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H. 0. Preuss,l D. fsagohi,2M. Da Departmentof Physio

C. V. S, &IO 3 D. ‘K. De

aDepartmentof Pharmacy 3Departmentof Genera

3 D. ‘K. De aDepartmentof Pharmacy 3Departmentof Genera Gymnemasylvestreextract (9$%/Z),on weight loss in
3 D. ‘K. De aDepartmentof Pharmacy 3Departmentof Genera Gymnemasylvestreextract (9$%/Z),on weight loss in
3 D. ‘K. De aDepartmentof Pharmacy 3Departmentof Genera Gymnemasylvestreextract (9$%/Z),on weight loss in

Gymnemasylvestreextract (9$%/Z),on weight loss in rn~rate~~o~~e

subjectswas

evaluatedby monitoringchangesin bodyweight, bodymass index ~~~I~,appetite, lipid protIles,serum leptin and excretionof urinaryfat metabolites.

HCA-SX hasbeen shownto reduceappetite,inhibitfat sy~~e~~,a~ddeqease

without stimulatingthe centraknerkus system, NBC hasdernon~~t~

healthyinsulinlevels,while GSE has beenshown to regulateweightloss and blood sugar

levels.

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Y ORIGINAL ARTlCLE Effects of a natural a cornbinatian of MC Gymraemi s yhstre extract,
Y ORIGINAL ARTlCLE Effects of a natural a cornbinatian of MC Gymraemi s yhstre extract,
Y ORIGINAL ARTlCLE Effects of a natural a cornbinatian of MC Gymraemi s yhstre extract,

Y

Y ORIGINAL ARTlCLE Effects of a natural a cornbinatian of MC Gymraemi s yhstre extract, o

ORIGINAL

ARTlCLE

Effects of a natural

a cornbinatian of MC Gymraemi s yhstre

extract, o .3-)-hydroxycijh7i~-a~id

X plus

n~~~in-b~~~

loss

n weight

@l

.3-)-hydroxycijh7i~-a~id X plus n~~~in-b~~~ loss n weight @l H. G. Preuss,l D. Bagchi,2 M. Bagchi,’ C.

H. G. Preuss,l

D. Bagchi,2 M. Bagchi,’ C. V. S. Rao,? D. K.

ey” and S. Satyanwayana5

‘Department of Physiology and Biophysics, Gkrgetown

University Medica Ckmter,Georgetown, Ww.hington, DC, USA

‘Department

of

PharmacySciences,Creighton$Jniversity Medical Center, Omaha. NE.

USA

aDepartmentof

General h4edicine, ASR Academi of Medical Sciences,Ellum, Andhra

Predesh, In&a

f

4Departmerrtof

Statistics, University of Conne&cut,

Storm. CT, USA

‘Department of Pharmacy,Andhra University,;Visakhapa~~~,

Andhra Pmdesb, India

University,;Visakhapa~~~, Andhra Pmdesb, India Aim The efficacy of optimal doses of highly bioavailabla
University,;Visakhapa~~~, Andhra Pmdesb, India Aim The efficacy of optimal doses of highly bioavailabla

Aim The efficacy of optimal doses of highly bioavailabla (-l-hydroxycitric acid (HCZA:gXlalone and in combination

with

ately obesesubjects was evaluated by monitoring changesin body weight, body mass index [BMIl, appetite, lipid

profiles, serum leptin and excretion of urinary fat metabolites. HCASX has been shown to reduce appetite, inhibit fat synthesis and decreasebody weight withoutstimufat~mg the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while $ZIBhas been shown to regulate weight loss and blood sugar levels. Methods: A randomized, double-blind, piacabo-controlled human study was c&due&d in Blluru, India for 8 weeks in 60 moderately obesesubjects (ages2140, BMI >Z$kg/m2f. Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 I&, group B wes administered a combination of FICA-SX&67mg, NBC 4 mg and GSE400 mg, while group C was given placebo daily in three equally divided duseS.30-60min before meals. AI1 subjects received a 200Okcal diet/day and participated in supervised waIking.

Results: At

cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were si~~~I~antly reduoed In both groups,

while high-density lipoprotein levels and hxcxcretionof urinary, fat metabolites increased In bath groups. A marginal or non-significant effect was observed in all parameters in group C. Conclusion: The present study shows thatoptimal doseaof HCA-SX and, to agreater degree, thecombination of HCA- SX, NBC and GSEcan serve as an effective and safeweight-loss formula that can fa$litate a reduction in excaasbody weight and BMI, while promoting healthy blood lipid levels.

niacin-bound chromium (NBC1and a standardized Gvnmama sylve&re extract (GSE] on weight loss in moder-

the end of 8 weeks, body weight~arid BNI decreasedby .+-@%-inboth groups A and B. Food intake, total

Keywords:i-+hydroxycitric acid f&rcinia cambogiaf,appetitesuppression,body massindex, Gymnemo~ylvesfro

extract,niacin-

bound chromium, semm leptin, total cholester&

 

Received 10 Fuly 2003; returned

for revision 16 October 2003; revised version accepted 22 October 2003

 

lntroductiion

Obesity is a complex, multifactorial

and. chronic con-

an imbalance between energy e&nditure

and caloric

dition characterized by excess body fat resulting from

intake

@,21. More

than

half

of

USA

adults

are

resulting from intake @,21. More than half of USA adults are Correspondence: H. G. Preuss, MD,

Correspondence:

H. G. Preuss,MD, Department of Physiology, Medicine and J?,athology,Georgetown University Medical Canter, 4000 Reservoir Rand

NW, Basic ScienceBuilding, Kwm 231B,

E-mail:

preusshgOgeorgetown.edu

Waskiqton,

DC 20057,

USA.

Diabetes,Obesity

and

Metebglm~,

8,

2004,

171-180

)

171

Waskiqton, DC 20057, USA. D i a b e t e s , O b e
Waskiqton, DC 20057, USA. D i a b e t e s , O b e
Waskiqton, DC 20057, USA. D i a b e t e s , O b e
overweight (61X), having a body mass index (BMI) greater than of USA adults are obese,
overweight (61X), having a body mass index (BMI) greater than of USA adults are obese,
overweight (61X), having a body mass index (BMI) greater than of USA adults are obese,
overweight (61X), having a body mass index (BMI) greater than of USA adults are obese,

overweight (61X), having a body mass index (BMI)

greater than

of USA adults are obese, having a BMI of greater than 30 kg/m’ ]31.Low levels of phygicaf activity, sedentary lifestyles, stress, depression md~ consumptmn of high- fat and fast foods are responsibl;efor unwanted weight gain 14-91. Recent studies ha& shown that approxi- mately a third of the variance $n adult body weights result from genetic influences (11.Leptin, an adipocyte- and placenta-derived circulating protein, regulates the magnitude of fat stores in the body leading to obesity (lo]. Gastrointestinal peptides, neurotrans@ters and adipose tissuemay also have an aetidogic rde in obesity [l’l]. Obesity and adipose tissue &pa&on increase the

risk of hypertension, type z diabetes, arthritis, elevated cholesterol, cancer and serious hormonal imbalances in women, leading to sterility [12]. :Low caiocic d&s with or without exercisecan help with temp,oraryFight loss; however, diet and exercise alone have not proven suc- cessful for long-term solutions in weight ,n&agement. In addition, supplementationw$& ,drugs tlnusuppress appetite, reducefood intake, increaseenergy&penditure and affect nutrient partitioning or metabolism have potential efficacy but is unfortunately accompanied by adverseside effects- some life t&eatening (141. (-)-Hydroxycitric acid (HCA), an extract from the

has been reported

dried fruit rind of Guxcinia carnbogia,

to causeweight loss in humans v&bout stimulating the central nervous system (141. H$% has b&n demon-

strated to reduce food intake in animals,

role in the treatment of obesity iand has bein demon-

availability of serotonin in iao-

strated to .increase the

lated rat brain cortex [15-231. HCA is a iompetitive inhibitor of ATP citrate lyase, an extra-mitochondrisl enzyme involved in the initial steps of & navy lipo- genesis.Consequently, HCA red&es the transformation of citrate into acetyl coemyme A, a step necessaryfor the formation of fatty acids in the livir. In addition, there is increased produoticn of hepati~ .glycogen in the @es- ence of HCA, which may activate glucomcel$ors, lead- ing to a sensation of fullness and reduced appetite

[17,20].

Niacin-bound chromium (NBC) plays an. importent role in regulating appetite and ,energyproduction, A human study involving African-An&can women who were administered 600&g of elemental chromium as NBC in two divided doses,a moderate diet and exercise regimen for 2 months resulted in we&ht and fat loss and snaring of muscle and body composition withno signifi- cant adverseeffects (241.Gram et d (251reported sig- nificant weight loss in young obesewomen consuming 400 pg of NBC pm day for &we& with exercise. This

25 kg/m2, while more than a quarter (36%)

suggesting its

H.

G

study also demonstrated an improved insulin

to au oral glucose load. In another animal study, rats were fed huge amounts of’NBC for over a year and demonstrated no evidence of toxicity (Z&J. Gymnemo sybesfre extract (GSE) helps promote weight loss and controls blood sugar levels [27,2Sl. GSE-derived pepti& gurrnarin inhibits the sweet taste response in rats (~81.Prcusa et al. (29) demonstrated a significant lower&g of choiasterol with GSEingestion in hypertunsive rats that vmm fed a high sucrosediet, while the placebo ‘group showed a significant increase in cholesterol lcvels.~ GSB administered (4~3mg/day) to insulin-dependent diabetes rnellitus patients for 10-12 months m&ted in slgnifiosnt improvement with no adverseside effects [30].

The efficacy of HGA in weight management has been pr~iously reported (3&34]. However, no systematic approach has been conducted so far to evaluate the effi- cacy and modulation of fat degradation, lipid profiles and leptin Ievel. Commercial sources of HGA are typ- ically available as caicium salts that are relatively insoluble in water, paorly absorbed and lack proven bioavailability studies. l%rthermore, earlier studies used a dose of 13OUmgof HCA per day but did not

provide a rationale for

adminiatraf&m. In this stttdy; we used a highly bioavail-

dose selection or timing for dose

response

able cah&un-potasshm~ salt ‘of HCA (HCA-SX) and the daily dose was extrapolated from earlier in vivo studies conducted by Sullivan et af. (%,19) and our recently conducted ex tivo study on serotonin release from iso- lated rat brain cortex [23,35& Accordingly, the human equivalent dosageof H&4-SX used in the present study was calculated to be ‘%OQmg’Jday,as explained in &f&o& and Procedurss, which is significantly greater than the 1500mglday typically recommended in dietary supplements )3fJ, &A-SX bioavailability was found to be significantly hi&or in fasting individuals as com-

pared with subjects consuming HCA-SX in

with food I361. Accordingly, HCA-SX was given to the study participants 3&-6~min before each meal, which

addresses the timing of dose. In addition, extensive safety studies have demonstmted the safety of HCA-SX

with

The present study examined the efficacy of HCA-SX alone and fn combmaria< with NBC and GSE given on an empty stoma& 3O-60min beforebreakfast,lunch and dinner in 60 human volunteers. Effects of these supple- ments were investigat0d on body weight, BMI, appetite (as df$ermined by weighing the remaining food), lipid profiles, serum 1eInin (a biomarker of obesity regulatory gene)and excretion of urinary fat metabolites (abiomarker

of fat oxidation).

conjunction

an LDa, (kttsfgreater‘than

~g/kg (35).

OA

1

I-I-Hydroxycitric

acid end weight

lose

Preuss et a/

172

1

Diabetes,

Obesrty

and

Metabolism.

6,2004,

171-180

(35). OA 1 I-I-Hydroxycitric acid end weight lose Preuss et a/ 172 1 Diabetes, Obesrty and
(35). OA 1 I-I-Hydroxycitric acid end weight lose Preuss et a/ 172 1 Diabetes, Obesrty and
(35). OA 1 I-I-Hydroxycitric acid end weight lose Preuss et a/ 172 1 Diabetes, Obesrty and
(35). OA 1 I-I-Hydroxycitric acid end weight lose Preuss et a/ 172 1 Diabetes, Obesrty and
Methods and Procedures experienced .any recent, unexplained weight ioss or gain. Subjects were required ta
Methods and Procedures experienced .any recent, unexplained weight ioss or gain. Subjects were required ta
Methods and Procedures experienced .any recent, unexplained weight ioss or gain. Subjects were required ta
Methods and Procedures experienced .any recent, unexplained weight ioss or gain. Subjects were required ta
Methods and Procedures experienced .any recent, unexplained weight ioss or gain. Subjects were required ta

Methods

and

Procedures

experienced .any recent, unexplained weight ioss or gain. Subjects were required ta fast avernight, and blood

and urine samples were obtained at each clinic

visit.

Group A

was given a

daily dose of

HCA-SX

4887 mg

(60% HCA providing 2880mg of IICA per day], group B was &ven a daily dose of ‘a comb&ration of RCA-SX 4667 mg, NBC.4 mg @mudding &IOpg of elemental chro- mium) plus GSE 4OOmg[psbviding ltpmg of gymnemic acid) and-group C was given a placebo [microcrystalline cellulose1 in three equally divided doses 30-60min before breakfast, lunchend dinner for 8 weeks. All sub- jects included in the study were provided a daily vege- tarian or non-vegeta+m, diet of 208Okcal containing approximately 17% protein, 25% fat and 58% carbohy- drate. The subjects alao participated in a walking exer- cise programme for 3[1min/day, 5days a week, which was supervised by an exe&se speciaiist. An individual diary was maintained for each subject. Subjects were in touch with the physicians under the supervision of Dr C. V, S, Rae on a daily basis, and a detailed evaluation was performed at the beginning, weak 4 and week 8 of treatment. Body weight, BMI, appeti&, lipid profile, serum leptjn 1eveIsand urinary fat ‘metabolite levels were ‘evaluated. Blood samples were drawn in the earIy morning [between 0600 hours and 0730 hours) to avoid. diurnal variation. Appetite suppression ‘was measured by weighing the remaining food after each meal.

Study

Materials

A natural, highly bioavailable, water-soluble, tasteless

and odourless ealcinm-potassium salt of 80% HCA extract from G. cumbogia [commercially known as

Super CiMMax (FICA-SXlli NBC l,commercially known

as ChromeMate (containing 10% elemental chromium)],

and a standardized extract of GSE lcommercidiy known 11sGYM-250 (containing 25% gymnemic acid)] were

obtained from EnterHealth Nutrace@i~als (Benicia,

CA,

USA), Unless stated otherwise, all other chemicals and

reagents were obtained from Sigma Chemical (St Louis, MO, USA) and were of analytical grade or the highest grade available. Body weights of the subjects were measured using an EssaeDigi (Made1DS~IOJ digital weighing scale Qssae- Teraoka, BangaloreY’Karnataka,India), Height was meas- ured using a Ben&n Track’and Field height scale. BMI was calcufated by body weight $11kil&rmm divided by square of height in meters. Appetite reduction was estimated by weighing’ the remaining food after esch meal. Lipid profile, including HDL, LDL, VLDL and triglycerides, was p~otome~cally dotermined using a

Institutional Review Board approval$, IRB 01-~01 (Elluru, India) and IRB W-142 (Georgetown University Medical Center, Washington, DC, USA) were obtained.

All subjects gave written

consent prior to p~tiicigation.

The following six key. factors were monitored in a

randomized, double-blind, placebo-co&rolled stt$y

whether optimal doses of ofHCA-SX,NBC and GSE

(HCA-SX formula) produce a greater rednction in body weight than piacebo; (ii) whether FICA-SK and HCA-SX formula produce a greater reduction in @MI than pla- cebo: (iii) whether HCA-SX and HCA-SX formula have an inhibitory effect on appetite as compared with placebo; (iv) whether HCA-SX and HCASX formtifa produce a beneficial effect on lipid profile, includ$ng low-density lipoprotein (LDL), high-den&y lipoprotein (HDL), triglycerides, very-low-density lipoprotein (VLDL) and total cholesterol, as compared with placebo; (v) whether HCA-SX and HCA-SX formulahave an inI& bitory effect on serum leptin levels compared-to ptacebo; and [vi) whether HCA-SX and HCA-SX formula causefat oxidation, ,a.sestimated by enhanced excr&ion of urinary fat metabolites, including malondialdehyde (MDA), acetaldehyde (ACT), formaldehyde {FAj and acetone (ACON), as compared with placebo. Advertisements were placed and overweight subjects who responded and met the inclusion criteria during a screening were scheduled for a baseline visit. The evaluation included a questionnaire, physical examination, elet$racardiogmm and screening blood data. Qualified subjects were then randomized into three groups with equal probability through a random number generator. ;

over a period of ewe&s: (i) HCA-SX and the combination

Subjects

The study was performed in Elluru, India, Each subj&t was obese,aged 21-60, with a BMI ranging from 29.8 ta 55.5 kg/m*. Additional inclusion criteria consisted of having a negative pregnancy test, possessing the ability to understand the risks and benefits of, the protocol, willingness to participate in a 8Omin.supervised wa$k-

ing exercise programme [5 days a week), eat the vegetar- ian or non-vegetarian prescribed diets of Qpproximatsly 2000kcallday, sign an informed consent form, complete

a standard health questionnaire and partir;ipate.in three

clinic visits at 0, 4 and 8 weeks. Subjects were excluded

if they were pregnant or nursing, presently takingother

weight-loss medications, had a history of thyroid dis- ease, cardiovascular disease or diabetes, suffered from intractable obesity, had defined weight limits or had

from intractable obesity, had defined weight limits or had @a2004 Blackwell l’ubbshmg Ltd Diabetes,Obesity end
from intractable obesity, had defined weight limits or had @a2004 Blackwell l’ubbshmg Ltd Diabetes,Obesity end
from intractable obesity, had defined weight limits or had @a2004 Blackwell l’ubbshmg Ltd Diabetes,Obesity end

@a2004 Blackwell

l’ubbshmg

Ltd

Diabetes,Obesityend Nietabalism,e,2004,

171-180

1

173

had defined weight limits or had @a2004 Blackwell l’ubbshmg Ltd Diabetes,Obesity end Nietabalism,e, 2004, 171-180 1
had defined weight limits or had @a2004 Blackwell l’ubbshmg Ltd Diabetes,Obesity end Nietabalism,e, 2004, 171-180 1
had defined weight limits or had @a2004 Blackwell l’ubbshmg Ltd Diabetes,Obesity end Nietabalism,e, 2004, 171-180 1
 

_’

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  _’ _ , _ _ OA 1 t-I-Hydmxycitdc acidandweight toss H G . P r
  _’ _ , _ _ OA 1 t-I-Hydmxycitdc acidandweight toss H G . P r
  _’ _ , _ _ OA 1 t-I-Hydmxycitdc acidandweight toss H G . P r
  _’ _ , _ _ OA 1 t-I-Hydmxycitdc acidandweight toss H G . P r

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1

t-I-Hydmxycitdc

acidandweight toss

H G .Preusset al.

DiagnosticaMERCK kit and Semi-automaticanalyser MICROLAB- (E-MerckIndia,‘Mumbai,India).Radio- immunoassay(RIA)was used ta determineserumieptin levels in the blood samplesaccordingto the manufac- turer’s instructions (Linco Research,St Louis, MO, USA).Excretionof urinary fat metaboliteswasmeasured using high pressureliquid chrtimatugrsphy(IiPLC) in conjunction with gas chromatffgraphicmass spectcov scopy (GCMS),using a selecti+ ion-monitoring tech- niqueas describedby Sharaet al. 1371.

Dose DeterminaJion

Earlieranimal studiesby Sulfiva&et of. [18,f9] indicate that higher levels of HCA than those typic&IIy recom- mendedin dietarysupplementsi@ humansarerequired to producesignificant weight-lossresults.T&e authors demonstratedthat rats (120-16$$ receiving t&odium salt of FICA at daily concentrat$msof 283, 1.32, 0.66 and0.33mmollkg developedsignificant lipogenesisand weight loss at concentrationsof 2.63and 1.32mmol/kg, whereas0.66and 6.33mmol/kg producedinsignificant

results.

human equivalency dose (NED) using the formula HED= animal dosex (humanbody ~eight/annnalbody weight)l’”[381.Thus, 2.63 and $.32mmol/kg/day dose equalsa human daily doseof 3bffZand 5981mg respec- tively. Taking an averageof thesetwo dosescomesto a daily dose of approximately 45&&g. Furthermore, a concentration-dependentstudy was conductedin our laboratoriesto evokepeaklevelsof serotoninreleasein rat brain cortex. A concentrationof 3OOpvHCA-SX exhibitedmaximum releaseof serotonin,beyondwhieb no further increaseof serotonin;raleasewas observed [23,35]. Consideringa five-fold faster metabolism in

These animals doses &tlle extrapolated to

rats comparedto humans,the 300pi ex viva doseextra- polatesto a human doseof i666.67mg of HGA per day. Basedon these t&o findings we used a daily doseof 4666.7mgof H&%43X,providing 2800mg free FICA in this study.

Statistical

Analysis

The dataset that was anaiysedin the first phasehas 10 variablesof interest. Thesevariablesare body weight, BML LDLs, IIDLs, trigIycerides, VLDLs, total choles- terol, serum leptin, excretios of urinary fat metabolites andremainingfood [39-411. Two-tailed Student’sb-testwith a level of 5% signifi- cancewas performedin three groups for each of the variables to detect. any sigrrificant differences. The groups administeredwere@A-SX (groupA], PICA-SX, NBC and CSE (group B) aed placebo (group C). The number of subjectswho completedthe study in group A, B and C was .$9,18and I& respectively. In- each gr.ouB,longitudinal data were collected for threetime points denotedby initial (I), middle (Ml and final”(F) for the first nine variables and at eight time points for the Iast variable, which is ‘remainingfood’. Thereareno missingol&eervatiotionsin this dataset. To comparethe’difference&at5% level of significance, we hiwe differencesfor ‘I & M’, ‘M & F’and ‘I & F’for the first nine variables.The p-value is reported in paren- thesis for the tests ‘I a-M’, ‘I & F’and ‘M & F’respect- ively, Forremailing food, as&&I were collectedat eight time points,’there.are 28 possible paired differences. Basic smmnary statistics and test for differenceswith respect to least-squaremeans among the time points were conducted for each group on each variable at threetime points,

Table1 Effectsof placebo(groupC), (-I-hydroxycitricacid&CA-SX)X alone~(greaupAl andHCA-SX formula (groupB) on body

weight,bodymassindex (RMI) andserumlepttnIeveIsin humansubjects

GrCitJp

-tni

point

-

Placebo(groupC)

I

rA

F

HCA-SX{groupAJ

1’

M

F

HCA-SXformula

(graupB)

1’

 

Y

F

 

Serum leptin bgfml)

80.4442.36e

32.49‘10.57a

79.16.1t2.26”

Fs.98 Ltto.54b

78.8412.30’

3t.a4*

0.54b

91,74* 3.50a

34%71f

I.228

30.22j: 2.96s

69.39323.30=

33.82f1.15”

25.05f

2.34b

87.21~t3.23~

32,99’&1.13G

18.37i2.38’

92.41~+~3.8C

37.33f

1,708

42.+1*

4.048

69.67f 3m*

3623f

1.69”

31.69h3.62b

66.72f

3.6-Ib

35.a5f

1.62”

23.55i

2.49’

66.72f 3.6-Ib 35.a5f 1.62” 23.55i 2.49’ 1 7 4 Dnbetes, Obesity and Metaknlwn, 6, 2004. 171-180
66.72f 3.6-Ib 35.a5f 1.62” 23.55i 2.49’ 1 7 4 Dnbetes, Obesity and Metaknlwn, 6, 2004. 171-180

174

Dnbetes,

Obesity

and

Metaknlwn,

6,

2004.

171-180

66.72f 3.6-Ib 35.a5f 1.62” 23.55i 2.49’ 1 7 4 Dnbetes, Obesity and Metaknlwn, 6, 2004. 171-180
66.72f 3.6-Ib 35.a5f 1.62” 23.55i 2.49’ 1 7 4 Dnbetes, Obesity and Metaknlwn, 6, 2004. 171-180
66.72f 3.6-Ib 35.a5f 1.62” 23.55i 2.49’ 1 7 4 Dnbetes, Obesity and Metaknlwn, 6, 2004. 171-180
H. G Preuss et al (-I-tiydroxycftria a&d sad weight loss 1 O A Results The
H. G Preuss et al (-I-tiydroxycftria a&d sad weight loss 1 O A Results The
H. G Preuss et al (-I-tiydroxycftria a&d sad weight loss 1 O A Results The
H. G Preuss et al (-I-tiydroxycftria a&d sad weight loss 1 O A Results The
H. G Preuss et al (-I-tiydroxycftria a&d sad weight loss 1 O A Results The

H. G

Preuss et al

(-I-tiydroxycftria

a&d sad weight

loss

1

OA

Results

The present study evaluated.the effect ?f,supplement- ation with optimal dosesof a highly bioavaiiable form of HCA (HCA-SX) alone or in combination‘with NBC qnd GSEon weight loss, BMI, appetite, lipid profiles, serurp leptin levels and fat oxidation. Table 1 summarizes the changesin body weigh;, BMl and serum leptin levels following supp~ementat$o~of placebo (group C), HCA-SX (group A) and FICA-SX’for-

mula (group B) over the period

of 8 weeks. There was a

distinct change observedat the end of 4 Bnd 8weeks in both groups A and B. In group C, approxi&at& 1.28 and 1.6kg reductions in body weight were observed at tie end of 4 and 8 weeks respectively. Unden the same con- ditions, approximately 2.35 and 4.53kg’reductions in body weight were observed in group A,and 2.74 and 5.69kg reductions in body weight were c$erved in the

group B, respectively, at the end of 4 and 8 weeks. T&s,

at the end of8 weeks,there were a 5 and 6.3% reductinn

in BMI observed in soup A

There was a reduction of 2% BMI in group C at the end of @weeks.No significant changes were observed in serum leptin levels in group C, while both @oup A aad group B exhibited a significant reduc&m. Approxi- mately, 17.1 and 39.2% reductions in: s%um @iin levels were observed in group A and 25,1 and 44.3% reductions in serum leptin levels were observed in group B, respectively, at the end of 4: and 8weoks. Approximately, 5.5 and 2.0% reductions in Serumleptin

levels were observedat the end of 4 and 8 tieeks, respec- tivety, in group C. Table2 summarizes the amount of rem$ning footi over the period of 8weeks for eachgroup, which refl&ts

a remarkabletrend towards appetite suppressiuu in both

group A and group B. No changeswere o@erved in tie appetite of group C. Approximately, a 15,.6end 21.2‘43, reduction in appetite was observed in &~up A and group B at the end of 8 weeks respectively,

and group B respectively.

Table3 summer&es thy chaqss in lipid profiles, including LDL, &L, triglycerides, VLDL and total cho-

lWerol,5n groups A, B and C. There was some reduction in LDL and triglycericlqs in group A; however, the changesthat were observedin group.R were even more

significant. Group Beznanstrated a boost in HDL levels,

while little effect was observedin group A. The overall total cholesterol levd decriassadsignificantly in both

groups A and R. A~~ox~ma~ly, 6.7 and 13.2% reduc-

tions ifi LDL levels we;re observed in group A, while under these same coa&ions, apprnximately 7.1 and 19% reductions in LDL levels weru bbserved in group

B at

increase in LPL levels, however, was,observedin group

C at both time points. ,Approxiunately, 4.7 and 8.0% increases in WI, levels were~observed in group A,

while‘ll.8 and Z2.Q% increases in HRL levels were

observed in group R, refipectively, at the end of 4 and

8 weeks. No significant changeswereobserved in

C. Approximately, 2.9 and 5.9% reductions in triglycer- ide levels ware observe.din group A and 14.2 and 2U.2%

reductions ig triglyceride levels were observed in group

B, respectively, at @e ena of 4 and 8 reeks respectively.

No significant changes were observed in group C. No

significant changes were observed iit the VLIIL levels

in any of the groups. Appsoximately, 3 and 7.2% reduc-

tions in total cholesterol levels were observedin group A and 1.2 and 9.5% reducti&s in totat cholesterol were observedin group 3 at the and of 4 and 8 weeks raspec- tively. No changesyere observedin grouij C. Enhanced excretion of urinary fat m#abolites, includ- ing MDA, ACT? PA and ACOP& was guantifiyd as a biomarker of Fat oxidation. Approximately, 35.6- 106,,4% increases in total urinary fat metabolites in group A and 56-134% inGreasesiu total urinary fat metabolites in goup & were observed at the end of

8 weeks, respectiveIF as comptid with the control sam- ple. In,group 6, 6.241% i&creaseswere observed at the end of 8 weeks.

the end

of

4 and ‘8we&

respectively. A

slight

group

Table 2 Effectsof placebo(groupCl, (-I-hydroxycitic acidINCA-SXIalone(groupAl andHCA-SX humansubjects

formula(groupl3)on appetitein

 

Remaining

food

(gl OII the platte-as aa index ef apt&e

euppraeaian

 

Week 1

Week:2

Week 4

Wmk 7

Week 8

Placebolgrwp

Ct

IlOtt 23.5

86.3fGL4

79.4j?23.0

93.8zt33.3

91.3zt2i.Z

88.8133.5

92.§3:4S.Q

93.4zk35.2

HCA-SX

(group A)

 

178 * 49.9

257 +&37.4

2883441.6

242 rir40.1

221 k 48x3

285zk33.7

3201-46.4

352 f

42.1

HCA-SX

formula

(arouo

5)

208 A 20.3

238 1.32.1

268LG228.2

369& 43.5

x31

a5G

444 * 55*7

422f41.1

478

rt 40.0

Data81~)preseniodasgroupmean-+s.e.mSubjects$em given+-bhydroxyc!trir:acid(HCX-SXIalone(groupA), Yt&X-SXformula(groupB)or

placebo(groupC) far 8 weeks.SeeMethodsand@aceduresfbr detail?Ja groupA, only threeaf thepossible28 pairs of diffeceacesam

significsnt.ID group l3. 17 of the possible28 pairkiai‘differen&s arc significant.while In group C, none of the 28 postihle differmces is signifiwnt all at 5% level of sig&icance.

differmces is signifiwnt all at 5% level of sig&icance. Diabetes.ObesityandMet&olism,,G,1004,171-180 1 1 7
differmces is signifiwnt all at 5% level of sig&icance. Diabetes.ObesityandMet&olism,,G,1004,171-180 1 1 7
differmces is signifiwnt all at 5% level of sig&icance. Diabetes.ObesityandMet&olism,,G,1004,171-180 1 1 7
differmces is signifiwnt all at 5% level of sig&icance. Diabetes.ObesityandMet&olism,,G,1004,171-180 1 1 7
OA 1 WHydroxycitric acid and weight%ss H . G P r e u s s
OA 1 WHydroxycitric acid and weight%ss H . G P r e u s s
OA 1 WHydroxycitric acid and weight%ss H . G P r e u s s
OA 1 WHydroxycitric acid and weight%ss H . G P r e u s s
OA 1 WHydroxycitric acid and weight%ss H . G P r e u s s

OA

1

WHydroxycitric

acid

and

weight%ss

H.

G

Preuss

et

al.

Table3

Effectsof placebo(groupC),$-)-hydroxycicricacid(RCA-SX)alone

in human subjects

_

(group A) and HCA-SXfcxmuia (group13)offlipid profile

Group

l-be

poibt

l&L

Lmgldlf

IifR.

(mgldt)

l&i~cerides

imgkffl

VIOL WjJdl)~

Total

cholesterol

lmg/dlJ

-

Placebo

(group

C)

1

105.38rt‘5.4Qa

27,31

~Y0.94~

125.0&

112.59’

250f3;OC

158.0f5.11a

 
 

M

1oa.~*6.25*

27.75~0.97

129,0*13,12~

 

Zt?.+k2,81=

161.Ork4.96'

F

109.7516.55

 

26.13f0.82*

126.0t

t1.S7a

24.133zzio*

160.0f6.30~

HCA-SX

(group

Al

I

114.2145.23'

30.05+1.78a

lk35.0zk9.96a

 

2&26YL4Sa

167.0+6,208

 

M

:

106.58&

4m72*

31.47*

1.2Sb

102.0tl-7.W

23.a&tj*134a

1t32.0*5.11*

F

99.11

k

4.70'

32.42

+ 1.26b

99.80f7.388

pm

* 2.36a

155.5 f5,25b

HCA-SX

formula

(group

B)

I

115.22J:i04a

29.725

1.27'

127.0i13>09a

24.17f2.596

169.Ort5.W'

 

M

107.0zk4.‘ifJb

33.22~l.lfib

W&Of

12.5@

28,66+3,268

167.015.7la

F

93.33+@i4c

36.28fl.W

lDl.uf9.44*

 

23*78&l.77?

153.0f5.14b

HIIL, high-densitylipoprotein; LDL, low-densitylipoprotein: VLDL. vary-low-densitylipaproteja

SubjectsweregivenHCA-SXalone(gr?upA), RCA-SX formula @oup

details.I, week0; M, week4; F, week8, Vnluaswith non.identicat superscriptscaresigntficanllydifferent @c 0.05).

Data82epresentedasgroupmean& s.e.m.

and Procsdures

for

R1or pkac&o

tghp

Q for 8 weclrs,~SeeM&hods

In group A, MDA, ACT, FA and ACOM increased by 1.3-, 1.3-, I.& and %.2-foldat the &nd of awe&s and I.%., 1.8-, 2.X- and 1.4-fold at the end:of’8weeks: In group B,

MDA, ACT, FA and &CON incrit&ed by 1%, 1.4-, I.& and 1.3-fold at the end of 4 we&g ar+d2.3-, 1.9-, 2.0- and l&fold at the end of 8weeks. In &roup C; MDA, ACT, FA and ACCJNincreasedby0.9-, 0.9., 1.2. and %&fold at

the end of aweeks and I.&

end of 8weeks (table4). In stmunary, we observethat wang the three grouts, group B showed a significant diff&ce a$ong the least- squaremeans for the thr&e time boints, whic$ ,were ‘I & M’, ‘I & F’and ‘M & F’‘for the tiariables body weight,

BMI, LDL, HDL, triglycerides, total cholestarol, serum leptin levels and exc?etionof ur+ary, fat m&+ol&es. It did not show any significant differ&r? for the variabl? VLDL. it also showed the most member,which is 37, out of the 28 paired differencas &&ween t&G variable ‘remaining food’ as significant. ‘Group A did show a

1.1~,11.2-and i&fold

at the

significant diffFrence among the least-squaremeans at

the threa time points for tie variables body weight, BMI, serum leptin ~levelsandcexcretion of uri&y fat metabo- lites. For Lik and’HlX, the ‘1-kM’and ‘I & F’differences me significant b& not t.be ‘M & P’difference. For the variable VLDL, there am ao significant paired differ- onceb.For total cholesterol, oaljr the ‘M & F’and ‘I & F’ differences are significant, It also showed only a few, which is three of&e 28, pa&d differences between the variable ‘rernaixurirrgfood’dssignificant. Group C showed some signifkan~ Sdi&emncein body weight, BMI and

six variables, it did not show

HDL. For the, remaining

any sign&ant Chmg8 in the k&s acrossthe three time points. As for t&k remaining food variable, none of the 28 paired differences was SigriiEcant. Thus, a statistically si@ifica& reduction in body yveight,BMI, appetite, LDL,

total cholesterol:and Wiglyceride Ievels, an increase in HDL levels, a decrease in serum leptin levels and enhanced eFreti& of urinm fat metabolites were

Table 4 Effects of placebo (groupC),&-I-hydror~ckricacid IHCA-SXJ alone (gruup A) and FICA-SXf*rm& (group B) on enhanced excretion of urinary fat metabolites&m&ml of u&m)

176

GKVUP

Time

-

Placebo

(group

C)

I

 

M

F

HCA-SX

(group

Al

I

 

M

F

HCA-SX

formula

(group

8)

I

 

M

F

-

point

MDA

ACT

FA

-I

ACON

q.155*0.014a

1.277~kU.125~

3.253*0.190~

18.09f0.677*

0.146*0.009=

1.181

h0.220*

3.78siA.279~

17.85

j: 0.881’

0.187rt0.011~

1.437JcO.264'

3.148LtO.240"

19.20k

1.032*

0.138~0.021s

1.077,0.0664

2.sEt*Q.140"

19.38f

1.054'

0.173zt0.021b

1.3fs*o.o96b

&293*0~406b

22.54~t1.125"

0.26+0.025c

1.97Zi0.126c

-6.152~kO.244’

26.2811.2W

0.123S0.030~

0.9310.04747"

3.806zkCi.234'

19.35zk1.006a

0.159f0.048a

1.342I0.101~

6.09sf0.321*

24.64f0.904b

0.288f0.058b

1.76410.593~

7.697

ItO.

30.19*0.947c

ACON,

acetone;ACT, acetaldehydo;FA, fqmuddehyde;MDA,

malondialddahyde+Dalaam prescrntedas group meenfs.e.m. Subjectswere

givenFICA-SXalone{groupA),HCA-SXformuie (g;oupR)or pk~c:ebo(groupcl for 8 W&S. Sea&f&n&

M, wnek4; F, week

8. Valueswith non-j&mtintieolsupe~criptsare significantlydiaeerent(p< 0.05).

a&. Procsdr~resfor details.I, week0:

1

Diabetes, Obesltvand Metabolism. 6,2004.

171-180

t 2004 BtackweilPubkzhlng Ltd

and Metabolism. 6,2004. 171-180 t ‘ 2 0 0 4 B t a c k w
and Metabolism. 6,2004. 171-180 t ‘ 2 0 0 4 B t a c k w
and Metabolism. 6,2004. 171-180 t ‘ 2 0 0 4 B t a c k w
and Metabolism. 6,2004. 171-180 t ‘ 2 0 0 4 B t a c k w
H. G. Preuss eta1 (-bHydraXyciWh2 acid and weight loss OA observedwhen taking WA-SX aloneand in
H. G. Preuss eta1 (-bHydraXyciWh2 acid and weight loss OA observedwhen taking WA-SX aloneand in
H. G. Preuss eta1 (-bHydraXyciWh2 acid and weight loss OA observedwhen taking WA-SX aloneand in
H. G. Preuss eta1 (-bHydraXyciWh2 acid and weight loss OA observedwhen taking WA-SX aloneand in
H. G. Preuss eta1 (-bHydraXyciWh2 acid and weight loss OA observedwhen taking WA-SX aloneand in

H.

G.

Preuss

eta1

(-bHydraXyciWh2 acid and weight

loss

OA

observedwhen taking WA-SX aloneand in c0mbinam.m with NBC and GSE.Supplementationwith a‘cambinatiun of HCA-SX, NBC and GSE (group B) resulted in greater improvements than HCA-SX (group A) alone in al! para- meters evaluated.

gason day 6 and diarrhoea on day 33, and at the end of

28 days,‘this subject @nsd approximately 1.0kg (body

weight: 79.5 kgt The fourth subject [lO6kg) reported no

adverseevents during

26 days, this subject fast approximately 1.5kg (body

weight: 104,5 kg).

these 48 days, and at the end of

Adverse

Events

Fifty-three of the initial 60 subjectscompleted the study. During the B-weekstudy, no seriousadverseeffectswere observedin any of the subjects.No patiext was remaved or dropped out of the study as a resuitjof an adverse event caused by the treatment. In the M&4-SX group (group A), one incidence of leg cramps, fwo incidences of heartburn, four incidences of diarrhbea, four in& dences of gas, one incidence of increased appetite, seven incidences of headaches,one irqidence of stb- math burn, one incidence of skin rash, &ne incidence of menstrual bleeding and two incidences of general weaknesswere reported. In the HCA-SX, NBC:and GSE group (&“a~ B), two incidences of leg cn&ps, five inci- dencesof mild diarrhoea, 10 incidences of mild gasand

one incidence of headacheswere observed

cebo group (group C), one incidence of leg cramps, two incidences of heartburn, nine incidences of diarrhoea, four incidences of gas,one incidence of icreased appyje- tite, one incidence of stomach burning, &ozincidences

of irregular periods, two incidences of menstrual bieed- ing and cme incidence of general weakness were reported. Taken together:the number of pptients report-

In the pla-

ing adverseeventsin the supplemented gkaups significantly different from the placebo &up.

was net

Drop

Outs

Seven subjects dropped out of this study. tie

subjects

dropped out of the study as a result of anadvenm event causedby the treatment, One subject dro&ed out of t&s HCA-SX group (group A) at the end of the Twenty-first day of the study. This subject (initial bodyjweight: 9Okg) reported a common headacheon day 5. ‘Two subjects dropped out of RCA-SX formula group (gFogp Bf at the

end of the twelfth and twenty-eight day. T&e first subject [initial body weight: 71kg) reported regu@rleg cfamps on day 3, while the secondsubject (94kg) ireporteddiar? rhoea on the eleventh day. Four subjectsdropped out of the placebo group (group Cl at the end of the twelfth, thirty-sixth, forty-third and forty-eighth day. The first subject (109.5kg) did not report any aqverse evenl5. The second subject (86kg) did not report nny adverse events,and at the end of the twenty-eighth day. his body weight was 84.5kg. The third subject (%.&kg) reported

Discussion

Obesity continues to be a major be&h problem in devel- oped and developing &untries. obesity increases the risk of hypertension, type 2 diabetes,arthritis, elevated cholesterol, cancer and serious hormond imbalances in women [42,431. Ubesity and its relatea metabolic and cardiovascular co+lications continue to present an escalatingchallenge,to contemporary medicine. Obesity signifies chronic disequilibrium betweenfood consump- tion and energyexpenditure [3-51. %A, derived from the fruit-rind of 6. combogio, exhibits a distinctive sour taste and has been used for dimtry purposesin south&m Asia far centuries to make me& more fslling I&&). HCA is known to reduce appe- tite, inhibit fat synthesis&id dwreaeebody weight with- out stimulating the cent& nervtius system. HCA does not causenervousness,rapid he&t rate, high blood pres- sure or insomnia; symptoms that are often assaciated with dietary stimulants suoh as epbedra (mahuang),caf- feine or ~~~n~ipro~~~l~~e [45j, HCA promotes weight reduction through suppressed de ROvofatty acid synthesis [14,96,173.One mechanism accounting for the beneficial effectsof HCA may involve inhibition of ATP citrate lyase, which will eventually limit the availability of acetyl coenzyme A and lipid synthesis during carbohydrate feeding [14,!6,17,44]. In bar previous study and &:the present study, we have demonstrated other important mechenisms including appetite suppression by I-ICA and .se*otonin releaseby rat brain cortex [Z&351,regulatary roles in the lowering of lipid profrles and serum.leptin levels and increased fat oxidation as demonstratedby eahenced excretion of urinary fat metabolitea. In exam&&g somepositive weight-bss studies, a ran- domized, placebo-controRedstudy on ‘fK&SX was con- ducted by Ramos et al. f3rl, in~+lving 20 overweight ad&s, for a period of 8waeks. It was demonstrated that 6OQmgof HCA-SX taken three times per day before

meals for 8week.sresulted in, 9~5% greater weight

loss

than thosetaking a placebo, This occurred without

any

side affects commonly associatedwith other dietary sti- mulants 145).Of added importance, a significant reduc- tion was observedin cholesterol and triglyceride levels.

iMetes,

Obsstr/and

Metabolwn,6,2004,171-180

]

177

reduc- tion was observedin cholesterol and triglyceride levels. iMetes, Obsstr/and Metabolwn,6,2004,171-180 ] 1 7 7
reduc- tion was observedin cholesterol and triglyceride levels. iMetes, Obsstr/and Metabolwn,6,2004,171-180 ] 1 7 7
reduc- tion was observedin cholesterol and triglyceride levels. iMetes, Obsstr/and Metabolwn,6,2004,171-180 ] 1 7 7
reduc- tion was observedin cholesterol and triglyceride levels. iMetes, Obsstr/and Metabolwn,6,2004,171-180 ] 1 7 7
@ I I I-bHydroxy&ric acid and weight&m W G . P r e u s
@ I I I-bHydroxy&ric acid and weight&m W G . P r e u s
@ I I I-bHydroxy&ric acid and weight&m W G . P r e u s
@ I I I-bHydroxy&ric acid and weight&m W G . P r e u s

@I I

I-bHydroxy&ric

acid and weight&m

W G. Preuss et a/.

Another study by Mattes and .Botmann 132) demon-

HCA &mg with a

daily diet of 502QkJfl200 kcal) fer?Z weeks resulted in a significant difference in weight loss (3.7f3.1 vs.

2.4 -f-2.9kg) compared to placebb. Waster&p-Plantenga and Kovacs 1341 conducted e 6-week randomized, placebo-controlled, single-blind; cross-over study in 12 males and 12 females using a daily dose of QOQmgof HCA-SX for 2 weeks. They de*ionstrated that HC&SX supplementation reduced 24-h energy intake in humans, while satiety was sustained.

strated that a daily dose of 1.2E of

In examining the ‘negative .&dies’, Heymsfield et oi.

[46) pmvided what became an eccepted daily dose of

a diet of SQZOkJlday or

1200kcallday for

1.5g of HCA along with

12 weeks and reported tfiet no signifi-

cant difference in weight loss was observedbetween the placebo and treatment groups. bveral problems with the study, however, may be responsible for $e negative results [46]. Heymsfield et cl. f461 qua&if&d the FICA content but did not assessthe bi~availability’ufthe HCA sample used in the study. ManyHCA products am less than 50% soluble in water and “pearly absdrbed. Also, this low-calorie diet (5OZOkJlday)may have accounted for the substantial decreeses in body weight of both treatment and placebo groups, blunting the’ability of

HCA to show curbed appetite a$

bio-

available, water-soluble calciumlpptassium salt of HCA (HCA-SX). Supplements were given an an empty sto- nrach at least 30-6Qmin before meals to enhance biol availability, which was previously demonstrated by Loe et al. 136).This more efficacious’dose was extrapolated from ex viva and in viva studies, as disc&ad in the Methods and Prqcedures, which is an increaaad dose of HGA compared to other studies. The’available sour& of HCA in the market today are a calcium salt thacis poorly soluble in water, allowing for co&promised absorption~ ‘Ibis study was designed to; better detern-dne the effects of FICA-SX, at a higher, more efficacious dose, on satiety. Subjects were admi&tered a 2060kcai or 8372kJ diet/day, and all remainjng food was,weighed after each meal to determine HGA&Ps effect on appetite reduction. Results demonstrated iasignificant reduction in appetite following supplement&ion of HCA-SX alone or in combination with NBd and &SE.

reduced faad intake.

Our present study was conducted using a highly

A statistically significant reduction in body weight

was observed between ‘I’ and ‘M hut not between ‘M’

and ‘F’in the placebo (group C),,whidfi signifies that a controlled diet and exercise initisliy result In weight reduction but eventually plateaus. ?his fact highlights

thts importance of a novel, efficacious for weight management.

Safe supplement

Perceived weight l&s in both the HCA-SX (group A) and’HC;A-SX formula @oup B) group is supported by the improvement in BIvfI, which implies a sparing of lean muscle and fat oxidation, as demonstrated by enhanced excretian df‘urinary fat metabolites ftable4). Mnsclr mass is denser and heavier, and thus, sparing lean muscle mass contributes to slow and steady fat loss that ii preferable to most people.

Ilownregulation of obesity regulatory gene may be an additional mechanism of HCA”s ability to reduce body weight and appetite. Leptin, a 167~amino acid protein hormone and a biomarker of the obesity regulatory gene, is synthesized and secreted by adipocytes and is present in the blaodstraam and is directly related to body fat. Leptin binds to receptors in the brain and activates sig- nals that inhibit food int,ake and increase energy expen- diture 147-4Q). Leptin ~resistance develops when receptor-binding activity is diminished and, as a result, plasma leptin,Iavels increase, which in turn lose their ability to inhibit food intake and increase energy expenditure. Generally, plasma leptin levels are higher in bverwefght ‘individuals t&an in normal individuals and higher in women than in men. Leptia has been shown to be abIe to modulate insulin secretion and action through these reca&ors 147). In the present study, it was’damonstrated that supplementation with H&-SX alone and in. combination with NBC and GSE significantly decreases aemm laptin levels, which may play a significant role in downregulating the obesity regulatory gene. The fatidegradation or fat-oxidation ability of HCA-SX was evaluated based on the excretion of urinary fat metabotites in&ding IvfDn, ACT, FA and ACON. Enhanced @-o&ation of ‘fat may be the prime sources of these four fat metabolites. Enhanced excretion of MDA was observed during increased oxidative stress [5dJ.In the same study* radiotabelled MDA administered to rats was found tu be extensively metabolized to acet-

ate and carbon dioxide. The enhanced excretion

ary ACT identif&d in the present study may be due to

the breakdown of MDA

lipid peroxidation. The enhanced urinary excretion of ACGN mwy occur in response to a consequence of enhanced g-oxidation, as reported earlier @l]. Meta- boiism of glycerol to FA has been reported in rat liver microsomes and is a result of the metabolism of trigly cerides by adipose tissue Andyother tissues that possess the enzyme that activates glycerol, namely glycerol kinase 152). High glycerol kinase lavels are found in

liver and brown tissues l52,53). Other possible sources of RA might include the breakdown of MDA to acetateor ACT and a one-carbon fragmsnt {501 and/or the cleavage

of urin-

or air a result of fat oxidation/

178

1

Diabetes, Obewy

andMetabolism?.S(2004, 171-180

0 X04

Blackwell

Pubbshmg Ud

8 1 Diabetes, Obewy and Metabolism?.S(2004, 171-180 0 X 0 4 B l a c k
8 1 Diabetes, Obewy and Metabolism?.S(2004, 171-180 0 X 0 4 B l a c k
8 1 Diabetes, Obewy and Metabolism?.S(2004, 171-180 0 X 0 4 B l a c k
8 1 Diabetes, Obewy and Metabolism?.S(2004, 171-180 0 X 0 4 B l a c k
Ii. G. Preuss eta/. of a one-carbon fragment from acetoacetic acid with the formation of
Ii. G. Preuss eta/. of a one-carbon fragment from acetoacetic acid with the formation of
Ii. G. Preuss eta/. of a one-carbon fragment from acetoacetic acid with the formation of
Ii. G. Preuss eta/. of a one-carbon fragment from acetoacetic acid with the formation of

Ii. G. Preuss eta/.

of a one-carbon fragment from acetoacetic acid with the formation of ACUN. In the present study, the trigly- ceride levels were significantly reduced in subjects sup- plemented with either HCA-SX or HGA-SX, NBC and GSE, accompanied by significant incresses in urin&y excretion of FA, which suggests that the<e q~pplem&s may induce enhanced production of glykerol kinase in the adipose tissues. Our earlier studies demonstrated that:+upplementa- tion with NBC is bioavailable and helps inweight red&- tion and regulation of blood lipids in overweight and hypercholesterolemic subjects 124,541. G:SE has been

demonstrated to promote weight sugar cravings and control blood

The current study demonstrates that supplementation with HCA-SX or HCA-SX, NBC and GSE &riificant~y improves the levels of total cholesterol, LIJL, HDL and triglycerides, which are primary risk fac;tors of card& vascular diseases. Our present findings demonstqte tbat the present dose of HCA-SX alone 0; in combination with k3G and GSE,

given 30-60min before meals, is highly bioavailabfe, effi- cacious and safe as weight-management: supplements. Furthermore, the present study demon&rated that HCA-

SX alone or in combination with

ively cause fat degradatiori and benefic<ally regulate IiTjid profiles and serum leptin levels. The reduced~weigbt lqss, BMI, serum leptin levels, appetite, food -intake and increased fat oxidation indicate that supplementation with HCASX alone and in combination @b NBC and GSE is a novel therapeutic tool far weight management.

loss by its &i&y to reduce sugar levels 127~30,55,56J.

NBC and (333 can effq&

1 Stunkard AJ. Current views on obesity, Am J Med 1996;

100:230-235.

2 Jequier Ii. Pathways to obesity. Int J Obes Relat Met& Disord 2002; 260: SlZ-S17.

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