Scientific Name(s): Garcinia cambogia (Gaertn.) Desr.
Common Name(s): Malabar tamarind
G. cambogia is most commonly found in the evergreen or semi-evergreen forests of southwest India, where 36 other species of Garcinia have been documented, as well as in Malaysia and Africa.1, 2 G. cambogia has variability in its branching pattern, fruit color, shape, and size,1 and the tree is small to medium with drooping branches. The leaves are dark green, glossy, and oval-shaped with a narrow end; they are 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, which contains HCA, ripens during the rainy season. It is ovoid in shape, measures 5 cm around, and has 6 to 8 seeds. The fruit of G. cambogia is listed in the US Department of Agriculture’s inventory of perennial edible fruits of the tropics.2 HCA is a common ingredient in weight loss products.
Throughout Southeast Asia, dried fruit rinds have been used extensively for centuries as condiments and flavoring agents 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, helping to prevent the formation of gas in the GI tract after a meal. When combined with salt, HCA and other organic acids from the dried rind help to lower pH and provide a bacteriostatic effect used in curing fish. In the traditional Ayurvedic medical system, the herb is considered beneficial for overall health. Rheumatism and bowel complaints have been treated with a decoction of the fruit rind. HCA has become popular as an ingredient in weight-loss products.2, 3, 4 A rinse from the herbal extract is also used in veterinary medicine for some diseases of the mouth in cattle.
HCA is the primary medicinal component contained in the fruit rinds of G. cambogia.5 HCA is present up to 30% by weight in the pericarp of G. cambogia fruit.6 At a dosage of 4,500 mg/day, the calcium-potassium salt of HCA (HCA-SX), which are water soluble and bioavailable, provides 495 mg of calcium and 720 mg of potassium.7 Studies also document potential production of HCA by using microorganisms.8, 9 Xanthones, xanthone derivatives, and polyisoprenylated benzophenones have been isolated.6, 10 Garcinol, otherwise known as camboginol, is another component of the fruit rinds of G. cambogia.11
Uses and Pharmacology
The medical literature primarily documents research on the weight loss and lipid-lowering activity of the plant.
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 receptor activity and an upregulation of the level of HMG-CoA reductase, resulting in decreased cholesterol synthesis.12 Flavonoids from the plant reduced lipid levels in normal and hypercholesterolemic rats.10 Reductions were also documented in triglycerides, phospholipids, and free fatty acids. The mechanism of action for the flavonoids may involve decreasing the rate of lipogenesis via a reduction in the activities of lipogenic enzymes, glucose-6-phosphate dehydrogenase, and isocitrate dehydrogenase and 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. Whereas dexamethasone typically elevates lipid profiles, G. cambogia extract maintained normal lipid levels in rats administered dexamethasone.13
A double-blind clinical trial evaluated the effect of G. cambogia extract on the lipid profile of overweight women.14 Women with a body mass index (BMI) of 25 kg/m2 or greater were randomized to receive G. cambogia extract (n = 30) or placebo (n = 13) for 60 days. The dosage of G. cambogia extract (50% HCA) was 800 mg 3 times daily, 30 minutes before meals. Participants received an individualized diet with an average calorie reduction to 1,523 ± 185 kcal/day. There was a significant reduction in triglycerides in women receiving the G. cambogia extract (−22.9 ± 5.34 mg/dL) compared with placebo (+4.53 ± 33.4 mg/dL; P = 0.04). There was no difference in other components of the lipid profile, body weight, BMI, or calorimetric indices.
A 10-week, double-blind, parallel-group trial compared Glycine max (soy) leaf extract with G. cambogia extract for the promotion of weight loss and lowering of plasma cholesterol.15 The study randomized 86 overweight adults to receive 2 g/day of Glycine max extract, 2 g/day of G. cambogia extract (60% HCA), or placebo. Primary outcome measures of the study were percent body fat and total cholesterol. Secondary outcome measures included components of the lipid profile, adipocytokines, and antioxidants. After 10 weeks, the Glycine max leaf extract group had 6% lower total cholesterol than that of the placebo group, the clinical importance of which is unclear because total cholesterol increased during the study in all treatment groups. Aside from an unspecified increase in high-density lipoprotein cholesterol for the Glycine max leaf extract, the supplements had no effect on other components of the lipid profile, adipocytokines, or antioxidants.
G. cambogia's suggested mechanism of action in obesity involves HCA-inhibiting lipogenesis, increase in lipid oxidation, and reduction of food intake.3, 16 HCA competitively inhibits adenosine triphosphate-citrate (pro-3S)-lyase, an extra-mitochondrial enzyme that plays a role in fatty acid biosynthesis.17
A study in obese rats found that high doses of HCA-containing G. cambogia (HCA 154 mmol/kg diet) were effective in suppressing epididymal adipose tissue. This same study also found testicular atrophy and toxicity at dosages of HCA 778 mg/kg body weight/day (HCA 102 mmol/kg diet) and higher.4 In another study in rats, administration of a high-fat diet and a mixture of G. cambogia extract, soy peptide, and L-carnitine led to a reduction in body weight and accumulation of visceral fat mass.18 The mixture also improved blood and hepatic lipid concentrations and improved dyslipidemia in rats with induced obesity. Other combination products with G. cambogia were also effective in reducing weight gain and improving dyslipidemia, hyperinsulinemia, hyperleptinemia, and fatty liver in mice. The antiobesity effect involved modulation of several genes associated with visceral adipogenesis.19 However, one study in adult nonobese cats found that G. cambogia had no effect on fat-free mass or energy expenditure.20
In a 12-week, randomized, double-blind, placebo-controlled study, 40 obese patients were treated with a combination supplement containing G. cambogia accompanied by a 1,200 kcal/day diet.21 Subjects on active treatment received Phaseolus vulgaris extract 400 mg, inulin 400 mg, and G. cambogia 100 mg 3 times daily after meals. Statistical analysis was applied to changes in body weight and fat compared with baseline but not to changes in body weight between groups. The treatment group attained a weight loss of 3.5 kg versus 1.2 kg on placebo. Body composition measurements assessed with near-infrared technique and bioimpedance indicated that more than 85% of weight loss in the active treatment group was due to a loss of body fat. Changes in body fat were not reported for the placebo group. The majority of the active group participants did not follow the diet regimen.21
In a 12-week, double-blind, placebo-controlled, parallel group trial, 89 mildly overweight women were given a 1,200 kcal diet along with 2 caplets of G. cambogia (HCA 50%) 400 mg or matched placebo 3 times a day before each meal. At the end of the trial, both groups lost weight, but the group treated with G. cambogia achieved a greater reduction in body weight (3.7 ± 3.1 kg vs 2.4 ± 2.9 kg; P = 0.026), although the weight loss was minimal. G. cambogia had no effect on appetitive variables or fat mass.16
A double-blind trial randomized 135 overweight adults with a mean BMI of 32 kg/m2 to 12 weeks of treatment with placebo or G. cambogia (50% HCA) 1,000 mg 3 times per day before meals.17 Subjects were given a high-fiber, 5,040 kJ/day diet plan. The primary outcomes of the study were effects on body weight and fat mass. The study was estimated to have 80% power at the 2-tailed alpha level of 0.05 to detect a significant difference in body weight. Forty-two patients in each group completed the study. By intention-to-treat analysis, weight loss was not significantly different for G. cambogia versus placebo (3.2 ± 3.3 kg vs 4.1 ± 3.9 kg, respectively; P = 0.14). Changes in body fat were also not significantly different. No patient discontinued treatment because of an adverse effect. Critics of the study raised concerns that the use of a high-fiber diet could have impaired the bioavailability of HCA, that no bioavailability data was available for HCA, and that the dose of HCA may have been too low to demonstrate weight loss.2
A double-blind study randomized 44 obese subjects with a visceral fat area greater than 90 cm2 to receive a dosage of G. cambogia providing 1,000 mg/day of HCA or placebo.22 Men received a 2,250 kcal/day diet and women received an 1,800 kcal/day diet. Subjects received treatment for 12 weeks and were observed for an additional 4 weeks to detect whether there was rebound fat accumulation after discontinuation of G. cambogia. The primary endpoint of the study was visceral fat accumulation as measured by CT scan. Secondary endpoints included body weight, BMI, and lipid levels. Compared with placebo, G. cambogia significantly reduced visceral, subcutaneous, and total fat (P < 0.001 for all) with no rebound after discontinuation. However, there was no significant difference in body weight, BMI, or lipid levels.
A 10-week, double-blind, parallel group trial compared the ability of soy leaf and G. cambogia extracts to promote weight loss and lower plasma cholesterol.15 The study randomized 86 overweight adults to receive soy leaf extract 2 g/day, G. cambogia extract (60% HCA) 2 g/day, or placebo. Primary outcomes of the study were percent body fat and plasma total cholesterol. Neither supplement caused weight loss or a clinically important change in percent body fat.
An 8-week study randomized moderately obese subjects (BMI greater than 26 kg/m2) to receive HCA-SX alone, a formula of HCA-SX combined with Gymnema sylvestre and niacin-bound chromium, or placebo.23 The total daily dose of HCA-SX 4,667 mg (60% HCA) was divided 3 times per day and given 30 to 60 minutes before meals. All subjects were given a 2,000 kcal/day diet and participated in a supervised exercise program. Study outcomes included changes in body weight, BMI, and appetite from baseline. The study did not compare weight loss among groups. Reduction in body weight was 4.53 kg with HCA-SX alone, 5.69 kg with the HCA-SX formula, and 1.6 kg with placebo. Reduction in BMI was 5%, 6.1%, and 2%, respectively. Appetite decreased by 15.6% with HCA-SX alone and 21.2% with the HCA-SX formula but did not change with placebo.
A meta-analysis evaluated the efficacy of G. cambogia extract for weight loss in randomized, double-blind, placebo-controlled trials.26 Studies that included other interventions or enrolled nonobese patients were excluded. The meta-analysis included 12 clinical trials. There was significantly greater weight loss with G. cambogia extract than with placebo (approximately 1% body weight loss with G. cambogia compared with placebo), but the effect size was small (mean difference, −0.88 kg; 95% confidence interval [CI], −1.75 to 0; P = 0.05). There was considerable heterogeneity among trials, with wide variation in the duration of treatment (2 to 12 weeks) and the dosage of G. cambogia extract (range, 1 to 2.8 g/day). An analysis restricted to the 2 studies with good methodological quality17, 23 found no significant difference in weight loss between G. cambogia extract and placebo (mean difference, +0.88 kg; 95% CI, −0.33 to 2.10). In the 4 studies that evaluated changes in BMI as an outcome, G. cambogia extract did not have an effect on BMI.
A second meta-analysis evaluated the weight-loss efficacy of natural plant extracts.27 It included double-blind, randomized studies lasting more than 2 weeks with a placebo or control intervention and with measurable outcomes on appetite or food intake and anthropometry that enrolled at least 20 adult participants (18 to 65 years of age) who were overweight or obese. Fourteen studies with an overall quality rating of 7.9 (range, 6 to 10) were included. Five of these studies evaluated extracts that included G. cambogia. One study that used a higher dose of HCA-SX reported a significant reduction in appetite (effect size, 2.79) and body weight (effect size, 0.61) for HCA-SX alone or in combination with niacin-bound chromium and G. sylvestre extract compared with placebo. The other 4 studies did not support an HCA effect on satiety. The authors concluded that the evidence for weight loss with HCA as a single ingredient is not compelling.
A guideline for the management of overweight and obesity from the American Heart Association, the American College of Cardiology, and the Obesity Society considers drug therapy as an adjunct to lifestyle interventions for motivated individuals with a BMI of 30 or more or with a BMI of 27 or more with at least 1 obesity-related comorbid condition.28 Based on expert opinion, the guideline advises that clinicians use drugs that are Food and Drug Administration (FDA)–approved for weight loss. The panel did not review comprehensive evidence for weight-loss pharmacotherapy. This guideline does not address the use of natural product extracts such as G. cambogia or HCA.
Other pharmacologic activity
Supplementation with G. cambogia may reduce oxidative damage.29
The fruit of G. cambogia contains xanthones, which inhibit preneoplastic lesions in mammary and colon cancer, and may also induce apoptosis in mouth, leukemia, breast, gastric, and lung cancer cell lines in vitro.30 Garcinol, a component of G. cambogia fruit rind, inhibited cell proliferation and induced apoptosis in cell lines for leukemia and breast, colon, prostate, and pancreatic cancer.31 Garcinol may have anticarcinogenic effects that are mediated by inhibition of histone acetyltransferases and modulation of 5-lipoxygenase and microsomal prostaglandin PGE2 synthase.
Combined therapy with lipoic acid and HCA (METABLOC™) has been proposed as an antineoplastic regimen that shifts the metabolism of cancer cells from aerobic glycolysis (the Warburg effect) to respiration. Combined lipoic acid and HCA were evaluated alone and in combination with cisplatin or methotrexate in a mouse syngeneic cancer model with LL/2 lung carcinoma, B16-F10 melanoma, and MBT-2 bladder carcinoma.32 Several case series and a case report describe the treatment of patients with advanced metastatic cancer with a combination regimen of lipoic acid and oral HCA in addition to standard chemotherapy; randomized clinical trials are needed.32, 33, 34
Mice treated with G. cambogia had lowered serum insulin levels, suggesting possible improvement in glucose metabolism with G. cambogia administration. Leptin is a hormone associated with appetite control; G. cambogia may have leptin-like activity because mice treated with G. cambogia had decreased serum leptin levels and a reduced leptin:white adipose tissue ratio.35 HCA treatment delayed and reduced intestinal glucose absorption in rats; the treatment caused delayed intestinal absorption of glucose rather than delayed gastric emptying.36
HCA promoted lipid oxidation and reduced carbohydrate use in mice at rest and during running.37 The use of respiratory gases was reduced for mice treated with HCA at rest and during exercise.
Antiulcer activity was observed against induced gastric mucosal injury in rats when they were pretreated with G. cambogia extract, which decreased the volume and acidity of gastric juice.38 A similar study in rats found activity against indomethacin-induced gastric ulcers.39 The anti-inflammatory activity of G. cambogia protected against induced colitis in rats.40
Red blood cell count
A G. cambogia extract caused an increase in the red blood cell count in rat tissue. The activity may be associated with the iron in G. cambogia, because iron is an erythropoietic agent; its antioxidant activity, which may decrease the rate of oxidant-induced hemolysis, increasing the life span of the red blood cell; or the content of bioflavonoids in the plant, which may increase the level of peripheral testosterone, a potential stimulant of erythropoiesis in humans.41
The dosages of G. cambogia extract used in clinical trials ranged from 1,500 to 4,667 mg/day (25 to 78 mg/kg/day). The equivalent HCA dosage used in the trials ranged from 900 to 2,800 mg/day (15 to 47 mg/kg/day).2, 16, 17, 21, 22, 42 G. cambogia is available in capsule or tablet form with a maximum dose of 1,500 mg/day.
Pregnancy / Lactation
Avoid use during pregnancy and lactation due to a lack of clinical and scientific information. One study in rats documented decreased maternal body weight gain during gestation.43
Iron: G. cambogia contains iron and thus may have additive adverse reactions for patients taking medications for anemia.41
Montelukast (or leukotriene receptor antagonists): One case report documented fatal liver failure in a patient taking montelukast and 2 dietary supplements, one of which included G. cambogia and citrus derivatives.45
Potassium and calcium supplements: Some commercial G. cambogia products contain adequate amounts of potassium and calcium.7 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.44 A case report documented suspected serotonin toxicity in a 35-year-old female who had been stable on escitalopram for over a year and developed serotonin toxicity 1 to 2 months after starting a G. cambogia supplement.67
Statins: A case report of rhabdomyolysis was documented in a patient taking a combination herbal medicine containing G. cambogia.46 Concern is raised for coadministration of statins with other drugs that can cause rhabdomyolysis.
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.47
Fifteen clinical studies involving approximately 900 patients documented very mild adverse reactions, with the most common including headache, dizziness, dry mouth, and GI complaints such as nausea and diarrhea.2, 48
In 2009, the FDA announced a voluntary recall of all Hydroxycut dietary supplements for weight loss and warned consumers that the products may cause potentially fatal hepatotoxicity.49 These actions were prompted by 23 cases of hepatic injury reported to the agency, including liver damage severe enough to necessitate liver transplant, as well as 1 death. The recall involved 14 multi-ingredient products with different formulations. Prior to the recall, the primary ingredients of Hydroxycut products included G. cambogia, G. sylvestre, chromium polynicotinate, caffeine, and green tea extract.50 Since 2009, reformulated Hydroxycut products do not contain G. cambogia.51
Criteria from the Drug-Induced Liver Injury Network study were applied to 17 cases of hepatotoxicity linked to Hydroxycut, most with hepatocellular damage, including 9 of the cases reported to the FDA.52 Causality was considered definite in 8 cases, highly likely in 5 cases, probable in 2 cases, and possible in 2 cases. Severity was moderate in 11 cases, was severe in 2 cases, required liver transplant in 4 cases, and was fatal in 1 case. Although G. cambogia was an ingredient in some formulations of Hydroxycut, its role in cases of hepatotoxicity associated with Hydroxycut is unclear.50, 51, 52, 53, 54, 55 A case of acute onset of abdominal pain was reported after ingestion of pure G. cambogia in an obese 42-year-old female with hypertension, stage V chronic kidney disease, and hemochromatosis.66 In the 1 case of fatal hepatotoxicity, the patient had taken montelukast for 5 years and had recently started taking 2 weight-loss dietary supplements that contained G. cambogia and citrus derivatives.43, 45 Acute liver failure in a 52-year-old woman who presented to a hepatology clinic with mild abdominal distention, jaundice, and elevated liver enzymes was attributed as probably due to G. cambogia supplement (60% HCA per serving) that the patient had started taking approximately 3 weeks previously for weight loss. Her condition deteriorated and approximately 50 days after initial symptom onset, she underwent successful liver transplantation.68 Various methods have been used to assess adverse hepatotoxicity causality to the use of weight-loss supplements containing G. cambogia. Reports of hepatotoxicity from case studies and case series have documented 13% to 25% of events as certainly and 50% to 80% as probably related to consumption of Garcinia. Causality, however, is difficult to determine from the small number of reports because in the majority of cases, patients were consuming more than one supplement and/or a multi-ingredient supplement.70
Other serious adverse effects associated with Hydroxycut products that were reported to the FDA included seizures, rhabdomyolysis, and cardiovascular disorders.49 Hydroxycut and other weight-loss dietary supplements containing G. cambogia have been associated with case reports of atrial fibrillation, hypertensive retinopathy, and acute renal failure.56, 57, 58
A near-fatal case of acute necrotizing eosinophilic myocarditis was believed to be associated with G. camobia supplementation in a previously healthy 48-year-old woman. Despite early complications, including acute kidney injury and sustained ventricular tachycardia that required cardiopulmonary resuscitation, she survived and stabilized quickly within 24 hours of high-dose corticosteroid therapy.65
Toxicology studies resulted in no toxicity or deaths in animals at dosages of HCA 5,000 mg/kg, equivalent to 350 g in humans, or 233 times the maximum recommended human dosage of HCA 1.5 g/day.5
A study in obesity-prone mice evaluated long-term supplementation of a high-fat diet with G. cambogia.62 Although G. cambogia reduced adiposity and glucose intolerance, it increased hepatic collagen accumulation, cytokine expression, and hepatic transaminase levels. The study suggests that long-term ingestion of G. cambogia could cause hepatic fibrosis and inflammation.
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.63 Patients receiving 1,667.3 mg/kg of G. cambogia extract (equivalent to HCA 1,000 mg/day) for 12 weeks exhibited no reproductive toxicity on serum testosterone, estrone, and estradiol levels.64
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