Health Care Professional Information

Scientific Name
Commiphora mukul
Common Name

Gum guggal, gum guggulu, Guggal

Clinical Summary

Guggul is derived from the resin of a medicinal plant that has been used for thousands of years in Ayurveda. Extracts of the plant are traditionally used alone and in combination with other botanicals to treat various clinical disorders including rheumatism, arthritis, neurological diseases, hemorrhoids, urinary disorders, and skin diseases.

Recent interest to determine the ability of guggul to treat obesity and related disorders of lipid metabolism has led to many studies.
Guggul was shown to protect against isoprenaline-induced cardiotoxicity in a study of rats (16). Results from clinical trials suggest comparable effectiveness of guggul to Clofibrate in reducing cholesterol and total lipid count (1) (2); but one trial showed that guggul may actually raise cholesterol levels (3). However, conclusions from a systematic review suggest effectiveness of guggul for hypercholesterolemia (11). Further research is warranted.

In vitro and in vivo (4) studies suggest that guggulsterone, a sterol from guggul, has anti-angiogenic (7) and anti-tumor properties, inducing cell cycle arrest and apoptosis in a variety of tumor cells (5) including those resistant to chemotherapy (6).
 

Purported Uses
  • Acne
  • Arthritis
  • Hemorrhoids
  • High cholesterol
  • Rheumatoid arthritis
  • Urinary tract disorders
  • Weight loss
Constituents

E- and Z-guggulsterone
Pregnane derivatives [cis- and trans-4,17(20)-pregnadiene-3,16-dione]
Cembrenes
(17) (18)

Mechanism of Action

In vitro studies point to the effect of guggulsterone on the biosynthesis of cholesterol in the liver (2). Another study proposes that the cholesterol-lowering activity of guggulsterone in mice comes from its inhibition of FXR, a nuclear hormone receptor that is activated by bile acids. FXR mediates a negative feedback loop that decreases the rate of bile acid production by the liver. This loop is an important component in the regulation of cholesterol metabolism (10). Hypolipidemic outcomes may be better in individuals with a relatively higher capacity of metabolizing Z-guggulsterone with moderate carboxylesterase (CES1) induction (19). Guggulsterone activates nuclear receptors such as estrogen receptor alpha, pregnane X receptor, and progesterone receptor and may induce CYP3A genes (8).
In tumor cells, guggulsterone induces apoptosis by activating JNK (5) and repressing Akt signaling (6).

Adverse Reactions

Reported: Headache, mild nausea, eructation, hiccough, and loose stools (2). Hypersensitivity rash (3).
Case report: A sixty-three year old woman developed severe hypertransaminasemia following use of Equisterol, an over-the-counter lipid-lowering product containing guggulsterol and red yeast rice extract, for six months. Her symptoms normalized after equisterol was discontinued (12).
Cases of allergic contact dermatitis to guggul in slimming and anticellulite creams have been reported (13) (14).

Case report: Fulminant hepatic failure requiring liver transplantation has been reported in a healthy woman who took a dietary supplement containing usnic acid, green tea and guggul tree extract (15).

Herb-Drug Interactions

Anticoagulants/Antiplatelets: Due to potential anticoagulant and antiplatelet effects, guggul theoretically may potentiate the effects of aspirin, NSAIDs and warfarin.
Thyroid supplements: Guggul may have thyroid stimulating activities. (2)
Cytochrome P450 enzymes: Guggul induces CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme. (8)

Herb Lab Interactions

Reduced serum triglycerides (2)
Elevated TSH, T3 and T4 (9)

Literature Summary and Critique

Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, DerMarderosian AH, Cirigliano MD et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290:765-72.
A clinical trial of 103 patients with hypercholesterolemia. Patients were randomly chosen to receive either 1 gram guggulipid, 2 grams guggulipid or placebo three times daily for eight weeks. Patients in both of the guggulipid groups failed to show any lowering of total cholesterol, HDL cholesterol, triglycerides or VLDL cholesterol. Furthermore, patients treated with guggulipid were found to have statistically significant increases in LDL cholesterol levels when compared with those in the placebo group. Researchers suggest that the diet or genetic makeup of patients in previous Indian trials of guggulipid may have accounted for some of the perceived cholesterol-lowering effects. Researchers also suggest that previous studies did not use the standard ultracentrifugation technique to directly measure levels of LDL cholesterol.

Dosage (Inside MSKCC Only)
This field is only visible to only OneMSK users.
References
  1. Kuppurajan K, et al. Effect of guggulu (Commiphora mukul—Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India 1978;26:367-73.
  2. 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;8:659-64.
  3. Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290:765-72.
  4. 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. Aug 5 2008.
  5. 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. Aug 1 2007;67(15):7439-7449.
  6. 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. Jun 30 2007;74(1):118-130.
  7. 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.
  8. 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. Aug 2004;310(2):528-535.
  9. DerMarderosian A, editor. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999.
  10. Urizar NL, et. al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 2002 May 31;296(5573):1703-6.
  11. Singh BB, Vinjamury SP, Der-Martirosian C, et al. Ayurvedic and collateral herbal treatments for hyperlipidemia: a systematic review of randomized controlled trials and quasi-experimental designs. Altern Ther Health Med. 2007 Jul-Aug;13(4):22-8.
  12. 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 Jun;50(6):1273-7.
  13. Salavert M, Amarger S, Le Bouedec MC, et al. Allergic contact dermatitis to guggul in a slimming cream. Contact Dermatitis. 2007 May;56(5):286-7.'
  14. Kölönte A, Guillot B, Raison-Peyron N. Allergic contact dermatitis to guggul extract contained in an anticellulite gel-cream. Contact Dermatitis. 2006 Apr;54(4):226-7.
  15. 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 Mar;25(3):157-60.
  16. Ojha S, Bhatia J, Arora S, Golechha M, Kumari S, Arya DS. Cardioprotective effects of Commiphora mukul against isoprenaline-induced cardiotoxicity: a biochemical and histopathological evaluation.J Environ Biol. 2011 Nov;32(6):731-8.
  17. Urizar NL, Moore DD. GUGULIPID: a natural cholesterol-lowering agent.Annu Rev Nutr. 2003;23:303-13.
  18. Bai S, Jain M. 1H and 13C assignments of five cembrenes from guggul.Magn Reson Chem. 2008 Aug;46(8):791-3.
  19. Yang D, Yang J, Shi D, et al.Hypolipidemic agent Z-guggulsterone: metabolism interplays with induction of carboxylesterase and bile salt export pump.J Lipid Res. 2012 Mar;53(3):529-39.

Consumer Information

How It Works

Bottom Line: Guggul has been shown effective in lowering cholesterol levels.

Guggul is a resin extract that has been used in Ayurvedic medicine for centuries. Scientists do not know exactly how guggul works. In laboratory experiments, a chemical in guggul called guggulsterone affects the production of cholesterol by the liver. Mice that are fed guggul have reduced levels of cholesterol synthesis by the liver compared to mice fed normal diets. A few clinical trials have suggested that dietary guggul can reduce blood cholesterol levels in humans.

Purported Uses
  • To treat acne
    No scientific evidence supports this use for guggul alone. See the Ayurveda monograph for more information on the treatment of acne.
  • To treat osteoarthritis and rheumatoid arthritis
    There are no data to back this claim.
  • To treat hemorrhoids
    No scientific evidence supports this use.
  • To reduce high cholesterol
    Guggul was shown in clinical trials to reduce high cholesterol.
  • To treat urinary tract disorders
    There are no data to support this claim.
  • To lose weight
    Clinical data are lacking to support this claim.
Research Evidence

High Cholesterol:
One hundred and three adults with hypercholesterolemia participated in this trial of guggul. Subjects were randomly assigned to receive either standard dose guggulipid, high-dose guggulipid or placebo for eight weeks. Total cholesterol levels did not change significantly for adults treated with guggulipid. Furthermore, levels of LDL (“bad”) cholesterol increased significantly in the groups treated with guggulipid when compared with those in the placebo group. Researchers suggest that previous trials did not measure LDL cholesterol levels accurately. Other possible areas of discrepancy include differences in diet or genetic makeup of subjects.

Do Not Take If
  • You are taking warfarin, aspirin, NSAIDs or other blood thinners (In theory, guggul may increase the risk of bleeding. Take with caution and ask your doctor).
  • You are taking thyroid supplements, have hyperthyroidism or hypothyroidism (Guggul may stimulate the thyroid gland).
  • You are taking drugs that are substrates of Cytochrome P450 3A4 (Guggul may make the drugs less effective).
Side Effects
  • Headache
  • Mild nausea
  • Belching
  • Hiccoughs
  • Loose stools
  • Rash
  • Case report: A sixty-three year old woman developed severe hypertransaminasemia following use of Equisterol, an over-the-counter lipid-lowering product containing guggulsterol and red yeast rice extract, for six months. Her symptoms normalized after equisterol was discontinued.
    Cases of allergic contact dermatitis to guggul in slimming and anticellulite creams have been reported.
    Case report: Fulminant hepatic failure requiring liver transplantation has been reported in a healthy woman who took a dietary supplement containing usnic acid, green tea and guggul tree extract.
E-mail your questions and comments to aboutherbs@mskcc.org.