![Risk of bias summary: determination of the risk of bias items for included studies. (+) = low risk of bias; (?) = unclear risk of bias. A total of 21 papers [7,23,24,25,26,30,34,35,42,43,44,45,46,47,48,49,50,51,52,53,54] were reviewed.](https://www.researchgate.net/publication/366661966/figure/fig2/AS:11431281212004125@1702515957494/Risk-of-bias-summary-determination-of-the-risk-of-bias-items-for-included-studies_Q320.jpg)
![Effect of caffeine ingestion as compared to placebo on time to exhaustion runs. The forest plot shows standardized mean differences with 95% confidence intervals (CI) for 12 unique placebo–caffeine comparisons in 7 studies [43,44,45,46,47,49,51]. The diamond at the bottom of the graph represents the pooled standardized mean difference following random effects meta-analyses. A positive value reflects an increase in the time to exhaustion with caffeine with respect to the placebo. The size of the plotted squares reflects the relative statistical weight of each study. Caf, caffeine; Dec, decaffeinated coffee; Pla, placebo.](https://www.researchgate.net/publication/366661966/figure/fig3/AS:11431281212012626@1702515957768/Effect-of-caffeine-ingestion-as-compared-to-placebo-on-time-to-exhaustion-runs-The_Q320.jpg)
![Effect of caffeine ingestion as compared to placebo on endurance running time trials. The forest plot shows standardized mean differences with 95% confidence intervals (CI) for 22 unique placebo–caffeine comparisons in 14 studies [7,23,24,25,26,30,34,35,42,48,50,52,53,54]. The diamond at the bottom of the graph represents the pooled standardized mean difference following random effects meta-analyses. A negative value reflects a reduction in the time employed to complete a given distance with caffeine with respect to the placebo. The size of the plotted squares reflects the relative statistical weight of each study. Caf, caffeine; Dec, decaffeinated coffee; Pla, placebo.](https://www.researchgate.net/publication/366661966/figure/fig4/AS:11431281212012627@1702515958304/Effect-of-caffeine-ingestion-as-compared-to-placebo-on-endurance-running-time-trials-The_Q320.jpg)
Access to this full-text is provided by MDPI.
Content available from Nutrients
This content is subject to copyright.
Citation: Wang, Z.; Qiu, B.; Gao, J.;
Del Coso, J. Effects of Caffeine Intake
on Endurance Running Performance
and Time to Exhaustion: A
Systematic Review and
Meta-Analysis. Nutrients 2023,15,
148. https://doi.org/10.3390/
nu15010148
Academic Editor: Marilyn Cornelis
Received: 21 November 2022
Revised: 21 December 2022
Accepted: 23 December 2022
Published: 28 December 2022
Copyright: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
nutrients
Systematic Review
Effects of Caffeine Intake on Endurance Running Performance
and Time to Exhaustion: A Systematic Review and
Meta-Analysis
Ziyu Wang 1,2,† , Bopeng Qiu 2 ,† , Jie Gao 1, 2,* and Juan Del Coso 3, *
1Graduate School, Beijing Sport University, Beijing 100084, China
2College of Swimming, Beijing Sport University, Beijing 100084, China
3Centre for Sport Studies, Rey Juan Carlos University, 28943 Fuenlabrada, Spain
*Correspondence: 1806@bsu.edu.cn (J.G.); juan.delcoso@urjc.es (J.D.C.)
† These authors contributed equally to this work.
Abstract:
Caffeine (1,3,7-trimethylxanthine) is one of the most widely consumed performance-
enhancing substances in sport due to its well-established ergogenic effects. The use of caffeine is
more common in aerobic-based sports due to the ample evidence endorsing the benefits of caffeine
supplementation on endurance exercise. However, most of this evidence was established with
cycling trials in the laboratory, while the effects of the acute intake of caffeine on endurance running
performance have not been properly reviewed and meta-analyzed. The purpose of this study was
to perform a systematic review and meta-analysis of the existing literature on the effects of caffeine
intake on endurance running performance. A systematic review of published studies was performed
in four different scientific databases (Medline, Scopus, Web of Science, and SportDiscus) up until
5 October 2022 (with no year restriction applied to the search strategy). The selected studies were
crossover experimental trials in which the ingestion of caffeine was compared to a placebo situation
in a single- or double-blind randomized manner. The effect of caffeine on endurance running was
measured by time to exhaustion or time trials. We assessed the methodological quality of each study
using Cochrane’s risk-of-bias (RoB 2) tool. A subsequent meta-analysis was performed using the
random effects model to calculate the standardized mean difference (SMD) estimated by Hedges’ g
and 95% confidence intervals (CI). Results: A total of 21 randomized controlled trials were included
in the analysis, with caffeine doses ranging between 3 and 9 mg/kg. A total of 21 studies were
included in the systematic review, with a total sample of 254 participants (220 men, 19 women and
15 participants with no information about gender; 167 were categorized as recreational and 87 were
categorized as trained runners.). The overall methodological quality of studies was rated as unclear-
to-low risk of bias. The meta-analysis revealed that the time to exhaustion in running tests was
improved with caffeine (g= 0.392; 95% CI = 0.214 to 0.571; p< 0.001, magnitude = medium). Subgroup
analysis revealed that caffeine was ergogenic for time to exhaustion trials in both recreational runners
(g= 0.469; 95% CI = 0.185 to 0.754; p= 0.001, magnitude = medium) and trained runners (g= 0.344;
95% CI = 0.122 to 0.566; p= 0.002, magnitude = medium). The meta-analysis also showed that the
time to complete endurance running time trials was reduced with caffeine in comparison to placebo
(g=
−
0.101; 95% CI =
−
0.190 to
−
0.012, p= 0.026, magnitude = small). In summary, caffeine intake
showed a meaningful ergogenic effect in increasing the time to exhaustion in running trials and
improving performance in running time trials. Hence, caffeine may have utility as an ergogenic aid
for endurance running events. More evidence is needed to establish the ergogenic effect of caffeine
on endurance running in women or the best dose to maximize the ergogenic benefits of caffeine
supplementation.
Keywords: caffeine; ergogenic aid; runners; dietary supplement; exercise
Nutrients 2023,15, 148. https://doi.org/10.3390/nu15010148 https://www.mdpi.com/journal/nutrients
Nutrients 2023,15, 148 2 of 18
1. Introduction
Caffeine (1,3,7-trimethylxanthine) is one of the most widely consumed performance-
enhancing substances in sport due to its well-established ergogenic effects in a myriad of
exercise situations [
1
–
3
]. Caffeine’s ergogenicity is obtained in humans through several
physiological mechanisms including increased central nervous system drive, increased
catecholamine release, and enhanced skeletal muscle contractile capacity [
4
–
6
]. The benefits
of caffeine in sport can also be obtained by psychobiological responses, mainly displayed as
an increase in physical performance when the individual believes that they have received
an ergogenic dose of caffeine, a phenomenon known as the placebo effect of caffeine [
7
,
8
].
However, there is a consensus establishing the ability of caffeine to act as an adenosine
A
1
and A
2A
receptor antagonist as the main mechanism to explain caffeine ergogenicity
during locomotor activities [
9
–
11
]. With this theory, the blockage of adenosine receptors
with caffeine would affect the release of norepinephrine, dopamine, acetylcholine, and
serotonin, among other neurotransmitters, reducing pain and perceived exertion during
exercise, and delaying fatigue. This mechanism would explain the ergogenic effect of
caffeine on endurance exercise [
12
,
13
], anaerobic-based exercise [
14
] and strength/power
exercise [15], and sports with an intermittent nature [16,17].
Although the effect of caffeine to enhance endurance exercise performance was pro-
posed several decades ago [
18
], and several international societies today consider caffeine
as an ergogenic substance for endurance exercise [
19
,
20
], the outcomes of previous studies
regarding the effect of caffeine on this topic are not unanimous, especially for running activ-
ities. Overall, it is established that consuming low-to-moderate doses of caffeine (from ~200
to ~400 mg, equivalent to 3 to 6 mg of caffeine per kg of body mass) ~1 h before exercise
(15~80 min) improves endurance performance by 2~7% [
12
,
21
,
22
]. Most of this evidence
was established with laboratory-based studies in which cycling on a cycle ergometer was
the exercise activity investigated. However, in experiments about caffeine ergogenicity on
endurance running performance, the benefits of this substance are less clear and there is a
certain discrepancy in the studies’ outcomes [23–26].
Currently, there is only one systematic review about the effect of caffeine on endurance
running performance, and the authors concluded that caffeine intake appeared to enhance
runners’ athletic performance by 1.1% [
22
]. However, this systematic review did not include
a meta-analysis to quantify the pooled effect of caffeine on running performance. Addi-
tionally, it was performed in 2013, and did not include the results of recent investigations
on this topic. Hence, the purpose of this study was to perform a systematic review of the
existing literature on the effects of caffeine intake on endurance running performance and
subsequently apply a meta-analysis to identify the effect of caffeine on time to exhaustion
and time trial runs. We hypothesized that caffeine supplementation would enhance time to
exhaustion during running trials and would reduce time to complete endurance running
trials with a fixed distance.
2. Methods Section
2.1. Search Strategy
This systematic review was developed following the Preferred Reporting Items for
Systematic Reviews and Meta-analyses (PRISMA) 2020 statement [
27
]. The search terms
included a mix of Medical Subject Headings (MeSH) and free-text words for key concepts
related to caffeine and endurance running performance (see Appendix A). No filters or
limits were used for the search. The sources of information were obtained by searching
for studies using MEDLINE (via OVID), Scopus, Web of Science, and SPORTDiscus (via
EBSCO). The search was established from the start of construction to 5 October 2022. The
search strategy was different for each database, and it can be consulted in Appendix A. All
titles and abstracts from the search were downloaded to Endnote 20 (Clarivate Analytics,
London, UK) and manual cross-referencing was performed to identify duplicates and any
potential missing studies. Titles and abstracts were then screened for a subsequent full-text
Nutrients 2023,15, 148 3 of 18
review. The search for published studies was independently performed by two authors
(Z.W. and B.Q.) and disagreements were resolved through discussion.
2.2. Inclusion Criteria
We defined the inclusion criteria according to PICOS principles [
28
]. We only incorpo-
rated in the review studies with crossover experimental designs in which the ingestion of
caffeine was compared to a placebo in a single- or double-blind randomized manner and
the outcomes were associated with endurance running performance. We considered any
form of caffeine intake to be included in the review, but only if the effect of caffeine on en-
durance performance could be isolated; meanwhile, we excluded dietary supplements and
foodstuffs where caffeine was provided in addition to other ergogenic aids (e.g., caffeinated
energy drinks). Data from the studies in which a comparison of caffeine and placebo was
made with an emphasis on placebo effects [
29
] or after sleep deprivation [
30
] were removed,
as this may exaggerate or reduce the true effect of caffeine and is also inconsistent with
single- or double-blind trials. We only considered samples that were categorized as healthy
runners irrespective of their fitness level, and participants were excluded if they reported
regular participation in other sports in addition to running (e.g., football, triathlon, etc.).
Systematic reviews and meta-analyses were excluded, in addition to those original studies
with no full text available, non-peer-reviewed articles, opinion pieces, commentaries, case
reports and editorials. See Table 1below for details of the inclusion criteria.
Table 1.
PICOS criteria for the inclusion of crossover experimental designs in which the ingestion of
caffeine was compared to a placebo in a single- or double-blind randomized manner. For inclusion,
the study outcomes should be associated with endurance running performance.
Parameters Inclusion Exclusion Extraction
P Healthy runners
Participants of other sports
disciplines or non-athletic
population
Number of participants, gender,
training level and experience, age, daily
caffeine intake, and anthropometric
characteristics
I Caffeine Caffeine intake in combination
with other ergogenic aids
Dosage, the form of administration,
and timing of ingestion
C Placebo Trials without a true
placebo/control situation
Components, dosage, the form of
administration
O Endurance running performance Any other form of endurance
exercise different from running
Time to exhaustion trials and time trials
S
Single- or double-blind
randomized controlled trials
published in peer-reviewed
journals
Systematic reviews, conference
abstracts, graduate student
dissertations, and editorials
Experimental design, date of
publication
2.3. Data Extraction
We performed data extraction in the following topics: (a) study design; (b) sample
characteristics and participants’ running experience; (c) training status; (d) caffeine dose
and administration form; (e) time of ingestion with respect to exercise onset; (f) running
conditions (i.e., on a standard 400 m track, road, or treadmill in laboratory conditions);
and (g) endurance performance outcomes, as the time to exhaustion or time employed
to complete a trial with fixed distance or amount of work. Two authors performed the
data extraction separately (Z.W. and B.Q.). In instances where data were presented in a
graphical format, images were enlarged to improve the precision of the data estimates
and data were extracted from studies’ figures using WebPlotDigitizer [
31
]. In the event of
disagreements between the two assessors regarding data extraction, they were resolved
through discussion and consultation with a third party when necessary.
Nutrients 2023,15, 148 4 of 18
2.4. Risk of Bias
The Cochrane’s risk-of-bias tool (RoB 2) was used to rate the methodological quality
of the included studies [
32
]. The seven areas covered by this tool are: random sequence
generation, allocation concealment, participant and personnel blinding, outcome asses-
sor blinding, insufficient outcome data, selective reporting of results, and other possible
sources of bias. The application of RoB 2 for the included studies was performed by two
separate authors (Z.W. and B.Q.), and disagreements were resolved through discussion
and consultation with a third party when necessary.
2.5. Data Analysis
The Comprehensive Meta-Analysis software (version 3; Biostat, Englewood, NJ, USA)
was used to compare the effects of caffeine vs. placebo ingestion on study outcomes
using standardized mean differences (SMDs), estimated by Hedges’ gand 95% confidence
intervals (CI). All the meta-analyses were performed using the random-effects model. We
considered the SMD of
≤
0.20, 0.20–0.49, 0.50–0.79, and
≥
0.8 as small, medium, large and
very large, respectively, based on a previous categorization [
33
]. The statistical significance
threshold was set at p< 0.050. For each outcome, the SMD was calculated using mean and
standard deviation values from the placebo and caffeine trials, the sample size from each
study, and the correlations between the trials. Only two studies [
34
,
35
] reported correlation
values for the performance data between the placebo and caffeine conditions, with a 0.87
correlation for Whalley et al. [
34
] and 0.86 correlation for Bell et al. [
35
], respectively.
For the remaining studies, a 0.5 correlation was assumed, as recommended by Follmann
et al. [
36
]. For each outcome, a minimum of three studies were required to perform
the meta-analysis [
37
]. In studies with several caffeine–placebo comparisons, such as
different doses or forms of caffeine administration, we obtained data independently for
each caffeine–placebo comparison. We assumed that the sample size was the same in each
separate caffeine–placebo comparison, as each participant completed all testing conditions
in multi-arm studies [
38
]. A subgroup analysis was conducted on the effects of caffeine
on endurance running performance based on the participants’ training levels (trained
vs. recreational). The assignation of each study’s sample to the subgroup of trained vs.
recreational runners was based on the participants’ characteristics reported in the study.
For instance, when the sample was described as “elite or sub-elite”, “varsity”, “competitive”
or “well-trained”, the participants were included in the subgroup of trained runners. If the
sample was described as “amateur” or “recreational”, the participants were included in
the subgroup of recreational runners. An additional subgroup analysis was conducted on
the effects of caffeine on endurance running performance based on the distance covered
during the running trial. The outcomes of running trials between 800 and 5000 m were
included in the subgroup of middle-distance, and running trials covering more than 5000
m were included in the subgroup of long-distance. Finally, the magnitude of caffeine’s
effect on endurance performance was presented as the percentage of change calculated by
the formula proposed by Lopez-Gonzalez et al. [39].
We used the I
2
statistic to assess the degree of heterogeneity, with values
≤
50% indi-
cating low heterogeneity, 50–75% indicating moderate heterogeneity, and >75% indicating
high heterogeneity [
40
]. Potential asymmetries in funnel plots and Egger’s linear regression
test were employed to detect publication bias [41].
3. Results
3.1. Search Outcomes
We obtained 6193 studies through database searching. After deleting duplicates and
screening the titles and abstracts of all the remaining original papers, we evaluated 127
full-text articles for inclusion in our research. We eliminated 106 papers for various reasons,
leaving only 21 studies to be included in the systematic review (Figure 1). The experiments
that met the inclusion criteria were published between 1991 and 2022.
Nutrients 2023,15, 148 5 of 18
Nutrients 2023, 15, x FOR PEER REVIEW 5 of 16
Figure 1. Flow diagram of literature search according to the PRISMA 2020 statement.
3.2. Study Characteristics
In the 21 studies included in this systematic review [7,23–26,30,34,35,42–54], there
was a total sample of 254 participants, including 220 men, 19 women and 15 participants
with no information about gender. The participants were all runners, of which 167 were
categorized as amateur and 87 were categorized as trained runners. All studies were cross-
over randomized controlled trials. A total of 18 studies [7,23–26,30,35,42,43,45,46,48–54]
provided caffeine in liquid or capsule form, with doses normalized by participants’ body
mass. In these studies, the doses of caffeine administered ranged from 3 to 9 mg/kg. A
total of three studies [34,44,47] provided absolute doses of caffeine in the form of caffeine
powder, gum, and mouth strips with doses ranging from 200 to 300 mg. The general data
of the experiments included in this systematic review are depicted in Table 2.
Figure 1. Flow diagram of literature search according to the PRISMA 2020 statement.
3.2. Study Characteristics
In the 21 studies included in this systematic review [
7
,
23
–
26
,
30
,
34
,
35
,
42
–
54
], there was
a total sample of 254 participants, including 220 men, 19 women and 15 participants with no
information about gender. The participants were all runners, of which 167 were categorized
as amateur and 87 were categorized as trained runners. All studies were crossover ran-
domized controlled trials. A total of 18
studies [7,23–26,30,35,42,43,45,46,48–54]
provided
caffeine in liquid or capsule form, with doses normalized by participants’ body mass. In
these studies, the doses of caffeine administered ranged from 3 to 9 mg/kg. A total of
three studies [
34
,
44
,
47
] provided absolute doses of caffeine in the form of caffeine powder,
gum, and mouth strips with doses ranging from 200 to 300 mg. The general data of the
experiments included in this systematic review are depicted in Table 2.
Nutrients 2023,15, 148 6 of 18
Table 2. Detailed characteristics of included trials (n= 21).
Author(s)
Year
Country
N (Male/Female)
Age
Body Mass
Running
Experience
Caffeine
Administration Timing Comparator Running
Conditions Measures Running Tests
Bell et al.,
2002
Canada [35]
12 (10/2)
33 ±8 years
75 ±11 kg
Recreational 4 mg/kg in capsules 60 min- pre-exercise 300 mg dietary fiber
capsules Treadmill 10 km time NS TTP
Borba et al.,
2019
Brazil [53]
13 (8/5)
28.46 ±5.63
23.58 ±3.90 kg/m2Recreational 6 mg/kg in hot water 60 min pre-exercise Hot water Track (400 m) 1600 m runs NS TTP
Bonetti de Poli et al.,
2016
Brazil [43]
18 (18/0)
29 ±7 years
72.1 ±5.8 kg
Recreational 6 mg/kg in capsules 60 min pre-exercise Dextrose capsules Treadmill TTE test ↑TTE
Bridge and Jones
2006
United Kingdom [
54
]
8 (8/0)
21.3 ±1.2 years
69.3 ±5.0 kg
Trained 3 mg/kg in capsules 60 min pre-exercise Glucose capsules Track (400 m) 8 km time ↑TTP
Clarke et al.,
2018
United Kingdo [23]
13 (13/0)
24 ±6 years
69.3 ±4.7 kg
Trained 0.09 g/kg coffee
(including 3 mg/kg) 60 min pre-exercise
1. Decaffeinated
coffee in warm water
2. Warm water with
coffee flavor and
color
Indoor 200 m
running track with
banked curves
mile race ↑TTP
Cohen et al.,
1996
United States of
America [42]
7 (5/2)
33.29 ±9.18 years
NI
Trained 1. 5 mg/kg in capsules
2. 9 mg/kg in capsules 60 min pre-exercise Baking flour
capsules Outdoor road 21 km runs NS TTP
Dittrich et al.,
2021
Brazil [44]
12 (12/0)
31.3 ±6.4 years
70.5 ±6.6 kg
Trained 300 mg in chewing gum immediately
pre-exercise
Noncaffeinated
chewing gum Treadmill TTE test ↑TTE
Graham and Spriet
1991
Canada [45]
7 (6/1)
28.3 ±5.63 years
67.2 ±8.33 kg
Trained 9 mg/kg in capsules 60 min pre-exercise 9 mg/kg dextrose
capsules Treadmill TTE test ↑TTE
Graham and
Sathasivam
1998
Canada [46]
9 (8/1)
21.1 ±6.5 years
73.1 ±5.5 kg
Recreational
1. 4.5 mg/kg in capsules
2. regular coffee
(including 4.5 mg/kg)
3. decaffeinated coffee
plus 4.5.mg/kg in
capsules
60 min pre-exercise
1. decaffeinated
coffee
2. dextrose capsules
Treadmill TTE test ↑TTE
Nutrients 2023,15, 148 7 of 18
Table 2. Cont.
Author(s)
Year
Country
N (Male/Female)
Age
Body Mass
Running
Experience
Caffeine
Administration Timing Comparator Running
Conditions Measures Running Tests
Hanson et al.,
2019
USA [24]
10 (6/4)
26 ±9 years
72.1 ±8.7 kg
Trained
1. 3 mg/kg in a flavored
water-based drink
2. 6 mg/kg in a flavored
water-based drink
60 min pre-exercise
Flavored
water-based drink
without caffeine
Treadmill 10 km runs NS TTP
Kasper et al.,
2016
Tunisia [47]
8 (8/0)
22 ±2 years
70.8 ±8.1 kg
Recreational
200 mg in capsules/ +
carbohydrate mouth
rinse
immediately
pre-exercise
placebo capsules +
carbohydrate rinse Treadmill TTE test ↑TTE
Khcharem et al.,
2021
Tunisia [48]
13 (13/0)
21.3 ±0.8 years
66.5 ±7.8 kg
Recreational 3 mg/kg in capsules 90 min pre-exercise 3 mg/kg sucrose
capsules Track (400 m) 3 km runs ↑TTP
Khcharem et al. a
2022
Tunisia [30]
10 (10/0)
21.7 ±1.1
66.7 ±8.7 kg
Recreational 5 mg/kg in capsules 90 min pre-exercise NI capsules Track (400 m) 8 km runs ↑TTP
Khcharem et al. b
2022
Tunisia [49]
12 (12/0)
21.7 ±0.9 years
64.4 ±9.4 kg
Recreational 6 mg/kg in capsules 90 min pre-exercise 6 mg/kg sucrose
capsules Track (400 m) TTE test ↑TTE
Manoel et al.,
2021
Brazil [25]
15 (15/0)
25.2 ±2.8 years
79.9 ±7.7 kg
Recreational 6 mg/kg in capsules 60 min pre-exercise Empty capsules Track (400 m) 10 km runs NS TTP
Marques et al.,
2018
Brazil [26]
12 (12/0)
23.50 ±3.94 years
70.38 ±8.41 kg
Recreational 5.5 mg/kg in soluble
coffee 60 min pre-exercise Decaffeinated coffee Track (400 m) 800 m run NS TTP
O’Rourke et al.,
2008
Australia [50]
15 (NI)
32.2 ±8.8 years
68.9 ±6.1 kg
Trained 5 mg/kg in tablets 60 min pre-exercise 5 mg/kg sugar
tablets Track (400 m) 5 km run ↑TTP
Ping et al.,
2010
Malaysia [51]
9 (9/0)
25.4 + 6.9 years
57.6 + 8.4 kg
Recreational 5 mg/kg in capsules 60 in pre-exercise 5 mg/kg placebo
capsules Treadmill TTE test ↑TTE
Ramos-Campo et al.,
2019
Spain [52]
15 (15/0)
23.7 ±8.2 years
64.6 ±9.8 kg
Trained 6 mg/kg in capsules 60 min pre-exercise 6 mg/kg sucrose
capsules Track (400 m) 800 m run NS TTP
Nutrients 2023,15, 148 8 of 18
Table 2. Cont.
Author(s)
Year
Country
N (Male/Female)
Age
Body Mass
Running
Experience
Caffeine
Administration Timing Comparator Running
Conditions Measures Running Tests
Rohloff et al.,
2022
Brazil [7]
22 (22/0)
25.5 ±8.4 years
75.0 ±7.1 kg
Recreational 4 mg/kg in capsules 60 min pre-exercise
4 mg/kg
maltodextrin
capsules
Treadmill 4 km runs NS TTP
Whalley et al.,
2019
New Zealand [34]
14 (10/4)
40 ±8 years
69 ±11 kg
Recreational
1. 200–300 mg in
chewing gum
2. 200–300 mg in tablets
3. 200–300 mg in mouth
strips
15 min pre-exercise 300 mg glucose
powder capsule Road 5 km runs ↑TTP
TTP time trial performance; TTE, time to exhaustion; NI, not informed; NS, a no statistically significant difference between caffeine condition and placebo condition;
↑
, a statistically
significant difference between caffeine condition and placebo condition indicating an ergogenic effect of caffeine.
Nutrients 2023,15, 148 9 of 18
3.3. Methodological Quality of Included Studies
Figure 2displays the categorization for each RoB 2 item for each included study.
Regarding selection bias, we judged only one study [
53
] as low risk because it reported
the appropriate method of participant randomization sequences. We defined all other
studies as unclear because none provided sufficient information for this item. In addition,
the allocation concealment process was not detailed in any of the studies; therefore, we
rated their risk as unclear for allocation concealment. We considered that four studies were
unclear regarding the blinding process of participants and researchers [
35
,
47
,
50
,
51
]. The
remaining studies were all low risk for this item. Only two studies [
7
,
26
] described the
blinding of outcome assessors, and they were rated as low-risk. All other studies did not
provide sufficient information; therefore, they were rated as having an unclear risk. Most of
the included studies [
7
,
23
,
24
,
26
,
30
,
35
,
43
,
44
,
46
,
47
,
49
,
50
,
52
,
54
] had no reported participant
dropouts, and therefore they were rated unclear. None of the included studies had trial
registration protocols. We identified no other sources of bias in the included studies. Thus,
we categorized the overall methodological quality as with an unclear-to-low risk of bias.
Nutrients 2023, 15, x FOR PEER REVIEW 8 of 16
3.3. Methodological Quality of Included Studies
Figure 2 displays the categorization for each RoB 2 item for each included study. Re-
garding selection bias, we judged only one study [53] as low risk because it reported the
appropriate method of participant randomization sequences. We defined all other studies
as unclear because none provided sufficient information for this item. In addition, the al-
location concealment process was not detailed in any of the studies; therefore, we rated
their risk as unclear for allocation concealment. We considered that four studies were un-
clear regarding the blinding process of participants and researchers [35,47,50,51]. The re-
maining studies were all low risk for this item. Only two studies [7,26] described the blind-
ing of outcome assessors, and they were rated as low-risk. All other studies did not pro-
vide sufficient information; therefore, they were rated as having an unclear risk. Most of
the included studies [7,23,24,26,30,35,43,44,46,47,49,50,52,54] had no reported participant
dropouts, and therefore they were rated unclear. None of the included studies had trial
registration protocols. We identified no other sources of bias in the included studies. Thus,
we categorized the overall methodological quality as with an unclear-to-low risk of bias.
Figure 2.
Risk of bias summary: determination of the risk of bias items for included studies. (+) = low
risk of bias; (?) = unclear risk of bias. A total of 21 papers [7,23–26,30,34,35,42–54] were reviewed.
Nutrients 2023,15, 148 10 of 18
3.4. Effects of Interventions
3.4.1. Time to Exhaustion Runs
Seven studies [
43
–
47
,
49
,
51
] including 12 placebo–caffeine comparisons investigated
the effect of caffeine on time-to-exhaustion runs. Pooled data from these investigations
showed that the caffeine intake was effective in prolonging the time to exhaustion compared
with the placebo (g= 0.392; 95% CI = 0.214 to 0.571; p< 0.001, magnitude = medium;
Figure 3). We observed no significant heterogeneity (Q = 11.436; df = 11; p= 0.408; I
2
=
3.809%). Overall, caffeine increased time to exhaustion during running trials by 16.97%
±
14.65%. The subgroup analysis of training status revealed that caffeine increased time to
exhaustion in recreational runners (g= 0.469; 95% CI = 0.185 to 0.754; p= 0.001, magnitude
= medium; I
2
= 0%) and trained runners (g= 0.344; 95% CI = 0.122 to 0.566; p= 0.002,
magnitude = medium; I
2
= 22.44%). Funnel plots showed evidence of non-publication bias,
which was confirmed by Egger’s linear regression test (p> 0.050; Appendix B).
Nutrients 2023, 15, x FOR PEER REVIEW 9 of 16
Figure 2. Risk of bias summary: determination of the risk of bias items for included studies. (+) =
low risk of bias; (?) = unclear risk of bias. A total of 21 papers
[7,23–26,30,34,35,42–54]
were re-
viewed.
3.4. Effects of Interventions
3.4.1. Time to Exhaustion Runs
Seven studies [43–47,49,51] including 12 placebo–caffeine comparisons investigated
the effect of caffeine on time-to-exhaustion runs. Pooled data from these investigations
showed that the caffeine intake was effective in prolonging the time to exhaustion com-
pared with the placebo (g = 0.392; 95% CI = 0.214 to 0.571; p < 0.001, magnitude = medium;
Figure 3). We observed no significant heterogeneity (Q = 11.436; df = 11; p = 0.408; I
2
=
3.809%). Overall, caffeine increased time to exhaustion during running trials by 16.97% ±
14.65%. The subgroup analysis of training status revealed that caffeine increased time to
exhaustion in recreational runners (g = 0.469; 95% CI = 0.185 to 0.754; p = 0.001, magnitude
= medium; I
2
= 0%) and trained runners (g = 0.344; 95% CI = 0.122 to 0.566; p = 0.002, mag-
nitude = medium; I
2
= 22.44%). Funnel plots showed evidence of non-publication bias,
which was confirmed by Egger’s linear regression test (p > 0.050; Appendix B).
Figure 3. Effect of caffeine ingestion as compared to placebo on time to exhaustion runs. The forest
plot shows standardized mean differences with 95% confidence intervals (CI) for 12 unique pla-
cebo–caffeine comparisons in 7 studies [43–47,49,51]. The diamond at the bottom of the graph rep-
resents the pooled standardized mean difference following random effects meta-analyses. A posi-
tive value reflects an increase in the time to exhaustion with caffeine with respect to the placebo.
The size of the plotted squares reflects the relative statistical weight of each study. Caf, caffeine; Dec,
decaffeinated coffee; Pla, placebo.
3.4.2. Endurance Time Trial Performance
Fourteen randomized controlled trials [7,23–26,30,34,35,42,48,50,52–54] including 22
placebo–caffeine comparisons evaluated the effect of caffeine on endurance running per-
formance in time trials. The meta-analysis revealed a significant reduction in the time em-
ployed to complete the running trials with caffeine vs. placebo (g = −0.101; 95% CI = −0.190
to −0.012, p = 0.026, magnitude = small; Figure 4), and this meta-analysis did not contain
substantial heterogeneity (Q = 8.580; df = 21; p = 0.992; I
2
= 0%). The average reduction in
time during endurance running events was −0.71% ± 0.83%. However, the subgroup anal-
ysis indicated that caffeine failed to improve endurance running performance in time trials
carried out by trained runners (g = −0.140; 95% CI = −0.295 to 0.014, p = 0.075) and by recre-
ational runners (g = −0.082; 95% CI = −0.190 to 0.027, p = 0.141; Table 3). The subgroup
analysis of distance also revealed that caffeine was not ergogenic in middle-distance or
long-distance time trials (Table 3). A funnel plot revealed no indication of publication bias,
which was confirmed by Egger’s linear regression test (p > 0.05; Appendix B).
Figure 3.
Effect of caffeine ingestion as compared to placebo on time to exhaustion runs. The forest
plot shows standardized mean differences with 95% confidence intervals (CI) for 12 unique placebo–
caffeine comparisons in 7 studies [
43
–
47
,
49
,
51
]. The diamond at the bottom of the graph represents
the pooled standardized mean difference following random effects meta-analyses. A positive value
reflects an increase in the time to exhaustion with caffeine with respect to the placebo. The size of the
plotted squares reflects the relative statistical weight of each study. Caf, caffeine; Dec, decaffeinated
coffee; Pla, placebo.
3.4.2. Endurance Time Trial Performance
Fourteen randomized controlled trials [
7
,
23
–
26
,
30
,
34
,
35
,
42
,
48
,
50
,
52
–
54
] including 22
placebo–caffeine comparisons evaluated the effect of caffeine on endurance running per-
formance in time trials. The meta-analysis revealed a significant reduction in the time
employed to complete the running trials with caffeine vs. placebo (g=
−
0.101; 95%
CI =
−
0.190 to
−
0.012, p= 0.026, magnitude = small; Figure 4), and this meta-analysis
did not contain substantial heterogeneity (Q = 8.580; df = 21; p= 0.992; I
2
= 0%). The
average reduction in time during endurance running events was
−
0.71%
±
0.83%. How-
ever, the subgroup analysis indicated that caffeine failed to improve endurance running
performance in time trials carried out by trained runners (g=
−
0.140; 95% CI =
−
0.295
to 0.014, p= 0.075) and by recreational runners (g=
−
0.082; 95% CI =
−
0.190 to 0.027,
p= 0.141; Table 3). The subgroup analysis of distance also revealed that caffeine was not
ergogenic in middle-distance or long-distance time trials (Table 3). A funnel plot revealed
no indication of publication bias, which was confirmed by Egger’s linear regression test
(p> 0.05; Appendix B).
Nutrients 2023,15, 148 11 of 18
Nutrients 2023, 15, x FOR PEER REVIEW 10 of 16
Figure 4. Effect of caffeine ingestion as compared to placebo on endurance running time trials. The
forest plot shows standardized mean differences with 95% confidence intervals (CI) for 22 unique
placebo–caffeine comparisons in 14 studies [7,23–26,30,34,35,42,48,50,52–54]. The diamond at the
bottom of the graph represents the pooled standardized mean difference following random effects
meta-analyses. A negative value reflects a reduction in the time employed to complete a given dis-
tance with caffeine with respect to the placebo. The size of the plotted squares reflects the relative
statistical weight of each study. Caf, caffeine; Dec, decaffeinated coffee; Pla, placebo.
Table 3. Subgroup analysis by training status and distance on the effect of the caffeine ingestion on
endurance running time trials.
Subgroup Grouping Criteria Number of Studies g 95%CI p I
2
Training status Recreational 10 −0.082 [−0.190, 0.027] 0.141 0%
Trained 12 −0.140 [−0.295, 0.014] 0.075 0%
Distance Middle-distance 14 −0.083 [−0.187, 0.020] 0.114 0%
Long-distance 8 −0.151 [−0.324, 0.023] 0.089 0%
4. Discussion
Caffeine supplementation is habitually recommended as an ergogenic aid for endur-
ance performance, including endurance running [19,20]. However, most of the evidence
on caffeine’s ergogenicity in aerobic-based scenarios is based on studies with cycling trials
[12]. Although the basics of caffeine’s ergogenicity can be transferred from endurance cy-
cling to endurance running (e.g., minimal effective dose, the timing of ingestion, habitua-
tion, etc.), the particularities of a footrace may mean that the magnitude of the ergogenic
effect is different in running than in cycling. A recently published review suggested that
caffeine supplementation in the form of coffee improved endurance performance by 3.1%
[55]. However, this review included a pool of cycling and running trials, and it is difficult
to ascertain if the ergogenic effect of caffeine is of similar magnitude for cycling and run-
ning. Interestingly, the effectiveness of caffeine in enhancing endurance running perfor-
mance has not been properly summarized, despite there being plenty of studies on this
topic to accurately determine the existence (or not) and magnitude of the ergogenic effect
of caffeine on endurance running. Hence, the aim of this systematic was to analyze the
existing literature on the effects of caffeine intake on endurance running performance and
subsequently apply a meta-analysis to identify the effect of caffeine on time to exhaustion
and time trial runs. The main results of this systematic review indicate that caffeine intake
Figure 4.
Effect of caffeine ingestion as compared to placebo on endurance running time trials. The
forest plot shows standardized mean differences with 95% confidence intervals (CI) for 22 unique
placebo–caffeine comparisons in 14 studies [
7
,
23
–
26
,
30
,
34
,
35
,
42
,
48
,
50
,
52
–
54
]. The diamond at the
bottom of the graph represents the pooled standardized mean difference following random effects
meta-analyses. A negative value reflects a reduction in the time employed to complete a given
distance with caffeine with respect to the placebo. The size of the plotted squares reflects the relative
statistical weight of each study. Caf, caffeine; Dec, decaffeinated coffee; Pla, placebo.
Table 3.
Subgroup analysis by training status and distance on the effect of the caffeine ingestion on
endurance running time trials.
Subgroup Grouping Criteria Number of Studies g95%CI pI2
Training status Recreational 10 −0.082 [−0.190, 0.027] 0.141 0%
Trained 12 −0.140 [−0.295, 0.014] 0.075 0%
Distance Middle-distance 14 −0.083 [−0.187, 0.020] 0.114 0%
Long-distance 8 −0.151 [−0.324, 0.023] 0.089 0%
4. Discussion
Caffeine supplementation is habitually recommended as an ergogenic aid for en-
durance performance, including endurance running [
19
,
20
]. However, most of the evidence
on caffeine’s ergogenicity in aerobic-based scenarios is based on studies with cycling tri-
als [
12
]. Although the basics of caffeine’s ergogenicity can be transferred from endurance
cycling to endurance running (e.g., minimal effective dose, the timing of ingestion, habitua-
tion, etc.), the particularities of a footrace may mean that the magnitude of the ergogenic
effect is different in running than in cycling. A recently published review suggested that caf-
feine supplementation in the form of coffee improved endurance performance by 3.1% [
55
].
However, this review included a pool of cycling and running trials, and it is difficult to
ascertain if the ergogenic effect of caffeine is of similar magnitude for cycling and running.
Interestingly, the effectiveness of caffeine in enhancing endurance running performance
has not been properly summarized, despite there being plenty of studies on this topic
to accurately determine the existence (or not) and magnitude of the ergogenic effect of
caffeine on endurance running. Hence, the aim of this systematic was to analyze the
existing literature on the effects of caffeine intake on endurance running performance and
Nutrients 2023,15, 148 12 of 18
subsequently apply a meta-analysis to identify the effect of caffeine on time to exhaustion
and time trial runs. The main results of this systematic review indicate that caffeine intake
in doses ranging from 3 to 9 mg per kg of body mass (1) enhanced time to exhaustion
during running trials with an effect of medium magnitude and an overall increase of
16.97%
±
14.65% and (2) produced a small but statistically significant effect on endurance
running time trial protocols with a mean reduction of
−
0.71%
±
0.83%. Collectively, all
this information supports the recommendation of caffeine intake for endurance runners,
but now with the meta-analytical support of specific studies in which caffeine’s benefits
were tested in endurance running protocols. Nevertheless, caffeine seems more ergogenic
for time-to-exhaustion runs than for time trials, suggesting that this substance may be more
useful for prolonged running events where time to exhaustion is a performance factor.
4.1. Effect of Caffeine Intake on Time to Exhaustion Runs
Both time-to-exhaustion and time-trial exercise test protocols are commonly used to
examine the influence of experimental interventions on endurance performance. In the
context of endurance running, time-to-exhaustion protocols represent an unusual scenario
with respect to real-environment running [
22
], as most endurance running events consist
of completing a given distance as fast as possible. However, time-to-exhaustion runs
provide a measure of an athlete’s endurance capacity and they are considered a valid
measure of endurance performance [
56
]. In the current systematic review, seven studies,
including 12 unique placebo–caffeine comparisons, tested the effect of caffeine on running
protocols that entailed participants performing submaximal intensity running until they
could no longer maintain the required speed. Overall, the values of time to exhaustion
were higher with caffeine than in the placebo situation, and the meta-analysis revealed a
statistically significant effect of caffeine in this performance variable (Figure 3). Caffeine
promotes the production of ß-endorphins and dopamine [57], which can lessen perceived
effort and discomfort [
58
,
59
]. These factors can explain the ergogenic effect of caffeine on
time to exhaustion runs, as the “exhaustion time” when runners decide to stop running is
associated with feelings of fatigue and muscle pain. Although running events consisting of
“run as long as you can” are scarce, the higher time to exhaustion induced by caffeine may
apply to ultra-endurance running events where athletes are required to run in scenarios
close to exhaustion, such as 24 h races and 100-mile races or mountain running events.
It is important to note that performance in time-to-exhaustion trials is habitually more
variable than in time trials, especially for those with a lower training background [
60
,
61
].
However, our subgroup analyses indicated that caffeine ingestion significantly increased
run-to-fatigue time to a moderate degree in both recreational and trained runners. In
summary, it seems safe to conclude that caffeine is an effective substance to enhance
running performance in situations that entail running until volitional fatigue.
4.2. Effect of Caffeine Intake on Endurance Running Time Trials
The use of time trials offers a better scenario to study the effect of caffeine on endurance
running performance, as runners’ performance is more reproducible in time-trial runs than
in running to exhaustion events [
56
]. This likely explains why 14 studies used time trials
while only seven studies used time-to-exhaustion runs to determine the effect of caffeine
on running performance. The meta-analysis revealed that caffeine has a small effect but
significant ergogenic effect to reduce time in endurance running for a given distance
(Figure 4). The ergogenic effect of caffeine on running time trials was lower compared to
the effect of this substance on time-to-exhaustion runs (0.71%
±
0.83% vs. 16.97%
±
14.65%,
respectively). The explanation for the different magnitude of caffeine’s benefits on these two
types of endurance performance running trials may be associated with the characteristics of
each running protocol. In time-to-exhaustion runs, the intensity is fixed, and runners cannot
adjust the pace during the running trial. However, in time trials, like in real running races,
runners may adjust their pace depending on their feelings of fatigue and the distance left
to complete the trial [
62
]. As an adenosine antagonist [
5
], caffeine can decrease fatigue by
Nutrients 2023,15, 148 13 of 18
crossing the blood–brain barrier and inhibiting A
1
and A
2
monoadenosine receptors [
5
,
9
].
So, caffeine may have an inhibitory effect on perceptual response during exercise, which
may give participants an increased ability to tolerate the discomfort associated with fatigue
during exercise, effectively masking the sensation of fatigue [
58
]. Therefore, caffeine
intake may produce a faster running speed than placebo intake with the same perceptual
response [
63
], thereby influencing running pacing strategies [
64
]. Independently of the
type of test employed, caffeine produced statistically significant benefits for both time-to-
exhaustion runs and time trials, suggesting that caffeine is a substance with the potential
for enhancing performance in different endurance running scenarios.
Interestingly, when analyzing the ergogenic effect of caffeine on time-trial runs accord-
ing to participants’ training status, the benefit of caffeine was not statistically significant for
trained runners or recreational runners (Table 3). Previous studies indicated that caffeine
is more effective in reducing the time to complete specific running distances in trained
athletes, and trained runners are more reliable [
60
,
61
]. Similar results have been found
in other types of exercise, such as swimming, as it has been suggested that caffeine has
a facilitative effect on trained but not “active” swimmers [
65
]. Although more studies
are granted on this topic, we can assume that training status is not a modifying factor
for the ergogenic effect of caffeine on endurance performance. Likewise, when consider-
ing the distance of the running time trials, caffeine did not reduce the time to complete
middle-distance or long-distance trials (Table 3), despite it previously being suggested that
caffeine is more effective in long endurance events than in short but intense endurance
events [
38
,
66
]. Overall, the effect of caffeine on improving running time trial performance
was statistically significant but small, which demonstrated that the potential ergogenic
effect of caffeine was the same across subgroups of training status and distance.
4.3. Limitations and Future Lines of Research
Although we only selected blinded randomized controlled studies, the placebo choice
appears to be diverse in some studies (e.g., sugar-free, sugary, and decaffeinated), and
caffeine was also taken with other compounds (e.g., carbohydrates and artificial sweeteners).
Thus, it is possible that the actual effects of caffeine may be masked or exaggerated by
some of these substances. In addition, different sources of caffeine (capsules, tablets, gums,
beverages, etc.) may affect the pharmacokinetics of caffeine [
11
], thus influencing the
results of different studies. Another limitation is that, due to the differences in participants’
characteristics and form of caffeine administration, it was not possible to meta-analyze the
effect of participants’ sex, form of caffeine intake or caffeine dose on the benefits obtained
with caffeine supplementation. In this regard, only 7.5% of the pooled sample of this
systematic review were women, suggesting that the outcomes of this study possess a sex
bias. For this reason, it is perhaps more accurate to indicate that caffeine’s ergogenicity on
endurance running performance in men is supported by the results of this study, while the
benefits of this substance for women endurance runners should be further investigated.
Last, in the current analysis, we only focused on running performance variables, namely
the time to exhaustion and the time to complete a given distance. The study of the effect
of caffeine on physiological and perceptual responses during endurance running such as
heart rate, blood lactate concentration and ratings of perceived fatigue requires further
investigation and analysis, as these responses may contribute to explaining the ergogenic
effect of caffeine. From a methodological perspective, it should be mentioned that most
of the studies were classified as having low risk of bias, as they all utilized randomized
crossover designs. Therefore, the outcomes of the current study are not influenced by
the inclusion of studies with poor methodological quality, which strengthens the main
conclusions.
5. Conclusions
Pre-exercise caffeine supplementation, in the range of 3 to 9 mg per kg of body mass,
showed a medium-size ergogenic effect to increase the time to exhaustion in running trials
Nutrients 2023,15, 148 14 of 18
and a small-size effect to improve performance in running time trials. These outcomes
confirm the utility of caffeine as an ergogenic aid for endurance running events where time
to exhaustion is key for performance or in competitions with a fixed distance. Still, the
evidence is not enough to determine whether the ergogenic effect of caffeine is of similar
magnitude in men and women, as women only represented a minor portion of the study
participants in this systematic review. Further investigation is also needed to establish the
minimal effective dose of caffeine, the existence of tolerance to caffeine’s ergogenicity with
chronic habituation, and the most common drawbacks of caffeine supplementation in the
context of endurance running.
Author Contributions:
Conceptualization, J.G. and J.D.C.; methodology, Z.W. and B.Q.; formal
analysis, Z.W. and B.Q.; writing—original draft preparation, Z.W., B.Q., J.G. and J.D.C.; writing—
review and editing, Z.W., B.Q., J.G. and J.D.C. All authors have read and agreed to the published
version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement:
The data presented in this study are available on request from the
corresponding author (J.G.).
Conflicts of Interest: The authors declare no conflict of interest.
Appendix A. Search Strategies Used for the Four Databases Used in the Investigation
MEDLINE (via OVID).
1(Caffedrine or caffeine or
Coffeinum or coffee or caffein*).ab,ti
46,031
2 Coffee/ 8042
3 Caffeine/ 24,875
4 1 or 2 or 3 51,853
5 Marathon Running/ or Running/ 22,700
6(run or runner or running or
marathon).ab,ti. 163,459
7 (endurance or aerobic).ab,ti. 127,679
8 5 or 6 or 7 287,903
9 4 and 8 1061
SPORTDiscus (via EBSCO).
S1 AB caffein* OR AB coffee OR AB
coffeinum OR AB caffedrine 4953
S2 AB run OR AB runner OR AB
running OR AB marathon 96,403
S3 AB endurance OR AB aerobic 40,490
S4 S2 OR S3 129,153
S5 S1 AND S4 672
Web of science.
Nutrients 2023,15, 148 15 of 18
#1 (TS=(endurance)) OR
TS=(aerobic) 211,671
#2
TS=(run) OR TS=(runner) OR
TS=(running) or
TS=(marathon)
675,833
#3
TS=(caffein*) OR TS=(coffee)
OR TS=(coffeinum) OR
TS=(caffedrine)
78,451
#4 #1 OR #2 871,860
#5 #3 AND #4 2066
Scopus.
(TITLE-ABS-KEY (run) OR TITLE-ABS-KEY
(runner) OR TITLE-ABS-KEY (running) OR
TITLE-ABS-KEY (marathon) OR
TITLE-ABS-KEY (endurance) OR
TITLE-ABS-KEY (aerobic)) AND
(TITLE-ABS-KEY (coffee) OR TITLE-ABS-KEY
(coffeinum) OR TITLE-ABS-KEY (caffedrine)
OR TITLE-ABS-KEY (caffeine))
2394
Appendix B. Results of the Egger’s Linear Regression Test
Outcomes Coef. SE 95% CI t pNumber of Trials
Time to
Exhaustion 0.856 1.69 −2.90 to 4.61 0.51 0.622 12
Running Time
Trials −0.740 0.72 −2.24 to
0.762 −
1.03
0.317 22
References
1.
Astorino, T.A.; Roberson, D.W. Efficacy of acute caffeine ingestion for short-term high-intensity exercise performance: A
systematic review. J. Strength Cond. Res. 2010,24, 257–265. [CrossRef] [PubMed]
2.
Warren, G.L.; Park, N.D.; Maresca, R.D.; McKibans, K.I.; Millard-Stafford, M.L. Effect of caffeine ingestion on muscular strength
and endurance: A meta-analysis. Med. Sci. Sport. Exerc. 2010,42, 1375–1387. [CrossRef] [PubMed]
3. Pickering, C.; Grgic, J. Caffeine and exercise: What next? Sport. Med. 2019,49, 1007–1030. [CrossRef] [PubMed]
4.
Davis, J.K.; Green, J.M. Caffeine and anaerobic performance: Ergogenic value and mechanisms of action. Sport. Med.
2009
,39,
813–832. [CrossRef]
5. Graham, T.E. Caffeine and exercise: Metabolism, endurance and performance. Sport. Med. 2001,31, 785–807. [CrossRef]
6.
Cristina-Souza, G.; Santos, P.S.; Santos-Mariano, A.C.; Coelho, D.B.; Rodacki, A.; DE-Oliveira, F.R.; Bishop, D.J.; Bertuzzi, R.;
Lima-Silva, A.E. Caffeine increases endurance performance via changes in neural and muscular determinants of performance
fatigability. Med. Sci. Sport. Exerc. 2022,54, 1591–1603. [CrossRef]
7.
Rohloff, G.; Souza, D.B.; Ruiz-Moreno, C.; Del Coso, J.; Polito, M.D. Stimulus expectancy and stimulus response of caffeine on
4-km running performance: A randomized, double-blind, placebo-controlled and crossover study. Int. J. Exerc. Sci.
2022
,15,
645–654.
8.
Baguet, A.; Bourgois, J.; Vanhee, L.; Achten, E.; Derave, W. Important role of muscle carnosine in rowing performance. J. Appl.
Physiol. 2010,109, 1096–1101. [CrossRef]
9.
Davis, J.M.; Zhao, Z.; Stock, H.S.; Mehl, K.A.; Buggy, J.; Hand, G.A. Central nervous system effects of caffeine and adenosine on
fatigue. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003,284, R399–R404. [CrossRef]
10.
Salinero, J.J.; Lara, B.; Del Coso, J. Effects of acute ingestion of caffeine on team sports performance: A systematic review and
meta-analysis. Res. Sport. Med. 2019,27, 238–256. [CrossRef]
11.
Guest, N.S.; VanDusseldorp, T.A.; Nelson, M.T.; Grgic, J.; Schoenfeld, B.J.; Jenkins, N.D.M.; Arent, S.M.; Antonio, J.; Stout, J.R.;
Trexler, E.T.; et al. International society of sports nutrition position stand: Caffeine and exercise performance. J. Int. Soc. Sport.
Nutr. 2021,18, 5. [CrossRef] [PubMed]
12.
Southward, K.; Rutherfurd-Markwick, K.J.; Ali, A. The Effect of Acute Caffeine Ingestion on Endurance Performance: A
Systematic Review and Meta-Analysis. Sport. Med. 2018,48, 1913–1928. [CrossRef]
Nutrients 2023,15, 148 16 of 18
13.
Souza, D.B.; Del Coso, J.; Casonatto, J.; Polito, M.D. Acute effects of caffeine-containing energy drinks on physical performance: A
systematic review and meta-analysis. Eur. J. Nutr. 2017,56, 13–27. [CrossRef] [PubMed]
14.
Grgic, J. Caffeine ingestion enhances Wingate performance: A meta-analysis. Eur. J. Sport Sci.
2018
,18, 219–225. [CrossRef]
[PubMed]
15.
Grgic, J.; Trexler, E.T.; Lazinica, B.; Pedisic, Z. Effects of caffeine intake on muscle strength and power: A systematic review and
meta-analysis. J. Int. Soc. Sport. Nutr. 2018,15, 11. [CrossRef] [PubMed]
16.
Diaz-Lara, J.; Grgic, J.; Detanico, D.; Botella, J.; Jiménez, S.L.; Del Coso, J. Effects of acute caffeine intake on combat sports
performance: A systematic review and meta-analysis. Crit. Rev. Food Sci. Nutr. 2022, 1–16. [CrossRef]
17.
Gomez-Bruton, A.; Marin-Puyalto, J.; Muñiz-Pardos, B.; Matute-Llorente, A.; Del Coso, J.; Gomez-Cabello, A.; Vicente-Rodriguez,
G.; Casajus, J.A.; Lozano-Berges, G. Does acute caffeine supplementation improve physical performance in female team-sport
athletes? Evidence from a systematic review and meta-analysis. Nutrients 2021,13, 3663. [CrossRef]
18.
Costill, D.L.; Dalsky, G.P.; Fink, W.J. Effects of caffeine ingestion on metabolism and exercise performance. Med. Sci. Sport.
1978
,
10, 155–158.
19.
Maughan, R.J. IOC Medical and Scientific Commission reviews its position on the use of dietary supplements by elite athletes. Br.
J. Sport. Med. 2018,52, 418–419. [CrossRef]
20.
Australian Sports Commission. Australian Institute of Sport Position Statement: Supplements and Sports Foods in High
Performance Sport. Available online: https://www.ais.gov.au/nutrition/supplements/group_a (accessed on 6 November 2022).
21.
Paton, C.; Costa, V.; Guglielmo, L. Effects of caffeine chewing gum on race performance and physiology in male and female
cyclists. J. Sport. Sci. 2015,33, 1076–1083. [CrossRef]
22.
Schubert, M.M.; Astorino, T.A. A systematic review of the efficacy of ergogenic aids for improving running performance. J.
Strength Cond. Res. 2013,27, 1699–1707. [CrossRef] [PubMed]
23.
Clarke, N.D.; Richardson, D.L.; Thie, J.; Taylor, R. Coffee ingestion enhances 1-mile running race performance. Int. J. Sport. Physiol.
Perform. 2018,13, 789–794. [CrossRef] [PubMed]
24.
Hanson, N.J.; Martinez, S.C.; Byl, E.N.; Maceri, R.M.; Miller, M.G. Increased rate of heat storage, and no performance benefits,
with caffeine ingestion before a 10-km run in hot, humid conditions. Int. J. Sport. Physiol. Perform.
2019
,14, 196–202. [CrossRef]
[PubMed]
25.
Manoel, F.A.; Kravchchyn, A.C.P.; Figueiredo, D.H.; Figueiredo, D.H.; Machado, F.A. Does isolated and combined acute
supplementation of caffeine and carbohydrate feeding strategies modify 10-km running performance and pacing strategy? A
randomized, crossover, double-blind, and placebo-controlled study. Arch. Med. Del Deporte 2021,38, 185–191. [CrossRef]
26.
Marques, A.C.; Jesus, A.A.; Giglio, B.M.; Marini, A.C.; Lobo, P.C.B.; Mota, J.F.; Pimentel, G.D. Acute Caffeinated Coffee
Consumption Does not Improve Time Trial Performance in an 800-m Run: A Randomized, Double-Blind, Crossover, Placebo-
Controlled Study. Nutrients 2018,10, 657. [CrossRef]
27.
Ardern, C.L.; Büttner, F.; Andrade, R.; Weir, A.; Ashe, M.C.; Holden, S.; Impellizzeri, F.M.; Delahunt, E.; Dijkstra, H.P.; Mathieson,
S.; et al. Implementing the 27 PRISMA 2020 Statement items for systematic reviews in the sport and exercise medicine,
musculoskeletal rehabilitation and sports science fields: The PERSiST (implementing Prisma in Exercise, Rehabilitation, Sport
medicine and SporTs science) guidance. Br. J. Sport. Med. 2022,56, 175–195.
28.
Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher, D.
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions:
Explanation and elaboration. BMJ 2009,339, b2700. [CrossRef]
29.
Hurst, P.; Schipof-Godart, L.; Hettinga, F.; Roelands, B.; Beedie, C. Improved 1000-m running performance and pacing strategy
with caffeine and placebo: A balanced placebo design study. Int. J. Sport. Physiol. Perform. 2019,15, 483–488. [CrossRef]
30.
Khcharem, A.; Souissi, M.; Atheymen, R.; Ben Mahmoud, L.; Sahnoun, Z. Effects of caffeine ingestion on 8-km run performance
and cognitive function after 26 hours of sleep deprivation. Biol. Rhythm. Res. 2022,53, 867–877. [CrossRef]
31. Rohatgi, A. WebPlotDigitizer. Available online: https://automeris.io/WebPlotDigitizer/ (accessed on 20 October 2022).
32.
Higgins, J.P.; Thomas, J.; Chandler, J.; Cumpston, M.; Li, T.; Page, M.J.; Welch, V.A. Cochrane Handbook for Systematic Reviews of
Interventions; John Wiley & Sons: Hoboken, NJ, USA, 2019.
33. Cohen, J. Statistical Power Analysis for the Behavioral Sciences; Elsevier Science: Burlington, MA, USA, 2013.
34.
Whalley, P.J.; Dearing, C.G.; Paton, C.D. The effects of different forms of caffeine supplement on 5-km running performance. Int. J.
Sport. Physiol. Perform. 2019,15, 390–394. [CrossRef]
35.
Bell, D.G.; McLellan, T.M.; Sabiston, C.M. Effect of ingesting caffeine and ephedrine on 10-km run performance. Med. Sci. Sport.
Exerc. 2002,34, 344–349. [CrossRef] [PubMed]
36.
Follmann, D.; Elliott, P.; Suh, I.; Cutler, J. Variance imputation for overviews of clinical trials with continuous response. J. Clin.
Epidemiol. 1992,45, 769–773. [CrossRef] [PubMed]
37.
Delleli, S.; Ouergui, I.; Messaoudi, H.; Trabelsi, K.; Ammar, A.; Glenn, J.M.; Chtourou, H. Acute effects of caffeine supplementation
on physical performance, physiological responses, perceived exertion, and technical-tactical skills in combat sports: A systematic
review and meta-analysis. Nutrients 2022,14, 2996. [CrossRef] [PubMed]
38.
Shen, J.G.; Brooks, M.B.; Cincotta, J.; Manjourides, J.D. Establishing a relationship between the effect of caffeine and duration
of endurance athletic time trial events: A systematic review and meta-analysis. J. Sci. Med. Sport
2019
,22, 232–238. [CrossRef]
[PubMed]
Nutrients 2023,15, 148 17 of 18
39.
López-González, L.M.; Sánchez-Oliver, A.J.; Mata, F.; Jodra, P.; Antonio, J.; Domínguez, R. Acute caffeine supplementation in
combat sports: A systematic review. J. Int. Soc. Sport. Nutr. 2018,15, 60. [CrossRef] [PubMed]
40.
Raya-Gonzalez, J.; Rendo-Urteaga, T.; Dominguez, R.; Castillo, D.; Rodriguez-Fernandez, A.; Grgic, J. Acute effects of caffeine
supplementation on movement velocity in resistance exercise: A systematic review and meta-analysis. Sport. Med.
2020
,50,
717–729. [CrossRef]
41.
Egger, M.; Smith, G.D.; Schneider, M.; Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ
1997
,315,
629–634. [CrossRef]
42.
Cohen, B.S. Effects of caffeine ingestion on endurance racing in heat and humidity. Eur. J. Appl. Physiol. Occup. Physiol.
1996
,73,
358–363. [CrossRef]
43.
De Poli, R.D.A.B.; Eiji Miyagi, W.; Yuzo Nakamura, F.; Moura Zagatto, A. Caffeine Improved Time to Exhaustion But Did Not
Change Alternative Maximal Accumulated Oxygen Deficit Estimated During a Single Supramaximal Running Bout. Int. J. Sport
Nutr. Exerc. Metab. 2016,26, 549–557. [CrossRef]
44.
Dittrich, N.; Serpa, M.C.; Lemos, E.C.; de Lucas, R.D.; Guglielmo, L.G.A. Effects of caffeine chewing gum on exercise tolerance
and neuromuscular responses in well-trained runners. J. Strength Cond. Res. 2021,35, 1671–1676. [CrossRef]
45.
Graham, T.E.; Spriet, L.L. Performance and metabolic responses to a high caffeine dose during prolonged exercise. J. Appl. Physiol.
1991,71, 2292–2298. [CrossRef] [PubMed]
46.
Graham, T.E.; Hibbert, E.; Sathasivam, P. Metabolic and exercise endurance effects of coffee and caffeine ingestion. J. Appl. Physiol.
1998,85, 883–889. [CrossRef] [PubMed]
47.
Kasper, A.M.; Cocking, S.; Cockayne, M.; Barnard, M.; Tench, J.; Parker, L.; McAndrew, J.; Langan-Evans, C.; Close, G.L.; Morton,
J.P. Carbohydrate mouth rinse and caffeine improves high-intensity interval running capacity when carbohydrate restricted. Eur.
J. Sport Sci. 2016,16, 560–568. [CrossRef] [PubMed]
48.
Khcharem, A.; Souissi, M.; Atheymen, R.; Souissi, W.; Sahnoun, Z. Acute caffeine ingestion improves 3-km run performance,
cognitive function, and psychological state of young recreational runners. Pharmacol. Biochem. Behav.
2021
,207, 173219. [CrossRef]
49.
Khcharem, A.; Souissi, W.; Masmoudi, L.; Sahnoun, Z. Repeated low-dose caffeine ingestion during a night of total sleep
deprivation improves endurance performance and cognitive function in young recreational runners: A randomized, double-blind,
placebo-controlled study. Chronobiol. Int. 2022,39, 1268–1276. [CrossRef]
50.
O’Rourke, M.P.; O’Brien, B.J.; Knez, W.; Paton, C.D. Caffeine has a small effect on 5-km running performance of well-trained and
recreational runners. J. Sci. Med. Sport 2008,11, 231–233. [CrossRef]
51.
Ping, W.C.; Keong, C.C.; Bandyopadhyay, A. Effects of acute supplementation of caffeine on cardiorespiratory responses during
endurance running in a hot & humid climate. Indian J. Med. Res. 2010,132, 36–41.
52.
Ramos-Campo, D.J.; Perez, A.; Avila-Gandia, V.; Perez-Pinero, S.; Rubio-Arias, J.A. Impact of Caffeine Intake on 800-m Running
Performance and Sleep Quality in Trained Runners. Nutrients 2019,11, 2040. [CrossRef]
53.
Borba, C.L.; Batista, J.S.F.; Novais, L.M.Q.; Silva, M.B.; Júnior, J.B.S.; Gentil, P.; Marini, A.C.B.; Giglio, B.M.; Pimentel, G.D. Acute
caffeine and coconut oil intake, isolated or combined, does not improve running times of recreational runners: A randomized,
placebo-controlled and crossover study. Nutrients 2019,11, 1661. [CrossRef]
54.
Bridge, C.A.; Jones, M.A. The effect of caffeine ingestion on 8 km run performance in a field setting. J. Sport. Sci.
2006
,24, 433–439.
[CrossRef]
55.
Higgins, S.; Straight, C.R.; Lewis, R.D. The Effects of Preexercise Caffeinated Coffee Ingestion on Endurance Performance: An
Evidence-Based Review. Int. J. Sport Nutr. Exerc. Metab. 2016,26, 221–239. [CrossRef] [PubMed]
56.
Laursen, P.B.; Francis, G.T.; Abbiss, C.R.; Newton, M.J.; Nosaka, K. Reliability of time-to-exhaustion versus time-trial running
tests in runners. Med. Sci. Sport. Exerc. 2007,39, 1374–1379. [CrossRef] [PubMed]
57.
Lee, J.B.; Lee, H.J.; Lee, S.J.; Kim, T.W. Blood dopamine level enhanced by caffeine in men after treadmill running. Chin. J. Physiol.
2019,62, 279–284. [PubMed]
58.
Doherty, M.; Smith, P.M. Effects of caffeine ingestion on rating of perceived exertion during and after exercise: A meta-analysis.
Scand. J. Med. Sci. Sport. 2005,15, 69–78. [CrossRef] [PubMed]
59.
Gliottoni, R.C.; Meyers, J.R.; Arngrimsson, S.A.; Broglio, S.P.; Motl, R.W. Effect of caffeine on quadriceps muscle pain during
acute cycling exercise in low versus high caffeine consumers. Int. J. Sport Nutr. Exerc. Metab. 2009,19, 150–161. [CrossRef]
60.
Sitko, S.; Cirer-Sastre, R.; López-Laval, I. Time to exhaustion at estimated functional threshold power in road cyclists of different
performance levels. J. Sci. Med. Sport 2022,25, 783–786. [CrossRef]
61.
Jeukendrup, A.; Saris, W.H.; Brouns, F.; Kester, A.D. A new validated endurance performance test. Med. Sci. Sport. Exerc.
1996
,28,
266–270. [CrossRef]
62.
Renfree, A.; Casado, A.; Pellejero, G.; Hanley, B. More Pace Variation and Pack Formation in Successful World-Class 10,000-m
Runners Than in Less Successful Competitors. Int. J. Sport. Physiol. Perform. 2020,15, 1369–1376. [CrossRef]
63.
Green, J.M.; Olenick, A.; Eastep, C.; Winchester, L. Caffeine effects on velocity selection and physiological responses during RPE
production. Appl. Physiol. Nutr. Metab. 2016,41, 1077–1082. [CrossRef]
64.
De Franca, E.; Xavier, A.P.; Dias, I.R.; de Souza, R.R.; Correa, S.C.; da Silva, M.A.R.; da Silva, C.A.R.; Martins, R.A.S.; Hirota, V.B.;
dos Santos, R.V.T.; et al. Caffeine supplementation can make runners run further and improve pace strategy. RBNE Braz. J. Sport
Nutr. 2017,11, 813–825.
Nutrients 2023,15, 148 18 of 18
65.
Collomp, K.; Ahmaidi, S.; Chatard, J.C.; Audran, M.; Préfaut, C. Benefits of caffeine ingestion on sprint performance in trained
and untrained swimmers. Eur. J. Appl. Physiol. Occup. Physiol. 1992,64, 377–380. [CrossRef] [PubMed]
66.
Doherty, M.; Smith, P.M. Effects of caffeine ingestion on exercise testing: A meta-analysis. Int. J. Sport Nutr. Exerc. Metab.
2004
,14,
626–646. [CrossRef] [PubMed]
Disclaimer/Publisher’s Note:
The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.
Available via license: CC BY
Content may be subject to copyright.
