Guggul

• How It Works

  Studies on whether guggul can lower cholesterol levels are mixed.

  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 cholesterol levels compared with mice that have normal diets.

  In humans however, studies on whether guggul can lower cholesterol levels are mixed. One study suggests it may actually raise cholesterol levels. Therefore, additional study is needed to determine whether guggul is safe and effective.

• Purported Uses
  • To treat acne
    Evidence is lacking to support this claim for guggul alone. See the Ayurveda monograph for more information on the treatment of acne.
  • To treat osteoarthritis and rheumatoid arthritis
    Evidence is lacking to support this claim.
  • To treat hemorrhoids
    Evidence is lacking to support this claim.
  • To reduce high cholesterol
    Studies on whether guggul can lower cholesterol levels are mixed.
  • To treat urinary tract disorders
    Evidence is lacking to support this claim.
  • To lose weight
    Evidence is lacking to support this claim.
• 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, or 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
  • Hiccups
  • Loose stools
  • Rash

  Case reports

  • Elevated liver enzymes: In a 63-year old woman after using an over-the-counter lipid-lowering product for 6 months that contained guggulsterol and red yeast rice extract. Her symptoms normalized after the product was discontinued.
  • Allergic reactions: Contact dermatitis related to guggul in slimming and anticellulite creams.
  • Liver failure requiring transplant: In a healthy woman who took a dietary supplement containing usnic acid, green tea, and guggul tree extract.
• Scientific Name

  Commiphora mukul

• 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.

  Studies on the safety and efficacy of guggul are limited. In an animal study, guggul had protective effects against cardiotoxicity ⁽¹⁶⁾.

  A few human studies suggest guggul may be effective for hypercholesterolemia ^{(1) (2) (11)}. However, other trials showed that guggul may have uncertain benefit ⁽²⁰⁾, or actually raise cholesterol levels ⁽³⁾. Additional research is needed to determine safety and efficacy.

  In vitro and in vivo ⁽⁴⁾ studies suggest that guggulsterone, a sterol from guggul, has antiangiogenic ⁽⁷⁾ and antitumor 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
• 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

  Headache, mild nausea, eructation, hiccups, and loose stools; hypersensitivity rash ^{(2) (3) (20)}

  Case reports

  • Severe hypertransaminasemia: In a 63-year old woman after using an over-the-counter lipid-lowering product for 6 months that contained guggulsterol and red yeast rice extract. Her symptoms normalized after the product was discontinued  ⁽¹²⁾.
  • Allergic reactions: Contact dermatitis attributed to guggul in slimming and anticellulite creams  ^(13) (14).
  • Fulminant hepatic failure requiring transplant: 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⁾

• 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. 2008 Oct;29(10):2011-8.

  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.

  20. 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. Jan 2009;17(1):16-22.