J Nutr Sci Vitaminol, 60, 22–27, 2014
The global increase in obesity and associated meta-
bolic disorders underscores the need for effective treat-
ments. In principle, obesity can be treated by reducing
energy intake and/or increasing energy expenditure
(EE). Some food ingredients have been proposed as tools
for increasing EE and decreasing body fat. A promi-
nent example is capsaicin, a pungent principle of hot
pepper that activates the adreno-sympathetic nervous
system and brown adipose tissue (BAT) thermogenesis,
increases EE and fat oxidation, and reduces body fat
(1–5). Our group recently (6) reported that a non-pun-
gent capsaicin analog (capsinoids) increases EE through
the activation of BAT in humans. Slight but signiﬁcant
fat-reducing effects of capsinoids are also reported in
mildly obese human subjects (7–9). Signiﬁcantly, the
effects of capsaicin and capsinoids are much attenu-
ated in mice lacking the transient receptor potential
vanilloid 1 (TRPV1) (10), a capsaicin receptor. This
suggests that the thermic and fat-reducing effects of
capsaicin and capsinoids are elicited by activation of the
pathway of TRPV1, the sympathetic nervous system,
Grains of paradise (Aframomumu melegueta [Rosco] K.
Schum.) (GP), also known as Guinea pepper or Alliga-
tor pepper, belong to the Zingiberaceae family native to
west Africa. GP seeds are used as a spice for food and
as an agent for wide-ranging ethnobotanical uses, for
example, as a remedy for treating stomachache, diar-
rhea, and snakebite (11). GP seeds are very rich in non-
volatile pungent compounds such as 6-paradol, 6-gin-
gerol, 6-shogaol and related compounds (12–14). These
compounds share an important structural feature with
capsaicin, namely, a vanilloid moiety. This feature may
equip them with the power to activate the pathway of
TRPV1 (15, 16), the sympathetic nervous system, and
BAT, and thereby to increase EE. In fact, Iwami et al.
found that the intragastric administration of an alco-
hol extract of GP and 6-paradol to rats enhanced the
efferent discharges of sympathetic nerves to BAT and
induced a signiﬁcant rise in BAT temperature (17). In
a previous study by our group, a single ingestion of GP
extract increased EE through the activation of BAT in
men (18). We can thus speculate that a repeated inges-
tion of GP extract will result in a sustained elevation of
EE and a consequent reduction of body fat. In the pres-
ent study we tested this hypothesis by examining the
effects of a daily ingestion of GP extract on EE and body
composition, particularly the subcutaneous and visceral
fat content, in healthy human volunteers.
Daily Ingestion of Grains of Paradise (Aframomum melegueta)
Extract Increases Whole-Body Energy Expenditure and
Decreases Visceral Fat in Humans
Jun Sugita1,2, Takeshi Yoneshiro3, Yuuki Sugishima4, Takeshi Ikemoto2,
Hideyo Uchiwa2, Isao Suzuki4,* and Masayuki Saito1,**
1 Department of Nutrition, School of Nursing and Nutrition, Tenshi Collage, Kita-13, Higashi-3,
Higashi-ku, Sapporo 065–0013, Japan
2 Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., Odawara 250–0002, Japan
3 Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060–8638, Japan
4 Environmental and Symbiotic Science, Prefectural University of Kumamoto, Kumamoto 862–8502, Japan
(Received May 28, 2013)
Summary We reported previously that a single ingestion of an alcohol extract of grains
of paradise (GP, Aframomum melegueta), a species of the ginger family, increases energy
expenditure (EE) through the activation of brown adipose tissue, a site of sympathetically
mediated metabolic theromogenesis. The present study aimed to examine a daily ingestion
of GP extract on whole-body EE and body fat in humans. Whole-body EE and body fat con-
tent were measured before and after daily oral ingestion of GP extract (30 mg/d) for 4 wk
in 19 non-obese female volunteers aged 20–22 y in a single-blind, randomized, placebo-
controlled, crossover design. Four-week daily ingestion of GP and a placebo decreased and
increased slightly the visceral fat area at the umbilicus level, respectively. The GP-induced
change was signiﬁcantly different from that induced by the placebo (p,0.05), and nega-
tively correlated with the initial visceral fat area (r520.64, p,0.01). Neither GP nor pla-
cebo ingestion affected subcutaneous or total fat. The daily ingestion of GP, but not the pla-
cebo, increased whole-body EE (p,0.05). These results suggest that GP extract may be an
effective and safe tool for reducing body fat, mainly by preventing visceral fat accumulation.
Key Words grains of paradise, 6-paradol, energy expenditure, visceral fat
* Present address: Department of Human Life Science, Na-
goya Keizai University, Aichi 484–8504, Japan
** To whom correspondence should be addressed.
A. melegueta Decreases Visceral Fat 23
MATERIALS AND METHODS
Subjects. Nineteen healthy female volunteers aged
20–22 y (20.260.2) were recruited and carefully
instructed on the procedures of the study. Every sub-
ject underwent a standardized health examination. The
study was conducted according to the guidelines laid
down in the Declaration of Helsinki, and all procedures
were approved by the institutional review boards of
Prefectural University of Kumamoto. Written informed
consent was obtained from every subject.
Test substances. GP extract was extracted from seeds
of Aframomum melegueta and encapsulated as described
in our previous report (18). HPLC analysis of the extract
revealed peaks respectively identiﬁed as 6-gingerol
(15.2%), 6-paradol (12.5%), 6-shogaol (1.7%), and
6-gingerdione (4.0%). Other components included in the
GP extract were caryophyllene and
triglyceride (20%) and palmitic and oleic acid (3%). It
also contained various phenolic glycosides of which the
content was not quantitated. Each capsule contained
0 mg (placebo) or 10 mg of a GP extract and 190 mg
of a mixture of rapeseed oil and beeswax. The GP and
placebo soft gels also contained caramel (7 mg/capsule)
to equalize the color. A preliminary safety assessment
conﬁrmed that daily oral ingestion of the test capsule (4
capsules after breakfast, 3 capsules after lunch, 3 cap-
sules after dinner) for 4 wk caused no noticeable symp-
toms or adverse events.
Test protocol. Each subject was given either 0 or
30 mg GP extract daily for 4 wk with a wash-out period
of 2 wk according to a randomized, single-blinded cross-
over design. Three capsules were given orally per day,
1 capsule 30 min before each of three regular meals.
Anthropometric and body composition measurements,
indirect calorimetry, and blood analyses were performed
before and after the 4-wk period.
Anthropometric and body composition measurements.
BMI was calculated as the body weight in kilograms
divided by the square of height in meters (kg/m2). The
percentage body fat was estimated by the multifrequency
bioelectric impedance method (InBody 230 Body Com-
position Analyzer, Biospace, Seoul, South Korea).
The body fat distribution was determined by a com-
puted tomography (CT) scan according to the procedure
described by Tokunaga et al. (19). The total cross-sec-
tional area, subcutaneous fat area, and visceral fat area
were measured at the level of the umbilicus. All CT scans
were performed in the supine position with a HiSpeed
NX/i CT scanner (General Electric Medical Systems, Mil-
waukee, WI). Digital Imaging and Communications in
Medicine (DICOM) uncompressed images were exported
to “Image J” software (National Institutes of Health,
Rockville, MD) for further analyses. The intraperitoneal
area with the same density as the subcutaneous fat layer
was deﬁned as the visceral fat area.
Indirect calorimetry. Whole-body EE was estimated
with a respiratory gas analyzer connected to a tight-ﬁt-
ting breathing mask (Oxycon Delta ERICHJAEGER B.V.,
Bunnick, Netherlands). After fasting for 6–12 h, the
subjects were asked to relax on a bed in light-clothing
in a room at 22˚C, and oxygen consumption and car-
bon dioxide production were continuously recorded for
30 min. The stable value of the ﬁnal 10-min period was
used to calculate the resting EE.
Blood analyses. Blood samples were taken in the
clinic after overnight fasting for measurement of the fol-
lowing in peripheral blood: blood properties (leucocyte
count, erythrocyte count, hemoglobin, platelet count),
aspartate aminotransferase, alanine aminotransfer-
-glutamyltranspeptidase, total protein, albumin,
alkaline phosphatase, urea nitrogen, creatinine, blood
glucose, hemoglobin A1c, total cholesterol, HDL-cho-
lesterol, LDL-cholesterol, TAG, and free fatty acid. The
blood was sampled after a 10-min rest in a sitting posi-
tion. All measurements were taken by the Japanese Red
Cross Kumamoto Hospital according to appropriate
Data analysis. Values were expressed as means
with their standard errors. A paired t-test was used to
compare each group with the baseline or placebo. Cor-
relations between initial values and changes of the
abdominal fat area were assessed using Pearson’s corre-
lation coefﬁcient. Statistics were calculated using SPSS
software, version 18 (IBM, Tokyo, Japan). A p value of
,0.05 was considered statistically signiﬁcant.
Nineteen healthy female subjects (20.260.2 y old)
were recruited and given an oral dose of either GP
Table 1. Body compositions before and after 4 wk of daily ingestion of GP extract or placebo.
0 wk 4 wk 0 wk 4 wk
Body weight (kg) 51.961.0 51.761.0 52.061.4 51.761.5
BMI (kg/m2) 20.760.3 20.560.3 20.760.5 20.660.5
Body fat (%) 26.460.6 25.960.6 26.060.9 25.760.9
Visceral fat (cm2) 41.262.7 38.362.1 38.762.2 43.463.7
Subcutaneous fat (cm2) 164.3612.6 160.6612.9 155.7613.0 152.8612.9
Total fat (cm2) 205.5614.6 198.9614.3 194.4614.7 196.2615.9
Mean values with their standard errors.
Sugita J et al.
extract or a placebo every day for 4 wk in a single-
blinded, randomized, crossover study. The height, body
weight, body fat content, and fat area at the level of the
umbilicus were measured in every subject before and
after the 4-wk period of GP or placebo ingestion. As sum-
marized in Table 1, there was no signiﬁcant change in
body weight, BMI, body fat content, or fat areas after the
4-wk treatment period. The pre-versus-post-treatment
differences in the GP group were compared with those
in the placebo group after the 4-wk ingestion period.
As shown in Fig. 1, the differences in body weight, BMI,
body fat content, subcutaneous fat area, and total fat
area were almost the same after GP and placebo inges-
tion. The visceral fat area decreased slightly in the GP
group (22.961.9 cm2) but rose in the placebo group
(4.762.4 cm2). These changes in visceral fat differed
signiﬁcantly between the two groups (p,0.05).
The correlation between the fat area before GP inges-
tion and the fat area change induced by GP ingestion
was examined to conﬁrm the effects of GP on visceral
fat. As shown in Fig. 2, the GP-induced change showed
a signiﬁcant negative correlation with the initial vis-
ceral fat (r520.64, p50.003). In contrast, no correla-
tion was found between the initial visceral fat and the
placebo-induced change (r50.34, p50.15). The initial
subcutaneous fat was uncorrelated with the change in
Fig. 1. Body composition changes after daily ingestion of GP extract or placebo. Body composition changes before and
after oral ingestion of 30 mg GP extract. Changes in body weight (A), body fat mass (BMI) (B), body fat percentage (C),
visceral fat area (D), subcutaneous fat area (E), and total fat area (F). * p,0.05 (vs. placebo). Mean values with their stan-
dard errors represented by vertical bars.
A B C
D E F
Body weight (kg)
Body fat (%)
Visceral fat (cm2)
Total fat (cm2)
Subcutaneous fat (cm2)
0 20 40 60
Initial visceral fat (cm
Visceral fat (cm2 )
0100 200 300
Initial subcutaneous fat (cm
Subcutaneous fat (cm2)
Fig. 2. Fat-reducing effect of GP in relation to the initial visceral fat and subcutaneous fat. A: Correlation between the
induced change in visceral fat and the initial visceral fat before ingestion of GP extract (closed circles, R520.64, p50.003)
or placebo (open circles, R50.34, p50.15). B: Correlation between the induced change in subcutaneous fat and the initial
subcutaneous fat before ingestion of GP extract (closed circles, R520.007, p50.77) or placebo (open circles, R520.12,
A. melegueta Decreases Visceral Fat 25
subcutaneous fat induced by GP (r520.007, p50.77)
or placebo (r520.12, p50.62) ingestion.
Whole-body EE was also measured under a rest-
ing condition before and after the 4-wk period of GP
or placebo ingestion (Fig. 3). The mean EE calculated
from oxygen consumption and carbon dioxide pro-
duction rose signiﬁcantly from 1,402624.7 kcal/d at
baseline to 1,499633.7 kcal/d after 4 wk of GP inges-
tion. It also rose in the placebo group, but only slightly
(1,444644.0 kcal/d). Table 2 shows the effects of GP
ingestion on blood parameters. Glucose and
decreased slightly and signiﬁcantly after 4 wk of inges-
tion in both the GP and placebo groups, but all of the
other parameters remained approximately unchanged,
at their normal levels.
The present study demonstrated that daily ingestion
of GP resulted in a signiﬁcant reduction of visceral fat
in humans. Earlier studies have shown that the inges-
tion of hot pepper, its pungent principle (capsaicin),
and capsinoids (non-pungent capsaicin analogs) acti-
vate TRPV1 (1–6, 9), the adreno-sympathetic nervous
system, and BAT thermogenesis, increase EE and fat
oxidation, and reduce body fat, particularly visceral fat,
in both humans and small rodents. Our results and ear-
lier results on GP extract share a common ﬁnding with
the earlier results on capsaicin and capsinoids, namely,
that GP is rich in 6-paradol, 6-gingerol, 6-shogaol, and
other pungent compounds that have the potential to
activate TRPV1 (15, 16). Intragastric administration of
either GP extract or 6-paradol enhances the efferent dis-
charges of sympathetic nerves to BAT and signiﬁcantly
increases BAT temperature in rats (17). Our group pre-
viously reported that a single ingestion of GP-extract
increased EE through the activation of BAT in men (18).
Here, in the present study, we have found that a daily
ingestion of GP-extract brings about a slight but signiﬁ-
cant increase in whole-body EE that may contribute, at
least in part, to the fat-reducing effects of GP extract.
As the test sample is an ethanol extract of GP seeds,
the compounds responsible for the observed effect of
Fig. 3. Whole-body energy expenditure (EE) before and
after 4 wk of daily ingestion of GP or placebo. Whole-
body energy expenditure under a resting condition was
measured before (open columns) and 4 wk after daily
ingestion of 30 mg GP extract or placebo (closed col-
umns). * p,0.05 (vs. before). Mean values with their
standard errors represented by vertical bars.
Table 2. Blood parameters before and after 4 wk of daily ingestion of GP extract or placebo.
0 wk 4 wk 0 wk 4 wk
Glucose (mg/dL) 84.260.9 81.561.1* 85.764.2 82.860.9*
HbA1c (%) 4.9260.04 4.9160.04 4.9160.04 4.9560.04
TC (mg/dL) 169.866.0 171.466.5 176.367.7 172.267.1
TAG (mg/dL) 64.764.4 63.864.4 61.265.0 61.163.3
HDL-C (mg/dL) 67.262.4 66.562.8 68.063.1 66.662.8
LDL-C (mg/dL) 95.065.3 96.165.4 101.966.4 98.566.4
L) 432.166.4 427.065.6 435.267.0 425.566.3
L) 5,2676382 5,5476287 5,5366286 5,3206388
Hb (g/dL) 12.360.2 12.060.2* 12.360.3 12.060.3
Free fat acid (mg/dL) 360.4635 424.4637 359.6642 431.5641
Total protein (g/dL) 7.3260.08 7.3460.05 7.3760.09 7.3160.08
Albumin (g/dL) 4.560.06 4.560.06 4.560.04 4.560.06
ALP (U/L) 172.665.8 175.366.6 184.166.8 177.467.2
ALT (U/L) 13.161.0 11.760.7 11.760.8 11.560.8
AST (U/L) 17.460.8 16.860.8 16.460.8 16.460.8
-GTP (U/L) 13.861.5 12.261.4* 13.961.2 12.361.2*
Urea nitrogen (mg/dL) 11.360.4 12.760.6 12.060.5 11.860.6
Creatinine (mg/dL) 0.6560.01 0.6660.01 0.6460.02 0.6660.01
HbA1c: hemoglobin A1c, TC: total cholesterol, Hb: hemoglobin, ALP: alanine aminotransferase, ALT: alkaline phosphatase,
AST: aspartate aminotransferase.
Mean values with their standard errors. * p,0.05 vs. 0 wk.
Sugita J et al.
GP extract are not known at present. The GP extract
contained various compounds with a vanilloid moiety
such as 6-paradol, 6-gingerol and 6-shogaol (15, 16).
All these compounds are capable of activating TRPV1,
which is involved in the thermic and anti-obesity effects
of capsaicin and capsinoids. The thermic effect of capsa-
icin and capsinoids are known to be mediated through
the activation of TRPV1 in the gastrointestinal tract.
Therefore, the effects of GP extract may also be via
gastrointestinal TRPV1, although it cannot be ruled
out that some vanilloid compounds are absorbed from
intestinal tract and directly activate BAT and some other
energy-consuming processes. Further studies are needed
to identify the compounds responsible for the thermic
and fat-reducing effects of GP extract, and to clarify the
action mechanism including their bioavailability.
Based on the acute stimulatory effect of GP extract on
BAT thermogenesis (18), it might be rational to consider
that the daily ingestion of GP extract results in a sus-
tained increase in the thermogenic activity of BAT and
thereby whole-body EE. In the present study, BAT activ-
ity could not be measured because of an ethical restric-
tion: the activity of human BAT can be accessed by
18F-ﬂuorodeoxyglucose-positron emission tomography
in combination with computed tomography (20), which
involves inevitable radiation exposure, and thereby its
use is strictly limited, particularly for normal young
The fat-reducing effects of GP extract were observed
only in visceral fat, not in subcutaneous or total body
fat. The effects seem similar to those of capsinoid inges-
tion, which signiﬁcantly reduces visceral fat, but not
total body fat (7, 8). The selective effects of these agents
may be attributable to the different metabolic properties
of visceral and subcutaneous fats. Speciﬁcally, visceral
fat is more sensitive to nutritional and hormonal chal-
lenges than subcutaneous fat. We note, with interest,
that the reducing effect of GP extract is negatively cor-
related to the initial levels of visceral fat. This implies
that GP extract may have a stronger fat-reducing effect
in individuals with more visceral fat. The subjects in the
present study were non-obese females, so we presume
they exhibited a weaker fat-reduction response than
what could be expected in obese subjects.
In conclusion, daily ingestion of GP extract increases
whole-body EE and decreases visceral fat in young non-
obese females. Although further studies on obese sub-
jects are needed, the present results suggest that GP
extract has the potential to become an effective and safe
tool for reducing body fat, mainly by preventing visceral
1) Kawada T, Watanabe T, Takaishi T, Tanaka T, Iwai K.
-adrenergic action on energy
metabolism in rats: inﬂuence of capsaicin on oxygen
consumption, the respiratory quotient, and substrate
utilization. Proc Soc Exp Biol Med 183: 250–256.
2) Kawada T, Hagihara K, Iwai K. 1986. Effects of capsa-
icin on lipid metabolism in rats fed a high fat diet. J Nutr
3) Yoshioka M, Lim K, Kikuzato S, Kiyonaga A, Tanaka H,
Shindo M, Suzuki M. 1995. Effects of red-pepper diet on
the energy metabolism in men. J Nutr Sci Vitaminol 41:
4) Lejeune MP, Kovacs EM, Westerterp-Plantenga MS.
2003. Effects of capsaicin on substrate oxidation and
weight maintenance after modest body-weight loss in
human subjects. Br J Nutr 90: 651–659.
5) Ludy MJ, Moore GE, Mattes RD. 2012. The effects of cap-
saicin and capsiate on energy balance: critical review
and meta-analyses of studies in humans. Chem Senses
6) Yoneshiro T, Aita S, Kawai Y, Iwanaga T, Saito M. 2012.
Non-pungent capsaicin analogs (capsinoids) increase
energy expenditure through the activation of brown
adipose tissue in humans. Am J Clin Nutr 95: 845–850.
7) Kawabata F, Inoue N, Yazawa S, Kawada T, Inoue K,
Fushiki T. 2008. Effects of CH-19 sweet, a non-pungent
cultivar of red pepper, in decreasing the body weight
and suppressing body fat accumulation by sympathetic
nerve activation in humans. Biosci Biotechnol Biochem
8) Snitker S, Fujishima Y, Shen H, Ott S, Pi-Sunyer X, Furu-
hata Y, Sato H, Takahashi M. 2009. Effects of novel cap-
sinoid treatment on fatness and energy metabolism in
humans: possible pharmacogenetic implications. Am J
Clin Nutr 89: 45–50.
9) Saito M, Yoneshiro T. 2013. Capsinoids and related
food ingredients activating brown fat thermogenesis
and reducing body fat in humans. Curr Opin Lipidol 24:
10) Kawabata F, Inoue N, Masamoto Y, Matsumura S,
Kimura W, Kadowaki M, Higashi T, Tominaga M, Inoue
K, Fushiki T. 2009. Non-pungent capsaicin analogs
(capsinoids) increase metabolic rate and enhance ther-
mogenesis via gastrointestinal TRPV1 in mice. Biosci
Biotechnol Biochem 73: 2690–2697.
11) Akendengué B, Louis AM. 1994. Medicinal plants used
by the Masango people in Gabon. J Ethnopharmacol 41:
12) Connell DW. 1970. Natural pungent compounds. III.
Paradols and associated compounds. Aust J Chem 23:
13) Connell DW, McLachlan R. 1972. Natural pungent
compounds. IV. Examination of the gingerols, shogaols,
paradols, and related compounds by thin-layer and gas
chromatography. J Chromatogr A 61: 29–35.
14) Tackie AN, Dwuma-Badu D, Ayim JSK, Dabra TT, Knapp
JE, Slatkin DJ, Schiff PL Jr. 1975. Constituents of West
African medicinal plants. VIII. Hydroxyphenylalkanones
from Amomum melegueta. Phytochemistry 14: 853–854.
15) Riera CE, Menozzi-Smarrito C, Affolter M, Michlig S,
Munari C, Robert F, Vogel H, Simon SA, le Coutre J.
2009. Compounds from Sichuan and Melegueta pep-
pers activate, covalently and non-covalently, TRPA1 and
TRPV1 channels. Br J Pharmacol 157: 1398–1409.
16) Morera E, De Petrocellis L, Morera L, Moriello AS, Nalli
M, Di Marzo V, Ortar G. 2012. Synthesis and biological
evaluation of -gingerol analogues as transient recep-
tor potential channel TRPV1 and TRPA1 modulators.
Bioorg Med Chem Lett 22: 1674–1677.
17) Iwami M, Mahmoud FA, Shiina T, Hirayama H, Shima T,
Sugita J, Shimizu Y. 2011. Extract of grains of paradise
and its active principle 6-paradol trigger thermogenesis
of brown adipose tissue in rats. Auton Neurosci 161:
A. melegueta Decreases Visceral Fat 27
18) Sugita J, Yoneshiro T, Hatano T, Aita S, Ikemoto T,
Uchiwa H, Iwanaga T, Kameya T, Kawai Y, Saito M.
2013. Grains of paradise (Aframomum melegueta) extract
activates brown adipose tissue and increases whole-
body energy expenditure in men. Br J Nutr 4: 733–738.
19) Tokunaga K, Matsuzawa Y, Ishikawa K, Tarui S. 1983.
A novel technique for the determination of body fat by
computed tomography. Int J Obes 7: 437–445.
20) Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe
K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa
M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. 2009.
High incidence of metabolically active brown adipose
tissue in healthy adult humans. Effects of cold exposure
and adiposity. Diabetes 58: 1526–1531.