Effects of a natural extract of (–)-hydroxycitric acid (HCA-SX) anda combination of HCA-SX plus niacin-bound chromium andGymnema sylvestre extract on weight loss H. G. Preuss,1 D. Bagchi,2 M. Bagchi,2 C. V. S. Rao,3 D. K. Dey4 and S. Satyanarayana51Department of Physiology and Biophysics, Georgetown University Medical Center, Georgetown, Washington, DC, USA2Department of Pharmacy Sciences, Creighton University Medical Center, Omaha, NE, USA3Department of General Medicine, ASR Academy of Medical Sciences, Elluru, Andhra Pradesh, India4Department of Statistics, University of Connecticut, Storrs, CT, USA5Department of Pharmacy, Andhra University, Visakhapatnam, Andhra Pradesh, India Aim: The efficacy of optimal doses of highly bioavailable (–)-hydroxycitric acid (HCA-SX) alone and in combinationwith niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moder-ately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipidprofiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fatsynthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its abilityto maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels.
Methods: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeksin 60 moderately obese subjects (ages 21–50, BMI >26 kg/m2). Subjects were randomly divided into three groups.
Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mgand GSE 400 mg, while group C was given placebo daily in three equally divided doses 30–60 min before meals. Allsubjects received a 2000 kcal diet/day and participated in supervised walking.
Results: At the end of 8 weeks, body weight and BMI decreased by 5–6% in both groups A and B. Food intake, totalcholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups,while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal ornon-significant effect was observed in all parameters in group C.
Conclusion: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess bodyweight and BMI, while promoting healthy blood lipid levels.
Keywords: (–)-hydroxycitric acid (Garcinia cambogia), appetite suppression, body mass index, Gymnema sylvestre extract, niacin-bound chromium, serum leptin, total cholesterolReceived 10 July 2003; returned for revision 16 October 2003; revised version accepted 22 October 2003 Obesity is a complex, multifactorial and chronic con- an imbalance between energy expenditure and caloric dition characterized by excess body fat resulting from intake [1,2]. More than half of USA adults are Correspondence:H. G. Preuss, MD, Department of Physiology, Medicine and Pathology, Georgetown University Medical Center, 4000 Reservoir RoadNW, Basic Science Building, Room 231B, Washington, DC 20057, USA. Diabetes, Obesity and Metabolism, 6, 2004, 171–180 overweight (61%), having a body mass index (BMI) study also demonstrated an improved insulin response greater than 25 kg/m2, while more than a quarter (26%) to an oral glucose load. In another animal study, rats of USA adults are obese, having a BMI of greater than were fed huge amounts of NBC for over a year and 30 kg/m2 [3]. Low levels of physical activity, sedentary demonstrated no evidence of toxicity [26].
lifestyles, stress, depression and consumption of high- Gymnema sylvestre extract (GSE) helps promote fat and fast foods are responsible for unwanted weight weight loss and controls blood sugar levels [27,28].
gain [4–9]. Recent studies have shown that approxi- GSE-derived peptide gurmarin inhibits the sweet taste mately a third of the variance in adult body weights response in rats [28]. Preuss et al. [29] demonstrated a result from genetic influences [1]. Leptin, an adipocyte- significant lowering of cholesterol with GSE ingestion in and placenta-derived circulating protein, regulates the hypertensive rats that were fed a high sucrose diet, while magnitude of fat stores in the body leading to obesity the placebo group showed a significant increase in [10]. Gastrointestinal peptides, neurotransmitters and cholesterol levels. GSE administered (400 mg/day) to adipose tissue may also have an aetiologic role in obesity insulin-dependent diabetes mellitus patients for 10–12 [11]. Obesity and adipose tissue expansion increase the months resulted in significant improvement with no risk of hypertension, type 2 diabetes, arthritis, elevated cholesterol, cancer and serious hormonal imbalances in The efficacy of HCA in weight management has been women, leading to sterility [12]. Low caloric diets with previously reported [31–34]. However, no systematic or without exercise can help with temporary weight loss; approach has been conducted so far to evaluate the effi- however, diet and exercise alone have not proven suc- cacy and modulation of fat degradation, lipid profiles cessful for long-term solutions in weight management.
and leptin level. Commercial sources of HCA are typ- In addition, supplementation with drugs that suppress ically available as calcium salts that are relatively appetite, reduce food intake, increase energy expenditure insoluble in water, poorly absorbed and lack proven and affect nutrient partitioning or metabolism have bioavailability studies. Furthermore, earlier studies potential efficacy but is unfortunately accompanied by used a dose of 1500 mg of HCA per day but did not adverse side effects – some life threatening [13].
provide a rationale for dose selection or timing for dose (–)-Hydroxycitric acid (HCA), an extract from the administration. In this study, we used a highly bioavail- dried fruit rind of Garcinia cambogia, has been reported able calcium–potassium salt of HCA (HCA-SX) and the to cause weight loss in humans without stimulating the daily dose was extrapolated from earlier in vivo studies central nervous system [14]. HCA has been demon- conducted by Sullivan et al. [18,19] and our recently strated to reduce food intake in animals, suggesting its conducted ex vivo study on serotonin release from iso- role in the treatment of obesity and has been demon- lated rat brain cortex [23,35]. Accordingly, the human strated to increase the availability of serotonin in iso- equivalent dosage of HCA-SX used in the present study lated rat brain cortex [15–23]. HCA is a competitive was calculated to be 2800 mg/day, as explained in inhibitor of ATP citrate lyase, an extra-mitochondrial Methods and Procedures, which is significantly greater enzyme involved in the initial steps of de novo lipo- than the 1500 mg/day typically recommended in dietary genesis. Consequently, HCA reduces the transformation supplements [31]. HCA-SX bioavailability was found to of citrate into acetyl coenzyme A, a step necessary for the be significantly higher in fasting individuals as com- formation of fatty acids in the liver. In addition, there is pared with subjects consuming HCA-SX in conjunction increased production of hepatic glycogen in the pres- with food [36]. Accordingly, HCA-SX was given to the ence of HCA, which may activate glucoreceptors, lead- study participants 30–60 min before each meal, which ing to a sensation of fullness and reduced appetite addresses the timing of dose. In addition, extensive safety studies have demonstrated the safety of HCA-SX Niacin-bound chromium (NBC) plays an important with an LD50 (rats) greater than 5 g/kg [35].
role in regulating appetite and energy production. A The present study examined the efficacy of HCA-SX human study involving African-American women who alone and in combination with NBC and GSE given on were administered 600 mg of elemental chromium as an empty stomach 30–60 min before breakfast, lunch and NBC in two divided doses, a moderate diet and exercise dinner in 60 human volunteers. Effects of these supple- regimen for 2 months resulted in weight and fat loss and ments were investigated on body weight, BMI, appetite sparing of muscle and body composition with no signifi- (as determined by weighing the remaining food), lipid cant adverse effects [24]. Grant et al. [25] reported sig- profiles, serum leptin (a biomarker of obesity regulatory nificant weight loss in young obese women consuming gene) and excretion of urinary fat metabolites (a biomarker 400 mg of NBC per day for 8 weeks with exercise. This Diabetes, Obesity and Metabolism, 6, 2004, 171–180 experienced any recent, unexplained weight loss orgain. Subjects were required to fast overnight, and blood Institutional Review Board approvals, IRB 01-001 and urine samples were obtained at each clinic visit.
(Elluru, India) and IRB 01–142 (Georgetown University Group A was given a daily dose of HCA-SX 4667 mg Medical Center, Washington, DC, USA) were obtained.
(60% HCA providing 2800 mg of HCA per day), group B All subjects gave written consent prior to participation.
was given a daily dose of a combination of HCA-SX The following six key factors were monitored in a 4667 mg, NBC 4 mg (providing 400 mg of elemental chro- randomized, double-blind, placebo-controlled study mium) plus GSE 400 mg (providing 100 mg of gymnemic over a period of 8 weeks: (i) whether optimal doses of acid) and group C was given a placebo (microcrystalline HCA-SX and the combination of HCA-SX, NBC and GSE cellulose) in three equally divided doses 30–60 min (HCA-SX formula) produce a greater reduction in body before breakfast, lunch and dinner for 8 weeks. All sub- weight than placebo; (ii) whether HCA-SX and HCA-SX jects included in the study were provided a daily vege- formula produce a greater reduction in BMI than pla- tarian or non-vegetarian diet of 2000 kcal containing cebo; (iii) whether HCA-SX and HCA-SX formula have approximately 17% protein, 25% fat and 58% carbohy- an inhibitory effect on appetite as compared with drate. The subjects also participated in a walking exer- placebo; (iv) whether HCA-SX and HCA-SX formula cise programme for 30 min/day, 5 days a week, which produce a beneficial effect on lipid profile, including was supervised by an exercise specialist. An individual low-density lipoprotein (LDL), high-density lipoprotein diary was maintained for each subject.
Subjects were in touch with the physicians under the (VLDL) and total cholesterol, as compared with placebo; supervision of Dr C. V. S. Rao on a daily basis, and a (v) whether HCA-SX and HCA-SX formula have an inhi- detailed evaluation was performed at the beginning, bitory effect on serum leptin levels compared to placebo; week 4 and week 8 of treatment. Body weight, BMI, and (vi) whether HCA-SX and HCA-SX formula cause fat appetite, lipid profile, serum leptin levels and urinary oxidation, as estimated by enhanced excretion of urinary fat metabolite levels were evaluated. Blood samples fat metabolites, including malondialdehyde (MDA), were drawn in the early morning (between 0600 hours acetaldehyde (ACT), formaldehyde (FA) and acetone and 0730 hours) to avoid diurnal variation. Appetite (ACON), as compared with placebo. Advertisements suppression was measured by weighing the remaining were placed and overweight subjects who responded and met the inclusion criteria during a screening werescheduled for a baseline visit. The evaluation included aquestionnaire, physical examination, electrocardiogram and screening blood data. Qualified subjects were then A natural, highly bioavailable, water-soluble, tasteless randomized into three groups with equal probability and odourless calcium–potassium salt of 60% HCA extract from G. cambogia [commercially known asSuper CitriMax (HCA-SX)], NBC [commercially knownas ChromeMate (containing 10% elemental chromium)], and a standardized extract of GSE [commercially known The study was performed in Elluru, India. Each subject as GYM-250 (containing 25% gymnemic acid)] were was obese, aged 21–50, with a BMI ranging from 29.9 to obtained from InterHealth Nutraceuticals (Benicia, CA, 55.5 kg/m2. Additional inclusion criteria consisted of USA). Unless stated otherwise, all other chemicals and having a negative pregnancy test, possessing the ability reagents were obtained from Sigma Chemical (St Louis, to understand the risks and benefits of the protocol, MO, USA) and were of analytical grade or the highest willingness to participate in a 30 min supervised walk- ing exercise programme (5 days a week), eat the vegetar- Body weights of the subjects were measured using an ian or non-vegetarian prescribed diets of approximately Essae Digi (Model DS-410) digital weighing scale (Essae- 2000 kcal/day, sign an informed consent form, complete Teraoka, Bangalore, Karnataka, India). Height was meas- a standard health questionnaire and participate in three ured using a Benson Track and Field height scale. BMI clinic visits at 0, 4 and 8 weeks. Subjects were excluded was calculated by body weight in kilogram divided by if they were pregnant or nursing, presently taking other square of height in meters. Appetite reduction was weight-loss medications, had a history of thyroid dis- estimated by weighing the remaining food after each ease, cardiovascular disease or diabetes, suffered from meal. Lipid profile, including HDL, LDL, VLDL and intractable obesity, had defined weight limits or had triglycerides, was photometrically determined using a Diabetes, Obesity and Metabolism, 6, 2004, 171–180 Diagnostica MERCK kit and Semi-automatic analyser rats compared to humans, the 300 mM ex vivo dose extra- MICROLAB-200 (E-Merck India, Mumbai, India). Radio- polates to a human dose of 4666.67 mg of HCA per day.
immunoassay (RIA) was used to determine serum leptin Based on these two findings, we used a daily dose of levels in the blood samples according to the manufac- 4666.7 mg of HCA-SX, providing 2800 mg free HCA in turer’s instructions (Linco Research, St Louis, MO, USA). Excretion of urinary fat metabolites was measuredusing high pressure liquid chromatography (HPLC) inconjunction with gas chromatographic mass spectro- scopy (GCMS), using a selective ion-monitoring tech- The data set that was analysed in the first phase has 10 nique as described by Shara et al. [37].
variables of interest. These variables are body weight,BMI, LDLs, HDLs, triglycerides, VLDLs, total choles-terol, serum leptin, excretion of urinary fat metabolites Earlier animal studies by Sullivan et al. [18,19] indicate Two-tailed Student’s t-test with a level of 5% signifi- that higher levels of HCA than those typically recom- cance was performed in three groups for each of the mended in dietary supplements for humans are required variables to detect any significant differences. The to produce significant weight-loss results. These authors groups administered were HCA-SX (group A), HCA-SX, demonstrated that rats (120–160 g) receiving trisodium NBC and GSE (group B) and placebo (group C). The salt of HCA at daily concentrations of 2.63, 1.32, 0.66 number of subjects who completed the study in group and 0.33 mmol/kg developed significant lipogenesis and A, B and C was 19, 18 and 16 respectively.
weight loss at concentrations of 2.63 and 1.32 mmol/kg, In each group, longitudinal data were collected for whereas 0.66 and 0.33 mmol/kg produced insignificant three time points denoted by initial (I), middle (M) and results. These animals doses were extrapolated to final (F) for the first nine variables and at eight time human equivalency dose (HED) using the formula points for the last variable, which is ‘remaining food’.
HED ¼ animal dose  (human body weight/animal body There are no missing observations in this data set.
weight)1/3 [38]. Thus, 2.63 and 1.32 mmol/kg/day dose To compare the differences at 5% level of significance, equals a human daily dose of 3002 and 5981 mg respec- we have differences for ‘I & M’, ‘M & F’ and ‘I & F’ for the tively. Taking an average of these two doses comes to a first nine variables. The p-value is reported in paren- daily dose of approximately 4500 mg. Furthermore, a thesis for the tests ‘I & M’, ‘I & F’ and ‘M & F’ respect- concentration-dependent study was conducted in our ively. For remaining food, as data were collected at eight laboratories to evoke peak levels of serotonin release in time points, there are 28 possible paired differences.
rat brain cortex. A concentration of 300 mM HCA-SX Basic summary statistics and test for differences with exhibited maximum release of serotonin, beyond which respect to least-square means among the time points no further increase of serotonin release was observed were conducted for each group on each variable at [23,35]. Considering a five-fold faster metabolism in Table 1 Effects of placebo (group C), (–)-hydroxycitric acid (HCA-SX) X alone (group A) and HCA-SX formula (group B) on bodyweight, body mass index (BMI) and serum leptin levels in human subjects Data are presented as group mean Æ s.e.m. Subjects were given (–)-hydroxycitric acid (HCA-SX) alone (group A), HCA-SX formula (group B) orplacebo (group C) for 8 weeks. See Methods and Procedures for details. I, week 0; M, week 4; F, week 8. Values with non-identical superscriptsare significantly different (p < 0.05).
Diabetes, Obesity and Metabolism, 6, 2004, 171–180 Table 3 summarizes the changes in lipid profiles, including LDL, HDL, triglycerides, VLDL and total cho- The present study evaluated the effect of supplement- lesterol, in groups A, B and C. There was some reduction ation with optimal doses of a highly bioavailable form of in LDL and triglycerides in group A; however, the HCA (HCA-SX) alone or in combination with NBC and changes that were observed in group B were even more GSE on weight loss, BMI, appetite, lipid profiles, serum significant. Group B demonstrated a boost in HDL levels, while little effect was observed in group A. The overall Table 1 summarizes the changes in body weight, BMI total cholesterol level decreased significantly in both and serum leptin levels following supplementation of groups A and B. Approximately, 6.7 and 13.2% reduc- placebo (group C), HCA-SX (group A) and HCA-SX for- tions in LDL levels were observed in group A, while mula (group B) over the period of 8 weeks. There was a under these same conditions, approximately 7.1 and distinct change observed at the end of 4 and 8 weeks in 19% reductions in LDL levels were observed in group both groups A and B. In group C, approximately 1.28 and B at the end of 4 and 8 weeks respectively. A slight 1.6 kg reductions in body weight were observed at the increase in LDL levels, however, was observed in group end of 4 and 8 weeks respectively. Under the same con- C at both time points. Approximately, 4.7 and 8.0% ditions, approximately 2.35 and 4.53 kg reductions in increases in HDL levels were observed in group A, body weight were observed in group A and 2.74 and while 11.8 and 22.0% increases in HDL levels were 5.69 kg reductions in body weight were observed in the observed in group B, respectively, at the end of 4 and group B, respectively, at the end of 4 and 8 weeks. Thus, 8 weeks. No significant changes were observed in group at the end of 8 weeks, there were a 5 and 6.1% reduction C. Approximately, 2.9 and 5.9% reductions in triglycer- in BMI observed in group A and group B respectively.
ide levels were observed in group A and 14.2 and 20.2% There was a reduction of 2% BMI in group C at the end reductions in triglyceride levels were observed in group of 8 weeks. No significant changes were observed in B, respectively, at the end of 4 and 8 weeks respectively.
serum leptin levels in group C, while both group A and No significant changes were observed in group C. No group B exhibited a significant reduction. Approxi- significant changes were observed in the VLDL levels mately, 17.1 and 39.2% reductions in serum leptin in any of the groups. Approximately, 3 and 7.2% reduc- levels were observed in group A and 25.1 and 44.3% tions in total cholesterol levels were observed in group A reductions in serum leptin levels were observed in and 1.2 and 9.5% reductions in total cholesterol were group B, respectively, at the end of 4 and 8 weeks.
observed in group B at the end of 4 and 8 weeks respec- Approximately, 5.5 and 2.0% reductions in serum leptin tively. No changes were observed in group C.
levels were observed at the end of 4 and 8 weeks, respec- Enhanced excretion of urinary fat metabolites, includ- ing MDA, ACT, FA and ACON, was quantified as a Table 2 summarizes the amount of remaining food biomarker of fat oxidation. Approximately, 35.6– over the period of 8 weeks for each group, which reflects 106.4% increases in total urinary fat metabolites in a remarkable trend towards appetite suppression in both group A and 56–134% increases in total urinary fat group A and group B. No changes were observed in the metabolites in group B were observed at the end of appetite of group C. Approximately, a 15.6 and 21.2% 8 weeks, respectively, as compared with the control sam- reduction in appetite was observed in group A and ple. In group C, 6.2–21% increases were observed at the group B at the end of 8 weeks respectively.
Table 2 Effects of placebo (group C), (–)-hydroxycitric acid (HCA-SX) alone (group A) and HCA-SX formula (group B) on appetite inhuman subjects Remaining food (g) on the plate as an index of appetite suppression Data are presented as group mean Æ s.e.m. Subjects were given (–)-hydroxycitric acid (HCA-SX) alone (group A), HCA-SX formula (group B) orplacebo (group C) for 8 weeks. See Methods and Procedures for details. In group A, only three of the possible 28 pairs of differences aresignificant. In group B, 17 of the possible 28 pairs of differences are significant, while in group C, none of the 28 possible differences issignificant all at 5% level of significance.
Diabetes, Obesity and Metabolism, 6, 2004, 171–180 Table 3 Effects of placebo (group C), (–)-hydroxycitric acid (HCA-SX) alone (group A) and HCA-SX formula (group B) on lipid profilein human subjects HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein. Data are presented as group mean Æ s.e.m.
Subjects were given HCA-SX alone (group A), HCA-SX formula (group B) or placebo (group C) for 8 weeks. See Methods and Procedures fordetails. I, week 0; M, week 4; F, week 8. Values with non-identical superscripts are significantly different (p < 0.05).
In group A, MDA, ACT, FA and ACON increased by significant difference among the least-square means at 1.3-, 1.3-, 1.8- and 1.2-fold at the end of 4 weeks and 1.9-, the three time points for the variables body weight, BMI, 1.8-, 2.1- and 1.4-fold at the end of 8 weeks. In group B, serum leptin levels and excretion of urinary fat metabo- MDA, ACT, FA and ACON increased by 1.3-, 1.4-, 1.6- lites. For LDL and HDL, the ‘I & M’ and ‘I & F’ differences and 1.3-fold at the end of 4 weeks and 2.3-, 1.9-, 2.0- and are significant but not the ‘M & F’ difference. For the 1.6-fold at the end of 8 weeks. In group C, MDA, ACT, variable VLDL, there are no significant paired differ- FA and ACON increased by 0.9-, 0.9-, 1.2- and 1.0-fold at ences. For total cholesterol, only the ‘M & F’ and ‘I & F’ the end of 4 weeks and 1.2-, 1.1-, 1.2- and 1.1-fold at the differences are significant. It also showed only a few, which is three of the 28, paired differences between the In summary, we observe that among the three groups, variable ‘remaining food’ as significant. Group C showed group B showed a significant difference among the least- some significant difference in body weight, BMI and square means for the three time points, which were ‘I & HDL. For the remaining six variables, it did not show M’, ‘I & F’ and ‘M & F’ for the variables body weight, any significant change in the levels across the three time BMI, LDL, HDL, triglycerides, total cholesterol, serum points. As for the remaining food variable, none of the leptin levels and excretion of urinary fat metabolites. It 28 paired differences was significant. Thus, a statistically did not show any significant difference for the variable significant reduction in body weight, BMI, appetite, LDL, VLDL. It also showed the most number, which is 17, out total cholesterol and triglyceride levels, an increase in of the 28 paired differences between the variable HDL levels, a decrease in serum leptin levels and ‘remaining food’ as significant. Group A did show a enhanced excretion of urinary fat metabolites were Table 4 Effects of placebo (group C), (–)-hydroxycitric acid (HCA-SX) alone (group A) and HCA-SX formula (group B) on enhancedexcretion of urinary fat metabolites (nmol/ml of urine) ACON, acetone; ACT, acetaldehyde; FA, formaldehyde; MDA, malondialdehyde. Data are presented as group mean Æ s.e.m. Subjects weregiven HCA-SX alone (group A), HCA-SX formula (group B) or placebo (group C) for 8 weeks. See Methods and Procedures for details. I, week 0;M, week 4; F, week 8. Values with non-identical superscripts are significantly different (p < 0.05).
Diabetes, Obesity and Metabolism, 6, 2004, 171–180 observed when taking HCA-SX alone and in combination gas on day 6 and diarrhoea on day 23, and at the end of with NBC and GSE. Supplementation with a combination 28 days, this subject gained approximately 1.0 kg (body of HCA-SX, NBC and GSE (group B) resulted in greater weight: 79.5 kg). The fourth subject (106 kg) reported no improvements than HCA-SX (group A) alone in all para- adverse events during these 48 days, and at the end of 28 days, this subject lost approximately 1.5 kg (bodyweight: 104.5 kg).
Fifty-three of the initial 60 subjects completed the study.
During the 8-week study, no serious adverse effects wereobserved in any of the subjects. No patient was removed Obesity continues to be a major health problem in devel- or dropped out of the study as a result of an adverse oped and developing countries. Obesity increases the event caused by the treatment. In the HCA-SX group risk of hypertension, type 2 diabetes, arthritis, elevated (group A), one incidence of leg cramps, two incidences cholesterol, cancer and serious hormonal imbalances in of heartburn, four incidences of diarrhoea, four inci- women [42,43]. Obesity and its related metabolic and dences of gas, one incidence of increased appetite, cardiovascular complications continue to present an seven incidences of headaches, one incidence of sto- escalating challenge to contemporary medicine. Obesity mach burn, one incidence of skin rash, one incidence signifies chronic disequilibrium between food consump- of menstrual bleeding and two incidences of general tion and energy expenditure [3–6].
weakness were reported. In the HCA-SX, NBC and GSE HCA, derived from the fruit rind of G. cambogia, group (group B), two incidences of leg cramps, five inci- exhibits a distinctive sour taste and has been used for dences of mild diarrhoea, 10 incidences of mild gas and culinary purposes in southern Asia for centuries to make one incidence of headaches were observed. In the pla- meals more filling [44]. HCA is known to reduce appe- cebo group (group C), one incidence of leg cramps, two tite, inhibit fat synthesis and decrease body weight with- incidences of heartburn, nine incidences of diarrhoea, out stimulating the central nervous system. HCA does four incidences of gas, one incidence of increased appe- not cause nervousness, rapid heart rate, high blood pres- tite, one incidence of stomach burning, two incidences sure or insomnia, symptoms that are often associated of irregular periods, two incidences of menstrual bleed- with dietary stimulants such as ephedra (mahuang), caf- ing and one incidence of general weakness were reported. Taken together, the number of patients report- HCA promotes weight reduction through suppressed ing adverse events in the supplemented groups was not de novo fatty acid synthesis [14,16,17]. One mechanism significantly different from the placebo group.
accounting for the beneficial effects of HCA may involveinhibition of ATP citrate lyase, which will eventuallylimit the availability of acetyl coenzyme A and lipid synthesis during carbohydrate feeding [14,16,17,44]. In Seven subjects dropped out of this study. No subjects our previous study and in the present study, we have dropped out of the study as a result of an adverse event demonstrated other important mechanisms including caused by the treatment. One subject dropped out of the appetite suppression by HCA and serotonin release by HCA-SX group (group A) at the end of the twenty-first rat brain cortex [23,35], regulatory roles in the lowering day of the study. This subject (initial body weight: 90 kg) of lipid profiles and serum leptin levels and increased reported a common headache on day 5. Two subjects fat oxidation as demonstrated by enhanced excretion of dropped out of HCA-SX formula group (group B) at the end of the twelfth and twenty-eight day. The first subject In examining some positive weight-loss studies, a ran- (initial body weight: 71 kg) reported regular leg cramps domized, placebo-controlled study on HCA-SX was con- on day 3, while the second subject (94 kg) reported diar- ducted by Ramos et al. [31], involving 20 overweight rhoea on the eleventh day. Four subjects dropped out of adults, for a period of 8 weeks. It was demonstrated the placebo group (group C) at the end of the twelfth, that 500 mg of HCA-SX taken three times per day before thirty-sixth, forty-third and forty-eighth day. The first meals for 8 weeks resulted in 215% greater weight loss subject (109.5 kg) did not report any adverse events.
than those taking a placebo. This occurred without any The second subject (86 kg) did not report any adverse side affects commonly associated with other dietary sti- events, and at the end of the twenty-eighth day, his body mulants [45]. Of added importance, a significant reduc- weight was 84.5 kg. The third subject (78.5 kg) reported tion was observed in cholesterol and triglyceride levels.
Diabetes, Obesity and Metabolism, 6, 2004, 171–180 Another study by Mattes and Bormann [32] demon- Perceived weight loss in both the HCA-SX (group A) strated that a daily dose of 1.2 g of HCA along with a and HCA-SX formula (group B) group is supported by daily diet of 5020 kJ (1200 kcal) for 12 weeks resulted in a the improvement in BMI, which implies a sparing of significant difference in weight loss (3.7 Æ 3.1 vs.
lean muscle and fat oxidation, as demonstrated by 2.4 Æ 2.9 kg) compared to placebo. Westerterp-Plantenga enhanced excretion of urinary fat metabolites (table 4).
and Kovacs [34] conducted a 6-week randomized, Muscle mass is denser and heavier, and thus, sparing placebo-controlled, single-blind, cross-over study in 12 lean muscle mass contributes to slow and steady fat loss males and 12 females using a daily dose of 900 mg of HCA-SX for 2 weeks. They demonstrated that HCA-SX Downregulation of obesity regulatory gene may be an supplementation reduced 24-h energy intake in humans, additional mechanism of HCA’s ability to reduce body weight and appetite. Leptin, a 167-amino acid protein In examining the ‘negative studies’, Heymsfield et al.
hormone and a biomarker of the obesity regulatory gene, [46] provided what became an accepted daily dose of is synthesized and secreted by adipocytes and is present 1.5 g of HCA along with a diet of 5020 kJ/day or in the bloodstream and is directly related to body fat.
1200 kcal/day for 12 weeks and reported that no signifi- Leptin binds to receptors in the brain and activates sig- cant difference in weight loss was observed between the nals that inhibit food intake and increase energy expen- placebo and treatment groups. Several problems with the study, however, may be responsible for the negative receptor-binding activity is diminished and, as a result, results [46]. Heymsfield et al. [46] quantified the HCA plasma leptin levels increase, which in turn lose their content but did not assess the bioavailability of the HCA ability to inhibit food intake and increase energy sample used in the study. Many HCA products are less expenditure. Generally, plasma leptin levels are higher than 50% soluble in water and poorly absorbed. Also, in overweight individuals than in normal individuals this low-calorie diet (5020 kJ/day) may have accounted and higher in women than in men. Leptin has been for the substantial decreases in body weight of both shown to be able to modulate insulin secretion and treatment and placebo groups, blunting the ability of action through these receptors [47]. In the present HCA to show curbed appetite and reduced food intake.
study, it was demonstrated that supplementation with Our present study was conducted using a highly bio- HCA-SX alone and in combination with NBC and GSE available, water-soluble calcium–potassium salt of HCA significantly decreases serum leptin levels, which may (HCA-SX). Supplements were given on an empty sto- play a significant role in downregulating the obesity mach at least 30–60 min before meals to enhance bio- availability, which was previously demonstrated by Loe The fat-degradation or fat-oxidation ability of HCA-SX et al. [36]. This more efficacious dose was extrapolated was evaluated based on the excretion of urinary fat from ex vivo and in vivo studies, as discussed in the metabolites including MDA, ACT, FA and ACON.
Methods and Procedures, which is an increased dose of Enhanced b-oxidation of fat may be the prime sources HCA compared to other studies. The available sources of of these four fat metabolites. Enhanced excretion of HCA in the market today are a calcium salt that is poorly MDA was observed during increased oxidative stress soluble in water, allowing for compromised absorption.
[50]. In the same study, radiolabelled MDA administered This study was designed to better determine the to rats was found to be extensively metabolized to acet- effects of HCA-SX, at a higher, more efficacious dose, ate and carbon dioxide. The enhanced excretion of urin- on satiety. Subjects were administered a 2000 kcal or ary ACT identified in the present study may be due to 8372 kJ diet/day, and all remaining food was weighed the breakdown of MDA or as a result of fat oxidation/ after each meal to determine HCA-SX’s effect on appetite lipid peroxidation. The enhanced urinary excretion of reduction. Results demonstrated a significant reduction ACON may occur in response to a consequence of in appetite following supplementation of HCA-SX alone enhanced b-oxidation, as reported earlier [51]. Meta- bolism of glycerol to FA has been reported in rat liver A statistically significant reduction in body weight microsomes and is a result of the metabolism of trigly- was observed between ‘I’ and ‘M’ but not between ‘M’ cerides by adipose tissue and other tissues that possess and ‘F’ in the placebo (group C), which signifies that a the enzyme that activates glycerol, namely glycerol controlled diet and exercise initially result in weight kinase [52]. High glycerol kinase levels are found in reduction but eventually plateaus. This fact highlights liver and brown tissues [52,53]. Other possible sources the importance of a novel, efficacious safe supplement of FA might include the breakdown of MDA to acetate or ACT and a one-carbon fragment [50] and/or the cleavage Diabetes, Obesity and Metabolism, 6, 2004, 171–180 of a one-carbon fragment from acetoacetic acid with the 8 Sobal J, Stunkard AJ. Socioeconomic status and obesity: formation of ACON. In the present study, the trigly- a review of the literature. Psychol Bull 1989; 105: 260–275.
ceride levels were significantly reduced in subjects sup- 9 Namnoum AB. Obesity: a disease worth treating. Female plemented with either HCA-SX or HCA-SX, NBC and GSE, accompanied by significant increases in urinary 10 Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS. Leptin levels reflect body lipid con- excretion of FA, which suggests that these supplements tent in mice: evidence for diet-induced resistance to may induce enhanced production of glycerol kinase in leptin action. Nat Med 1995; 1: 1311–1314.
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13 Haller CA, Benowitz NL. Adverse cardiovascular and The current study demonstrates that supplementation central nervous system events associated with dietary with HCA-SX or HCA-SX, NBC and GSE significantly supplements containing ephedra alkaloids. N Engl JMed 2000; 343: 1833–1838.
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Diabetes, Obesity and Metabolism, 6, 2004, 171–180



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