Obesity is a chronic disease characterized by an accumulation of excess adipose tissue and is associated with an increased risk of multiple morbidities and mortality. Unfortunately, once adipose tissue accumulates, a system of overlapping neuroendocrine responses prevents it from diminishing. When food intake is limited, counter-regulatory mechanisms cause an increase in appetite and a decrease in energy expenditure as protective measures against starvation and make volitional weight loss through dieting difficult to achieve.

Pharmacological intervention is considered necessary in overweight and obese patients with a body mass index greater than 27 kg/m2, particularly in the presence of other risk factors such as type 2 diabetes, or hypertension when conservative measures such as behavioral therapy, diet and exercise have not resulted in achieving the desired weight loss. Most cardiovascular risk factors improve even at modest weight reduction because loss of visceral fat leads to disproportionate improvement in risk of developing complications. The National Institute of Health (USA) guidelines recommend that if a chosen medication dies not lead to a 2-kg weight loss in the first month of treatment, the dose should be adjusted or the medication stopped.

Hydroxycitric acid (HCA), the active ingredient in the herbal compound Garcinia cambogia, competitively inhibits the extramitochondrial enzyme adenosine triphosphate-citrate (pro-3S)-lyase, which is needed for the conversion of carbohydrate into fat.. As a citrate cleavage enzyme that may play an essential role in de novo lipogenesis inhibition, G cambogia has been shown to lower body weight and reduce fat mass in experimental animals and humans. Since excess carbohydrates cannot be stored, especially if the consumption of carbohydrate is high, this results in a loss of appetite and suppression of hunger and hence reduced food intake and weight loss. One study in mice suggest that chronic administration of HCA promotes lipid oxidation and spares carbohydrate utilization in mice at rest and during running.

5-Hydroxytryptamine (serotonin, 5-HT) is a neurotransmitter implicated in the regulation of eating behavior and appetite control. To examine the effect of HCA on 5-HT in rat brain cortex, isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 min and then transferred to buffer solution containing [3H]-5-HT for different time intervals. A time-dependent uptake of [3H]-5-HT occurred in cortical slices reaching a maximum at 60 min. Furthermore, HCA can inhibit serotonin uptake, thus increase its availability, in a manner similar to other serotonin receptor re-uptake inhibitors. The authors concluded that HCA might prove beneficial in controlling appetite as well as treatment of depression, insomnia, migraine headaches and other serotonin-deficient conditions. Another study showed that garcinia efficiently improved glucose metabolism and displayed leptin-like activity. In a very recent study, HCA was shown to delay the intestinal absorption of enterally administered glucose at the level of small intestinal mucosa in rats. HCA strogly attenuated postprandial blood glucose levels after both intragastric and intraduodenal glucose administration, excluding a major effect of HCA on gastric emptying. HCA delayed the systemic appearance of exogenous glucose but did not affect the total fraction of glucose absorbed over the study period of 150 min.

A number of studies have evaluated the safety/toxicity of garcinia extract. The LD50 of HCA was found to be greater than 5,000 mg/kg body weight when administered once orally by gastric intubation to fasted male and female albino rats. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of garcinia. In placebo-controlled, double blind trials employing up to 2,800 mg/day HCA, no treatment-related adverse effects were reported.