Scientific Name(s): Commiphora mukul Hook. ex Stocks. Family: Burseraceae.
Common Name(s): Guggul , guggal , gum guggal , gum guggulu , gugulipid
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.
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.
None identified. Caution may be warranted in patients previously experiencing adverse effects to statins.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
None well documented.
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.
Research reveals little information regarding toxicology with the use of guggul.
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
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
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 PharmacologyAnti-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 , 18Animal 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. 23Clinical 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
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
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. 35Clinical 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. 2Diabetes
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. 40Endocrine effects
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 , 44Clinical data
Research reveals no clinical trials regarding the use of guggul for endocrine disorders.Hyperlipidemia
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 , 46Clinical 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 , 54Other effects
A guggul-based kshar sutra ligation was more effective in healing but was less favored than rubber band ligation of hemorrhoids. 56
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.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Case reports of any interactions are lacking.
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
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
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
Bibliography1. Commiphora mukul . USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , 30 June 2011). National Plant Data Team, Greensboro, NC 70874-4490 USA.
2. Shishodia S, Harikumar KB, Dass S, Ramawat KG, Aggarwal BB. The guggul for chronic diseases: ancient medicine, modern targets. Anticancer Res . 2008;28(6A):3647-3664.
3. Satyavati GV. Gum guggul ( Commiphora mukul )—the success story of an ancient insight leading to a modern discovery. Indian J Med Res . 1988;87:327-335.
4. Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev . 2007;25(4):375-390.
5. Duke JA. CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 2002.
6. Mesrob B, Nesbitt C, Misra R, Pandey RC. High-performance liquid chromatographic method for fingerprinting and quantitative determination of E- and Z-guggulsterones in Commiphora mukul resin and its products. J Chromatogr B Biomed Sci Appl . 1998;720(1-2):189-196.
7. Nagarajan M, Waszkuc TW, Sun J. Simultaneous determination of E- and Z-guggulsterones in dietary supplements containing Commiphora mukul extract (guggulipid) by liquid chromatography. J AOAC Int . 2001;84(1):24-28.
8. Cui J, Huang L, Zhao A, et al. Guggulsterone is a farnesoid X antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem . 2003;278(12):10214-10220.
9. Urizar NL, Liverman AB, Dodds DT, et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science . 2002;296(5573):1703-1706.
10. Wu J, Xia C, Meier J, Li S, Hu X, Lala DS. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol . 2002;16(7):1590-1597.
11. Kimura I, Yoshikawa M, Kobayashi S, et al. New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice. Bioorg Med Chem Lett . 2001;11(8):985-989.
12. Su SL, Duan JA, Tang YP, et al. Isolation and biological activities of neomyrrhaol and other terpenes from the resin of Commiphora myrrha . Planta Med . 2009;75(4):351-355.
13. Ahmed R, Ali Z, Wu Y, et al. Chemical characterization of a commercial Commiphora wightii resin sample and chemical profiling to assess for authenticity. Planta Med . 2011;77(9):945-950.
14. Sumantran VN, Kulkarni AA, Harsulkar A, et al. Hyaluronidase and collagenase inhibitory activities of the herbal formulation Triphala guggulu . J Biosci . 2007;32(4):755-761.
15. Francis JA, Raja SN, Nair MG. Bioactive terpenoids and guggulusteroids from Commiphora mukul gum resin of potential anti-inflammatory interest. Chem Biodivers . 2004;1(11):1842-1853.
16. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of traditional Iranian medicine for inflammatory bowel disease. World J Gastroenterol . 2010;16(36):4504-4514.
17. Song JJ, Kwon SK, Cho CG, Park SW, Chae SW. Guggulsterone suppresses LPS induced inflammation of human middle ear epithelial cells (HMEEC). Int J Pediatr Otorhinolaryngol . 2010;74(12):1384-1387.
18. Manjula N, Gayathri B, Vinaykumar KS, Shankernarayanan NP, Vishwakarma RA, Balakrishnan A. Inhibition of MAP kinases by crude extract and pure compound isolated from Commiphora mukul leads to down regulation of TNF-alpha, IL-1beta and IL-2. Int Immunopharmacol . 2006;6(2):122-132.
19. Duwiejua M, Zeitlin IJ, Waterman PG, Chapman J, Mhango GJ, Provan GJ. Anti-inflammatory activity of resins from some species of the plant family Burseraceae. Planta Med . 1993;59(1):12-16.
20. Sharma JN, Sharma JN. Comparison of the anti-inflammatory activity of Commiphora mukul (an indigenous drug) with those of phenylbutazone and ibuprofen in experimental arthritis induced by mycobacterial adjuvant. Arzneimittelforschung . 1977;27(7):1455-1457.
21. Khanna D, Sethi G, Ahn KS, et al. Natural products as a gold mine for arthritis treatment. Curr Opin Pharmacol . 2007;7(3):344-351.
22. Mencarelli A, Renga B, Palladino G, Distrutti E, Fiorucci S. The plant sterol guggulsterone attenuates inflammation and immune dysfunction in murine models of inflammatory bowel disease. Biochem Pharmacol . 2009;78(9):1214-1223.
23. Kalariya NM, Shoeb M, Reddy AB, Zhang M, van Kuijk FJ, Ramana KV. Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone. Invest Ophthalmol Vis Sci . 2010;51(10):5105-5113.
24. Singh BB, Mishra LC, Vinjamury SP, Aquilina N, Singh VJ, Shepard N. The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther Health Med . 2003;9(3):74-79.
25. Macha MA, Matta A, Chauhan SS, Siu KW, Ralhan R. Guggulsterone targets smokeless tobacco induced PI3K/Akt pathway in head and neck cancer cells. PLoS One . 2011;6(2):e14728.
26. Shishodia S, Sethi G, Ahn KS, Aggarwal BB. Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. Biochem Pharmacol . 2007;74(1):118-130.
27. Leeman-Neill RJ, Wheeler SE, Singh SV, et al. Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis . 2009;30(11):1848-1856.
28. Xiao D, Singh SV. z-Guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul , inhibits angiogenesis in vitro and in vivo. Mol Cancer Ther . 2008;7(1):171-80.
29. Singh SV, Zeng Y, Xiao D, et al. Caspase-dependent apoptosis induction by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul , in PC-3 human prostate cancer cells is mediated by Bax and Bak. Mol Cancer Ther . 2005;4(11):1747-1754.
30. Singh SV, Choi S, Zeng Y, Hahm ER, Xiao D. Guggulsterone-induced apoptosis in human prostate cancer cells is caused by reactive oxygen intermediate dependent activation of c-Jun NH2-terminal kinase. Cancer Res . 2007;67(15):7439-7449.
31. Xiao D, Zeng Y, Prakash L, Badmaev V, Majeed M, Singh SV. Reactive oxygen species-dependent apoptosis by gugulipid extract of Ayurvedic medicine plant Commiphora mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase. Mol Pharmacol . 2011;79(3):499-507.
32. Sarfaraz S, Siddiqui IA, Syed DN, Afaq F, Mukhtar H. Guggulsterone modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in SENCAR mice. Carcinogenesis . 2008;29(10):2011-2018.
33. Ichikawa H, Aggarwal BB. Guggulsterone inhibits osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand and by tumor cells by suppressing nuclear factor-kappaB activation. Clin Cancer Res . 2006;12(2):662-668.
34. Ojha SK, Nandave M, Arora S, et al. Effect of Commiphora mukul extract on cardiac dysfunction and ventricular function in isoproterenol-induced myocardial infarction. Indian J Exp Biol . 2008;46(9):646-652.
35. Kaul S, Kapoor NK. Cardiac sarcolemma enzymes and liver microsomal cytochrome P450 in isoproterenol treated rats. Indian J Med Res . 1989;90:62-68.
36. Miller AL. Botanical influences on cardiovascular disease. Altern Med Rev . 1998;3(6):422-431.
37. Bordia A, Chuttani SK. Effect of gum guggulu on fibrinolysis and platelet adhesiveness in coronary heart disease. Indian J Med Res . 1979;70:992-996.
38. Sharma B, Salunke R, Srivastava S, Majumder C, Roy P. Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats. Food Chem Toxicol . 2009;47(10):2631-2639.
39. Cornick CL, Strongitharm BH, Sassano G, et al. Identification of a novel agonist of peroxisome proliferator-activated receptors alpha and gamma that may contribute to the anti-diabetic activity of guggulipid in Lep(ob)/Lep(ob) mice. J Nutr Biochem . 2009;20(10):806-815.
40. Bhatt AD, Dalal DG, Shah SJ, et al. Conceptual and methodologic challenges of assessing the short-term efficacy of Guggulu in obesity: data emergent from a naturalistic clinical trial. J Postgrad Med . 1995;41(1):5-7.
41. Panda S, Kar A. Guggulu ( Commiphora mukul ) potentially ameliorates hypothyroidism in female mice. Phytother Res . 2005;19(1):78-80.
42. Tripathi YB, Malhotra OP, Tripathi SN. Thyroid stimulating action of Z-guggulsterone obtained from Commiphora mukul . Planta Med . 1984;50(1):78-80.
43. Burris TP, Montrose C, Houck KA, et al. The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand. Mol Pharmacol . 2005;67(3):948-954.
44. Brobst DE, Ding X, Creech KL, Goodwin B, Kelley B, Staudinger JL. Guggulsterone activates multiple nuclear receptors and induces CYP3A gene expression through the pregnane X receptor. J Pharmacol Exp Ther . 2004;310(2):528-535.
45. Khanna N, Arora D, Halder S, et al. Comparative effect of Ocimum sanctum , Commiphora mukul , folic acid and ramipril on lipid peroxidation in experimentally-induced hyperlipidemia. Indian J Exp Biol . 2010;48(3):299-305.
46. Yu BZ, Kaimal R, Bai S, et al. Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod . 2009;72(1):24-28.
47. Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India . 1989;37(5):323-328.
48. Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther . 1994;8(4):659-664.
49. Thompson Coon JS, Ernst E. Herbs for serum cholesterol reduction: a systematic review. J Fam Pract . 2003;52(6):468-478.
50. Sahni S, Hepfinger CA, Sauer KA. Guggulipid use in hyperlipidemia: case report and review of the literature. Am J Health Syst Pharm . 2005;62(16):1690-1692.
51. Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA . 2003;290(6):765-772.
52. Hasani-Ranjbar S, Nayebi N, Moradi L, Mehri A, Larijani B, Abdollahi M. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Curr Pharm Des . 2010;16(26):2935-2947.
53. Nohr LA, Rasmussen LB, Straand J. Resin from the mukul myrrh tree, guggul, can it be used for treating hypercholesterolemia? A randomized, controlled study. Complement Ther Med . 2009;17(1):16-22.
54. Shields KM, Moranville MP. Guggul for hypercholesterolemia. Am J Health Syst Pharm . 2005;62(10):1012-1014.
55. Thappa DM, Dogra J. Nodulocystic acne: oral gugulipid versus tetracycline. J Dermatol . 1994;21(10):729-731.
56. Singh R, Arya RC, Minhas SS, Dutt A. A comparative study of Barron's rubber band ligation with Kshar Sutra ligation in hemorrhoids. Int J Ayurveda Res . 2010;1(2):73-81.
57. Chauhan CK, Joshi MJ, Vaidya AD. Growth inhibition of struvite crystals in the presence of herbal extract Commiphora wightii . J Mater Sci Mater Med . 2009;20 (suppl 1):S85-S92.
58. Raut AA, Sunder S, Sarkar S, Pandita NS, Vaidya AD. Preliminary study on crystal dissolution activity of Rotula aquatica , Commiphora wightii and Boerhaavia diffusa extracts. Fitoterapia . 2008;79(7-8):544-547.
59. Bianchi A, Cantú P, Firenzuoli F, Mazzanti G, Menniti-Ippolito F, Raschetti R. Rhabdomyolysis caused by Commiphora mukul , a natural lipid-lowering agent. Ann Pharmacother . 2004;38(7-8):1222-1225.
60. Dalvi SS, Nayak VK, Pohujani SM, Desai NK, Kshirsagar NA, Gupta KC. Effect of gugulipid on bioavailability of diltiazem and propranolol. J Assoc Physicians India . 1994;42(6):454-455.
61. Antarkar DS, Pande R, Athavale AV, et al. Phase I tolerability study of Yogaraj-guggulua-popular ayurvedic drug. J Postgrad Med . 1984;30(2):111-115.
62. Gelfand JM, Crawford GH, Brod BA, Szazpary PO. Adverse cutaneous reactions to guggulipid. J Am Acad Dermatol . 2005;52(3, pt 1):533-534.
63. Salavert M, Amarger S, Le Bouedec MC, Roger H, Souteyrand P, D'incan M. Allergic contact dermatitis to guggul in a slimming cream. Contact Dermatitis . 2007;56(5):286-287.
64. Kölönte A, Guillot B, Raison-Peyron N. Allergic contact dermatitis to guggul extract contained in an anticellulite gel-cream. Contact Dermatitis . 2006;54(4):226-227.
65. Grieco A, Miele L, Pompili M, et al. Acute hepatitis caused by a natural lipid-lowering product: when “alternative” medicine is no “alternative” at all. J Hepatol . 2009;50(6):1273-1277.
66. Yellapu RK, Mittal V, Grewal P, Fiel M, Schiano T. Acute liver failure caused by fat burners' and dietary supplements: a case report and literature review. Can J Gastroenterol . 2011;25(3):157-160.
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