Assessment of essential oil as a potential anti-obesity agent: a narrative review

Abstract

Several species of medicinal plants have long been used for the complementary treatment of obesity-diabetes in various systems of medicine. Among them are the plant-derived essential oils which are rich sources of volatile organic compounds. The objective of this review is to assess the effectiveness of essential oils as anti-obesity agents. All the literatures were extracted from three databases (PubMed, EBSCO Discovery Service and Ovid) from year 2000 to 2015 using the Medical subject heading (MeSH) terms ‘essential oil’, crossed with the term ‘obesity’, ‘anti-obesity’ or ‘antiobesity’. Nine articles were selected and divided into five broad categories of experiments. The attenuation effects of essential oils on obesity may be mediated by several possible mechanisms that include anti-lipase activity, increasing the plasma glycerol concentration and suppressing fat accumulation. Only one randomized controlled trial (RCT) study on essential oil was identified so far and these data were not conclusive to provide evidence-based health claim on this issue.

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Assessment of essential oil as a potential anti-
obesity agent: a narrative review
Aswir Abd Rashed, Mohd Naeem Mohd Nawi & Kasmawati Sulaiman
To cite this article: Aswir Abd Rashed, Mohd Naeem Mohd Nawi & Kasmawati Sulaiman (2016):
Assessment of essential oil as a potential anti-obesity agent: a narrative review, Journal of
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JOURNAL OF ESSENTIAL OIL RESEARCH, 2016
http://dx.doi.org/10.1080/10412905.2016.1213668
the active drugs reduced weight ranging from a mean
change of -2.65 kg for orlistat to -11.23 kg for rimonabant.
However, it was reported that sibutramine 15 mg had the
largest probability (62.4%) of being the best intervention
in terms of BMI reduction (10). It was also reported that
lifestyle advice alone can lead to weight reduction at 6 and
12 months, but was less eective than pharmacological
interventions (10). However, sibutramine overdose can
result in serotonin syndrome, a potentially life-threatening
condition caused by excessive serotonin stimulation of
the central nervous system (11). Conversely, rimonabant
was reported to cause neurologic and psychiatric adverse
events that were frequently reported in clinical trials of
the drug (12). Furthermore, the use of conventional anti-
obesity drugs has been limited by side eects including
mood changes, suicidal thoughts, and gastrointestinal or
cardiovascular complications (13). us, there may be a
place in clinical practice for similar drugs if side eects of
those drugs could be avoided.
At present, the most eective treatment of severe obe-
sity is by performing a bariatric surgery (14). However,
due to the higher cost, shortage of bariatric surgeons, side
eects and complications, gastric bypass surgery is not
an option for treatment of common obesity at the popu-
lation level. Instead of performing a bariatric surgery, it
Introduction
In 2008, it was estimated that more than 1.4 billion adults
worldwide were overweight (1). Of these over 500 million
of them were obese. In 2011, it was reported that more
than 40 million children under the age of ve were over-
weight (2).
Obesity is associated with an increased risk of morbid-
ity and mortality in a later life (3). Obesity is associated
with increased risk for more than twenty chronic diseases
and health conditions, including hypertension, type 2 dia-
betes (T2DM), osteoarthritis, dyslipidaemia, high choles-
terol, stroke, obstructive sleep apnea, and some cancers
(4). Many of these diseases can be prevented or amelio-
rated with a reduction in body weight (5). Overweight,
obesity and the associated health problems have substan-
tial economic consequences for the health care system (6).
ere are several conventional anti-obesity medications
widely available in the market. Some of these drugs like
sibutramine and rimonabant have now been withdrawn
from use as anti-obesity drug because of their harmful side
eects. Several randomized controlled trials (RCTs) on
orlistat, rimonabant or sibutramine had reported weight
or body mass index (BMI) change from baseline at 3, 6
or 12 months (7–9). It was found that all the active drugs
were eective at reducing weight and BMI. At 3 months,
Assessment of essential oil as a potential anti-obesity agent: a narrative review
Aswir Abd Rasheda†, Mohd Naeem Mohd Nawia† and Kasmawati Sulaimanb†
aNutrition Unit, Cardiovascular, Diabetes and Nutrition Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia; bFaculty of
Quranic and Sunnah Studies, Islamic Science and University of Malaysia, Nilai, Negeri Sembilan, Malaysia
ABSTRACT
Several species of medicinal plants have long been used for the complementary treatment of
obesity-diabetes in various systems of medicine. Among them are the plant-derived essential
oils which are rich sources of volatile organic compounds. The objective of this review is to assess
the eectiveness of essential oils as anti-obesity agents. All the literatures were extracted from
three databases (PubMed, EBSCO Discovery Service and Ovid) from year 2000 to 2015 using the
Medical subject heading (MeSH) terms ‘essential oil’, crossed with the term‘obesity’, ‘anti-obesity’ or
‘antiobesity’. Nine articles were selected and divided into ve broad categories of experiments. The
attenuation eects of essential oils on obesity may be mediated by several possible mechanisms
that include anti-lipase activity, increasing the plasma glycerol concentration and suppressing fat
accumulation. Only one randomized controlled trial (RCT) study on essential oil was identied so far
and these data were not conclusive to provide evidence-based health claim on this issue.
KEYWORDS
Essential oil; anti-obesity;
in vitro; in vivo; clinical trial
ARTICLE HISTORY
Received 13 December 2015
Accepted 12 July 2016
© 2016 Informa UK Limited, trading as Taylor & Francis Group
CONTACT Aswir Abd Rashed aswir@imr.gov.my
†These authors contributed equally to this work.

2 A. A. RASHED ET AL.
subject heading (MeSH) terms ‘essential oil’, crossed
with the term ‘obesity’, ‘anti-obesity’ or ‘antiobesity’.
Publications with available abstracts were reviewed and
limited to studies published in the English and Malay
languages. Papers on human and animal studies, clinical
trials, and related to plant-based obesity medication were
included. However, review articles and letters to the edi-
tor were excluded. Duplicate articles were eliminated. e
study identication process and reasons for exclusion are
illustrated in Figure 1.
Results
All the related articles were printed out for further assess-
ment of evidence-based to determine the eectiveness of
essential oil as an anti-obesity treatment. Aer conduct-
ing the comprehensive literature review, the articles were
selected and divided into ve categories of experiments:
one article was categorized as a chemical composition
study, two articles were categorized based on their in
vitro studies, one article was categorized based on their
combination study on in vitro and in vivo experiments,
four articles were categorized based on their in vivo stud-
ies, and one article was related to randomized controlled
trial (RCT). e amount of information available for this
particular topic at a set period of time was only nine arti-
cles. Due to the lack of RCTs (only one article), this topic
can only proceed for a further assessment as a narrative
review.
Discussion
Essential oil is a concentrated hydrophobic liquid contain-
ing volatile aroma compounds from plants. Our electronic
searches and subsequent full paper screening identied
nine informative articles related to essential oils and
anti-obesity. e essential oils can be classied according
to the type of plants they originated from: Citrus (Citrus
paradisi, Citrus aurantifolia and Citrus (+)-Limonene),
Pinus koraiensis, Momordica charantia, Acorus calamus
and Nigella sativa (Table 1).
One of the selected articles was related to the chem-
ical composition, antioxidant activity and anti-lipase
activity of essential oils from two types of aromatic
plants which are oregano and Lippia. Both plants are
commonly used for flavoring foods and containing
preserving properties (32–34). Furthermore, these
plants have been shown to possess antioxidant, anti-
bacterial, antifungal, antispasmodic, analgesic activities
and anti-lipase properties. A study done by Quiroga
et al. (23) found that oregano and Lippia had anti- lipase
activity at IC50 5.09 and 7.26 μg/mL respectively. Their
anti-lipase activity is related to the hydrolysis of dietary
was reported that increasing the secretion of glucagon-like
peptide (GLP-1) is capable of mimicking the eects of
bariatric surgery (15). GLP-1 has a dual action, acts as a
satiety signal, leading to reduced food intake (16, 17) and
as a regulator of gastric emptying (18).
Herbal medicines have been used in Asia and Southeast
Asia for centuries. Some of the well-known herbal medi-
cines are traditional Chinese medicine, Japanese traditional
medicines and Indian traditional medicine. For example,
the eectiveness and safety of traditional Chinese medicine
including Chinese herbal medicine (CHM) and acupunc-
ture provide an alternative established therapy for the med-
ical challenges of obesity (13). ere was a published review
paper that compared 4861 subjects in the CHM treatment
groups and 3821 in the control groups, with treatment dura-
tion ranging from 2 weeks to 4 months. e CHM and acu-
puncture exhibited risk ratio (RR) of 1.84 and 2.14 in body
weight reduction with a mean dierence in body weight
reduction of 4.03 kg and 2.76 kg, and a mean dierence in
BMI reduction of 1.32 kg m−2 and 2.02 kg m−2compared
with placebo or lifestyle modication, respectively (13).
When the treatments were compared with the pharmaco-
logical treatments of sibutramine, fenuramine or orlistat,
the reported RR was 1.11 and 1.14 in body weight reduc-
tion, mean dierence in body weight reduction of 0.08 kg
and 0.65 kg, and mean dierence in BMI reduction of 0.18
kg m
−2
and 0.83 kg m
−2
, respectively. ese nding showed
that CHM and acupuncture were more eective than pla-
cebo or lifestyle modication in reducing body weight.
Additionally, they had a similar ecacy as the anti-obesity
drugs but with fewer reported adverse eects.
Several species of medicinal plants have long been
used for the complementary treatment of obesity-diabe-
tes in various systems of medicine (19). Among them are
the plant-derived essential oils which are rich sources of
volatile organic compounds. e essential oils have been
known to have anti-obesity properties (20, 21). It has been
widely reported by the media that grapefruit and citrus
essential oil are the most common oil used in aromather-
apy for weight loss program (22).
Since there are many reported studies on the medicinal
use of essential oils as anti-obesity agents, it is important to
further investigate the worthiness of these claims. Hence,
the objective of this paper is to assess the eectiveness of
essential oils for treating obesity conducted in vitro, in
vivo or at a clinical research settings.
Materials and methods
Search strategy
e original articles were identied through searches of
three databases (PubMed, EBSCO Discovery Service and
Ovid) for the period of 2000 to 2015 using the Medical

JOURNAL OF ESSENTIAL OIL RESEARCH 3
triacylglycerols (TAG), and thus, if its movement from
the intestinal lumen into the body is stopped or mini-
mized, the prevalence of obesity can be reduced (35).
Most of the common compounds that are found in sev-
eral other plants species with anti-lipase activity are
polyphenols, saponins and terpinenes (35).
Some essential oils have been reported to react as anti-
hyperlipidemic agents. Hyperlipidemia is a progression
step of inducing metabolic syndrome such as obesity, dia-
betes and cardiovascular diseases. A study done by Kim
et al. (25) used an essential oil derived from P. koraiensis
(EOPK) to investigate the antihyperlipidemic eect on
hepatocarcinoma (HepG2) cells. EOPK was found to be
eective to reduce the circulating low density lipopro-
tein cholesterol (LDL-C)in the cells by increasing the
expression of low density lipoprotein receptor (LDLR),
decreasing 3-hydroxy-3-methyl-glutaryl-CoA reductase
(HMGCR), inhibiting cholesterol acyltransferase (ACAT)
activity and reducing sterol-regulatory element-binding
protein (SREBP)-2 in a dose-dependent manner. Reducing
LDL-C levels is the key factor to reduce the burden of
non-communicable diseases (NCDs) which include obe-
sity, diabetes and cardiovascular diseases.
A native plant of India from Acoraceae family and
widely distributed in other countries has also recently been
found to attenuate adipogenesis. e puried compound
from Acorus calamus oil was identied as β-Asarone and
it was capable to inhibit the dierentiation of 3T3-L1 adi-
pocytes and decreased the expression of PPARγ, C/EBPγ
and C/EBPβ, as well as the phosphorylation of p-ERK in
3T3-L1 cells (26).
From the database searched, only one article on
essential oil provides in vitro and in vivo ndings in
the same manuscript. e related study was conducted
by Ko and his colleagues (27) on the essential oil of the
Korean pine, Pinus koraiensis (EOPK) using in vitro
3T3-L1 cells and in vivo HFD-fed rats. In the study, they
found that EOPK markedly suppressed fat accumulation
and intracellular triglyceride. Pinus koraiensis contains
bioactive chemicals such as camphene, (+)-limonene,
α-pinene, borneol, β-pinene, 4-carene, bicyclohept-
3-ene, 3-carene, β-phellandrene, and fencyl (36). e
SEARCH ENGINE
EBSCO Discovery Service
PubMed Ovid
Original studies and review articles related to essential oils and obesity published from 2000
to 2015 (Boolean/Phrase) (52 articles in PubMed, 3,026 articles in EBSCO, 20 articles in
Ovid)
All articles concerned with keywords essential oils in the title and abstract from 2000-2015
with linked to full text, peer reviewed and available in library collection (5 articles in
PubMed, 4 original articles in EBSCO and 2 articles in Ovid )
Data tabulation
Analysis
Report preparation
Dissemination of result
All articles concerned with keywords essential oil, obesity and anti-obesity from 2000-2015
with linked to full text, peer reviewed and available in library collection only (5 articles
in PubMed, 4 original articles in EBSCO and 2 articles in Ovid)
Figure 1. PRISMA Flow diagram of the identification of literature for inclusion in this review.

4 A. A. RASHED ET AL.
Table 1.Summary of literature search on essential oils as anti-obesity agents.
No/Area Title Method Findings Conclusion Recommendation
1. Origanumvulgare and
Lippia turbinate
Chemical composition, antiox-
idant activity and anti-lipase
activity of Origanumvulgare and
Lippia turbinate essential oils.
• Two treatments (O.vulgareand
L.turbinata essential oils) x 3
repetitions. Essential oils (EO)
composition was determined by
gas–liquid chromatography and
mass spectrometry (GC-MS), total
phenol content by Folin-Ciocalteu
method, free radical scavenging
activity on 2,2-diphenyl-1-picryl-
hydrazyl radical (DPPH), antioxi-
dant activity index by RANCIMAT
(Metrohm Ltd., Herisau, Switzer-
land) and anti-lipase activities by
using Lomolino
et al. (24) method.
• The major compounds found in oregano essential
oil were c-terpinene (32.10%), α-terpinene (15.10%),
p-cymene (8.00%) and thymol (8.00%).
• In lippia essential oil, α-limonene (76.80%) and
1,8-cineole (4.95%) represented the major com-
pounds.
• Oregano essential oil had higher phenolic content
(12.47 mg/mL gallic acid) and DPPH scavenging
activity (IC50 0.357 g/mL) than lippia essential
oil (7.94 mg/mL gallic acid and IC50 0.400 g/ mL,
respectively).
• Both essential oils had similar antioxidant indexes
(about 1.2). Moreover, oregano and lippia essential
oils had also anti-lipase activity (IC50 5.09 and 7.26
g/mL).
Higher phenolic
content in the
essential oils was
related with higher
scavenging and an-
ti-lipase activities.
(chemical composition) Quiroga et al. (23) Oregano and lippia
essential oils could
be used as natural
antioxidants on
food products.
2. Anti- hyperlipidemia Essential oil of Pinuskoraiensis
leaves exerts anti-hyperlipidem-
ic eects via up-regulation of
low-density lipoprotein receptor
and inhibition of acyl-coenzyme
A: Cholesterol acyltransferase
(ACAT ). Kim et al. (25)
• Extraction of essential oil (EOPK)
by steam distillation
• Human hepatocarcinomaHepG2
cells were utilized for cytotoxicity
study
• Western blotting and reverse
transcription polymerase chain
reaction(RT-PCR)
• ACAT activity assay – a target
molecule for hyperlipidemia
treatment
• Low-density lipoprotein (LDL)
isolation and oxidation assay
• EOPK concentration up to 100 g/mL was no toxic
effect to HepG2 cells.
• EOPK up-regulated low-density lipoprotein receptor
(LDLR), implying accelerated clearance of circulating
LDL cholesterol (LDL-C)
• EOPK significantly increased the activity of LDL-ox-
idation with IC50 value of 40 g/mL (a potent ACAT
inhibitor).
EOPK can be a potent
antihyperlipidemic
agent via enhance-
ment of LDLR and
inhibition of ACAT
activity
(In vitro)
-Pinuskoraiensis
3. Inhibition of adipogen-
esis in cell culture
Inhibitory eect of β-asarone, a
component of Acoruscalamus
essential oil, on inhibition of
adipogenesis in 3T3-L1 cells.
• Isolation of β-asarone by GC
• Cytotoxicity study of 3T3-L1
cells by 3-(4,5-dimethyl-2-thi-
azolyl)-2,5-diphenyl-2Htetrazoli-
umbromide (MTT) assay
• RT-PCR for analysis of theex-
tracellular signal-regulated
kinases(ERK1/2), families of
transcription factors(C/EBPβ and
C/EBPα) and the peroxisome
proliferator-activated receptors(P-
PARγ) mRNA
• Western blot analysis with
SDS-PAGE for analysis of phos-
phor-ERK1/2, C/EBPβ, C/EBPα and
PPARγ protein.
• Calamus oil concentrations of up to 125g/mL did
not significantly influence cell viability.
• The main component of calamus oil determined
by GC/MS and GC/FID were β-asarone (56.8%),
euasarone (17.4%), cinnamaldehyde (4.7%), methyl
eugenol (3.8%), cis-methyl isoeugenol (2.5%), α-asa-
rone (2.3%) and β-caryophyllene (1.3%).
• The accumulation of lipid droplets within cells
was greatly reduced by treatment with β-asarone
compared to untreated differentiated cells and was
concentration-dependent.
• β-asarone attenuates the expression of C/EBPβ, C/
EBPα and PPARγ and the phosphorylation of ERK1/2.
β-asarone isolated
from the essential
oil of Acoruscalamus
suppresses the
differentiation of
3T3-L1 preadipo-
cytes to adipocytes
and inhibit PPARγ
expression.
Although the A. calamusrhizome
extract had significant anti
inflammatory effects in acute,
chronic, and immunologic
models of inflammation the
anti-inflammatory effects of
β-asarone treatment (0.25
mM) on adipose tissue warrant
further investigation.
(In vitro)
-Acoruscalamus Lee et al. (26)
(Continued)

JOURNAL OF ESSENTIAL OIL RESEARCH 5
No/Area Title Method Findings Conclusion Recommendation
4. Antiobesity Essential oil of Pinuskoraiensis
(EOPK) exerts antiobesic and
hypolipidemic activity via inhi-
bition of peroxisome prolifera-
tor-activated receptors gamma
signaling.
• Extraction of essential oil by
distillation
• Cell culture work for cytotoxicity
study
• Anti-obesity and hypolipidemic
mechanism of EOPK using in vitro
3T3-L1 cells and in vivo HFD-fed
rats which include RT-PCR and
Western Blotting.
• EOPK suppressed fat accumulation and intracellular
triglyceride associated with downregulation of
adipogenic transcription factor expression, including
PPARγ and CEBPα in the differentiated 3T3-L1
adipocytes.
• EOPK attenuated the expression levels of FABP and
GPDHas target genes of PPARγ during adipocyte dif-
ferentiation. Furthermore, PPARγ inhibitor GW9662
enhanced the decreased expression of FABP and
PPARγ and fat accumulation induced by EOPK.
• In vitro activity of EOPK was confirmed by in vivo
study by administering normal diet, HFD, and/or
EOPK at the dose of 100 or 200mg/kg for 6 weeks.
• EOPK significantly suppressed body weight gain,
serumtriglyceride, total cholesterol, LDL cholesterol,
and AI value and increased HDL cholesterol in a
dose-dependent manner.
• Immunohistochemistry revealed that EOPK treat-
ment abrogated the expression of PPARγ in the liver
tissue sections of EOPK-treated rats.
These findings sug-
gest that EOPK has
the antiobesic and
hypolipidemic po-
tential via inhibition
of PPARγ-related
signaling.(In vitro and in vivo) Ko et al. (27).
-Pinuskoraiensis
5. Olfactory stimulation Eect of olfactory stimula-
tion with grapefruit oil and
sibutramine in obese rats.
• Thirty female Sprague-Dawley
albino rats (120–140g) for 3
weeks. Two dietary groups; the
control (n = 6) with standard
pellets and obese group (n = 24)
with high calorie diet (chocolates
and cookies). Grp I: no treatment
(as positive control). Grp II: olfac-
tory stimulation with grapefruit
oil (3times/weekly). Grp III: oral
sibutramine. Grp IV: olfactory
stimulation with grapefruit oil and
oral sibutramine
• Determination of monoamines
neurotransmitter in brain by high
performance liquid chromatogra-
phy (HPLC).
• Grp II, III and IV decreased body weight after 2
weeks intervention. However, only Grp III and Grp IV
decreased body week at the end of week 3.
• Sibutramine significantly decreased food consump-
tion by week 2. However, no significant effect was
recorded on food consumption for all groups by
week 3 compared with the control.
Olfactory stimulation
with grapefruit oil
produced its effect
on body weight
after a lag period
of 2 weeks without
affecting food con-
sumption or brain
adrenaline
(In vivo) Farouk et al. (20).
-Citrus paradisi
(Continued)
Table 1.(Continued).

6 A. A. RASHED ET AL.
No/Area Title Method Findings Conclusion Recommendation
6. Prevent weight gain
(In vivo)
Esssential oil from Citrus auranti-
folia prevents ketotifen-induced
weight-gain in mice.
• GC-MS analysis for chemical
profile
• Fifty-six male mice weighing
at 25–30 g were selected and
divided into 7 groups for 45 days.
Control Grp I and II: normal saline
and DMSO. Grp III: ketotifen, Grp
IV, V, VI: different doses of lime
essential oil (125, 250, 500 mg/kg)
and Grp VII: a mixture of ketotifen
and lemon essential oil
• Groups treated with lime essential oil displayed a
reduction in body weight and food consumption in
mice, possibly through promoting anorexia which
might have played a role in weight loss.
• Co-administration of the lime essential oil and
ketotifen caused significant suppression in gaining
weight,as well as decreased body weights of mice.
Lime essential oil
playsan important
role in weight loss
and could be useful
in the treatment
of drug-induced
obesity and
related diseases.22
components were
identified with GC-
MS and limonene
was the highest at
28.2%.
These data suggest that lime
essential oil could play an im-
portant role in weight loss and
could be useful in the treatment
of obesity and related diseases,
as well as in preventing weight
gain side effects of a number of
drugs, e.g. ketotifen.
-Citrus aurantifolia Asnaashari et al. (28).
7. Antilipidemia and
anti-hyperglycemia
(In vivo)
Preventive and ameliorating
eects of citrus d-limonene on
dyslipidemiaand hyperglycemia
in mice with high-fat diet-in-
duced obesity.
• Mice were fed with low-fatdiet
(LFD), high-fat diet (HFD, or HFD
enriched with (+)-limonene
(0.5%w/w), for 4 weeks.
• Analysis of serum triglyceride,
total cholesterol high-density li-
poprotein cholesterol (HDL-C) and
(LDL-Cby automatic analyser.
• Blood samples were obtained
from the tail vein of each mouse
to determine theglucoselevels
• Measurement of luciferase activity.
• The gene expression levels were
analyzed byRT-PCR.
• The structure of fat tissue was
examined by scanning electron-
microscopy
• (+)-Limonene,naringeninandauraptenewerefound-
tohaveclearinhibitoryeffectson3T3-L1adipocytedif-
ferentiation.
• There was no significant difference in body weight
between(+)-limonene-fed andHFD-fedgroupsafter
treatment, showingthat(+)-limonene doesnotpre-
ventbodyweightgaining HFD-fedmice.
• (+)-Limonene decreasedserumtriglyceride(TG) by
(P < 0.01)comparedwiththecontrolHFDgroup and
obese mice respectively. However, (+)-limonene
hadnoeffectonserumTCandLDL-C,compared withthe-
HFD-fedmice and obese mice.
• The addition of(+)-limonene reducedtheincreasein-
bloodglucoselevelsby29.1%(P < 0.01)comparedwith-
theHFDgroup.
• (+)-Limonenetreatmentreducedthesizeofbothwhite-
andbrownadipocytes, comparedwiththecontrolmice,
indicatingthat (+)-limonenemayprotectagainsttheH-
FD-inducedincreaseinfatmass.
• (+)-Limonene at 50 M increased the transactivity
of PPARα by 51.2% (P < 0.05), compared with its
agonist WY-14643, indicating that (+)-limonene may
be an agonist for PPARα.
• The expression of PPARα target genes, which is
essential for cellular cholesterol homeostasis and the
development of obesity, were markedly increased by
(+)-limonene.
(+)-Limonene
protects against
the development
of dyslipidemia
and hyperglycemia
in HFD-fed mice.
In obese mice,
(+)-limonene
ameliorates insulin
resistance and
regulates lipid pro-
files. These effects
appear to bemedi-
ated through the
activation of PPARα
and the inhibition
ofLXRβ signaling.
(+)-Limonene may be used as a
potential dietary strategy for
preventing hyperlipidemia and
type 2 diabetes.
-Citrus d-limonene Jing et al. (29).
Table 1.(Continued).
(Continued)

JOURNAL OF ESSENTIAL OIL RESEARCH 7
No/Area Title Method Findings Conclusion Recommendation
8. Anti-adiposity effect
of bitter melon seed oil
(BMSO) (In vivo)
Bitter melon seed oil–attenuat-
ed body fataccumulation in
diet-induced obese mice isas-
sociated with cAMP-dependent
proteinkinase activation and cell
death in whiteadipose tissue.
• Fatty acid analysis was determined
in bitter melon powder using GC.
• Cold tolerance test and ex vivo
analysis was performed on the
mice on the day before being
killed.
• Biochemical indices were meas-
ured for lipids, cholesterol, TG,
fatty acids (FFA), leptin, insulin,
glucose and TNFα.
• Quantification of adipocytes size
and detection of apoptosis
• Immunoblotting of adipose tissue
and quantification of Abhd5,
Acaca, Acacb, Adrb3, Dgat1,
Fabp4,Fasn,Lep, Lpl, Plin1, Ppara,
Ppargcla, Ucp1, and Ucp2 mRNA
levels
• The HBM [15%soybean oil (SBO) + 15% BMSO]
group, but not the HS (high-fat diet alone; 30%SBO)
group, had a lower (P < 0.001) body fat percent-
age (21%), adipocyte size (38%), and serum leptin
concentration (42%) than the HB (high-fat diet; 29%
butter + 1% soybean oil (SBO) group.
• The anti-adiposity effect of BMSO was dose depend-
ent.
• The HBM group had lower Lep (P < 0.0001), Fasn,
and Lpl (P < 0.05) mRNA levels and higher Ucp2 (P
< 0.05) mRNA levels than the HB and HS groups,
suggesting that BMSO might exert its antiadiposity
effect byinhibiting lipogenesis in the WAT (white
adipose tissue).
This study demon-
strates the
anti-adiposity
potential of BMSO.
The reducedlipo-
genesis and
enhanced lipolysis
and thermogenesis
might contribute to
the attenuation of
body fat deposition
via cAMP-activated
protein kinase
(PKA) and leptin
activation in the
WAT of BMSO-treat-
ed mice.
The greater TNFα concentration
and thegreater number of
crown-like structure (CLS)
detected in the WAT of mice fed
the HBM diet compared with
the soybean oil-based, high-fat
diet (HS) controls indicate
the occurrence ofextensive
inflammation and cell death,
as seen in lipodystrophy.These
unexpected results highlight
the importance of evaluating-
safety issues, such as insulin
resistance, dyslipidemia, and
hepaticsteatosis, before consid-
ering BMSOsupplementation.
-Momordicacharantia Chen et al. (30)
9. Reduced weight
regain-
γ-Linolenate (GLA) reduces
weight regain in formerly obese
humans.
• Fifty formerly obese humans,
randomized double-blind study
and given either 890mg/d of GLA
(5 g/d borage oil) or 5 g/d olive oil
(controls) for 1 y.
• Body weight and composition
and adipose fatty acids of fasting
subjects were assessed at 0, 3, 12,
and 33 mo.
• Weight regain differed between the GLA (2.17 ± 1.78
kg) and control (8.78 ± 2.78 kg) groups (P < 0.03)
after 1 yr.
• Unbinding revealed weight regains of 1.8 ±1.6 kg in
the GLA group and 7.6 ± 2.1 kg in controls for the 13
and 17 subjects, respectively.
• Adipose triglyceride GLA levels increased 152% (P
< 0.0001) in the GLA group at 12 mo., but did not
increase further after 33 mo. of GLA administration.
GLA reduced weight
regain in humans
following major
weight loss, sug-
gesting a role for
essential fatty acids
in fuel partitioning
in humans prone to
obesity.
The accumulation ofGLA in body
lipid pools has the potential
for greater throughputinto ara-
chidonate (ARA) pools as well.
Because ARA has many effects,
including mediating inflamma-
tion, platelet aggregation, and
cell proliferation,more careful
studies with extended duration
of GLAsupplementation must
be done before this substance
can berecommended for treat-
ment of obesity.
-Randomized clinical trial
(RCT)
Schirmer and Phinney (31).
Table 1.(Continued).

8 A. A. RASHED ET AL.
(29). Additionally, the addition of (+)-limonene reduced
blood glucose levels by 29.1% (P < 0.01) compared with
the HFD-fed control mice. Furthermore, (+)-limonene
was found to decrease serum TG by (P < 0.01) compared
with the control HFD group and obese mice respectively.
However, (+)-limonene had no eect on serum total cho-
lesterol (TC) and LDL-C, compared with the HFD-fed
control mice and obese mice.
To date, several other plant seed oils like pomegranate
seed oil, rapeseed oil and calendula seed which contain
various compositions of fatty acids have also been shown
to reduce body fat mass when tested in animal models
(43–45). For example, bitter melon seed oil (BMSO)
(also called Momordica charantia) which is rich in cis-9,
trans-11, trans-13-conjugated linolenic acids when tested
in mice was found to increase phosphorylation of acetyl-
CoA carboxylase, cAMP-activated protein kinase (PKA),
and signal transducer and activator of transcription 3 in
white adipose tissue (WAT), suggesting that PKA and lep-
tin signaling might be involved in the BMSO-mediated
reduction of body fat deposition. e anti-adiposity
eect of BMSO was dose dependent. BMSO has also
been shown to be a potent PPARα activator, suggesting a
possibility to improve obesity-induced dyslipidemia and
hepatic steatosis.
e clinical study conducted by Schirmer and Phinney (31)
was the only RCT identied so far. In their double-blind
study, y formerly obese humans were randomized into
the treatment group who were givenγ-linolenate (GLA)
supplementation (5 g/d borage oil) and the control group
given 5 g/d olive oil (controls) for 1 year. It was found
that GLA was able to reduce weight regain in humans
following major weight loss. e essential fatty acids
available in GLA will probably help fuel partitioning in
humans prone to obesity.
Conclusion
In conclusion, based on the published articles, citrus
family was found to be the most investigated essential
oil for obesity study. A number of in vitro and in vivo
studies reported that the anti-obesity eects of essential
oils are mediated through several possible mechanism
of action that include anti-lipase activity, antihyperlipi-
demia, by down-regulating adipogenetic transcription
factors including PPARγ and CEBPα in both protein and
mRNA levels, by increasing the plasma glycerol concen-
tration (a marker of lipolysis) as well as by suppressing
fat accumulation and intracellular triglyceride. Only one
RCT study on essential oil was identied so far and these
data were not conclusive to provide evidence-based health
claim on this issue.
action found in 3T3-L1 adipocytes was associated with
down-regulation of adipogenic transcription factor
expression, including PPARγ and CEBPα in both protein
and mRNA levels which was similar that the previously
reported article on calamus oil by Lee and his colleagues
(26). EOPK signicantly reduced retroperitoneal and
epididymis fat weight compared with control rats most
probably via inhibition of lipid metabolism. Moreover, the
anti-obesity eect of essential oil has also been reported
via the down-regulation of adipogenetic transcription
factors thus inhibiting adipogenesis (27, 37, 38). It seems
that adipose tissue provides a critical link in maintaining
systemic energy balance. Adipogenesis is a mechanism
leading to high incidence of obesity and type 2 diabetes.
ere are several families of transcription factors that are
known to be linked to adipogenesis, such as the CCAAT/
enhancers-binding proteins (C/EBPs) and peroxisome
proliferator-activated receptors (PPARs) (39, 40).
In another in vivo study done by Farouk et al. (20), they
found that olfactory stimulation with scent of grapefruit
oil (SGFO) (also called Citrus paradisi)produced its eect
on body weight aer a lag period of 2 weeks without aect-
ing food consumption or brain adrenaline in rats. Prior to
that study, Tanida and his colleague (41) found that SGFO
was also responsible for increasing the plasma glycerol
concentration (a marker of lipolysis) and body tempera-
ture and decreases appetite and body weight in rats.
e eects of essential oils as an anti-obesity agent are
immensely complex. In a study done by Asnaashari et al.
(28) on essential oil from Citrus aurantifolia, the group of
mice that was treated with lime essential oil displayed a
reduction in body weight and food consumption during
the 45 days experimental period. Interestingly, lime essen-
tial oil was found to be eective in suppressing weight
gain, as well as decreasing body weight from 33 g to 23 g
in mice with in drug-induced obesity.
Citrus peel essential oils have an impressive range of
health benets. (+)-Limonene is one of the important
compounds derived from citrus peel essential oil that
has an anti-obesity property (42). (+)-Limonene has been
widely used as a avoring agent in common foods. In a
study by Jing et al. (29), (+)-limonene was reported to
have a benecial eect on hyperglycemic mice with high-
fat diet-induced (HFD) obesity. ey did a study on the
body weight gain and serum lipid levels using C57BL/6
mice. C57BL/6 mouse was used because it is the recognize
danimal model for severe obesity and diabetes if weaned
onto high-fat diets. By using a scanning electron micro-
scope (SEM), (+)-limonene has been shown to reduce
the size of both white and brown adipocytes compared
with HFD-fed control mice, indicating that (+)-limonene
may protect against the HFD-induced increase in fat mass

JOURNAL OF ESSENTIAL OIL RESEARCH 9
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Acknowledgments
e authors wish to thank the Director General of Health and
the Director of Institute for Medical Research (IMR) for giving
the permission to publish this article. We thank Dr Rohani
Ahmad, Dr Mohd Fairulnizal, Ms Fauziahand Ms Ten Sew
Keoh (IMR) for comments on the manuscript; and Dr Ami
Fazlin and Ms Siti Habsah (Globinmed Secretariat, IMR) for
their interest, cooperation and technical support.
Disclosure statement
No potential conict of interest was reported by the authors.
ORCiD
Aswir Abd Rashed http://orcid.org/0000-0002-2380-8171
Mohd Naeem Mohd Nawihttp://orcid.org/0000-0002-3391-
017X
Kasmawati Sulaimanhttp://orcid.org/0000-0003-1214-7707
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