International Scientific Conference on Complementary, Alternative & Integrative Medicine Research Boston Marriott Copley Place Boston, MA April 12-14, 2002 141 WEIGHT MANAGEMENT AND MECHANISM OF APPETITE SUPPRESSION BY A NOVEL, NATURAL EXTRACT OF (-)-HYDROXYCITRIC ACID D. Bagchi, H.G. Preuss, S.E. Ohia, C.V.S. Rao, S. Satyanarayana and M. Bagchi Georgetown University Medical Center, Washington DC; Creighton University, Omaha, NE; ASR Academy of Medical Science, Elluru, India, Andhra University, Visakhapatnam, India A growing body of evidence indicates that Garcinia cambogia-derived natural extract, (-)-hydroxycitric acid (HCA-SX, Super CitriMaxTM) is a potent appetite suppressant and an inhibitor of fat biosynthesis, however its exact mechanism of action is not clearly understood. In our previous study, HCA was demonstrated to increase the release/availability of radiolabeled 5-HT ( [3H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior. The aim of the present study was two-fold: (a) to determine the effect of HCA on 5-HT uptake in rat brain cortex in vitro and (b) to evaluate its role in weight management in human volunteers. Isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 min. and then transferred to buffer solutions containing [3H]-5-HT for different time intervals. In some experiments, tissues were exposed to HCA-SX (10 mM-1 mM), fluoxetine (100 uM) and clomipramine (10 uM). Uptake of [3H]-5-HT was expressed as d.p.m./mg wet weight. A time dependent uptake of [3H]-5-HT occurred in cortical slices reaching a maximum at 60 min. HCA-SX, fluoxetine and/or clomipramine inhibited the time-dependent uptake of [3H]-5-HT. At 90 min. HCA-SX (300 uM) caused a 20% decrease whereas fluoxetine plus clomipramine inhibited [3H]-5-HT uptake by 30%. We conclude that HCA can inhibit [3H]-5-HT uptake (and increase 5-HT availability) in isolated rat brain cortical slices in a manner similar to that of SSRI. Also, we examined the effects of oral administration of HCA-SX in 48 moderately obese human subjects (Age 21-50) in a randomized, double blind, placebo-controlled study. Subjects received either placebo or HCA-SX (2,800 mg per day) 30 min before meals for 8 weeks. Both groups received approximately a 2,000 kcal diet per day and participated in a supervised walking program. Approximately 5% and 6.8% loss in body weight and BMI were observed at the end of 8 weeks following supplementation of HCA-SX, respectively. HCA-SX supplementation reduced plasma leptin levels by 40% at the end of 8 weeks. HCA-SX supplementation reduced LDL, total cholesterol and triglycerides by 13%, 7.4% and 10%, respectively, and increased HDL by 9%. We conclude that HCA-SX can serve as a novel tool in weight management by modulating the obesity gene.

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