Introduction
A well-functioning gut is a key, albeit sometimes overlooked, contributor to athlete
performance and health. Indeed, increases in gastrointestinal (GI) symptoms
correspond with worsened performance [1]
[2]
[3], and certain GI
symptoms such as nausea, intestinal cramping, and loose stools can even cause
athletes to drop out of competition or be unable to complete an exercise task [4]
[5]. Hoffman and Fogard
[4], for example, found that Western States
100-mile Endurance Run participants reported nausea and/or vomiting as the
leading reason for withdraw from the race. This contrasts with other symptoms
(e. g. flatulence, belching) which are unlikely to affect performance or
lead to competition withdrawal.
Dietary supplements are frequently used to improve athletic performance, training,
and recovery, particularly in elite athletes [6].
Certain supplements (e. g. probiotics, glutamine, bovine colostrum) have
been studied as gut function enhancers in the context of exercise [3]
[7]
[8], and various manufacturers are marketing these and
other supplements to exercisers/athletes to improve performance and GI
function. Conversely, other sports nutrition supplements have known GI-related side
effects that can impair performance or interfere with training in some situations.
These include supplements with a long track record of study and use (carbohydrate,
caffeine, sodium bicarbonate) as well as more novel products (exogenous ketones).
Athletes who decide to use these supplements may need to implement mitigation
strategies to minimize GI-related adverse effects and maximize these
supplements’ ergogenic properties.
Given the widespread use of dietary supplements and their potential impacts on the
gut, the aims of this narrative review were twofold: 1) to address the potential of
certain dietary supplements to enhance gut function and reduce exercise-associated
GI symptoms; and 2) to discuss strategies for reducing GI-related side effects from
using popular sports nutrition supplements.
Supplements Purported to Enhance Gut Function with Exercise
Probiotics
A typical human may host approximately 38 trillion bacteria, with the vast
majority residing in the colon [9]. Investigations
using both animals and humans have shown the importance of gut microorganisms
(particularly bacteria) and the gut microbiome to health [10]. Although gut microbiome research has
traditionally focused on its relationships to health and disease, there is
growing interest in how it impacts performance and body composition in athletes
[11]. Unsurprisingly, administering probiotics
(defined as live microorganisms that confer benefits when taken in adequate
amounts) has been suggested as a way to manipulate gut microbiome composition
and function [12]. Much of the interest in
probiotics among athletes is related to their purported ability to reduce GI
symptoms during competition, as well as lessen the odds of transitory infectious
GI illnesses that interfere with training.
The mechanisms by which probiotics may influence GI function during exercise are
varied, including modulation of the immune system via adhesion to the mucosa,
stabilization of gut barrier function, improved nutrient absorption, and
production of short-chain fatty acids [13]. It is
beyond the scope of this review to discuss all these mechanisms in detail, and
interested readers are pointed to the following reviews for more detail on
proposed mechanisms [13]
[14]. Specific to the literature on probiotics and exercise, a major
barrier to understanding how probiotics could exert benefits is that most
studies have not quantified changes in the gut microbiome itself [13]. Further, the most common method of assessing
gut microbiota composition (fecal sampling) may be a poor surrogate for
colonization of probiotics in the mucosa [15]. In
large part these issues explain why in 2019 the International Society of Sports
Nutrition (ISSN) reported in a position stand that the mechanisms of probiotics
remain largely unknown in the setting of sport and exercise [13].
Recent reviews have summarized the effectiveness of probiotics for GI-related
outcomes in athletes and regular exercisers [13]
[16]
[17], with a summary of conclusions in [Table
1]. In general, these reviews reported some positive results
(e. g. reduced GI symptoms, altered markers of GI permeability), but
findings have been marked by inconsistency and substantial differences in
methodology. One investigation that illustrates this inconsistency is West et
al. [18], who found that taking Lactobacillus
fermentum for 11 weeks increased the number and duration of mild
GI-symptom episodes, yet reduced the severity of such episodes. Differences in
study methodology have come in the form of the probiotic species and strains
used, dosages and durations of supplementation, and approaches to measuring and
defining GI symptoms and illnesses [13].
Table 1 Overview of recent position statements and reviews
on probiotic use in sports and exercise.
|
Source
|
Summary of Conclusions
|
|
IOC Consensus Statement on Dietary Supplements [16]
|
Additional evidence is required to document the effectiveness
for reducing GI distress and infections
|
|
International Society of Sports Nutrition Position Stand on
Probiotics [13]
|
A small number of trials have evaluated GI outcomes in
athletes/exercisers, with largely mixed results due
to variation in methodology
|
|
Möller et al. systematic review [17]
|
Three of the identified studies showed somewhat positive
effects on GI symptoms, but the results were mixed and not
consistent
|
GI, gastrointestinal; IOC, International Olympic Committee.
It is notable that among the studies to show reductions in GI symptoms with
probiotic use in athletes, the benefits have been modest [3]
[19]. These
observed modest benefits in athletes parallel the magnitude of symptom
improvements observed in non-athletes; a meta-analysis by Ford et al. [20], for instance, reported a standardized mean
difference of − 0.31 in global symptom scores when comparing
combination probiotics against placebo in irritable bowel syndrome patients.
Consequently, athletes who use probiotics should have realistic expectations
about the likely size of benefit to be obtained. In addition, research on
probiotics and direct measures of physical performance (strength, endurance,
speed, etc.) is limited, with largely unconvincing data, particularly in trained
athletes [13].
If an athlete uses a probiotic despite the mixed evidence, they should keep
several considerations in mind. First, with respect to safety, there is general
agreement that probiotics are safe in healthy individuals, and that individuals
with certain conditions (HIV, severe acute pancreatitis, liver diseases) are
perhaps at higher risk of moderate-to-serious adverse events [13]. Second, probiotics from the
Bifidobacterium and Lactobacillus genuses are best studied
[13]
[21],
meaning that efficacy and safety data for specific species and strains is most
likely to be available for products that contain these bacteria. Third, others
have suggested that probiotics’ benefits are dependent on achieving a
minimum duration (2–4 weeks) of supplementation [13]
[22]. In terms of dosage, the
ISSN’s position stand on probiotics notes that doses usually fall
between 1×109 and 1×1011 colony
forming units (CFUs) per day [13]. Likewise, the
IOC’s consensus statement on dietary supplements reported moderate
evidence for probiotics when taken for several weeks at 1011
CFUs/day [16]. Looking across these
groups’ recommendations, it can be concluded that supplementing for two
or more weeks with a probiotic containing Bifidobacterium- and
Lactobacillus-based species at 109 and 1011
CFUs/day may be required to obtain benefits.
Importantly, there are likely to be interactions between dose, duration of
supplementation, and the probiotic species and strain(s) used [13]. Moreover, these interactions may depend on the
specific outcome being measured. Indeed, a review of probiotic meta-analyses
reported that higher dosages (e. g.>1010 CFUs) were
more beneficial than lower dosages for preventing antibiotic-associated diarrhea
and lowering blood pressure, but dose-response effects were absent for other
outcomes (e. g. Clostridium difficile-associated diarrhea, atopic
dermatitis) [23]. Additionally, Lactobacillus
rhamnosus GG reportedly exhibited dose-response effects in acute
pediatric gastroenteritis, but two other strains did not [23]. Unfortunately, dose-response studies in
athletes are largely non-existent [13], so making
conclusions about these interactions as they relate to probiotic use in sports
is not yet possible.
Glutamine
Glutamine is the most abundant amino acid in plasma and is found in skeletal
muscle [24]. It is a key substrate for rapidly
proliferating cells, including GI cells [25]. Over
half of ingested glutamine is sequestered by the splanchnic bed and never enters
systemic blood [26], and most of this sequestered
glutamine is used for oxidative purposes [27]. It
has been proposed that situations leading to high glutamine utilization (trauma,
illness, extreme/heavy exercise) and its subsequent depletion contribute
negatively to changes in GI barrier integrity [28]. In turn, GI barrier dysfunction is hypothesized to induce
endotoxemia and systemic inflammatory responses, which have been tied to a
higher rate of exercise-associated GI symptoms in some, but not all, studies
[29]. In addition, reduced gut barrier
integrity could provoke GI symptoms by leading to the malabsorption of ingested
nutrients [29]. In theory, then, ingesting
glutamine before or during exercise could maintain gut function and reduce GI
symptoms through several mechanisms, including maintaining mucosal thickness,
limiting the release of pro-inflammatory cytokines, and activating protein
kinases that regulate the expression of tight junction proteins [25].
Zuhl et al. [7] supplemented eight
endurance-trained adults with 0.9 g/kg of fat-free mass of
glutamine for seven days prior to 60 minutes of running at
65–70% ̇VO2max in 30°C,
12–20% relative humidity conditions. Participants also completed
the protocol with a glutamine-free placebo, and condition order was randomized.
Overall, glutamine reduced exercise-induced intestinal permeability (as measured
through a sugar-probe test) versus placebo. Similarly, another study showed that
glutamine supplementation (0.9 g/kg of fat-free mass) two hours
before 60 minutes of running in the heat reduces intestinal permeability
versus placebo [30]. Pugh et al. [31] essentially repeated this acute experiment,
except they used varying doses (0.25, 0.5 and 0.9 g/kg of
fat-free mass); overall, they confirmed that a high dose reduces GI permeability
versus placebo, with lower doses also possibly having small-to-moderate
benefits.
Collectively, these experiments point to glutamine as effective for reducing GI
permeability. However, the placebos used in these three studies were sugar-free
drinks and devoid of carbohydrate or protein, which is important given that
administration of these macronutrients reduces GI permeability with exercise as
compared to water [32]. In addition, Lambert et
al. [33] found that a 6% carbohydrate
beverage with a small amount of glutamine (0.6%) did not reduce gut
permeability markers as compared to the carbohydrate beverage alone when
subjects ran for 60 minutes at 70% ̇VO2max in
temperate conditions. This was also true when aspirin was ingested, which is
known to increase GI permeability. Other evidence indicates that reliance of
intestinal cells on glutamine may be diminished when both glutamine and glucose
are available [34]. Consequently, it remains
unclear whether glutamine offers any additional benefits to GI barrier function
when carbohydrate (or protein) is ingested during prolonged exercise.
Another caveat to consider is that these studies either failed to assess GI
symptoms [7]
[30] or
did not find differences in GI symptoms between conditions [31]. Of note, a recent tolerance study found that
glutamine, particularly at high doses (0.6–0.9 g/kg of
fat-free mass), induces mild-moderate GI symptoms in a substantial proportion of
people (e. g.>50%) over the initial two hours
post-supplementation [35]. Given the lack of data
showing an improvement in GI symptoms with glutamine, its clinical utility among
athletes remains speculative. Future work should use validated questionnaires
(e. g. [36]) to assess the occurrence of
exercise-associated GI symptoms with glutamine versus placebo. Ideally, placebos
should provide a source of energy, such as glucose, maltodextrin, or whole
protein. Finally, studies conducted in naturalistic sporting environments are
warranted, as the literature is largely limited to laboratory settings.
Bovine Colostrum
Colostrum is the fluid produced by mammary glands following parturition and is
markedly different from mature milk, in that it is lower in lactose and higher
in protein, growth factors, enzymes, enzyme inhibitors, cytokines, and
nucleotides [37]. The components of bovine
colostrum have been proposed to favorably alter gut integrity and resilience
through several mechanisms, including reducing apoptosis signaling and
bolstering tight junctions via actions on transmembrane proteins such as
occludin and claudin [38]. Experiments conducted
in the late 1990s and early 2000s showed that administrating bovine colostrum to
rodents reduced GI injury from non-steroidal anti-inflammatory drugs and heat
exposure [39]
[40],
providing a strong impetus for human research. Given the increases in GI
permeability that occur with intense and prolonged exercise (especially in the
heat) [32], bovine colostrum has received
considerable interest as gut-barrier-enhancer over the past decade.
The evidence supporting bovine colostrum for mitigating exercise-induced
gut-barrier dysfunction has been somewhat positive but mixed, with several
studies showing gut barrier biomarker improvements [41]
[42]
[43]
[44]
[45], others reporting null findings [8]
[46], and one reporting an increase
in GI permeability [47]. Notably, the doses used
have been extremely variable, with lower and upper amounts of
0.5 g/day [45] and
~130 g/day [8],
respectively. The most common dose is 20 g/day [42]
[43]
[44]
[46], typically
taken for two weeks. No clear dose-response relationship is apparent across the
literature, as the lowest daily dose was associated with improvements in gut
barrier biomarkers [45] while the highest daily
dose did not elicit benefits [8]. One potential
explanation for the lack of dose-response relationship across studies is that
the concentration/activity of bioactive compounds in bovine colostrum
varies markedly [48].
As is the case with glutamine research, the cited bovine colostrum experiments
largely neglected to assess GI symptoms [41]
[42]
[43]
[44]
[46]. Among those
that did evaluate subjective GI complaints, symptom occurrence with bovine
colostrum was not significantly different than placebo [8]
[45]
[47]. In contrast to the glutamine studies that used sugar-free,
non/low-caloric placebos, the selection of placebos has been better in
these bovine colostrum experiments (milk protein concentrate [41]
[42]
[43]
[44]; skim milk
and milk protein [46]; dehydrated whey and banana
[45]; concentrated whey protein [47]; corn flour [8]).
The totality of evidence indicates that supplementing up to
20 g/day with bovine colostrum for at least 1–2 weeks
may reduce GI permeability from prolonged and/or intense exercise in
some situations, but its clinical utility is uncertain given the lack of
benefits on subjective GI symptoms. Other controlled studies have found some
improvements in physical performance and immune function (reduced respiratory
infection risk or severity) with bovine colostrum, particularly during
intensified training periods [48]. Thus,
supplementation may be worthwhile for some athletes, but athletes who undergo
doping control tests should know that the World Anti-Doing Agency (WADA)
recommends against using bovine colostrum because it is a source of insulin-like
growth factor (IGF)-1 [48]. However, the soundness
of WADA’s recommendation has been questioned, and interested readers may
refer to Davison [48] for additional information
on the controversy.
Other Potential GI Barrier Enhancers
Several additional nutrients and nutraceuticals have been investigated for their
effects on exercise-induced changes in GI barrier integrity. Supplementation
with vitamin C (1 g) two hours before exercise was found to reduce
exercise-induced increases in plasma lipopolysaccharide [49], a marker of endotoxemia that correlates with GI barrier
permeability [50]. Likewise, 14 days of zinc
carnosine supplementation (37.5 mg, twice daily) reduced post-exercise
intestinal permeability by 71% in comparison to placebo, possibly
through the enhancement of tight junction formation and stability [44]. Ingesting 10 g of L-citrulline, which
is a non-proteinogenic amino acid that acts as a precursor to arginine,
30 minutes prior to exercise was shown in one randomized, crossover
trial to reduce splanchnic hypoperfusion and a marker of enterocyte damage
(intestinal fatty acid binding protein) in comparison to L-alanine, though
intestinal permeability via a sugar probe test was unaffected [51]. Three days of supplementing with
500 mg/day of curcumin, the principle bioactive component of
turmeric, was also shown in a crossover experiment to reduce the rise in
intestinal fatty acid binding protein with 60 minutes of running in the
heat [52]. As is the case with glutamine and
bovine colostrum, the practical relevance of using these supplements to prevent
or reduce subjective GI complaints is unknown, primarily due to failure of these
investigations to assess GI symptoms in a systematic manner.
Other nutritional substances have been investigated in relation to GI
permeability in non-athletes or animal models but are yet to be tested as it
relates to exercise-induced gut barrier dysfunction in humans, including vitamin
D, vitamin A, and short-chain fatty acids [53].
These may be targets for future study, but for now there is little that can be
concluded regarding their relevance to the management of exercise-related GI
dysfunction.
Ginger
The plant Zingiber officinale is the source of ginger, a spice used over
millennia for its purported health effects [54].
As it relates to athletes and exercise, ginger has been most studied as an
analgesic and recovery supplement, with several randomized trials demonstrating
benefits on muscle soreness and pain [55]
[56]. In contrast, little attention has been paid to
the possible GI benefits of ginger in the context of exercise, despite there
being abundant literature on its gut-influencing properties in clinical and
non-athlete populations [57].
Ginger is a 5-HT3 antagonist [58], which
partly explains why it may reduce nausea in several contexts (pregnancy,
chemotherapy, motion sickness) [59]. Anecdotally,
ginger is used an anti-emetic by ultra-endurance athletes [60], but to date, its use in that setting has not
been evaluated in a published randomized trial. An abstract from a 2015
scientific meeting reported that consuming a ginger-containing sports drink
before 5-km running slightly reduced nausea post-run relative to a placebo and
water [61]. Given the causes of exercise-related
nausea can vary considerably [62], it will be
important for future studies to examine the potential anti-emetic effects of
ginger in a range of exercise settings (e. g. sprinting, interval
exercise, ultra-exercise, in the heat, etc.).
Although ginger may reduce nausea in certain situations, other trials have found
the rate of GI-related side effects to be higher with ginger than placebo.
Altman and Marcussen [63] found that daily ginger
supplementation led to more mild-moderate GI adverse events (e. g.
eructation, dyspepsia). In addition, a meta-analysis of randomized trials on the
use of ginger for symptomatic osteoarthritis relief revealed that the withdrawal
rate due to adverse events was higher than with placebo, with most events being
related to bad taste or types of GI upset [64].
Notably, dosages ranged from 0.5–1.0 g/day [64]; hence, even small doses can lead to side
effects in susceptible individuals. Athletes who plan to utilize ginger to
mollify exercise-related nausea will need to weigh the (unverified) benefits
against the potential for GI side effects like burping, heartburn, dyspepsia,
etc. Consequently, these athletes should trial low doses (e. g.
0.5 g) before and during training sessions, increasing the dose
gradually to determine the likelihood and severity of side effects.
In the author’s judgment, athletes suffering from frequent bouts of
nausea and vomiting should be evaluated for potential underlying causative
conditions or diseases. Assuming no underlying, identifiable, treatable
conditions are identified, these athletes may consider ginger as a relatively
low risk treatment despite the lack of evidence around its efficacy. This
recommendation is based on the fact that 1) side effects of ginger are almost
always transitory/mild [65] and 2) there
are currently few other evidence-based treatments for exercise-induced nausea
and vomiting [62].
Summary
[Figure 1] provides a concise overview of the
evidence base behind the dietary supplements discussed, specific to their
effects on GI barrier biomarkers and symptoms. Although multiple supplements
have been shown to reduce biomarkers of GI barrier damage/dysfunction,
the volume and consistency of evidence varies. To date, glutamine and bovine
colostrum have the most supportive evidence, in that more than half of
investigations found positive effects. (The author acknowledges this approach to
evaluating strength of evidence is limited, but it nonetheless provides some
indication of where the literature stands.) As depicted in [Fig. 1], the evidence is either very limited or
nonexistent as it relates to these supplements’ impacts on subjective GI
symptoms. Probiotics have some limited support, but due to the multitude of
species/strains, formulations, and doses that can be utilized,
straightforward recommendations remain elusive. Lastly, [Table 2] displays an overview of the
supplements’ proposed mechanisms as well as practical considerations,
including typical dosing used in the relevant literature and potential side
effects.
Fig. 1 Summary of evidence for nutritional supplements that may
have some positive effects on gut barrier integrity and/or GI symptoms.
A single check mark indicates very limited favorable or mixed evidence,
while two check marks indicate that the majority of studies (more than
half) have found positive effects. A question mark indicates that the
effects are largely unknown, primarily due to a lack of evaluation. An X
represents a general lack of benefit among available studies.
Table 2 Description of mechanisms,
dosing/formulation considerations, and possible side effects
of supplements that may have favorable gastrointestinal
effects.
|
Probiotics
|
Glutamine
|
Bovine Colostrum
|
Vitamin C
|
Zinc Carnosine
|
L-citrulline
|
Curcumin
|
Ginger
|
|
Gut mechanism(s)
|
Immune system modulation, gut barrier stabilization, improved
nutrient absorption, short-chain fatty acid production
|
Mucosal thickness maintenance, pro-inflammatory cytokine
modulation, tight junction protein expression
|
Apoptosis signaling, tight junction protein regulation
|
Reduced oxidative stress, decreased endotoxemia
|
Apoptosis signaling, tight junction protein regulation
|
Splanchnic blood flow maintenance via increased arginine for
nitric oxide-induced vasodilatation
|
Cytokine modulation, apoptosis signaling, reduced oxidative
stress
|
5-HT3 receptor antagonism
|
|
Typical formulations
|
Capsules, milk-based drinks, powder sachets
|
Powders mixed with fluid, capsules
|
Powders mixed with fluid, capsules
|
Capsules, tablets
|
Capsules, tablets, powder sachets
|
Powders mixed with fluid, capsules
|
Capsules, tablets
|
Capsules, chewable tablets, powders
|
|
Dosing
|
109–1011 CFUs/day
for>2 weeks, usually from Bifidobacteria and
Lactobacillus species
|
0.25–0.9 g/kg of body mass daily or
1 h before exercise
|
Up to 20 g/day for≥1–2
weeks
|
1 g, 2 h before exercise
|
37.5 mg x 2 daily, for 2 weeks
|
10 g, 30 min prior to exercise
|
0.5 g/day for 3 days
|
0.5–2 g daily or prior to acute
nausea-provoking stimuli
|
|
Possible side effects
|
Mild GI symptoms, systemic infections, immune system
stimulation
|
Mild-moderate GI symptoms at high doses
|
GI complaints, skin rashes
|
Diarrhea, nausea, GI complaints at high doses
(≥2 g)
|
GI upset
|
Stomach discomfort
|
GI complaints, yellow stools
|
Belching, stomach upset, heartburn
|
Supplements that Cause Gut Symptoms
Carbohydrate
Despite their well-documented use as ergogenic aids, exogenous carbohydrate
supplements can exacerbate GI symptoms, which, in severe cases, can lead to
worsened performance or dropping out of competition. In general, the
GI-symptom-inducing effects of carbohydrate are dependent on dose. For example,
Triplett et al. [66] found that seven of nine
participants reported their stomachs did not feel as if they were emptying and
were very full when they ingested an exceptionally high amount of glucose
(144 g/h) during prolonged cycling. Another experiment showed
that high carbohydrate gel intake (1.4 g/min) during 16-km runs
induced more severe nausea than an intake of 1.0 g/min [67]. Likewise, increasing carbohydrate
concentration of a beverage often leads to more severe GI symptoms like
bloating, fullness, and side ache [68]
[69]. In terms of delivery form, bars may induce
more GI symptoms than carbohydrate gels and beverages during intense exercise
[2].
One strategy to reduce GI symptoms associated exogenous carbohydrate ingestion is
using mixed glucose-fructose products/foods [70]. Glucose and fructose rely on separate, saturable transporters
for intestinal absorption, and when carbohydrate intakes exceed
50–60 g/h, supplying carbohydrate as a glucose-fructose
mixture (as opposed to a single saccharide) enhances stomach emptying and
reduces malabsorption and its associated symptoms [70]. In practice, it can be a challenge to determine the
glucose-to-fructose ratio of any given product or food since there is no
labelling requirement in the United States to list amounts of individual
saccharides, but Wilson et al. [71] does provide
estimates of the glucose-to-fructose ratio of 80 different foods and products
used during a 70.3-mile triathlon.
Another way to manage carbohydrate-associated GI problems is training the gut.
Repeatedly exposing the gut to high carbohydrate intakes may lead to several
positive physiological adaptions, including enhanced gastric emptying,
upregulation of intestinal transporters, and greater exogenous carbohydrate
oxidation [72]. To date, limited experimental
evidence has documented that gut training with carbohydrate supplements reduces
GI symptoms and malabsorption when athletes ingest high rates of carbohydrate
(e. g. [73]
[74]). Performance improvements occurred in one trial [73], but this may be an overstated effect given the
improvement was relative to a baseline test in which participants experienced
considerable GI symptoms due to the high carbohydrate intake. Further, there is
uncertainty as to how gut training should be optimally implemented since prior
investigations devoted large proportions of training volume over 1–2
weeks to gut training sessions, which may not be realistic for many high-level
athletes. Still, for athletes planning to ingest a high rate of carbohydrate, it
is prudent to implement some form of gut training in the weeks preceding
competition.
The ingestion of carbohydrate-hydrogel (sodium alginate and/or pectin)
products has recently received much attention to manage GI symptoms associated
with carbohydrate feeding. The basic principle is that when a
carbohydrate-alginate/pectin mixture enters the stomach, the low pH
environment causes a gel to form and encapsulate the carbohydrate, which may
lessen activation of saccharide receptors in the proximal duodenum [75]. This, in turn, may facilitate stomach emptying
and absorption of fluid and carbohydrate. Yet, of the available randomized
trials on carbohydrate-hydrogel ingestion during exercise, most have not found
physiological, GI, or performance benefits relative to standard carbohydrate
formulations [76]. The main exception is Rowe et
al. [77], who found that, in comparison to a
non-hydrogel carbohydrate (glucose-fructose) beverage, ingesting a
carbohydrate-hydrogel beverage at 90 g/h during two hours of
running at 68% VO2max led to less GI distress, greater
exogenous carbohydrate oxidation, and improved subsequent 5-km time trial
performance. Clearly, more research is needed to better understand which
situations carbohydrate-hydrogel products may offer benefits in terms of GI
function and performance.
Caffeine
Meta-analyses report that caffeine improves physical performance across a variety
of exercise types (e. g. [78]). Even so,
caffeine’s potential side effects – which include GI-related
effects – should be considered when designing a supplementation regimen.
At high doses (≥500 mg), caffeine may induce nausea in some
individuals [79], and this can interfere with the
completion of exercise in extreme cases [80].
Other factors may amplify the risk of caffeine-induced nausea, including mixing
it with other stimulants or taking it when fasted or anxious [62]. Notably, although caffeine has improved
performance in numerous studies, most of these investigations were not carried
out under conditions of high mental stress and anxiety that often accompany
real-life competition [81]. In order to minimize
the risk of caffeine-induced nausea, athletes should take an individualized
approach to supplementation that considers their individual tolerance and the
situation (low- vs. high-stakes competition).
Beyond nausea, caffeine can also exacerbate other GI symptoms such as intestinal
cramping, urges to defecate, etc. Withdrawing high caffeine intakes, for
example, has been observed to lead to less GI complaints [82]. In one crossover study, a daily caffeine dose
of 3 mg/kg of body mass resulted in higher ratings of
“GI distress” relative to placebo over much of a 20-day period
[83]. In a sport-specific wrestling study, a
high dose of caffeine (10 mg/kg) given before simulated
competition led to higher GI complaints and discomfort than a moderate dose or
placebo [84]. Unfortunately, these studies did not
distinguish between different GI symptoms, and a general lack of controlled
research on caffeine’s GI-related side effects means there is
uncertainty as to which symptoms are most likely to occur, especially during
exercise. Although caffeine (particularly from coffee) has a reputation for
increasing intestinal motility, promoting defecation, and causing loose stools
[85], the evidence for this in humans is
rather limited [86].
Due to a lack of data on the GI-side-effect profile of caffeine in the context of
exercise, recommendations for avoiding GI disturbances from caffeine use
currently lack specificity. As pointed out by others, there is much
inter-individuality in the physiological and performance responses to caffeine
ingestion, partly due to genetic differences [81].
It is reasonable to speculate that, as is the case with caffeine’s
performance effects, its GI effects may be dictated by (yet to be identified)
genes. Until more data are available, current recommendations include: 1)
avoiding high doses (>5 mg/kg of body mass); 2) managing
exacerbating factors (psychological stress, anxiety, other stimulants, etc.);
and 3) trialing different dosages and timings of ingestion to develop an
individual side-effect profile.
As it relates to reducing caffeine’s GI side effects, one interesting
area of future research is the use of caffeinated gum as a delivery method.
Studies generally show that caffeine delivered via gum appears in the
bloodstream more quickly than swallowed caffeine [87]. This could be advantageous because direct contact of caffeine
with intestinal tissue may mediate some of its effects on the GI tract [88], meaning that bypassing the intestinal tract
could reduce GI side effects. To date, however, this hypothesis remains
unverified.
Sodium Bicarbonate
The evidence underpinning sodium bicarbonate ingestion for high-intensity
exercise performance and muscular endurance is strong, with meta-analyses
reporting favorable standardized effects sizes of approximately 0.4 [89]
[90]. Yet, few
athletes report using it [91]
[92]. In a survey of elite and sub-elite Dutch
athletes, only 4.2% had ever used it, with less than 1%
reporting use in the previous four weeks [91].
Likewise, in a survey of elite Japanese track and field athletes, none reported
using sodium bicarbonate [92].
One potentially important explanation for this infrequent use of sodium
bicarbonate is its tendency to cause GI disturbances. In 1992, McNaughton [93] reported that a 0.3-g/kg of body mass
dose exerted the most favorable effects on maximal 60-second cycling
performance, while higher doses caused GI disturbances without further improving
performance. Subsequent research has shown that, with typical sodium bicarbonate
solutions, upper GI symptoms (e. g. nausea, bloating) usually peak
30–60 min post-ingestion, while lower GI symptoms (e. g.
bowel urgency, diarrhea) tend to peak 60–90 min post-ingestion
[94]. The exact nature and timing of the
GI-symptom peak, however, varies depending on several factors, including dose,
delivery form (capsules vs. solution), and whether food is co-ingested [95].
Neutralization of bicarbonate by stomach acid seems to play a key role in the
generation of upper GI symptoms through the production of CO2, which
results in bloating, nausea, reflux, etc. [96].
Thus, enteric-coated formulations have been purported to reduce GI symptoms
since neutralization of bicarbonate in the stomach is largely bypassed. Indeed,
a pair of crossover trials by Hilton et al. [97]
[98] showed that enteric-coated and
delayed-release formulations reduced the typical GI symptoms associated with
sodium bicarbonate while still eliciting increases in blood bicarbonate anion
concentrations. In addition, an enteric-coated formulation led to an equivalent
improvement in 4-km cycling performance with a lower incidence of GI symptoms as
compared to sodium bicarbonate in gelatin capsules [99].
There are several other strategies that lessen sodium bicarbonate’s GI
side-effect profile. An athlete can use a multi-day loading regimen [100], which typically involves ingesting smaller
doses (0.1 g/kg of body mass) 3–5 times daily for
5–7 days, with a few hours between doses [101]. Although less research has examined this type of strategy, most
results to date have been favorable [102]. Another
approach is to simply use a smaller acute pre-exercise dose
(0.2 g/kg of body mass) than what is often stated as the optimal
dose (0.3 g/kg of body mass) [103]. While a 0.3-g/kg dose may lead to better average
performance for a group of athletes, a 0.2-g/kg dose may be superior for
athletes who have moderate-to-severe GI symptoms with sodium bicarbonate [104]. Lastly, ingesting sodium bicarbonate with
carbohydrate-rich foods may reduce its associated GI symptoms [95].
Exogenous Ketones
Ketones are lipid-derived compounds produced by the liver in situations of very
low dietary carbohydrate intake or starvation [105]. There is growing interest in using exogenous ketones to improve
performance, particularly in endurance sports, and there have been reports of
teams utilizing them at the Tour de France recently [106]. Although some experimental evidence suggests that ingesting
ketones can alter substrate use and perhaps spare muscle glycogen, effects on
performance have been inconsistent, with some studies showing positive effects
[107] but others showing neutral or even
harmful effects [108]
[109]
[110]. While the reasons for the
equivocal results are probably multifactorial in nature, one explanation is that
GI problems from supplementation may override any metabolic benefits in some
situations [109]. This type of scenario was
demonstrated by Leckey et al. [110], who showed
that, as compared to placebo, pre-exercise ketone diester ingestion
(2×250 mg/kg) led to GI symptoms in all participants
(ranging from mild to severe) and a 2% impairment in 31-km cycling
performance. Other investigations have also reported greater GI symptoms during
exercise with exogenous ketone ingestion than placebo [111].
Still, others have argued that different choices can be made around ketone form,
dose, timing, and frequency of ingestion to minimize GI-related side effects
during exercise [112]. Stubbs et al. [113] reported that ketone consumption (in the form
of ketone salts or monoester) at rest led to mild (on average) transient GI
symptoms, and during prolonged cycling, a ketone monoester beverage did not lead
to greater GI symptoms as compared to an iso-caloric carbohydrate beverage. In
general, ketone salts elicit worse GI symptoms than other forms, as do high
doses of all types of ketones [109]
[112]. Yet, as can be seen in the graphs of
individual responses in Stubbs et al. [113], there
is substantial inter-individuality in GI symptoms even at a high dose of ketone
salts (some people had no symptoms). As such, athletes should trial a variety of
supplement protocols during training before implementing exogenous ketone use in
competition.
Concluding Remarks
A well-functioning GI tract is needed for digestion, absorption, and assimilation of
ingested energy and nutrients before and during exercise. Intense and/or
prolonged exercise causes physiological disturbances to the gut that contribute to
symptoms, which, in some cases, interfere with performance. Several supplements,
including probiotics, glutamine, and bovine colostrum, have been studied as
GI-function enhancers with exercise. Despite some evidence that they may help
maintain GI barrier integrity, the clinical ramifications of these findings are
uncertain, as improvements in GI symptoms have not been consistently observed. Among
these supplements, probiotics modestly reduced GI symptoms in exercisers and
athletes in a few studies, suggesting they may be the leading choice for athletes
looking to manage GI symptoms through supplementation. Future studies on glutamine
should use energy-matched carbohydrate placebos to examine whether glutamine
provides unique benefits to gut barrier function. Additionally, future work on
glutamine and other supposed gut-barrier enhancers (bovine colostrum, zinc
carnosine, vitamin C, L-citrulline, curcumin) must incorporate valid assessments of
GI symptomology into their designs in order to evaluate the true practical
meaningfulness of these supplements to athletes.
Although they are ergogenic, carbohydrate, caffeine, and sodium bicarbonate can also
trigger GI symptoms. Ingesting glucose-fructose mixtures is advantageous when the
carbohydrate ingestion rate is high, and undertaking gut training sessions over the
weeks preceding competition may also be helpful, though research on such protocols
is sparse. The main strategies for preventing caffeine-induced GI issues include
avoiding high doses (>5 mg/kg) and minimizing exacerbating
factors (stress, anxiety, other stimulants, fasting). Sodium bicarbonate’s
GI side effects can be lessened by using low acute doses (0.2 g/kg),
enteric-coated formulations, and multi-day loading protocols.
