A Little Pepper-Upper? Systematic Review of Randomized Controlled Studies on Capsaicinoids, Capsinoids, and Exercise Performance

Abstract

Capsaicinoids and capsinoids are bioactive compounds mostly found in peppers. Although preclinical studies have reported that these compounds can improve exercise performance due to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated thermogenesis, sympathetic modulation, and releasing calcium, it is still unclear how they affect exercise performance in humans as ergogenic supplements. Conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guide 2020, this systematic review examined the ergogenic effect of capsaicinoids and capsinoids on exercise performance in healthy adults. A total of 19 randomized placebo-controlled trials were included in the study. Studies were accessed by searching five databases (PubMed, Scopus, SPORTDiscus, Web of Science, and Cochrane Library). The quality of the studies was evaluated using the Cochrane risk-of-bias assessment tool. According to the study results, 10 studies examining the effect of capsaicinoid and capsinoid supplements on exercise performance reported positive effects. Also, the effect of capsaicinoids and capsinoids on exercise performance is more pronounced in resistance training. This difference, which varies according to the type of exercise, may be due to the correlation between capsaicin transient receptor potential vanilloid subtype 1 and insulin-like growth factor-1.

Full text

A Little Pepper-Upper? Systematic Review of Randomized
Controlled Studies on Capsaicinoids, Capsinoids,
and Exercise Performance
Betül Sukan-Karaça ˘gıl, Gamze Akbulut, Yasemin Açar, and Meleknur Demirkoparan
Nutrition and Dietetics, Gazi University, Ankara, Turkey
Capsaicinoids and capsinoids are bioactive compounds mostly found in peppers. Although preclinical studies have reported that these
compounds can improve exercise performance due to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated thermo-
genesis, sympathetic modulation, and releasing calcium, it is still unclear how they affect exercise performance in humans as ergogenic
supplements. Conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guide 2020,
this systematic review examined the ergogenic effect of capsaicinoids and capsinoids on exercise performance in healthy adults. A
total of 19 randomized placebo-controlled trials were included in the study. Studies were accessed by searching five databases
(PubMed, Scopus, SPORTDiscus, Web of Science, and Cochrane Library). The quality of the studies was evaluated using the
Cochrane risk-of-bias assessment tool. According to the study results, 10 studies examining the effect of capsaicinoid and capsinoid
supplements on exercise performance reported positive effects. Also, the effect of capsaicinoids and capsinoids on exercise
performance is more pronounced in resistance training. This difference, which varies according to the type of exercise, may be
due to the correlation between capsaicin transient receptor potential vanilloid subtype 1 and insulin-like growth factor-1.
Keywords:capsaicin, capsiate, dihydrocapsaicin, training
Capsaicinoids are compounds accountable for the appealing
pungency of Capsicum (chili pepper) species. The main source of
natural capsaicinoids is chili peppers, which consist of capsaicin,
dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, and
homocapsaicin (Luo et al., 2011). Capsaicin and dihydrocapsaicin
are essential representatives of capsaicinoids (Naves et al., 2019).
Capsaicinoids have demonstrated antioxidant, antitumoral, and anti-
inflammatory properties in vitro and in vivo animal studies (Bogusz
et al., 2018;Chapa-Oliver & Mejia-Teniente, 2016). Capsaicin
(CAP), 8-methyl-N-vanillyl-6-nonenamide (C18H27NO3), is found
mostly in chili peppers and other spicy foods. CAP is the major active
component of red peppers, and about 70% of the burn of hot peppers is
attributed to CAP (Iwai et al., 2003;Ludy et al., 2012). Capsinoids are
CAP-like compounds found in a type of sweet red pepper and include
capsiate, dihydrocapsiate, and nordihydrocapsiate (Whiting et al.,
2012). Although capsinoids are much less pungent than CAP, there
are studies reporting that both are effective at reducing body fat in mice
and humans, as well as increasing energy expenditure and fat oxidation
(Ludy et al., 2012;Rogers et al., 2018;Yokoyama et al., 2020).
Previous studies have indicated that the action of CAP is
mediated by transient receptor potential vanilloid subtype 1
(TRPV1; Jordt & Julius, 2002;Kwon et al., 2021). Activation
of TRPV1 accelerates blood flow by inducing nitric oxide syn-
thesis, a potent vasodilator, increases sports performance by
providing better oxygenation of muscle tissue, and improves
exercise endurance and energy metabolism by upregulating
peroxisome proliferator-activated receptor-γcoactivator-1αin
animal models (Luo et al., 2012;Yang et al., 2010). CAP also
induces the rise of sympathetic modulation and thermogenesis in
human studies. Increased plasma catecholamines have been sug-
gested as a potential mechanism for the ergogenic effects of caffeine
ingestion, and CAP is known to stimulate adrenal catecholamine
secretion. These processes support energy expenditure, lipolysis,
and lipid oxidation (Shin & Moritani, 2007). In addition, CAP
implements peripheral effects on mouse muscle cells by boosting
the release of calcium by the endoplasmic reticulum, allowing force
production (Lotteau et al., 2013). The most probably limiting factors
for sustaining exercise performance are creatine phosphate avail-
ability, accumulation of inorganic phosphate, latency effects on
calcium used by the sarcoplasmic reticulum, and central nervous
system drive (Glaister, 2005). Athletes therefore use stimulants
such as ephedrine or caffeine, supplements that increase or improve
creatine phosphate stores, or buffering agents such as sodium
bicarbonate to improve exercise performance (Glaister et al., 2008;
McNaughton et al., 2008;Mujika et al., 2000). Because of all these
potential effects, CAP has received attention among those interested
in exercise and sport sciences (de Moura e Silva, Cholewa, Billaut,
et al., 2021).
In vitro and in vivo animal studies reporting the favorable
effects of capsaicinoids and capsinoids have recently led to clinical
trials. Therefore, we aim to elucidate the effect of capsaicinoids and
capsinoids on exercise performance markers so that we can explain
how these promising results are reflected in human studies. This
systematic review is one of the comprehensive studies discussing
capsaicinoids and the effect of capsinoids on exercise performance.
A systematic review (de Moura e Silva, Cholewa, Billaut, et al.,
2021) with eight human studies on similar topics and a meta-
analysis with 14 studies (Grgic et al., 2022) have been published
previously. Our study is currently the most up-to-date and com-
prehensive systematic review, as it includes 19 studies. In addition,
Akbulut https://orcid.org/0000-0003-0197-1573
Açar https://orcid.org/0000-0002-3567-0384
Demirkoparan https://orcid.org/0000-0001-8492-9236
Sukan-Karaça˘gıl(betulsukan@gmail.com,betul.sukan@gazi.edu.tr) is corresponding
author, https://orcid.org/0000-0003-3469-6408
1
International Journal of Sport Nutrition and Exercise Metabolism, (Ahead of Print)
https://doi.org/10.1123/ijsnem.2023-0016
© 2023 Human Kinetics, Inc. ORIGINAL RESEARCH
First Published Online: July 6, 2023

we tried to include both mechanistic and methodological details in
the evaluation of the outputs.
Methods
This systematic review was conducted according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses state-
ment guideline 2020 (Page et al., 2021) with the following research
question: Does capsaicinoid or capsinoid supplementation improve
exercise performance in healthy and physically active adults? The
study protocol has been registered in the International Prospective
Register of Systematic Reviews (PROSPERO) (registration num-
ber CRD42022371436).
Search Strategy
Two researchers independently performed a systematic search of
the literature across the PubMed/MEDLINE, Scopus, SPORTDiscus,
Cochrane Library, and Web of Science databases using the key-
words “capsaicin”OR “8-Methyl-N-Vanillyl-6-Nonenamide”
OR “capsiate”OR “dihydrocapsaicin”OR “capsaicinoid”OR
“nordihydrocapsaicin”OR “homodihydrocapsaicin”OR “homo-
capsaicin”OR “capsinoid”AND “exercise”OR “acute exercise”
OR “aerobic Exercise”OR “exercise training”OR “isometric
exercise”OR “physical activity.”To keep the articles included in
the review up-to-date, articles published in the last 15 years were
preferred. For this reason, articles published since 2009 are
included. The language was restricted to English only.
Inclusion and Exclusion Criteria
The studies that met the following criteria were included in the
study using the populations, interventions, comparison, outcome,
and study design strategy. Populations, interventions, comparison,
outcome, and study design strategy is presented in Table 1.
The following are the exclusion criteria used in this study:
•Individuals under the age of 18 years or over the age of 65 years.
•Studies with no full-text access.
•Studies written in languages other than English.
•Studies that do not meet populations, interventions, compari-
son, outcome, and study design strategy criteria.
•Animal studies, in vitro studies, cross-sectional studies, re-
views, comments, and letters.
Data Extraction
Two researchers independently screened the results based on titles
and abstracts to eliminate duplicate studies and evaluate them
based on the inclusion/exclusion criteria. The results of database
searches were combined, and duplicate studies were removed
manually and using Mendeley Reference Manager. For further
evaluation, two independent researchers extracted the following
data from the included studies:
•Name of the author(s), year, and country of the study.
•Study design.
•Participants’characteristics (sex, exercise status, and age).
•Type of exercise.
•Dose and duration of supplementation protocols.
•Relevant parameters.
Quality Evaluation
The revised Cochrane risk-of-bias tool for randomized trials was
used to assess the quality of the included studies (Sterne et al.,
2019). The revised Cochrane risk-of-bias tool for randomized trials
evaluates the risk of bias in five domains including: Domain 1: bias
arising from the randomization process, Domain 2: bias due to
deviations from intended interventions, Domain 3: bias due to
missing outcome data, Domain 4: bias in measurement of the
outcome, and Domain 5: bias in selection of the reported result. All
studies were classified as “low risk,”“some concerns,”or “high
risk.”The methodological quality of the included studies was
evaluated independently by two authors.
Results
Search Results
Preferred Reporting Items for Systematic Reviews and Meta-
Analyses flow diagram (Figure 1) shows that 822 studies were
searched from all databases; 360 of these studies were manually
and automatically identified as duplicates by Mendeley Reference
Manager software (v.2.80.1; Elsevier). The remaining 462 studies
were filtered based on their titles and abstracts, with 324 being
excluded due to unrelated topics. Following the completion of both
phases of the search process, 19 studies were included for analysis
in this review.
Supplementation Protocols
Most of the included studies used the capsule form of CAP or
capsiate. However, two studies (Cross et al., 2020;Langan &
Grosicki, 2020) provided chewable supplementation. In total, five
studies administer capsiate supplementation (6 and 12 mg) before
exercise (Costa et al., 2020;de Moura e Silva, Cholewa, Jager,
Table 1 PICO(S) Criteria
PICO(S) criteria Defines
Populations (P) Healthy and physically active adults (18–65 years)
Interventions (I) All supplements containing capsaicin or capsaicinoid derivatives (including direct supplement or extracts and food if ingredient
has been analyzed)
Comparison (C) Inert or pure placebos
Outcome (O) Primary outcome: Exercise performance test results (time to exhaustion, lifted weight, muscle strength and force, number of
repetitions, and summed and peak torque)
Secondary outcome: Heart rate, fatigue, RPE, blood lactate concentration, and oxygen consumption
Study design (S) Randomized controlled trials
Note. RPE = rating of perceived exertion.
2SUKAN-KARAÇAG
˘
IL ET AL.
(Ahead of Print)

et al., 2021;Dos Santos Gomes et al., 2022;Dos Santos Nunes de
Moura et al., 2022;von Ah Morano et al., 2021). Josse et al. (2010)
used capsinoid form (10 mg), and Walter et al. (2009) used
capsicum extract form (33 and 34 mg). Most studies used starch
as the placebo, but some also used dietary fiber (maltodextrin) or
gelatin capsule (Opheim & Rankin, 2012;Volino-Souza et al.,
2022). Supplements have been given to participants 45 min before
exercise in most studies. But, it has been given participants
supplementation 30 and 50 min before exercise in two studies
(Giuriato et al., 2022;Walter et al., 2009).
Participants and Exercise Tasks
The studies included in this study were generally conducted with
physically active adult males. However, three studies were con-
ducted with active females and males (Cross et al., 2020;Langan &
Grosicki 2020;von Ah Morano et al., 2021).
Exercise types are running (Costa et al., 2020,de Freitas,
Cholewa, Gobbo, et al., 2018;de Freitas et al., 2019;Padilha et al.,
2020;von Ah Morano et al., 2021), squat (de Freitas et al., 2022;de
Freitas, Cholewa, Freire, et al., 2018;Simões et al., 2022), cycling
(Giuriato et al., 2022,Josse et al., 2010,Langan & Grosicki 2020;
Walter et al., 2009), leg and bench press (da Silva et al., 2022,de
Moura e Silva, Cholewa, Jager, et al., 2021;dos Santos Nunes de
Moura et al., 2022), knee and leg extension (Cross et al., 2020;dos
Santos Gomes et al., 2022;Volino-Souza et al., 2022), and sprint
(Opheim & Rankin, 2012).
Relevant Outcomes
The results of all studies included in the review are summarized in
Table 2. From the studies, rating of perceived exertion (RPE), heart
rate (HR), blood lactate concentration, and oxygen consumption
(VO
2
), which are exercise performance indicators, and exercise
performance test results were obtained.
Rating of Perceived Exertion
A total of 14 of the included studies (Costa et al., 2020;de Freitas,
Cholewa, Freire, et al., 2018;de Freitas, Cholewa, Gobbo, et al., 2018;
de Freitas et al., 2019,2022;Dos Santos Nunes de Moura et al., 2022;
Giuriato et al., 2022;Josse et al., 2010;Langan & Grosicki, 2020;
Opheim & Rankin, 2012;Padilha et al., 2020;Simões et al., 2022;
von Ah Morano et al., 2021;Walter et al., 2009) evaluated RPE.
Figure 1 —PRISMA flow diagram. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
SYSTEMATIC REVIEW OF CAPSAICINOIDS AND CAPSINOIDS 3
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Table 2 Summary of Included Studies
References Country Participants Supplementation Exercise task
Relevant
outcomes Notable significant (p<.05) findings
Costa et al.
(2020)
Brazil Twelve physically active
men (age:
28.6 ± 5.4 years)
45 min before the intervention
12 mg capsiate or placebo
400- or 3,000-m time-trial running RPE, HR, and
exercise test
results
•The time in seconds was significantly less in the
capsiate compared to placebo groups (for the
3,000 m; p= .015, for the 400 m; p= .046).
•No differences were found for RPE and HR
between groups.
Cross et al.
(2020)
United
States
Nine young active fe-
males and males age:
(age: 23.6 ± 1.5 and
24.2 ± 3.3 years,
respectively)
45 min before the intervention
1.2 mg capsaicin or placebo
Isokinetic knee extensor contractile
function test (per second, 120 maxi-
mal isokinetic knee extensions at
120° with passive flexion at 240°)
Exercise test
results
•Peak torque was significantly greater in cap-
saicin than in the placebo (p= .04).
•No significant differences were found for
summed torque or fatigue index between the
groups.
de Freitas
et al. (2022)
Brazil Eleven resistance-trained
men (age:
23.3 ± 2.2 years)
45 min before the intervention
24 mg capsaicin or placebo
5-km HIIE, 10-min passive rest
interval, and then 4 sets ×70% 1RM
squat exercise (separated with 2-min
rest interval)
RPE, HR, and
exercise test
results
•The number of repetitions (p= .019) and vol-
ume (Repetitions ×Weight lifted [in kilograms];
p= .028) were significantly greater in the cap-
saicin compared with the placebo group.
•RPE and mean HR were significantly lower in
the capsaicin group compared with the placebo.
da Silva et al.
(2022)
Brazil Twenty male Brazilian
Jiu-Jitsu athletes (age:
24.3 ± 1.5 years)
45 min before the intervention
12 mg capsaicin or placebo
Four sets of five repetitions of free
bench press exercise at 60% of body
mass (separated with 5-min rest
interval)
Exercise test
results
•The mean power output (p= .001) and mean
peak velocity (p<.001) were significantly higher
in capsaicin compared with the placebo during
the exercise.
de Freitas,
Cholewa,
Freire, et al.
(2018)
Brazil Ten resistance-trained
men (age:
22.7 ± 4.0 years)
45 min before the intervention
12 mg capsaicin or placebo
4 sets ×70% of the 1RM squat
exercise (separated with 90-s rest
interval)
RPE, lactate,
and exercise test
results
•The number of repetitions and total weight
lifted (in kilograms; p= .002) were greater in the
capsaicin group than placebo during the exercise.
•RPE was significantly lower in the capsaicin
group compared with the placebo group.
•No difference was found for blood lactate
concentration between groups.
de Freitas
et al. (2019)
Brazil Thirteen physically
active men (age:
24.4 ± 4.0 years)
45 min before the intervention
12 mg capsaicin or placebo
HIIE running, for 15 s at 120% of
VO
2
max, interspersed by 15 s of
passive recovery
RPE, VO
2
, lac-
tate, and exer-
cise test results
•Time to exhaustion was longer in the capsaicin
group than placebo (p<.001).
•No differences were found for blood lactate
concentration, RPE, and VO
2
between groups.
de Freitas,
Cholewa,
Gobbo, et al.
(2018)
Brazil Ten physically active
men (age:
23.5 ± 1.9 years)
45 min before the intervention
12 mg capsaicin or placebo
1,500-m time-trial running RPE, lactate,
and exercise test
results
•The time in seconds (p= .009) was significantly
less in the capsaicin group compared with the
placebo.
•No difference was found for blood lactate
concentration between groups.
•RPE was significantly lower in the capsaicin
group compared with the placebo.
de Moura e
Silva, Cho-
lewa, Jager,
et al. (2021)
Brazil Twenty untrained men
(age: 18–30 years)
6 weeks 12 mg capsiate or placebo 6-week resistance training program
with capsiate or placebo intervention,
and then acute resistance exercise
(leg and bench press)
Exercise test
results
•Muscle strength at leg press did not differ
significantly between the groups.
•Capsiate significantly increased relative upper
body strength in the capsiate group compared the
placebo.
(continued)
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Table 2 (continued)
References Country Participants Supplementation Exercise task
Relevant
outcomes Notable significant (p<.05) findings
Dos Santos
Nunes de
Moura et al.
(2022)
Brazil Twenty resistance-
trained men (age:
28 ± 4.1 years)
45 min before the intervention 6 mg
capsiate, 12 mg capsiate, or placebo
4 sets ×70% of the 1RM bench press
exercise (separated with 2-min rest
interval)
RPE, lactate,
and exercise test
results
•Total weight lifted (p= .039) and the number of
repetitions (p= .043) were significantly higher in
the capsiate groups compared with the placebo.
•RPE and blood lactate concentration did not
differ significantly between the groups.
Dos Santos
Gomes et al.
(2022)
Brazil Thirteen healthy young
men (age:
25.2 ± 3.2 years)
45 min before the intervention
12 mg capsiate or placebo
5×10-s maximal voluntary isometric
contraction test (knee extension;
separated with 45-s rest interval)
Exercise test
results
•Capsaicin supplementation improved peak
force and fatigue index compared to placebo
(p<.05).
•The mean and minimum force did not change
significantly between groups.
Giuriato et al.
(2022)
United
States
Ten healthy young men
(age: 22.3 ± 3.6 years)
50 min before the intervention
∼1.914 mg capsaicin + 0.658 mg
dihydrocapsaicin or placebo
Time-to-exhaustion tests with con-
stant-load cycling exercise (85%
maximal work rate)
RPE, HR, VO
2
,
and exercise test
results
•No significant differences were found for time
to exhaustion, RPE, HR, and VO
2
between the
groups.
Josse et al.
(2010)
Canada Twelve healthy active
young men (age:
24.3 ± 3 years)
45 min before the intervention
10 mg capsinoid or placebo
Cycling at 55% VO
2
max, and for
30 min into recovery
RPE, HR, VO
2
,
and lactate
•Resting VO
2
was higher in capsinoid group.
•RPE, HR, and blood lactate concentration did
not change significantly between groups.
Langan and
Grosicki
(2020)
United
States
Thirteen active males
and females (age:
25.3 ± 3.1 and
22.3 ± 2.1 years,
respectively)
45 min before the intervention
1.2 mg capsaicin or placebo
Time-to-exhaustion tests on a cycle
ergometer at a workload eliciting
∼90% VO
2
max
RPE, HR, and
exercise test
results
•No significant differences were found for time
to exhaustion, RPE, and HR between the groups.
Opheim and
Rankin
(2012)
United
States
Nineteen healthy male
experienced athletes or
runners (age:
22.6 ± 2.6 years)
45 min before the intervention
25.8 mg capsaicin or placebo
Repeated sprint test consisting of 15-
to 30-m maximal effort sprint
(separated with 35-s rest interval)
RPE and exer-
cise test results
•Mean repeated sprint test times and RPE did not
differ significantly between groups.
Padilha et al.
(2020)
Brazil Fifteen trained men (age:
22.1 ± 3.07 years)
45 min before the intervention
12 mg capsaicin or placebo
Running at 90% of VO
2
max to
exhaustion
RP, HR, lactate,
and exercise test
results
•RPE, HR, blood lactate concentration, and time
to reach
˙
VO2 max did not differ significantly
between groups.
Simões et al.
(2022)
Brazil Eleven young resistance-
trained men (age:
21.5 ± 2.1 years)
45 min before the intervention
12 mg capsaicin, 400 mg caffeine,
12 mg capsaicin + 400 mg caffeine,
or placebo
4 sets ×70% 1RM squat exercise
(separated with 90-s rest interval)
RPE, HR, and
exercise test
results
•The total volume, RPE, and HR between the
four experimental conditions did not change.
Volino-
Souza et al.
(2022)
Brazil Eight active males (age:
33.33 ± 7.42 years)
45 min before the intervention
12 mg capsaicin or placebo
Three sets of leg extension exercise at
70% of 1RM until muscle fatigue
Lactate and
exercise test
results
•Blood lactate concentration, number of
repetitions, and time of exercise did not differ
significantly between groups.
von Ah
Morano et al.
(2021)
Brazil Twenty-one male ama-
teur athletes (age:
29.3 ± 5.5 years)
45 min before the intervention
24 mg capsiate or placebo
10-km time-trial running RPE, HR, lac-
tate, and exer-
cise test results
•Blood lactate concentration, RPE, HR, and
running time did not differ significantly between
groups.
Walter et al.
(2009)
United
States
Twenty healthy men
(age: 21.5 ± 1.4 years)
30 min before the intervention
200 mg caffeine, 33.34 mg capsi-
cum extract, 20 mg niacin, and 5 mg
black pepper extract or placebo
Cycling at 80% of VO
2
max to
exhaustion followed by 1RM leg and
bench press test
RPE and exer-
cise test results
•RPE and muscular strength did not differ
significantly between groups.
Note. RPE = rating of perceived exertion; HIIE = high-intensity intermittent exercise; 1RM = one-repetition-maximum; VO
2
max = maximal oxygen consumption; HR = heart rate.
(Ahead of Print) 5

In total, three studies (de Freitas, Cholewa, Freire, et al., 2018;de
Freitas, Cholewa, Gobbo, et al., 2018;de Freitas et al., 2022) reported
that the RPE was reduced in the intervention groups.
Heart Rate
In total, eight of the included studies (Costa et al., 2020;de Freitas
et al., 2019;Giuriato et al., 2022;Josse et al., 2010;Langan &
Grosicki, 2020;Padilha et al., 2020;Simões et al., 2022;von Ah
Morano et al., 2021) evaluated HR. One study (de Freitas et al.,
2022) reported that the HR was reduced in the intervention groups.
Blood Lactate Concentration
A total of eight of the included studies (de Freitas, Cholewa, Freire,
et al., 2018;de Freitas, Cholewa, Gobbo, et al., 2018;de Freitas et al.,
2019;Dos Santos Nunes de Moura et al., 2022;Josse et al., 2010;
Padilha et al., 2020;Volino-Souza et al., 2022;von Ah Morano et al.,
2021) evaluated blood lactate levels. None of the studies reported
significant between-group changes in blood lactate concentrations.
Oxygen Consumption
Three of the included studies’(de Freitas et al., 2019;Giuriato
et al., 2022;Josse et al., 2010) outputs related to VO
2
and muscle
oxygenation during or after exercise. Josse et al. (2010) reported
that resting VO
2
was significantly higher in intervention group
compared the placebo group.
Performance Test
In total, 10 of the studies (Costa et al., 2020;de Freitas, Cholewa,
Gobbo, et al., 2018;de Freitas et al., 2019;Giuriato et al., 2022;
Langan & Grosicki, 2020;Opheim & Rankin, 2012;Padilha et al.,
2020;Volino-Souza et al., 2022;von Ah Morano et al., 2021;
Walter et al., 2009) evaluated performance as time-dependent.
A total of five studies (de Freitas, Cholewa, Gobbo, et al., 2018;de
Freitas et al., 2022;de Moura e Silva, Cholewa, Jager, et al., 2021;
Dos Santos Nunes de Moura et al., 2022;Volino-Souza et al.,
2022) reported that measuring the number of repetitions. A total of
seven studies (Cross et al., 2020;da Silva et al., 2022;de Freitas,
Cholewa, Freire, et al., 2018;de Moura e Silva, Cholewa, Jager,
et al., 2021;Dos Santos Gomes et al., 2022;Dos Santos Nunes de
Moura et al., 2022;Simões et al., 2022) evaluated muscle strength,
force, lifted mass weight, torque, or total volume (Lifted Weight ×
Number of Repetitions). According to the performance test results,
10 studies (Costa et al., 2020;da Silva et al., 2022;de Freitas,
Cholewa, Freire, et al., 2018;de Freitas, Cholewa, Gobbo, et al.,
2018;de Freitas et al., 2019,2022;de Moura e Silva, Cholewa,
Jager, et al., 2021;Dos Santos Gomes et al., 2022;Dos Santos
Nunes de Moura et al., 2022) reported that exercise performance
increased significantly in the intervention group.
Quality Evaluation
For all domains (1, 2, 3, 4, and 5), the classification for the included
studies was scored “low risk”or “some concerns.”The overall risk-of-
bias assessment on the revised Cochrane risk-of-bias tool for ran-
domized trials for all included studies was “some concerns.”Figure 2
displays the evaluation of the risk of bias for all included trials.
Discussion
Exercise performance test results, which was our primary output in
our study, 10 of 19 studies reported positive effects on improved
performance in the intervention group. While seven of these
10 studies that reported the advantageous effects of capsaicinoids
and capsinoids supplements tested the exercise performance with
resistance training (Cross et al., 2020;da Silva et al., 2022;de
Freitas, Cholewa, Freire, et al., 2018;de Freitas et al., 2022;de
Moura e Silva, Cholewa, Jager, et al., 2021;Dos Santos Gomes
et al., 2022;Dos Santos Nunes de Moura et al., 2022). Mechanisti-
cally, what we know so far gives us some ideas that capsaicinoids
and capsinoids will improve exercise performance. As we men-
tioned previously, the most focus is on TRPV1 activation. CAP
induces TRPV1 activation, which modulates muscle contraction by
releasing Ca
+2
ions into the cell or increasing sympathetic activity
by inducing catecholamines (Iida et al., 2003;Kalmar, 2005;
Lotteau et al., 2013). This improves muscle actin–myosin interac-
tion, force generation processes, and intramuscular triglyceride
consumption. This results in preserving muscle glycogen and
increased time to exhaustion (Lotteau et al., 2013). Another
mechanism is that TRPV1 partially increases fat metabolism
through its neuroadrenergic effects, which may positively affect
performance in long-term sports (Oshioka et al., 1995).
However, these possible physiological mechanisms cannot fully
explain why CAP is more effective in resistance exercise than in
endurance exercise. Comparing it with the result of the study, which
reported a positive effect of CAP and capsiates on resistance ex-
ercises, previously published by Grgic et al. (2022), it seems to be
compatible with our findings. In addition to those studies, we reported
two more resistance exercise studies reporting significant results. But
we also hope to explain the reason for this difference here. One of the
main physiological differences between endurance and resistance
exercises is that endurance exercises are mostly dependent on mito-
chondrial biogenesis, whereas resistance exercises are mostly depen-
dent on ribosomal biogenesis. This indicates that endurance exercise
performance mostly depends on adenosine monophosphate-activated
protein kinase (AMPK) activity, while resistance exercises depend
on mammalian target of rapamycin complex 1 (mTORC1) activity.
AMPK activity is dependent on energy sources (glucose, triglycerides),
while mTOR activation requires positive signals from both nutrients
and growth factors. Insulin-like growth factor-1 (IGF-1) induces
phosphoinositide 3 kinase/AKT serine/threonine kinase 1/mTORC1
pathway, protein synthesis, and muscle hypertrophy (Li et al.,
2014;Mesquita et al., 2021). It has been reported that there is a link
between the insulin family and vanilloid receptors (Li et al., 2014;
Rostaetal.,2022). Lilja et al. (2007) have previously shown that
IGF-1 and insulin upregulate TRPV1 protein levels. Van Buren
et al. (2005) also reported that TRPV1 is sensitized and translo-
cated by insulin and IGF-1. In this case, increased IGF-1 signaling
in acute resistance exercise may help to explain the positive effects
by modulating TRPV1 (Figure 3).
Based on the results of the quality assessment, four studies
(Cross et al., 2020;Giuriato et al., 2022;Langan & Grosicki, 2020;
Opheim & Rankin, 2012) used a single-blind design and were
methodological of lower quality. If even one of the domains
included in the quality evaluation is evaluated as having some
concerns, the resulting quality of the study is evaluated in that way.
Although all of the studies included in the systematic review were
randomized controlled studies, all of them were concluded as
having some concerns because there was no explanation about
how the randomization was made.
Secondary outcomes of our study focus on RPE, fatigue, HR,
blood lactate concentration, and VO
2
. The RPE assesses an
individual’s physical activity intensity based on physical sensa-
tions such as breathing, HR, sweating, and muscle fatigue
6SUKAN-KARAÇAG
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experienced by the individual during physical work. The studies we
included used three different RPE scales (Borg, 1998;Robertson,
2004). This indicates that the RPE results of the studies we included
have a heterogeneous distribution and confounding in terms of
meta-analysis. Although the scales seem easy to apply and have
found a wide range of applications, there are various situations that
should be considered methodologically (Lopes et al., 2022). First ,
since the scales are in English, the realization of language and
culture adaptation will affect the results (Cabral et al., 2020).
Ideally, it should be applied during or immediately after exercise.
In addition, individuals should be encouraged to distinguish
somatic sensations, avoid judgments about honesty, and exercise
intensity (Lopes et al., 2022). Among the studies in which the scale
was used in nonnative English countries, Padilha et al. (2020) was
the only study that used the Portuguese validated version and
included methodological details.
There is a high correlation between RPE and HR (Williams,
2017). When evaluating RPE, an increased workload for the same
effort is associated with increased performance. Less HR can be
evaluated similarly in response to more workload (Pageaux, 2016).
Figure 2 —Quality evaluation of included studies.
SYSTEMATIC REVIEW OF CAPSAICINOIDS AND CAPSINOIDS 7
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However, accumulated fatigue in interval training can result in
increased effort despite decreased HR (Buchheit et al., 2012).
Therefore, monitoring HR and RPE together may help in better
evaluation (Lopes et al., 2022). HR responses of our included
studies seem to be compatible with RPE.
Another condition that determined the performance of exercise
is skeletal muscle fatigue. Muscle fatigue can be monitored and
evaluated using a variety of methods (Finsterer & Mahjoub, 2014;
Roete et al., 2021). The lactic acid hypothesis, which is defined as
the accumulation of lactate and acidosis in the working muscle,
causing the inhibition of contraction in the muscles, and the
decrease in exercise performance, has become controversial for
the last decades, and it is thought that it is not appropriate to use it
alone as an indicator of fatigue (Theofilidis et al., 2018). Even,
lactate has been shown to support aerobic adaptations by regulating
intramuscular triglyceride metabolism (Cairns, 2006). Blood lac-
tate measurements are used as a practical method of estimating the
acid–base status in muscle. This assumes that blood lactate reflects
muscle lactate, but this is not always the case, especially when
lactate flow from working muscle and distribution of lactate to
other muscles or tissues is uneven during intense and intermittent
exercise. Other factors such as a previous exercise that reduces
glycogen levels or a high-carbohydrate diet may affect blood
lactate concentration and the timing of reaching predefined thresh-
olds (Jamnick et al., 2018;Juel, 2008). Therefore, it needs appro-
priate to follow diet and exercise protocols for accurate evaluation.
None of the studies reported significant changes during or after
exercise lactate levels between the groups. However, only von Ah
Morano et al. (2021) evaluated the difference between macronu-
trient distribution 24 hr before each trial group.
The cardiopulmonary exercise test, which is another exercise
performance indicator, provides a complete assessment of the
physiological responses of the pulmonary, cardiovascular, muscle,
and cellular oxidative systems to exercise (Lima-Silva et al., 2013).
Maximum VO
2
is the most important parameter for evaluating
cardiopulmonary capacity, especially in endurance sports, and it is
the human body’s maximum oxygen uptake and defines the
maximum amount of energy that can be accessed by aerobic
metabolism at the peak of exercise (Guazzi et al., 2017;Zinner
et al., 2015). Athletes in different sports disciplines have a wide
range of maximum VO
2
, so for better interindividual comparisons,
it is better to express this as a percent-predicted value or in
milliliters of oxygen per kilogram of body weight per minute.
In fact, it is recommended to use lean mass for interdisciplinary
comparisons, since the ideal body weight varies (Mazaheri et al.,
2021;Mezzani, 2017). A total of three of the included studies
(de Freitas et al., 2019;Giuriato et al., 2022;Josse et al., 2010)
reported results related to VO
2
. Josse et al. (2010) reported that
resting VO
2
levels were higher in the intervention group.
Limitations
We have generally adapted to our preregistration plan. We had
planned to include pepper consumption outside of supplements.
However, since the phytochemical amount and bioavailability of
pepper ingredients are changed, we considered it appropriate to
include only supplements. Our initial intention was to conduct a
meta-analysis on this topic, but we opted for a systematic review
instead for the first phase of our research. However, we are not giving
up on our original goal. We will keep track of the latest studies and
incorporate them into our analysis. Our aim is to publish a meta-
analysis study as the second phase of our research in the near future.
We think that subgroup analyses are important. However, the current
table is not yet sufficient to illuminate issues such as gender, dose, and
type of exercise. In addition to revealing more studies worth reporting,
our study also contains remarkable insight in terms of mechanism. We
also drew attention to the methodological deficiencies in the studies as
much as possible. Therefore, we think that it would be good to publish
an updated meta-analysis in the coming years when good-quality
studies are added to the literature. We believe that a systematic review
would provide a more comprehensive and critical overview of the
existing literature, as well as identify the gaps and limitations that need
to be addressed in future studies.
Conclusions
Capsaicinoid and capsinoid supplementation seem to have positive
effects, especially on resistance exercise performance. However,
the reasons why this effect does not occur in endurance exercises
should be investigated better. In addition, it is necessary to deter-
mine the appropriate dose and the side effects better. Many studies
have not reported the side effects. Also, the effects of long-term use
are not yet fully known.
Acknowledgments
This study was conducted only by the authors whose contributions are
listed below. We thank the referees and editors for all their opinions and
suggestions, especially their advice on quality evaluation. This systematic
review was conducted according to the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses statement guideline 2020. The
study protocol has been registered in PROSPERO (registration number
CRD42022371436). Author Contributions: Conceptualization, investi-
gation, data curation, visualization, writing, review, and editing: Sukan-
Karaça˘gıl. Project administration and supervision: Akbulut. Investigation,
data curation, and writing: Açar, Demirkoparan. Both authors approved
the final version of the manuscript.
Figure 3 —Relationship between TRPV1 and IGF-1 in resistance
exercise. TRPV1 = transient receptor potential vanilloid subtype 1; IGF-
1 = insulin-like growth factor-1.
8SUKAN-KARAÇAG
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