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Acute Effects of Capsaicin on Energy Expenditure and Fat Oxidation in Negative Energy Balance

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Acute Effects of Capsaicin on Energy Expenditure and Fat Oxidation in Negative Energy Balance

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Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy. We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance. Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions '100%CAPS', '100%Control', '75%CAPS' and '75%Control'. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU)) with every meal. An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at 75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions. In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly. Nederlands Trial Register; registration number NTR2944.
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Acute Effects of Capsaicin on Energy Expenditure and Fat
Oxidation in Negative Energy Balance
Pilou L. H. R. Janssens*, Rick Hursel, Eveline A. P. Martens, Margriet S. Westerterp-Plantenga
Department of Human Biology, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, The Netherlands
Abstract
Background:
Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is
an interesting target for anti-obesity therapy.
Aim:
We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25%
negative energy balance.
Methods:
Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure,
substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions
‘100%CAPS’, ‘100%Control’, ‘75%CAPS’ and ‘75%Control’. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper,
39,050 Scoville heat units (SHU)) with every meal.
Results:
An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting
mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT
and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02
respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control
was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with
75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at
75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions.
Conclusion:
In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative
energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy
expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and
does not increase blood pressure significantly.
Trial Registration:
Nederlands Trial Register; registration number NTR2944
Citation: Janssens PLHR, Hursel R, Martens EAP, Westerterp-Plantenga MS (2013) Acute Effects of Capsaicin on Energy Expenditure and Fat Ox idation in Negative
Energy Balance. PLoS ONE 8(7): e67786. doi:10.1371/journal.pone.0067786
Editor: Daniel Tome
´
, Paris Institute of Technology for Life, Food and Environmental Sciences, France
Received August 7, 2012; Accepted May 15, 2013; Published July 2, 2013
Copyright: ß 2013 Janssens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was sponsored by McCormick EMEA and the McCormick Science Institute. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The study was sponsored by McCormick EMEA and the McCormick Science Institute. This does not alter the authors’ adherence to all the
PLOS ONE policies on sharing data and materials.
* E-mail: plhr.janssens@maastrichtuniversity.nl
Introduction
Obesity is a result of an energy imbalance that develops when
energy intake exceeds energy expenditure. Overweight and obesity
are the fifth leading risk for global deaths, at least 2.8 million adults
die each year as a result of being overweight or obese [1].
Capsaicin, the major pungent principle of red chili pepper, is a
thermogenic ingredient which stimulates energy expenditure and
contains negligible amounts of energy itself. Therefore, capsaicin
may be an interesting target for anti-obesity therapy. Several
studies have shown that capsaicin stimulates thermogenesis by
increasing the energy expenditure [2,3,4,5,6]. Furthermore, a
decrease in RQ [4] and a beneficial effect of capsaicin on fat
oxidation was found [2,3].
Capsaicin is one of the five naturally occurring capsaicinoids:
capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin
and homodihydrocapsaicin. The number of Scoville heat units
(SHU) indicates the amount of capsaicin present in the pepper.
The Scoville scale reflects concentrations of all capsaicinoids, and
also expresses the pungency of other capsaicinoids such as
nordihydrocapsaicin and dihydrocapsaicin. If a pepper contains
50,000 SHU, this means that its alcoholic extract needs to be
diluted 1:50,000 to be pungent on the human tongue [7]. Red chili
pepper can be ingested orally or in capsule form, whereby oral
exposure is relatively more effective with respect to thermogenesis
[8]. One explanation for effects of capsaicin may be that it
produces pain and stimulates thermogenesis caused by stimulating
the Transient Receptor Potential Vanilloid receptor 1 (TRPV1)
[7,9]. Another explanation may be that capsaicin causes an
increase in catecholamine (epinephrine, norepinephrine and
dopamine) secretion and sympathetic nervous system (SNS)
PLOS ONE | www.plosone.org 1 July 2013 | Volume 8 | Issue 7 | e67786
Maastricht,
activity and consequently, increases blood pressure
[4,10,11,12,13,14]. Human studies have shown that capsaicin
increased the diet-induced thermogenesis [3,4,10]. Both human
and animal studies investigated the effect of capsaicin after
administration of b-adrenergic blockers such as propranolol, and
showed that the thermogenic effect of capsaicin is reduced after
administration of beta-adrenergic blockers [12,15]. This implies
that the increased thermogenesis by capsaicin is probably based on
b-adrenergic stimulation. Whether, in negative energy balance, a
reduction in energy expenditure can be prevented by consuming
capsaicin, remains to be shown.
Taken together, since capsaicin supplementation adds only
negligible amounts of energy to food intake while it increases
energy expenditure at least in energy balance, it is of importance
to study whether these characteristics may be used as a concept for
prevention of the yo-yo effect when entering negative energy
balance. Normally, introduction of a negative energy balance by
reducing energy intake causes reduction in energy expenditure.
We hypothesize that capsaicin supplementation vs. control during
negative energy balance counteracts the normal decrease in energy
expenditure. Thereby, capsaicin may increase fat oxidation
relative to control. The aim of the present study was to investigate
the 24 h effects of capsaicin in 25% negative energy balance on
energy expenditure and substrate oxidation. We investigated
whether the 24 h effects of capsaicin in 25% negative energy
balance counteracted the effects of a negative energy balance on
energy expenditure and enlarged fat oxidation compared to 100%
energy intake without capsaicin.
Methods
Subjects
Nineteen healthy Caucasian subjects, aged between 18–50
years, with a body mass index (BMI, kg/m
2
) between 20–30 were
recruited for this study. Subjects were recruited by advertisements
in local newspapers and on notice boards at Maastricht University.
All subjects underwent a medical screening; during this screening
subjects underwent anthropometric measurements, and completed
questionnaires related to health, smoking behaviour, use of
medication, alcohol consumption, physical activity and eating
behaviour.
The inclusion criteria, besides an age between 18–50 years and
a BMI between 20–30 kg/m
2
, were a good health, non-smoking,
not using a more than moderate amount of alcohol (,10
consumptions per week) or caffeine-containing beverages (,2 cups
per day). Subjects had to be weight stable (weight change ,3kg
during the last 6 months), not using medication except for oral
contraceptives in women and had to be dietary unrestraint. The
Three Factor Eating Questionnaire (TFEQ) was used to determine
eating behaviour [16]. Only non-restrained eaters (,10 scores on
factor 1), these are persons who are not consciously occupied with
food or who are caloric restricted, were selected. Subjects had to
be moderately active (,5 hours exercise per week) and used to
consuming spicy foods on a regular basis (1–2 days per week, in a
low dosage with one meal/day). Pregnant or lactating women
were also excluded. Individuals with allergies for the food items
used in the study were excluded from participation. Subject
sample size was calculated where a was 0.05, b was 0.95 using
energy expenditure changes from past papers [11] to calculate the
effect size. The sample size was finalized as 14 subjects. The a-
level was two-sided.
A written informed consent was obtained from all the
participants. The Medical Ethics Committee of the Academic
Hospital in Maastricht approved the study. The study was
registered as follows: Nederlands Trial Register, registration
number NTR2944. The protocol for this trial and supporting
CONSORT checklist are available as supporting information; see
Checklist S1 and protocol S1.
Study Protocol
The study had a single-blinded, randomized crossover design
with four randomly sequenced experimental conditions. Subjects
underwent four 36 h sessions in a respiration chamber for
measurements of energy expenditure and substrate oxidation.
Two days prior to each session, subjects were provided with a
standardized diet to consume at home in order to be fed in energy
balance (energy % protein/fat/carbohydrate: 15/30/55), and to
receive the same macronutrient proportions as during the
respiration chamber experiment. The subjects were instructed to
maintain their habitual activity level on the two days before each
visit. Subjects were asked to abstain from alcohol consumption on
the two days before each visit. Furthermore, they were asked not
to drink caffeine after 10:00 PM on the day before each visit. The
four test sessions were conducted at least one week apart for male
subjects and four weeks apart for female subjects to prevent
possible treatment-induced effects and to take possible effects of
menstrual cycle phase on energy intake and energy expenditure in
women into account.
Energy Expenditure
Oxygen consumption and carbon dioxide production were
measured in a respiration chamber [17]. The respiration chamber
is a 14m
3
room, which is furnished with a bed, chair, computer,
television, radio, telephone, intercom, sink and toilet. The room
was ventilated with fresh air at a rate of 70–80 l/min. The
ventilation rate was measured with a dry gas meter (type 4;
Schlumberger, Dordrecht, Netherlands), and concentrations of
oxygen and carbon dioxide were measured with the use of an
infrared carbon dioxide analyzer (Uras 3G; Hartmann and Braun,
Frankfurt, Germany and 2 paramagnetic oxygen analyzers:
Magnos 6G; Hartmann and Braun, and type OA184A; Servomex,
Crowborough, United Kingdom). During each 15-min period, 6
samples of outgoing air for each chamber, 1 sample of fresh air,
zero gas, and calibration gas were measured. The gas samples to
be measured were selected by a computer that also stored and
processed the data. 24 h energy expenditure ( = TEE) consists of
SMR, DIT and activity-induced energy expenditure (AEE). 36 h
energy expenditure and 36 h RQ were measured from 08:00 h on
the day subjects enter the respiration chamber to 20:00 h on the
next day. SMR was defined as the lowest mean energy
expenditure measured over 3 consecutive hours between 00:00 h
and 07:00 h. REE was calculated by plotting energy expenditure
against radar output, that are both averaged over 30-min periods.
The intercept of the regression line at the lowest radar output
represents the energy expenditure in the inactive state ( = REE),
which consists of SMR and DIT. DIT was determined by
subtracting SMR from REE. AEE was determined by subtracting
SMR and DIT from TEE.
Substrate Oxidation
Carbohydrate, fat, and protein oxidation were calculated from
the measurements of oxygen consumption, carbon dioxide
production, and urinary nitrogen excretion by using the formula
of Carpenter in Brouwer et al [18]. Urine samples were collected
from the second void on the day subjects entered the respiration
chamber to 20:00 h on the next day. Samples, 3 per 36 hrs, in
order to determine substrate oxidation were collected in containers
with 10 ml HCl to prevent nitrogen loss through evaporation.
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Volume and nitrogen concentration were measured, the latter
with a nitrogen analyzer (CHN-O-Rapid; Heraeus, Hanau,
Germany). Urinary nitrogen was collected to calculate the RQ
and protein balance correctly.
Blood Pressure
Blood pressure (BP) was measured 15 minutes before each meal;
these measurements were taken in sitting position and were made
before the meal to avoid variability due to recent (within 2–3 h)
food intake [19]. Subjects were instructed to perform triplicate
measurements 15 minutes before breakfast, lunch and dinner and
were asked to record the mean of these three measurements.
Body Composition
Body weight was measured using a digital balance and height
was measured using a wall-mounted stadiometer. BMI was
calculated as body weight (kg) divided by height (m) squared.
The deuterium dilution method according to the Maastricht
protocol [20] was used to measure total body water (TBW). The
subjects were asked to collect a urine sample in the evening just
before drinking a deuterium-enriched water solution. After
ingestion of this solution, the subject went to bed and no
additional consumption was allowed for this period of time. Ten
hours after drinking the water solution, another urine sample was
collected. The dilution of the deuterium isotope is a measure of the
TBW of the subject. Fat mass (FM) was calculated as body weight
minus TBW divided by the hydration factor 0.73. Additionally,
FM was determined by Bodpod [21] measurements. Fat mass
index (FMI) was calculated by FM (kg) divided by height (m)
squared. BMI, FM (%) and FMI were used to define body
composition. Waist and hip circumference were determined in
standing position by a tape measure. Waist circumference was
measured at the smallest circumference between rib cage and iliac
crest, and hip circumference at the level of the spina iliaca anterior
superior. Accordingly, waist-to-hip ratio (WHR) was calculated by
dividing waist by hip circumference. Both waist circumference and
waist-to-hip ratio were used to define different patterns of body fat
distribution.
Energy Intake and Food Choice
Subjects were fed in energy balance during two days before the
test sessions. Subject specific daily energy requirements were
calculated based on basal metabolic rate (BMR), which was
individually calculated with the equation of Harris-Benedict [22],
and multiplied by a physical activity level (PAL) of 1.7. This PAL
value of 1.7 represents the average PAL of modern humans, which
ranges from 1.5 to 2.0 [23]. In our population in the south of the
Netherlands the PAL value of 1.7 is the mean (range 1.6–1.8) of
the subjects, with the subject characteristics assessed in the present
study. The energy intake level was estimated as such that subjects
were not in a positive or a negative energy balance before they
entered the respiratory chamber. In the respiration chamber
energy requirements were calculated based on a PAL of 1.35.
Subject received 100% of their daily energy requirements in the
conditions ‘100%Control’ and ‘100%CAPS’ (energy% protein/
fat/carbohydrate: 15/30/55), and received 75% of their daily
energy requirements in the condition ‘75%Control’ and
‘75%CAPS’ (energy% protein/fat/carbohydrate: 15/30/55). En-
ergy intake was divided over the meals as 20% for breakfast, 40%
for lunch, and 40% for dinner. Subjects had to completely finish
all drinks and meals within 30 minutes. Negative energy balance in
both 75% conditions was calculated by energy intake minus TEE
divided by 100% of their daily energy requirements.
Dosage
Red chili pepper from the Capsicum frutescens L and Capsicum
annuum L (McCormick; USA, capsaicin 2484
m/g, nordihydro-
capsaicin 278
m/g and dihydrocapsaicin 1440 m/g) was used as
source for capsaicin. With respect to the daily dose for capsaicin,
the daily value has not been established. The generally recom-
mended daily dose is 1350 mg capsicum with 0.25% capsaicin
(40,000 SHU). Capsaicin was given at a dose of 2.56 mg (1.03 g of
red chili pepper, 39,050 SHU) with every meal. This dosage was
based upon the maximal dosage given in previous studies and in
our pre-test [2,8,24]. Divided over three meals, a daily total dose
of 7.68 mg CAPS was consumed by the subjects.
Preceding the study in the respiration chamber, several tests
concerning pungency and spiciness were conducted. In a pre-test
several food items were tested in combination with different
dosages of red chili pepper. Before the dosage of red chili pepper
in the food was determined, the pleasantness of taste, spiciness and
pungency of different food products with red chili pepper were
assessed to determine whether the amount of red chili pepper was
tolerable. Based upon this pre-study the products we chose to offer
during the experiment were; breakfast drink original with red chili
pepper concentration of 2.0 g/l, paˆte´ with 1.0 g red chili pepper/
30 g, tomato juice with 2.0 g red chili pepper/l and pizza
containing 2.0 g red chili pepper. The given dose of each
component did not exceed the maximum tolerable dose among
our subjects.
Data Analysis
The Statistical Package for the Social Sciences (SPSS) 17.0 was
used to perform univariate within-subject analyses. Repeated-
measures ANOVA was used to determine possible differences in
energy expenditure and its components, substrate oxidation,
energy balances and macronutrient balances within-subjects,
between the four conditions. Step-down tests were used for pair
wise comparisons, post hoc, including Bonferroni corrections.
Shapiro-Wilk test was used to determine normality of the
variables, these appeared to be normally distributed. All statistical
tests are two-sided and differences are considered statistical
significant if p,0.05. Values are expressed as means and standard
deviations or standard errors.
Results
Subject Characteristics
Nineteen healthy subjects (nine males, ten females) started the
experiments; four subjects dropped-out due to agenda problems
.
Subjects were used to consuming spicy foods on a regular basis, in
general they consumed red chili pepper once per week (0.25–0.5
grams of dried red pepper or 1–2 grams of fresh red pepper).
Fifteen subjects (seven female and eight male) completed the four
conditions (Figure 1); 100% CAPS, 100%Control, 75%CAPS
and 75%Control; the subjects had a mean age of 29.7610.8 y and
a mean BMI of 23.362.9 kg/m
2
(Table 1).
Energy Expenditure
In two conditions subjects received 100% of the daily energy
requirements and in the other two conditions they received 75% of
the daily energy requirements. Energy balance during 36 h in the
100%CAPS and the 100%Control conditions did not significantly
differ from 0 (Table 2). During the 75%CAPS and 75%Control
conditions negative energy balance was 20.561.4% respectively
19.261.3%.
Total energy expenditure (TEE) in 100%CAPS and 100%Con-
trol did not differ significantly. As expected, total energy
Acute Effects of Capsaicin
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expenditure (TEE) was higher in the 100% conditions than in the
75% conditions (Table 2); overall an effect on TEE was observed
(p = 0.018). With respect to the components of energy expenditure
(EE), the following appeared. DIT in the 75%CAPS condition did
not differ from DIT in the 100%Control condition, while DIT
tended to be lower in 75%Control condition compared with
100%Control condition (p = 0.05). Similarly, REE in the
75%CAPS condition did not differ from REE in the 100%Control
condition, while REE was significantly lower in 75%Control
condition compared with 100%Control condition (p = 0.02).
Taken together, 75%CAPS did not differ from 100%Control
with respect to DIT and REE, while at 75%Control DIT tended
to be lower and REE was lower than at 100%Control. Likewise,
75%CAPS did not differ from 100%CAPS regarding SMR, while
SMR at 75%Control was lower than SMR at 100%CAPS
(p = 0.04).
Substrate Oxidation
Addition of capsaicin to the meals significantly increased the
24 h fat oxidation in negative energy balance. Fat oxidation in the
75%CAPS condition was significantly higher than fat oxidation in
the 100%Control condition (p = 0.03), while at 75%Control fat
oxidation did not differ significantly from fat oxidation at
100%Control. Carbohydrate oxidation in 75%CAPS and
75%Control were lower than in 100%Control (p,0.01 and
p,0.01 respectively) and than 100%CAPS (p,0.001 and
p,0.001 respectively).
An overall effect of protein balance was observed (p,0.001).
Protein balance in the 100%Caps condition was significantly
higher than in the 75%CAPS (p,0.05) and in the 75%Control
condition (p,0.01); similar findings were present between
100%Control and both 75% conditions (75%CAPS p,0.01,
75%Control p = 0.01). Fat balance was more negative in both
75% conditions and seemed to be more negative in the 75%CAPS
than in the 75%Control condition while carbohydrate balance was
more negative in the 75%Control (p,0.01) than in the 75%CAPS
(p,0.05) condition, vs. 100% conditions. Separate macronutrient
balances are shown in Figure 2.
RQ
No significant differences in RQ were seen between the two
conditions in energy balance (100%CAPS 0.9260.02 and
100%Control 0.9260.02) nor between the two conditions in
negative energy balance (75%CAPS 0.8960.02 and 75%Control
0.9060.01). RQ was decreased in both 75%CAPS and 75%Con-
trol conditions when compared with 100%Control condition.
However, RQ was significantly more decreased in the 75%CAPS
Figure 1. Flow diagram (CONSORT).
doi:10.1371/journal.pone.0067786.g001
Table 1. Subject characteristics (mean values and standard
deviations).
Male (n = 8) Female (n = 7) Total (n = 15)
Age (year) 26.868.4 33.0612.9 29.7610.8
Height (m) 1.8260.05 1.6560.05 1.7460.10
Body weight (kg) 79.86 10.0 61.2610.3 71.2613.7
BMI (kg/m
2
) 24.062.6 22.463.1 23.362.9
FMI (kg/m
2
)4.462.0 6.862.0 5.562.3
FFMI (kg/m
2
) 19.661.5 15.561.3 18.663.6
WHR 0.8060.04 0.6960.04 0.7560.07
FM (kg) 14.666.6 18.866.0 16.666.5
FFM (kg) 65.366.9 42.464.8 54.6613.1
Body fat (%) 17.867.1 30.164.5 23.668.6
TFEQ F1 2.562.6 3.162.9 2.862.7
TFEQ F2 4.961.2 5.463.4 5.162.4
TFEQ F3 4.164.3 5.963.4 4.963.9
BMI: Body mass index; FMI: Fat mass index; FFMI: Fat free mass index; WHR:
Waist-to-hip ratio; FM: Fat mass; FFM: Fat free mass; TFEQ: Three Factor Eating
Questionnaire; F1, cognitive restraint; F2, disinhibition; F3, hunger. #The TFEQ
measures three different factors of human eating behaviour.
doi:10.1371/journal.pone.0067786.t001
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condition (p = 0.04) than in the 75%Control condition (p = 0.05)
when compared with 100%Control (Table 2).
Blood Pressure
No significant differences were found when systolic and diastolic
blood pressure readings were compared between the four
conditions (Table 3).
Discussion
In the present study we tested the hypothesis that the 24 h
effects of capsaicin in 25% negative energy balance would
counteract the effects of a negative energy balance on energy
expenditure and enlarge fat oxidation compared to 100% energy
intake without capsaicin. Therefore we investigated the effects of
capsaicin on energy expenditure, substrate oxidation, macronu-
trient balance and RQ in 100% energy balance and in 75%
Table 2. Total energy expenditure, components of energy expenditure, energy intake, substrate oxidation and mean RQ during
the four conditions (n = 15).
100%CAPS 100%Control 75%CAPS 75%Control
EI (MJ/d) 9.0960.4 9.0960.4 6.8160.3**
##
6.8160.3**
##
EB (MJ/d) 0.1560.2 0.2260.2 21.8160.1**
##
21.7160.1**
##
TEE (MJ/d) 8.8260.4 8.7560.4 8.5260.4*
#
8.4160.4**
#
REE (MJ/d) 7.7060.4 7.5560.3 7.4960.3 7.3560.3*
#
SMR (MJ/d) 6.6960.3 6.4760.3 6.4560.3 6.3960.3*
DIT (MJ/d) 1.0060.1 1.0960.1 1.0360.1 0.9560.1
#
AEE (MJ/d) 1.1260.1 1.2060.1 1.0360.1 1.0660.1
Fat oxidati on (MJ/d) 1.6360.2 1.6360.2 2.3860.2*
#
2.1760.2*
Carbohydrate oxidation (MJ/d) 5.8960.2 5.9760.2 5.0360.2**
##
5.1860.2**
##
RQ 0.9260.02 0.9260.02 0.8960.02**
#
0.9060.01**
#
*p,0.05 compared to 100%CAPS, ** p,0.01 compared to 100%CAPS.
#
p,0.05 compared to 100%Control,
##
p,0.01 compared to 100%Control.
EI: Energy intake; EB: Energy balance; TEE: Total energy expenditure; REE: Resting energy expenditure; SMR: Sleeping metabolic rate; DIT: Diet-induced thermogenesis;
AEE: Activity-induced energy expenditure; RQ: Respiratory quotient.
doi:10.1371/journal.pone.0067786.t002
Figure 2. Macronutrient balances for 100%CAPS (black), 100%Control (light grey), 75%CAPS (dark grey) and 75%Control (white)
conditions in fifteen subjects (seven female and eight male).
doi:10.1371/journal.pone.0067786.g002
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negative energy balance. Capsaicin was given at a dose of 2.56 mg
capsaicin (1.03 g of red chili pepper, 39,050 SHU) with every
meal. The induced negative energy balance of 25%, which was
obtained by feeding 25% less energy than in energy balance,
resulted in a real negative energy balance of 20.5% with CAPS,
and of 19.2% with Control.
The strong negative energy balance with capsaicin was due to
two main findings. First, DIT and REE in the 75%CAPS
condition did not lead to a significant decrease compared with
100%Control, while DIT and REE tended to be or were
significantly lower in the 75%Control condition compared with
100%Control. Thus, the effects of capsaicin vs. control in negative
energy balance counteracted the effects of the negative energy
balance on DIT and REE compared to 100% energy intake
without capsaicin. Second, there was a significant increase in fat
oxidation when capsaicin was added to the meals in negative
energy balance, while there was no significant increase in fat
oxidation in the 75%Control condition compared with the
100%Control condition. Since blood pressure did not differ
between the four conditions, capsaicin contributed to counteract-
ing effects of negative energy balance without a significant increase
in blood pressure. In line with previous studies, that assessed
administration of capsaicin in energy balance [3,4,5,6], we
expected an increased TEE with 100%CAPS vs. 100%Control.
However, this did not reach statistical significance, neither did the
components of TEE, namely SMR and DIT. Before, we did
observe a larger TEE with 100%CAPS vs. 100%Control [25];
although in the present study differences were observed, lack of
statistical significance may be due to the number of subjects
included. A long-term study by Lejeune et al. on the effect of
135 mg capsaicin/d on body-weight regain after weight loss found
no limiting effect on weight regain after weight loss, yet an increase
in thermogenesis and fat oxidation [2]. In this study and another
study a similar finding on fat oxidation has been reported, these
studies found that capsaicin increased fat oxidation over the long
term (3 months) and over the short term (after one breakfast) [2,3].
The effects of capsaicin on protein oxidation, fat oxidation and
carbohydrate oxidation contribute to beneficial effects on body
composition and herewith promote an increase in fat free mass
and a reduction in FM [26]. Although these beneficial effects on
fat oxidation will not guarantee body weight loss or body-weight
maintenance, they may counteract a decrease in EE. Yoshioka
et al. found that the increase in fat oxidation after capsaicin
administration was mainly observed when the meals had a high fat
content (energy % protein/fat/carbohydrate: 15/45/40) [3]. In
our study the fat content of the meals was normal (energy %
protein/fat/carbohydrate: 15/30/55), thus the effect of capsaicin
on fat oxidation might have been higher if we would have
increased the fat content of the meals. The effects of capsaicin on
EE and substrate oxidation do not seem to be acute, but to build
up over a few days, since another one-meal study with Caucasians
on the acute effect of red chili pepper on satiety, energy
expenditure and substrate oxidation found no effect of capsaicin
[24]. Given its strong pungency, the long-term use of capsaicin
may be limited. A possible solution may be capsinoids. Capsinoids
including ‘capsiate’ are non-pungent capsaicinoid analogues.
Capsinoids have similar beneficial effects on energy expenditure
and substrate oxidation to those of capsaicin [27].
In the present study the subjects received 3.09 g red chili pepper
per day (7.68 mg capsaicin); this dosage is relatively low compared
to dosages used in studies with Asians [3,10,28]. However, there is
a difference in maximum tolerable dose of red chili pepper
between Asians and Caucasians. This difference in tolerable dose
is due to the difference in red chili pepper consumption. Red chili
pepper is more common in the food pattern in Asian population.
For example, the capsaicin consumption in India is 25–200 mg/
day while the average daily consumption in Europe is estimated to
be 1.5 mg [29]. Next to studies investigating effects of capsaicin in
Caucasians [2,10,24,30], several studies that investigated the
effects of capsaicin on appetite and energy intake have been
conducted in Asian populations [3,10,28].
In summary, the present study shows that the effects of capsaicin
vs. control in 25% negative energy balance did prevent the effects
of the negative energy balance on DIT and REE compared to
100% energy intake without capsaicin. Moreover, it increased fat
oxidation in negative energy balance. The presumed negative
energy balance of 25% led to a negative energy balance of
20.561.4% when capsaicin was added to the meals and
19.261.3% without addition of capsaicin. Since DIT and REE
at 75%CAPS were similar as DIT and REE at 100%Control, we
conclude that in an effectively 20.5% negative energy balance
consumption of 2.56 mg capsaicin per meal supports negative
energy balance by counteracting the unfavorable negative energy
balance effect of a decrease in components of energy expenditure.
Moreover, consumption of 2.56 mg capsaicin per meal promotes
fat oxidation in negative energy balance, and does not increase
blood pressure significantly.
Supporting Information
Protocol S1 Trial Protocol.
(PDF)
Checklist S1 CONSORT Checklist.
(DOC)
Table 3. Systolic and diastolic blood pressure measurements for the conditions 100%CAPS, 100%Control, 75%CAPS and
75%Control as measured 15 minutes before the meals (n = 15).
Systolic (mmHg) Diastolic (mmHg)
Day Moment in time 100%CAPS 100%Control 75%CAPS 75%Control 100%CAPS 100%Control 75%CAPS 75%Control
1 Before breakfast 116.1611.7 117.567.2 119.9610.5 114.9610.5 72.067.9 70.666.5 72.967.9 69.567.8
Before lunch 118.1611.3 118.5611.0 117.7614.5 113.5610.2 71.468.5 71.868.7 70.5610.1 70.267.5
Before dinner 114.4611.9 117.6610.6 120.869.9 113.3612.2 71.969.9 70.969.0 73.468.7 69.368.8
2 Before breakfast 116.9612.9 118.5612.1 118.5 610.5 116.3612.3 72.767.7 70.768.9 69.667.2 70.4610.8
Before lunch 116.1611.0 117.569.3 119.9610.4 114.9613.8 72.068.3 70.668.1 72.969.3 69.5610.3
Before dinner 118.1610.8 118.5612.2 117.7611.4 113.5611.7 71.467.4 71.867.5 70.56
9.3 70.2 610.1
doi:10.1371/journal.pone.0067786.t003
Acute Effects of Capsaicin
PLOS ONE | www.plosone.org 6 July 2013 | Volume 8 | Issue 7 | e67786
Acknowledgments
Paul Schoffelen and Loek Wouters are gratefully acknowledged for their
assistance.
Author Contributions
Conceived and designed the experiments: PLHRJ RH EAPM MSW-P.
Performed the experiments: PLHRJ. Analyzed the data: RH. Contributed
reagents/materials/analysis tools: PLHRJ. Wrote the paper: PLHRJ
MSW-P.
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Acute Effects of Capsaicin
PLOS ONE | www.plosone.org 7 July 2013 | Volume 8 | Issue 7 | e67786
... Lejuene et al., 2003;Westerterp-Plantenga et al., 2005 ;Diepvens et al., 2007; Zhang, 2007;Snitker et al., 2009;Zsombok, 2013;Janssens et al., 2013;Janssens et al., 2014 Gut health-capsaicin has a gastroprotective effect as it inhibits acid secretion and stimulates alkali and mucus secretion and helps in the prevention and healing of ulcers. Dietary capsaicin increased the Firmicutes/Bacteroidetes ratio and Faecalibacterium abundance,accompanied with increased plasma levels of glucagon-like peptide 1 and gastric inhibitory polypeptide and decreased plasma ghrelin level Yeoh et al., 1995; Mózsik et al., A type doubly linked procyanidin oligomers of the catechins and/or epicatechins) Antioxidants and blood glucose control-Cinnamon and cinnamon extracts are antioxidants, potentiate insulin action, and may be beneficial in the control of glucose intolerance and diabetes. ...
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