Medication Guide App

Garcinia (hydroxycitric acid)

Scientific Name(s): Garcinia cambogia (Gaertn.) Desr. Family: Clusiaceae (Guttiferae)

Common Name(s): Malabar tamarind , hydroxycitric acid ( HCA )

Uses

The medical literature primarily documents weight loss and lipid-lowering activity for the plant. However, trials supporting its use are limited.

Dosing

The dosages of G. cambogia extract in clinical trials ranged from 1,500 to 4,667 mg/day (25 to 78 mg/kg/day). The equivalent hydroxycitric acid (HCA) dose in the trials ranged from 900 to 2,800 mg/day (15 to 47 mg/kg/day). G. cambogia is available in capsule or tablet form with a maximum dose of 1,500 mg/day.

Contraindications

Avoid use if there is a known allergy or hypersensitivity to any components of G. cambogia .

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

The herb has documented drug interactions.

Adverse Reactions

At least 15 clinical studies involving approximately 900 patients document very mild adverse reactions. Most adverse reactions included headache, dizziness, dry mouth, and GI complaints such as nausea and diarrhea.

Toxicology

Toxicology studies resulted in no toxicity or deaths in animals at dosages of HCA 5,000 mg/kg, equivalent to 350 g or 233 times the maximum dosage of 1.5 g/day of HCA. In patients taking certain combination weight-loss supplements containing G. cambogia , severe or even fatal hepatotoxicity may occur.

Botany

The genus Garcinia is mainly distributed in tropical regions and includes approximately 200 species. G. cambogia belongs to the family Guttiferae and is found in India, Malaysia, and Africa. G. cambogia is commonly found in evergreen or semievergreen forests of southwest India, where 36 other species have been documented. 1 , 2 The plant species has variability in its branching pattern, fruit color, shape, and size. 1 The tree is small-to-medium in size with drooping branches. The leaves are dark green and glossy, oval-shaped with a narrow end, 5 to 12 cm in length, and 2 to 7 cm around. The tree is tolerant to drought and flowers during the hot season. The yellow, orange, or red fruit ripens during the rainy season and contains HCA. It is ovoid in shape, 5 centimeters around, has 6 to 8 seeds, and is listed in the US Department of Agriculture inventory of perennial edible fruits. 2

History

Dried fruit rinds have been used extensively for centuries throughout Southeast Asia for culinary purposes as a condiment and flavoring agent in place of tamarind or lemon. Additional culinary uses include the flavoring of curries, meat, and seafood. The fruit extract has been used as a flavoring agent for beverages and gourmet spices, as well as a carminative, thereby helping to prevent the formation of gas in the GI tract after a meal. HCA and other organic acids from the dried rind combined with salt help lower pH and provide a bacteriostatic effect used in curing fish. The herb is considered beneficial for overall health in the traditional Ayurvedic medical system. Rheumatism and bowel complaints are treated with a decoction of the fruit rind. A rinse is used from the herbal extract in veterinary medicine for some diseases of the mouth in cattle. HCA has also become popular as an ingredient for weight loss. 2 , 3 , 4

Chemistry

HCA is the primary medicinal component contained in the fruit rinds of G. cambogia . 5 HCA is present as up to 30% by weight in the pericarp of G. cambogia fruit. 6 Xanthones, xanthone derivatives, and polyisoprenylated benzophenones have been isolated. 6 , 7 Some salts used in commercial products are water soluble and bioavailable, and are a good source of calcium (495 mg) and potassium (720 mg). 8 Studies also document interest in production of HCA by using microorganisms. 9 , 10

Uses and Pharmacology

The medical literature primarily documents research on the weight loss and lipid-lowering activity of the plant.

Dyslipidemia
In vitro and animal data

In 2 experiments using the human hepatoma cell line HepG2, overnight exposure to G. cambogia extract caused an upregulation of low-density lipoprotein (LDL) receptor activity and an upregulation of the level of HMG-CoA reductase resulting in decreased cholesterol synthesis. 11 Flavonoids from the plant reduced lipid levels in normal and hypercholesterolemic rats. 7 Reductions were also documented in triglycerides, phospholipids, and free fatty acids. The mechanism of action for the flavonoids may involve: (1) reducing the rate of lipogenesis by reducing the activities of lipogenic enzymes, glucose-6-phosphate dehydrogenase, and isocitrate dehydrogenase; and (2) increasing the rate of degradation of cholesterol leading to higher levels of hepatic and fecal bile acids, as well as neutral sterols in rats treated with the herb. While dexamethasone typically elevates lipid profiles, G. cambogia extract maintained normal lipid levels in rats administered dexamethasone. 12

Clinical data

In a 4-week randomized, double-blind, placebo-controlled trial, 150 obese patients were treated with a dietary supplement ( G. cambogia extract 55 mg, chitosan 240 mg, and chrome 19 mg) together with a weight reduction regimen. Treatment groups administered the dietary supplement showed statistically significant dose-related reductions in weight, total and LDL cholesterol, and triglycerides, and improvement in high density lipoprotein cholesterol. 13

Obesity

The suggested mechanism of action involves HCA-inhibiting lipogenesis, increasing lipid oxidation, and reducing food intake. 3 , 14

Animal data

A study in obese rats found high doses of HCA-containing G. cambogia (154 mmol HCA/kg diet) effective in suppressing epididymal adipose tissue. This same study also found testicular atrophy and toxicity at dosages of 778 mg HCA/kg body weight/day (102 mmol HCA/kg diet) and higher. 4 Another study in rats administered a high-fat diet and a mixture of G. cambogia extract, soypeptide, and L-carnitine, led to a reduction in body weight and accumulation of visceral fat mass. 15 The mixture also improved blood and hepatic lipid concentrations or the induced dyslipidemia in the rats. Other combination products with G. cambogia are also effective in reducing weight gain and improving dyslipidemia, hyperinsulinemia, hyperleptinemia, and fatty liver in mice. 16 The antiobesity effect involves modulation of several genes associated with visceral adipogenesis. One study in adult, nonobese cats found no effect on fat-free mass or energy expenditure. 17

Clinical data

In an 8-week randomized clinical trial, 40 patients were given either placebo or G. cambogia extract (500 mg/capsule) by mouth before each meal. Patients administered the extract exhibited weight loss and improvement in cholesterol and triglycerides when compared with the placebo group. 2

In a 12-week, randomized, double-blind, placebo-controlled study, 40 obese patients were treated with a combination supplement containing G. cambogia 50 mg as well as a 1,200 calorie diet per day. Two tablets of the supplement were taken by mouth 3 times a day after meals. The treatment group attained a 3.5 kg weight loss versus 1.2 kg on placebo, and a more than 85% reduction in fat loss in body composition measurements. The majority of the active group participants did not follow the diet regimen. 18

In a 12-week, double-blind, placebo-controlled, parallel group trial, 89 mildly overweight women were treated with a 1,200 kcal diet along with 2 caplets of G. cambogia 400 mg or matched placebo 3 times a day before each meal. At the end of the trial, both groups lost weight, but the treatment group achieved greater reduction in body weight. G. cambogia had no effect on appetitive variables. 14

Numerous studies document the safety profile of the calcium-potassium double salt of 60% HCA preparation (HCA-SX), as well as its bioavailability and efficacy in helping patients attain a healthy body weight. 3 , 19 , 20 , 21 , 22 , 23

An 8-week, randomized, placebo-controlled, double-blind study examined the efficacy of HCA-SX in 54 overweight patients. The treatment group was administered a combination supplement containing G. cambogia 500 mg 3 times a day while the control group received the placebo. All patients were asked to maintain a low-fat diet and drink 64 oz of water per day. The treatment group lost an average weight of 11.14 lb/person as compared with the control group, which lost an average of 4.2 lb/person. 19

Another 8-week, randomized, placebo-controlled, double-blind study examined the efficacy of HCA in 60 obese patients. The dosage regimen for HCA was 400 mg 3 times a day before each meal. All patients were on a low-fat diet and also instructed to exercise 3 times a week. Results indicated weight loss for the experimental group compared with the placebo group and that 87% of the weight loss in the HCA group was because of fat loss. Appetite scores were also reduced in the HCA-treated group. 19

Visceral, subcutaneous, and total fat accumulation were reduced in 39 patients over 16 weeks in a double-blind, randomized, placebo-controlled trial. The dosage regimen included HCA 1,000 mg/day versus placebo. At the end of the treatment, both groups were administered placebo for 4 weeks and no rebound effect was documented. 24

Another clinical study documented that treatment with HCA failed to produce weight change and fat mass change in patients. 25 However, the design of the clinical trial, the lack of bioavailability, and dosage of HCA used have been criticized. 2

Other pharmacologic activity
Antioxidant

Some studies found that supplementation with G. cambogia can reduce oxidative damage. 26

Cancer

The fruit contains xanthones, which inhibit pre-neoplastic lesions in mammary and colon cancer. The xanthones may also induce apoptosis in mouth, leukemia, breast, gastric, and lung cancer cell lines in vitro. 27

Diabetes

Glucose metabolism may be improved by lowering serum insulin levels in mice treated with G. cambogia . Leptin is a hormone associated with appetite control. G. cambogia may have leptin-like activity as mice treated with G. cambogia had decreased serum leptin levels and a reduced leptin/white adipose tissue ratio. 28 HCA treatment delayed and reduced intestinal glucose absorption in rats; the treatment causes delayed intestinal absorption of glucose rather than delayed gastric emptying. 29

Exercise endurance

HCA promoted lipid oxidation and reduced carbohydrate use in mice at rest and during running. 30 The utilization of respiratory gases was reduced for mice treated with HCA at rest and during exercise. Some studies on herbal coffee supplements with HCA showed an increase in resting energy expenditure to enhance metabolic rates and promote weight and fat loss. 31 , 32

GI disorders

Antiulcer activity was observed against induced gastric mucosal injury in rats with pretreatment of G. cambogia extract that decreased volume and acidity of gastric juice. 33 A similar study in rats found activity against indomethacin-induced gastric ulcers. 34 The anti-inflammatory activity of G. cambogia protected against induced colitis in rats. 35

Red blood cell count

A G. cambogia extract caused an increase in the red blood cell (RBC) count in rat tissue. The activity may be (1) associated with the iron in G. cambogia , as iron is an erythropoietic agent; (2) antioxidant activity and may decrease the rate of oxidant-induced hemolysis, which increases the life span of the RBC; or (3) the content of bioflavonoids in the plant, which may increase the level of peripheral testosterone, which can stimulate erythropoiesis in humans. 36

Dosage

The dosages of G. cambogia extract in clinical trials ranged from 1,500 to 4,667 mg/day (25 to 78 mg/kg/day). The equivalent HCA dose in the trials ranged from 900 to 2,800 mg/day (15 to 47 mg/kg/day). 2 , 14 , 18 , 19 , 23 , 24 , 25 G. cambogia is available in capsule or tablet form with a maximum dose of 1,500 mg/day.

Pregnancy/Lactation

Due to lack of clinical and scientific information, use should be avoided during pregnancy and lactation. One animal study in rats documented decreased maternal body weight gain during gestation. 37

Interactions

Diabetic/insulin medications

In patients taking medications for diabetes by mouth or insulin, G. cambogia may lower blood sugar levels. 28 , 29

Iron

G. cambogia contains iron and thus may have additive adverse reactions for patients taking medications for anemia. 36

Potassium and calcium supplements

Some commercial G. cambogia products contain adequate amounts of potassium and calcium. 8 Caution is advised for patients taking medications for heart disease, high blood pressure, or arrhythmia while supplementing with any product containing this herb.

Serotonin

A mouse study using a commercial polyherbal product containing G. cambogia found a potential serotonergic effect on food intake. Caution is advised for patients being treated for pain or taking medications for any psychiatric condition. 38

Singulair (or leukotriene receptor antagonists)

One case report documented fatal liver failure in a patient taking Singulair and 2 dietary supplements, one of which included G. cambogia and citrus derivatives. 39

Statins

A case report of rhabdomyolysisis is documented in a patient taking a combination herbal medicine containing G. cambogia . 40

Warfarin

In one case report, the international normalized ratio of a patient returned to normal after he stopped taking a combination herbal product containing G. cambogia . 41

Adverse Reactions

A total of 15 clinical studies involving approximately 900 patients documented very mild adverse reactions. Most adverse reactions included headache, dizziness, dry mouth, and GI complaints such as nausea and diarrhea. 2 , 42

Toxicology

Toxicology studies resulted in no toxicity or deaths in animals at HCA dosages of 5,000 mg/kg, equivalent to 350 g or 233 times the maximum dose of 1.5 g/day of HCA. 5 In patients taking certain combination weight-loss supplements containing G. cambogia , severe or even fatal hepatotoxicity may occur. 43 , 44 Some animal studies document testicular toxicity, 4 , 45 while other studies do not. 46 , 47

No unusual electrocardiographic effects (QTc interval or other electrocardiograph variables) were seen over 5 hours in patients taking half the recommended dose of a multicomponent weight loss supplement containing G. cambogia . 48 Patients receiving G. cambogia extract (1,667.3 mg/kg equivalent to 1,000 mg HCA/day) for 12 weeks exhibited no reproductive toxicity on serum testosterone, estrone, and estradiol levels. 49

Bibliography

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15. Kim YJ, Kim KY, Kim MS, Lee JH, Lee KP, Park T. A mixture of the aqueous extract of Garcinia cambogia , soy peptide and L: -carnitine reduces the accumulation of visceral fat mass in rats rendered obese by a high fat diet. Genes Nutr . 2008;2(4):353-358.
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18. Thom E. A randomized, double-blind, placebo-controlled trial of a new weight-reducing agent of natural origin. J Int Med Res . 2000;28(5):229-233.
19. Lau FC, Bagchi M, Sen C, Roy S, Bagchi D. Nutrigenomic analysis of diet-gene interactions on functional supplements for weight management. Curr Genomics . 2008;9(4):239-251.
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40. Mansi IA, Huang J. Rhabdomyolysis in response to weight-loss herbal medicine. [Published correction appears in: Am J Med Sci . 2004;328(2):129.] Am J Med Sci . 2004;327(6):356-357.
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45. Anno T, Oono H, Tamura K. Improvement of testicular toxicity in F/344DuCrj male rats fed Ca-type Garcinia cambogia extract by zinc supplemented diets. Nippon Shokuhin Kagaku Gakkaishi . 2005;12(3):121-127.
46. Shara M, Ohia SE, Yasmin T, et al. Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and histopathological data over a period of 90 days. Mol Cell Biochem . 2003;254(1-2):339-346.
47. Burdock G, Soni M, Bagchi M, Bagchi D. Garcinia cambogia toxicity is misleading. [Published correction appears in: Food Chem Toxicol . 2007;45(3):515.] Food Chem Toxicol . 2005;43(11):1683-1684; author reply 1685-1686.
48. Min B, McBride BF, Kardas MJ, et al. Electrocardiographic effects of an ephedra-free, multicomponent weight-loss supplement in healthy volunteers. Pharmacotherapy . 2005;25(5):654-659.
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