weight loss blog

Weight loss

I like to compile as much helpful info on weight loss as possible to help people interested in improving their health.

Before starting any weight loss program please check with your doctor first! This information in not meant to replace any medical advice but rather inform you of some helpful products on the market.

Hydroxycitric acid (HCA), the principle constituent (10-50%) of the dried fruit rind of Garcinia cambogia, has been assessed for its potential to cause weight loss.[15] In late 2012, a United States television personality, Dr. Oz, promoted Garcinia cambogia extract as “an exciting breakthrough in natural weight loss”.[16][17] Dr. Oz’s endorsements of dietary supplements having no or little scientific evicence of efficacy have often led to a substantial increase in consumer purchases of the promoted products.[17]

However, medical evidence is lacking, and the results of clinical trials do not strongly support claims that extracts derived from Garcinia cambogia are effective weight-loss aids.[18][19][20][21] Meta-analyses of clinical trials offers evidence for limited short term weight loss with increases of up to two-fold in adverse events.[6][22] A 1998 randomized, controlled trial looked at the effects of hydroxycitric acid, the purported active component in G. gummi-gutta, as a potential antiobesity agent in 135 people. The conclusion from this trial was that Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo.[18] A more recent report stated that a meta-analysis, had clear limitations, suggesting:

…a small, statistically significant difference in weight loss favouring HCA over placebo (MD: −0.88 kg; 95% CI: −1.75, −0.00). [but with] Gastrointestinal adverse events… twice as common in the HCA group compared with placebo in one included study… [leading them to conclude that while] …Garcinia extracts/HCA can help short-term weight loss. The magnitude of the effect is small, and the clinical relevance is uncertain.[6]
Do your own reasearch before taking any products, but this is a great over the counter weight loss product.
While it has received considerable media attention purporting impact on weight loss, the limited clinical evidence for Garcinia cambogia supports no clear effect,[18] while gastrointestinal adverse events were two-fold more common over the placebo in a 2011 meta-analysis indicating the extract may be unsafe for human consumption.[6]
Adverse effects

Orally, 500 mg of hydroxycitric acid four times daily can cause nausea, gastrointestinal discomfort, and headaches.[24] Proceed with caution and listen to your body as everyone is different.
Drug Interactions
When the fruit is sun dried for several days, it becomes black with a shrivelled body.

There have been several case reports of patients developing “Serotonin Syndrome” after combining their serotonergic medicines with Garcinia cambogia.[25] Caution should be exercised in patients treated with the following class of medications who are looking to manage their weight issue using Garcinia cambogia:

SSRIs: such as Fluoxetine, Paroxetine, Escitalopram and Sertraline
Tricyclic Antidepressant (TCAs): Doxepine, Amitriptyline, etc.
Dextromethorphan: a common cough suppressant found in many cough syrups and cold&flu remedies.
Original Contribution
November 11, 1998
Garcinia cambogia (Hydroxycitric Acid) as a Potential Antiobesity AgentA Randomized Controlled Trial
Steven B. Heymsfield, MD; David B. Allison, PhD; Joseph R. Vasselli, PhD; et al Angelo Pietrobelli, MD; Debra Greenfield, MS, RD; Christopher Nunez, MEd
Author Affiliations
JAMA. 1998;280(18):1596-1600. doi:10.1001/jama.280.18.1596

Context.— Hydroxycitric acid, the active ingredient in the herbal compound Garcinia cambogia, competitively inhibits the extramitochondrial enzyme adenosine triphosphate–citrate (pro-3S)-lyase. As a citrate cleavage enzyme that may play an essential role in de novo lipogenesis inhibition, G cambogia is claimed to lower body weight and reduce fat mass in humans.

Objective.— To evaluate the efficacy of G cambogia for body weight and fat mass loss in overweight human subjects.

Design.— Twelve-week randomized, double-blind, placebo-controlled trial.

Setting.— Outpatient weight control research unit.

Participants.— Overweight men and women subjects (mean body mass index [weight in kilograms divided by the square of height in meters], approximately 32 kg/m2).

Intervention.— Subjects were randomized to receive either active herbal compound (1500 mg of hydroxycitric acid per day) or placebo, and both groups were prescribed a high-fiber, low-energy diet. The treatment period was 12 weeks. Body weight was evaluated every other week and fat mass was measured at weeks 0 and 12.

Main Outcome Measures.— Body weight change and fat mass change.

Results.— A total of 135 subjects were randomized to either active hydroxycitric acid (n=66) or placebo (n=69); 42 (64%) in the active hydroxycitric acid group and 42 (61%) in the placebo group completed 12 weeks of treatment (P=.74). Patients in both groups lost a significant amount of weight during the 12-week treatment period (P<.001); however, between-group weight loss differences were not statistically significant (mean [SD], 3.2 [3.3] kg vs 4.1 [3.9] kg; P=.14). There were no significant differences in estimated percentage of body fat mass loss between treatment groups, and the fraction of subject weight loss as fat was not influenced by treatment group. Conclusions.— Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo. A widely used practice by the general public,is the use of herbal weight loss products. The small amount of weight loss can aid in your long term goal if it is combined with exercise and a well balanced diet. An herb-derived compound, hydroxycitric acid, is now incorporated into many commercial weight loss products. Obtained from extracts of related plants native to India, mainly Garcinia cambogia and Garcinia indica , hydroxycitric acid was first identified by Watson and Lowenstein4,5 in the late 1960s as a potent competitive inhibitor of the extramitochondrial enzyme adenosine triphosphate–citrate (pro-3 S)-lyase. These investigators and others subsequently demonstrated both in vitro and in vivo that hydroxycitric acid in animals not only inhibited the actions of citrate cleavage enzyme and suppressed de novo fatty acid synthesis,6 but also increased rates of hepatic glycogen synthesis,7 suppressed food intake,8 and decreased body weight gain.9 Although hydroxycitric acid appears to be a promising experimental weight control agent, studies in humans are limited and results have been contradictory10- 14 (also R. Ramos, J. Flores Saenz, F. Alarcon, unpublished data, 1996, and G. Kaats, D. Pullin, L. Parker, S. Keith, unpublished data, 1996). Supporting evidence of human hydroxycitric acid efficacy for weight control is based largely on studies with small sample sizes,11,12 studies that failed to include a placebo-treated group,10 and use of inaccurate measures of body lipid change.12 Although hydroxycitric acid effectiveness remains unclear, at least 14 separate hydroxycitric acid–containing products are presently sold over-the-counter to consumers.15 This investigation was designed to overcome limitations of earlier studies and examine the effectiveness of hydroxycitric acid for weight loss and fat mass reduction in a rigorous controlled trial. Methods Protocol We tested 2 primary hypotheses in a randomized, double-blind, placebo-controlled trial: (1) G cambogia produces a greater reduction in body weight than placebo, and (2) G cambogia produces a greater reduction in total body fat mass than placebo. Advertisements were placed in local newspapers, and overweight subjects who responded and met entry criteria during a telephone screening interview were scheduled for a baseline visit. The evaluation included a physical examination, electrocardiogram, and screening blood studies. Subjects meeting entry criteria were seen within 2 weeks for randomization at treatment week 0. Subjects were assigned to placebo or active compound with equal probability through a random number generator. The protocol with active herbal compound included G cambogia extract (50% hydroxycitric acid by chemical analysis), taken 3 times daily as two 500-mg caplets 30 minutes before meal ingestion. Total daily dose was G cambogia extract, 3000 mg, and hydroxycitric acid, 1500 mg. Placebo-treated subjects followed an identical protocol in which active compound was replaced with inert ingredients. Subjects taking active compound or placebo were provided a high-fiber, 5040-kJ/d diet plan, with 20%, 50%, and 30% of energy as fat, carbohydrate, and protein, respectively. The recommended daily food provision was divided into 3 meals with an evening snack. Subjects were asked to maintain a stable physical activity level and return for evaluation every 2 weeks for a total treatment interval of 12 weeks. Body weight was measured at each visit, and clinical information, including potential herb or weight loss adverse effects, was obtained. Biweekly pill counts and diaries were used to check patient medication compliance. Diet compliance was not quantitatively monitored during the study. The study was approved by the institutional review board of St Luke's–Roosevelt Hospital Center, New York, NY, and all subjects gave written consent prior to participation. Subjects Subjects were overweight but otherwise healthy adults aged 18 to 65 years who had a body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) of more than 27 kg/m2and at most 38 kg/m2. Subjects were excluded if they were pregnant, had any clinically significant medical condition, were taking prescription medications or appetite suppressants on a regular basis, had a history of alcohol or other drug abuse, were allergic to any of the study products, or had dieted with weight loss in the past 6 months. Body Composition Body weight and height were measured to the nearest 0.1 kg and 0.5 cm using a digital scale (Weight Tronix, New York, NY) and stadiometer (Holtain, Crosswell, Wales), respectively. Total body fat mass was measured at baseline and at the 12-week visit using several different procedures. A pencil-beam dual-energy x-ray absorptiometry (DXA) scanner (Lunar DPX, Madison, Wis) was used to estimate total body fat mass. Subjects completed the slow-mode whole body scan and fat mass estimates were provided by Lunar, Version 3.6g, software.16 The technical error of DXA percentage fat mass estimates in our laboratory is 3.1%.17 The remaining body fat mass measurement methods used in our laboratory for this study included underwater weighing,18 skinfold thicknesses,19 and bioimpedance analysis.20 Statistical Analysis Based on previous research,1 we estimated that a study that included at least 30 completed subjects in each of 2 groups would have more than 80% power at the 2-tailed α level of .05 to detect any significant differences in body weight. The 2 study hypotheses were tested in separate sets of statistical analyses. Statistical models were used in which the outcome variable, either loss of body weight or percentage of fat mass, was set as dependent variable and assigned treatment and other covariates were set as independent variables in an intent-to-treat analysis.21 Within the intent-to-treat analysis, missing data due to measurement failure or subject dropout were imputed by carrying the last observation forward (LOCF).22 The baseline value of the dependent variable (ie, initial body weight or percentage of fat mass) served as a potential independent variable in each analysis. Patient age and sex also served as additional independent variables. All analyses were conducted at the 2-tailed α level of .05. For each of the 2 dependent variables, a set of secondary analyses were conducted, including (1) evaluation of completers only; (2) imputation of all missing data with a regression procedure rather than the LOCF; (3) imputation of missing data using the EM23 algorithm rather than the LOCF; (4) use of weight loss slopes as outcomes24 rather than the simple baseline to final measurement change when more than 2 time points for weight were available; (5) performance of a full repeated-measures analysis of variance using all time points; and (6) performance of a multivariate analysis of covariance using all time points simultaneously in the statistical model. In no case did any of these secondary sensitivity analyses lead to different conclusions than the primary LOCF intent-to-treat analysis. We therefore report only the results of the primary intent-to-treat analysis. At baseline, DXA readings were unavailable for several subjects who had technically poor scans or who were evaluated during a brief period in which the DXA system was undergoing repair. However, each of these subjects had 1 or more measurements of fat mass taken with the other techniques mentioned herein and summarized in earlier articles.16- 20 Estimates of total body fat mass for these subjects by DXA were inferred using single imputation plus random error models based on multiple regression analysis of all other available measurements of fat mass for that subject, as described by Graham et al.25 Similarly, several subjects completed the entire course of treatment and received some measurement of body fat mass after treatment but not by DXA. For these subjects, estimates of total body fat mass by DXA also were imputed using the same statistical methods and the other available measurements of body fat mass. The purported fat-mobilizing properties of hydroxycitric acid were evaluated by computing the slope of change in fat mass vs change in body weight for the 2 treatment groups. Assuming approximately a zero intercept for this relation, the anticipated regression line slopes should approach 0.7 to 0.8, the generally acknowledged fraction of weight loss as fat mass in obesity trials.26 Promotion of fat mass loss by active hydroxycitric acid would be associated with an increased fraction of weight loss as fat mass. Group results are expressed as mean (SD) in text and tables. Data were analyzed using the statistical programs SPSSWIN, Version 7.5, and SPSSMVA, Version 7.5 (SPSS Inc, Chicago, Ill). Results Baseline Characteristics At baseline, 180 moderately overweight subjects were screened and, of those, 135 were randomized to placebo and active compound (Table 1 and Figure 1). There were 69 subjects (BMI, 31.9 [3.1] kg/m2) in the placebo-treated group (14 men and 55 women) and 66 subjects (BMI, 31.3 [2.8] kg/m2) in the G cambogia– treated group (5 men and 61 women). Of the 69 placebo-treated subjects, 42 (61%) completed the 12-week protocol. The reasons for subject withdrawal (27 cases) are summarized in Figure 1. Of the 66 subjects randomized to active compound, 42 (64%) completed the 12 weeks of treatment. The reasons for subject withdrawal from this group (24 cases) are also summarized in Figure 1. There were no significant differences in age, body weight, or BMI between subjects who withdrew from the study and those who completed the 12-week protocol. There was also no significant difference between the 2 groups in the proportion of subjects who completed the entire course of treatment (χ2=0.11, P =.74). Among subjects completing the 12 weeks of treatment, medication compliance was 88.6% (10.9%) and 92.1% (10.0%) in the treatment and placebo groups, respectively (P=.30). Weight Loss Primary Analysis.— The weight loss curves for placebo and treatment groups are shown in Figure 2 for subjects in the intent-to-treat analysis with LOCF. The estimated mean (SD) [median (interquartile range)] weight loss for the placebo group was 4.1 (3.9) [3.9 (4.7)] kg and for the treatment group was 3.2 (3.3) [2.6 (4.1)] kg. The weight loss within each group was significantly different from baseline (t134=11.795, P <.001), although between-group weight loss differences were not statistically significant (t133=1.474, P =.14). Body weight change differences remained nonsignificant after controlling for patient starting weight, sex, and age. Assumptions of the applied parametric statistical analysis such as homogeneity of variance and normality of residuals were tested and no meaningful violations were detected. Given the lack of significant findings, questions of statistical power are important. Therefore, using the observed distributions of weight change and the within-group SD thereof, we estimated that the power of the current study to detect differences between the treatment and placebo groups in terms of weight change was 89% to detect a between-group difference in weight loss as small as 2 kg at the 2-tailed α level of .05. Secondary Analyses.— In no case did any secondary analysis indicate any statistically significant effect for the active compound to produce more weight loss than placebo. Fat Mass Loss Primary Analysis.— Results for body fat mass analysis were imputed for 9 baseline and 4 post–weight loss subjects. With the LOCF intent-to-treat analysis, the estimated mean (SD) [median (interquartile range)] percentage of body fat mass loss for the placebo group was 2.16% (2.06%) [2.20% (2.7%)] and the estimated percentage of fat mass loss for the treatment group was 1.44% (2.15%) [1.60% (1.9%)]. This difference was tested using the Welch test because the variances were significantly heterogeneous by the Levene test (P for variance heterogeneity=.03). Using the Welch test, the placebo and treatment group mean differences were not statistically significant (t129=1.7, P =.08). This finding was consistent with that of the ordinary t test (t132=1.78, P =.08). Using analysis of covariance with age, sex, and pretest percentage of fat mass as covariates, the percentage of fat mass differences also was nonsignificant (F1129=1.57, P=.21). Secondary Analyses.— As for weight loss, all of the secondary analyses were consistent with the primary analysis. That is, in no case did analysis indicate any statistically significant effect for the active compound to produce a different percentage of body fat mass loss than the placebo. Examination of the change in fat mass relative to change in body weight derived using least squares regression analysis for all subjects combined resulted in the relation, Δfat mass (kg)=0.77 × Δbody weight (kg) − 0.44, with r=0.89 and P <.001. The association was not changed significantly (P>.91) by adding treatment group as a second independent variable, even after adjusting for 3 additional potential covariates: initial body weight, sex, and age.
Adverse Events

No patient was removed from the study protocol for a treatment-related adverse event, and the number of reported adverse events was not significantly different between the placebo and treatment groups (eg, headache, 12 vs 9, respectively; upper respiratory tract symptoms, 13 vs 16, respectively; and gastrointestinal tract symptoms, 6 vs 13, respectively).

In 1883 von Lippmann isolated hydroxycitric acid, a minor constituent of sugar beets.27 More than half a century later, in 1941, Martius and Maué28 discovered that the (+) isomer of a racemic hydroxycitric acid mixture is attacked by the enzyme isocitrate dehydrogenase. The (−) hydroxycitric acid isomer of hydroxycitric acid was first isolated by Lewis and Neelakantan in 1964,29 and by 1969 Watson and colleagues5 reported the powerful inhibition by (−) hydroxycitric acid of citrate cleavage enzyme. Evidently, the additional hydroxyl group’s steric position, compared with citric acid, enhances its binding affinity and competitively inhibits catalytic action by the enzyme. Citrate, entering the cytoplasm from mitochondria, cannot be cleaved to release acetyl coenzyme A, the substrate for de novo fatty acid synthesis. Despite these century-old, well-grounded observations, there has been little effort to critically test the basic assumption underlying therapeutic use of hydroxycitric acid in overweight humans: that hydroxycitric acid inhibition of lipid synthesis will significantly reduce body fat mass beyond that observed with a placebo capsule.

The present study, carried out during a 12-week evaluation period and using accepted experimental design and in vivo analytic methods, failed to support the hypothesis that hydroxycitric acid as prescribed promotes either additional weight or fat mass loss beyond that observed with placebo. Specifically, body weight and fat mass change during the 12-week study period did not differ significantly between placebo and treatment groups. These results apply to both the primary and secondary statistical analyses. Additionally, there were no observed selective fat-mobilizing effects specifically attributable to the active agent, hydroxycitric acid.

Seven earlier G cambogia trials have appeared in peer-reviewed literature,11,14 as abstracts,12,13 and in industrial publications as an open-label study10 and randomized controlled trials.11- 14 We chose to collectively review these studies even though G cambogia typically was used in combination with other ingredients for the claimed purpose of enhancing weight loss.

Of the 7 studies reviewed, 5 reported significant (P<.05) effects of G cambogia alone or in combination with other ingredients on body weight or fat mass loss in overweight humans (Table 2). These earlier studies all have limitations when specifically considering G cambogia as a weight loss agent, including lack of placebo control or double-blinding in 1 study,10 coadministration of G cambogia in combination with other potentially active ingredients in 5 studies,10,11,13,14 use of an inaccurate body composition method (near-infrared interactance)12 in 1 study, and failure as of yet to publish study results in peer-reviewed literature in all but 213,14 of the 7 studies. However, our present investigation, carried out using accepted clinical trial design procedures and applying accurate body composition methods, failed to support a specific weight loss effect of G cambogia administered as recommended. The present 12-week study period also exceeded in duration all previous study treatment periods, which ranged from 4 to 8 weeks. In our present investigation we failed to detect a weight loss or fat-mobilizing effect of active herb. The question therefore arises whether there exist conditions differing from those used in the present study that might support hydroxycitric acid efficacy. The 5040-kJ/d low-fat diet recommended in our current study was intended to mimic diets commonly prescribed as a component of weight control programs. The possibility exists that the lipid synthesis–inhibiting properties of hydroxycitric acid may be more evident in subjects relapsing following a failed diet attempt, particularly if high-carbohydrate foods are ingested.30 Another concern is related to the timing and dosage considerations of hydroxycitric acid. Sullivan and colleagues31 showed that the effects of hydroxycitric acid in animals depend on time of administration in relation to a meal, with hydroxycitric acid maximally effective when administered 30 to 60 minutes prior to feeding. The approach used in our study and the others we reviewed suggested hydroxycitric acid ingestion about 30 minutes prior to meal intake, the lower end of the maximally effective range. A related concern is that hydroxycitric acid provided in divided doses also was found to be more effective than the same amount given as a single dose.8 Although divided doses typically are used in weight loss protocols, human doses ranging between 750 and 1500 mg/d of hydroxycitric acid are at the extreme low end of the in vivo dose-response range established by Sullivan and colleagues.32 Thus, in light of the many requirements for its effective use, it seems unlikely that the maximal effects of hydroxycitric acid will be realized in human weight loss studies unless treatment conditions are well defined and patient diet and medication compliance are tightly monitored. Our study explored product safety only in the form of clinical evaluations and reported adverse events. No significant differences were observed between placebo and treatment groups in number of reported adverse events and no subjects were removed from the study for a treatment-related adverse event. Additional studies, potentially with larger subject groups, are needed to gather specific information on the long-term safety of G cambogia. An important concern in all pharmacological trials, particularly those in which herbal products are evaluated, is the amount and bioavailability of the active agent. As standard procedure, we confirmed the presence and quantity of hydroxycitric acid in the supplied capsules using an independent testing laboratory. However, we did not measure hydroxycitric acid blood levels or evaluate tissue or cytosolic citrate-cleavage enzyme activity. Although the format of our experiment closely resembles current use of G cambogia as a weight loss product, our conclusions should not be interpreted as a failure to support the validity of the biochemical effects of hydroxycitric acid identified by earlier investigators. In conclusion, our study evaluated the hypothesis that the active ingredient of G cambogia, hydroxycitric acid, has beneficial weight and fat mass loss effects. Our findings, obtained in a prospective, randomized, double-blind study, failed to detect either weight loss or fat-mobilizing effects of hydroxycitric acid beyond those of placebo. These observations, the first, to our knowledge, to appear in a peer-reviewed article using currently accepted experimental and statistical methods, do not support a role as currently prescribed for the widely used herb G cambogia as a facilitator of weight loss. References 1. National Task Force on the Prevention and Treatment of Obesity. Long-term pharmacotherapy in the management of obesity. JAMA.1996;276:1907-1915. 2. Bray GA. Use and abuse of appetite suppressant drugs in the treatment of obesity. Ann Intern Med.1993;119:707-713. 3. National Institutes of Health Consensus Development Conference statements: gastrointestinal surgery for severe obesity. Am J Clin Nutr.1992;55(suppl):487S-619S. 4. Watson JA, Lowenstein JM. Citrate and the conversion of carbohydrate into fat. J Biol Chem.1970;245:5993-6002. 5. Watson JA, Fang M, Lowenstein JM. Tricarballylate and hydroxycitrate: substrate and inhibitor of ATP: citrate oxaloacetate lyase. Arch Biochem Biophys.1969;35:209-217. 6. Lowenstein JM. Effect of (−)-hydroxycitrate on fatty acid synthesis by rat liver in vivo. J Biol Chem.1971;246:629-632. 7. Sullivan AC, Triscari J, Neal Miller O. The influence of (−)-hydroxycitrate on in vivo rates of hepatic glycogenesis: lipogenesis and cholesterol-genesis. Fed Proc.1974;33:656. 8. Sullivan AC, Triscari J, Hamilton JG, Neal Miller O. Effect of (−)-hydroxycitrate upon the accumulation of lipid in the rat: appetite. Lipids.1973;9:129-134. 9. Nageswara Rao R, Sakeriak KK. Lipid-lowering and antiobesity effect of (−) hydroxycitric acid. Nutr Res.1988;8:209-212. 10. Badmaev V, Majeed M. Open field, physician controlled, clinical evaluation of botanical weight loss formula citrin. Presented at: Nutracon 1995: Nutriceuticals, Dietary Supplements and Functional Foods; July 11-13, 1995; Las Vegas, Nev. 11. Conte AA. A non-prescription alternative on weight reduction therapy. Am J Bariatr Med.Summer 1993:17-19. 12. Thom E. Hydroxycitrate (HCA) in the treatment of obesity. Int J Obes.1996;20(suppl 4):48. 13. Rothacker DQ, Waitman BE. Effectiveness of a Garcinia cambogia and natural caffeine combination in weight loss: a double-blind placebo-controlled pilot study. Int J Obes.1997;21(suppl 2):53. 14. Girola M, De Bernardi M, Contos S. et al. Dose effect in lipid-lowering activity of a new dietary intetrator (chitosan, Garcinia cambogia extract, and chrome). Acta Toxicol Ther.1996;17:25-40. 15. Hobbs LS. (–)-Hydroxycitrate (HCA). In: The New Diet Pills . Irvine, Calif: Pragmatic Press; 1994:161-174. 16. Pietrobelli A, Formica C, Wang ZM, Heymsfield SB. Dual-energy x-ray absorptiometry body composition model: review of physical concepts. Am J Physiol.1996;271:E941-E951. 17. Russel-Aulet M, Wang J, Thornton J, Pierson Jr RN. Comparison of dual photon absorptiometry system for total body bone and soft tissue measurements: dual-energy x-ray versus gadolinium 153. J Bone Miner Res.1991;6:411-415. 18. Heymsfield SB, Wang ZM, Withers R. Multicomponent molecular-level models for body composition analysis. In: Roche AF, Heymsfield SB, Lohman TG, eds. Human Body Composition . Champaign, Ill: Human Kinetics; 1996:129-147. 19. Heymsfield SB, Tighe A, Wang ZM. Nutritional assessment by anthropometric and biochemical methods. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease . Philadelphia, Pa: Lea & Febiger; 1992:812-841. 20. Heymsfield SB, Visser M, Gallagher D, Pierson Jr RN, Wang ZM. Techniques used in measurement of body composition: an overview with emphasis on bioelectrical impedance analysis. Am J Clin Nutr.1996;64(suppl):478S-484S. 21. Committee for Proprietary Medicinal Products. Note for Guidance on Clinical Investigation of Drugs Used in Weight Control . London, England: The European Agency for the Evaluation of Medical Products; 1997. 22. Niklson IA, Reimitz PE, Sennef C. Factors that influence the outcome of placebo-controlled antidepressant clinical trials. Psychopharmacol Bull.1997;33:41-51. 23. Dempster AP, Laird NH, Rubin DB. Maximum likelihood from incomplete data via the EM algorithm. J R Stat Soc.1977;39B:1-38. 24. Burstein L, Kim KS, Delandshere G. Multilevel Investigations of Systematically Varying Slopes: Issues, Alternatives, and Consequences . New York, NY: Academic Press; 1989. 25. Graham JW, Hoofer SM, Picnic AM. Analysis with missing data in drug prevention research. In: Des Collins LM, Seats LA, eds. Advances in Data Analysis for Prevention Intervention Research . Washington, DC: US Dept of Health and Human Services; 1994:13. NIDA Research Monograph 142. 26. Webster JD, Hesp R, Garrow JS. The composition of excess weight in obese women estimated by body density, total body water and total body potassium. Hum Nutr Clin Nutr.1984;38:299-306. 27. von Lippmann EO. Uber eine neue, im Rübensaft vorkommende Säure. Ber Dtsch Chem Ges.1883;16:1078-1081. 28. Martius C, Maué R. Darstellung, physiologisches Verhalten und Bedeutung der (+)− Oxycitronensäure und ihrer Isomeren. Z Physiol Chem.1941;269:33-40. 29. Lewis YS, Neelakantan S. (−)-Hydroxycitric acid: the principal acid in the fruits of Garcinia cambogia. Phytochemistry.1965;4:610-625. 30. Vasselli JR, Shane E, Boozer CN, Heymsfield SB. Garcinia cambogia extract inhibits body weight gain via increased energy expenditure (EE) in rats. FASEB J.1998;12(part I):A505. 31. Sullivan AC, Hamilton JG, Neal Miller O, Wheatley VR. Inhibition of lipogenesis in rat liver by (−)-hydroxycitrate. Arch Biochem Biophys.1972;150:183-190. 32. Sullivan AC, Trescari J, Hamilton JG, Neal Miller O, Wheatley VR. Effect of (–)-hydroxycitrate upon the accumulation of lipid in the rat, I: lipogenesis. Lipids.1973;9:121-128. J Obes. 2011; 2011: 509038. Published online 2010 Dec 14. doi: 10.1155/2011/509038 PMCID: PMC3010674 The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials Igho Onakpoya,* Shao Kang Hung, Rachel Perry, Barbara Wider, and Edzard Ernst Author information ► Article notes ► Copyright and License information ► This article has been cited by other articles in PMC. Go to: Abstract The aim of this systematic review is to examine the efficacy of Garcinia extract, hydroxycitric acid (HCA) as a weight reduction agent, using data from randomised clinical trials (RCTs). Electronic and nonelectronic searches were conducted to identify relevant articles, with no restrictions in language or time. Two independent reviewers extracted the data and assessed the methodological quality of included studies. Twenty-three eligible trials were identified and twelve were included. Nine trials provided data suitable for statistical pooling. The meta-analysis revealed a small, statistically significant difference in weight loss favouring HCA over placebo (MD: −0.88 kg; 95% CI: −1.75, −0.00). Gastrointestinal adverse events were twice as common in the HCA group compared with placebo in one included study. It is concluded that the RCTs suggest that Garcinia extracts/HCA can cause short-term weight loss. The magnitude of the effect is small, and the clinical relevance is uncertain. Future trials should be more rigorous and better reported. Go to: 1. Introduction The prevalence of overweight and obesity has increased over the last decade [1], and current measures have not been able to stem the tide. A wide variety of weight management strategies are presently available, and some involve the use of dietary supplements marketed as slimming aids. One such slimming aid is Garcinia extract, (-)-hydroxycitric acid (HCA). HCA is a derivative of citric acid and can be found in plant species native to South Asia such as Garcinia cambogia, Garcinia indica, and Garcinia atroviridis [2]. HCA is usually marketed as a weight loss supplement either alone or in combination with other supplements [2, 3]. Some authors have suggested that HCA causes weight loss by competitively inhibiting the enzyme adenosine triphosphatase-citrate-lyase [3–6]. HCA has also been reported to increase the release or availability of serotonin in the brain, thereby leading to appetite suppression [7]. Other postulated weight loss mechanisms include inhibition of pancreatic alpha amylase and intestinal alpha glucosidase, thereby leading to a reduction in carbohydrate metabolism [8]. Animal studies have suggested that HCA causes weight loss [3, 9], and human trials involving the use of HCA as a weight loss supplement have been carried out [3]. The primary objective of this systematic review was to examine the efficacy of HCA in reducing body weight in humans, using data from randomised clinical trials. Go to: 2. Methods Electronic searches of the literature were conducted in the following databases: Medline, Embase, The Cochrane Library, Amed, and Cinahl. The search terms used included dietary supplements, antiobesity agents, body weight, hydroxycitrate, garcinia, and derivatives of these. Each database was searched from inception until March, 2010. We also searched the Internet for relevant conference proceedings and hand searched relevant medical journals, and our own files. The bibliographies of all located articles were also searched. Only randomised, double-blind, placebo-controlled studies were included in this paper. To be considered for inclusion, studies had to test the efficacy of oral HCA or any of its salts for weight reduction in obese or overweight humans. Included studies also had to report body weight as an outcome. No age, time, or language restrictions were imposed for inclusion of studies. Studies which involved the use of HCA as part of a combination treatment (dietary interventions containing other supplements in addition to HCA), or not involving obese or overweight subjects based on body mass index (BMI) values, were excluded from this paper. Two independent reviewers assessed the eligibility of studies to be included in the paper. Data were extracted systematically by two independent reviewers according to the patient characteristics, interventions, and results. The methodological quality of all included studies was assessed by the use of a quality assessment checklist adapted from the Consolidated Standard of Reporting Trials (CONSORT) guidelines [10, 11]. In addition, the Jadad score [12] was also used to assess the quality of included studies. Disagreements were resolved through discussion with the other authors. Data are presented as means with standard deviations. Mean changes in body weight were used as common endpoints to assess the differences between HCA and placebo groups. Using the standard meta-analysis software [13], we calculated mean differences (MDs) and 95% confidence intervals (CIs). Studies included in the meta-analysis were weighted by SD (a proxy for study size). If a trial had 3 arms, only the HCA and placebo arms were included in the meta-analysis. The I2 statistic was used to assess for statistical heterogeneity amongst studies. A funnel plot was used to test for publication bias. Go to: 3. Results Our searches produced 5002 “hits” of which 23 potentially relevant articles were identified (Figure 1). Six trials were excluded because they involved the use of HCA in combination with other therapies [7, 14–18]. One trial was excluded because it was not blinded [19], and another because it was single blinded [20]. Two articles were excluded because they were duplicates. One of these articles [21] was the same trial published in another journal which had been earlier excluded, while the other article [22] was a report of two individual trials which were included in this systematic review. One trial was excluded because the investigators did not measure weight as an outcome [23]. Thus 12 randomised clinical trials (RCTs) including a total of 706 participants met our inclusion criteria, and were included in this systematic review [2, 4–6, 24–31]. Their key details are summarized in Tables ​Tables1,1, ​,2,2, and ​and3.3. Figure 1 Figure 1 Flow chart showing the process for the inclusion of randomised controlled trials. Table 1 Table 1 Characteristics of included studies.a Table 2 Table 2 Results table for studies with adequate data for meta-analysis.b Table 3 Table 3 Results of included studies without suitable data for meta-analysis.ρ All of the studies had one or more methodological weaknesses (Table 1). None of the included studies reported on how double blinding was carried out, and all studies were also unclear about how the allocation was concealed. The randomization procedure was clear in only a third of included studies [4, 6, 25, 29]. Three RCTs [4, 28, 31] did not provide actual values to enable statistical pooling (Table 3). One of these RCTs reported a nonsignificant difference in BMI or body weight between groups [4], another reported a significant difference (P < .001) in the HCA group compared with placebo [31]. The third RCT [28] reported a decrease in body weight and (BMI) from baseline for the HCA group, without providing results of intergroup differences. A forest plot (random effect model) for studies with data suitable for statistical pooling is shown in Figure 2. The meta-analysis reveals a statistically significant difference in body weight between the HCA and placebo groups. The average effect size was, however, small (MD: −0.88 kg; 95% CI: −1.75, −0.00), with a P value of  .05. This translates to about 1% in body weight loss in HCA group compared with placebo. The I2 statistic suggests that there was considerable heterogeneity amongst the trials, the duration of treatment, and the dosages of HCA used in the different trials varied widely. A funnel plot of mean difference plotted against trial sample size (Figure 3) indicated that most of the studies (which had small sample sizes) were distributed around the mean difference of all the trials. Figure 2 Figure 2 Forest plot of comparison showing the effect of hydroxycitrate on body weight. The vertical line represents no difference in weight loss between HCA and placebo. Figure 3 Figure 3 Funnel plot of the mean difference in body weight reduction trials of HCA, plotted against sample size. The vertical line depicts the weighted mean difference of all trials. Sensitivity analyses were performed to test the robustness of the overall analysis. The first included 7 trials [2, 5, 6, 24, 25, 29, 30] with parallel-group design, excluding two studies which were crossover [26, 27]. Meta-analysis of these trials revealed MD of −1.22 kg (95% CI: −2.29, −0.14). Heterogeneity was substantial. A second meta-analysis for studies with parallel group designs and dosage ranges of HCA between 1 and 1.5 g per day [5, 24, 25, 30] did not reveal a significant difference between HCA and placebo; heterogeneity was also substantial in this analysis. A third meta-analysis excluding three studies with outlying data for MD [6, 29, 30] did not reveal a significant difference in weight loss between HCA and placebo, but heterogeneity was considerable. A further meta-analysis of the two trials with good methodological quality [6, 25] revealed a nonsignificant difference in weight loss (MD: 0.88 kg; 95% CI: −0.33, 2.10) between HCA and placebo, with I2 value of 0, suggesting that heterogeneity might not be important. Finally, a meta-analysis of the change in BMI for four studies [6, 24, 29, 31] did not reveal any significant difference between HCA and placebo (MD: −0.34 kg; 95% CI: −0.88, 0.20), with I2 value of 0. One study [2] reported a significant decrease in fat mass in the HCA group compared with placebo (P < .05), while two studies [4, 24] reported a significant decrease in visceral, subcutaneous, and total fat areas in the HCA group compared with placebo (P < .001). In contrast two other studies [5, 25] found no significant difference in body fat loss between HCA and placebo. Adverse events reported in the RCTs included headache, skin rash, common cold, and gastrointestinal (GI) symptoms. In most of the studies, there were no major differences in adverse events between the HCA and placebo groups. However, in one trial, GI adverse events were twice as frequent in the HCA group compared with the placebo group [25]. In total, there were 88 drop outs. A further 45 participants were reported to have been excluded from the analysis in one trial [5] because they either took a mixture of HCA and placebo (28), or were males (17).