the threshold at which significant
GI perturbations manifest [5]. Specifically, motility alterations have been observed in
different levels of the GI tract, including the esophagus, the stomach, and the intestines,
and generally are summarized as a slow gastric emptying and a delay of orocecal transit
time (OCTT). In more detail, esophageal modifications are represented by a decrease in
Dietetics 2023, 2 293

esophageal peristaltic activity, a decrease in lower esophageal sphincter tone, and increased
transient lower sphincter relaxation, which together could be linked to gastro-esophageal
reflux symptoms (GERD) experienced during exercise [33]. Effects on gastric emptying
are less clear, and especially in this case, the intensity of physical activity appears to be
the key regulator of the gastric emptying rate. Indeed, a very early work [34] reported
no effect of moderate exercise on gastric emptying, while later studies demonstrated a
reduction following very-high-intensity exercise or during intermittent activity [35]. En-
durance sports, through stress and the potent sympathetic activation, cause the inhibition
of gastric motility [36]. These data were also confirmed in an animal model, in which by
decreasing the sympathetic activity through the electrical stimulation of the spinal cord,
there was an increase in gastric emptying and intestinal transit [37]. Information about
small intestine and colonic motility is scarce, and the impact of exercise on OCTT is unclear.
For instance, Rao KA and colleagues measured OCTT using a telemetric pH sensor and
demonstrated that symptomatic and asymptomatic runners presented similar small bowel
and colonic transit times during rest and exercise sessions. Interestingly, the diarrhea seen
in the study did not result from an accelerated colonic transit and hence the researchers
concluded that other mechanisms must be sought [38]. In contrast, the OCTT measured
with lactulose breath tests decreased in both running [39] and cycling [40,41]. Considering
the heterogeneity of results and the complex interaction of hormonal and neurological
factors in the control of motility, other studies are needed to better elucidate the effect of
different kinds of exercise (duration, intensity, and mode) on OCTT [5].

3.2. Circulatory–Gastrointestinal Pathways

The splanchnic vasculature is a system with an extraordinary capacity to adapt to
physiological stressors affecting vasodilation or constriction in response to neuroendocrine,
humoral, and paracrine mechanisms [42]. During strenuous exercise, the release of nore-
pinephrine generates splanchnic vasoconstriction, thereby raising total splanchnic vascular
resistance [43]. Blood is rapidly redistributed from the splanchnic vasculature to the pe-
riphery for use in tissues with increased activity during exercise, such as the heart, lungs,
active muscles, and skin [10]. As a result, the splanchnic blood flow (SBF) can be depleted
by up to 80%, leading to significant gastrointestinal tract hypoperfusion and damage [44].
SBF hypoperfusion can be assessed through gastric tonometry [45], a functional test
that measures the accumulated mucosal carbon dioxide (CO2 ). In response to inadequate
tissue perfusion and tissue hypoxia, the gap between gastric and systemic PCO2 reflects
the adequacy of splanchnic perfusion [46]. The application of tonometry during exercise
shows the most pronounced change in splanchnic perfusion during the first 10 min of
strenuous exercise [11], indicating a rapid response of the splanchnic vascular bed. In
addition, tonometry shows that splanchnic hypoperfusion can be aggravated by younger
age, exercise intensity and duration, dehydration, and high environmental temperature [3].
The reductions in SBF are less conspicuous in the elderly (mean age 64 years) compared
with younger people [47]. SBF hypoperfusion despoils enterocytes of oxygen and adenosine
triphosphate (ATP), leading to cell damage and loss of epithelial integrity [48], which may
be responsible for the mucosal erosions and GI bleeding observed during endoscopy after
strenuous endurance running [49]. Consequently, the loss of epithelial integrity in the
intestine is reflected by significantly increased plasma levels of intestinal fatty acid binding
protein (I-FABP), a small cytosolic protein present in the enterocytes of the small intestinal
villi, rapidly released into circulation upon cellular injury [50]. Van Wijck et colleagues
demonstrated that 1 h of moderate physical exercise results in splanchnic ischemia followed
by an increase in I-FABP, suggesting that hypoperfusion occurs in the early stages of exercise
and intestinal epithelial damage occurs over time [11].
Loss of epithelial integrity, including disruption of the tight junctions interconnecting
the intestinal epithelial cells, is associated with increased GI permeability, intestinal in-
flammation, and bacterial translocation [51]. Bacterial translocation induces endotoxemia,
which is characterized by the presence of circulating bacterial lipopolysaccharides (LPSs).
 [11].
Loss of epithelial integrity, including disruption of the tight junctions interconnecting
Loss ofepithelial
the intestinal epithelial cells, integrity, including disruption
is associated with increased of the GI tight junctions interconnectin
permeability, intestinal
the intestinaland
inflammation, epithelial
bacterial cells,translocation
is associated [51]. with increased
Bacterial GI permeability,induces
translocation intestin
inflammation, and bacterial translocation
endotoxemia, which is characterized by the presence of circulating bacterial [51]. Bacterial translocation induc
Dietetics 2023, 2 endotoxemia, which
lipopolysaccharides (LPSs).isLoss characterized
of tight junction by the presence
integrity and/or of enterocyte
circulating 294 bacteri
damage
causelipopolysaccharides
passage of LPSs (LPSs). into theLoss of tight which
circulation, junction in integrity
turn triggers and/or theenterocyte
activation damag of T
cause passage
lymphocytes, of LPSsand
monocytes, intotissue
the circulation,
macrophages. which Theinlocal turnimmune
triggersresponse
the activationinducesof
the lymphocytes, monocytes, and
release of proinflammatory tissue macrophages.
cytokines such as tumorThe localfactor
necrosis immune andresponse
interleukin-1,induc
Loss of tight junction integrity and/or enterocyte damage cause passage of LPSs into the
the release of proinflammatory cytokines such as
interferon-γ, and nitric oxide (NO) [52], which can generate a vicious cycle that promotes tumor necrosis factor and interleukin-
circulation, which in turn triggers the activation of T lymphocytes, monocytes, and tissue
interferon-γ,
greater intestinal and nitricdysfunction
barrier oxide (NO)through [52], which can generate
production of thesea vicious
mediatorscycle[53].that promote
macrophages. The local immune response induces the release of proinflammatory cytokines Brock-
Utne greater
and intestinal
colleagues barrier
[54] dysfunction
provided the through
initial evidence
such as tumor necrosis factor and interleukin-1, interferon-γ, and nitric oxide (NO) [52], production
that the of these
intestinal mediators
barrier [53].
was Broc
being
Utne
compromised and colleagues
during [54]
prolonged, provided strenuous the initial evidence
exercise.
which can generate a vicious cycle that promotes greater intestinal barrier dysfunction In that that the
study, intestinal
81% of the barrier
89 was
marathon bein
compromised
runners (89.4 km) during
were prolonged,
found to be strenuous
endotoxemic
through production of these mediators [53]. Brock-Utne and colleagues [54] provided exercise.[54]. In that
Several study,
other 81% of the
investigators 89 maratho
have
the initial runners (89.4
subsequently
evidence that km)intestinal
reported
the were found
increased barrier to be endotoxemic
intestinal
was permeability
being [54]. Several
compromised and/orduring other
endotoxemiainvestigators
prolonged, during hav
subsequently
strenuous exercise, reported
intensified increased
by heat intestinal
stress
strenuous exercise. In that study, 81% of the 89 marathon runners (89.4 km) were found permeability
conditions [55,56] and/or
or by endotoxemia
dehydration durin
[57].
strenuous
Endotoxemia
to be endotoxemic exercise,
[54]. restingintensified
in Several humans
other by heat stress
produces
investigators conditions increased
GI symptoms,
have subsequently [55,56]
reported or pro-inflammatory
by dehydration [57
increased
Endotoxemia
release, in
and resting
fever. humans
Similar produces
effects are also GI
intestinal permeability and/or endotoxemia during strenuous exercise, intensified by heatduring
cytokine symptoms,
likely mediated increased
by pro-inflammator
endotoxemia
cytokine
exercise
stress conditions heat release,
[55,56] stress
or by and
[53]. fever. Similar
In extreme
dehydration effects
endurance
[57]. are also
Endotoxemia likely
exercise mediated
where
in resting an by
humans endotoxemia
increased
produces durin
intestinal
GI symptoms, exercise
permeability heat
increased or stress
significant [53]. increase
pro-inflammatory In extreme in endurance
cytokine plasma
release, LPS exercise
and and where an effects
pro-inflammatory
fever. Similar increased intestin
cytokine
are
also likely permeability
concentration
mediated bywas or described,
significant
endotoxemia GIincrease
during symptoms
exercisein heat
plasma
suchstressas LPS [53].and
nausea, pro-inflammatory
In vomiting,
extreme cramping,cytokin
endurance and
concentration
diarrhea were was
reported described,
[56,58,59]. GI symptoms
exercise where an increased intestinal permeability or significant increase in plasma LPS such as nausea, vomiting, cramping, an
diarrhea
The were
translocation reported of [56,58,59].
endotoxic microorganisms
and pro-inflammatory cytokine concentration was described, GI symptoms such as nausea, into circulation may also be
dependent
vomiting, Theontranslocation
cramping, the diarrhea
and presencewere of endotoxic
of indigenous microorganisms
bacterial species into
reported [56,58,59]. within circulation
the GI tract, may such alsoas b
The dependent on
Enterobacteriaceae,
translocation the presence
Proteobacteria,
of endotoxic of indigenous
Firmicutes,
microorganisms bacterial
Bacteroides,
into circulationandspecies
may within
also be the
Actinobacteria [40].GIThe
dependent tract, such a
impact
Enterobacteriaceae,
of exercise
on the presence on GM composition
of indigenous Proteobacteria,
bacterial species and Firmicutes,
structure
within the Bacteroides,
needs
GI tract, and
to such Actinobacteria
be mentioned in [40].
as Enterobacteriaceae, this The impa
context.
of exercise
Remarkable
Proteobacteria, Firmicutes, on Bacteroides,
differences GM composition
have and and structure
beenActinobacteria
described [40]. needs
between The to be of
competing
impact mentioned
athletes
exerciseand oninGM this contex
sedentary
composition Remarkable
people, andrelated
structure differences
to a huge tohave
needsmicrobiota been described
be mentioned in thisbetween
context. competing
Remarkableathletes differences and sedentar
have been people,
described related
between to a huge
competing microbiotaathletes and sedentary people, related to a huge
microbiota Ⲁ -diversity in athletes—mostly associated with dietary patterns and protein
consumption. Ⲁ -diversity is an index to describe the quality of the GM and is expected
to decrease -diversity
in disturbed in conditions
athletes—mostly such as disease associatedand poor with health dietary [60–62].
patterns Zhaoand et al.protein
described the GM
consumption. and
-diversity Ⲁ-diversity
fecal
in metabolites
athletes—mostly
is an index oftorunners before
associated
describe and after
with
the quality thea GM
dietary
of half marathon,
patterns
and and prote
is expected to
demonstrating
decrease an
in increase
consumption. disturbedⲀ-diversity
in conditions
GM atisseveral suchdifferent
an index to disease
as taxonomic
describe the quality
and poor levels of[9].
health A total
the[60–62].
GM andof is26
Zhao expected
et al.
operational taxonomic
decrease
described theinGM units
disturbed
and(OTUs) were
conditions
fecal detected
metabolites suchof in the
asrunnersgroup
disease afterpoor
and
before running
andhealthaftergroup, halfwhile
a[60–62]. Zhao et a
marathon,
15 special OTUs
demonstrating were
described the found
an GM in the
and in
increase before
fecal running
GMmetabolites group. Lentisphaerae
of runners
at several different before and
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Considering the potential of GM, it is reasonable to speculate how dietary regimens or
probiotic supplementation may modulate microbiota composition and consequently the
systemic response to physical exercise [65].
There is also evidence that exercise impairs intestinal nutrient absorption transport
mechanisms, leading to malabsorption [66]. The urinary excretion of non-metabolizable
glucose analogs, used to evaluate the intestinal carbohydrate transporter activity, was
lower in response to running compared to rest or after running in one study [65]. A study
conducted with 25 healthy endurance-trained runners showed that 68% of them presented
carbohydrate malabsorption during the recovery period, and breath H2 responses also
correlated with the incidence and severity of GI symptoms [67].
Dietetics 2023, 2 295

In conclusion, the first mechanism of Ex-GIS onset depends on the alteration of the
circulatory-GI pathways caused by endurance activity. This damage is directly dependent
on the unavoidable gut hypoperfusion, which causes ischemic damage of the intestinal
barrier. In addition to intestinal ischemia, the resulting bacterial translocation with endo-
toxemia and inflammatory response then trigger intestinal symptoms. However, these are
not the only changes dependent on endurance exercise; indeed, endurance also causes an
alteration in the neuroendocrine-GI pathway.

4. Gastrointestinal Symptoms during Exercise

If an athlete experiences GI symptoms during exercise, it should be ascertained that
they are not a sign of underlying disease. Once medical causes have been excluded, Ex-GIS
can be considered. The vascular and neuroendocrine alterations that occur during en-
durance physical activity led to the occurrence of GI symptoms that can affect the athlete’s
physical performance and psychophysical well-being [5]. There is a great variability in the
severity of symptoms amongst individuals, and these may range from minor discomfort to
significant health disturbances that impair their ability to compete in races and even lead
to hospitalization in some cases [5]. Symptoms may appear hours to days after exposure
and range from GI (e.g., abdominal bloating, loose stool, abdominal pain) to extraintesti-
nal symptoms including fatigue, headaches, and cognitive difficulties. Several of these
symptoms can be confused with irritable bowel syndrome (IBS) [5], a functional disorder
of gut–brain interaction (DGBI) [68]. IBS and EX-GIS share similar pathogenesis in some
respects, including alterations in the GM, intestinal permeability, gut immune function,
motility, visceral sensation, brain–gut interactions, and psychosocial status [69]. Further-
more, in strenuous exercise resulting in impaired gastrointestinal function and integrity as
described above, the undigested food molecules entering the small bowel may contribute
to osmotic translocation of water and an increased fecal volume, resulting in loose stools or
diarrhea, in a similar manner to that observed in IBS. Moreover, like IBS patients, many ath-
letes who experience EX-GIS believe that certain foods are responsible for their symptoms.
This concept could explain why EX-GIS responds to the analogous nutritional strategy of
IBS in some cases (see next paragraph concerning “low FODMAP diet”).
We underline that IBS has the possibility of being underdiagnosed in endurance
athletes, specifically marathon, ultramarathon, half-distance triathlon, and full-distance
triathlon participants. One assessment of IBS in endurance sport showed that a great
percentage of symptoms met the Rome Criteria, but they were not diagnosed. Killian LA
and colleagues documented an IBS prevalence of 9.8% overall with 2.8% diagnosed, and an
additional 10.8% had not been diagnosed [70]. Similar results were observed by Hungin
et al., who reported an IBS prevalence of 14.1% overall with 10.8% undiagnosed meeting
either the Manning or Rome (I or II) diagnostic criteria [71]. Underdiagnosed IBS may occur
in those athletes who have not consulted a medical professional regarding their symptoms
and are attempting to manage their symptoms through various strategies. In theory, if
these strategies are not effective in managing their symptoms, these athletes will not be
considered as IBS sufferers. Furthermore, while Ex-GIS tended to decrease between rest
and exercise, athletes with IBS did not experience the same decreases as those without IBS.
In our opinion, those athletes would experience Ex-GIS as a manifestation of IBS triggered
by strenuous exercise and endurance sports, and they would have the same benefit from
dietetic and pharmacological strategies of IBS.
Regarding Ex-GIS, an estimated 30–90% of endurance athletes engaging in marathons,
triathlons, and running report experiencing GI symptoms during exercise [1]. To investigate
the prevalence of Ex-GIS, Ter Steege and colleagues included 2076 athletes competing in a
long-distance run to assess the prevalence, risk factors, and timing of GI disturbances [72].
They received a questionnaire where the reported GI complaints were related to variables
such as age, gender, distance, fluid, and food ingestion, running experience, and environ-
mental conditions. Three athletes dropped out because of GI complaints, 45% had at least
one GI complaint during running, 11% referred to serious GI complaints, and 2.7% had
Dietetics 2023, 2 296

complaints during the first 24 h after the run [72]. In another study, Pfeiffer et al. reported
severe GI distress ranging from 4% in marathon running and cycling up to 32% in Ironman
races [73]. Currently, several observational studies have exhaustively assessed GI symp-
toms during endurance sport; they can be divided into upper- (e.g., regurgitation, upper
abdominal bloating, belching, epigastric pain, and heartburn) and lower- (e.g., flatulence,
urge to defecate, lower abdominal bloating, abdominal pain, abnormal defecation including
loose water stools, diarrhea, and fecal blood loss) GI tract symptoms. Upper-GI symptoms
are reported in up to 40% of runners but may rise to 70% in cyclists [3]. The prevalence of
reflux/heartburn is usually the most frequent of the upper-GI symptoms and is estimated
between 15% and 20% in runners [74]. As described above, exercise induces an increase
in intra-gastric pressure and perturbation of LES function, leading to GI symptoms like
heartburn, chest pain, belching, and dyspepsia [40]. Moreover, the intragastric pressure
may rise due to ingestion of hyperosmolar carbohydrate sport drinks delaying the gastric
emptying time in athletes [75,76]. On the other hand, athletes emptied their stomachs
significantly faster than controls both at rest and during exercise, suggesting an effect of
training [77]. Effectively, athletes not trained for fluid/food ingestion had a twofold risk
of developing GI symptoms compared with athletes habituated to fluid/food ingestion
during exercise [72]. Effectively, the adaptation observed in athletes may protect against the
development of GI symptoms associated with delayed gastric emptying, such as nausea,
vomiting, and side stitch.
Concerning other GI symptoms, side ache, stitch, and subcostal pain, commonly
referred to as exercise-induced transient abdominal pain (ETAP), are common during
exercise. ETAP was reported in 18% of the competitors in a recreational run, whereas 4%
reported severe abdominal pain, but the incidence of ETAP is influenced by the type of
sport [78]. In a study conducted on 965 sporting participants, ETAP was most prevalent in
activities that involved repetitive torso movements, bouncing, or longitudinal rotation [78].
Furthermore, the incidence of ETAP was higher in young patients and after recent ingestion
of fluid and food [76,79].
Finally, the lower-GI-tract symptoms, such as abdominal pain, flatulence, cramping,
the urge to defecate, diarrhea, and rectal bleeding, are more severe compared to upper-GI
disturbances, having the potential to impair performance [80]. The incidence of severe
lower GI symptoms during a recreational run is up to 30%, but the percentage may increase
up to 50% in cyclists and to 70% in competitive long-distance runners [81]. Recreational
athletes are least likely to report symptoms. Usually, they are competing at lower intensities
and thus have fewer symptoms, as GI symptoms are reported to increase with distance
and exercise intensity [82].
In addition to performance level, other variables can influence symptom severity [83].
Jill A. Parnell et al. [83] showed a higher prevalence of GI symptoms in younger female
athletes, who experienced urge to defecate, diarrhea, and the highest rates of gas, nausea,
fullness, and stomach pain/cramps. Other studies support a higher prevalence of GI
symptoms in female athletes [84,85], suggesting further research to determine the potential
relationship to sex hormones and female gut physiology. Age is another variable that can
impact GI symptoms’ prevalence [84–86]. Increased age may protect against GI symptoms
due to reduced splanchnic vasoconstriction through impaired catecholamine response and
consequently increased oxygen supply [86].
Finally, exercise is beneficial for mental status, resulting in an improved mood and a
better quality of life. In turn, a good state of mind is needed to achieve better sports perfor-
mance [87]. In this context, observational studies linked chronic stress to the development
of GI disorders such as IBS [88]. We specified that even in the healthy general population,
stressful events can trigger GI symptoms, and it is plausible that the link between stress,
anxiety, and GI symptoms observed under resting conditions also occurs during exercise.
In this direction, psychological factors may influence the development of GI distress during
exercise [89]. Patrick B. Wilson conducted a study to evaluate if stress and anxiety may
contribute to running-related GI distress [90]. Runners (74 men, 76 women) prospectively
Dietetics 2023, 2 297

recorded running duration and intensity and GI symptoms for 30 days. After 30 days,
participants completed a questionnaire on GI symptoms and filled in the Perceived Stress
Scale (PSS) and Beck Anxiety Inventory (BAI). The analysis of the data showed PSS scores
and BAI scores were positively correlated with GI distress occurrence [90]. To date, most
research on EX-GIS has focused on nutritional, pharmacologic, and mechanical origins, but
this study provides rationale for further research into psychological sources of GI distress
with exercise.

5. Nutritional and Behavior Strategies to Reduce Ex-GIS

We believe that in the framework of Ex-GIS, risk factors screening should be recom-
mended. Exercise modality, state of dehydration, environmental temperature, concomitant
therapies, and diet should be evaluated, and if risk elements are present, an attempt should
be made to modify them. Since Ex-GIS may also be linked to food-related reactions, the
habitual diet should be investigated. Food intolerance appears to be on the rise among
athletes, but unvalidated food intolerance tests and self-reported incidence do not allow
an accurate estimate of true intolerances [91]. Given the multifaced food intolerances or
malabsorption manifestation, there is a tendency for athletes to self-diagnose intolerances
and subsequently restrict foods or food groups. Lactose and fructose malabsorption, which
result from insufficient enzyme and functional capability of the transporter, respectively,
are the most-reported food intolerances [92]. To ensure adequate energy intake, current
guidelines recommend a carbohydrate intake of about 60 g for exercise lasting for up to
2 h. When the exercise lasts 2 h, slightly greater amounts of carbohydrates (90 g/h) would
be recommended, and generally, these carbohydrates should consist of a mix of multiple
transportable carbohydrates, e.g., glucose and fructose or maltodextrin and fructose [93].
Finally, food choice pre-exercise has a significant impact on the gut’s tolerance to running,
and athletes self-manage their diet to reduce Ex-GIS.
Dietary elements including high fiber, fat, and protein intake, as well as concentrated
carbohydrate loads, have been reported to trigger GI symptoms in triathletes [83]. Dark
chocolate needs to be mentioned in this paragraph, since it has been proposed as an er-
gogenic aid via increased nitric oxide [94], but caution should be advised for chocolate since
it has been described as a food that provokes GI disturbance, particularly constipation [95].
GI effects may depend on the concentration of cocoa or other biologically active compounds,
including caffeine and fat, which may aggravate EX-GIS [96]. This evidence may explain
why morning caffeine intake has been associated with increased lower GI symptoms in
triathletes [97]. On the other hand, competitive athletes and longer-distance runners were
less likely to avoid coffee or tea, and this may be due to the potential ergogenic effects of
caffeine in endurance exercise [98]. Concerning sport beverages, energy drinks are a mix
of vitamins, sugars, sweeteners, and plant extracts, especially stimulants, but GI upset is
included in the list of commonly reported symptoms after their use [99].
To assess dietary restrictions pre-racing and GI symptoms, Jill A. Parnell et al. [83]
designed a questionnaire and administered it to 388 runners. Their analysis showed the
foods regularly avoided were meat (32%), milk products (31%), fish/seafood (28%), poultry
(24%), and high-fiber foods (23%). Caffeinated beverages were commonly avoided in events
10 km or less, while high-fiber foods were avoided in females. Rates of food avoidance
were elevated in younger and more competitive runners. Interestingly, athletes did not
identify the consumption of high-osmolarity carbohydrate supplements as a risk factor
for the development of symptoms. In fact, symptoms may depend on the quantity and
quality of carbohydrates ingested before exercise. Besides its importance in maintaining
energy stores [100], a way to reduce the incidence of GI symptoms is to try to incorporate
high carbohydrate intake into the weekly routine and regularly ingest carbohydrates
during exercise. With these strategies, the gut may be trained to absorb and oxidize more
carbohydrates, which in turn should result in less GI distress and better performance [93].
The ability to absorb carbohydrates is a result of an upregulation of SGLT1 transporters of
the intestinal lumen. Considering this, Cox and colleagues [101] suggest “gut training” in
Dietetics 2023, 2 298

endurance cycling, which means several days and 2 weeks of a high-carbohydrate daily
diet [101].
Another strategy to manage Ex-GIS was proposed by van Wijck et al. [10]. Since the
perfusion of the gut is implicated in EX-GIS pathogenesis, upregulating intestinal nitric
oxide (NO) production could be a way to reduce symptoms. Manipulation of intestinal NO
can be obtained through nitric-oxide-synthase-dependent (glutamine–arginine–citrulline)
and nitric-oxide-synthase-independent (nitrate–nitrite) supplementations or by increasing
the dietary nitrate intake [10]. However, currently recognized vegetable sources of dietary
nitrate, such as chard, celery, rapeseed, spinach, radish, and lettuce, are also sometimes
associated with GI symptoms. Therefore, a way to supplement dietary nitrate would be to
take these foods as vegetable extract juice.
We propose an overview of the principal nutritional and behavioral strategies to
reduce Ex-GIS in accordance with the current evidence (Table 1).

Table 1. Possible nutritional and behavioral strategies to manage Ex-GIS in endurance sports.

GI Symptoms Nutritional and Behavior Strategies

Upper-GI symptoms

• Reflux and regurgitation Avoid high-calorie and fatty meals three hours prior to exercise [50,53]
• Nausea Avoid hypertonic fluids during exercise [50,53]
• Vomiting
Lower-GI symptoms Defecate prior to exercise to prevent the urge to defecate during exercise [71]
Drink small amounts of hypotonic carbohydrate fluids to prevent the risk of osmotic diarrhea [72]
• Urgency Avoid hypertonic solutions, including fatty, high-calorie meals, or high-glycemic-index foods
• Diarrhea three hours before exercising and during exercise [73]
• Bloating Train the gut to ingest a high amount of carbohydrates and fluids before competition [70]
• Abdominal cramps Avoidance of food and fluid intake at least two hours prior to exercise [3]
Wait 2–3 h before exercising after a meal or drink [74]
Side stitch or ETAP
Take small amounts of drink during exercise and abstain from hypertonic fluids [3]
Abbreviations: Ex-GIS: exercise-induced gastrointestinal symptoms, GI: gastro-intestinal, ETAP: exercise-induced
transient abdominal pain.

6. Efficacy of Specific Diets Applied by Endurance Athletes to Avoid Ex-GIS

Endurance athletes need a regular nutrition program to fill their energy stores before
training/racing and to provide nutritional support during training/racing and effective
recovery after training/racing. Some nutritional regimens may benefit the performance of
athletes but somehow have a negative impact on the development of symptoms [102–105].
An example is represented by the vegetarian diet; it has been suggested that a vegetarian
diet may improve endurance performance by increasing exercise capacity and performance,
modulating exercise-induced oxidative stress [106] and inflammatory processes, including
anti-inflammatory, immunologic responses [107], and upper-respiratory-tract infections
(URTIs) [108], finally providing better cardiovascular parameters. On the other hand, a
vegetarian diet may theoretically result in developing GI symptoms due to high fiber
content, but some cross-sectional studies and available case reports have not evaluated this
aspect [109].
Another diet applied by endurance athletes aiming to improve performance is a high-
fat diet (HFD), but results of studies are conflicting. This regimen has been widely applied
as a treatment option for neurological diseases such as epilepsy or as an effective dietary
strategy for weight loss [110]. The goal of an HFD is to increase the body’s ability to use
ketone bodies (KBs) and fatty acids as energy sources. The utilization of fatty acids and
KBs may lead to many advantages, such as sparing muscle glycogen stores, increasing
body fat mass loss, improving aerobic capacity, improving time to exhaustion and time-
trial performance, and increasing cognitive performance [109]. Conversely, unresolved
aspect includes the ability of long-term keto-adaptation to restore muscle glycogen content
to levels normally achieved with a carbohydrate (CHO)-rich diet and the impairment
Dietetics 2023, 2 299

of muscle’s ability to use glycogen for oxidative fates [107]. Moreover, potential risks
regarding an HFD are GI symptoms, including nausea, reflux, dizziness, euphoria, and
upper-abdominal discomfort [111,112], which in turn may potentially reduce athletes’
performances. Finally, to alleviate exercise-associated GI symptoms, numerous nutritional
interventions have been investigated. Gluten-free and low-fermentable oligosaccharides,
disaccharides, monosaccharides, and polyols (FODMAP) diets appear to be the most
effective for this purpose [113–116].
In the last decade, one of the most common dietary strategies used to manage GI
symptoms has been the exclusion of gluten from the diet. In recent years, the GFD has
become a trendy diet among the general population, followed in about 5–10% of cases, and
it is even more widespread among non-celiac athletes (NCAs), in whom the percentage
rises to over 40% [114] since many athletes believe that gluten removal might reduce GI
symptoms [73]. The elimination of gluten from the diet is particularly prominent within
endurance athletes, likely due to their higher frequency of EX-GIS (15–30%) compared
to other types of athletes [73]. Despite the paucity of supportive evidence, NCAs choose
to adhere to a GFD for various reasons including clinically or self-diagnosed NCGS and
the belief that a GFD is healthier because it reduces inflammation and gastrointestinal
discomfort, or it may improve exercise performance through the reduction in fatigue [114].
The main clinical beneficial effect of a GFD reported by athletes is the resolution of ab-
dominal bloating, gas, diarrhea, and fatigue [114]. One of the first surveys conducted on
endurance cyclists, by Fritscher K. and colleagues [117], reported that GFD was the most
popular “special diet” among this group of athletes since it improved GI symptoms in
approximately 80% of survey respondents. A successive and broader survey conducted
on 910 athletes spanning various sports and levels, including world and/or Olympic
medalists, concluded that 41.2% of NCAs followed a GFD for 50–100% of the time and
that most of them were endurance sport athletes (70%) [114]. Interestingly, a successive
controlled, randomized, double-blind, crossover study conducted by the same group on
thirteen competitive endurance cyclists with no positive clinical screening for CD or history
of IBS concluded that a short-term GFD had no overall effect on performance, symptoma-
tology, and inflammation. In this study, athletes, allocated to a 7-day gluten-containing
diet (GCD) or GFD, were tested for performance, GI symptoms, well-being, and select
indicators of intestinal injury and inflammation, and at the end of the study, clinical and
biochemical index results were similar in both groups [118]. Furthermore, it is plausible
that a placebo effect could contribute to the symptomatic improvement experienced by
athletes. A review by Halson and Martin confirmed that the “belief effect” can contribute to
a performance improvement of between 1% and 3%, whether it has ergogenic mechanisms
or not [119]. Moreover, following a GFD may increase awareness of food choices and
encourage a healthier diet containing more fruit, vegetables, and gluten-free whole-grain,
and in turn, these positive dietary changes may influence perceptions of improved health,
psychology, or exercise performance [114]. Gluten should not be considered the only culprit
of symptoms; amylase-trypsin inhibitors (ATIs) and fructans (rich in FODMAPs), which
are all components of wheat and other gluten-containing and non-gluten foodstuffs, may
also be responsible for GI disturbances [120,121]. Although gluten and fructans co-exist in
cereals, historically, gluten alone has been incorrectly blamed for related GI disturbances
and thus is often promptly eliminated from the diet [122–124]. In truth, it is more likely that
the other proteins and carbohydrate nutrients are the actual culprits of athletes’ symptoma-
tology. In fact, it was widely demonstrated in a series of clinical studies that fructan and not
gluten elimination reduced GI symptoms in IBS patients with self-reported NCGS [125,126].
Therefore, athletes following a GFD unknowingly reduce high-FODMAP foods, which may
reduce Ex-GIS, and the decrease in FODMAP intake and not gluten itself may be the true
reason for improved GI disturbances obtained in a GFD.
This justifies the new dietary strategy to address the multifactorial nature of gas-
trointestinal disorders in athletes using a “low FODMAP” approach and not a GFD [127].
FODMAPs are a family of fermentable short-chain carbohydrates found in a wide as-
Dietetics 2023, 2 300

sortment of foods/food constituents [128]. In predisposed individuals, FODMAPs are

partially digested, remaining in the intestinal lumen, particularly in the colon, where they
are subsequently fermented by the microbiota, releasing gas, recalling water, and leading
to exacerbation of the symptoms of IBS [129]. The distension of the intestinal wall initiates
a painful visceral response conveyed by the nerve fibers that are present in the intestine.
Several controlled clinical trials and meta-analyses have demonstrated the superiority of
the low-FODMAP diet (LFOD) over control diets in patients with IBS [129]. As reported
above, adverse GI symptomatology during exercise can be analogous to IBS [130]. In
strenuous exercise with a subsequent impairment of GI function and integrity (i.e., trans-
porters), undigested food molecules, such as FODMAPs, may increase the osmotic water
translocation and fecal volume, with physiological consequences such as loose stool or
diarrhea [131]. Furthermore, high-FODMAP foods are common in an athlete’s diet [115],
especially due to FODMAPs that are contained in certain sports foods specifically for-
mulated for and marketed to athletes or snacks containing dry dates (fructans), fructose,
inulin (fructans), honey (fructose), and chicory root (oligosaccharides) [127]. A quantitative
recommendation in an LFOD is to reduce FODMAP intake from 15–30 g FODMAP/day
to 5–18 g FODMAP/day [132] and specifically less than 0.5 g FODMAP per meal or less
than 3 g per day in IBS patients [133]. However, endurance athletes suffering from Ex-GIS
consume 2 times more FODMAPs (up to 43 g/day). Considering this, the LFOD is becom-
ing a strategy to reduce GI distress parameters in athletes with a history of non-clinical
exercise-associated GI symptoms [109].
Four studies [116,134–136] have evaluated the potential efficacy of an LFOD in Ex-GIS.
A case study about a multisport athlete with Ex-GIS showed that a 6-day restriction of
FODMAPs (81 ± 5 g vs. 7.2 ± 5.7 g FODMAP/day) resulted in a decrease in GI symptoms
both during exercise and on resting days of the athlete [136]. Another case report [135]
presented the effect of a 4-week LFOD in a female ultra-endurance runner diagnosed
with IBS. Apart from severe nausea, minimal GI symptoms including bloating and flat-
ulence were observed throughout the race [135]. Another evaluated a 6-day LFOD or
high-FODMAP (HFOD) diet in eleven recreationally competitive runners [116]. The study
reported a significant decrease in Ex-GIS, particularly in flatulence, urge to defecate, loose
stool, and diarrhea, in 9 of 11 athletes after the low-FODMAP trial [116]. Finally, a crossover
study [134] analyzed the effects of a 24 h HFOD or LFOD before exertional heat stress on
GI integrity, function, and symptoms. The authors proved that even if an HFOD ame-
liorates GI integrity, it results in greater carbohydrate malabsorption compared with an
LFOD and correlates with more severe Ex-GIS during exertional heat stress compared to
an LFOD [134]. In addition, Scrivin et al. [105] recently performed an exploratory study
to review the specific self-reported strategies used to manage symptomology amongst en-
durance athletes who experience Ex-GIS. Avoiding disaccharides (lactose and sucrose) was
the most popular strategy to avoid or reduce Ex-GIS, followed by galacto-oligosaccharides,
polyols, and fructose. Other popular dietary strategies were dietary fiber reduction and
dairy avoidance [105].
We want to emphasize that specific regimens are not only a way to alleviate GI
discomfort but should provide specific nutrients and energy intake in an efficient manner.
Therefore, after a first exclusion phase, it is recommended to proceed to a reintroduction
phase, which should be carefully applied by a trained nutritionist to identify which foods
high in FODMAPs cause these symptoms to personalize the diet and maintain a healthy
GM [127]. Since long-term outcomes and the safety of low-FODMAP diets remain to be
investigated, further studies are required to evaluate their long-term effects on GM, cost
effectiveness, and efficacy compared with other regimens [137,138]. Similar considerations
also apply to GFDs, which may have potential negative issues in terms of diet restriction
with suboptimal nutrient intake, the increased difficulties of, the organization of the diet, the
potential impact on GM and increased food costs [139,140]. Unnecessary food restrictions
should always be considered a concern for athletes given increased energy requirements
and the importance of a balanced diet on general health and performance.
 also apply to GFDs, which may have potential negative issues in terms of diet restriction
with suboptimal nutrient intake, the increased difficulties of, the organization of the diet,
Dietetics 2023, 2 the potential impact on GM and increased food costs [139,140]. Unnecessary food 301 re-
strictions should always be considered a concern for athletes given increased energy re-
quirements and the importance of a balanced diet on general health and performance.
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symptoms;
GERD: in
Ex-GIS gastro-esophageal
endurance sports. reflux disease; CD: Ex-GIS:
Abbreviation: celiac disease; IBD: inflammatory
exercise-induced bowel disease;
gastrointestinal SIBO:
symptoms;
small intestinal bowel overgrowth; VO2max: maximal oxygen consumption; NSAIDs:
GERD: gastro-esophageal reflux disease; CD: celiac disease; IBD: inflammatory bowel disease; SIBO: non-steroidal
anti-inflammatory
small intestinal bowel drugs; HFOD: VO2max:
overgrowth; high-FODMAP maximal diet; HFD:consumption;
oxygen high-fat diet; NSAIDs:
GFD: gluten-free diet;
non-steroidal
LFOD: low-FODMAP diet.
anti-inflammatory drugs; HFOD: high-FODMAP diet; HFD: high-fat diet; GFD: gluten-free diet;
LFOD: low-FODMAP diet.
7. Conclusions
7. Conclusions
Endurance exercise causes physiological and pathological disturbances that alter GI
Endurance
function exercisewhich
and integrity, causeseventually
physiological and
results inpathological disturbances
Ex-GIS. Endurance that acute
can cause alter GI
GI
function
symptoms and integrity,
even whichgut
in a healthy eventually
through results
multiplein pathological
Ex-GIS. Endurance
changescan cause acute
associated with
GI symptoms even in a healthy gut through multiple pathological changes associated
with hypoperfusion, ischemia, epithelial injury, impaired barrier function, endotoxemia,
local and systemic inflammation, impaired nutrient absorption, and altered gastric and
intestinal motility. These changes are the result of multifactorial interactions between the
gastrointestinal tract and the circulatory, immune, enteric, and central nervous systems,
Dietetics 2023, 2 302

analogous in some respects to the pathogenesis of IBS, as well as in terms of the symp-
tomatology triggered. Ex-GIS can impact the physical and psychological performance of
athletes during competitions and vice versa; the psychological stress to which they are
subjected may worsen GI disturbances. Numerous nutritional and behavioral interventions
have been investigated to alleviate Ex-GIS; diet is perhaps the principal one and should be
personalized and planned by experts to avoid self-managed diets.
In conclusion, although more research is needed to gain insight into gastrointestinal
physiology during exercise and to better understand the most appropriate individualized
dietary strategies to address the multifactorial nature of GI disorders in athletes, nutritional
intervention appears to be a promising tool to manage them.

Author Contributions: Conceptualization, E.R. and G.S.; writing—review and editing, E.R., G.S.,
A.C. and C.M.; supervision, E.S.C., C.S. and N.P. All authors have read and agreed to the published
version of the manuscript.
Funding: The research leading to these results has received funding from MUR under PNRR
M4C2I1.4 project Rome Technopole Flagship 4 CUP Sapienza University of Rome.
Conflicts of Interest: The authors declare no conflict of interest.

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