review article updates on antiobesity effect of garcinia

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2013 Article ID 751658 17 pageshttpdxdoiorg1011552013751658

Review ArticleUpdates on Antiobesity Effect of Garcinia Origin (minus)-HCA

Li Oon Chuah1 Wan Yong Ho2 Boon Kee Beh3 and Swee Keong Yeap4

1 School of Industrial Technology University Science Malaysia 11800 Penang Malaysia2 School of Biomedical Sciences The University of Nottingham Malaysia Campus Jalan Broga 43300 Semenyih Selangor Malaysia3 Department of Bioprocess Technology Faculty of Biotechnology and Biomolecular Sciences University Putra Malaysia43400 Serdang Selangor Malaysia

4 Institute of Bioscience University Putra Malaysia 43300 Serdang Selangor Malaysia

Correspondence should be addressed to Swee Keong Yeap skyeap2005gmailcom

Received 15 June 2013 Accepted 7 July 2013

Academic Editor Vincenzo De Feo

Copyright copy 2013 Li Oon Chuah et al This is an open access article distributed under the Creative Commons Attribution Licensewhich 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 flavouring agent Various phytochemicals includingflavonoids and organic acid have been identified in this plant Among all types of organic acids hydroxycitric acid or morespecifically (minus)-hydroxycitric acid has been identified as a potential supplement for weight management and as antiobesity agentVarious in vivo studies have contributed to the understanding of the anti-obesity effects ofGarciniahydroxycitric acid via regulationof serotonin level and glucose uptake Besides it also helps to enhance fat oxidation while reducing de novo lipogenesis Howeverresults from clinical studies showed both negative and positive antiobesity effects of Garciniahydroxycitric acid This review wasprepared to summarise the update of chemical constituents significance of in vivoclinical anti-obesity effects and the importanceof the current market potential of Garciniahydroxycitric acid

1 Introduction

The world is in health transition Infection as a major causeof suffering and death is giving way to new epidemics ofnoncommunicable disorders such as cancer cardiovasculardiseases and diabetes which continue to plague the worldat an alarming rate [1] A trend of increasing prevalence ofobesity and obesity-related comorbidity and mortality wasobserved over the last few decades [2] The InternationalAssociation of the Study of Obesity (IASO) reported on thecountry rankings in terms of percentage global prevalence ofadult obesity (BMI ge 30 kgm2) in the year of 2012 whereTonga ranks first with 560 obese adults (466 of obesemale and 703 of obese female) In the United StatesIASO reported that 355 of men and 358 women wereobese (BMI ge 30) [1 3] Overweight and obesity are diag-nosed zbased on the bodymass index (BMI) which is definedas 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 valuesin the range of 25ndash2999 Obesity itself defined as BMI ge 30

is associated with several chronic and debilitating healthproblems including hyperlipidemia hypertension coronaryheart disease diabetes cancer disease of the gall bladderosteoarthritis shortage of breath abnormal dilation of theveins backache and even psychological problems [2 4]

There are a few drugs in the market to ameliorate orprevent obesity but there are costs efficacy and side effectsto be considered For example the currently available phar-macological agents Sibutramine Rimonabant Orlistat andPhenterminewhich are licensed forweight reduction therapyappear to possess some adverse effects [5ndash7] Phenterminefor instance has been reported to cause drymouth insomniaheadache dizziness fatigue and palpitation [6 7] In year2010 FDA had announced the market withdrawal of Meridia(Sibutramine) due to its risk of serious cardiovascular events[6 7] Natural products and plant-based dietary supplementshave been used by people for centuries Evidence is startingto emerge to shed light on the consumption of herbs asan effective strategy for disease treatment and health main-tenance Several ethnobotanical studies have reported thebioprospecting surveys on the positive application of herbs

2 Evidence-Based Complementary and Alternative Medicine

Table 1 Comparison of G cambogia G atroviridis and G indica [9 11 13 44]

Species Common name Origin Feature

G cambogia Asam Gelugor

India found commonly in the evergreenforests of Western Ghats from Konkansouthward to Travancore and in theShola forests of Nilgiri

Small- or medium-sized tree with a rounded crown andhorizontal or drooping branches under the family ofGuttiferae Its fruits are ovoid about 5 cm in diameter yellowor red when ripe with six to eight grooves enclosing six toeight seeds and are edible

G atroviridis Asam Gelugor Southeast Asia

Small- or medium-sized fruit tree with drooping branchesand ovoid fruits The fruits are bright orange-yellow whenripe globose with 12ndash16 grooves about 7ndash10 cm in diameterand fluted with a firmly textured outer rind and a rather thinand translucent pulp surrounding the seeds

G indica KokumIndia the tropical rain forests of WesternGhats from Konkan southward toMysore Coorg and Wayanad

Slender evergreen tree with drooping branches Its fruits areglobose or spherical 2ndash4 cm in diameter dark purple whenripe with five to eight large seeds surrounded

in the treatments for obesity [8] Garcinia has been usedfor centuries in Asian countries for culinary purposes as acondiment and flavoring agent in place of tamarind or lemonand to make meals more filling [9 10] Besides its use as aflavouring agent the dried rind of G cambogia combinedwith salt and other organic acids can help to lower thepH and thus provides a bacteriostatic effect in curing fishG cambogia contains large amounts of hydroxycitric acid(HCA) Similar to G cambogia G atroviridis and G indicaalso contain significant HCA content and are sometimesused interchangeably with G cambogia in food preparationThe different features among these three different types ofGarcinia are summarised in Table 1 [9 11ndash14]

A myriad of health effects have been attributed to Garci-nia (including G cambogia G atroviridis and G indica)such as antiobesity effects [15ndash17] antiulcerogenic [18ndash20]antioxidative [21ndash24] antidiabetes [25] antimicrobial [2226ndash28] antifungal [29] anti-inflammatory [30 31] andanticancer effects [22 32ndash34] In particular the antiobesityeffects of Garcinia or more specifically of its HCA contenthave been elucidated with unprecedented clarity over the lastfew decades Besides its efficacy in the reduction of bodyweight and food intake GarciniaHCA has been proven tobe beneficial in ameliorating obesity-related complicationssuch as inflammation oxidative stress and insulin resistance[21] The results obtained from several studies supported thepositive effects of HCA administration alone or in combina-tionwith other ingredients on bodyweight loss reduced foodintake increased fat oxidation or energy expenditure (EE)[16 17 35ndash39] whereas some studies did not [40ndash42]

In spite of the vastly reported prominent role of HCAin inducing satiety reduced energy intake and weight gainand improved blood parameters and substrate oxidationcontroversial results regarding its efficacy and safety asan antiobesity dietary supplement had also been reportedEvidence from the in vitro in vivo and clinical trials onthe safety of GarciniaHCA as a dietary supplement fortreating obesity had been extensively reviewed [43] Howeverthe efficacy of GarciniaHCA remains the subject of debateDespite the previously stated issues on conclusive evidencefor HCArsquos efficacy in promoting weight loss and suppressingfood intake the marketing of a plethora of over-the-counter

slimming aids containing HCA has taken place The aim ofthis review is to critically assess the evidence from a verybroad range of reports rigorous clinical trials systematicreviews and meta-analyses on the efficacy and potential ofGarciniaHCA as an antiobesity dietary supplement

2 Uses in Traditional Medical Systems

Botanical dietary supplements usually contain a complexmixture of phytochemicals which have additive or synergisticinteractions Aside from its use as a preservative and as acondiment in cuisine Garcinia extract has been used in thetraditional Ayurvedic medical system [9 13] A decoction ofG cambogia is given as purgative in the treatment of intestinalworms and other parasites for bilious digestive conditionsfor dysentery rheumatism and in the treatment of tumoursLess commonly extracts are employed as cardiotonics to treatangina In veterinarymedicine it is used as a rinse for diseasesof the mouth in cattle [12 77]The fruit rind is used in ricketsand enlargement of spleen and to heal bone fractures [13] InSoutheast Asian folkloric medicine a decoction of G atro-viridis (leaves and roots) is sometimes used for the treatmentof cough dandruff earache stomach pains associated withpregnancy and throat irritation [49] The dried fruit of Gatroviridis is used for improving blood circulation for thetreatment of coughs as a laxative and as a expectorant Thefruit is used in a lotion with vinegar to rub over the abdomenof women after confinement [9] Fruit ofG indica is antiscor-butic cholagogue cooling antibilious emollient and demul-cent The anthelmintic properties of the fruit of G indicacontributed to its use in haemorrhoids dysentery tumorpains and heart complaints Bilious affected sites are treatedwith syrup from the fruit juice Kokum butter is astringentand demulcent and is used in diarrhea and dysentery It is alsoapplied externally for ulcerations sinuses fissures of handlip chapped skin and skin diseases [12 13 44 77]

3 Phytoconstituents

The several compounds which have been isolated fromvarious species ofGarcinia are summarised inTable 2 Several

Evidence-Based Complementary and Alternative Medicine 3

Table 2 Phytochemicals of Garcinia

Phytochemicals G cambogia G indica G atroviridisOrganic acids

(minus)-HCA Fruit rind [45 46] Fruit rind [45] Fruit rind [45]

Citric acid Fruit rind [46] Leave and fruit rind[47]

Herbal products[48]

Tartaric acid [46]nd [47]nd Herbal products[48]

Malic acid Fruit rind [46] [47]nd Herbal products[48]

Succinic acid mdash [47]nd mdashPrenylated benzoquinone

Atrovirinone mdash mdash Root [27]Prenylated depsidone

Atrovirisidone mdash mdash Root [27]Atrovirisidone B mdash mdash Root [49]

Prenylated hydroquinone4-Methylhydroatrovirinone mdash mdash Root [50]14-cis-Docosenoic acid mdash mdash Root [50]14-cis-Docosenoic acid mdash mdash Root [50]

FlavonoidMorelloflavone mdash mdash Root [50]Fukugiside mdash mdash Root [50]Naringenin Root [49]3810158401015840-Binaringenin Root [49]

XanthoneGarbogiol Root [51] mdash mdashRheediaxanthone A Bark [51] mdash mdash

Dioxygenated xanthone17-Dihydroxyxanthone mdash Heartwood [52] mdash

Tetraoxygenated xanthoneAtroviridin mdash mdash Stem bark [53]

Tetracyclic xanthoneOxyguttiferone K Fruit [54] mdash mdash

Polyisoprenylated benzophenone

Garcinolcamboginol (enantiomer of xanthochymol)

Fruit rinds[55 56]Latex [57]Bark [51]

[55]ndFruit rinds [58] mdash

Isogarcinolcambogin (enantiomer of isoxanthohumol ) Latex [57]Bark [51] Fruit rinds [58] mdash

Isoxanthohumol Fruit rinds [55] [55]nd mdashGuttiferone I Fruit [54] mdashGuttiferone J Fruit [54] mdashGuttiferone K Fruit [54] mdashGuttiferone M Fruit [54] mdashGuttiferone N Fruit [54] mdash

nd none detected mdash not reported


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

SerotoninFatty acids supply

Insulin leptin

Glucose intake

Carbohydrate oxidation

EE-workout (YES)

resting

RER (YES) RQ

lowastaffecting adipose conversion

Appetite

A

B

C

D

and

GarciniaHCA

OHOH

OHOO

OHO

HO

Figure 1 Possiblemultiplemechanisms that contribute to antiobesity effect ofGarciniaHCA uarr indicated increase or stimulation darr indicatedreduce or inhibitionwhile indicated that the effect is yet to be confirmed (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 effect of GarciniaHCA while (B) and (C) contribute to antiobesity of GarciniaHCA

types of organic acids such as HCA citric tartaric malicand succinic acids are isolated from Garcinia HoweverHCA is the principal acid of the fruit rinds of G cambogiaG indica and G atroviridis [12 27 45] with its contentascending as listed [46ndash48] A substantial amount of (minus)-HCA up to 30 by weight is present in the pericarpof the fruit of G cambogia In similar studies conductedby Sullivan et al [78 79] and Stallings et al [80] theyobserved that of the four isomers of HCA [(ndash)-HCA (+)-HCA (ndash)-allo-HCA and (+)-allo-HCA] (minus)-HCA which isalso known as (2S 3S)-HCA was the only potent inhibitorof ATP citrate lyase (minus)-HCA can be chemically synthe-sized using citric acid as starting material Synthetic (minus)-HCA offers several advantages including higher purity andlactone stable as compared to natural (minus)-HCA [81] Onthe other hand (minus)-HCA is a good starting material tosynthesize other important chiral synthons and compounds[82]

(minus)-HCA is one of the important supplements for anti-obesity and weight management Its effect on weight man-agement is mainly contributed by giving the feeling of fulland satisfaction while the antiobesity effect is by reductionof de novo lipogenesis and acceleration of fat oxidation(Figure 1) In this paper we aimed to review the mechanismfor antiobesity and weight management effects by (minus)-HCA(hereafter referred to as HCA)G cambogiaG atroviridisGindica extracts and the assessment of these effects in theclinical settings

4 Salts of HCA

On account to the discovery of (minus)-HCA as an effectivecompound in weight management market demand for theacid has increased tremendously The commercially availableG cambogia extracts which contain approximately 50 (minus)-HCA are prepared from the fruit rind [12 69] HCA can existas a free acid or in the lactone form The former form isconsidered to be biologically active However the free acidis unstable and is usually converted to its less active lactoneform to attain higher stability To prevent the cyclization ofHCA into its less potent lactone the acid has been combinedwith various counter ions to form stable salts [83]

Commercial HCA is available in free acid form and assingle double or triple salts Preparations with differentcounter ions contribute to different degree of solubility aswell as bioavailability [84] For example Na+ salt of HCA hadbeen shown to be more effective than its lactone in inhibitinglipogenesis However Na+ salt is highly hygroscopic whenbound to (minus)-HCA which would deemed unfavorable for theproduction of pharmaceuticals for dry delivery [85]

To address the need to achieve higher solubility andstability recent approaches have been focused more on thepreparation of (minus)-HCA in the form of a double or triplesalt Similar to its single salts these double or triple salts alsoserve as good supply for essential ions [84] A remarkableexample of these would be the Ca2+K+ salt of (minus)-HCA(HCA-SX) or Super CitriMax In contrast to the single salts


HCA-SX is completely soluble in water and thus confershigher bioavailability [84] A number of studies on the safetyof HCA-SX had been reported [43] Daily intake of HCA-SX at this dosage was shown to be effective in reducingbody weight and BMI of healthy and obese adults afterclinical trials of 8 weeks [16 64] Gene expression studiesalso provided additional evidence for the safety of HCA-SXwhere genes essential formitochondrialnuclear proteins andfor fundamental support of adipose tissue were shown to beindependent of the regulation by HCA-SX [17 86]

A typical reduction of food appetite and an increasedserotonin availability were observed in all the weight controlstudies of HCA-SX on both animal and human subjectsThese were associated with reduced levels of total cholesterolLDL triglycerides and serum leptin as well as increasedHDL level and urinary excretion of fat metabolites [15 1664 84 87] In rats the salt also caused downregulation ofgenes encoding abdominal fat leptin while expressions of theplasma leptin genes remained unaltered [17] Nevertheless itwas postulated that a set of obesity regulatory genes [84] andinhibition to the uptake of [3H]-5-HT release in the brain [15]are involved in the appetite suppressing activity of HCA-SX

In relation to this gene expression profiling carriedout by a research group demonstrated the modulation ofa specific set of genes (about 1 of 9960 genes and ESTs)in the adipocytes by dietary HCA-SX supplementation [17]Further study on culturedmature human adipocytes revealedsignificant upregulation of 366 and downregulation of 348the fat- and obesity-related genes [88] Notably also in themicroarray analyses HCA-SX demonstrated a distinct effecton appetite suppression whereby genes encoding serotoninreceptors were shown to be selectively upregulated by thesalt [17] Besides HCA-SX was also found to be capableof activating hypoxia inducible factor (HIF) a transcriptionfactor involved in energy metabolism [88] and restoredthe increase in oxidative stress inflammation and insulinresistance in obese Zucker rats [21]

5 Antiobesity Effects of GarciniaHCA

Obesity particularly caused by accumulation of visceral fat isa serious risk factor of various life-style diseases such as coro-nary heart disease diabetes hyperlipidemia hypertensionand cancer [2 4] Human obesity is influenced by geneticand environmental factors and particularly by changes in dietand physical activity which contributes greatly to the devel-opment of insulin resistance a most common underlyingabnormality in human obesity [89] Studies on food sourcesexerting antiobesity effects have focused on the developmentof herbal extracts or functional food which can suppress theaccumulation of body fat Several studies were conducted toprovide scientific basis on the extensive usage of G cambogiaand G atroviridis associated with high-fat diet- (HFD-) induced obesity where dyslipidemia fatty liver insulinresistance and hyperleptinemia were acquired along with theoverexpression of leptin TNF-120572 resistin PPAR1205742 CEBP120572and SREBP1c genes in epididymal adipose tissue The effectof G cambogia was largely attributed to its HCA content[90 91] Subsequent researches proved that the antiobesity

effects of G cambogiaHCA resulted from the combinedactions of several mechanisms including suppressing de novofatty acid biosynthesis and appetite [16 60] and increasingenergy expenditure [39] subsequently reducing body fataccumulation and weight gain in experimental animals [3738 92] In this review we arranged the antiobesity effects ofGarciniaHCA based on their distinct mechanisms (1) sero-tonin regulation and food intake suppression (2) decreasedde novo lipogenesis (3) increased fat oxidation and (4)downregulation of a spectrum of obesity-associated genes

51 Serotonin (5-Hydroxytryptamine 5-HT) Regulation andFood Intake Suppression HCA the primary acid in the fruitrinds of G cambogia G atroviridis and G indica [45] hasbeen reported as the active ingredient in inhibiting ATPcitrate lyase (EC 4138) [78 93] ATP citrate lyase whichis an extramitochondrial enzyme catalyzing the cleavage ofcitrate to oxaloacetate and acetyl-CoA was inhibited byHCA Thus the availability of two-carbon units required forthe initial steps of fatty acid and cholesterol biosynthesisduring carbohydrate feeding was limited [78 79 94ndash97] As aresult the consumed carbon source was diverted to glycogensynthesis in liver A signal was then sent to the brain due tothis metabolic alteration resulting in rising of serotonin levelconcomitant with a reduced appetite HCA might exhibiteits anorectic effect by a second possible mechanism namelyreducing acetyl CoA subsequently decreasing malonyl CoAlevels and thereby reducing negative feedback on carnitineacyltransferase (CPT-1) The substrate of CPT-1 long-chainacyl CoA(s) may act as a mediator(s) of appetite [9899] More recently neuropeptide Y (NPY) had also beenimplicated in the appetite suppression of HCA Basal concen-tration of the neurotransmitterwas claimed to be significantlyreduced in the hypothalamic tissues as a result of supplemen-tation with HCA-SX [84] However the role of NPY in thisis still vague to date Several reports supported the serotoninregulation of HCA Ohia et al [100] demonstrated that HCA-SX enhanced serotonin availability in isolated rat brain cortexby acting as a mild serotonin receptor reuptake inhibitor(SRRI) without stimulating the central nervous system Kaurand Kulkarni [36] conducted a study to elucidate the effectof OB-200G a polyherbal preparation containing aqueousextracts of G cambogia Gymnema sylvestre Zingiber offici-nalePiper longum and resin fromCommiphoramukul on themodulation of food intake by serotoninmodulators in femalemice The results obtained were compared with fluoxetine adrug that was reported to enhance 5-HT neurotransmission[101] Both OB-200G and fluoxetine significantly (119875 lt 005)antagonized the hyperphagic effect of p-chlorophenylalanine(PCPA) 8-hydroxy-2-(di-N-propylamino)-Tetralin (8-OH-DPAT) cyproheptadine and 2-deoxy-D-glucose (2-DG)which further instigate possible serotonergic involvement inthe effects of OB-200G on food intake in female mice Preusset al [16] reported that HCA caused a significant reductionin appetite weight loss and plasma leptin level concomitantwith an increase in the serum serotonin level and a favorablelipid profile in human clinical trials Similar results were alsoobtained in a study conducted by Asghar et al [87] Theyreported on increased brain serotonin level in obese Zucker


rats receiving G cambogia extract suggesting that the abilityof HCA in body weight gain reduction was most probablydue to its combined effects on the metabolic and serotoninpathways In addition Roy et al [17] reported that HCA-SX supplementation upregulated prostaglandin D synthase(PDS) aldolase B (AldB) and lipocalin (LCN2) genes inabdominal fat tissue Further mapping of the candidate genesof known pathways associated with fat metabolism by usingfunctional categorization and pathway construction softwareshowed that supplementation of HCA-SX targeted on theserotonin receptor

Leonhardt et al [102] reported that HCA reduced bodyweight regain in rats after a period of substantial bodyweight loss Besides HCA temporarily reduced food intakeof rats with diets of varying nutrient contents (groundedstandard rat chow high glucose and high glucose + fat)HCA supplementation caused pronounce suppression offood intake during the entire 10 days of ad libitum feedingperiod in rats fed with high glucose + fat diet a diet that hada nutritionally relevant level of dietary fat (24 of energy)These data therefore extended those of the previous studieswhich reported on the anorectic effects of HCA [96 97 103ndash105] Moreover the results obtained were consistent withstudies which reported on particularly strong food intakesuppression byHCAwith high glucose + fat diet and a smallerbut still significant suppression with the high glucose diet inother rat models and in different orders [37 39 102] Hencethe feed conversion efficiency [cumulative bodyweight regain(g)cumulative food intake (MJ)] in the high glucose andhigh glucose + fat groups during the 10 ad libitum dayswas reduced which indirectly supported that HCA increasedenergy expenditure in these groups

Leonhardt and Langhans [39] then extended their studyon the long-term effects of HCA on body weight regain andfood intake as well as the effects of HCA on the circadiandistribution of food intake and on meal patterns duringthe dark and light phases HCA administration significantlyreduced the food intake of rats fed with 12 fat diet butnot 1 fat diet concomitant with significant reduction inweight regain (overall 119875 lt 001) in both groups In the studythe rats underwent restrictive feeding for 10 days prior toad libitum feeding (Experiment 1 normal 1 fat diet and1 fat diet + 3 HCA Experiment 2 normal 12 fat dietand 12 fat diet + 3 HCA) The control groups of bothexperiments had compensated the body weight loss whereasthe HCA-fed rats groups regained only 68 plusmn 4 (1 fat diet)and 61 plusmn 8 (12 fat diet) of the body weight regained bytheir respective control groups after 22 days of such ad libitumfeeding Despite significant reduction in weight regain inrats fed with 1 and 12 fat diet long-term suppressionof HCA on food intake was only detected in combinationwith 12 fat diet (Experiment 2) This was in line with theresults obtained by Leonhardt et al [106] who suggested thatHCA increased energy expenditure Studies on the effects ofHCA on the circadian distribution of food intake and onmeal patterns showed that the suppression of food intakeoccurred predominantly during the dark phase of the firstad libitum days However later on HCA suppression of foodintake was more effective during the light phase Further

experiments elucidating the effects of HCA in combinationwith the 12 fat diet on meal size and meal number duringthe light phase revealed that HCA markedly reduced themeal number but not the meal size HCA did not affectany metabolic variables tested (plasma glucose lactate tri-acylglycerol HDL free fatty acids 120573-hydroxybutyrate andinsulin hepatic fact and glycogen concentrations) in bothexperiments except decreasing plasma triacylglycerol levelsand increasing the liver fat concentration in Experiment 2(rats fed with 12 fat diet) The fact that HCA did not affectplasma 120573-hydroxybutyrate (BHB) levels did not support thehypothesis that HCA suppressed food intake via increasedhepatic fatty acid oxidation

However contradicting results were obtained by Kovacset al [41 71] who reported that two-week supplementationwith HCA and HCA combined with medium-chain triglyc-erides did not result in increased satiety The findings werein line with previous reports where no significant treatmenteffects were observed on appetite indices (inclusive of meanpeak or nadir hunger ratings mean ratings of desire to eatprospective consumption fullness or sensations of thirststomach growling headache distraction irritability or as acheck onmalingering itchiness) [69]The lack of efficacy andtransient food intake suppression by HCA raised questionsabout its clinical significance While negative findings arealways open to methodological questions several questionsneed to be answered before drawing a definite conclusionFirst the diet administered to the subjects should notpromote extreme sensations in the evaluation of the foodintake suppression effects ofHCAunder conditions of energyrestriction However Mattes and Bormann imposed mildrestrictions and thus ruled out this possibility as evidencedby ratings falling in the middle range of the responsescales Second an energy-restricted diet would prevent therequired enzyme alterations (reduction of acetyl-CoA andsuppression of formation of carnitine palmitoyltransferase Iinhibitor malonyl CoA) which altered substrate metabolismand satiety However it was unlikely that themoderate energyrestricted diet prescribed in the study conducted by Mattesand Bormann [69] hindered the satiety effect of HCA as itstill contained at least 30 of energy from fat

Several factors might contribute to the controversialresults of the efficacy of HCA in human studies One ofcontributing factors is the highly variable doses used in thehuman trials which ranged from 5 to 250mgkg of HCAper day [42 70] Besides the discrepancy might also bedue to the differences in the preparation or extraction ofHCA For instance the extractionmethodmight increase theformation of HCA in a lactone form which is less potentin the inhibition of ATP citrate lyase [85 107] In order toprevent the cyclization of HCA into the less potent lactoneform preparation using different counte rions (such aspotassium sodium or calcium) had been applied [84] whichcontributed to the different degrees of stability bioavailabilityor solubility ofHCA [86] In this respect Louter-VanDeHaaret al [83] conducted a study on the efficacy of three commer-cially available HCA products on suppression of food intakein male Wistar rats Many human studies which reportedlack of efficacy used Super CitriMax at considerably lower


doses [41 70 71] On the contrary Preuss et al [16] reportedthat high doses of Super CitriMax exerted significant effectsin human Thus Louter-Van De Haar et al [83] suggestedthat the reported lack of efficacy of HCA in suppressing foodintake in human subjects might be due to the low dosesof a relatively low-effective HCA preparation Neverthelesssignificant suppression of food intake was observed in thestudies conducted by Leonhardt and Langhans [39] whereSprague-Dawley rats were supplemented with HCA for 10days after substantial fasting-induced weight loss It seemedthat HCA might be more effective in regulating weight gainthanpromotingweight loss thus it wasmore useful forweightmaintenance after an initial loss [39 102] Hence differencesin the experimental setups such as the difference in rat strainscould contribute to such discrepancy

52 Decreased De Novo Lipogenesis The reduction of theacetyl-CoA by HCA and thus limiting the availability ofbuilding blocks required for fatty acid and cholesterol biosyn-thesis has led to suggestions that HCA inhibited lipogenesisSeveral studies conducted by Sullivan and colleagues hadconfirmed the inhibition of in vivo and in vitro rates of lipoge-nesis in several tissues reported to convert carbohydrate intofatty acids (such as liver adipose tissue and small intestine)in which HCA was predominantly given to rodent models[78 79 85 96 97 108] Lowenstein [108] demonstrated thatHCA greatly inhibited in vivo fatty acid synthesis in rat liverThe rats were placed on chow diet for 7ndash10 days followed by45 h of fasting prior to a scheduled diet high in fructose orglucose for 10 to 15 daysThe sodium salt ofHCAat dose levelsof 2 to 20mMwas administered by intraperitoneal injections45min before injection of 3H

2O Fatty acid biosynthesis in

rat liver (120583moles 3H2O incorporatedg liverh) wasmeasured

35ndash5 h after starting of the final feeding Profound decreasein fatty acid synthesis by 25 to 30 days was obtained withan intraperitoneal dose of 01 mmole per kg of body weight(equivalent to approximately 29mg of HCA per 150 g rat) Inaddition 50 of inhibitionwas detected at a dose level of 028mmole per kg body weight

It was reported that G cambogiaHCA affected respira-tory quotient (RQ) and EE in rats and human Lim et al[109 110] showed that short-term administration of HCAdecreased the RQ in athletes and in untrained women Leon-hardt et al [106] further extended their study to determinethe effect of HCA on RQ and EE in rats fed ad libitum aftera period of substantial weight loss They reported that HCAmarkedly decreased RQ and EE during the first two days of adlibitum reflecting suppression of de novo lipogenesis in ratswhich is consistent with the findings ofWesterterp-Plantengaand Kovacs [61] in humans

In this respect Kovacs and Westerterp-Plantenga [60]further extended their study where the effects of HCAon net fat synthesis as de novo lipogenesis were investi-gated A double-blind placebo-controlled randomized andcrossover design experiment was conducted on 10 sedentarymale subjects The subjects performed glycogen depletionexercise followed by a 3-day high-fat low-carbohydrate(FCHOP 602515 energy 100 of EE depletion period)intake in order to create a similar glycogen storage capacity

Subsequently a 7-day high-carbohydrate diet (FCHOPlt5gt8510 energy 130ndash175 of EE overfeeding period)supplemented with either 500mg of regulator HCA (HOBIreland Ltd) or placebo was administered Each interventionended with a 60 h stay in the respiratory chamber (days 9 and10)De novo lipogenesis occurred as indicated by RQgt 100 inall subjects Significantly lower 24 h EE (119875 lt 005 on day 9)resting metabolic rate (119875 lt 001 on day 10) and RQ at night(119875 lt 005 on day 10) were detected with HCA as comparedto placebo Fat balance and thus net fat synthesis as de novolipogenesis tended to be lower (119875 lt 01) with HCA as com-pared to placebo Taken all together Kovacs andWesterterp-Plantenga concluded that the administration of HCA duringoverfeeding of carbohydratesmay reduce de novo lipogenesis

However opinions differ widely with respect to this issueThe mechanism underlying the anorectic effect of HCA isstill unclear Furthermore whether the suppression of bodyweight regained was solely due to reduced food intake orwhether there was involvement of increased EE remainedunknown Contradictory results were reported on the effectsof HCA on EE Previous reports by Leonhardt and colleagues[39 102] and the results obtained in pair-feeding studies[103] showed reduction of body weight regain and energyconversion ratio by HCA supporting the finding that HCAincreased EE However reduced energy conversion ratiocould be due to decreased nutrient absorption Vasselli et al[111] demonstrated an increment in 24 h EE in rats fed withmixed high-carbohydrate diet ad libitum by directly measur-ing the EE in a whole-body respirometer albeit no effect onthe RQ was detected Another study conducted by Leray etal [112] reported that 6 months of HCA administration didnot affected EE in adult neutered cats Besides most humanstudies [41 42 70] reported that HCA had no effect on EEKriketos et al [42] reported that HCA administration exhib-ited no effect on lipid oxidation in men during either rest ormoderately intense exercise on a cycle ergometer Howeverin these studies the subjects received a much smaller dosenamely a daily dose of 30 g per subject [nearly equal to15mgdaymouse] Furthermore their experimental periodof 3 days was quite short when compared with other studies

Blunden [113] reported that when Garcinia extract andinsulin were added simultaneously the number of largerdroplets markedly decreased while the smaller droplets (10ndash20120583m2 or lt10 120583m2) increased in 3T3-L1 cell The activityof cytosolic glycerophosphate dehydrogenase (GPDH) whichconverts dihydroxyacetne phosphate to glycerol 3-phosphate(predominant substrate for triglyceride synthesis) increasedfrom undetectable levels to between 100 and 187Umg ofcytosolic protein after adipose conversion However nosignificant decrease in enzymatic activity was detected afteradministration of the Garcinia extract Taken together theauthors therefore suggested that Garcinia extract interfereswith lipid synthesis in fat cells via fatty acid supply inhibitionwithout affecting adipose conversion

53 Increased Fat Oxidation Ishihara et al [35] conducteda study on acute and chronic effects of HCA on energymetabolism Acute administration of 10mg100120583L of a048molL HCA solution per mice significantly increased


(119875 lt 005) serum free fatty acid levels and concentration ofglycogen in the gastrocnemius muscle even though therespiratory exchange ratio was not different from that inthe control group On the other hand chronic adminis-tration of 10mg HCA twice a day significantly lowered(119875 lt 001) the RQ during resting and exercising conditionsin mice Lipid oxidation calculated from RQ and oxygenconsumption were significantly enhanced and carbohydrateoxidation was significantly less in these mice during theearly stages of running (119875 lt 001) Taken all together theauthors therefore suggested that chronic administration ofHCA augmented the endurance exercise performance inmice via the attenuation of glycogen consumption caused bythe promotion of lipid oxidation during running exerciseFurthermore Ishihara et al [35] suggested that chronic HCAadministration might have increased EE during the 3-weekexperimental period

In addition Lim et al [109 110] also showed that short-term administration of HCA increased fat oxidation duringexercise in athletes and in untrained women Lim et al [110]conducted a randomized placebo-controlled study wheresubjects (athletes) consumed HCA (250mg) or placebo for5 days after each time performing cycle ergometer exerciseat 60 VO

2max for 60min followed by 80 VO

2max until

exhaustion The results obtained showed that the respiratoryexchange ratio (RER) was significantly lower in theHCA trialthan in the control trial (119875 lt 005) Fat oxidation was sig-nificantly increased by short-term administration of HCAand carbohydrate oxidation was significantly decreased (119875 lt005) during exercise in athletes In a continuation of theirstudy Lim et al [109] conducted a similar study to evaluatethe effects of HCA administration on fat oxidation duringexercise in untrained women The results showed that HCAdecreased the RER and carbohydrate oxidation during 1 hourof exercise In addition exercise time to exhaustion wassignificantly enhanced (119875 lt 005)

A more recent approach for determining fat metabolismby HCA was conducted by measuring urinary concentrationof malondialdehyde (MDA) acetaldehyde (ACT) formalde-hyde (FA) and acetone (ACON) of the tested subjects Theurinary excretion of these four metabolites was proposedto be a consequence of enhanced 120573-oxidation of fats inbody tissues [16] The effect of HCA-SX had been studiedextensively by Preuss et al on obese human subjects [16 64]as well as on male and female Sprague-Dawley rats In therandomized double-blind and placebo-controlled clinicalstudies on obese human a group of subjects were given4667mg of HCA-SX daily (provided 2800mg HCAday)while the other given a combination of HCA-SX 4667mg4mg of niacin-bound chromium (NBC) and 400mg ofgymnema sylvestre extract (GSE) daily The control groupreceived placebo in 3 equal doses daily at 30 to 60min beforemeals In the trial involving 30 subjects urinary excretionof fat metabolites was increased by approximately 125ndash258whereas in trial involving 60 and 90 obese subjects themetabolite excretion increased by about 356ndash1064 [16] and32ndash109 [64] respectively As excretion of fat metaboliteswas enhanced in groups receiving the combination formulait was also suggested that HCS-SX either alone or in

combination with NBC and GSE could effectively promotebreakdown of fats [16 64]

54 Downregulation of a Spectrum of Obesity-AssociatedGenes Lipogenic transcription factors including SREBP1cliver X receptors PPAR120574 and CEBP120572 are highly expressedin the adipose tissue and actively participate in the lipidmetabolism of adipocytes by coordinating lipogenic andadipocyte-specific gene expression [114] PPAR120574 interactswith several other transcription factors CEBP120572 and PPAR120574interact via a positive feedback loop in the differentiatedadipocytes to induce each otherrsquos expression [115] Besidescoexpression of PPAR120574with SREBP1c increases the transcrip-tional activity of PPAR120574 [116] aP2 (a marker of terminaladipocyte differentiation) together with several adipocyte-specific genes including adiponectin insulin receptor leptinglucose transporter 4 (GLUT4) and glycerol phosphatedehydrogenase are induced during the adipogenic differ-entiation process [114] Leptin a 167-amino acid hormoneand a biomarker of the obesity regulatory gene is producedby fat tissue and is known to regulate energy intake andmetabolism Leptin binds to the medial nucleus of thehypothalamus and induces a sensation of satiety and thuscontrolling the appetite [98 117 118]

Fatty acid synthase acetyl-CoA carboxylase 1 andSREBP1c mRNA concentrations were decreased in the adi-pose tissue of the obese animal models [119] On the con-trary the mRNA and protein expression of TNF120572 (whichis involved in proinflammation apoptosis lipid metabolismand insulin resistance) were increased in the adipose tissuesof the obese rodents and humans [120] A high level of TNF120572suppressed transcription factors such as PPAR120574 and CEBP120572which in turn activated the GLUT4 gene [121 122]

Hayamizu et al [123] evaluated the effects of G cambogiafruit rind extract containing 60 (ndash)-HCA on serum leptinand insulin in mice G cambogia extract reduced serum totalcholesterol triacylglycerol and nonesterified fatty acids inmice Nevertheless the body weight gain and fat pad weightwere not affected in the treatment No significant differencein blood glucose level was detected between groups but a sig-nificant reduction of serum insulin (119875 lt 005) was detectedsuggesting that the G cambogia extract efficiently improvedglucose metabolism in the treated animals In addition thetreatment decreased serum leptin levels and the leptinWATratio Besides the changed ratio of body weight correlatedpositively with leptin levels in their study Furthermore it hadbeen reported that leptin suppressed the signal transductionof insulin via cytokine interactions [124 125] Hayamizu et al[123] suggested that the observed effect ofG cambogia extracton serum insulin in their study occurred through leptin-likeactivity

The antiobesity effects of Garcinia on visceral fat masslipid profiles in the serum and liver serum adipocytokinelevels and regulation of the expression of multiple adiposetissue genes were reviewed Kim et al [37] reported theantiobesity effects of a mixture composed of aqueous extractof G cambogia soy peptide and L-carnitine (12 03 002www) on rats rendered obese by high-fat diet (HFD)An HFD (40 fat calories) with identical composition of


Table 3 Summary of clinical studies of GarciniaHCA that have shown significant antiobesity effect

Duration Subject Treatment Outcome References

10 days 44 healthy volunteers 4 g for the 1st day followed by 3 guntil day 10 Not recorded [59]

11 daysNormal groups placebo HCAof total 10 sedentary male underhigh-fat diet

1500mg HCA daily

No significant effects on body weightgain appetite-related and plasmaparameters but decreased fat depositionlowastlowastComments suggest that (minus)-HCA mayreduce net fat deposition from de novolipogenesis during weight gain

[60]

2 weeksBMI 275 groups placebo HCAof 24 subjects each (12 males 12females)

300mg HCA Reduced of energy intake and slightdecreased of body weight [61]

4 weeksObese hypocaloric diet groupsplacebo 1 capsule 2 capsule (50subjects each group)

55mg G cambogia + 19mgchromium + 240mgchitosanday

Weight loss associated with lowerTCLDL and higher HDL [62]

8 weeks BMI 25ndash35 groups placebotreatment of 20 each 1000mg HCAday Reduced of visceral and subcutaneous fat

area [63]

8 weeksModerate obese groups placeboHCA-SX HCA-SX + NBC + GSEof total 60

HCA-SX 4667mg (60 HCA)4667mg HCA-SX + 400120583gniacin-bound chromium +400mg Gymnema sylvestreextract

Significant (119875 lt 005) decrease in BMIfood intake total cholesterol low-densitylipoproteins triglycerides and serumleptin levels increase in high-densitylipoprotein levels and enhancedexcretion of urinary fat metabolites(biomarker of fat oxidation includingmalondialdehyde acetaldehydeformaldehyde and acetone) in HCA andHCA-NBC-GSE groups

[16]

8 weeks

BMI 30ndash50 groups placebo2800mg HCA 2800mg HCA +400120583g chromium of 30 subjectseach

2800mg HCA 2800mg ofHCA-SX + 400120583g chromium +100mg gymnemic acidday

Decreased of body weight BMI LDLand TG and increased fat oxidation [64]

8 weeksNormal group 35 healthysubjects on diets 1000 1200 or1500 kcal

1500mg G cambogia extractdaily

Significant reduction of total cholesteroltriacylglycerol and body weightassociated with reduced appetite

[65]

8 weeks Obese groups placebo andtreatment of total 50 F 345 g G atroviridis

Significant reduction of body weightBMI body fat lean body mass andanthropometric parameters (bicepssubscapular suprailiac crest skinfoldthicknesses and upper armcircumference) but no change of serumlipid profile

[66]

60 days Over weight to obese groupsplacebo and treatment of total 58

285mg (minus)-HCA in Slim339 Gcambogia extract daily Significant reduced of body weight (47) [67]

12 weeksBMI 275ndash39 groups placeboand treatment (18 females2males each) of total 40

300mg G cambogia + 1200mgPhaseolus vulgaris + 1200mginulinday

Significant body weight lost (35 kg versus12 kg) [68]

12 weeks BMI sim28 groups placebo 47treatment 42 2400mg G cambogiaday Significant body weight lost [69]

the high-fat control diet (CD) applied in the study was fedto five-week-old male Sprague-Dawley rats for 9 weeks tocreate an obese conditions in rats that mimic to humanobesity Body weight gain visceral fat-pad weight and serumand hepatic biochemistry of rats were measured The 038mixture-supplemented HFD (D + M) reduced the totalbody weight and the accumulation of visceral fat mass andlowered the blood and hepatic lipid levels which led to theimprovement of insulin resistance in the HFD-induced obese

rats Moreover the mixture of G cambogia soy peptide andL-carnitine improved dyslipidemia in rat models with HFD-induced obesity Downregulation of the expression of leptintumor necrosis factor-alpha and sterol regulatory elementbinding protein 1c genes in the epididymal fat tissue of rats fedwith CD + M diet was obtained In contrary upregulation ofthe uncoupling protein 2 (UCP2) gene in epididymal adiposetissues was induced with CD + M diet No effect on the foodintake of the animals was observed in the study suggesting


Table 4 Summary of clinical studies of GarciniaHCA that have shown none significant antiobesity effect


1 day Normal groups placebo HCAof total 10 cyclists 4300 g HCA No significant changes in total fat and

carbohydrate oxidation rates [70]

2 weeks

Normal-moderately obesegroup placebo HCA and HCA+MCT of total 7 males and 14females

500mg HCA 500mg HCA + 3 gmedium chain triacylglycerols(MCT)

No significant differences in satiety dailyenergy intake and body weight losswithin all groupslowastlowastComment subjects were undernegative energy balance conditions(eliminating the possibility of de novolipogenesis and reservation of glycogenreserves had occurred thus the onlypossible remaining mechanism increasedhepatic fatty acid oxidation)

[71]

2 weeksNormal-moderately obesegroups placebo HCA and HCA+MCT of total 11 male


No significant differences in body weightreduction EE appetite ratings andsubstrates oxidation (protein fat andcarbohydrate oxidation) within all groupslowastlowastComment 2-week intervention is tooshort

[41]

2 weeks

Normal-moderately obesegroups placebo HCA of total 10sedentary males with or withoutmoderately intense exercise

3 g (minus)-HCA dailyNo significant difference in RQ EE andblood parameters during rest nor duringexercise

[42]

8 weeks 39 subjects 1500mg G cambogia + 300 120583gchromium picolinateday

No significant difference in control andplacebo [72]

10 weeks Overweight groups treatment29 placebo 29 2 g G cambogia extract daily

No clinically significant differences inbody composition plasma lipid profilesantioxidant enzyme activity and plasmaadipocytokines

[73]

12 week Obese treatment 5M 61 Fplacebo 14M 55 F

G cambogia extract 3000mg of(50 of HCA)Diet 5020 kJday (1200 kcalday)

No significant difference in body weightand fat mass loss [40]

12 weeks Obese groups treatment 36 F11M placebo 41 F 10M

Botanical extract (1000mg HCAdaily)

No difference between placebo andtreatment group but significant change ofthe body composition improvementindex body free fat mass weight BMIand some other anthropometricmeasurements in both treatment andplacebo groups

[74]


24 g G cambogia (524 HCA)+ 15 g A konjac (949glucomannan)

No significantvariation in bodyweightother anthropometric andcalorimetric parameters but significanthypercholesterolemic

[75]

12 weeks BMI 28 groups placebo 23treatment 21

16673mg of G cambogiaextractday (1000mg HCAday) No significant effect [76]

that the mixture exerted antiobesity effect via modulation ofthe metabolic derangement induced by HFD during whichinteractions between the multiple genes implicated in theprocess of adipogenesismight be involved rather than simplysuppressing appetite A similar observation was obtained byKim et al [38] where in addition to the reduction of foodintake the food efficiency ratio (FER) was also significantlylower in the G cambogia diet administrated group than inthe HFD mice implying less efficient transformation of thefeed mass into body mass

6 Human Clinical Trials

The antiobesity effects of G cambogia in terms of promotingweight loss and lowering cholesterol level were extensivelystudied However evidence for the effectiveness of G cambo-gia or its derivative products was largely derived from animalstudies [126] Despite the intriguing evidence of antiobesityeffects of G cambogia from in vitro and animal studiesmore equivocal results were obtained from randomizeddouble-blind placebo-controlled experiments dealing with


Table 5 Commercialized dietary supplements that contain G cambogia extractHCA

Product name Company Concentration ofHCA

Doses recommended(daily) Formulation of supplement

Super CitriMaxHCA-600-SXS

Inter healthNI

60 (minus)-HCA in itsfree form 10(minus)-HCA in itslactone form

3 capsules 3 timesdaily 30ndash60minbefore meal

3 capsules per serving G cambogia extract 1500mg(providing 900mg of HCA) calcium 150mg potassium225mg 05 sodium 01 magnesium 003 iron 005total phytosterols 03 total protein 45 moisture and85 soluble dietary fiber

GarCitrin SabinsaCorporation 50 (minus)-HCA 500mg 3 times daily 500mg of GarCitrin (providing 250mg of HCA) and 5

Garcinol

Sci-Fit Pro Cut 50 (minus)-HCA4 capsules 2-3 timesdaily 30ndash60minbefore meal

4 capsules per serving G cambogia 1000mg (providing500mg of HCA) green tea extract 500mg (98polyphenols) (45 epigallocatechinEGCG) guaranaextract 910mg (22 caffeine) caffeine 100mg L-carnitine100mg white willow bark extract 100mg (standardizedfor 15 salicin) dandelion 100mg juniper berry extract100mg buchu extract 100mg and chromium 200mg

G cambogia andKola Nut450mg

TerraVita mdash 1 capsule 3 timesdaily with meals 225mg G cambogia fruit 225mg kola nut

G cambogia ProTheraInc 50 (minus)-HCA 1ndash6 capsules daily

before meals

500mg G cambogia (providing min 250mg of HCA)vegetarian capsule (hydroxypropyl methylcellulosewater) cellulose magnesium stearate and silicon dioxide

G cambogiaPlus Atrium Inc 50 (minus)-HCA 2 capsules 3 times

daily

Chromium 166120583g (as Cr picolinate 500mg and Crarginate 160mg) G cambogia 340mg (providing 170mgof HCA) atractylodes 80mg citrus aurantii 80mggelatin rice powder and magnesium staerate

G cambogiaPlus BioCare Ltd 50 (minus)-HCA 3 capsules daily

20min before food

G cambogia 500mg vitamin B5 (calcium pantothenate)6mg vitamin C (ascorbic acid) 5mg manganesegluconate(providing 270 120583g elemental manganese) 25mgand chromium polynicotinate 09mg (providing 100120583gelemental chromium)

Garcinia 1000 SourceNaturals 50 (minus)-HCA 1 tablet twice daily 1

hour before meal

Chromium (as chromiumpolynicotinate [ChromeMate]and chromium picolinate) 150120583g sodium 25mg Gcambogia fruit extract (providing 500mg of HCA) 1 g

Garcinia 1000hydroxycitricacid

Naturersquos life 50 (minus)-HCA mdashG cambogia rind concentrate (providing 500mg of HCA)1 g cellulose silicon dioxide magnesium stearate andldquoMicro-Celluloserdquo coating

Citrin NaturalNirvana mdash 1 capsule 2 times

daily G cambogia 495mg BioPerine 5mg

HCA 450mgtablet

Highernature

450mg HCA pertablet

1-2 tablets 3 timesdaily 30min beforemeal

Tamarind fruit extract microcrystalline cellulosemagnesium stearate (vegetarian source) hydroxypropylmethylcellulose coating silicon dioxide and acaciapowder

HCA Hydroxycitric acid

ViridianNutrition

Ltd50 (minus)-HCA 1 capsule 3 times

daily before meal

G cambogia (providing 250mg HCA) 500mg viridianbilberry extract alfalfa spirulina blend 150mg andvegetarian cellulose capsule 120mg

HCAhydroxycitricacid

LifeExtensionFoundation

50 (minus)-HCA

1 capsule 3 timesdaily 45min beforemeals with 1 capsuleof CitriChrome

G cambogia (fruit) (providing 250mg of HCA) 500mg

Hydroxycitrate Solgar 50 (minus)-HCA 1 capsule 30ndash60minbefore meal

G cambogia fruit powdered extract (providing 250mg[50] HCA) 500mg hydroxypropylmethyl cellulosevegetable magnesium stearate and silicon dioxide

HydroxycitratePlus Metagenics mdash

1 tablet 3 times daily30ndash60min beforemeal

Garcinia fruit extract (G cambogia) 500mg L-carnitine100mg niacin (as niacinamide) 50mg pantothenic acid(as D-calcium pantothenate) 25mg riboflavin 10mgmanganese (as manganese arginine) 750 120583g andchromium (as chromium nicotinate glycinate) 75 120583g


human subjects [127ndash130] Hayamizu et al [59] conducteda crossover design randomized controlled trials (RCTs) todetermine the ldquono observed adverse effect level (NOAEL)rdquoof G cambogia extract in 44 healthy volunteers (22 malesand 22 females) and concluded that G cambogia is generallysafe to be consumed Several equivocal findings of RCTswere reported on the effectiveness of supplements containingHCA (Table 3) Some studies reported that HCA exerted nosignificant effects as compared to the placebo group [40 4270] (Table 4) All the above findings were in agreement withthemost recent meta-analysis of RCTs which revealed thatGcambogia extract possessed limited or no effects on weight-loss in human subjects [131] Moreover this study showed noeffect on satiety or calorie intake in overweight individualsconsuming their habitual diet which is in agreement withpast studies [41 60 75] However such comparisons must bemadewith caution as the variations in the formulations dosesadministered RCTs designs and study populations mightcontribute to the discrepancy of the results

Preclinical studies using rodent models have confirmedthe body weight reduction appetite suppression and subse-quently food intake reduction effects of HCA in rats Clin-ically however HCA failed to perform well Several factorsthatmight contribute to this scenario are theATP citrate lyasewhich might be important only at very high carbohydratediets a type of diet that most studies did not prescribeBesides a high-fiber diet can bind to HCA and block itthus reducing its efficacy HCA and G cambogia exertedpotential effects in weight management but clinical studieshave yet to prove optimumconditions forHCA to be effectiveFor instance Sullivan et al [85] reported that hepatic lipidsynthesis was reduced only if HCA was administered beforethe beginning of feeding reaching optimum 30ndash60 minutesprior to feeding The reason for this remains unknown

7 Patents and Commercialization

The claims on enhanced human health associated withGarciniaHCA had been reviewed in Section 4 In particularthe antiobesity effects of GarciniaHCA were extensivelyreported This has resulted in the availability of numerouscommercialized weight-management products derived fromGarciniaHCA (Table 5) Several products of G cambogiaor its derivatives had been patented and commercializedAs of August 2012 a total of 66 patents that apply to Gcambogia or HCA derived from Garcinia were filed with theUS Patent and Trademark Office (USPTO) since 1976 (searchof US Patents and Trademark Office in year 2012 usingGoogle patent search) These patents are on various aspectsincluding HCA enrichment from Garcinia rind HCA andfood productsdietary supplements prepared therefrommethods of production and their use The majority of thepatents are related to G cambogiaatroviridis andor HCAderived from Garcinia on obesity and weight loss Thepatent numbers are as follows 8197867 8097286 80171478003138 7943186 7943183 7927636 7858128 78469707772428 7741370 7687082 7550161 7507421 74319517335651 7311929 7230131 7214823 7208615 71894167179488 7063861 6982098 6899891 6875891 6855358

6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions

The nutraceutical industry is flourishing and interest inestablishing scientific credibility has attained importance formany companies and scientists In the recent years moreclinical trials had been conducted to elucidate the functionaleffects of GarciniaHCA supplementation on promotinghuman health A multitude of metabolic functions had beenreported for HCA or HCA-containing Garcinia extract suchas reducing blood lipids inducing weight loss suppressingappetite and reducing food intake based on results obtainedin both animal trials and human clinical trials (Figure 1)These discoveries make the development of evidence-basedadjuvant modalities to curb the trend of the increasingprevalence of obesity and obesity-related comorbidity andmortality possible We have previously reviewed and con-cluded that Garcinia extract and HCA were generally safeto be consumed Collective results from 17 clinical studieswhich involved 873 subjects demonstrated the safety of HCAand HCA-SX for human consumption [43] These studiesprovided scientific evidence that intake of HCA andHCA-SXalone did not produce adverse effects and a dietary dosage ofup to 2800mgday was regarded as the ldquono observed adverseeffect level (NOAEL)rdquo of HCA-SX in human [84] Based onthese animal and human safety data HCA-SX also receivedself-affirmed GRAS status in the USA by the Burdock Groupin year 2003 [132] However definitive conclusions thatGarciniaHCA supplements are efficient tools against varioushealth problems especially obesity remain to be proven inlarger-scale and longer-term clinical trials despite substantialpublic interest in such supplements Many diet supplementscontaining GarciniaHCA marketed as weight managementproducts are the combination of active ingredients ratherthan containing a single agent Thus it is difficult to evaluatethe effectiveness of single agents when the combinationproducts are tested In addition awareness of the safety andefficacy of the weight management supplements available inthe market should be raised among health care providers inorder to assist their patients in analyzing the risks and benefitsof the dietary supplements Thus scientific investigations onthe potential health promoting effects of herbal preparationsas diet supplement are prerequisites for new discoveries ofalternative therapies

Acknowledgment

The authors would like to thanks Professor S G Tan for theproofreading of this paper


References

[1] WHO ldquoGlobal database on body mass indexrdquo httpappswhointbmiindexjsp 2012

[2] W H O expert consultation ldquoAppropriate body-mass indexfor Asian populations and its implications for policy andintervention strategiesrdquoThe Lancet vol 363 pp 157ndash163 2004

[3] International Association for the Study of Obesity (IASO) ldquoGlobal prevalence of adult obesity (BMI ge 30 kgm2) countryrankings 2012rdquo httpwwwiasoorgsite mediauploadsGlobal prevalence of adult obesity Ranking by country 2012pdf 2012

[4] WHO ldquoObesity preventing andmanaging the global epidemicreport of a WHO consultationrdquo WHO Technical Report Series894 World Health Organization Geneva Switzerland 2000

[5] G A Bray and F L Greenway ldquoPharmacological treatment ofthe overweight patientrdquo Pharmacological Reviews vol 59 no 2pp 151ndash184 2007

[6] United States Food and Drug Administration Center for DrugEvaluation and Research ldquoEndocrinologic andmetabolic drugsadvisory committeerdquo httpwwwfdagovdownloadsAdvi-soryCommitteesCommitteesMeetingMaterialsDrugsEndo-crinologicandMetabolicDrugsAdvisoryCommitteeUCM224180pdf 2012

[7] United States Food and Drug Administration ldquoMeridia(sibutramine) market withdrawal due to risk of seriouscardiovascular eventsrdquo httpwwwfdagovsafetymedwatchsafetyinformationsafetyalertsforhumanmedicalproductsucm228830htm 2010

[8] D Heber ldquoHerbal preparations for obesity are they usefulrdquoPrimary Care vol 30 no 2 pp 441ndash463 2003

[9] T K Lim Edible Medicinal and Non-Medicinal Plants vol 2 ofFruits Springer Heidelberg Germany 2012

[10] W Sergio ldquoA natural food the Malabar Tamnarind may beeffective in the treatment of obesityrdquo Medical Hypotheses vol27 no 1 pp 39ndash40 1988

[11] H DruryThe Useful Plants of India With Notices of Their ChiefValue in Commerce Medicine and the Arts William H Allen ampCo London UK 2nd edition 1873

[12] B S Jena G K Jayaprakasha R P Singh and K K SakariahldquoChemistry and biochemistry of (minus)-hydroxycitric acid fromGarciniardquo Journal of Agricultural and Food Chemistry vol 50no 1 pp 10ndash22 2002

[13] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[14] A Sreenivasan andRVenkataraman ldquoChromatographic detec-tion of the organic constituents of Gorikapuli (Garcinia cam-bogia Desr) used in pickling fishrdquo Current Science vol 28 pp151ndash152 1959

[15] S E Ohia C A Opere A M LeDay M Bagchi D Bagchiand S J Stohs ldquoSafety and mechanism of appetite suppressionby a novel hydroxycitric acid extract (HCA-SX)rdquoMolecular andCellular Biochemistry vol 238 no 1-2 pp 89ndash103 2002

[16] HG PreussD BagchiM Bagchi CV S RaoDKDey and SSatyanarayana ldquoEffects of a natural extract of (minus)-hydroxycitricacid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weightlossrdquoDiabetes Obesity andMetabolism vol 6 no 3 pp 171ndash1802004

[17] S Roy C Rink S Khanna et al ldquoBody weight and abdominalfat gene expression profile in response to a novel hydroxycitric

acid-based dietary supplementrdquo Gene Expression vol 11 no 5-6 pp 251ndash262 2003

[18] A B Deore V D Sapakal N L Dashputre andN S NaikwadeldquoAntiulcer activity ofGarcinia indica linn fruit rindsrdquo Journal ofApplied Pharmaceutical Science vol 1 pp 151ndash154 2011

[19] P Mahendran A J Vanisree and C S Shyamala Devi ldquoTheantiulcer activity of Garcinia cambogia extract against indome-thacin induced gastric ulcer in ratsrdquo Phytotherapy Research vol16 no 1 pp 80ndash83 2002

[20] F Yamaguchi M Saito T Ariga Y Yoshimura and H Naka-zawa ldquoFree radical scavenging activity and antiulcer activity ofgarcinol fromGarcinia indica fruit rindrdquo Journal of Agriculturaland Food Chemistry vol 48 no 6 pp 2320ndash2325 2000

[21] M Asghar E Monjok G Kouamou S E Ohia D Bagchiand M F Lokhandwala ldquoSuper CitriMax (HCA-SX) attenuatesincreases in oxidative stress inflammation insulin resistanceand body weight in developing obese Zucker ratsrdquo Molecularand Cellular Biochemistry vol 304 no 1-2 pp 93ndash99 2007

[22] M M Mackeen A M Ali N H Lajis et al ldquoAntimicrobialantioxidant antitumour-promoting and cytotoxic activities ofdifferent plant part extracts of Garcinia atroviridis Griff ex TAndersrdquo Journal of Ethnopharmacology vol 72 no 3 pp 395ndash402 2000

[23] F Yamaguchi T Ariga Y Yoshimura and H Nakazawa ldquoAnti-oxidative and anti-glycation activity of garcinol from Garciniaindica fruit rindrdquo Journal of Agricultural and Food Chemistryvol 48 no 2 pp 180ndash185 2000

[24] Y Yonei Y Takahashi S Hibino M Watanabe and T Yosh-ioka ldquoEffects on the human body of a dietary supplementcontaining L-carnitine and Garcinia cambogia extract a studyusing double-blind testsrdquo Journal of Clinical Biochemistry andNutrition vol 42 no 2 pp 89ndash103 2008

[25] P Y Wielinga R E Wachters-Hagedoorn B Bouter et alldquoHydroxycitric acid delays intestinal glucose absorption in ratsrdquoAmerican Journal of Physiology vol 288 no 6 ppG1144ndashG11492005

[26] P S Negi and G K Jayaprakasha ldquoControl of foodbornepathogenic and spoilage bacteria by garcinol and Garciniaindica extracts and their antioxidant activityrdquo Journal of FoodScience vol 69 no 3 pp FMS61ndashFMS65 2004

[27] D Permana N H Lajis M M Mackeen et al ldquoIsolation andbioactivities of constitutents of the roots ofGarcinia atroviridisrdquoJournal of Natural Products vol 64 no 7 pp 976ndash979 2001

[28] K N Varalakshmi C G Sangeetha A N Shabeena S RSunitha and J Vapika ldquoAntimicrobial and cytotoxic effects ofGarcinia indica fruit rind extractrdquoAmerican-Eurasian Journal ofAgricultural amp Environmental Sciences vol 7 pp 652ndash656 2010

[29] MMMackeen A M Ali N H Lajis K Kawazu H KikuzakiandN Nakatani ldquoAntifungal garcinia acid esters from the fruitsof Garcinia atroviridisrdquo Zeitschrift fur Naturforschung C vol 57no 3-4 pp 291ndash295 2002

[30] S B D Reis C C De Oliveira S C Acedo et al ldquoAttenuationof colitis injury in rats using Garcinia cambogia extractrdquoPhytotherapy Research vol 23 no 3 pp 324ndash329 2009

[31] A Syahida D A Israf D Permana et al ldquoAtrovirinone inhibitspro-inflammatory mediator release from murine macrophagesand human whole bloodrdquo Immunology and Cell Biology vol 84no 3 pp 250ndash258 2006

[32] E A Mazzio and K F A Soliman ldquoIn vitro screening forthe tumoricidal properties of international medicinal herbsrdquoPhytotherapy Research vol 23 no 3 pp 385ndash398 2009


[33] M A Parasramka and S V Gupta ldquoGarcinol inhibits cell prolif-eration and promotes apoptosis in pancreatic adenocarcinomacellsrdquo Nutrition and Cancer vol 63 no 3 pp 456ndash465 2011

[34] S Prasad J Ravindran B Sung M K Pandey and B B Aggar-wal ldquoGarcinol potentiates TRAIL-induced apoptosis throughmodulation of death receptors and antiapoptotic proteinsrdquoMolecular Cancer Therapeutics vol 9 no 4 pp 856ndash868 2010

[35] K Ishihara S Oyaizu K Onuki K Lim and T FushikildquoChronic (minus)-hydroxycitrate administration spares carbohy-drate utilization and promotes lipid oxidation during exercisein micerdquo Journal of Nutrition vol 130 no 12 pp 2990ndash29952000

[36] G Kaur and S K Kulkarni ldquoInvestigations on possible sero-tonergic involvement in effects of OB-200G (polyherbal prepa-ration) on food intake in female micerdquo European Journal ofNutrition vol 40 no 3 pp 127ndash133 2001

[37] Y J Kim K Kim M S Kim J H Lee K P Lee and T ParkldquoA mixture of the aqueous extract of Garcinia cambogia soypeptide and L-carnitine reduces the accumulation of visceralfat mass in rats rendered obese by a high fat dietrdquo Genes andNutrition vol 2 no 4 pp 353ndash358 2008

[38] K Kim H N Lee Y J Kim and T Park ldquoGarcinia cambogiaextract ameliorates visceral adiposity in C57BL6J mice fed ona high-fat dietrdquo Bioscience Biotechnology and Biochemistry vol72 no 7 pp 1772ndash1780 2008

[39] M Leonhardt andW Langhans ldquoHydroxycitrate has long-termeffects on feeding behavior body weight regain andmetabolismafter bodyweight loss inmale ratsrdquo Journal of Nutrition vol 132no 7 pp 1977ndash1982 2002

[40] S B Heymsfield D B Allison J R Vasselli A Pietrobelli DGreenfield and C Nunez ldquoGarcinia cambogia (hydroxycitricacid) as a potential antiobesity agent a randomized controlledtrialrdquo Journal of the American Medical Association vol 280 no18 pp 1596ndash1600 1998

[41] E M R Kovacs M S Westerterp-Plantenga and W H MSaris ldquoThe effects of 2-week ingestion of (minus)-hydroxycitrate and(minus)-hydroxycitrate combined with medium-chain triglycerideson satiety fat oxidation energy expenditure and body weightrdquoInternational Journal of Obesity vol 25 no 7 pp 1087ndash10942001

[42] A D Kriketos H R Thompson H Greene and J O Hillldquo(minus)-Hydroxycitric acid does not affect energy expenditure andsubstrate oxidation in adult males in a post-absorptive staterdquoInternational Journal of Obesity vol 23 no 8 pp 867ndash873 1999

[43] L O Chuah S K Yeap W Y Ho B K Beh and N BanuAlitheen ldquoIn vitro and in vivo toxicity of Garcinia or hydro-xycitric acid a reviewrdquo Evidence-Based Complementary andAlternative Medicine vol 2012 Article ID e197920 12 pages2012

[44] P C Sharma M B Yelne and T J Dennis Database onMedicinal Plants Used in Ayurveda vol 2 Central Council forResearch in Ayurveda amp Siddha New Delhi India 2005

[45] Y S Lewis and S Neelakantan ldquo(minus)-Hydroxycitric acid-theprincipal acid in the fruits of Garcinia cambogia desrrdquo Phyto-chemistry vol 4 no 4 pp 619ndash625 1965

[46] G K Jayaprakasha and K K Sakariah ldquoDetermination oforganic acids in Garcinia cambogia (Desr) by high- perfor-mance liquid chromatographyrdquo Journal of Chromatography Avol 806 no 2 pp 337ndash339 1998

[47] G K Jayaprakasha and K K Sakariah ldquoDetermination oforganic acids in leaves and rinds of Garcinia indica (Desr) by

LCrdquo Journal of Pharmaceutical and Biomedical Analysis vol 28no 2 pp 379ndash384 2002

[48] L Muensritharam V Tolieng C Chaichantipyuth A Petsomand T Nhujak ldquoCapillary zone electrophoresis for separationand analysis of hydroxycitric acid and hydroxycitric acidlactone application to herbal products of Garcinia atroviridisGriffrdquo Journal of Pharmaceutical and Biomedical Analysis vol46 no 3 pp 577ndash582 2008

[49] D Permana F Abas M Maulidiani et al ldquoAtrovirisidone Ba new prenylated depsidone with cytotoxic property from theroots of Garcinia atroviridisrdquo Zeitschrift fur Naturforschung Cvol 60 no 7-8 pp 523ndash526 2005

[50] D Permana N H Lajis K Shaari et al ldquoA new prenylatedhydroquinone from the roots of Garcinia atroviridis Griff ex TAnders (Guttiferae)rdquo Zeitschrift fur Naturforschung B vol 58no 4 pp 332ndash335 2003

[51] M Iinuma T Ito R Miyake H Tosa T Tanaka and V Chel-ladurai ldquoA xanthone from Garcinia cambogiardquo Phytochemistryvol 47 no 6 pp 1169ndash1170 1998

[52] P J Cotterill F Scheinmann and G S Puranik ldquoPhenoliccompounds from the heartwood of Garcinia indicardquo Phyto-chemistry vol 16 no 1 pp 148ndash149 1977

[53] J Kosin N Ruangrungsi C Ito and H Furukawa ldquoA xanthonefrom Garcinia atroviridisrdquo Phytochemistry vol 47 no 6 pp1167ndash1168 1998

[54] M Masullo C Bassarello H Suzuki C Pizza and S PiacenteldquoPolyisoprenylated benzophenones and an unusual polyiso-prenylated tetracyclic xanthone from the fruits of Garciniacambogiardquo Journal of Agricultural and Food Chemistry vol 56no 13 pp 5205ndash5210 2008

[55] S Kumar S Sharma and S K Chattopadhyay ldquoHigh-performance liquid chromatography and LC-ESI-MS methodfor identification and quantification of two isomeric polyiso-prenylated benzophenones isoxanthochymol and camboginolin different extracts ofGarcinia speciesrdquoBiomedical Chromatog-raphy vol 23 no 8 pp 888ndash907 2009

[56] S K Chattopadhyay and S Kumar ldquoA rapid liquid chromato-graphy-tandem mass spectrometry method for quantificationof a biologically active molecule camboginol in the extract ofGarcinia cambogiardquo Biomedical Chromatography vol 21 no 1pp 55ndash66 2007

[57] A V Rama Rao G Venkatswamy andA D Pendse ldquoCambogi-nol and camboginrdquoTetrahedron Letters vol 21 no 20 pp 1975ndash1978 1980

[58] N Krishnamurthy Y S Lewis and B Ravindranath ldquoOn thestructures of garcinol isogarcinol and camboginolrdquo Tetrahe-dron Letters vol 22 no 8 pp 793ndash796 1981

[59] K Hayamizu Y Ishii I Kaneko M Shen Y Okuhara HSakaguchi et al ldquoNo-Observed-Adverse-Effect Level (NOAEL)and sequential-high- dose administration study on Garciniacambogia extract in humansrdquo Journal of Oleo Science vol 51pp 365ndash369 2002

[60] E M R Kovacs and M S Westerterp-Plantenga ldquoEffects of(minus)-hydroxycitrate on net fat synthesis as de novo lipogenesisrdquoPhysiology and Behavior vol 88 no 4-5 pp 371ndash381 2006

[61] M S Westerterp-Plantenga and E M R Kovacs ldquoThe effect of(minus)-hydroxycitrate on energy intake and satiety in overweighthumansrdquo International Journal of Obesity vol 26 no 6 pp 870ndash872 2002

[62] M Girola M De Bernardi and S Contos ldquoDose effect inlipid lowering activity of a new dietary integrator (Chitosan


Garcinia cambogia extract and Chrome)rdquo Acta Toxicologica EtTherapeutica vol 17 pp 25ndash40 1996

[63] K Hayamizu Y Ishii I Kaneko et al ldquoEffects of Garciniacambogia (Hydroxycitric Acid) on visceral fat accumulationa double-blind randomized placebo-controlled trialrdquo CurrentTherapeutic Research vol 64 no 8 pp 551ndash567 2003

[64] H G Preuss R I Garis J D Bramble et al ldquoEfficacy of a novelcalciumpotassium salt of (minus)-hydroxycitric acid in weight con-trolrdquo International Journal of Clinical Pharmacology Researchvol 25 no 3 pp 133ndash144 2005

[65] R Roman Ramos J Flores Saenz and M C F AlarconAguilar en ldquoControl of obesity withGarcinia cambogia extractrdquoInvestigacion Medica Internacional vol 22 no 3 pp 97ndash1001996

[66] C Roongpisuthipong R Kantawan andW RoongpisuthipongldquoReduction of adipose tissue and body weight Effect of watersoluble calcium hydroxycitrate in Garcinia atroviridis on theshort term treatment of obese women inThailandrdquo Asia PacificJournal of Clinical Nutrition vol 16 no 1 pp 25ndash29 2007

[67] E Toromanyan G Aslanyan E Amroyan E Gabrielyan andA Panossian ldquoEfficacy of Slim339 in reducing body weight ofoverweight and obese human subjectsrdquo Phytotherapy Researchvol 21 no 12 pp 1177ndash1181 2007

[68] EThom ldquoA randomized double-blind placebo-controlled trialof a new weight-reducing agent of natural originrdquo Journal ofInternationalMedical Research vol 28 no 5 pp 229ndash233 2000

[69] R D Mattes and L Bormann ldquoEffects of (minus)-hydroxycitric acidon appetitive variablesrdquo Physiology and Behavior vol 71 no 1-2pp 87ndash94 2000

[70] L J C Van Loon J J M Van Rooijen B Niesen H VerhagenW HM Saris and A J MWagenmakers ldquoEffects of acute (minus)-hydroxycitrate supplementation on substratemetabolism at restand during exercise in humansrdquo American Journal of ClinicalNutrition vol 72 no 6 pp 1445ndash1450 2000

[71] E M R Kovacs M S Westerterp-Plantenga M De Vries FBrouns andW H M Saris ldquoEffects of 2-week ingestion of (minus)-hydroxycitrate and (minus)-hydroxycitrate combinedwithmedium-chain triglycerides on satiety and food intakerdquo Physiology andBehavior vol 74 no 4-5 pp 543ndash549 2001

[72] A A Conte ldquoA non-prescription alternative in weight reduc-tion therapyrdquo American Journal of Bariatric Medicine pp 17ndash19summer1993

[73] J Kim S Jeon K Park et al ldquoDoes Glycine max leavesor Garcinia cambogia promote weight-loss or lower plasmacholesterol in overweight individuals a randomized controltrialrdquo Nutrition Journal vol 10 no 1 article 94 2011

[74] T Opala P Rzymski I Pischel M Wilczak and J WozniakldquoEfficacy of 12 weeks supplementation of a botanical extract-based weight loss formula on body weight body composi-tion and blood chemistry in healthy overweight subjectsmdasha randomised double-blind placebo-controlled clinical trialrdquoEuropean Journal ofMedical Research vol 11 no 8 pp 343ndash3502006

[75] C A R Vasques S Rossetto G Halmenschlager et al ldquoEvalu-ation of the pharmacotherapeutic efficacy ofGarcinia cambogiaplus amorphophallus konjac for the treatment of obesityrdquoPhytotherapy Research vol 22 no 9 pp 1135ndash1140 2008

[76] K Hayamizu H Tomi I Kaneko M Shen M G Soni andG Yoshino ldquoEffects of Garcinia cambogia extract on serum sexhormones in overweight subjectsrdquo Fitoterapia vol 79 no 4 pp255ndash261 2008

[77] TheWealth of India RawMaterials IV CSIR New Delhi India1956

[78] A C Sullivan J Triscari and H E Spiegel ldquoMetabolic reg-ulation as a control for lipid disorders I Influence of(minus)-hydroxycitrate on experimentally induced obesity in therodentrdquoAmerican Journal of Clinical Nutrition vol 30 pp 767ndash776 1977

[79] A C Sullivan J Triscari and H E Spiegel ldquoMetabolicregulation as a control for lipid disorders II Influence of(minus)-hydroxycitrate on genetically and experimentally inducedhypertriglyceridemia in the ratrdquo American Journal of ClinicalNutrition vol 30 no 5 pp 777ndash784 1977

[80] W C Stallings J F Blount P A Srere and J P GluskerldquoStructural studies of hydroxycitrates and their relevance tocertain enzymatic mechanismsrdquo Archives of Biochemistry andBiophysics vol 193 no 2 pp 431ndash448 1979

[81] J Kjeldstadli and E Thom ldquoSynthetically prepared composi-tion for treatment andor prophylaxis of overweight and usethereofrdquo US patent EP 1007027 A2 2000

[82] S Haleema P V Sasi I Ibnusaud P L Polavarapu and HB Kagan ldquoEnantiomerically pure compounds related to chi-ral hydroxy acids derived from renewable resourcesrdquo RSCAdvances vol 2 pp 9257ndash9285 2012

[83] J Louter-Van DeHaar P YWielinga A JW Scheurink and AGNieuwenhuizen ldquoComparison of the effects of three different(minus)-hydroxycitric acid preparations on food intake in ratsrdquoNutrition and Metabolism vol 2 article 23 2005

[84] B W Downs M Bagchi G V Subbaraju M A Shara HG Preuss and D Bagchi ldquoBioefficacy of a novel calcium-potassium salt of (minus)-hydroxycitric acidrdquo Mutation Researchvol 579 no 1-2 pp 149ndash162 2005

[85] A C Sullivan J G Hamilton O N Miller and V R WheatleyldquoInhibition of lipogenesis in rat liver by (minus)-hydroxycitraterdquoArchives of Biochemistry and Biophysics vol 150 no 1 pp 183ndash190 1972

[86] D Bagchi G Trimurtulu A V K Raju K Sengupta P B SMurthy and T V N Rao ldquoComparative bioavailability of (minus)-hydroxycitric acid from oral administration of HCA calciumsalt and calcium-potassium double salt in Albino Wistar ratsrdquoJournal of the Federation of American Societies For ExperimentalBiology vol 24 p 505 2010

[87] M Asghar R Zeyssig E Monjok et al ldquoHydroxycitric acid(HCA-SX) decreases oxidative stress and insulin resistanceand increases brain serotonin levels in obese Zucker ratsrdquoExperimental Biology Meeting vol 20 Article ID A6554 2006

[88] S Roy H Shah C Rink et al ldquoTranscriptome of primaryadipocytes from obese women in response to a novel hydrox-ycitric acid-based dietary supplementrdquo DNA and Cell Biologyvol 26 no 9 pp 627ndash639 2007

[89] R Uauy and E Dıaz ldquoConsequences of food energy excess andpositive energy balancerdquo Public Health Nutrition vol 8 no 7 App 1077ndash1099 2005

[90] M Shara S E Ohia T Yasmin et al ldquoDose- and time-dependent effects of a novel (minus)-hydroxycitric acid extract onbody weight hepatic and testicular lipid peroxidation DNAfragmentation and histopathological data over a period of 90daysrdquoMolecular and Cellular Biochemistry vol 254 no 1-2 pp339ndash346 2003

[91] M Shara S E Ohia R E Schmidt et al ldquoPhysico-chemicalproperties of a novel (minus)-hydroxycitric acid extract and itseffect on body weight selected organ weights hepatic lipid


peroxidation and DNA fragmentation hematology and clinicalchemistry and histopathological changes over a period of 90daysrdquo Molecular and Cellular Biochemistry vol 260 no 1 pp171ndash186 2004

[92] K A Amin H H Kamel and M A Abd Eltawab ldquoProtectiveeffect of Garcinia against renal oxidative stress and biomarkersinduced by high fat and sucrose dietrdquo Lipids in Health andDisease vol 10 article 6 2011

[93] J A Watson M Fang and J M Lowenstein ldquoTricarballylateand hydroxycitrate substrate and inhibitor of ATP citrateoxaloacetate lyaserdquoArchives of Biochemistry and Biophysics vol135 no C pp 209ndash217 1969

[94] T A Berkhout L M Havekes N J Pearce and P H E GrootldquoThe effect of (minus)-hydroxycitrate on the activity of the low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2rdquoBiochemical Journal vol 272 no 1 pp 181ndash186 1990

[95] H Chee D R Romsos and G A Leveille ldquoInfluence of (minus)hydroxycitrate on lipogenesis in chickens and ratsrdquo Journal ofNutrition vol 107 no 1 pp 112ndash119 1977

[96] A C Sullivan J Triscari J G Hamilton and O N MillerldquoEffect of (minus)-hydroxycitrate upon the accumulation of lipid inthe rat II Appetiterdquo Lipids vol 9 no 2 pp 129ndash134 1974

[97] A C Sullivan J Triscari and J G Hamilton ldquoEffect of (minus)-hydroxycitrate upon the accumulation of lipid in the rat ILipogenesisrdquo Lipids vol 9 no 2 pp 121ndash128 1974

[98] G D Lopaschuk J R Ussher and J S Jaswal ldquoTargetingintermediary metabolism in the hypothalamus as a mechanismto regulate appetiterdquo Pharmacological Reviews vol 62 no 2 pp237ndash264 2010

[99] N B Rederman A K Saha D Vavvas and L A WittersldquoMalonyl-CoA fuel sensing and insulin resistancerdquo AmericanJournal of Physiology vol 276 pp E1ndashE18 1999

[100] S E Ohia S O Awe A M LeDay C A Opere and D BagchildquoEffect of hydroxycitric acid on serotonin release from isolatedrat brain cortexrdquoResearchCommunications inMolecular Pathol-ogy and Pharmacology vol 109 no 3-4 pp 210ndash216 2001

[101] J McGuirk R Muscat and P Willner ldquoEffects of chronicallyadministerd fluoxetine and fenfluramine on food intake bodyweight and the behavioural satiety sequencerdquo Psychopharmacol-ogy vol 106 no 3 pp 401ndash407 1992

[102] M Leonhardt B Hrupka and W Langhans ldquoEffect of hydrox-ycitrate on food intake and body weight regain after a periodof restrictive feeding in male ratsrdquo Physiology and Behavior vol74 no 1-2 pp 191ndash196 2001

[103] M R Greenwood M P Cleary R Gruen et al ldquoEffect of (minus)-hydroxycitrate on development of obesity in the Zucker obeseratrdquoTheAmerican journal of physiology vol 240 no 1 pp E72ndashE78 1981

[104] A C Sullivan and J Triscari ldquoMetabolic regulation as a controlfor lipid disorders I Influence of (minus)-hydroxycitrate on exper-imentally induced obesity in the rodentrdquo American Journal ofClinical Nutrition vol 30 no 5 pp 767ndash776 1977

[105] J Triscari and A C Sullivan ldquoComparative effects of (minus)-hydroxycitrate and (+)-allo hydroxycitrate on acetyl CoA car-boxylase and fatty acid and cholesterol synthesis in vivordquo Lipidsvol 12 no 4 pp 357ndash363 1977

[106] M Leonhardt B Balkan andW Langhans ldquoEffect of hydroxyc-itrate on respiratory quotient energy expenditure and glucosetolerance in male rats after a period of restrictive feedingrdquoNutrition vol 20 no 10 pp 911ndash915 2004

[107] S Cheema Dhadli M L Halperin and C C LeznoffldquoInhibition of enzymes which interact with citrate by (minus)-hydroxycitrate and 123 tricarboxybenzenerdquo European Journalof Biochemistry vol 38 no 1 pp 98ndash102 1973

[108] J M Lowenstein ldquoEffect of (minus)-hydroxycitrate on fatty acidsynthesis by rat liver in vivordquo Journal of Biological Chemistryvol 246 no 3 pp 629ndash632 1971

[109] K Lim S Ryu H Nho et al ldquo(minus)-Hydroxycitric acid ingestionincreases fat utilization during exercise in untrained womenrdquoJournal of Nutritional Science and Vitaminology vol 49 no 3pp 163ndash167 2003

[110] K Lim S Ryu Y Ohishi et al ldquoShort-term (minus)-hydroxycitrateingestion increases fat oxidation during exercise in athletesrdquoJournal of Nutritional Science and Vitaminology vol 48 no 2pp 128ndash133 2002

[111] J R Vasselli E Shane C N Boozer and S B HeymsfieldldquoGarcinia cambogia extract inhibits body weight gain viaincreased Energy Expenditure (EE) in ratsrdquoThe FASEB Journalvol 12 no 4 p A505 1998

[112] V Leray H Dumon L Martin et al ldquoNo effect of conjugatedlinoleic acid or Garcinia cambogia on fat-free mass and energyexpenditure in normal catsrdquo Journal of Nutrition vol 136 no 72006

[113] G Blunden ldquoGarcinia extract inhibits lipid droplet accumu-lation without affecting adipose conversion in 3T3-L1 cellsrdquoPhytotherapy Research vol 15 no 2 pp 172ndash173 2001

[114] E D Rosen C J Walkey P Puigserver and B M SpiegelmanldquoTranscriptional regulation of adipogenesisrdquo Genes and Devel-opment vol 14 no 11 pp 1293ndash1307 2000

[115] E D Rosen C Hsu X Wang et al ldquoCEBP120572 induces adipoge-nesis through PPAR120574 a unified pathwayrdquo Genes and Develop-ment vol 16 no 1 pp 22ndash26 2002

[116] J B Kim H M Wright M Wright and B M SpiegelmanldquoADD1SREBP1 activates PPAR120574 through the production ofendogenous ligandrdquo Proceedings of the National Academy ofSciences of the United States of America vol 95 no 8 pp 4333ndash4337 1998

[117] S Dagogo-Jack ldquoHuman leptin regulation and promise inpharmacotherapyrdquo Current Drug Targets vol 2 no 2 pp 181ndash195 2001

[118] H Staiger O Tschritter J Machann et al ldquoRelationship ofserum adiponectin and leptin concentrations with body fatdistribution in humansrdquoObesity Research vol 11 no 3 pp 368ndash372 2003

[119] S T Nadler J P Stoehr K L Schueler G Tanimoto B SYandell and A D Attie ldquoThe expression of adipogenic genesis decreased in obesity and diabetes mellitusrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 97 no 21 pp 11371ndash11376 2000

[120] G S Hotamisligil N S Shargill and B M SpiegelmanldquoAdipose expression of tumor necrosis factor-120572 direct role inobesity-linked insulin resistancerdquo Science vol 259 no 5091 pp87ndash91 1993

[121] J M Stephens and P H Pekala ldquoTranscriptional repression ofthe CEBP-120572 and GLUT4 genes in 3T3-L1 adipocytes by tumornecrosis factor-120572 Regulation is coordinate and independent ofprotein synthesisrdquoThe Journal of Biological Chemistry vol 267no 19 pp 13580ndash13584 1992

[122] H Xing J P Northrop J Russell Grove K E Kilpatrick SU Jui-Lan and G M Ringold ldquoTNF120572-mediated inhibitionand reversal of adipocyte differentiation is accompanied by


suppressed expression of PPAR120574 without effects on Pref-1expressionrdquo Endocrinology vol 138 no 7 pp 2776ndash2783 1997

[123] K Hayamizu H Hirakawa D Oikawa et al ldquoEffect ofGarciniacambogia extract on serum leptin and insulin in micerdquo Fitoter-apia vol 74 no 3 pp 267ndash273 2003

[124] K Laubner T J Kieffer N T Lam X Niu F Jakob and JSeufert ldquoInhibition of preproinsulin gene expression by leptininduction of suppressor of cytokine signaling 3 in pancreatic 120573-cellsrdquo Diabetes vol 54 no 12 pp 3410ndash3417 2005

[125] R H Lustig ldquoChildhood obesity behavioral aberration or bio-chemical drive Reinterpreting the first law of thermodynam-icsrdquoNature Clinical Practice Endocrinology andMetabolism vol2 no 8 pp 447ndash458 2006

[126] M H Pittler and E Ernst ldquoDietary supplements for body-weight reduction a systematic reviewrdquo American Journal ofClinical Nutrition vol 79 no 4 pp 529ndash536 2004

[127] V Badmaev M Majeed A A Conte et al ldquoGarcinia cambogiafor weight loss [letter]rdquo Journal of the American Medical Associ-ation vol 282 no 3 pp 233ndash235 1999



[130] J L Schaller ldquoGarcinia cambogia for weight loss [letter]rdquo Thejournal of the American Medical Association vol 282 no 3 pp234ndash235 1999

[131] I Onakpoya S K Hung R Perry B Wider and E ErnstldquoThe use of Garcinia extract (Hydroxycitric Acid) as a weightloss supplement a systematic review and meta-analysis ofrandomized clinical trialsrdquo Journal of Obesity vol 2011 ArticleID 509038 9 pages 2011

[132] N S Deshmukh M Bagchi T Yasmin and D Bagchi ldquoSafetyof a novel calciumpotassium salt of hydroxycitric acid (HCA-SX) I Two-generation reproduction toxicity studyrdquo ToxicologyMechanisms and Methods vol 18 no 5 pp 433ndash442 2008

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Table 1 Comparison of G cambogia G atroviridis and G indica [9 11 13 44]

Species Common name Origin Feature

G cambogia Asam Gelugor

India found commonly in the evergreenforests of Western Ghats from Konkansouthward to Travancore and in theShola forests of Nilgiri

Small- or medium-sized tree with a rounded crown andhorizontal or drooping branches under the family ofGuttiferae Its fruits are ovoid about 5 cm in diameter yellowor red when ripe with six to eight grooves enclosing six toeight seeds and are edible

G atroviridis Asam Gelugor Southeast Asia

Small- or medium-sized fruit tree with drooping branchesand ovoid fruits The fruits are bright orange-yellow whenripe globose with 12ndash16 grooves about 7ndash10 cm in diameterand fluted with a firmly textured outer rind and a rather thinand translucent pulp surrounding the seeds

G indica KokumIndia the tropical rain forests of WesternGhats from Konkan southward toMysore Coorg and Wayanad

Slender evergreen tree with drooping branches Its fruits areglobose or spherical 2ndash4 cm in diameter dark purple whenripe with five to eight large seeds surrounded

in the treatments for obesity [8] Garcinia has been usedfor centuries in Asian countries for culinary purposes as acondiment and flavoring agent in place of tamarind or lemonand to make meals more filling [9 10] Besides its use as aflavouring agent the dried rind of G cambogia combinedwith salt and other organic acids can help to lower thepH and thus provides a bacteriostatic effect in curing fishG cambogia contains large amounts of hydroxycitric acid(HCA) Similar to G cambogia G atroviridis and G indicaalso contain significant HCA content and are sometimesused interchangeably with G cambogia in food preparationThe different features among these three different types ofGarcinia are summarised in Table 1 [9 11ndash14]

A myriad of health effects have been attributed to Garci-nia (including G cambogia G atroviridis and G indica)such as antiobesity effects [15ndash17] antiulcerogenic [18ndash20]antioxidative [21ndash24] antidiabetes [25] antimicrobial [2226ndash28] antifungal [29] anti-inflammatory [30 31] andanticancer effects [22 32ndash34] In particular the antiobesityeffects of Garcinia or more specifically of its HCA contenthave been elucidated with unprecedented clarity over the lastfew decades Besides its efficacy in the reduction of bodyweight and food intake GarciniaHCA has been proven tobe beneficial in ameliorating obesity-related complicationssuch as inflammation oxidative stress and insulin resistance[21] The results obtained from several studies supported thepositive effects of HCA administration alone or in combina-tionwith other ingredients on bodyweight loss reduced foodintake increased fat oxidation or energy expenditure (EE)[16 17 35ndash39] whereas some studies did not [40ndash42]

In spite of the vastly reported prominent role of HCAin inducing satiety reduced energy intake and weight gainand improved blood parameters and substrate oxidationcontroversial results regarding its efficacy and safety asan antiobesity dietary supplement had also been reportedEvidence from the in vitro in vivo and clinical trials onthe safety of GarciniaHCA as a dietary supplement fortreating obesity had been extensively reviewed [43] Howeverthe efficacy of GarciniaHCA remains the subject of debateDespite the previously stated issues on conclusive evidencefor HCArsquos efficacy in promoting weight loss and suppressingfood intake the marketing of a plethora of over-the-counter

slimming aids containing HCA has taken place The aim ofthis review is to critically assess the evidence from a verybroad range of reports rigorous clinical trials systematicreviews and meta-analyses on the efficacy and potential ofGarciniaHCA as an antiobesity dietary supplement

2 Uses in Traditional Medical Systems

Botanical dietary supplements usually contain a complexmixture of phytochemicals which have additive or synergisticinteractions Aside from its use as a preservative and as acondiment in cuisine Garcinia extract has been used in thetraditional Ayurvedic medical system [9 13] A decoction ofG cambogia is given as purgative in the treatment of intestinalworms and other parasites for bilious digestive conditionsfor dysentery rheumatism and in the treatment of tumoursLess commonly extracts are employed as cardiotonics to treatangina In veterinarymedicine it is used as a rinse for diseasesof the mouth in cattle [12 77]The fruit rind is used in ricketsand enlargement of spleen and to heal bone fractures [13] InSoutheast Asian folkloric medicine a decoction of G atro-viridis (leaves and roots) is sometimes used for the treatmentof cough dandruff earache stomach pains associated withpregnancy and throat irritation [49] The dried fruit of Gatroviridis is used for improving blood circulation for thetreatment of coughs as a laxative and as a expectorant Thefruit is used in a lotion with vinegar to rub over the abdomenof women after confinement [9] Fruit ofG indica is antiscor-butic cholagogue cooling antibilious emollient and demul-cent The anthelmintic properties of the fruit of G indicacontributed to its use in haemorrhoids dysentery tumorpains and heart complaints Bilious affected sites are treatedwith syrup from the fruit juice Kokum butter is astringentand demulcent and is used in diarrhea and dysentery It is alsoapplied externally for ulcerations sinuses fissures of handlip chapped skin and skin diseases [12 13 44 77]

3 Phytoconstituents

The several compounds which have been isolated fromvarious species ofGarcinia are summarised inTable 2 Several






Herbal products[48]




















Antiobesity

Weight management



De novo lipogenesis

Fat oxidation



Glycogen synthesis


Insulin leptin

Glucose intake


EE-workout (YES)

resting

RER (YES) RQ


Appetite

A

B

C

D

and

GarciniaHCA

OHOH

OHOO

OHO

HO




4 Salts of HCA



































2max until













1500mg HCA daily


[60]







area [63]




[16]

8 weeks







[65]



[66]














2 weeks




[71]




[41]

2 weeks



[42]





[73]







[74]




[75]











Inter healthNI





Garcinol






before meals



daily



20min before food



hour before meal






HCA 450mgtablet

Highernature

450mg HCA pertablet




ViridianNutrition


daily before meal




50 (minus)-HCA













6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















Herbal products[48]




















Antiobesity

Weight management



De novo lipogenesis

Fat oxidation



Glycogen synthesis


Insulin leptin

Glucose intake


EE-workout (YES)

resting

RER (YES) RQ


Appetite

A

B

C

D

and

GarciniaHCA

OHOH

OHOO

OHO

HO




4 Salts of HCA



































2max until













1500mg HCA daily


[60]







area [63]




[16]

8 weeks







[65]



[66]














2 weeks




[71]




[41]

2 weeks



[42]





[73]







[74]




[75]











Inter healthNI





Garcinol






before meals



daily



20min before food



hour before meal






HCA 450mgtablet

Highernature

450mg HCA pertablet




ViridianNutrition


daily before meal




50 (minus)-HCA













6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Antiobesity

Weight management



De novo lipogenesis

Fat oxidation



Glycogen synthesis


Insulin leptin

Glucose intake


EE-workout (YES)

resting

RER (YES) RQ


Appetite

A

B

C

D

and

GarciniaHCA

OHOH

OHOO

OHO

HO




4 Salts of HCA



































2max until













1500mg HCA daily


[60]







area [63]




[16]

8 weeks







[65]



[66]














2 weeks




[71]




[41]

2 weeks



[42]





[73]







[74]




[75]











Inter healthNI





Garcinol






before meals



daily



20min before food



hour before meal






HCA 450mgtablet

Highernature

450mg HCA pertablet




ViridianNutrition


daily before meal




50 (minus)-HCA













6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of















































2max until













1500mg HCA daily


[60]







area [63]




[16]

8 weeks







[65]



[66]














2 weeks




[71]




[41]

2 weeks



[42]





[73]







[74]




[75]











Inter healthNI





Garcinol






before meals



daily



20min before food



hour before meal






HCA 450mgtablet

Highernature

450mg HCA pertablet




ViridianNutrition


daily before meal




50 (minus)-HCA













6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















1500mg HCA daily


[60]







area [63]




[16]

8 weeks







[65]



[66]














2 weeks




[71]




[41]

2 weeks



[42]





[73]







[74]




[75]











Inter healthNI





Garcinol






before meals



daily



20min before food



hour before meal






HCA 450mgtablet

Highernature

450mg HCA pertablet




ViridianNutrition


daily before meal




50 (minus)-HCA













6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















2 weeks




[71]




[41]

2 weeks



[42]





[73]







[74]




[75]











Inter healthNI





Garcinol






before meals



daily



20min before food



hour before meal






HCA 450mgtablet

Highernature

450mg HCA pertablet




ViridianNutrition


daily before meal




50 (minus)-HCA













6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















Inter healthNI





Garcinol






before meals



daily



20min before food



hour before meal






HCA 450mgtablet

Highernature

450mg HCA pertablet




ViridianNutrition


daily before meal




50 (minus)-HCA













6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















6770782 6706899 6676977 6610277 65658476541026 6489492 6485710 6476071 64478076428806 6426077 6413545 6399089 63952966277396 6221901 6217898 6160172 6147228 61139496054128 5972357 5911992 5783603 5656314 56120395536516 4007208 4006166 4005086 7119110 39949273993668 7153877 3993667 4028397 7153528 70152506638542 6579866 6482858 6441041 63834826207714 5817329 5626849 and 3965121

8 Conclusions


Acknowledgment



References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















References



















































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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