REVIEWS Chemistry and Biochemistry of (-)-Hydroxycitric Acid from Garcinia B. S. JENA, G. K. JAYAPRAKASHA, R. P. SINGH, AND K. K. SAKARIAH* Human Resource Development, Central Food Technological Research Institute, Mysore 570 013, India (-)-Hydroxycitric acid [(-)-HCA] is the principal acid of fruit rinds of Garcinia cambogia, Garcinia indica, and Garcinia atroviridis. (-)-HCA was shown to be a potent inhibitor of ATP citrate lyase (EC 4.1.3.8), which catalyzes the extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA: citrate + ATP + CoA f acetyl-CoA + ADP + P i + oxaloacetate. The inhibition of this reaction limits the availability of acetyl-CoA units required for fatty acid synthesis and lipogenesis during a lipogenic diet, that is, a diet high in carbohydrates. Extensive animal studies indicated that (-)-HCA suppresses the fatty acid synthesis, lipogenesis, food intake, and induced weight loss. In vitro studies revealed the inhibitions of fatty acid synthesis and lipogenesis from various precursors. However, a few clinical studies have shown controversial findings. This review explores the literature on a number of topics: the source of (-)-HCA; the discovery of (-)-HCA; the isolation, stereochemistry, properties, methods of estimation, and derivatives of (-)-HCA; and its biochemistry, which includes inhibition of the citrate cleavage enzyme, effects on fatty acid synthesis and lipogenesis, effects on ketogenesis, other biological effects, possible modes of action on the reduction of food intake, promotion of glycogenesis, gluconeogenesis, and lipid oxidation, (-)-HCA as weight-controlling agent, and some possible concerns about (-)-HCA, which provides a coherent presentation of scattered literature on (-)-HCA and its plausible mechanism of action and is provocative of further research. Keywords: Garcinia cambogia; Garcinia indica; Garcinia atroviridis;(-)-hydroxycitric acid; ATP:citrate lyase; fatty acid synthesis; lipogenesis; appetite; antiobesity INTRODUCTION Garcinia (family: Guttiferae) is a large genus of polygamous trees or shrubs, distributed in tropical Asia, Africa, and Polynesia. It consists of 180 species, of which ∼30 species are found in India (1). For the past several years, small and complex molecules have been isolated from the various species of Garcinia, which include xanthones and xanthone derivatives (2-4). However, the isolation of (-)-hydroxycitric acid [(-)- HCA] from a few species of Garcinia and its biological properties have attracted the attention of biochemists and health practitioners. The physiological and biochemical effects of (-)-HCA have been studied extensively for its unique regulatory effect on fatty acid synthesis, lipogenesis, appetite, and weight loss. The derivatives of (-)-HCA have been incorporated into a wide range of pharmaceutical preparations in combination with other ingredients for the claimed purpose of enhancing weight loss, cardioprotection, correcting conditions of lipid abnormalities, and endurance in exercise (5-22). In the present review attempts have been made to pool, analyze, and summarize the available information on the chemical, physiological, and biochemical aspects of (-)-HCA. SOURCES OF (-)-HCA (-)-HCA is found in the fruit rinds of certain species of Garcinia, which include G. cambogia, G. indica, and G. atroViridis (23-25). These species thrive prolifically on the Indian subcontinent and in western Sri Lanka (1, 26). G. cambogia is a small or medium-sized tree with a rounded crown and horizontal or drooping branches; its leaves are dark green and shiny, elliptic obovate, 2-5 in. long and 1-3 in. broad; its fruits are ovoid, 2 in. in diameter, yellow or red when ripe with six to eight grooves, and the fruits have six to eight seeds surrounded by a succulent aril. The tree is found commonly in the evergreen forests of Western Ghats, from Konkan southward to Travancore, and in the Shola forests of Nilgiris up to an altitude of 6000 ft. It flowers during the hot season, and fruits ripen during the rainy season. The seeds of G. cambogia contain 31% edible fat. 10 J. Agric. Food Chem. 2002, 50, 10-22 10.1021/jf010753k CCC: $22.00 © 2002 American Chemical Society Published on Web 11/29/2001