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Daily Ingestion of Grains of Paradise (Aframomum melegueta) Extract Increases Whole-Body Energy Expenditure and Decreases Visceral Fat in Humans

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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 content 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 negatively correlated with the initial visceral fat area (r=-0.64, p<0.01). Neither GP nor placebo ingestion affected subcutaneous or total fat. The daily ingestion of GP, but not the placebo, 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.
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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
(15). 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 (79). 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,
and BAT.
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 (1214). 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.
E-mail: saito@tenshi.ac.jp
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
a
-humulene (5%),
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-
ase,
g
-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
methods.
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.
RESULTS
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.
GP
(n519)
Placebo
(n519)
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.
24
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
*
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
GP Placebo
Body weight (kg)
-0.3
-0.2
-0.1
0.0
0.1
0.2
0.3
GP Placebo
BMI
-0.9
-0.6
-0.3
0.0
0.3
0.6
0.9
GP Placebo
Body fat (%)
-8.0
-6.0
-4.0
-2.0
0.0
2.0
4.0
6.0
8.0
GP Placebo
Visceral fat (cm2)
-12.0
-8.0
-4.0
0.0
4.0
8.0
12.0
GP Placebo
Total fat (cm2)
-15.0
-10.0
-5.0
0.0
5.0
10.0
15.0
GP Placebo
Subcutaneous fat (cm2)
A B
-20
-10
0
10
20
30
0 20 40 60
Initial visceral fat (cm
2
)
Visceral fat (cm2 )
-100
-75
-50
-25
0
25
50
75
100
0100 200 300
400
Initial subcutaneous fat (cm
2
)
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,
p50.62).
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
g
-GTP
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.
DISCUSSION
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 (16, 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.
*
1,300
1,350
1,400
1,450
1,500
1,550
1,600
GP Placebo
EE (kcal/d)
Table 2. Blood parameters before and after 4 wk of daily ingestion of GP extract or placebo.
GP
(n519)
Placebo
(n519)
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
RBC (104/
m
L) 432.166.4 427.065.6 435.267.0 425.566.3
WBC (104/
m
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
g
-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.
26
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
females.
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
fat accumulation.
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... Repeated ingestion of GP. GP extract was extracted from seeds of A. melegueta (Thiercelin Co., Paris, France) and encapsulated as described in our previous report (12,16). Each capsule contained either no GP extract (placebo) or 10 mg GP extract including 6-gingerol (1.52 mg), 6-paradol (1.25 mg), 6-shogaol (0.17 mg), 6-gingeredione (0.40 mg), and 190 mg of a mixture of rapeseed oil (158 mg) and beeswax (32 mg) in a capsule. ...
... Such beneficial effects can be mimicked by oral ingestion of food ingredients that have agonistic activities on temperature-sensitive TRP channels (3,15). As GP contains several TRP agonists, including 6-paradol, it is capable of decreasing visceral fat mass in healthy women (16). Consistently, we observed a significant reduction in body fat percentage following GP treatment in healthy men, whereas no change was observed after placebo treatment. ...
... Consistently, we observed a significant reduction in body fat percentage following GP treatment in healthy men, whereas no change was observed after placebo treatment. It should be noted that the body fat change following GP treatment is negatively correlated with the initial levels of visceral fat for the participants (16). This implies that GP may have a stronger fat-reducing effect in individuals with more visceral fat. ...
Article
Increasing adaptive thermogenesis through the activation of brown adipose tissue (BAT) is a promising practical strategy for preventing obesity and related disorders. Ingestion of a single dose of 40 mg of an extract of Grains of Paradise (GP), a ginger family species, reportedly triggers BAT thermogenesis in individuals with high but not in those with low BAT activity. We hypothesized that prolonged treatment with GP might revive BAT in individuals who have lost active BAT. In the present study, we recruited 9 healthy young male volunteers with reduced BAT that was assessed by fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) following 2-h cold exposure at 19ºC. The subjects ingested GP extract (40 mg/d) or placebo every day for 5 wk. Before and after the treatment with either GP or placebo, their body composition and BAT-dependent cold-induced thermogenesis (CIT)—a non-invasive index of BAT—were measured in a single-blinded, randomized, placebo-controlled cross-over design. Their whole-body resting energy expenditure at a thermoneutral condition remained unchanged following GP treatment. However, CIT after treatment was significantly higher in GP-treated individuals than in placebo-treated individuals. Body weight and fat-free mass did not change significantly following GP or placebo treatment. Notably, body fat percentage slightly but significantly decreased after GP treatment but not after placebo treatment. These results suggest that repeated ingestion of GP elevates adaptive thermogenesis through the re-activation of BAT, thereby reducing body fat in individuals with low BAT activity.
... officinale, dried ginger, ginger powder) was used in six of the human studies as a supplement and Aframoum melegueta forms were given to the participants in two of the studies. [8,[31][32][33][34][35][36][37] Seven of the studies were randomized design with control groups who have received placebo. [8,31,32,[34][35][36][37] Only one of the studies had no control group which was designed as 24 h treatment. ...
... [8,[31][32][33][34][35][36][37] Seven of the studies were randomized design with control groups who have received placebo. [8,31,32,[34][35][36][37] Only one of the studies had no control group which was designed as 24 h treatment. [33] Study results Goyal et al. (2006) and Abdel Raoof et al. (2017) achieved weight loss in the mice (n = 24) and Sprague-Dawley rats (n = 42) with Z.officinale (250 mg, 8 weeks) and ginger powder (200 mg/kg, 6 weeks) compared to obese control groups. ...
... [31] Sugita et al. (2014) also found no effect of Aframoum melegueta (30 mg) supplementation for 4 weeks on body weight but a significant decrease in visceral fat in non-obese female compare to control group (n = 19, 20-22 y). [32] Attari et al. (2015) also reported an association of ginger (2 g/day, 30 min before meals in 12 weeks) with a significant decrease of total hunger score of the healthy obese female participants (n = 80, 18-45 y). [36] Such results comply with the result of the study of Mansour et al. (2012) where they assessed the appetite by analog scale. ...
Article
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Ginger called Zingiber officinale (Z. officinale) belongs to Zingiberaceae family. In recent years, studies have shown that ginger may have effects on appetite, thermogenesis, and gastric motility. Due to these effects, the present study aimed to review of studies evaluating the effect of ginger on energy metabolism and obesity. The screening of the studies published was performed in 4 databases (PubMed-Web of Science-Lilacs-The Cochrane Library). Among the 1428 studies, only 20 studies had sufficient data to be included in the systematic review. Literature shows that ginger may have important effects on energy metabolism and obesity in animal models via decreased carbohydrate and lipids oxidation, increased nerve activity, changes in hormone (leptin, insulin) and enzymes (amylase, lipase). Some human studies also show positive effects; however, the results are conflicting because of difference in active ingredients, low dose, and short administration period (single dose, 24 hours). In meta-analysis of studies showed that ginger significantly decrease BMI (95% CI:1.33 −4.02 to 1.84, p = .003). In conclusion, the association of ginger with energy metabolism and obesity may have positive effects. However, before a clear recommendation can be made determination of the active ingredient and optimal duration and dose, as well as possible effects with long-term usage.
... In humans, we found thermogenic responses to oral ingestion of an alcohol extract of GP in individuals with metabolically active BAT, but not in those without it (146), implying a BATdependent thermogenesis by GP extract. In line with the acute effects, in one study, daily ingestion of GP extract for 4 weeks resulted in a slight reduction in visceral fat (147). These results suggest that GP, like capsinoids and catechins, increases wholebody EE through the activation of BAT, thereby decreasing body fatness. ...
Article
Full-text available
Since the recent rediscovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has been attracting increasing interest. The inverse relationship between BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. Cold exposure activates and recruits BAT, resulting in increased energy expenditure and decreased body fatness. The stimulatory effects of cold exposure are mediated through transient receptor potential (TRP) channels and the sympathetic nervous system (SNS). Most TRP members also function as chemesthetic receptors for various food ingredients, and indeed, agonists of TRP vanilloid 1 such as capsaicin and its analog capsinoids mimic the effects of cold exposure to decrease body fatness through the activation and recruitment of BAT. The antiobesity effect of other food ingredients including tea catechins may be attributable, at least in part, to the activation of the TRP–SNS–BAT axis. BAT is also involved in the facultative thermogenesis induced by meal intake, referred to as diet-induced thermogenesis (DIT), which is a significant component of the total energy expenditure in our daily lives. Emerging evidence suggests a crucial role for the SNS in BAT-associated DIT, particularly during the early phase, but several gut-derived humoral factors may also participate in meal-induced BAT activation. One intriguing factor is bile acids, which activate BAT directly through Takeda G-protein receptor 5 (TGR5) in brown adipocytes. Given the apparent beneficial effects of some TRP agonists and bile acids on whole-body substrate and energy metabolism, the TRP/TGR5–BAT axis represents a promising target for combating obesity and related metabolic disorders in humans.
... Kaempferia parviflora (with dose of 100 mg/day; Matsushita et al., 2015), Aframomum melegueta (with dose of 30 mg/day; Sugita et al., 2014), oolong tea (with dose of 5,000 mg/day; Komatsu et al., 2003), and green tea, a combination of tyrosine, green tea and caffeine (Belza, Toubro, & Astrup, 2009), and a combination of Camellia sinensis, Capsicum Annum Oleoresin, Fucus vesiculosus, Allium sativa, mint essential oil, and Piper nigrum (Rondanelli et al., 2013; Figure 2). ...
Article
Obesity is a medical situation in which excess body fat has gathered because of imbalance between energy intake and energy expenditure. In spite of the fact that the variety of studies are available for obesity treatment and management, its “globesity” still remains a big challenge all over the world. The current systematic review and meta‐analysis aimed to evaluate the efficacy, safety, and mechanisms of effective herbal medicines in the management and treatment of obesity and metabolic syndrome in human. We systematically searched all relevant clinical trials via Web of Science, Scopus, PubMed, and the Cochrane database to assess the effects of raw or refined products derived from plants or parts of plants on obesity and metabolic syndrome in overweight and obesity adult subjects. All studies conducted by the end of May 2019 were considered in the systematic review. Data were extracted independently by two experts. The quality assessment was assessed using Consolidated Standards of Reporting Trials checklist. The main outcomes were anthropometric indices and metabolic syndrome components. Pooled effect of herbal medicines on obesity and metabolic syndrome were presented as standardized mean difference (SMD) and 95% confidence interval (CI). A total of 279 relevant clinical trials were included. Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredients were found to be effective in the management of obesity and metabolic syndrome. In addition, C. fimbriata, flaxseed, spinach, and fenugreek were able to reduce appetite. Meta‐analysis showed that intake of green tea resulted in a significant improvement in weight ([SMD]: −0.75 [−1.18, −0.319]), body mass index ([SMD]: −1.2 [−1.82, −0.57]), waist circumference ([SMD]: −1.71 [−2.66, −0.77]), hip circumference ([SMD]: −0.42 [−1.02, −0.19]), and total cholesterol, ([SMD]: −0.43 [−0.77, −0.09]). In addition, the intake of P. vulgaris and N. sativa resulted in a significant improvement in weight ([SMD]: −0.88, 95 % CI: [−1.13, −0.63]) and triglyceride ([SMD]: −1.67, 95 % CI: [−2.54, −0.79]), respectively. High quality trials are still needed to firmly establish the clinical efficacy of the plants in obesity and metabolic syndrome.
... Moreover, daily ingestion of GP extract (40 mg/day, 3 weeks) results in an increase in CIT, an index of BAT activity in healthy young volunteers (Yoneshiro et al. 2018). This thermogenic effect of GP was coupled with a significant decrease in visceral fat area (À7.0%) (Sugita et al. 2014). As these responses are almost similar to those seen after capsinoid ingestion, it is likely that GP extract enhances EE as a result of BAT activation and recruitment. ...
Chapter
Since the rediscovery of brown adipose tissue (BAT) in humans, its energy-dissipating ability has been well-recognized. The negative correlations of BAT activity with adiposity and insulin sensitivity provided an obvious rationale for discerning reliable and practical strategies for stimulating BAT. Though cold exposure or use of pharmacological adrenomimetics can activate BAT, they may have adverse effects. Therefore, determining alternative stimulants of BAT with lower risks such as commonly used food ingredients is highly desirable. Recent observations revealed that chemical activation of temperature-sensitive transient receptor potential (TRP) channels by food ingredients can recruit BAT in humans. Furthermore, animal studies have identified several food-derived stimulants of BAT acting through multiple mechanisms distinct from a TRP-mediated process. Dietary compounds acting as an activator of Sirtuin 1, a critical regulator of mitochondrial biogenesis and brown adipocyte differentiation, are one such class of promising food-derived BAT activators in humans. While the individual effects of various dietary factors are increasingly established in a laboratory setting, the potential synergistic effects of multiple stimulants on BAT remain to be tested in a clinical environment. These investigations may support the development of efficient, flexible dietary regimens capable of boosting BAT thermogenesis.
Article
Two vanilloids, (5E)-8-(4-hydroxy-3-methoxyphenyl)oct-5-en-4-one (1) and 4-[3-hydroxydecyl]-2-methoxyphenol (2), isolated from the dried seeds of Grains of Paradise (Aframomum melegueta), were synthesized; the latter compound was made as the S-enantiomer and the material derived from the seeds was found to be a 1:1.7 mixture of the R and S isomers. The synthetic route used should allow the preparation of analogs having extended alkyl chains and consequently different lipophilicity, and 3, a homolog of 2, was also prepared.
Chapter
Human brown adipose tissue (BAT) is experimentally modeled to better understand the biology of this important metabolic tissue, and also to enable the potential discovery and development of novel therapeutics for obesity and sequelae resulting from the persistent positive energy balance. This chapter focuses on translation into humans of findings and hypotheses generated in nonhuman models of BAT pharmacology. Given the demonstrated challenges of sustainably reducing caloric intake in modern humans, potential solutions to obesity likely lie in increasing energy expenditure. The energy-transforming activities of a single cell in any given tissue can be conceptualized as a flow of chemical energy from energy-rich substrate molecules into energy-expending, endergonic biological work processes through oxidative degradation of organic molecules ingested as nutrients. Despite the relatively tight coupling between metabolic reactions and products, some expended energy is incidentally lost as heat, and in this manner a significant fraction of the energy originally captured from the environment nonproductively transforms into heat rather than into biological work. In human and other mammalian cells, some processes are even completely uncoupled, and therefore purely energy consuming. These molecular and cellular actions sum up at the physiological level to adaptive thermogenesis, the endogenous physiology in which energy is nonproductively released as heat through uncoupling of mitochondria in brown fat and potentially skeletal muscle. Adaptive thermogenesis in mammals occurs in three forms, mostly in skeletal muscle and brown fat: shivering thermogenesis in skeletal muscle, non-shivering thermogenesis in brown fat, and diet-induced thermogenesis in brown fat. At the cellular level, the greatest energy transformations in humans and other eukaryotes occur in the mitochondria, where creating energetic inefficiency by uncoupling the conversion of energy-rich substrate molecules into ATP usable by all three major forms of biological work occurs by two primary means. Basal uncoupling occurs as a passive, general, nonspecific leak down the proton concentration gradient across the membrane in all mitochondria in the human body, a gradient driving a key step in ATP synthesis. Inducible uncoupling, which is the active conduction of protons across gradients through processes catalyzed by proteins, occurs only in select cell types including BAT. Experiments in rodents revealed UCP1 as the primary mammalian molecule accounting for the regulated, inducible uncoupling of BAT, and responsive to both cold and pharmacological stimulation. Cold stimulation of BAT has convincingly translated into humans, and older clinical observations with nonselective 2,4-DNP validate that human BAT’s participation in pharmacologically mediated, though nonselective, mitochondrial membrane decoupling can provide increased energy expenditure and corresponding body weight loss. In recent times, however, neither beta-adrenergic antagonism nor unselective sympathomimetic agonism by ephedrine and sibutramine provide convincing evidence that more BAT-selective mechanisms can impact energy balance and subsequently body weight. Although BAT activity correlates with leanness, hypothesis-driven selective β3-adrenergic agonism to activate BAT in humans has only provided robust proof of pharmacologic activation of β-adrenergic receptor signaling, limited proof of the mechanism of increased adaptive thermogenesis, and no convincing evidence that body weight loss through negative energy balance upon BAT activation can be accomplished outside of rodents. None of the five demonstrably β3 selective molecules with sufficient clinical experience to merit review provided significant weight loss in clinical trials (BRL 26830A, TAK 677, L-796568, CL 316,243, and BRL 35135). Broader conclusions regarding the human BAT therapeutic hypothesis are limited by the absence of data from most studies demonstrating specific activation of BAT thermogenesis in most studies. Additionally, more limited data sets with older or less selective β3 agonists also did not provide strong evidence of body weight effects. Encouragingly, β3-adrenergic agonists, catechins, capsinoids, and nutritional extracts, even without robust negative energy balance outcomes, all demonstrated increased total energy expenditure that in some cases could be associated with concomitant activation of BAT, though the absence of body weight loss indicates that in no cases did the magnitude of negative energy balance reach sufficient levels. Glucocorticoid receptor agonists, PPARg agonists, and thyroid hormone receptor agonists all possess defined molecular and cellular pharmacology that preclinical models predicted to be efficacious for negative energy balance and body weight loss, yet their effects on human BAT thermogenesis upon translation were inconsistent with predictions and disappointing. A few new mechanisms are nearing the stage of clinical trials and may yet provide a more quantitatively robust translation from preclinical to human experience with BAT. In conclusion, translation into humans has been demonstrated with BAT molecular pharmacology and cell biology, as well as with physiological response to cold. However, despite pharmacologically mediated, statistically significant elevation in total energy expenditure, translation into biologically meaningful negative energy balance was not achieved, as indicated by the absence of measurable loss of body weight over the duration of a clinical study.
Article
Background: Grains of Paradise (GP) is the seed of Aframomum melegueta, which is widely distributed throughout West Africa and has been used as a spice and a folk remedy for a long time. The anti-obesity effect by GP intake was demonstrated in our previous report. In this present study, we tried to isolate some compounds in GP and clarify the anti-obesity mechanism. Results: Ten vanilloid compounds were determined. Among ten vanilloids, 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol and 1-(4'-hydroxy-3'-methoxyphenyl)-3-octen-5-one were determined as novel compounds and 6-gingerol, 6-paradol, and 6-shogaol were identified as the major constituents in GP extract. Moreover, the extract and 6-gingerol, which is one of the principal components of GP extract, were orally administered to rats to investigate the effect on sympathetic nerve activity (SNA) in brown adipose tissue (BAT). The injection of GP extract and 6-gingerol decreased BAT-SNA, whereas capsaicin, which is a major component of chili pepper, activates the sympathetic nervous system. Conclusion: This study suggested that GP extract and 6-gingerol were largely unrelated to the anti-obesity effect by the activation of interscapular BAT-SNA and had a different anti-obesity mechanism to capsaicin.
Article
Biele tukové tkanivo je orgán, ktorý dokáže v adipocytoch akumulovať obrovské množstvo energie a v závislosti od stavu naplnenia energetických zásob produkovať celé spektrum bioaktívnych látok (adipokínov). Týmito mediátormi reguluje napríklad príjem potravy alebo metabolickú aktivitu tkanív s cieľom zabezpečiť asi všetky energeticky náročné biologické procesy v našom tele. Hnedé tukové tkanivo sa zasa špecializuje najmä na tvorbu tepla, ktoré dokáže veľmi elegantne vytvoriť využitím energie protónového gradientu na vnútornej membráne mitochondrií. Hnedý tuk produkuje tiež množstvo biologicky aktívnych látok (batokínov), ktoré sa podieľajú aj na regulácii metabolickej a redoxnej rovnováhy. V tele malých cicavcov tvorí hnedý tuk funkčne a morfologicky od bieleho tuku jednoznačne oddelený orgán, ktorého esenciálnou úlohou je tvoriť teplo v odpovedi na chlad. U človeka nájdeme takto definované tkanivo len zriedka, a to najmä v blízkosti veľkých ciev na krku. Oveľa častejšie pozorujeme hnedé tukové bunky roztrúsené či zosieťované vo vnútri bieleho tukového tkaniva. Takéto tkanivo označujeme ako béžové a o jeho schopnosti regulovať telesnú teplotu sa stále diskutuje. S určitosťou však vieme, že metabolická aktivácia tohto tkaniva zvyšuje výdaj energie a mohla by sa tak využiť na zmiernenie negatívnych metabolických dôsledkov obezity. Obezita sa však spája s nadmerným ukladaním lipidov v tukových bunkách, a ak je ich kapacita uskladňovať lipidy prekročená, ukladajú sa tiež v hnedých tukových bunkách, v hepatocytoch či v bunkách kostrového svalu, čo limituje ich normálnu fyziologickú funkciu. Chlad či fyzická aktivita zatiaľ nie celkom známym mechanizmom indukujú hnednutie (metabolickú aktiváciu) tuku u človeka, a farmakologicky či nefarmakologicky navodená aktivácia týchto procesov by mohla mať terapeutický potenciál pre pacientov s obezitou. Objasnenie termogénnych mechanizmov však zatiaľ komplikuje obrovská bunková heterogenita a dynamika fyziologickej regulácie jednotlivých bunkových populácií hnedého a béžového tukového tkaniva u ľudí.
Article
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Consumption of spicy foods containing capsaicin, the major pungent principle in hot peppers, reportedly promotes negative energy balance. However, many individuals abstain from spicy foods due to the sensory burn and pain elicited by the capsaicin molecule. A potential alternative for nonusers of spicy foods who wish to exploit this energy balance property is consumption of nonpungent peppers rich in capsiate, a recently identified nonpungent capsaicin analog contained in CH-19 Sweet peppers. Capsiate activates transient receptor potential vanilloid subtype 1 (TRPV1) receptors in the gut but not in the oral cavity. This paper critically evaluates current knowledge on the thermogenic and appetitive effects of capsaicin and capsiate from foods and in supplemental form. Meta-analyses were performed on thermogenic outcomes, with a systematic review conducted for both thermogenic and appetitive outcomes. Evidence indicates that capsaicin and capsiate both augment energy expenditure and enhance fat oxidation, especially at high doses. Furthermore, the balance of the literature suggests that capsaicin and capsiate suppress orexigenic sensations. The magnitude of these effects is small. Purposeful inclusion of these compounds in the diet may aid weight management, albeit modestly.
A new series of pungent compounds, the 1-(4'-hydroxy-3'-methoxyphenyl). alkan-3-ones, has been isolated from grains of paradise (Amomum melegueta Roscoe) and detected in ginger (Zingiber officinale Roscoe). The name, paradol, which has been previously applied to a mixture of these compounds and the gingerols, is suggested as a group name prefixed with a number corresponding to that given to the gingerol with the same side-chain length to distinguish individual members. The structure of [6]-paradol, as suggested by spectroscopic techniques, was confirmed by synthesis from [6]-gingerol. It occurred in grains of paradise in quantities up to 1.5% and was accompanied by (+)-[6]- gingerol in almost equal amounts. Trace quantities of [8]-gingerol, [a]-paradol, and [6]-shogaol were also present.
Article
The gingerols, shogaols, paradols and related compounds have been examined by thin-layer (silica gel) and gas chromatography (SE-30 and VO-17 liquid phases) and reference retention times and RF values reported. Thin-layer chromatography gives only partial separation of the various homologous series of compounds, whereas good resolution is obtained with gas chromatography. Compounds containing a β-hydroxyketone grouping, e.g., the gingerols, decompose to aliphatic aldehydes and zingerone under the conditions of gas chromatography. The methods described are particularly applicable to the qualitative analysis of the oleoresins from ginger and grains of paradise.
Article
Brown adipose tissue (BAT) is responsible for cold- and diet-induced thermogenesis, and thereby contributes to the control of whole-body energy expenditure (EE) and body fat content. BAT activity can be assessed by fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) in human subjects. Grains of paradise (GP, Aframomum melegueta), a species of the ginger family, contain pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol. An alcohol extract of GP seeds and 6-paradol are known to activate BAT thermogenesis in small rodents. The present study aimed to examine the effects of the GP extract on whole-body EE and to analyse its relation to BAT activity in men. A total of nineteen healthy male volunteers aged 20-32 years underwent FDG-PET after 2 h of exposure to cold at 19°C with light clothing. A total of twelve subjects showed marked FDG uptake into the adipose tissue of the supraclavicular and paraspinal regions (BAT positive). The remaining seven showed no detectable uptake (BAT negative). Within 4 weeks after the FDG-PET examination, whole-body EE was measured at 27°C before and after oral ingestion of GP extract (40 mg) in a single-blind, randomised, placebo-controlled, crossover design. The resting EE of the BAT-positive group did not differ from that of the BAT-negative group. After GP extract ingestion, the EE of the BAT-positive group increased within 2 h to a significantly greater (P< 0·01) level than that of the BAT-negative group. Placebo ingestion produced no significant change in EE. These results suggest that oral ingestion of GP extract increases whole-body EE through the activation of BAT in human subjects.
Article
Capsaicin and its nonpungent analog (capsinoids) are known to be food ingredients that increase energy expenditure and decrease body fat. This article reviews the role of brown adipose tissue (BAT) for the thermogenic effect of these compounds in humans and proposes the possibility of some other antiobesity food ingredients. A single oral ingestion of capsinoids increases energy expenditure in human individuals with metabolically active BAT, but not those without it, indicating that capsinoids activate BAT and thereby increase energy expenditure. This finding gave a rational explanation for discrepant results of the effects of capsinoids in the previous studies. Human BAT may be largely composed of inducible 'beige' adipocytes more than typical brown adipocytes because its gene expression patterns are similar to beige cells isolated from murine white fat depots. In fact, preadipocytes isolated from supraclavicular fat deposits - where BAT is often detected - are capable of differentiating into brown-like adipocytes in vitro, providing evidence of inducible brown adipogenesis in adult humans. As human BAT may be inducible, a prolonged ingestion of capsinoids would recruit active BAT and thereby increase energy expenditure and decrease body fat. In addition to capsinoids, there are numerous food ingredients that are expected to activate BAT and so be useful for the prevention of obesity in daily life.
Article
Capsinoids-nonpungent capsaicin analogs-are known to activate brown adipose tissue (BAT) thermogenesis and whole-body energy expenditure (EE) in small rodents. BAT activity can be assessed by [¹⁸F]fluorodeoxyglucose-positron emission tomography (FDG-PET) in humans. The aims of the current study were to examine the acute effects of capsinoid ingestion on EE and to analyze its relation to BAT activity in humans. Eighteen healthy men aged 20-32 y underwent FDG-PET after 2 h of cold exposure (19°C) while wearing light clothing. Whole-body EE and skin temperature, after oral ingestion of capsinoids (9 mg), were measured for 2 h under warm conditions (27°C) in a single-blind, randomized, placebo-controlled, crossover design. When exposed to cold, 10 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining 8 subjects (BAT-negative group) showed no detectable uptake. Under warm conditions (27°C), the mean (±SEM) resting EE was 6114 ± 226 kJ/d in the BAT-positive group and 6307 ± 156 kJ/d in the BAT-negative group (NS). EE increased by 15.2 ± 2.6 kJ/h in 1 h in the BAT-positive group and by 1.7 ± 3.8 kJ/h in the BAT-negative group after oral ingestion of capsinoids (P < 0.01). Placebo ingestion produced no significant change in either group. Neither capsinoids nor placebo changed the skin temperature in various regions, including regions close to BAT deposits. Capsinoid ingestion increases EE through the activation of BAT in humans. This trial was registered at http://www.umin.ac.jp/ctr/ as UMIN 000006073.
Article
In order to explore the structural determinants for the TRPV1 and TRPA1 agonist properties of gingerols, a series of nineteen analogues (1b-5) of racemic [6]-gingerol (1a) was synthesized and tested on TRPV1 and TRPA1 channels. The exploration of the structure-activity relationships, by modulating the three pharmacophoric regions of [6]-gingerol, led to the identification of some selective TRPV1 agonists/desensitizers of TRPV1 channels (3a, 3f, and 4) and of some full TRPA1 antagonists (2c, 2d, 3b, and 3d).
Article
Grains of paradise (GP) is a species of the ginger family, Zingiberaceae, extracts of which have a pungent, peppery taste due to an aromatic ketone, 6-paradol. The aim of this study was to explore the thermogenic effects of GP extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering the interscapular brown adipose tissue were recorded. Intragastric injection of a GP extract or 6-paradol enhanced the efferent discharges of the sympathetic nerves in a dose-dependent manner. The enhanced nerve discharges were sustained for as long as 3h. The rats did not become desensitized to the stimulatory effects these compounds on sympathetic nerve activity. The tissue temperature of brown adipose tissue showed significant increase in rats injected with 6-paradol. These results demonstrate that GP extracts and 6-paradol activate thermogenesis in brown adipose tissue, and may open up new avenues for the regulation of weight loss and weight maintenance.