Guggul

Scientific Name(s): Commiphora mukul Hook. ex Stocks. Family: Burseraceae.

Common Name(s): Guggul , guggal , gum guggal , gum guggulu , gugulipid

Uses

Guggul has been used in the traditional Ayurvedic medical system for centuries and has been studied extensively in India. Commercial products are promoted for use in hyperlipidemia; however, clinical studies do not substantiate this claim. Anti-inflammatory and cardiovascular effects are being evaluated, as well as use in cancer, obesity, and diabetes.

Dosing

Clinical trials are lacking to provide dosage guidelines; however, in a US clinical trial of hyperlipidemia, 75 to 150 mg of standardized guggulsterones were administered daily. In a study evaluating the anti-inflammatory effect of guggul, 500 mg of gum guggul was taken 3 times per day.

Contraindications

None identified. Caution may be warranted in patients previously experiencing adverse effects to statins.

Pregnancy/Lactation

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

Interactions

None well documented.

Adverse Reactions

Although generally accepted as relatively safe, case reports of adverse events exist. Moderate to severe generalized acute eczematous reactions to oral guggul have been reported, and caution may be warranted. A case report exists of rhabdomyolysis possibly caused by guggul consumption.

Toxicology

Research reveals little information regarding toxicology with the use of guggul.

Botany

The guggul plant is widely distributed throughout India and adjacent dry regions. The tree is a small shrub with thorny branches. The gum, called “guggul” or “gum guggulu,” is tapped from the stem of the plant, and the fragrant yellow latex solidifies as it oozes out. Excessive production of the gum eventually kills the plant. C. mukul is synonymous with Commiphora wightii and is in the same genus as Commiphora myrrha , the myrrh mentioned in the Bible. 1 , 2

History

The plant has been used in the traditional Ayurvedic medical system for centuries in the treatment of a variety of disorders, most notably arthritis, and as a weight-reducing agent in obesity. Other traditional uses have included liver dysfunction, tumors, ulcers and sores, urinary complaints, intestinal worms, edema, seizures, and as a cardiac tonic. In 1966, the first medical studies in animals were conducted, and in 1986, guggal was approved for marketing in India as a hypolipidemic drug. A commercial product, Guggulow , claiming cholesterol-lowering properties, is widely available on the internet. 2 , 3 , 4

Chemistry

Guggul is the dry gum resin obtained from the bark of the tree. The gum contains minerals, resin, volatile oils, sterols, ferulates, flavones, sterones, and other chemical constituents.

Several pharmacologically active components have been identified in the plant, including guggulsterone (E- and Z-stereoisomers) and gugulipid, both found in the ethyl acetate extract of the plant. Studies have shown that the guggulsterones are antagonist ligands for the bile acid receptor farnesoid X receptor, which is activated by bile salts, thus reducing cholesterol. A triterpene, myrrhanol A, has been described to have potent anti-inflammatory effects. High-performance liquid chromatography and thin-layer chromatography methods for standardization have been described, and adulterants have been found in commercial preparations. 2 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13

Uses and Pharmacology

Anti-inflammatory effects

Down-regulation of the expression of inflammatory mediators, including interleukins, transcription factors and cytokines, and hyaluronidase and collagenase enzymes have been demonstrated for extracts of C. mukul . 4 , 14 , 15 , 16 , 17 , 18

Animal data

Extracts of the plant have anti-inflammatory action and inhibit carrageenan-induced rat paw edema in animal models. Guggul was as effective as phenylbutazone and ibuprofen in an animal model of acute and chronic inflammation. 11 , 19 , 20 , 21

In mice with induced colitis, guggulsterone decreased the severity of the inflammatory disease. 16 , 22 In rats with induced uveitis, guggulsterone demonstrated a protective effect against inflammatory mediators. 23

Clinical data

A clinical study conducted in 30 elderly patients with osteoarthritis of the knee showed significant improvement in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scores after taking 500 mg of C. mukul (guggulsterone 3.5%) 3 times daily with food. However, not all outcome measures showed improvement at the 2-month point. 24 Clinical studies in GI inflammatory disease are lacking.

Cancer
Animal data

In vitro studies have evaluated the effect of C. mukul extracts in a wide variety of cancer cell lines, including leukemia, myeloma, and head and neck, lung, breast, ovarian, prostate, skin, and bone cancers. 2 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 Induction of apoptosis and inhibition of angiogenesis and cell signaling, as well as the down-regulation of transcription factors, have all been demonstrated.

Clinical data

Research reveals no clinical trials regarding the use of guggul for cancer.

Cardiac effects
Animal data

In rats with isoproterenol-induced ischemia, a hydroalcoholic extract of C. mukul improved cardiac function and prevented myocardial ischemic impairment. 34 Guggulsterone also exerts a protective effect on cardiac enzymes against drug-induced myocardial necrosis. 35

Clinical data

In an older trial, C. mukul in combination with Inula racemosa (another Ayurvedic botanical) was studied in 200 patients with ischemic heart disease and found to improve electrocardiogram readings and decrease episodes of dyspnea and chest pain. 36 Gum guggul fraction increased fibrinolytic activity and decreased platelet adhesiveness. 37 However, there were no adverse effects on hemodynamic parameters in a safety study. 2

Diabetes
Animal data

In mice with induced diabetes, administration of C. mukul extracts improved glucose tolerance, decreased plasma insulin levels, reduced weight gain, and improved the lipid profile. 38 , 39

Clinical data

Research reveals no clinical trials regarding the use of guggul for diabetes. However, a small trial with 58 adult obese patients demonstrated that diet and guggulu taken over 30 days increased weight loss in patients who weighed more than 90 kg. 40

Endocrine effects
Animal data

In mice with induced hypothyroidism, coadministration of C. mukul extracts reversed the hypothyroid state and increased triiodothyronine levels in euthyroid animals. 41 , 42 In vitro laboratory experiments have shown that guggulsterone is able to bind to mineralocorticoid, glucocorticoid, androgen, and progesterone receptors with either antagonist or agonist action. 43 , 44

Clinical data

Research reveals no clinical trials regarding the use of guggul for endocrine disorders.

Hyperlipidemia
Animal data

Rabbits with induced hyperlipidemia showed decreases of high-density lipoprotein (HDL) and triglycerides after 14 weeks of receiving C. mukul extracts. 45 Studies have shown that the guggulsterones are antagonist ligands for the bile acid receptor farnesoid X receptor, which is activated by bile salts, thus reducing cholesterol. 2 , 46

Clinical data

Limited quality clinical trials have been conducted, with the majority of studies in eastern Indian populations. Reviews of these studies have been published. In most studies, total cholesterol and HDL were reduced. However, in a study conducted in a US population, increases in low-density lipoprotein (LDL) were observed, and case reports of increased LDL with guggul consumption exist. Until larger, long-term quality trials have been conducted and the incidence of adverse events clarified, C. mukul extracts cannot be routinely recommended for the management of hyperlipidemia. 4 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54

Other effects

One small study has shown guggulsterone to be as effective as tetracycline in the treatment of nodulocystic acne. 55 In vitro antibacterial effects have been described. 16

A guggul-based kshar sutra ligation was more effective in healing but was less favored than rubber band ligation of hemorrhoids. 56

Studies have demonstrated the ability of C. wightii extracts (synonymous with C. mukul ) to inhibit the growth of struvite crystals associated with the development of urinary stone/calculi. 57 , 58

Dosage

Clinical trials are lacking to provide dosage guidelines; however, in a US clinical trial in hyperlipidemia, 75 mg to 150 mg of standardized guggulsterones were administered daily. 51 1,000 mg capsules containing 21 mg of guggulsterones were used in this study. In a study evaluating the anti-inflammatory effect of guggul, 500 mg of gum guggul was used 3 times daily. 24

Various formulations (eg, tablets, capsules, powders) of guggul are available. Guggul and gugulipid are typically standardized to provide a fixed amount, normally 2.5% or 3.5%, of guggulsterones. However, liquid chromatography has shown commercial over-the-counter products contain less or none of claimed guggulsterone content. 6 , 7 , 13 Standardization of herbal products is warranted.

Pregnancy/Lactation

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

Interactions

Case reports of any interactions are lacking.

Experiments in rats have shown C. mukul extracts to increase the expression of the cytochrome P450 system. 2 , 44 , 59

Guggul may stimulate thyroid hormone production; dosage adjustment of thyroid medication may be required. 41 Gugulipid reduced bioavailability of propranolol and diltiazem in a single-dose study. 2 , 60 Increased fibrinolytic activity of guggul could potentially add to the risk of bleeding in patients taking anticoagulants/antiplatelet medications. However, no adverse effect on hemodynamic parameters was demonstrated in a safety study. 2 , 37

Adverse Reactions

While the human safety profile of the extract has not been well described for children, pregnant or breast-feeding women, or patients with severe hepatic or renal disease, no adverse events have been reported in clinical studies; the adverse effects were primarily GI-related (diarrhea, nausea) as well as several cases of headache, hiccough, and rash. 2 , 4 , 48 , 52 , 61

In a study evaluating the effect of oral guggulipid on hyperlipidemia, moderate to severe generalized cutaneous reactions were noted in 9% of participants, leading to dropouts from the study. 62 Case reports exist of acute eczematous reactions to guggul-containing creams. 63 , 64

A case report exists of rhabdomyolysis in a patient taking an extract of C. mukul 300 mg 3 times daily who was previously sensitized (increased creatine kinase) to lipid-lowering statins. 59 A similar case report of increased transaminases exists for a combination preparation containing guggulsterol and red yeast rice extract; however, fungal metabolites found in the red yeast rice extract were suspected to be responsible for the adverse effect because the metabolites are structurally similar to lovastatin. The patient had previously experienced hepatotoxicity while taking lovastatin. 65 A case report of hepatotoxicity exists for a combination product (fat burner) that included guggul. 66

Toxicology

Research reveals little information regarding toxicology with the use of guggul. In rats, dogs, and monkeys, no acute, subacute, or chronic toxicity has been reported. No mutagenesis or teratogenicity has been described for gum guggul. 2

Bibliography

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