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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral garcinia is beneficial for improving athletic performance. Details: Two very small, exploratory studies in untrained females and in elite athletes show that taking hydroxycitric acid (HCA), the active ingredient of garcinia, 250 mg daily for 5 days increases time to exhaustion and lowers the respiratory exchange ratio when compared with taking placebo (19151,26858).
• Hyperlipidemia. It is unclear if oral garcinia is beneficial in patients with hyperlipidemia. Details: A small open-label study of adults with obesity shows that taking garcinia 600 mg twice daily for 3 months may reduce total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides when compared to baseline (111243). The validity of these findings is limited by a lack of a comparator group and blinding.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral garcinia is beneficial in patients with NAFLD. Details: A small clinical study in females with obesity and NAFLD shows that taking a specific product containing garcinia bark leaf extract (HCA Garcinia Vita Plus, Vitamin House) 312.5 mg daily for 8 weeks in combination with a calorie-restricted diet improves body weight, body mass index (BMI), triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol when compared to baseline. However, liver enzyme levels increased slightly (111240). While a calorie-restricted control group was included, a lack of appropriate statistical comparison limits the validity of any between-group findings. Thus, it is unclear if these results are due to garcinia, the calorie-restricted diet, or the combination.
• Obesity. Despite contradictory evidence, oral garcinia seems to produce a very modest weight reduction in some people who are obese or overweight. Details: A meta-analysis of 8 small clinical trials shows that taking garcinia for 8-12 weeks seems to reduce weight by about 1.3 kg and body mass index (BMI) by about 1 kg/m2 when compared with control (104432). This analysis is limited by prominent heterogeneity in the included studies and a lack of sensitivity analyses. Most studies included in the analyses used garcinia 1000-4667 mg (standardized to 50% or 60% hydroxycitric acid) in divided doses daily as non-branded extracts or as specific branded supplements (Super CitriMax, InterHealth Nutraceuticals; Citrin, Sabinsa Corporation) (728,19152,19153,88158,104432). It is unclear which dose, if any, may be most beneficial. More recently, a small, open-label trial in adults with obesity shows that taking garcinia 600 mg twice daily for 3 months reduces body weight and BMI by 1.7 kg and 0.7 kg/m^2 when compared to baseline (111243). The validity of these findings is limited by a lack of a comparator group and blinding. Limited research has also studied garcinia in combination with glucomannan for 6 months, with evidence of moderate benefit for weight loss (96536). More evidence is needed to rate garcinia for these uses.

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There is insufficient reliable information available about the safety of garcinia extract when used orally. However, there is some concern about liver toxicity. There are numerous case reports of elevated liver enzymes and symptoms of liver toxicity in patients who have taken garcinia alone or in combination with other ingredients for as little as one week. In at least two reports, hepatotoxicity occurred in patients who were taking garcinia alone. Most other reports occurred in patients taking multi-ingredient products (13037,53511,93380,93381,93384,93385,93392,93393,93394,96535)(102544,102545,111241).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details HCA inhibits platelet aggregation in vitro. The inhibitory effect seems to be greater in platelets extracted from diabetic subjects than non-diabetic subjects (26862).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.  Details HCA reduces fasting and postprandial blood glucose levels in animal models, theoretically by delaying glucose absorption (26863,26867,26868). This effect has not been reported in humans.

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage.  Details There have been reports of acute hepatitis with elevated liver enzymes associated with garcinia, when taken alone or in combination with other ingredients (13037,53511,93380,93381,93384,93392,93393,93394,102544,102545). Case reports collected from the Drug Induced Liver Injury Network suggest this risk may be greater in people who carry the HLA B*35:01 allele (108401).

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining garcinia with other serotonergic drugs might increase the risk of serotonergic side effects, including serotonin syndrome.  Details In one report, a patient experienced serotonin syndrome after taking garcinia extract (60% hydroxycitric acid) 1000 mg daily in combination with escitalopram 20 mg, which had been taken for a year. The patient was switched to sertraline 50 mg daily and again experienced serotonin syndrome (23545).

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General ...Orally, garcinia and its constituent, hydroxycitric acid (HCA), seem to be generally well tolerated in clinical research.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal discomfort, headache, and nausea.
Serious Adverse Effects (Rare):
Orally: Garcinia has been linked with cases of hepatotoxicity and liver failure. There have also been rare cases of mania and pancreatitis.

Cardiovascular ...There is a case report of a 48-year-old female who developed acute necrotizing eosinophilic myocarditis (ANEM) after using a garcinia supplement orally for 2. 5 weeks. On admission to hospital, she was hypotensive and had an elevated serum troponin level, progressing to fulminant heart failure, acute kidney failure, and sustained ventricular arrhythmias. She recovered after treatment with extra-corporeal membrane oxygenation (ECMO) and high-dose corticosteroids (88160). Although the patient had no prior medical history and was not taking any medications, this cannot conclusively be attributed to garcinia.
When taken orally, a specific formulation of the multi-ingredient product Hydroxycut (Iovate Health Sciences Inc.), which was available until 2009, has been associated with malignant hypertension and hypertensive retinopathy. Hydroxycut contains caffeine, garcinia, gymnema, green tea, glucomannan, guarana extract, and willow bark. The suspected causal agent is caffeine, which is dosed at 600 mg daily if Hydroxycut is taken as recommended; however, the responsibility of the other ingredients cannot be ruled out (16527).

Endocrine ...In one case report, a 56-year-old female with pre-existing diabetes, hepatitis C, and hypertension developed diabetic ketoacidosis (DKA) and pancreatitis after taking an unknown amount of garcinia and African mango for one month. Upon admission, she presented with altered mental status, elevated serum glucose and lipase, and high anion gap metabolic acidosis. After 3 days of intensive supportive care, the DKA and pancreatitis resolved. The suspected probable causal agent was garcinia; however, African mango cannot be ruled out (97341). There have been at least 3 other cases of acute pancreatitis associated with use of garcinia (unknown dose) for 2 weeks and up to 7 months in adults ages 36-82 years (105056,105058,105071).

Gastrointestinal ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) have caused mild and infrequent nausea, diarrhea, and other gastrointestinal symptoms (728,11977,19153,88158,88159).

Hepatic ...Orally, garcinia and its constituent hydroxycitric acid (HCA) might cause liver toxicity. Several cases of acute liver toxicity have been reported in patients taking garcinia supplements (93392,93393,93394,95573,102544,102545,104431,111241). Reported doses of garcinia extract range from 480-1800 mg daily, providing up to 900 mg HCA daily (93392,93394,95573,102544,104431). However, not all experts agree that HCA plays a causal role in the hepatotoxicity associated with garcinia supplements; some suggest other mechanisms may be in play, such as immune-mediated processes (95576,108401). In most cases, patients presented with a hepatocellular pattern of toxicity and symptoms of abdominal pain, coagulopathy, jaundice, and elevated transaminases after taking garcinia for several weeks to several months (93393,93394,95573,102544,102545,104431,108401,111241). In most of these cases, there was no evidence of other natural causes of liver disease, such as viral hepatitis. Some of these patients used acetaminophen at recommended doses for limited durations, suggesting that a potential synergistic effect may occur when multiple hepatotoxic agents are used concomitantly.
The Drug-Induced Liver Injury Network has identified 22 cases (11 moderate; 7 severe) of liver injury from garcinia, with 5 cases occurring with garcinia alone, 16 cases occurring in combination with green tea, and 1 case occurring in combination with ashwagandha. Clinical presentations of liver injury related to garcinia closely resemble green tea-related liver injury. Most patients (82%) presented with a hepatocellular pattern of enzyme elevations. The median age of these case reports was 35 years, 41% identified as Hispanic, and most patients were overweight but not obese. In case reports involving garcinia alone, the carrier frequency on HLAB*35:01 was 60%, which is higher than the carrier frequency found in reports of liver injury due to other supplements (19%) and in population controls (11%). Within 3 months of injury onset, 1 patient required liver transplantation and 1 patient died from liver injury (108401).
There have been at least four cases of liver failure requiring transplantation associated with garcinia supplements (93392,95573,98425,104431). In one case related specifically to garcinia, a 52-year-old female had been taking a combination product (USA Nutra Labs) providing garcinia 1000 mg daily, standardized to 60% HCA. The supplement also provided calcium 50 mg, chromium 200 mcg, and potassium 50 mg. Symptoms started within a few weeks of initiation of the product (93392). In another case, a 34-year-old Hispanic male experienced acute liver failure requiring transplant after taking a specific garcinia product (Garcinia Cambogia 5:1 Extract, Swanson Vitamins) 160 mg three times daily before meals for 5 months (95573). In other reports, one 26-year-old male and one female presented to the emergency room with liver failure after 2-7 months of taking a supplement containing garcinia and green tea, with or without whey protein, Veldt raisin, and coffea arabica (98425,104431).
There have also been numerous cases of acute liver toxicity associated with combination products containing garcinia, such as Hydroxycut (Iovate Health Sciences Inc) (13037,53511,93380,93381,93384,93385,96535,98425,104431). Available until 2009, Hydroxycut contained garcinia, green tea, chromium, caffeine, calcium, potassium, and gymnema. A currently available garcinia-containing combination product called Seryburn Day Triple has also been associated with supplement-induced liver injury. (13037,93380,93381,95570,95572,95575,111241). In most of these cases, patients had elevated levels of liver enzymes without evidence of chronic liver disease. Patients usually developed symptoms within 1-12 weeks of taking the product. The clinical pattern of liver damage was often hepatocellular. Most cases reported altered liver enzyme values including ALT, AST, bilirubin, alkaline phosphatase, and international normalized ratio. In most cases, symptoms resolved with near normalization of enzyme levels once the garcinia-containing combination product was discontinued (13037,53511,93380,93381,93384,95567,95572,95575,111241).
However, there is one report of transplant related to Hydroxycut use (93381). As the suspected causal agents, garcinia and green tea were removed from the product during reformulation in 2009 (13037,53511,93380,93381,93384). Hepatotoxicity has been reported in at least one new formulation of Hydroxycut not containing garcinia (93394). Consequently, some experts believe that there is not enough information to attribute hepatotoxicity from this product to garcinia or HCA (95576). Also, in some cases, causality of hepatotoxicity was less clear because patients were taking many other supplements and drugs (95570).There is also a report of fatal liver failure in an obese female taking montelukast while also taking two dietary supplements containing multiple ingredients, including garcinia, gymnema, chromium, bitter orange, and many others. The authors speculated that the combination of montelukast with one or more ingredients in these dietary supplements may have resulted in liver failure (93385).

Musculoskeletal ...Orally, garcinia-containing products have been associated with rhabdomyolysis. There is a case report of a patient who developed rhabdomyolysis 3 hours after ingestion of an herbal product containing ephedra, guarana, chitosan, gymnema, garcinia, and chromium (19154). Since there were multiple ingredients, the effect cannot be conclusively attributed to garcinia. Another case of rhabdomyolysis has been reported for a patient taking an undetermined formulation of Hydroxycut at a dose of 4 caplets daily, naproxen sodium 220 mg as needed for pain, dextroamphetamine daily for 5 days, and hydrocodone-acetaminophen and cyclobenzaprine for pain. Two weeks later, after stopping Hydroxycut and receiving supportive care, the rhabdomyolysis resolved. Hydroxycut was determined to be possibly associated with the rhabdomyolysis (95566). Since Hydroxycut contains multiple ingredients and garcinia content was possible but not confirmed, a causal relationship with garcinia could not be determined.

Neurologic/CNS ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) may cause headache and dizziness (11977). A 35-year-old female reported ocular complications, headache, dizziness, and nausea after taking garcinia extract, providing more than 500 mg of HCA, three times daily for one week. The patient's neurologic symptoms resolved one day after discontinuing the garcinia extract (102546). It is unclear if these neurologic adverse effects were separate from or related to the patient's visual disturbances.

Ocular/Otic ...In one case, a 35-year-old female presented with ocular pain in both eyes, decreased vision in the left eye, headache, dizziness, and nausea after taking garcinia extract orally for one week. Ophthalmologic testing was consistent with adverse ocular effects, showing myopic shift with anterior chamber shallowing and swelling of retinal nerve fiber and macula. The patient reported taking a garcinia product containing hydroxycitric acid 500 mg three times daily, which was more than double the recommended dose per the product label. Symptoms resolved upon discontinuation of the garcinia extract and treatment with oral and topical steroids (102546).

Psychiatric ...Orally, garcinia supplements have been linked to several cases of mania. Typically, symptoms develop 1-8 weeks after starting garcinia. In a report of three patients, symptoms included reduced need for sleep, increased activities and spending, delusions of grandiosity, pressured speech, and agitation. Two of the patients were previously diagnosed with bipolar disorder, and use of garcinia was believed to precipitate episodes during stable phases of the disease. The third patient had no history of bipolar disorder, and use of garcinia was thought to possibly have unmasked previously undiagnosed primary bipolar disorder. In all three cases, recovery included discontinuation of garcinia (95568). In a separate case report, a 23-year-old male taking a specific combination product containing garcinia (Hydroxycut) 1-2 capsules daily for 1 month presented to the emergency room with mania. The patient had no history of bipolar disorder. Although the patient was started on risperidone and clonazepam, symptoms resolved following discontinuation of the supplement. Treatment was discontinued within 4 days of initiation, and the patient remained asymptomatic (95574). A 22-year-old female with no history of bipolar disorder developed mania and psychosis, presenting 10 days after starting Garcinia Cambogia Plus (Apex Vitality Health) 500-1500 mg daily, and Cleanse and Detox (Apex Vitality Health). The latter supplement contains raspberry ketones, licorice root, pumpkin seed, buckthorn root, Cascara sagrada, Irvingia gabonensis, rhubarb, pectin, Lactobacillus acidophilus, and aloe. Symptoms improved upon stopping the supplements and starting lithium and quetiapine (99421).

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