Garcinia

Scientific Name(s): Garcinia cambogia (Gaertn.) Desr., Garcinia gummi-gutta (L.) Roxb.
Common Name(s): Camboginol, Garcinia, Garcinol, Malabar tamarind

Medically reviewed by Drugs.com. Last updated on Jun 1, 2022.

Clinical Overview

Use

The medical literature primarily documents weight-loss and lipid-lowering activities of G. cambogia, although trials supporting use are limited. In short-term clinical trials lasting 12 weeks or less, G. cambogia was ineffective or moderately effective for weight loss in overweight patients. Results have also been inconsistent in studies evaluating the effect of G. cambogia on lipids.

Dosing

Clinical trial data supporting use are limited. G. cambogia extract dosages and treatment durations varied among clinical studies evaluating lipid-lowering and weight-loss effects. Study results have been inconsistent.

Contraindications

Avoid use in the case of known allergy or hypersensitivity to any components of garcinia.

Pregnancy/Lactation

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

Interactions

Garcinia may interact with green tea, montelukast, and selective serotonin reuptake inhibitors.

Adverse Reactions

Very mild adverse reactions, including headache, dizziness, dry mouth, and GI complaints such as nausea and diarrhea, have been reported.

Toxicology

Hydroxycut dietary supplements for weight loss were voluntarily recalled from the US market in 2009 because of hepatotoxicity concerns. Although G. cambogia was an ingredient in some formulations of Hydroxycut, its role in cases of hepatotoxicity associated with Hydroxycut is unclear. Other cases of hepatotoxicity have been reported as "probably" related to ingestion of G. cambogia supplements.

Scientific Family

• Clusiaceae/Guttiferae (Mangosteen)

Botany

The G. cambogia tree is most commonly found in the evergreen or semi-evergreen forests of southwest India, where 36 other Garcinia species have been documented, as well as in Malaysia and Africa.(Abraham 2006, Soni 2004) G. cambogia is variable in its branching pattern and fruit color, shape, and size.(Abraham 2006) The small to medium tree has drooping branches, is tolerant to drought, and flowers during the hot season. The leaves are 5 to 12 cm in length and 2 to 7 cm around, dark green, glossy, and oval shaped with a narrow end. The yellow, orange, or red fruit, which contains hydroxycitric acid (HCA), ripens during the rainy season, is oval 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.(Soni 2004)

Other synonyms for G. gummi-gutta (L.) Roxb. include Cambogia gummi-gutta L., C. gutta L., and Mangostana cambogia Gaetn.(Royal Botanical Gardens 2022)

History

Throughout Southeast Asia, garcinia dried fruit rinds have been used extensively for centuries as condiments and flavoring agents in place of tamarind or lemon. Additional culinary uses include flavoring of curries, meat, and seafood. 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. Rheumatism and bowel complaints have been treated with a decoction of the fruit rind. Garcinol derived from the fruit rind inhibits skin glycation, thus reducing inflammation and injury to the extracellular matrix. The fruit extract has been used as a flavoring agent for beverages and gourmet spices, as well as a carminative to prevent formation of gas in the GI tract after a meal. In the traditional Ayurvedic medical system, the herb is considered beneficial for overall health.(Lodén 2007, Ohia 2002, Saito 2005, Soni 2004) A rinse from the herbal extract is also used in veterinary medicine for some diseases of the mouth in cattle.(Lodén 2007) HCA has become popular as an ingredient in weight-loss products.(Onakpoya 2011)

Chemistry

HCA is the primary medicinal component contained in the fruit rind of G. cambogia.(Jena 2002) HCA is present (up to 30% by weight) in the pericarp of the G. cambogia fruit.(Masullo 2008) At a dosage of 4,500 mg/day, the calcium-potassium salt of HCA (HCA-SX), which is water soluble and bioavailable, provides 495 mg of calcium and 720 mg of potassium.(Downs 2005) Studies also document potential production of HCA by using microorganisms.(Hida 2005, Yamada 2007) Xanthones, xanthone derivatives, and polyisoprenylated benzophenones have been isolated.(Koshy 2001, Masullo 2008) Garcinol, otherwise known as camboginol, is another component of the fruit rinds of G. cambogia(Padhye 2009) and G. indica.(Ciochina 2006) Garcinol is an example of a prenylated chalcone, which has many beneficial effects in human health and disease.(Padhye 2009)

Uses and Pharmacology

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

Alzheimer disease

In vitro data

Garcinol has anticholinesterase activity toward acetyl cholinesterase (AChE) and butylcholinesterase. The 50% inhibitory concentration (IC₅₀) of garcinol (0.66 mcM) against AChE was comparable with the reference compound galanthamine (0.5 mcM).(Lenta 2007)

Anti-inflammatory effects

Animal and in vitro data

Garcinol and its derivatives inhibited release of arachidonic acid metabolites in human colon adenocarcinoma cells. Several key proteins involved in inflammation were also inhibited, and the inhibitory effect on nitric oxide synthesis was concentration dependent. The proposed molecular mechanism of action of garcinol is modulation of inflammatory processes associated with phosphorylation, inflammatory cytokines, and membrane phospholipids.(Hong 2006) Garcinol is a direct and potent inhibitor of the catalytic activity of 2 crucial enzymes involved with inflammation: 5-lipoxygenase and microsomal prostaglandin E₂ (PGE₂) synthase-1.(Koeberle 2009) In a study evaluating effects of garcinol on cigarette smoke extract–induced airway inflammation, which may be regulated by cyclooxygenase 2 (COX-2) expression and PGE₂ synthesis, pretreatment of human tracheal smooth muscle cells with garcinol markedly inhibited COX-2 expression stimulated by the cigarette smoke extract.(Yang 2009)

Topical application or oral administration of garcinol inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced ear inflammation in a dose-dependent manner in CD-1 mice. TPA-induced expression of proinflammatory cytokine interleukin 6 (IL-6) protein was inhibited by topical garcinol application to the ears of CD-1 mice. Ultraviolet B–induced ear inflammation and proinflammatory cytokines IL-1 beta and IL-6 were inhibited in mice after oral administration of garcinol. Topical application of garcinol strongly inhibited TPA-induced skin tumor promotion in mice.(Huang 2008)

Antimicrobial activity

In vitro data

In an in vitro study, garcinol inhibited the growth of methicillin-resistant Staphylococcus aureus, with activity comparable to that of vancomycin.(Iinuma 1996, Rukachaisirikul 2005) G. indica rind extracts and garcinol inhibited the growth of some foodborne gram-positive and gram-negative bacteria.(Negi 2004) In vitro bactericidal activities of clarithromycin with garcinol on Helicobacter pylori were time- and concentration-dependent. In the same study, garcinol showed greater bactericidal activity on H. pylori compared with resveratrol.(Chatterjee 2003, Chatterjee 2005)

In a growth inhibition assay, several concentrations of an extract from G. indica, with garcinol as the major compound, inhibited the growth of Aspergillus flavus and subsequent mycotoxin aflatoxin B1 production.(Tamil Selvi 2003)

Garcinol has moderate antiplasmodial activity against the chloroquine-resistant strain of Plasmodium falciparum (FcB1).(Marti 2009)

Antioxidant activity

In vitro data

Supplementation with G. cambogia may reduce oxidative damage.(Yonei 2008) Garcinol has free radical–scavenging activity against the hypoxanthine/xanthine oxidase system, superoxide anion, hydroxyl radical, and methyl radical.(Yamaguchi 2000) The activity of emulsified garcinol was almost comparable with that of DL-alpha-tocopherol by weight but was less than that of ascorbic acid. However, garcinol suppressed hydroxyl radical more strongly than DL-alpha-tocopherol. Garcinol’s antioxidant mechanism of action may be associated with a reaction with peroxyl radicals followed by deprotonation of the hydroxyl group.(Sang 2001, Sang 2002) Garcinol has chelating and antiglycation activity (glycation plays a role in diabetic complications) and is a lipid-soluble superoxide anion scavenger.(Yamaguchi 2000)

Garcinol had a neuroprotective effect in rat cortical astrocyte cultures by decreasing production of nitric oxide and expression of the lipopolysaccharide-induced inflammatory mediators iNOS and COX-2.(Liao 2005)

Antiviral activity

In vitro data

A chemical study examining 2 ethers of garcinol and isogarcinol documented inhibitory activity against Epstein-Barr virus early antigen activation induced by TPA in Raji cells; the activity was comparable to or stronger than that of the anti-tumor promoter glycyrrhetic acid.(Ito 2003) In vitro and in vivo, garcinol is a potent, nonspecific inhibitor of histone acetyltransferase, a key regulatory step in gene expression in eukaryotic cells.(Arif 2009, Balasubramanyam 2004) Garcinol is also the first reported cell-permeable histone acetyltransferase inhibitor.(Varier 2004) In one study, garcinol-derived molecules inhibited a critical step in integration of HIV-1 virus into the human genome and inhibited HIV multiplication in T cells at nontoxic concentrations.(Dekker 2009, Mantelingu 2007)

Cancer

Animal and in vitro data

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.(Mazzio 2009) Garcinol inhibited cell proliferation and induced apoptosis in cell lines for leukemia and breast, colon, prostate, and pancreatic cancer.(Saadat 2012) Garcinol’s anticarcinogenic effects may be mediated by inhibition of histone acetyltransferases and modulation of 5-lipoxygenase and microsomal prostaglandin PGE₂ synthase.(Koeberle 2009)

Garcinol showed potent inhibitory growth activity against HT-29 and HCT-116 colon cancer cells.(Hong 2007) Garcinol inhibited cell invasion by inhibiting the downstream signaling of FAK, which is involved in protecting against apoptosis.(Liao 2005) Findings in rats with chemically induced colon carcinogenesis administered dietary garcinol (elevation of the detoxifying enzyme glutathione S-transferase and quinine reductase in the liver, reduction of free radicals, and modulation of arachidonic acid metabolites) suggest possible ability to suppress colon tumorigenesis.(Tanaka 2000) In human leukemia HL-60 cells, garcinol inhibited activity in a dose- and time-dependent manner by inducing DNA fragmentation and apoptotic cell death.(Pan 2001) A similar study with human leukemia HL-60 cells documented the loss of mitochondrial membrane potential by garcinol-induced apoptosis.(Matsumoto 2003) Dietary administration of garcinol in rats inhibited development of 4-nitroquinoline 1-oxide–induced tongue carcinogenesis and preneoplasms when compared with the control diet. The mechanism of action of garcinol involves suppression of cell proliferation activity in affected tissues and/or COX-2 expression in the tongue lesions.(Yoshida 2005) Garcinol induced caspase-mediated apoptosis in highly metastatic human breast cancer cells (MDA-MD-231) through downregulation of the nuclear factor kappa B signaling pathway.(Ahmad 2010)

Dyslipidemia

Animal and in vitro data

In 2 experiments using the human hepatoma cell line HepG2, overnight exposure to G. cambogia extract caused an upregulation of LDL receptor activity and an upregulation of HMG-CoA reductase, resulting in decreased cholesterol synthesis.(Berkhout 1990) Flavonoids from the plant reduced lipid levels in normal and hypercholesterolemic rats. Reductions were also documented in triglycerides, phospholipids, and free fatty acids. The mechanism of action of 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.(Koshy 2001) In a study in rats administered dexamethasone, which typically elevates lipid profiles, cotreatment with G. cambogia extract resulted in maintained normal lipid levels.(Mahendran 2001)

Clinical data

In a double-blind clinical trial evaluating the effects of G. cambogia extract on lipid profiles in obesity, w omen with a body mass index (BMI) of 25 kg/m² or more 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.(Vasques 2014)

In a 10-week, double-blind, parallel-group trial comparing Glycine max (soy) leaf extract with G. cambogia extract for weight-loss and plasma cholesterol–lowering effects, 86 overweight adults were randomized to receive 2 g/day of Glycine max extract, 2 g/day of G. cambogia extract (60% HCA), or placebo. Primary outcome measures were percent body fat and total cholesterol. Secondary outcome measures included other lipid profile components, adipocytokine concentration, and antioxidant enzyme activity. After 10 weeks, there were no significant differences in body weight, BMI, or waist-to-hip ratio with Glycine max or G. cambogia extracts. Total cholesterol was significantly lower in the Glycine max leaf extract group compared with the G. cambogia and placebo groups (P<0.05), the clinical importance of which is unclear because total cholesterol increased during the study in all treatment groups. Aside from an unspecified increase in HDL cholesterol for the Glycine max leaf extract, the supplements had no effect on other components of the lipid profile, adipocytokines, or antioxidant enzymes.(Kim 2011)

Erythropoietic effects

In vitro data

A G. cambogia extract caused an increase in red blood cell count in rat tissue. The activity may be associated with the iron in G. cambogia. Content of bioflavonoids in the plant may increase the level of peripheral testosterone, a potential stimulant of erythropoiesis in humans.(Oluyemi 2007)

Exercise endurance

Animal data

HCA administration in mice promoted lipid oxidation and reduced carbohydrate use at rest and while running. The use of respiratory gases was also reduced under both resting and exercising conditions.(Ishihara 2000)

GI disorders

Animal and in vitro data

Antiulcer activity against induced gastric mucosal injury was observed in rats pretreated with G. cambogia extract, which decreased the volume and acidity of gastric juice.(Mahendran 2002) Other studies in rats identified activity against indomethacin-induced gastric ulcers. The mechanism of action may be associated with garcinol interaction with reactive oxygen species on the surface of gastric mucosa.(Mahendran 2002, Yamaguchi 2000) Garcinol exerted time- and concentration-dependent effects against H. pylori that were greater than those with resveratrol.(Chatterjee 2003, Chatterjee 2005)

In a study in rats, the anti-inflammatory activity of G. cambogia protected against induced colitis.(dos Reis 2009)

Glycemic effects

Animal data

Mice treated with G. cambogia had lowered serum insulin levels, suggesting possible improvement in glucose metabolism with G. cambogia administration. G. cambogia may have leptin-like activity; mice treated with G. cambogia had decreased serum leptin levels and a reduced leptin:white adipose tissue ratio.(Hayamizu 2003) HCA treatment delayed and reduced intestinal glucose absorption in rats but did not have an effect on gastric emptying.(Wielinga 2005)

Neurodegeneration

A review of garcinol's documented neuroprotective effects reports strong inhibitory effects on histone acetyltransferases via a reduction in gene transcription.(Deb 2019)

Obesity

G. cambogia's suggested mechanism of action in obesity involves HCA-inhibiting lipogenesis, increased lipid oxidation, and reduction of food intake.(Mattes 2000, Ohia 2002) HCA competitively inhibits adenosine triphosphate-citrate (pro-3S)-lyase, an extra-mitochondrial enzyme that plays a role in fatty acid biosynthesis.(Heymsfield 1998)

Reviews of the literature for G. cambogia and garcinol report appetite suppressant effects and activity in models of diabetes and cardiovascular disease.(Behera 2016, Semwal 2015)

Animal data

In a study in obese rats, high doses of HCA-containing G. cambogia (HCA 154 mmol/kg diet) were effective in suppressing epididymal adipose tissue. This same study also showed testicular atrophy and toxicity at HCA dosages of 778 mg/kg body weight per day (HCA 102 mmol/kg diet) and higher.(Saito 2005) 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 reductions in body weight and accumulation of visceral fat mass. The mixture also improved blood and hepatic lipid concentrations and improved dyslipidemia in rats with induced obesity. Other G. cambogia combination products were also effective in reducing weight gain and improving dyslipidemia, hyperinsulinemia, hyperleptinemia, and fatty liver in mice. The antiobesity effect involves modulation of several genes associated with visceral adipogenesis.(Kim 2008) However, one study in adult nonobese cats found that G. cambogia had no effect on fat-free mass or energy expenditure.(Leray 2006)

Clinical data

In a 12-week, randomized, double-blind, placebo-controlled study (N=40), obese patients were treated with a combination supplement containing G. cambogia accompanied by a 1,200 kcal/day diet.

In a 12-week, double-blind, placebo-controlled, parallel-group trial (N=89), mildly overweight women were given a 1,200 kcal/day 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 had 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); however, the weight loss was minimal, and G. cambogia had no effect on appetitive variables or fat mass.(Mattes 2000)

In a double-blind trial (N=135), overweight adults with a mean BMI of 32 kg/m² were randomized to 12 weeks of treatment with placebo or G. cambogia (50% HCA) 1,000 mg 3 times per day before meals; 42 patients in each group completed the study. Subjects were given a high-fiber, 5,040 kJ/day diet plan. The primary outcomes 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. In the 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 regarding use of a high-fiber diet, which could have impaired the bioavailability of HCA; lack of bioavailability data for HCA; and use of an HCA dose that may have been too low to demonstrate weight loss.(Heymsfield 1998)

In a double-blind study (N=44), obese subjects with a visceral fat area greater than 90 cm² were randomized to receive G. cambogia (containing 1,000 mg/day of HCA) or placebo. Men were placed on a 2,250 kcal/day diet and women on an 1,800 kcal/day diet. Subjects were treated for 12 weeks and were observed for an additional 4 weeks to assess potential rebound fat accumulation after discontinuation of G. cambogia. The primary end point was visceral fat accumulation as measured by CT scan. Secondary end points 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.(Hayamizu 2003)

In a 10-week, double-blind, parallel-group trial to compare the ability of soy leaf and G. cambogia extracts to promote weight loss and lower plasma cholesterol, overweight adults (N=86) were randomized to receive soy leaf extract 2 g/day, G. cambogia extract (60% HCA) 2 g/day, or placebo. Primary outcomes were percent body fat and plasma total cholesterol. Neither supplement was associated with weight loss or a clinically important change in percent body fat.(Kim 2011)

In an 8-week study (N=60), moderately obese subjects (BMI greater than 26 kg/m²) were randomized to receive HCA-SX alone, a formula of HCA-SX combined with Gymnema sylvestre and niacin-bound chromium, or placebo. The total daily dose of HCA-SX 4,667 mg (60% HCA) was administered in 3 equally divided doses 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.(Preuss 2004)

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.(Hoffman 2006, Taylor 2007)

Meta-analyses

A meta-analysis evaluated the efficacy of G. cambogia extract for weight loss in randomized, double-blind, placebo-controlled trials. 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% 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 quality found no significant difference in weight loss between G. cambogia extract and placebo (mean difference, +0.88 kg; 95% CI, −0.33 to 2.1). In the 4 studies that evaluated changes in BMI as an outcome, G. cambogia extract did not have an effect on BMI.(Onakpoya 2011)

A second meta-analysis evaluating weight-loss efficacy of natural plant extracts included double-blind, randomized studies of more than 2 weeks' duration, with inclusion of a placebo or control intervention, with measurable outcomes on appetite or food intake and anthropometry, and enrollment of 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.(Astell 2013)

Obesity guidelines

A guideline for the management of adults who are overweight or obese from the American Heart Association, the American College of Cardiology, and the Obesity Society considers drug therapy 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. Based on expert opinion, the guideline advises that clinicians use drugs that are U.S. 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.(Jensen 2014)

Osteoporosis

Animal and in vitro data

In vitro, garcinol showed strong inhibitory activity on osteoclast formation and bone resorption, results that were supported by protection against osteolytic bone loss in a mouse model. The mechanism involved inhibition of several signaling pathways that promote expression of osteoclastic-related genes.(Jia 2019)

Dosing

Clinical trial data supporting use are limited. G. cambogia extract dosages and treatment durations varied among clinical studies evaluating lipid-lowering and weight-loss effects. Study results have been inconsistent.

Toxicological studies suggest a "no observed adverse effect level" with Garcinia extract up to 2,800 mg/day.(Semwal 2015)

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.(Deshmukh 2008) Testicular atrophy and toxic effects on spermatogenesis in rats administered G. cambogia extract have been reported.(Semwal 2015)

Interactions

Theoretically, when used with stomach acid–reducing medications (eg, proton pump inhibitors), garcinol may provide an additive effect but should be used cautiously with antioxidant products or cancer medications.

Green tea: Garcinia may enhance the hepatotoxic effect of green tea. Monitor therapy.(Ferreira 2020, Gavric 2018, Vuppalanchi 2021)

Montelukast: Garcinia may enhance the hepatotoxic effect of montelukast. Monitor therapy.(Singulair February 2021, Ferreira 2020, Vuppalanchi 2021)

Selective serotonin reuptake inhibitors: Garcinia may enhance the serotonergic effect of selective serotonin reuptake inhibitors. This could result in serotonin syndrome. Monitor therapy.(Lopez 2014)

Adverse Reactions

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.(Pittler 2005, Soni 2004)

Toxicology

Toxicology studies in animals showed no toxicity or deaths at HCA dosages of 5,000 mg/kg, equivalent to 350 g in humans, or 233 times the maximum recommended human HCA dosage of 1.5 g/day.(Jena 2002) Most reports from animal studies suggest dietary administration of garcinol results in low toxicity, with no histological or pathological changes in liver, kidney, lung, heart, or esophageal organ systems.(Tanaka 2000, Yoshida 2005) G. cambogia is available in capsule or tablet form with a maximum dose of 1,500 mg/day.

Some animal studies document testicular toxicity with G. cambogia,(Anno 2005, Saito 2005, Semwal 2015) whereas other studies do not.(Burdock 2005, Shara 2003)

A study in obesity-prone mice evaluated long-term supplementation of a high-fat diet with G. cambogia.(Kim 2013) 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.(Min 2005) 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, or estradiol levels.(Hayamizu 2008)

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.(FDA 2014) 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.(Dara 2008) Since 2009, reformulated Hydroxycut products do not contain G. cambogia.(Lobb 2009)

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.(Fong 2010) 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.(Dara 2008, Fong 2010, Lobb 2009, Sharma 2010, Shim 2009, Stevens 2005) A case of acute-onset 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.(Melendez-Rosado 2015) 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.(Actis 2007, Deshmukh 2008) 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 considered probably due to G. cambogia supplement (60% HCA per serving), which 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.(Corey 2016) Similarly, fulminant hepatic failure with near total necrosis requiring liver transplant was reported in a 34-year-old man who consumed a G. cambogia supplement (160 mg/day) for 5 months.(Lunsford 2016) Various methods have been used to assess causality in cases of adverse hepatotoxicity with 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 related and 50% to 80% as probably related to consumption of Garcinia. Causality 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.(Crescioli 2018)

Other serious adverse effects associated with Hydroxycut products and reported to the FDA included seizures, rhabdomyolysis, and cardiovascular disorders.(FDA 2009) 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.(Karth 2010, Li 2011, Willis 2006)

A near-fatal case of acute necrotizing eosinophilic myocarditis was believed to be associated with G. cambogia 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.(Allen 2014)

Index Terms

• Cambogia gummi-gutta L.
• Cambogia gutta L.
• Mangostana cambogia Gaetn.

References

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