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Updates on Antiobesity Effect of Garcinia Origin (−)-HCA

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  • Xiamen University Malaysia

Abstract and Figures

Garcinia is a plant under the family of Clusiaceae that is commonly used as a flavouring agent. Various phytochemicals including flavonoids and organic acid have been identified in this plant. Among all types of organic acids, hydroxycitric acid or more specifically (-)-hydroxycitric acid has been identified as a potential supplement for weight management and as antiobesity agent. Various in vivo studies have contributed to the understanding of the anti-obesity effects of Garcinia/hydroxycitric acid via regulation of serotonin level and glucose uptake. Besides, it also helps to enhance fat oxidation while reducing de novo lipogenesis. However, results from clinical studies showed both negative and positive antiobesity effects of Garcinia/hydroxycitric acid. This review was prepared to summarise the update of chemical constituents, significance of in vivo/clinical anti-obesity effects, and the importance of the current market potential of Garcinia/hydroxycitric acid.
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Evidence-Based Complementary and Alternative Medicine
Volume , Article ID ,  pages
http://dx.doi.org/.//
Review Article
Updates on Antiobesity Effect of Garcinia Origin ()-HCA
Li Oon Chuah,1Wan Yong Ho,2Boon Kee Beh,3and Swee Keong Yeap4
1SchoolofIndustrialTechnology,UniversityScienceMalaysia,11800Penang,Malaysia
2School of Biomedical Sciences, e University of Nottingham Malaysia Campus, Jalan Broga, 43300 Semenyih, Selangor, Malaysia
3Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia,
43400Serdang,Selangor,Malaysia
4Institute of Bioscience, University Putra Malaysia, 43300 Serdang, Selangor, Malaysia
Correspondence should be addressed to Swee Keong Yeap; skyeap@gmail.com
Received  June ; Accepted  July 
Academic Editor: Vincenzo De Feo
Copyright ©  Li Oon Chuah et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Garcinia is a plant under the family of Clusiaceae that is commonly used as a avouring agent. Various phytochemicals including
avonoids and organic acid have been identied in this plant. Among all types of organic acids, hydroxycitric acid or more
specically ()-hydroxycitric acid has been identied as a potential supplement for weight management and as antiobesity agent.
Various in vivo studies have contributed to the understanding of the anti-obesityeects of Garcinia/hydroxycitric acid via regulation
of serotonin level and glucose uptake. Besides, it also helps to enhance fat oxidation while reducing de novo lipogenesis. However,
results from clinical studies showed both negative and positive antiobesity eects of Garcinia/hydroxycitric acid. is review was
prepared to summarise the update of chemical constituents, signicance of in vivo/clinical anti-obesity eects, and the importance
of the current market potential of Garcinia/hydroxycitric acid.
1. Introduction
e world is in health transition. Infection as a major cause
of suering and death is giving way to new epidemics of
noncommunicable disorders such as cancer, cardiovascular
diseases, and diabetes, which continue to plague the world
at an alarming rate []. A trend of increasing prevalence of
obesity and obesity-related comorbidity and mortality was
observed over the last few decades []. e International
AssociationoftheStudyofObesity(IASO)reportedonthe
country rankings in terms of percentage global prevalence of
adult obesity (BMI  kg/m2) in the year of , where
Tonga ranks rst with .% obese adults (.% of obese
male and .% of obese female). In the United States,
IASOreportedthat.%ofmenand.%womenwere
obese (BMI ) [,]. Overweight and obesity are diag-
nosed zbased on the body mass index (BMI), which is dened
as quotient of body weight (kg) over the square of stature
(m2). According to the World Health Organization (WHO)
standard, overweight subjects are diagnosed with BMI values
in the range of –.. Obesity itself, dened as BMI ,
is associated with several chronic and debilitating health
problems including hyperlipidemia, hypertension, coronary
heart disease, diabetes, cancer, disease of the gall bladder,
osteoarthritis, shortage of breath, abnormal dilation of the
veins, backache, and even psychological problems [,].
ere are a few drugs in the market to ameliorate or
prevent obesity, but there are costs, ecacy, and side eects
to be considered. For example, the currently available phar-
macological agents, Sibutramine, Rimonabant, Orlistat, and
Phentermine which are licensed for weight reduction therapy,
appear to possess some adverse eects []. Phentermine,
for instance, has been reported to cause dry mouth, insomnia,
headache, dizziness, fatigue, and palpitation [,]. In year
,FDAhadannouncedthemarketwithdrawalofMeridia
(Sibutramine) due to its risk of serious cardiovascular events
[,]. Natural products and plant-based dietary supplements
have been used by people for centuries. Evidence is starting
to emerge to shed light on the consumption of herbs as
an eective strategy for disease treatment and health main-
tenance. Several ethnobotanical studies have reported the
bioprospecting surveys on the positive application of herbs
Evidence-Based Complementary and Alternative Medicine
T : Comparison of G. cambogia,G. atroviridis,andG. indica [,,,].
Species Common name Origin Feature
G. cambogia Asam Gelugor
India: found commonly in the evergreen
forests of Western Ghats, from Konkan
southward to Travancore, and in the
Shola forests of Nilgiri.
Small- or medium-sized tree with a rounded crown and
horizontal or drooping branches, under the family of
Guttiferae. Its fruits are ovoid, about  cm in diameter, yellow
or red when ripe with six to eight grooves, enclosing six to
eight seeds, and are edible.
G. atroviridis Asam Gelugor Southeast Asia
Small- or medium-sized fruit tree, with drooping branches
and ovoid fruits. e fruits are bright orange-yellow when
ripe, globose with – grooves, about – cm in diameter,
and uted with a rmly textured outer rind and a rather thin
and translucent pulp surrounding the seeds.
G. indica Kokum
India: the tropical rain forests of Western
Ghats, from Konkan southward to
Mysore,Coorg,andWayanad
Slender evergreen tree with drooping branches. Its fruits are
globose or spherical, – cm in diameter, dark purple when
ripe with ve to eight large seeds surrounded.
in the treatments for obesity []. Garcinia has been used
for centuries in Asian countries for culinary purposes as a
condiment and avoring agent in place of tamarind or lemon
andtomakemealsmorelling[,]. Besides its use as a
avouring agent, the dried rind of G. cambogia combined
with salt and other organic acids can help to lower the
pH and thus provides a bacteriostatic eect in curing sh.
G. cambogia contains large amounts of hydroxycitric acid
(HCA). Similar to G. cambogia,G. atroviridis and G. indica
also contain signicant HCA content and are sometimes
used interchangeably with G. cambogia in food preparation.
e dierent features among these three dierent types of
Garcinia are summarised in Table  [,].
AmyriadofhealtheectshavebeenattributedtoGarci-
nia (including G.cambogia,G.atroviridis,andG. indica),
such as antiobesity eects [], antiulcerogenic [],
antioxidative [], antidiabetes [], antimicrobial [,
], antifungal [], anti-inammatory [,], and
anticancer eects [,]. In particular, the antiobesity
eects of Garcinia or more specically of its HCA content
have been elucidated with unprecedented clarity over the last
few decades. Besides its ecacy in the reduction of body
weight and food intake, Garcinia/HCA has been proven to
be benecial in ameliorating obesity-related complications
such as inammation, oxidative stress, and insulin resistance
[]. e results obtained from several studies supported the
positive eects of HCA administration alone or in combina-
tion with other ingredients on body weight loss, reduced food
intake, increased fat oxidation, or energy expenditure (EE)
[,,] whereas some studies did not [].
In spite of the vastly reported prominent role of HCA
in inducing satiety, reduced energy intake and weight gain,
and improved blood parameters and substrate oxidation,
controversial results regarding its ecacy and safety as
an antiobesity dietary supplement had also been reported.
Evidence from the in vitro,in vivo, and clinical trials on
the safety of Garcinia/HCA as a dietary supplement for
treating obesity had been extensively reviewed []. However,
the ecacy of Garcinia/HCA remains the subject of debate.
Despite the previously stated issues, on conclusive evidence
for HCA’s ecacy in promoting weight loss and suppressing
food intake, the marketing of a plethora of over-the-counter
slimming aids containing HCA has taken place. e aim of
this review is to critically assess the evidence from a very
broad range of reports, rigorous clinical trials, systematic
reviews, and meta-analyses on the ecacy and potential of
Garcinia/HCA as an antiobesity dietary supplement.
2. Uses in Traditional Medical Systems
Botanical dietary supplements usually contain a complex
mixture of phytochemicals which have additive or synergistic
interactions. Aside from its use as a preservative and as a
condiment in cuisine, Garcinia extracthasbeenusedinthe
traditional Ayurvedic medical system [,]. A decoction of
G. cambogia is given as purgative in the treatment of intestinal
worms and other parasites, for bilious digestive conditions,
for dysentery, rheumatism, and in the treatment of tumours.
Less commonly, extracts are employed as cardiotonics to treat
angina. In veterinary medicine, it is used as a rinse for diseases
of the mouth in cattle [,]. e fruit rind is used in rickets
and enlargement of spleen and to heal bone fractures []. In
Southeast Asian folkloric medicine, a decoction of G. atro-
viridis (leaves and roots) is sometimes used for the treatment
of cough, dandru, earache, stomach pains associated with
pregnancy, and throat irritation []. e dried fruit of G.
atroviridis is used for improving blood circulation, for the
treatment of coughs, as a laxative, and as a expectorant. e
fruit is used in a lotion with vinegar to rub over the abdomen
of women aer connement []. Fruit of G. indica is antiscor-
butic, cholagogue, cooling, antibilious, emollient, and demul-
cent. e anthelmintic properties of the fruit of G. indica
contributedtoitsuseinhaemorrhoids,dysentery,tumor,
pains, and heart complaints. Bilious aected sites are treated
with syrup from the fruit juice. Kokum butter is astringent
and demulcent and is used in diarrhea and dysentery. It is also
applied externally for ulcerations, sinuses, ssures of hand,
lip, chapped skin, and skin diseases [,,,].
3. Phytoconstituents
e several compounds which have been isolated from
various species of Garcinia aresummarisedinTab l e .Several
Evidence-Based Complementary and Alternative Medicine
T : Phytochemicals of Garcinia.
Phytochemicals G. cambogia G. indica G. atroviridis
Organic acids
()-HCA Fruit rind [,]Fruitrind[]Fruitrind[]
Citric acid Fruit rind []Leave and fruit rind
[]
Herbal products
[]
Tartaric acid []nd []nd Herbal products
[]
Malic acid Fruit rind [][]nd Herbal products
[]
Succinic acid []nd
Prenylated benzoquinone
Atrovirinone Root []
Prenylated depsidone
Atrovirisidone Root []
Atrovirisidone B Root []
Prenylated hydroquinone
-Methylhydroatrovirinone Root []
,-cis-Docosenoic acid Root []
-cis-Docosenoic acid Root []
Flavonoid
Morelloavone Root []
Fukugiside Root []
Naringenin Root []
,󸀠󸀠-Binaringenin Root []
Xanthone
Garbogiol Root []— —
Rheediaxanthone A Bark []— —
Dioxygenated xanthone
,-Dihydroxyxanthone Heartwood []—
Te tr a o x y ge n a te d x a nt h o ne
Atroviridin Stem bark []
Tetrac y c l i c x a n t h o n e
Oxyguttiferone K Fruit []— —
Polyisoprenylated benzophenone
Garcinol/camboginol (enantiomer of xanthochymol)
Fruit rinds
[,]
Latex []
Bark []
[]nd
Fruit rinds []
Isogarcinol/cambogin (enantiomer of isoxanthohumol ) Latex []
Bark []Fruit rinds []—
Isoxanthohumol Fruit rinds [][]nd
Guttiferone I Fruit []—
Guttiferone J Fruit []—
Guttiferone K Fruit []—
Guttiferone M Fruit []—
Guttiferone N Fruit []—
nd: none detected; —: not reported.
Evidence-Based Complementary and Alternative Medicine
Antiobesity
Weight management
Serotonin regulation
Food intake suppression
De novo lipogenesis
Fat oxidation
Citrate to oxaloacetate
and acetyl-CoA
Fatty acid and
cholesterol
biosynthesis
Glycogen
synthesis
Serotonin
Fatty acids supply
Insulin, leptin
Glucose intake
Carbohydrate
oxidation
EE
-workout (YES);
resting ??
RER (YES);
RQ ??
aecting adipose conversion
Appetit e
A
B
C
D
and
Garcinia/HCA
OH
OH
OHO
O
O
HO
HO
F : Possible multiple mechanisms that contribute to antiobesity eect of Garcinia/HCA. indicated increase or stimulation; indicated
reduce or inhibition while ?? indicated that the eect is yet to be conrmed. (A) summary of Serotonin regulation and food intake suppression;
(B) summary of reduction of de novo lipogenesis; (C) summary of stimulation on fat oxidation; (D) summary of reduce on glucose intake;
(A) and (B) contribute to the weight management eect of Garcinia/HCA while (B) and (C) contribute to antiobesity of Garcinia/HCA.
types of organic acids such as HCA, citric, tartaric, malic,
andsuccinicacidsareisolatedfromGarcinia.However,
HCA is the principal acid of the fruit rinds of G. cambogia,
G. indica, and G. atroviridis [,,], with its content
ascending as listed []. A substantial amount of ()-
HCA, up to % by weight is present in the pericarp
of the fruit of G. cambogia. In similar studies conducted
by Sullivan et al. [,]andStallingsetal.[], they
observed that of the four isomers of HCA [(–)-HCA, (+)-
HCA, (–)-allo-HCA, and (+)-allo-HCA], ()-HCA, which is
also known as (S, S)-HCA, was the only potent inhibitor
of ATP citrate lyase. ()-HCA can be chemically synthe-
sized using citric acid as starting material. Synthetic ()-
HCA oers several advantages including higher purity and
lactone stable as compared to natural ()-HCA []. On
the other hand, ()-HCA is a good starting material to
synthesize other important chiral synthons and compounds
[].
()-HCA is one of the important supplements for anti-
obesity and weight management. Its eect on weight man-
agement is mainly contributed by giving the feeling of full
and satisfaction while the antiobesity eect is by reduction
of de novo lipogenesis and acceleration of fat oxidation
(Figure ). In this paper, we aimed to review the mechanism
for antiobesity and weight management eects by ()-HCA
(hereaer referred to as HCA)/G. cambogia/G. atroviridis/G.
indica extracts and the assessment of these eects in the
clinical settings.
4. Salts of HCA
Onaccounttothediscoveryof()-HCA as an eective
compound in weight management, market demand for the
acid has increased tremendously. e commercially available
G. cambogia extracts which contain approximately % ()-
HCA are prepared from the fruit rind [,]. HCA can exist
as a free acid or in the lactone form. e former form is
considered to be biologically active. However, the free acid
is unstable and is usually converted to its less active lactone
form to attain higher stability. To prevent the cyclization of
HCA into its less potent lactone, the acid has been combined
with various counter ions to form stable salts [].
Commercial HCA is available in free acid form and as
single, double, or triple salts. Preparations with dierent
counter ions contribute to dierent degree of solubility as
well as bioavailability []. For example, Na+salt of HCA had
beenshowntobemoreeectivethanitslactoneininhibiting
lipogenesis. However, Na+salt is highly hygroscopic when
bound to ()-HCA, which would deemed unfavorable for the
production of pharmaceuticals for dry delivery [].
To address the need to achieve higher solubility and
stability, recent approaches have been focused more on the
preparation of ()-HCAintheformofadoubleortriple
salt. Similar to its single salts, these double or triple salts also
serve as good supply for essential ions []. A remarkable
example of these would be the Ca2+/K+salt of ()-HCA
(HCA-SX) or Super CitriMax. In contrast to the single salts,
Evidence-Based Complementary and Alternative Medicine
HCA-SX is completely soluble in water and thus confers
higher bioavailability []. A number of studies on the safety
of HCA-SX had been reported []. Daily intake of HCA-
SX at this dosage was shown to be eective in reducing
body weight and BMI of healthy and obese adults aer
clinical trials of  weeks [,]. Gene expression studies
also provided additional evidence for the safety of HCA-SX,
where genes essential for mitochondrial/nuclear proteins and
for fundamental support of adipose tissue were shown to be
independent of the regulation by HCA-SX [,].
A typical reduction of food appetite and an increased
serotonin availability were observed in all the weight control
studies of HCA-SX on both animal and human subjects.
ese were associated with reduced levels of total cholesterol,
LDL, triglycerides, and serum leptin as well as increased
HDL level and urinary excretion of fat metabolites [,,
,,]. In rats, the salt also caused downregulation of
genes encoding abdominal fat leptin while expressions of the
plasma leptin genes remained unaltered []. Nevertheless, it
was postulated that a set of obesity regulatory genes []and
inhibition to the uptake of [3H]--HT release in the brain []
areinvolvedintheappetitesuppressingactivityofHCA-SX.
In relation to this, gene expression proling carried
out by a research group demonstrated the modulation of
a specic set of genes (about % of  genes and ESTs)
in the adipocytes by dietary HCA-SX supplementation [].
Further study on cultured mature human adipocytes revealed
signicant upregulation of  and downregulation of 
the fat- and obesity-related genes []. Notably also in the
microarray analyses, HCA-SX demonstrated a distinct eect
on appetite suppression whereby genes encoding serotonin
receptors were shown to be selectively upregulated by the
salt []. Besides, HCA-SX was also found to be capable
of activating hypoxia inducible factor (HIF), a transcription
factor involved in energy metabolism []andrestored
the increase in oxidative stress, inammation, and insulin
resistance in obese Zucker rats [].
5. Antiobesity Effects of Garcinia/HCA
Obesity, particularly caused by accumulation of visceral fat, is
a serious risk factor of various life-style diseases such as coro-
nary heart disease, diabetes, hyperlipidemia, hypertension,
and cancer [,]. Human obesity is inuenced by genetic
and environmental factors and particularly by changes in diet
and physical activity, which contributes greatly to the devel-
opment of insulin resistance, a most common underlying
abnormality in human obesity []. Studies on food sources
exerting antiobesity eects have focused on the development
of herbal extracts or functional food which can suppress the
accumulation of body fat. Several studies were conducted to
provide scientic basis on the extensive usage of G. cambogia
and G. atroviridis associated with high-fat diet- (HFD-
) induced obesity where dyslipidemia, fatty liver, insulin
resistance, and hyperleptinemia were acquired along with the
overexpression of leptin, TNF-𝛼,resistin,PPAR𝛾, C/EBP𝛼,
and SREBPc genes in epididymal adipose tissue. e eect
of G. cambogia waslargelyattributedtoitsHCAcontent
[,]. Subsequent researches proved that the antiobesity
eects of G. cambogia/HCA resulted from the combined
actions of several mechanisms including suppressing de novo
fatty acid biosynthesis and appetite [,] and increasing
energy expenditure [], subsequently reducing body fat
accumulation and weight gain in experimental animals [,
,]. In this review, we arranged the antiobesity eects of
Garcinia/HCAbasedontheirdistinctmechanisms:()sero-
tonin regulation and food intake suppression, () decreased
de novo lipogenesis, () increased fat oxidation, and ()
downregulation of a spectrum of obesity-associated genes.
5.1. Serotonin (5-Hydroxytryptamine, 5-HT) Regulation and
Food Intake Suppression. HCA, the primary acid in the fruit
rinds of G. cambogia,G. atroviridis,andG. indica [], has
been reported as the active ingredient in inhibiting ATP
citrate lyase (EC ...) [,]. ATP citrate lyase, which
is an extramitochondrial enzyme catalyzing the cleavage of
citrate to oxaloacetate and acetyl-CoA, was inhibited by
HCA. us, the availability of two-carbon units required for
the initial steps of fatty acid and cholesterol biosynthesis
during carbohydrate feeding was limited [,,]. As a
result, the consumed carbon source was diverted to glycogen
synthesis in liver. A signal was then sent to the brain due to
this metabolic alteration, resulting in rising of serotonin level
concomitant with a reduced appetite. HCA might exhibite
its anorectic eect by a second possible mechanism, namely,
reducing acetyl CoA, subsequently decreasing malonyl CoA
levels and thereby reducing negative feedback on carnitine
acyltransferase (CPT-). e substrate of CPT-, long-chain
acyl CoA(s), may act as a mediator(s) of appetite [,
]. More recently, neuropeptide Y (NPY) had also been
implicated in the appetite suppression of HCA. Basal concen-
tration of the neurotransmitter was claimed to be signicantly
reduced in the hypothalamic tissues as a result of supplemen-
tation with HCA-SX []. However, the role of NPY in this
is still vague to date. Several reports supported the serotonin
regulation of HCA. Ohia et al. [] demonstrated that HCA-
SX enhanced serotonin availability in isolated rat brain cortex
by acting as a mild serotonin receptor reuptake inhibitor
(SRRI), without stimulating the central nervous system. Kaur
and Kulkarni [] conducted a study to elucidate the eect
of OB-G, a polyherbal preparation containing aqueous
extracts of G. cambogia,Gymnema sylvestre,Zingiber oci-
nale,Piper longum, and resin from Commiphora mukul on the
modulation of food intake by serotonin modulators in female
mice. e results obtained were compared with uoxetine, a
drug that was reported to enhance -HT neurotransmission
[]. Both OB-G and uoxetine signicantly (𝑃 < 0.05)
antagonized the hyperphagic eect of p-chlorophenylalanine
(PCPA), -hydroxy--(di-N-propylamino)-Tetralin (-OH-
DPAT), cyproheptadine, and -deoxy-D-glucose (-DG)
which further instigate possible serotonergic involvement in
the eects of OB-G on food intake in female mice. Preuss
et al. []reportedthatHCAcausedasignicantreduction
in appetite, weight loss, and plasma leptin level, concomitant
with an increase in the serum serotonin level and a favorable
lipid prole in human clinical trials. Similar results were also
obtained in a study conducted by Asghar et al. []ey
reported on increased brain serotonin level in obese Zucker
Evidence-Based Complementary and Alternative Medicine
rats receiving G. cambogia extract, suggesting that the ability
of HCA in body weight gain reduction was most probably
due to its combined eects on the metabolic and serotonin
pathways. In addition, Roy et al. []reportedthatHCA-
SX supplementation upregulated prostaglandin D synthase
(PDS), aldolase B (AldB), and lipocalin (LCN) genes in
abdominal fat tissue. Further mapping of the candidate genes
of known pathways associated with fat metabolism by using
functional categorization and pathway construction soware
showed that supplementation of HCA-SX targeted on the
serotonin receptor.
Leonhardt et al. []reportedthatHCAreducedbody
weight regain in rats aer a period of substantial body
weight loss. Besides, HCA temporarily reduced food intake
of rats with diets of varying nutrient contents (grounded
standard rat chow, high glucose, and high glucose + fat).
HCA supplementation caused pronounce suppression of
food intake during the entire  days of ad libitum feeding
period in rats fed with high glucose + fat diet, a diet that had
anutritionallyrelevantlevelofdietaryfat(%ofenergy).
ese data therefore extended those of the previous studies
whichreportedontheanorecticeectsofHCA[,,
]. Moreover, the results obtained were consistent with
studies which reported on particularly strong food intake
suppression by HCA with high glucose + fat diet and a smaller
but still signicant suppression with the high glucose diet in
other rat models and in dierent orders [,,]. Hence,
the feed conversion eciency [cumulative body weight regain
(g)/cumulative food intake (MJ)] in the high glucose and
high glucose + fat groups during the  ad libitum days
was reduced, which indirectly supported that HCA increased
energy expenditure in these groups.
Leonhardt and Langhans [] then extended their study
on the long-term eects of HCA on body weight regain and
food intake, as well as the eects of HCA on the circadian
distribution of food intake and on meal patterns during
the dark and light phases. HCA administration signicantly
reduced the food intake of rats fed with % fat diet, but
not % fat diet, concomitant with signicant reduction in
weight regain (overall 𝑃 < 0.01)inbothgroups.Inthestudy,
the rats underwent restrictive feeding for  days prior to
ad libitum feeding (Experiment : normal % fat diet and
% fat diet + % HCA; Experiment : normal % fat diet
and % fat diet + % HCA). e control groups of both
experiments had compensated the body weight loss, whereas
the HCA-fed rats groups regained only 68 ± 4% (% fat diet)
and 61 ± 8% (% fat diet) of the body weight regained by
their respective control groups aer  days of such ad libitum
feeding. Despite signicant reduction in weight regain in
rats fed with % and % fat diet, long-term suppression
of HCA on food intake was only detected in combination
with % fat diet (Experiment ). is was in line with the
results obtained by Leonhardt et al. []whosuggestedthat
HCA increased energy expenditure. Studies on the eects of
HCA on the circadian distribution of food intake and on
meal patterns showed that the suppression of food intake
occurred predominantly during the dark phase of the rst
ad libitum days. However later on, HCA suppression of food
intake was more eective during the light phase. Further
experiments elucidating the eects of HCA in combination
with the % fat diet on meal size and meal number during
the light phase revealed that HCA markedly reduced the
meal number, but not the meal size. HCA did not aect
any metabolic variables tested (plasma glucose, lactate, tri-
acylglycerol,HDL,freefattyacids,𝛽-hydroxybutyrate, and
insulin, hepatic fact, and glycogen concentrations) in both
experiments, except decreasing plasma triacylglycerol levels
and increasing the liver fat concentration in Experiment 
(rats fed with % fat diet). e fact that HCA did not aect
plasma 𝛽-hydroxybutyrate (BHB) levels did not support the
hypothesis that HCA suppressed food intake via increased
hepatic fatty acid oxidation.
However, contradicting results were obtained by Kovacs
et al. [,] who reported that two-week supplementation
with HCA and HCA combined with medium-chain triglyc-
erides did not result in increased satiety. e ndings were
in line with previous reports where no signicant treatment
eects were observed on appetite indices (inclusive of mean,
peak or nadir hunger ratings, mean ratings of desire to eat,
prospective consumption, fullness or sensations of thirst,
stomach growling, headache, distraction, irritability, or, as a
check on malingering, itchiness) []. e lack of ecacy and
transient food intake suppression by HCA raised questions
about its clinical signicance. While negative ndings are
always open to methodological questions, several questions
need to be answered before drawing a denite conclusion.
First, the diet administered to the subjects should not
promote extreme sensations in the evaluation of the food
intake suppression eects of HCA under conditions of energy
restriction. However, Mattes and Bormann imposed mild
restrictionsandthusruledoutthispossibilityasevidenced
by ratings falling in the middle range of the response
scales. Second, an energy-restricted diet would prevent the
required enzyme alterations (reduction of acetyl-CoA and
suppression of formation of carnitine palmitoyltransferase I
inhibitor malonyl CoA) which altered substrate metabolism
and satiety. However, it was unlikely that the moderate energy
restricted diet prescribed in the study conducted by Mattes
and Bormann [] hindered the satiety eect of HCA as it
still contained at least % of energy from fat.
Several factors might contribute to the controversial
results of the ecacy of HCA in human studies. One of
contributingfactorsisthehighlyvariabledosesusedinthe
human trials which ranged from  to  mg/kg of HCA
per day [,]. Besides, the discrepancy might also be
due to the dierences in the preparation or extraction of
HCA. For instance, the extraction method might increase the
formation of HCA in a lactone form, which is less potent
in the inhibition of ATP citrate lyase [,]. In order to
prevent the cyclization of HCA into the less potent lactone
form, preparation using dierent counte rions (such as
potassium, sodium, or calcium) had been applied [], which
contributed to the dierent degrees of stability, bioavailability,
or solubility of HCA []. In this respect, Louter-Van De Haar
et al. []conductedastudyontheecacyofthreecommer-
cially available HCA products on suppression of food intake
in male Wistar rats. Many human studies which reported
lack of ecacy used Super CitriMax at considerably lower
Evidence-Based Complementary and Alternative Medicine
doses [,,]. On the contrary, Preuss et al. []reported
that high doses of Super CitriMax exerted signicant eects
in human. us, Louter-Van De Haar et al. []suggested
that the reported lack of ecacy of HCA in suppressing food
intake in human subjects might be due to the low doses
of a relatively low-eective HCA preparation. Nevertheless,
signicant suppression of food intake was observed in the
studies conducted by Leonhardt and Langhans []where
Sprague-Dawley rats were supplemented with HCA for 
days aer substantial, fasting-induced weight loss. It seemed
that HCA might be more eective in regulating weight gain
than promoting weight loss; thus it was more useful for weight
maintenance aer an initial loss [,]. Hence, dierences
in the experimental setups such as the dierence in rat strains
could contribute to such discrepancy.
5.2. Decreased De Novo Lipogenesis. e reduction of the
acetyl-CoA by HCA and thus limiting the availability of
building blocks required for fatty acid and cholesterol biosyn-
thesis has led to suggestions that HCA inhibited lipogenesis.
Several studies conducted by Sullivan and colleagues had
conrmed the inhibition of in vivo and in vitro rates of lipoge-
nesis in several tissues reported to convert carbohydrate into
fatty acids (such as liver, adipose tissue, and small intestine),
in which HCA was predominantly given to rodent models
[,,,,,]. Lowenstein [] demonstrated that
HCA greatly inhibited in vivo fatty acid synthesis in rat liver.
e rats were placed on chow diet for – days, followed by
 h of fasting prior to a scheduled diet high in fructose or
glucose for  to  days. e sodium salt of HCA at dose levels
of  to  mM was administered by intraperitoneal injections
 min before injection of 3H2O. Fatty acid biosynthesis in
rat liver (𝜇moles 3H2O incorporated/g liver/h) was measured
.– h aer starting of the nal feeding. Profound decrease
in fatty acid synthesis by  to  days was obtained with
an intraperitoneal dose of . mmole per kg of body weight
(equivalent to approximately .mg of HCA per  g rat). In
addition, % of inhibition was detected at a dose level of .
mmole per kg body weight.
It was reported that G. cambogia/HCA aected respira-
tory quotient (RQ) and EE in rats and human. Lim et al.
[,] showed that short-term administration of HCA
decreased the RQ in athletes and in untrained women. Leon-
hardt et al. [] further extended their study to determine
the eect of HCA on RQ and EE in rats fed ad libitum aer
a period of substantial weight loss. ey reported that HCA
markedly decreased RQ and EE during the rst two days of ad
libitum, reecting suppression of de novo lipogenesis in rats,
which is consistent with the ndings of Westerterp-Plantenga
and Kovacs []inhumans.
In this respect, Kovacs and Westerterp-Plantenga []
further extended their study where the eects of HCA
on net fat synthesis as de novo lipogenesis were investi-
gated. A double-blind, placebo-controlled, randomized, and
crossover design experiment was conducted on  sedentary
male subjects. e subjects performed glycogen depletion
exercise, followed by a -day high-fat low-carbohydrate
(F/CHO/P, //% energy; % of EE; depletion period)
intake in order to create a similar glycogen storage capacity.
Subsequently, a -day high-carbohydrate diet (F/CHO/P,
</>/% energy; –% of EE; overfeeding period)
supplemented with either  mg of regulator HCA (HOB
Ireland Ltd.) or placebo was administered. Each intervention
ended with a  h stay in the respiratory chamber (days  and
). De novo lipogenesis occurred as indicated by RQ >. in
all subjects. Signicantly, lower  h EE (𝑃 < 0.05;onday),
resting metabolic rate (𝑃 < 0.01;onday),andRQatnight
(𝑃 < 0.05; on day ) were detected with HCA as compared
to placebo. Fat balance and thus net fat synthesis as de novo
lipogenesis tended to be lower (𝑃 < 0.1)withHCAascom-
pared to placebo. Taken all together, Kovacs and Westerterp-
Plantenga concluded that the administration of HCA during
overfeeding of carbohydrates may reduce de novo lipogenesis.
However, opinions dier widely with respect to this issue.
e mechanism underlying the anorectic eect of HCA is
still unclear. Furthermore, whether the suppression of body
weight regained was solely due to reduced food intake or
whether there was involvement of increased EE remained
unknown. Contradictory results were reported on the eects
of HCA on EE. Previous reports by Leonhardt and colleagues
[,] and the results obtained in pair-feeding studies
[] showed reduction of body weight regain and energy
conversion ratio by HCA supporting the nding that HCA
increased EE. However, reduced energy conversion ratio
could be due to decreased nutrient absorption. Vasselli et al.
[] demonstrated an increment in h EE in rats fed with
mixedhigh-carbohydratedietadlibitumbydirectlymeasur-
ing the EE in a whole-body respirometer, albeit no eect on
the RQ was detected. Another study conducted by Leray et
al. [] reported that  months of HCA administration did
not aected EE in adult neutered cats. Besides, most human
studies [,,] reported that HCA had no eect on EE.
Kriketos et al. [] reported that HCA administration exhib-
ited no eect on lipid oxidation in men during either rest or
moderately intense exercise on a cycle ergometer. However,
in these studies, the subjects received a much smaller dose,
namely, a daily dose of . g per subject [nearly equal to
. mg/day/mouse]. Furthermore, their experimental period
of  days was quite short when compared with other studies.
Blunden []reportedthatwhenGarcinia extract and
insulin were added simultaneously, the number of larger
droplets markedly decreased while the smaller droplets (–
 𝜇m2or < 𝜇m2) increased in T-L cell. e activity
of cytosolic glycerophosphate dehydrogenase (GPDH) which
converts dihydroxyacetne phosphate to glycerol -phosphate
(predominant substrate for triglyceride synthesis) increased
from undetectable levels to between  and  U/mg of
cytosolic protein aer adipose conversion. However, no
signicant decrease in enzymatic activity was detected aer
administration of the Garcinia extract. Taken together, the
authors therefore suggested that Garcinia extract interferes
with lipid synthesis in fat cells via fatty acid supply inhibition
without aecting adipose conversion.
5.3. Increased Fat Oxidation. Ishihara et al. []conducted
a study on acute and chronic eects of HCA on energy
metabolism. Acute administration of  mg/ 𝜇Lofa
. mol/L HCA solution per mice signicantly increased
Evidence-Based Complementary and Alternative Medicine
(𝑃 < 0.05) serum free fatty acid levels and concentration of
glycogen in the gastrocnemius muscle, even though the
respiratory exchange ratio was not dierent from that in
the control group. On the other hand, chronic adminis-
tration of  mg HCA twice a day signicantly lowered
(𝑃 < 0.01) the RQ during resting and exercising conditions
in mice. Lipid oxidation, calculated from RQ, and oxygen
consumption were signicantly enhanced, and carbohydrate
oxidation was signicantly less in these mice during the
early stages of running (𝑃 < 0.01). Taken all together, the
authors therefore suggested that chronic administration of
HCA augmented the endurance exercise performance in
mice via the attenuation of glycogen consumption caused by
the promotion of lipid oxidation during running exercise.
Furthermore, Ishihara et al. []suggestedthatchronicHCA
administration might have increased EE during the -week
experimental period.
In addition, Lim et al. [,] also showed that short-
term administration of HCA increased fat oxidation during
exercise in athletes and in untrained women. Lim et al. []
conducted a randomized, placebo-controlled study where
subjects (athletes) consumed HCA ( mg) or placebo for
 days, aer each time performing cycle ergometer exercise
at % VO2maxforminfollowedby%VO
2max until
exhaustion. e results obtained showed that the respiratory
exchange ratio (RER) was signicantly lower in the HCA trial
than in the control trial (𝑃 < 0.05). Fat oxidation was sig-
nicantly increased by short-term administration of HCA,
and carbohydrate oxidation was signicantly decreased (𝑃<
0.05) during exercise in athletes. In a continuation of their
study, Lim et al. []conductedasimilarstudytoevaluate
the eects of HCA administration on fat oxidation during
exercise in untrained women. e results showed that HCA
decreased the RER and carbohydrate oxidation during  hour
of exercise. In addition, exercise time to exhaustion was
signicantly enhanced (𝑃 < 0.05).
A more recent approach for determining fat metabolism
by HCA was conducted by measuring urinary concentration
of malondialdehyde (MDA), acetaldehyde (ACT), formalde-
hyde (FA), and acetone (ACON) of the tested subjects. e
urinary excretion of these four metabolites was proposed
to be a consequence of enhanced 𝛽-oxidation of fats in
body tissues []. e eect of HCA-SX had been studied
extensively by Preuss et al. on obese human subjects [,]
as well as on male and female Sprague-Dawley rats. In the
randomized, double-blind, and placebo-controlled clinical
studies on obese human, a group of subjects were given
, mg of HCA-SX daily (provided , mg HCA/day)
while the other given a combination of HCA-SX , mg,
 mg of niacin-bound chromium (NBC), and  mg of
gymnema sylvestre extract (GSE) daily. e control group
received placebo in  equal doses daily at  to min before
meals. In the trial involving  subjects, urinary excretion
of fat metabolites was increased by approximately –%
whereas in trial involving  and  obese subjects, the
metabolite excretion increased by about .–.% []and
–% [], respectively. As excretion of fat metabolites
was enhanced in groups receiving the combination formula,
it was also suggested that HCS-SX, either alone or in
combination with NBC and GSE, could eectively promote
breakdown of fats [,].
5.4. Downregulation of a Spectrum of Obesity-Associated
Genes. Lipogenic transcription factors, including SREBPc,
liver X receptors, PPAR𝛾,andC/EBP𝛼, are highly expressed
in the adipose tissue and actively participate in the lipid
metabolism of adipocytes by coordinating lipogenic and
adipocyte-specic gene expression []. PPAR𝛾interacts
with several other transcription factors. C/EBP𝛼and PPAR𝛾
interact via a positive feedback loop in the dierentiated
adipocytes, to induce each other’s expression []. Besides,
coexpression of PPAR𝛾with SREBPc increases the transcrip-
tional activity of PPAR𝛾[]. aP (a marker of terminal
adipocyte dierentiation), together with several adipocyte-
specic genes, including adiponectin, insulin receptor, leptin,
glucose transporter  (GLUT), and glycerol phosphate
dehydrogenase, are induced during the adipogenic dier-
entiation process []. Leptin, a -amino acid hormone
and a biomarker of the obesity regulatory gene, is produced
by fat tissue and is known to regulate energy intake and
metabolism. Leptin binds to the medial nucleus of the
hypothalamus and induces a sensation of satiety and thus
controlling the appetite [,,].
Fatty acid synthase, acetyl-CoA carboxylase , and
SREBPc mRNA concentrations were decreased in the adi-
pose tissue of the obese animal models []. On the con-
trary, the mRNA and protein expression of TNF𝛼(which
is involved in proinammation, apoptosis, lipid metabolism,
andinsulinresistance)wereincreasedintheadiposetissues
of the obese rodents and humans []. A high level of TNF𝛼
suppressed transcription factors such as PPAR𝛾and C/EBP𝛼
which, in turn, activated the GLUT gene [,].
Hayamizu et al. []evaluatedtheeectsofG. cambogia
fruit rind extract containing % (–)-HCA on serum leptin
and insulin in mice. G. cambogia extract reduced serum total
cholesterol, triacylglycerol, and nonesteried fatty acids in
mice. Nevertheless, the body weight gain and fat pad weight
were not aected in the treatment. No signicant dierence
in blood glucose level was detected between groups, but a sig-
nicant reduction of serum insulin (𝑃 < 0.05) was detected,
suggesting that the G. cambogia extract eciently improved
glucose metabolism in the treated animals. In addition, the
treatment decreased serum leptin levels and the leptin/WAT
ratio. Besides, the changed ratio of body weight correlated
positively with leptin levels in their study. Furthermore, it had
been reported that leptin suppressed the signal transduction
of insulin via cytokine interactions [,]. Hayamizu et al.
[] suggested that the observed eect of G. cambogia extract
on serum insulin in their study occurred through leptin-like
activity.
e antiobesity eects of Garcinia on visceral fat mass,
lipid proles in the serum and liver, serum adipocytokine
levels, and regulation of the expression of multiple adipose
tissue genes were reviewed. Kim et al. []reportedthe
antiobesity eects of a mixture composed of aqueous extract
of G. cambogia, soy peptide, and L-carnitine (.:.:.,
w/w/w) on rats rendered obese by high-fat diet (HFD).
An HFD (% fat calories) with identical composition of
Evidence-Based Complementary and Alternative Medicine
T : Summary of clinical studies of Garcinia/HCA that have shown signicant antiobesity eect.
Duration Subject Treatment Outcome References
 days  healthy volunteers  g for the st day followed by  g
until day . Not recorded []
 days
Normal, groups: placebo, HCA
of total  sedentary male under
high-fat diet
 mg HCA daily
No signicant eects on body weight
gain, appetite-related, and plasma
parameters but decreased fat deposition
∗∗Comments: suggest that ()-HCA may
reduce net fat deposition from de novo
lipogenesis during weight gain
[]
weeks
BMI ., groups: placebo, HCA
of  subjects each ( males, 
females)
 mg HCA Reduced of energy intake and slight
decreased of body weight []
weeks
Obese, hypocaloric diet, groups:
placebo,  capsule,  capsule, (
subjects each group)
 mg Gcambogia+mg
chromium +  mg
chitosan/day
Weightlossassociatedwithlower
TC/LDL and higher HDL []
weeks BMI –, groups: placebo,
treatment of  each  mg HCA/day Reduced of visceral and subcutaneous fat
area []
weeks
Moderate obese, groups: placebo,
HCA-SX, HCA-SX + NBC + GSE
of total 
HCA-SX  mg ( % HCA),
 mg HCA-SX +  𝜇g
niacin-bound chromium +
 mg Gymnema sylvestre
extract
Signicant (𝑃 < 0.05) decrease in BMI,
food intake, total cholesterol, low-density
lipoproteins, triglycerides, and serum
leptin levels, increase in high-density
lipoprotein levels, and enhanced
excretion of urinary fat metabolites
(biomarker of fat oxidation, including
malondialdehyde, acetaldehyde,
formaldehyde, and acetone) in HCA and
HCA-NBC-GSE groups
[]
weeks
BMI –, groups: placebo,
 mg HCA;  mg HCA +
 𝜇g chromium of  subjects
each
 mg HCA;  mg of
HCA-SX +  𝜇gchromium+
 mg g ymnemic acid/day
Decreased of body weight, BMI, LDL,
and TG and increased fat oxidation []
weeks
Normal, group:  healthy
subjects on diets , , or
 kcal
 mg G. cambogia extract
daily
Signicant reduction of total cholesterol,
triacylglycerol, and body weight
associated with reduced appetite
[]
weeks Obese, groups: placebo and
treatment of total  F . g G. atroviridis
Signicant reduction of body weight,
BMI, body fat, lean body mass, and
anthropometric parameters (biceps,
subscapular, suprailiac crest skinfold
thicknesses, and upper arm
circumference) but no change of serum
lipid prole
[]
 days Over weight to obese, groups:
placeboandtreatmentoftotal
 mg ()-HCA in Slim G.
cambogia extract daily Signicant reduced of body weight (.%) []
 weeks
BMI .–, groups: placebo
and treatment ( females/
males each) of total 
 mg G. cambogia +mg
Phaseolus vulgaris +mg
inulin/day
Signicant body weight lost (. kg versus
. kg) []
 weeks BMI , groups: placebo: ;
treatment:   mg G. cambogia/day Signicant body weight lost []
the high-fat control diet (CD) applied in the study was fed
to ve-week-old male Sprague-Dawley rats for  weeks to
create an obese conditions in rats that mimic to human
obesity. Body weight gain, visceral fat-pad weight, and serum
and hepatic biochemistry of rats were measured. e .%
mixture-supplemented HFD (D + M) reduced the total
body weight and the accumulation of visceral fat mass and
loweredthebloodandhepaticlipidlevels,whichledtothe
improvement of insulin resistance in the HFD-induced obese
rats. Moreover, the mixture of G. cambogia,soypeptide,and
L-carnitine improved dyslipidemia in rat models with HFD-
induced obesity. Downregulation of the expression of leptin,
tumor necrosis factor-alpha, and sterol regulatory element
binding protein c genes in the epididymal fat tissue of rats fed
with CD + M diet was obtained. In contrary, upregulation of
the uncoupling protein  (UCP) gene in epididymal adipose
tissues was induced with CD + M diet. No eect on the food
intake of the animals was observed in the study, suggesting
 Evidence-Based Complementary and Alternative Medicine
T : Summary of clinical studies of Garcinia/HCA that have shown none signicant antiobesity eect.
Duration Subject Treatment Outcome References
day Normal, groups: placebo, HCA
of total  cyclists  g HCA No signicant changes in total fat and
carbohydrate oxidation rates []
weeks
Normal-moderately obese,
group: placebo, HCA, and HCA
+MCToftotalmalesand
females
 mg HCA;  mg HCA +  g
medium chain triacylglycerols
(MCT)
No signicant dierences in satiety, daily
energy intake and body weight loss
within all groups
∗∗Comment: subjects were under
negative energy balance conditions
(eliminating the possibility of de novo
lipogenesis and reservation of glycogen
reserves had occurred; thus, the only
possible remaining mechanism increased
hepatic fatty acid oxidation)
[]
weeks
Normal-moderately obese,
groups:placebo,HCA,andHCA
+MCToftotalmale
 mg HCA;  mg HCA +  g
medium chain triacylglycerols
(MCT)
No signicant dierences in body weight
reduction, EE, appetite ratings, and
substrates oxidation (protein, fat, and
carbohydrate oxidation) within all groups
∗∗Comment: -week intervention is too
short
[]
weeks
Normal-moderately obese,
groups: placebo, HCA of total 
sedentary males, with or without
moderately intense exercise
g()-HCA daily
No signicant dierence in RQ, EE, and
blood parameters during rest nor during
exercise
[]
 weeks  subjects  mg G. cambogia +𝜇g
chromium picolinate/day
No signicant dierence in control and
placebo []
 weeks Overweight, groups: treatment:
; placebo:  gG. cambogia extract daily
No clinically signicant dierences in
body composition, plasma lipid proles,
antioxidant enzyme activity, and plasma
adipocytokines
[]
 week Obese, treatment: M,  F;
placebo:  M,  F
G. cambogia extract:  mg of
(% of HCA);
Diet:  kJ/day ( kcal/day)
No signicant dierence in body weight
and fat mass loss []
 weeks Obese,groups:treatment:F,
 M; placebo:  F,  M
Botanical extrac t ( mg HCA
daily)
No dierence between placebo and
treatment group but signicant change of
the body composition improvement
index, body free fat mass, weight, BMI,
and some other anthropometric
measurements in both treatment and
placebo groups
[]
 weeks Obese,groups:treatment:F,
M;placebo:F,M.
. g G. cambogia (.% HCA)
+.gA. konjac (.%
glucomannan)
No signicantvariation in body
weight/other anthropometric and
calorimetric parameters but signicant
hypercholesterolemic
[]
 weeks BMI , groups: placebo: ;
treatment: 
,. mg of G. cambogia
extract/day (, mg HCA/day) No signicant eect []
that the mixture exerted antiobesity eect via modulation of
the metabolic derangement induced by HFD during which
interactions between the multiple genes implicated in the
process of adipogenesis might be involved, rather than simply
suppressing appetite. A similar observation was obtained by
Kim et al. [], where in addition to the reduction of food
intake, the food eciency ratio (FER) was also signicantly
lower in the G. cambogia diet administrated group than in
the HFD mice, implying less ecient transformation of the
feed mass into body mass.
6. Human Clinical Trials
e antiobesity eects of G. cambogia in terms of promoting
weight loss and lowering cholesterol level were extensively
studied. However, evidence for the eectiveness of G. cambo-
gia or its derivative products was largely derived from animal
studies []. Despite the intriguing evidence of antiobesity
eects of G. cambogia from in vitro and animal studies,
more equivocal results were obtained from randomized
double-blind placebo-controlled experiments dealing with
Evidence-Based Complementary and Alternative Medicine 
T : Commercialized dietary supplements that contain G. cambogia extract/HCA.
Product name Company Concentration of
HCA
Doses recommended
(daily) Formulation of supplement
Super CitriMax
HCA--SXS
Inter health
N.I.
% ()-HCA in its
free form, .%
()-HCA in its
lactone form
capsules,times
daily, – min
before meal
capsulesperserving:G. cambogia extract  mg
(providing  mg of HCA), calcium  mg, potassium
 mg, .% sodium, .% magnesium, .% iron, .%
total phytosterols, .% total protein, .% moisture, and
.% soluble dietary ber
GarCitrin Sabinsa
Corporation % ()-HCA  mg,  times daily  mg of GarCitrin (providing  mg of HCA) and %
Garcinol
Sci-Fit Pro Cut % ()-HCA
capsules,-times
daily, – min
before meal
capsulesperserving:G. cambogia  mg (providing
 mg of HCA), green tea extract  mg (%
polyphenols) (% epigallocatechin/EGCG), guarana
extract  mg (% caeine), caeine mg, L-carnitine
 mg, white willow bark extract  mg (standardized
for % salicin), dandelion  mg, juniper berry extract
 mg, buchu extract  mg, and chromium  mg
G. cambogia and
Kola Nut
 mg
TerraVit a — capsule,times
daily, with meals  mg G. cambogia fruit,  mg kola nut
G. cambogia Proera,
Inc. % ()-HCA – caps ules daily,
before meals.
 mg G. cambogia (providing min.  mg of HCA),
vegetarian capsule (hydroxypropyl methylcellulose,
water), cellulose, magnesium stearate, and silicon dioxide
G. cambogia
Plus Atrium Inc % ()-HCA capsules,times
daily
Chromium  𝜇g(asCrpicolinatemgandCr
arginate  mg), G. cambogia  mg (providing  mg
of HCA), atractylodes  mg, citrus aurantii  mg,
gelatin, rice powder, and magnesium staerate
G. cambogia
Plus BioCare Ltd. % ()-HCA capsulesdaily,
 min before food
G. cambogia  mg, vitamin B (calcium pantothenate)
mg,vitamin C (ascorbic acid)  mg, manganese
gluconate(providing  𝜇g elemental manganese) . mg ,
and chromium polynicotinate . mg (providing  𝜇g
elemental chromium)
Garcinia  Source
Naturals % ()-HCA tablet,twicedaily,
hour before meal
Chromium (as chromiumpolynicotinate [ChromeMate]
and chromium picolinate)   𝜇g, sodium   mg, G.
cambogia fruit extract (providing  mg of HCA)  g
Garcinia 
hydroxycitric
acid
Nature’s life % ()-HCA —
G. cambogia rind concentrate (providing  mg of HCA)
 g, cellulose, silicon dioxide, magnesium stearate and
Micro-Cellulose”coating
Citrin Natural
Nirvana capsule,times
daily G. cambogia  mg, BioPerine  mg
HCA   mg
tablet
Higher
nature
 mg HCA per
tablet
- tablets,  ti me s
daily,  min before
meal
Tamarind fruit extract, microcrystalline cellulose,
magnesium stearate (vegetarian source), hydroxypropyl
methylcellulose coating, silicon dioxide, and acacia
powder
HCA Hydroxy
citric acid
Viridian
Nutrition
Ltd.
% ()-HCA capsule,times
daily, before meal
G. cambogia (providing  mg HCA)  mg, viridian
bilberry extract, alfalfa, spirulina blend  mg, and
vegetarian cellulose capsule  mg
HCA
hydroxycitric
acid
Life
Extension
Foundation
% ()-HCA
capsule,times
daily,  min before
meals with  capsule
of CitriChrome
G. cambogia (fruit) (providing  mg of HCA)   mg
Hydroxycitrate Solgar % ()-HCA  capsule, – min
before meal
G. cambogia fruit powdered extrac t (providing  mg
[%] HCA)  mg, hydroxypropylmethyl cellulose,
vegetable magnesium stearate, and silicon dioxide
Hydroxycitrate
Plus Metagenics —
tablet,timesdaily,
– min b efore
meal
Garcinia fruit extract (G. cambogia)mg,L-carnitine
 mg, niacin (as niacinamide)  mg, pantothenic acid
(as D-calcium pantothenate)  mg, riboavin  mg,
manganese (as manganese arginine)  𝜇g, and
chromium (as chromium nicotinate glycinate)  𝜇g
 Evidence-Based Complementary and Alternative Medicine
human subjects []. Hayamizu et al. []conducted
a crossover design randomized controlled trials (RCTs) to
determine the “no observed adverse eect level (NOAEL)”
of G. cambogia extract in  healthy volunteers ( males
and  females) and concluded that G. cambogia is generally
safe to be consumed. Several equivocal ndings of RCTs
were reported on the eectiveness of supplements containing
HCA (Table  ). Some studies reported that HCA exerted no
signicant eects as compared to the placebo group [,,
](Ta b l e  ). All the above ndings were in agreement with
themostrecentmeta-analysisofRCTswhichrevealedthatG.
cambogia extract possessed limited or no eects on weight-
loss in human subjects []. Moreover, this study showed no
eectonsatietyorcalorieintakeinoverweightindividuals
consuming their habitual diet, which is in agreement with
past studies [,,]. However, such comparisons must be
made with caution as the variations in the formulations, doses
administered, RCTs designs, and study populations might
contribute to the discrepancy of the results.
Preclinical studies using rodent models have conrmed
the body weight reduction, appetite suppression, and subse-
quently food intake reduction eects of HCA in rats. Clin-
ically, however, HCA failed to perform well. Several factors
thatmightcontributetothisscenarioaretheATPcitratelyase
which might be important only at very high carbohydrate
diets, a type of diet that most studies did not prescribe.
Besides, a high-ber diet can bind to HCA and block it,
thus reducing its ecacy. HCA and G. cambogia exerted
potential eects in weight management, but clinical studies
have yet to prove optimum conditions for HCA to be eective.
For instance, Sullivan et al. [] reported that hepatic lipid
synthesis was reduced only if HCA was administered before
the beginning of feeding, reaching optimum – minutes
prior to feeding. e reason for this remains unknown.
7. Patents and Commercialization
e claims on enhanced human health associated with
Garcinia/HCAhadbeenreviewedinSection .Inparticular,
the antiobesity eects of Garcinia/HCA were extensively
reported. is has resulted in the availability of numerous
commercialized weight-management products derived from
Garcinia/HCA (Tab l e  ). Several products of G. cambogia
or its derivatives had been patented and commercialized.
As of August , a total of  patents that apply to G.
cambogia or HCA derived from Garcinia were led with the
US Patent and Trademark Oce (USPTO) since  (search
of US Patents and Trademark Oce in year  using
Google patent search). ese patents are on various aspects,
including HCA enrichment from Garcinia rind, HCA and
food products/dietary supplements prepared therefrom,
methods of production, and their use. e majority of the
patents are related to G. cambogia/atroviridis and/or HCA
derived from Garcinia on obesity and weight loss. e
pa t en t n u m b er s a re a s f ol l o w s :  , , ,  , , ,  , , ,
,,, ,,, ,,, ,,, ,,, ,,,
, , , , , , , , , , , , , , , , , ,
,,, ,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, ,,, ,,,
,,, ,,, ,,, and ,,.
8. Conclusions
e nutraceutical industry is ourishing, and interest in
establishing scientic credibility has attained importance for
many companies and scientists. In the recent years, more
clinical trials had been conducted to elucidate the functional
eects of Garcinia/HCA supplementation on promoting
human health. A multitude of metabolic functions had been
reported for HCA or HCA-containing Garcinia extract, such
as reducing blood lipids, inducing weight loss, suppressing
appetite, and reducing food intake based on results obtained
in both animal trials and human clinical trials (Figure ).
ese discoveries make the development of evidence-based
adjuvant modalities to curb the trend of the increasing
prevalence of obesity and obesity-related comorbidity and
mortality possible. We have previously reviewed and con-
cluded that Garcinia extract and HCA were generally safe
to be consumed. Collective results from  clinical studies
which involved  subjects demonstrated the safety of HCA
and HCA-SX for human consumption []. ese studies
provided scientic evidence that intake of HCA and HCA-SX
alone did not produce adverse eects and a dietary dosage of
up to  mg/day was regarded as the “no observed adverse
eect level (NOAEL)” of HCA-SX in human []. Based on
these animal and human safety data, HCA-SX also received
self-armedGRASstatusintheUSAbytheBurdockGroup
in year  []. However, denitive conclusions that
Garcinia/HCA supplements are ecient tools against various
health problems especially obesity remain to be proven in
larger-scale and longer-term clinical trials, despite substantial
public interest in such supplements. Many diet supplements
containing Garcinia/HCA marketed as weight management
products are the combination of active ingredients rather
than containing a single agent. us it is dicult to evaluate
the eectiveness of single agents when the combination
products are tested. In addition, awareness of the safety and
ecacy of the weight management supplements available in
themarketshouldberaisedamonghealthcareprovidersin
order to assist their patients in analyzing the risks and benets
of the dietary supplements. us, scientic investigations on
the potential health promoting eects of herbal preparations
as diet supplement are prerequisites for new discoveries of
alternative therapies.
Acknowledgment
e authors would like to thanks Professor S. G. Tan for the
proofreading of this paper.
Evidence-Based Complementary and Alternative Medicine 
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... Pharmacological inhibition of ACLY ameliorates T cellmediated autoimmunity 2-HC is a competitive inhibitor of ACLY and found naturally in fruits of the Garcinia cambogia tree (Chuah et al., 2013). Garcinia preparations are traditionally used to treat infections and rheumatism, highlighting an anti-inflammatory effect of 2-HC (Chuah et al., 2013). ...
... Pharmacological inhibition of ACLY ameliorates T cellmediated autoimmunity 2-HC is a competitive inhibitor of ACLY and found naturally in fruits of the Garcinia cambogia tree (Chuah et al., 2013). Garcinia preparations are traditionally used to treat infections and rheumatism, highlighting an anti-inflammatory effect of 2-HC (Chuah et al., 2013). Treatment of Th17 cells with 5 mM 2-HC reduced their total acetyl-CoA levels by $50% (Figure 7A), comparable to the reduction observed in GLUT3 ( Figure 5B) and ACLY-deficient T cells ( Figure 5D). ...
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In brief Hochrein et al. report that inflammatory T cells express high levels of GLUT3. Ablation of GLUT3 curtailed Th17-cell-mediated immune responses and protected mice from autoimmune colitis and encephalomyelitis. GLUT3-dependent glucose metabolism controls the generation of nucleo-cytosolic acetyl-CoA and the epigenetic regulation of cytokine responses through histone acetylation. SUMMARY Metabolic reprogramming is a hallmark of activated T cells. The switch from oxidative phosphorylation to aer-obic glycolysis provides energy and intermediary metabolites for the biosynthesis of macromolecules to support clonal expansion and effector function. Here, we show that glycolytic reprogramming additionally controls inflammatory gene expression via epigenetic remodeling. We found that the glucose transporter GLUT3 is essential for the effector functions of Th17 cells in models of autoimmune colitis and encephalomyelitis. At the molecular level, we show that GLUT3-dependent glucose uptake controls a metabolic-transcriptional circuit that regulates the pathogenicity of Th17 cells. Metabolomic, epigenetic, and transcriptomic analyses linked GLUT3 to mitochondrial glucose oxidation and ACLY-dependent acetyl-CoA generation as a rate-limiting step in the epigenetic regulation of inflammatory gene expression. Our findings are also important from a translational perspective because inhibiting GLUT3-dependent acetyl-CoA generation is a promising metabolic checkpoint to mitigate Th17-cell-mediated inflammatory diseases.
... Several studies proved that taking Garcinia could reduce body fat composition. [21,[35][36][37] Based on Figure 4, the effects of various Garcinia herbs could be seen to have similar bioactivity and pharmacological properties related to metabolic syndrome disorder. Garcinia herbs had several mechanisms of action reducing body weight such as through increasing FAS, activating the scavenger receptor CD36, and regulating PPR-γ, which could decrease lipid level, cholesterol production, and triglyceride level. ...
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The incidence rate is directly proportional to the incidence of obesity or overweight and Type 2 diabetes mellitus. Garcinia is a plant that has been proven empirically, preclinically, and clinically to have activities for the avoidance and treatment of metabolic syndrome and on the pathogenesis and pathophysiology caused by the disease. The aim of this study is to create a discussion and summarize information regarding the activity or usefulness of the Garcinia plant. This review article was based on the published journals obtained from Google Scholar, Scopus, and PubMed databases using the keywords Garcinia obesity, Garcinia overweight, and Garcinia metabolic syndrome. Garcinia had many activities related to metabolic syndrome because it was able to reduce body fat mass, blood sugar level, body weight, total cholesterol, and triglyceride level. These activities were mediated by numerous apparatuses of feat together with a reserve of fatty acid synthase, α-amylase, α-glucosidase, and several other enzymes and pathways associated with the metabolic syndrome. Garcinia plant was able to be used as a candidate for a new herbal that had a good effect in treating metabolic syndrome in future.
... Garcinia cambogia (Malabar tamarind) and Garcinia indica (kokum) are small tropical trees grown in Africa, Asia (western ghats of India), and Pacific regions [1]. Parts or extracts of these food plants have been used in traditional Ayurvedic medical system to treat various gastric ailments and skin-related problems because of its therapeutic efficiency [2]. The ripe fruits and dried fruit rinds are used as condiment and flavoring agent without any adverse effect. ...
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Full-text available
Garcinol is an active constituent of Garcinia indica and Garcinia cambogia. Recent studies have proven that garcinol has anti-inflammatory, anti-cancer, and anti-oxidant activities. The objective of this study was to evaluate the inhibitory effects of garcinol on the activities of the drug metabolizing cytochrome P450 (CYP) isozymes to predict potential herb-drug interactions with co-administered drugs. Garcinol was incubated with a mixture of rat liver microsomes and eight CYP probe substrate cocktail under optimized incubation conditions and the samples were analyzed using a validated method on LC-MS/MS. Garcinol showed strong inhibition with IC50 values of CYP1A2 (7.6 µM), CYP2C9 (8.0 µM), CYP2B6 (2.1 µM), CYP2D6 (9.5 µM), and CYP3A4 (5.1 µM), respectively, and moderate inhibition towards CYP2C19 (16.4 µM) and CYP2E1 (19.0 µM). Molecular docking studies were performed on garcinol against the active sites of CYP2B6 and CYP3A4 proteins. These results further confirmed that the inhibitory activity of garcinol occurred by occupying the active sites of these human CYPs and by making favorable interactions with its key residues. In-vivo CYP inhibition studies were carried out in Sprague-Dawley rats. These results suggest garcinol may cause herb-drug interactions, mediated by inhibition of CYPs involved in drug metabolism in-vivo by altering the pharmacokinetic parameters like AUC and Cmax in a clinically significant manner. Garcinol was found to upregulate the expression and activity of P-gp in western blotting study and P