Hydroxycitrate, Hydroxycitric Acid (HCA)
Hydroxycitrate [(-)hydroxycitric acid, HCA], is a popular component of over-the-counter weight-loss formulations. Hydroxycitrate is found in high concentrations in Garcinia cambogia (a plant from India), as well as two other plants of the genus Garcinia, and these plants are used for commercial preparations of the compound. Other names applied to these plants include "brindall berry" and "Malabar Tamarind".
Hydroxycitric acid, in addition to being called (-)- hydroxycitric acid, is also known as hydroxycitrate, (-) — threohydroxycitric acid and 4S-hydroxycitric acid. It is abbreviated as (-)-HCA and sometimes as HCA. It is a different substance than either citric acid or isocitric acid, which are key intermediates in the tricarboxylic acid or Krebs cycle. The terms for the acid and anion forms, hydroxycitric acid and hydroxycitrate, respectively, are used interchangeably. However, the anion form is the form that occurs under biological conditions.
Garcinia cambogia has been promoted for weight loss due to various possible effects on the body. First, it is believed to interfere with the body’s ability to store fat, possibly causing more fat from foods to be eliminated from the body. In addition, Garcinia cambogia may cause the body to use existing fat stores for energy during prolonged exercise. Ordinarily, carbohydrates are used first during exercise. In animal studies, hydroxycitric acid (HCA), a major component of Garcinia cambogia, also seemed to reduce appetite by raising the amount of serotonin in the body. Serotonin is a neurotransmitter that is thought to affect appetite control. In clinical studies of humans, however, individuals who took Garcinia cambogia while following a weight-reduction diet had no more weight loss than members of a control group who only followed the same diet. Other human studies have mixed results on appetite reduction; one showed little or no effect, while another reported a 15% to 30% decrease in food intake. More studies are needed to prove or disprove the effectiveness of Garcinia cambogia in weight control.
The reputed effects of hydroxycitrate are based on its action as a potent inhibitor of the enzyme ATP citrate lyase (also known as citrate cleavage enzyme), which is required for the synthesis of fatty acids. The enzyme takes citrate, which has been exported from the mitochondria to the cytoplasm, and forms acetyl CoA and oxaloacetate from it. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides and also in the synthesis of acetylcholine in the central nervous system. Oxaloacetate may enter the gluconeogenic pathway, which can lead to the production of glucose and glycogen. It is believed that the putative antiobesity effect of hydroxycitric acid is due to suppression of fatty acid and fat synthesis. In addition, hydroxycitric acid is thought to suppress food intake via an anorectic effect. This is believed to be accounted for by hydroxycitric acid's stimulation of liver gluconeogenesis.