Guggul

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

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

Uses of Guggul

Traditionally used to treat arthritis, obesity, and other disorders, guggul has been shown to lower cholesterol and triglycerides and to stimulate thyroid activity in a few small studies.

Guggul Dosing

Hypercholesterolemia:75 to 150 mg standardized guggulsterones daily. Obesity: Guggulu 250 mg 3 times/day. Acne: Gugulipid (standardized to 25 mg guggulsterone) twice daily for 3 months. Dosage adjustment of thyroid medication may be necessary.

Contraindications

Do not use in patients who are on propranolol or diltiazem. Use with caution by patients taking thyroid medication.

Pregnancy/Lactation

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

Guggul Interactions

During coadministration, gugulipid significantly reduces propranolol and diltiazem bioavailability. Guggul can also potentially add to bleeding risk in patients taking anticoagulants/antiplatelet medications.

Guggul Adverse Reactions

Adverse GI effects have been reported.

Toxicology

Research reveals little or no information regarding toxicology with the use of guggul.

Botany

The guggul plant is widely distributed throughout India and adjacent regions. It is in the same genus as C. myrrha , the myrrh mentioned in the Bible. Guggul and gum guggulu are the names given to a yellowish resin produced by the stem of the plant.

History

The plant has been used in traditional Ayurvedic medicine for centuries in the treatment of a variety of disorders, 1 most notably arthritis, and as a weight-reducing agent in obesity. 2 More recently, extracts of the plant have been investigated for their ability to reduce serum lipid levels. A commercial product ( Guggulow ) has been introduced in the US claiming the cholesterol-lowering properties of the plant. This has raised interest in the activity of the plant.

Chemistry

The majority of the published research studies on the plant and its extracts have originated in India. 3 Guggul contains resin, volatile oils, and gum. Several pharmacologically active components have been identified in the plant, including guggulsterones (E- and Z-stereoisomers) 4 and gugulipid, both found in the ethyl acetate extract of the plant. 5 , 6 , 7 Studies have shown that the guggulsterones are antagonist ligands for the bile acid receptor (BAR) farnesoid X receptor (FXR), which is activated by bile salts, thus reducing cholesterol. 8 , 9 , 10 A new triterpene, myrrhanol A, has been discovered to have potent anti-inflammatory effects. 11

Guggul Uses and Pharmacology

Hypolipidemia
Animal data

Research reveals no animal data regarding the use of guggul for hypolipidemia.

Clinical data

When treated with 500 mg gugulipid for 12 weeks, a lowering of serum cholesterol (24% average) and serum triglycerides (23% average) was observed in 80% of patients. 12 A crossover follow-up to this preliminary investigation compared gugulipid with the antihyperlipidemic drug clofibrate (eg, Atromid-S ) in 233 patients. With gugulipid, the average fall in serum cholesterol and triglycerides was 11% and 17%, respectively. These effects were evident within 3 to 4 weeks of starting therapy. Hypercholesterolemic patients responded better to the gugulipid therapy than did hypertriglyceridemic patients. High-density lipoprotein (HDL) cholesterol increased in 60% of responders to gugulipid therapy. Clofibrate had no effect on this parameter. 12

A 24-week, double-blind, placebo-controlled study of gugulipid involving 61 patients resulted in a decrease in total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides compared with no changes in the placebo group. 13

One study of healthy subjects conducted in the United States demonstrated a reduction in total serum cholesterol. 3

Obesity

Guggulsterone has been shown to stimulate thyroid activity. 14 This effect has been used to promote gugulipid as a weight loss product that increases the body's rate of metabolism.

Animal data

Research reveals no animal data regarding the use of guggul for obesity.

Clinical data

A small trial with 58 adult obese patients demonstrated that diet and guggulu taken over 30 days showed increased weight loss in patients who weighed more than 90 kg. 15

Cardiac and fibrinolytic effects

Guggulsterone has been shown to exert a protective effect on cardiac enzymes and the cytochrome P450 system against drug-induced myocardial necrosis. 16

Animal data

Research reveals no animal data regarding the use of guggul for cardiac and fibrinolytic effects.

Clinical data

Commiphora mukul in combination with Inula racemosa (another Ayurvedic botanical) was studied in 200 patients with ischemic heart disease. It was found to improve patients' ECG readings and decrease episodes of dyspnea and chest pain. 17 Gum guggul fraction increased fibrinolytic activity and decreased platelet adhesiveness. 18

Anti-inflammatory effects
Animal data

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

Clinical data

A recent outcome study in 30 patients showed significant improvement ( P < 0.0001) in osteoarthritis symptoms after taking 500 mg Commiphora mukul 3 times per day with food for 1 month. 21

Acne
Animal data

Research reveals no animal data regarding the use of guggul for acne.

Clinical data

One small study has shown guggulsterone to be as effective as tetracycline in the treatment of nodulocystic acne. 22

Dosage

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

Hypercholesterolemia

75 to 150 mg standardized guggulsterones daily. 3 , 15 , 23

Obesity

Guggulu 250 mg 3 times/day. 15

Acne

Gugulipid (standardized to 25 mg guggulsterone) twice daily for 3 months. 22

Pregnancy/Lactation

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

Interactions

Guggul may stimulate thyroid hormone production; dosage adjustment of thyroid medication may be required. 14

Gugulipid has been shown to reduce bioavailability of propranolol and diltiazem. Cross-class effects are unknown. Concomitant use should be avoided. 24

Increased fibrinolytic activity of guggul can potentially add to the risk of bleeding in patients taking anticoagulants/antiplatelet medications. 18

Adverse Reactions

While the human safety profile (including children, pregnant or nursing women, and patients with severe hepatic or renal disease) of the extract has not been well described, no significant adverse events were reported in clinical studies; the adverse effects were primarily GI and several cases of headache, hiccup, and rash. 1 , 3 , 13

Toxicology

Research reveals little or no information regarding toxicology with the use of guggul.

Bibliography

1. Antarkar DS, Pande R, Athavale AV, et al. Phase I tolerability study of Yogaraj-guggulu—a popular ayurvedic drug. J Postgrad Med . 1984;30:111-115.
2. 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.
3. Thompson Coon JS, Ernst E. Herbs for serum cholesterol reduction: a systematic review. J Fam Pract . 2003;52:468-478.
4. Singh V, Kaul S, Chander R, Kapoor NK. Stimulation of low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats. Pharmacol Res . 1990;22:37-44.
5. Gopal K, Saran RK, Nityanand S, et al. Clinical trial of ethyl acetate extract of gum gugulu (gugulipid) in primary hyperlipidemia. J Assoc Physicians India . 1986;34:249-251.
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;720:189-196.
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;84:24-28.
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;278:10214-10220.
9. Urizar NL, Liverman AB, Dodds DT, et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science . 2002;296:1703-1706.
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;16:1590-1597.
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;11:985-989.
12. Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India . 1989;37:323-328.
13. 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;8:659-664.
14. Tripathi YB, Malhotra OP, Tripathi SN. Thyroid stimulating action of Z-guggulsterone obtained from Commiphora mukul . Planta Med . 1984;1:78-80.
15. 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;41:5-7.
16. Kaul S, Kapoor NK. Cardiac sarcolemma enzymes and liver microsomal cytochrome P450 in isoproterenol treated rats. Indian J Med Res . 1989;90:62-68.
17. Miller AL. Botanical influences on cardiovascular disease. Altern Med Rev . 1998;3:422-431.
18. 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.
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;59:12-16.
20. 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;27:1455-1457.
21. 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;9:74-79.
22. Thappa DM, Dogra J. Nodulocystic acne: oral gugulipid versus tetracycline. J Dermatol . 1994;21:729-731.
23. Morelli V, Zoorob RJ. Alternative therapies: Part II. Congestive heart failure and hypercholesterolemia. Am Fam Physician . 2000;62:1325-1330.
24. 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;42:454-455.
25. Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA . 2003;290:765-772.

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