This material was prepared for the National Cancer Institute (NCI) for consideration by the Chemical Selection Working Group (CSWG) by Technical Resources International, Inc. under contract no. N02-07007.
Garcinia cambogia extract came to the attention of the NCI Division of Cancer Biology in follow-up to a previous nomination of ephedra to the National Toxicology Program (NTP). Used alone or with other ingredients, Garcinia cambogia extract is marketed as an ephedra-free diet aid.
Although studies supporting its use have been published, no information supporting the safety of this product was identified in the available literature. Some distributors of dietary supplements containing Garcinia cambogia extract do not recommend its use for persons with diabetes or dementia, or for pregnant or lactating women. However, studies concerning these safety issues were not found in the available literature.
NOMINATION OF GARCINIA CAMBOGIA EXTRACT TO THE NTP
Based on a review of available relevant literature and the recommendations of the Chemical Selection Working Group (CSWG) on December 17, 2003, NCI nominates this substance for testing by the National Toxicology Program (NTP) and forwards the following information:
$ The attached Summary of Data for Chemical Selection
$ Copies of references cited in the Summary of Data for Chemical Selection
$ CSWG recommendations to:
(1) Evaluate the extract and the lactone for genetic toxicology,
(2) Evaluate the extract for toxicity in a 90-day subchronic study,
(3) Expand the toxicological review of this extract for the following endpoint: developmental toxicology.
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PRIORITY
The CSWG suggested that the recommended testing be conducted with high priority.
COMMENTS
Garcinia cambogia is used for weight reduction, raising concerns about developmental endpoints, such as fetal size and ossification.
At least one member of the CSWG felt that a structure-activity analysis could be based on pure hydroxycitric acid.
Following the CSWG meeting in December 2003, important new information relevant to the assessment of Garcinia cambogia was published.
Using the preincubation method and doses of 492-5,000 :g/plate, Super CitriMax, a calcium/potassium-hydroxycitrate extract (HCA-SX) was not mutagenic in the presence or absence of metabolic activation in Salmonella typhimurium strains TA98 and TA102. HCA-SX-induced increases in the number of revertants in other strains (TA100 and TA1535 in the absence of metabolic activation and in strain TA1537 in the presence of metabolic activation). No dose relationship was observed. Tests in S. typhimurium using the plate incorporation method were negative (Soni et al., 2004).
Shara and coworkers (2004) evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry for periods of up to 90 days. Histopathological evaluation was performed at 90 days. The animals were administered 0, 0.2, 2.0, and 5.0% HCA-SX in feed and were killed at 30, 60, or 90 days. A time-, but not dose-dependent increase in hepatic lipid peroxidation was observed. Under identical conditions, HCA-SX caused no effect on hepatic DNA fragmentation. Selected organ weights individually and as a percent of body weight and brain weight at 90 days of treatment exhibited no significant difference between the groups. No difference was observed in hematology and clinical
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chemistry results. Histopathological evaluation of 26 tissue/organ sites showed no changes due to HCA-SX treatment with the exception of the gastric mucosa. The mucosa of the glandular stomach of one animal was atrophied and mineralizedl and foci of glandular dilatation were noted in a number of animals.
Rhabdomyolysis following the ingestion of weight-loss herbal medicine was reported in an otherwise healthy 54-year-old woman. Three hours after ingestion of a herbal medicine containing ma huang (12 mg ephedrine), guarana (190 mg), chitosan (250 mg), Gymnena sylvestre (100 mg), Garcinia cambogia (50% hydroxycitric acid) (50 mg), and chromium (200 mg), the patient suffered chest pain that continued for two hours and resolved gradually. Laboratory investigation showed the presence of rhabdomyolysis with peak serum creatine kinase (CK) of 1028 IU/L, which gradually decreased and normalized after the herbal medicine was discontinued. The role of hydroxycitric acid is uncertain (Mansi & Huang, 2004).
Citations to these three reports are included in the reference list and full articles are included in the attached references.
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SUMMARY OF DATA FOR CHEMICAL SELECTION
CHEMICAL IDENTIFICATION
CAS Registry Number: 90045-23-1
Chemical Abstracts Service Name: Garcinia cambogia extract (ChemID, 2003)
Synonyms and Trade Names: Brindal Berry; Gamboge; Gorikapuli; Malabar Tamarind; Mangosteen; Uppagi (Drug Digest, 2003; HerbalProvider.com, 2003; Kalyx.com, 2003)
Chemical and Physical Properties:
Description: Off-white to pale brown powder (Siris Impex, 2003)
Solubility: Soluble in ethanol and water (MDidea, 2001)
Reactivity: Stable at room temperature in closed containers; incompatible with oxidizing agents; decomposes in carbon monoxide and carbon dioxide among other products (MDidea, 2001)
Technical Products and Impurities: Garcinia cambogia is a small- or medium-sized tree, with drooping branches and ovoid fruits, native to Southeast Asia. Several compounds have been isolated from certain species of Garcinia, including xanthones, xanthones derivatives, and (-)-hydroxycitric acid [CAS No. 27750-10-3]. (-)-Hydroxycitric acid is present in the pericarp of the fruit of Garcinia cambogia up to 30% by weight. Commercially available Garcinia cambogia extracts are prepared from the fruit rind and contain 50% (-)-hydroxycitric acid (Jena et al., 2002; Mattes & Bormann, 2000; Siris Impex, 2003).
Sigma-Aldrich (2002) offers Garcinia cambogia extract as the (-)-calcium threo-hydroxycitrate tribasic hydrate salt.
Garcinia cambogia extract powder (100%) and Garcinia cambogia extract liquid (100%), standardized to 50% and 30% of (-)-hydroxycitric acid, respectively, can also be obtained from Premier Specialties (Premier Specialties, 2003).
Prepared for NCI to support chemical nomination by Technical Resources International, Inc. under Contract No. N02-CB-07007 (10/03; 08/04)
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Among the components of the Garcinia cambogia extract, (-)-hydroxycitric acid exists as a free acid and as hydroxycitric acid lactone forms. The free acid form is considered to be biologically active. However, the free acid is unstable and is converted to its more stable lactone form. For consumer products, the free acid is often stabilized by forming salts of (-)-hydroxycitric acid (Majeed et al., 1998).
HOOOHOHOHOOHO
(-)-Hydroxycitric acid
Prepared for NCI to support chemical nomination by Technical Resources International, Inc. under Contract No. N02-CB-07007 (10/03; 08/04)
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EXPOSURE INFORMATION
Production and Producers:
Manufacturing process: All procedures described in the available literature to obtain Garcinia cambogia extract were ultimately conducted to produce extracts with a high content of (-)-hydroxycitric acid.
(-)-Hydroxycitric acid extracts can be prepared from Garcinia cambogia rind by water extraction. The crude extract is loaded on an anion exchange column to adsorb (-)-hydroxycitric acid, and elution is carried out with sodium/potassium hydroxide. This fraction is then passed through a cation exchange column to yield the free acid. The final extract contains 54% (-)-hydroxycitric acid (Moffet et al., 1996).
Potassium or calcium salts of (-)-hydroxycitric acid extracts are generally known as Garcinia cambogia extracts and are used in consumer products. A method to produce the potassium salt of (-)-hydroxycitric acid extract involves the extraction of the fruit rind with methanol. This process is repeated several times. After the extracts are combined, they are treated with methanolic potassium hydroxide. The resulting precipitated potassium hydroxycitrate extract is filtered, dried under vacuum, and packed under a nitrogen blanket (Majeed et al., 1998).
Producers and importers: One US producer or distributor of Garcinia cambogia is listed by Chemical Sources International (2003).
According to a recent issue of a chemical buyer’s directory, Garcinia cambogia extract is manufactured and/or distributed by Alchem International Ltd.; Ampak Co., Inc.; Barrington Chemical Corp.; Buckton Scott Nutrition, Inc.; CPB International, Inc.; Fabrichem, Inc.; Har-Met International Inc.; Indo German Alkaloids; International Sourcing Inc.; MDS Chemical Co.; M.M.P., Inc.; Pharmachem Laboratories, Inc.; Pharmed Medicare (P) Ltd.; Pharmline, Inc.; Paul Schueller International Inc.; Spectrum Chemical Mfg. Corp.; and Unibar Corp. (Tilton, 2002).
Prepared for NCI to support chemical nomination by Technical Resources International, Inc. under Contract No. N02-CB-07007 (10/03; 08/04)
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Production/import/export level: Garcinia cambogia extract is not listed in the TSCA Inventory (ChemID, 2003).
Information on Garcinia cambogia, (-)-hydroxycitric acid extract, and Garcinia cambogia extract were combined to assess the import level of Garcinia cambogia extract. The Port Import/Export Reporting Service (PIERS) reported imports with a cargo weight of 497,540 pounds over the 41 month period from March 2000 to September 2003. Additional import entries of Garcinia-derived products were found in the PIERS database but were not included in this calculation (Dialog Information Services, 2003).
Use Pattern:
Dietary Supplement: Garcinia cambogia extract, used alone or in combination with other ingredients, is marketed as a dietary aid that suppresses the appetite, inhibits the synthesis of lipids, and burns fat via thermogenesis (HerbalProvider.com, 2003; InterHealth, 2003).
Over 50% of the US population is overweight and about 25% of the US population is obese. In a recent survey, 42% of US adults reported that they had tried one or more forms of alternative medicine in 1997 and it is estimated that 38% of women and 24% of men are trying to lose weight at any point in time (Allison et al., 2001; Williamson & Bowman, 2001).
Several limited clinical trials studying the effectiveness of Garcinia cambogia extract on weight loss have produced contradictory results. Supporting evidence for its efficacy is largely based on studies with small sample sizes, without placebo-treated groups or with inaccurate measures of body lipid changes. A 12-week, randomized, double-blind, placebo-controlled trial was conducted in 42 subjects that received 3,000 mg of Garcinia cambogia extract per day. Garcinia cambogia extract failed to produce significant weight loss and fat mass loss beyond that observed with placebo (Heymsfield et al., 1998).
Prepared for NCI to support chemical nomination by Technical Resources International, Inc. under Contract No. N02-CB-07007 (10/03; 08/04)

This entry was posted on Friday, June 23rd, 2006 @ 6:11 pm on the category Uncategorized .