Plant Part Used
Resin
Active Constituents
Oleoresin (guggulsterones Z and E)(1),(2)
[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]
Introduction
Guggul oleoresin has been used in the Indian (Ayurvedic) medical system for centuries as an anti-arthritic, carminative, antispasmodic, diaphoretic, and aphrodisiac.(3) It has also been described as an agent for treating obesity and other eating disorders including “coating and obstruction of channels.”(3)
In the early 1960s, researchers began to explore the ancient Sanskrit description of guggul being used by Ayurvedic physicians in the management of lipid disorders. After years of research and scientific studies, guggul was approved for marketing in India in 1986 as a lipid-lowering drug.(1) Guggul is also frequently used in India for the management of arthritis and inflammatory conditions.(4)
Interactions and Depletions
Interactions
- propranolol
- diltiazem
- Antihyperlipidemic medications
- Anticoagulant medications
- Antiplatelet medications
- Thyroid medications
- Chemotherapeutic Drugs – components of guggul have been reported to inhibit P-glycoprotein metabolism of chemotherapy drugs, including doxorubicin, increasing the effects of these medications.(14)
Dosage Info
Dosage Range
500-1000mg (standardized extract), 3 times a day.
Most Common Dosage
500mg (standardized extract), 3 times a day.
Standardization
[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]
The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 2.5-10% guggulsterones Z and E.
Uses
Frequently Reported Uses
- Hypercholesterolemia
- Atherosclerosis
- Weight Management
Other Reported Uses
- Anti-Inflammatory.
- Arthritis
- Cancer therapy adjunct
- Antibacterial/antifungal
Toxicities & Precautions
General
Guggul is reported to be safe in recommended doses.
Health Conditions
Based on pharmacology, use with caution in individuals with hyperthyroidism.
Side Effects
Some individuals may experience transient side effects such as minor GI distress, skin rash, diarrhea, and nausea. Allergic contact dermatitis has been reported when using topical guggul extract in several case reports.(15),(16)
Pregnancy/ Breast Feeding
Based on pharmacology, use with caution in individuals who are pregnant.
Age Limitations
Do not use in children under 2 years of age unless recommended by a physician.
Pharmacology
Cholesterol Lowering
Guggul oleoresin has been the subject of clinical studies in the management of lipid disorders.(5),(6),(7) Studies report that guggul lowers both cholesterol and triglyceride levels and also alters lipoproteins by lowering LDL and VLDL levels while increasing HDL.(10) Guggul preparations are reported to be most useful in Type IIb (increased LDL, VLDL, and triglycerides) and Type IV (increased VLDL and triglycerides) hyperlipidemias.
In one clinical study of 205 patients using guggul for hypercholesterolemia, serum lipid levels were lowered an average of 23.6 percent in a 12 week period, while triglyceride levels were lowered an average of 22.6 percent.(6) Another double-blind study compared the use of guggul to clofibrate (Lopid) in 125 patients.(6) The average fall in serum cholesterol and triglycerides in patients treated with guggul was 11 and 16.8 percent, respectively and with clofibrate, 10 and 21.6 percent respectively. HDL cholesterol was increased in 60 percent of cases responding to guggulipid therapy.
The lipid lowering effects of guggul may be explained by four proposed mechanisms of action.(9),(10) First, guggul reportedly inhibits the biosynthesis of cholesterol in the liver, interfering with the formation of lipoproteins (LDL, VLDL). Secondly, it may increase the fecal excretion of bile acids and cholesterol, resulting in a low rate of absorption of fat and cholesterol in the intestines. Thirdly, it is claimed to stimulate the LDL receptor binding activity in the liver cellular membranes, reducing serum LDL levels. Lastly, guggul reportedly stimulates thyroid function, which may lead to blood lipid lowering and weight loss.(10) In addition to its lipid lowering effects, guggul has been reported to prevent the formation of atherosclerosis and aid in the regression of pre-existing atherosclerotic plaques in animals.(11) Guggul has also been reported to inhibit platelet aggregation and have fibrinolytic activity, as well as being an excellent antioxidant, preventing the heart from being damaged by free radicals.(12)
Antiinflammatory
Guggul has also been reported to be a potent anti-inflammatory agent and has been compared to pharmaceutical agents, such as ibuprofen. Guggul was claimed to be comparable to NSAIDs, decreasing the thickness of the joint swelling during the course of drug treatment.(13) Laboratory studies have found that guggulsterones inhibit tissue factor (TF) expression in vascular cells as well as thrombus formation in vivo, impairing vascular smooth muscle cell activation.(17) The results suggest guggul may be a therapeutic option to inflammatory diseases associated with an increased risk of thrombosis. Other laboratory studies have reported inhibitory effects of guggulsterones on interleukin (IL)-1beta-induced inflammatory responses, suggesting guggulsterones may be beneficial in joint destruction in patients with rheumatoid arthritis.(18) Guggulsterones also have been reported to potently inhibit the activation of nuclear factor-kappaB (NF-kappaB), a critical regulator of inflammatory responses.(19)
Guggulsterones have been found to inhibit osteoclastogenesis and bone resporption induced by receptor activator of nuclear factor-kappaB ligand, suggesting a potential use of guggulsterones in preventing age-related bone loss.(20)
Other Uses
The guggulsterones are being researched for their anticancer activity in various human cancer cell lines, and positive laboratory studies include treating head and neck, prostate and colon cancers.(21) An in vitro study found that use of guggulsterones in conjunction with the monoclonal antibody cetuximab increased inhibition of STAT3 and HIF-1alpha, helping to increase the apoptosis of head and neck cancer cells.(22) Other laboratory studies have reported z-guggulsterone inhibits growth of human prostate cancer cells by apoptosis and by inhibiting angiogenesis in vivo and in vitro. z-Guggulsterone was reported to inhibit angiogenesis by suppressing the vascular endothelial growth factor (VEGF-VEGF-R2-Akt) signaling axis.(23) Also, multidrug resistance can be a major problem in cancer chemotherapy. Guggulsterones have been reported in laboratory studies to inhibit P-glycoprotein, leading to increased cell killing ability of chemotherapy agents such as doxorubicin.(14) Further research needs to be performed to determine the clinical significance of this interaction.
Guggul may also help with blood sugar regulation. Laboratory animal studies have reported that mice treated with guggul extract lowered fasting blood glucose and plasma insulin levels, partly due to guggul’s PPARalpha/gamma agonism.(24) The authors also report that guggul’s cholesterol lowering ability may be in part due to stimulation of activated liver X receptor alpha (LXRalpha).
Read More
1) Ayuverda
References
- Satyavati GV, et al. Experimental Studies on the Hypocholesterolemic Effect of Commiphora Mukul. Indian J Med Res. 1969;57(10):1950-62.
- View Abstract: Mesrob B, Nesbitt C, Misra R, et al. 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. Dec1998;720(1-2):189-96.
- Satyavati GV. Gum Guggul (Commiphora Mukul)–The Success Story of an Ancient Insight Leading to a Modern Discovery. Indian J Med Res. 1988;87:327-35.
- View Abstract: 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. May2003;9(3):74-9.
- View Abstract: Singh RB, et al. Hypolipidemic and Antioxidant Effects of Commiphora Mukul as an Adjunct to Dietary Therapy in Patients with Hypercholesterolemia. Cardiovasc Drugs Ther. 1994;8(4):659-64.
- View Abstract: Nityanand S, et al. Clinical Trials with Gugulipid. A New Hypolipidaemic Agent. J Assoc Physicians India. 1989;37(5):323-28.
- Agarwal RC, et al. Clinical Trial of Gugulipid–a New Hypolipidemic Agent of Plant Origin in Primary Hyperlipidemia. Indian J Med Res. 1986;84:626-34.
- View Abstract: Singh V, et al. Stimulation of Low Density Lipoprotein Receptor Activity in Liver Membrane of Guggulsterone Treated Rats. Pharmacol Res. 1990;22(1):37-44.
- Verma SK, et al. Effect of Commiphora Mukul (Gum Guggulu) in Patients of Hyperlipidemia with Special Reference to HDL-Cholesterol. Indian J Med Res. Apr1988;87:356-60.
- Tripathi YB, et al. Thyroid Stimulatory Action of (Z)-Guggulsterone: Mechanism of Action. Planta Med. 1988;54(4):271-77.
- Baldwa VS, et al. Effects of Commiphora Mukul (Guggul) in Experimentally Induced Hyperlipidemia and Atherosclerosis. J Assoc Physicians India. 1981;29(1):13-17.
- Satyavati GV, et al. Guggulipid: A Promising Hypolipidemic Agent from Gum Guggul (Commiphora Wightii). Econ Med Plant Res. 1991;5:48-82.
- View Abstract: Sharma JN, et al. 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. Arzneim-Forsch/Drug Res. Jul1977;27(7):1455-57.
- Xu HB, Li L, Liu GQ. Reversal of P-glycoprotein-mediated multidrug resistance by guggulsterone in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. Pharmazie. Oct 2009;64(10):660-665.
- Kölönte A, Guillot B, Raison-Peyron N. Allergic contact dermatitis to guggul extract contained in an anticellulite gel-cream. Contact Dermatitis. Apr 2006;54(4):226-227. No abstract available.
- 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. May 2007;56(5):286-287. No abstract available.
- Gebhard C, Stämpfli SF, Gebhard CE, et al. Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis. Basic Res Cardiol. May 2009;104(3):285-294. Epub 2008 Oct 24.
- Lee YR, Lee JH, Noh EM, et al. Guggulsterone blocks IL-1beta-mediated inflammatory responses by suppressing NF-kappaB activation in fibroblast-like synoviocytes. Life Sci. 6 Jun 2008;82(23-24):1203-1209. Epub 2008 Apr 20.
- Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev. Winter 2007;25(4):375-390. Review.
- 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. 15 Jan 2006;12(2):662-668.
- An MJ, Cheon JH, Kim SW, Kim ES, Kim TI, Kim WH. Guggulsterone induces apoptosis in colon cancer cells and inhibits tumor growth in murine colorectal cancer xenografts. Cancer Lett. 28 Jun 2009;279(1):93-100. Epub 2009 Feb 18.
- 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. Nov 2009;30(11):1848-1856. Epub 2009 Sep 16.
- Xiao D, Singh SV. z-Guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo. Mol Cancer Ther. Jan 2008;7(1):171-180.
- 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. Oct 2009;20(10):806-815. Epub 2008 Oct 15.
