Guggul for Hypercholesterolemia

Kelly M. Shields, Pharm.D., Michael P. Moranville, Pharm.D. degree candidate

Am J Health Syst Pharm. 2005;62(10):1012-1014. 


The mukul myrrh tree ( Commiphora mukul ), a native of India, secretes the substance guggul (also known as guggulu or guggulipid) when its bark is injured. Guggul has been used in Ayurvedic medicine for thousands of years to treat arthritis and obesity. Guggul extracts were first used in Asia to help manage cholesterol levels and are becoming increasingly popular in the United States. It is believed that guggul can reduce total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides.

The use of cholesterol-lowering agents has increased rapidly, reflecting changes in cholesterol management guidelines and general health trends in American patients. A recent decision by the British government to make a low-dose (10-mg) version of simvastatin available without a prescription has launched additional conversation about the role of nonprescription products in the management of blood cholesterol in the United States. The high cost of the prescription medications may drive patients to seek alternative agents like guggul.


Guggul is promoted as a traditional Ayurvedic treatment for osteoarthritis and obesity. It has also been used for cholesterol management and for skin disorders, specifically nodulocystic acne.[1,2]

Mechanism of Action

Several mechanisms have been proposed for the effects of guggul. Guggul may decrease hepatic steroid production, ultimately increasing the catabolism of plasma LDL cholesterol.[3] Alternatively, the proposed active components of guggul, guggulsterones E and Z, may increase hepatic binding sites for LDL cholesterol, thus increasing LDL clearance.[4] Still another possibility is prevention of cholesterol synthesis in the liver by ketonic steroids.[3]

Guggulsterones E and Z act as antagonists at the farnesoid X receptor, allowing more cholesterol catabolism and excretion from the body.[4] This receptor mediates the conversion of cholesterol to bile acids; by antagonizing this receptor, 7α-hydroxylase is released, stimulating cholesterol catabolism.[3,5]

Clinical Studies

A double-blind, randomized, placebo-controlled trial in 103 ambulatory, community-dwelling adults with hypercholesterolemia was conducted over an eight-week period.[6] The patients had fasting triglyceride concentrations of <400 mg/dL and LDL cholesterol concentrations of 130-200 mg/dL, had no concurrent diseases, and were taking no lipid-lowering medications or supplements. The patients were randomized (after stratification by baseline LDL cholesterol levels) to receive guggul 1000 mg orally three times daily (standard dose), guggul 2000 mg three times daily (high dose), or placebo. The primary outcome measure was change in LDL cholesterol after eight weeks of therapy; impact on other major lipoproteins and adverse effects were also assessed.

At eight weeks, the placebo group had a 5% decrease in LDL cholesterol, compared with a 4% increase in the standard-dose group and a 5% increase in the high-dose group. The results for both guggul groups differed significantly from those for the placebo group. There were no significant changes in any secondary measures, although the reduction in high-density-lipoprotein (HDL) cholesterol levels in both the standard-dose and high-dose groups approached statistical significance. However, with respect to patients with LDL cholesterol concentrations greater than 160 mg/dL, both guggul groups showed a significant reduction in triglycerides compared with the placebo group: 14% for the standard-dose group ( p = 0.02) and 10% for the high-dose group ( p = 0.03). Adverse effects were reported by 42 patients, and there were no significant differences in overall adverse-effect rates among groups. The guggul groups did have a significantly higher frequency of hypersensitivity rash, which led five patients to withdraw from the study. This trial differs from many other studies of guggul, because it evaluated the therapy in conjunction with a traditional Western diet. The trial was well designed and suggested that guggul offers only negligible benefit, even at high dosages, when used without concomitant lifestyle or dietary changes in the average North American patient.

Another randomized, double-blind, placebo-controlled trial evaluated guggul use in conjunction with a fruit- and vegetable-enriched diet in 64 adult patients.[7] The patients had cholesterol concentrations above 200 mg/dL and no other chronic diseases. The study lasted 52 weeks and consisted of a 4-week observation period, a 12-week diet-stabilization period, a 24-week intervention period, and a 12-week washout period. All participants kept food diaries and received counseling about maintaining a low-fat, low-cholesterol, high-fiber diet. Patients received either 50 mg of guggulsterones orally twice daily or matched placebo. The primary outcome measures were total cholesterol values and changes in body weight.

There was no statistically significant change in body weight during the trial. All groups saw a decrease in total cholesterol ( p < 0.05), triglycerides ( p < 0.01), and LDL cholesterol ( p < 0.05) from baseline to the end of the diet-stabilization period; the guggul group also had a significant reduction in total cholesterol, triglycerides, and LDL cholesterol from the diet phase to the end of treatment. During the washout period after treatment, total cholesterol, triglycerides, and LDL cholesterol increased substantially in the guggul group but not the control group. Adverse effects included nausea, vomiting, eructation, hiccups, headache, and loose stools. The results indicate that long-term therapy in conjunction with dietary modification significantly changes cholesterol levels in patients with hypercholesterolemia.

A randomized four-month trial focused on the effects of guggul on HDL cholesterol levels in 40 patients between the ages of 40 and 60 years with a history of coronary artery disease, serum cholesterol concentrations of ≥275 mg/dL, and triglyceride concentrations of >200 mg/ dL.[8] The patients received either 4.5 g of guggul orally daily in two divided doses or matching placebo. Outcome measures included total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and very-low-density-lipoprotein (VLDL) cholesterol. At the end of the 16 weeks of therapy, total cholesterol and triglycerides had decreased by an average of 72 mg/ mL ( p < 0.01) and 43 mg/dL ( p < 0.05), respectively, in the treatment group. Significant reductions were also seen at 8 weeks in LDL cholesterol and VLDL cholesterol (averaging 59 and 6 mg/dL, respectively), and there were significant increases in mean ± S.E. HDL cholesterol (from 62.1 ± 4.2 mg/dL to 66.4 ± 3.5 mg/ dL) ( p < 0.05). Adverse effects were not reported. While the descriptions of the study's methods and results were rather limited and the sample was small, the trial appears to indicate a benefit of guggul therapy in the absence of dietary or lifestyle changes in patients with coronary artery disease. The authors stated that an additional benefit may derive from a theorized effect of guggul on platelet adhesiveness or fibrinolytic activity.

One trial compared guggul and clofibrate.[9] This crossover study, which had an open-label phase and a double-blind phase, was conducted in 108 patients (men older than 20 years and women older than 40 years who had total cholesterol concentrations of >220 mg/dL or triglyceride concentrations of >150 mg/ dL). After baseline data were gathered, all patients were placed on a low-fat diet for 6 weeks, followed by 2 weeks of placebo treatment three times daily and then 12 weeks of guggul 500 mg orally or clofibrate 500 mg orally three times daily. A placebo washout period was followed by treatment with guggul or clofibrate until lipids returned to predrug levels, and then the patients were crossed over to treatment with the opposite drug, which was followed by another washout period. Serum cholesterol levels declined by 12.6% with guggul and 14.7% with clofibrate, and mean triglyceride levels fell 16.4% and 23.2%, respectively. Statistical significance was not reported. Two patients receiving clofibrate discontinued participation because of flu-like symptoms, and one guggul recipient complained of gastrointestinal distress. The patients continued to take pretrial medications and were to have no dietary changes during the study period. The duration of the washout periods was not stated.

Other trials with small samples also suggest a benefit of guggul therapy on cholesterol levels, as well as body composition, but have many limitations.[10-13] One trial comparing guggul with allicin and whole germinated seeds of bengal gram in 30 patients found significant decreases in overall cholesterol levels for all three interventions.[10] Minimal information was provided, however, and the sample size of 10 patients per treatment group casts doubt on the usefulness of the results. A placebo-controlled trial in 19 patients indicated benefits of guggul therapy on serum cholesterol after four weeks.[11] There were no adverse effects after four weeks of therapy, except that one patient complained of fullness after meals. A study in 20 overweight adults indicated that guggul might have an impact on body composition.[12] However, the guggul product used had multiple ingredients, including Garcinia cambogia, which could have affected the results. Changes in diet and exercise undertaken by the subjects could have accounted for most or all of the weight change observed. A noncontrolled trial of guggul in 22 patients found that over half had a significant reduction ( p < 0.001) in cholesterol levels at four weeks.[13]


The dosages of guggul used in clinical trials have varied greatly, as has standardization. A normal dosage of guggul extract for hypercholesterolemia would range from 75 to 150 mg of standardized guggulsterones orally daily. However, 1000-2000 mg of guggul given multiple times daily has been used.[1,2]

Adverse Effects

One case of guggul possibly causing rhabdomyolysis after two weeks of therapy has been reported.[14] Other than this report, there is little evidence of severe adverse effects. Most adverse effects consist of rash, abdominal pain, diarrhea, nausea, headache, restlessness, and hiccups.[1,2]

Precautions and Contraindications

Guggul may lower thyroid-stimulating hormone levels by increasing the production of triiodothyronine,[1] so patients with thyroid disorder should either avoid guggul or be monitored closely if they choose to use it. Pregnant patients should also avoid guggul, since guggul gum resin appears to stimulate menstrual flow. Information about possible effects on lactation is lacking.


Guggul is likely to interact with other drugs whose metabolism may be increased by pregnane X receptor activation.[5] There are reports of decreased bioavailability of propranolol or diltiazem used concurrently with guggul. The fibrinolytic activity of guggul may lead to an increased risk of bleeding in patients taking anticoagulant or antiplatelet medication.[1]


Studies of the efficacy of guggul for hypercholesterolemia have produced conflicting results. Information currently available indicates that guggul may be effective for lowering total cholesterol and triglycerides in patients on a non-Western diet. The one study involving a typical American diet did not show any benefits; in fact, patients taking guggul had slight increases in LDL cholesterol. The effectiveness of guggul, if any, may depend on dietary practices.

Although most adverse effects have not been serious, the one reported case of rhabdomyolysis raises concern, especially if guggul is used in conjunction with other lipid-lowering therapies. Also, since hypercholesterolemia is a chronic disease, the long-term effects of guggul should be assessed. Until more is known, patients electing to use guggul should be closely monitored and counseled about the need for dietary modifications and exercise.


Guggul may lower lipid levels in some populations but requires more study before its place in therapy can be established.


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