In this pilot study, the efficacy of a novel, natural extract of a highly bioavailable, calcium-potassium salt of (–)-hydroxycitric acid (HCA-SX) alone and in combination with a niacin-bound chromium (NBC) and Gymnema sylvestra extract (GSE) was evaluated for weight loss in moderately obese subjects by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and serotonin levels, and enhanced excretion of urinary fat metabolites. Garcinia cambogia-derived (–)-hydroxycitric acid (HCA) has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has shown the ability to restore insulin function, metabolize fat, turn protein into muscle, and convert sugar into energy, which plays a role in appetite regulation and facilitates weight loss. Gymnema sylvestre is a traditional herb that helps to promote weight loss possibly through its ability to reduce cravings for sweets and control blood sugar levels. A randomized, double-blind, placebo-controlled human clinical study was conducted in thirty obese subjects (ages 21-50, BMI>26 kg/m 2) for eight weeks in Elluru, India. The subjects were randomly divided into three groups (10 subjects/group) and given HCA-SX 4,667 mg (60% HCA providing 2,800 mg HCA/day) (Group A), a combination of HCA-SX 4,667 mg, NBC 4 mg (providing 400 μg elemental Cr) and GSE 400 mg (providing 100 mg gymnemic acid) (Group B), or placebo (Group C) daily in 3 equally divided doses 30-60 min before each meal. This HCA-SX dose was extrapolated from previously conducted in vitro and in vivo studies. In addition, subjects received 2,000 kcal diet/day and underwent a 30 min/day supervised walking program, 5 days/week. At the end of 8 weeks, body weight and BMI decreased by 6.3%, respectively, in Group A. Food intake was reduced by 4%. Total cholesterol, LDL and triglycerides levels were reduced by 6.3%, 12.3% and 8.6%, respectively, while HDL and serotonin levels increased by 10.7% and 40%, respectively. Serum leptin levels were decreased by 36.6%, and the enhanced excretion of urinary fat metabolites, including malondialdehyde (MDA), acetaldehyde (ACT), formaldehyde (FA) and acetone (ACON), increased by 125-258%. Under these same conditions, Group B reduced body weight and BMI by 7.8% and 7.9%, respectively. Food intake was reduced by 14.1%. Total cholesterol, LDL and triglyceride levels were reduced by 9.1%, 17.9% and 18.1%, respectively, while HDL and serotonin levels increased by 20.7% and 50%, respectively. Serum leptin levels decreased by 40.5% and enhanced excretion of urinary fat metabolites increased by 146-281%. Group C reduced body weight and BMI by only 1.6% and 1.7%, respectively, food intake was increased by 2.8%, and LDL, triglycerides and total cholesterol decreased by 0.8%, 0.2% and 0.8%, respectively. HDL were reduced by 4.1% while serum leptin levels were increased by 0.3%, and excretion of urinary fat metabolites did not change in MDA, ACT and FA, and marginally increased in the case of ACON. No adverse effects were observed. Results demonstrate that HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as safe weight management supplements.