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GARCINIA CAMBOGIA

Various species of Garcinia occur in South Asia and in tropical Africa. Fruits, seeds, leaves, and wood of individual species or extracts thereof are used for medicinal purposes or technical uses (HOPPE, 1975). The fruits of the species Garcinia cambogia which is native to South India are considered to be edible, they are, however, too sour to be eaten raw. Instead dried fruit rinds are used in curry mixtures and together with salt for the curing of fish. Decoctions of the rinds are given as medication against rheumatism and bowel complaints in the local folk medicine. The fruits contain as principal fruit acid (-)hydroxycitric acid (LEWIS, 1965). (-)Hydroxycitric acid is an effective inhibitor of the fatty acid synthesis (LOWENSTEIN, 1971). The inhibiting mechanism consists in an interruption of the supply of acetyl Coenzyme A, the building block used for the synthesis of fatty acids. Acetyl Coenzyme A is formed in the mitochondria but cannot pass the mitochondrial membrane unless it has reacted with oxaloacetate to form citrate. Having migrated to the cytosol the citrate is cleaved by the enzyme citrate lyase into acetyl Coenzyme A and oxaloacetate again. (The oxaloacetate returns to the mitochondria in form of certain intermediates). If hydroxycitrate is present the back cleavage is inhibited. Hydroxycitrate - because of its similarity to citrate - "docks" to the citrate lyase but cannot be cleaved like citrate and remaining at the active side of the enzyme blocks its activity. No more citrate is cleaved and therefore no more acetyl Coenzyme A is formed. The concentration of the citrate increases and its migration from the mitochondria ceases. It is assumed that the backlog of metabolites inhances the glycogen synthesis which in turn leads to diminished food intake (SULLIVAN 1976). Hydroxycitrate acts thus at the metabolic level and not at the central nervous system as classical appetite depressants do. It was found that (-)hydroxycitrate does indeed lower the feed intake of lean (SULLIVAN, 1964) and obese (GREENWOOD, 1981) rats, of mice (SULLIVAN, 1977) and chickens (CHEE, 1977). At the same time a significant inhibition of the cholesterol synthesis was observed when rats consumed hydroxycitrate containing feed (SULLIVAN, 1972). Hydroxycitrate as feed additive reduced the feed intake of rats in the first seven weeks of the experiment but not in the following seven weeks (SULLIVAN, 1977). Despite of this normalization of the feed intake there was no overeating or compensation for the earlier reduction in food intake. (-)Hydroxycitric acid is a gamma-hydroxy-carbonic acid. It has therefore a tendency to form an internal ester, a so-called lacton under release of a molecule water. In acidic environment a reversible equilibrium is formed in which depending on the amount of water available about 30 to 50% free acid are present. By removal of the free acid (by metabolisation or neutralisation with alcali) the equilibrium is shifted completely to the side of the free acid.

References

CHEE, H., ROMSOS, D.R., LEVEILLE, G.A., 1977: J. Nutr., 107,112 GREENWOOD, M.R.C., et al., 1981: Effect of (-)hydroxycitrate on development of obesity in the Zucker obese rat. Am. J. Physiol. 1981; 240: E72-E78

HOPPE, HEINZ A., 1975: Drogenkunde, Band 1, de Gruyter, S. 521 LEWIS, Y.S., NEELAKANTAN S., 1965: (-)Hydroxycitric acid - the principal acid in the fruits of Garcinia cambogia. Phytochemsitry 4:610-525 LOWENSTEIN, J.M., 1971: Effect of (-)Hydroxycitrate on Fatty Acid Synthesis by Rat Liver in Vivo. J. Biol. Chem., 246, 629

SULLIVAN, A.C., HAMILTON J.G., MILLER; O.N., WHEATLEY W.R., 1972: Inhibition of Lipogenesis in Rat Liver by (-)Hydroxycitrate. Arch. Biochem. Biophys. 150, 183-190.

SULLIVAN, A.C., TRISCARI, J., HAMILTON J.G., MILLER; O.N., 1974: Lipids, 9, 129

SULLIVAN, A.C., TRISCARI, J., 1976: "Possible Interrelationship Between Metabolite Flux and Appetite" in D. Novin, W. Wywicka, G. Bray Eds., Hunger: Basic Mechanisms and Clinical Implications, Raven, New York, p. 115

SULLIVAN, A.C., TRISCARI, J., 1977: Am. J. Clin. Nutr., 30, 767


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