Guggul for hyperlipidemia: A review by the Natural Standard Research Collaboration

Massachusetts General Hospital, USA.
Complementary Therapies in Medicine (Impact Factor: 2.22). 01/2006; 13(4):279-90. DOI: 10.1016/j.ctim.2005.08.003
Source: PubMed

ABSTRACT To evaluate the scientific evidence on guggul for hyperlipidemia including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
Electronic searches were conducted in nine databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on language or quality of publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanism of action. Standardized inclusion/exclusion criteria were utilized for selection.
Before 2003, most scientific evidence suggested that guggulipid elicits significant reductions in serum total cholesterol, low-density lipoprotein (LDL), and triglycerides, as well as elevations in high-density lipoprotein (HDL) [Kotiyal JP, Bisht DB, Singh DS. Double blind cross-over trial of gum guggulu (Commiphora mukul) Fraction A in hypercholesterolemia. J Res Indian Med Yoga Hom 1979;14(2):11-6; Kotiyal JP, Singh DS, Bisht DB. Gum guggulu (Commiphora mukul) fraction 'A' in obesity-a double-blind clinical trial. J Res Ayur Siddha 1985;6(1, 3, 4):20-35; Gaur SP, Garg RK, Kar AM, et al. Gugulipid, a new hypolipidaemic agent, in patients of acute ischaemic stroke: effect on clinical outcome, platelet function and serum lipids. Asia Pacif J Pharm 1997;12:65-9; Urizar NL, Liverman AB, Dodds DT, et al. A natural product that lowers cholesterol as an antagonist ligand for the FXR. Science 3 May 2002 [Science Express Reports]; Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India 1989;37(5):323-8; Kuppurajan K, Rajagopalan SS, Rao TK, et al. Effect of guggulu (Commiphora mukul-Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India 1978;26(5):367-73; 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(4):249-51; Agarwal RC, Singh SP, Saran RK, et al. Clinical trial of gugulipid-a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res 1986;84:626-34; Verma SK, Bordia A. Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL-cholesterol. Indian J Med Res 1988;87:356-60; 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):659-64; Ghorai M, Mandal SC, Pal M, et al. A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum gugglu. Phytother Res 2000;14(3):200-02]. However, most published studies were small and methodologically flawed. In August 2003, a well-designed trial reported small significant increases in serum LDL levels associated with the use of guggul compared to placebo [Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290(6):765-72]. No significant changes in total cholesterol, high-density lipoprotein (HDL), or triglycerides were measured. These results are consistent with two prior published case reports [Das Gupta R. Gugulipid: pro-lipaemic effect. J Assoc Physicians India 1990;38(12):346].
The effects of guggulipid in patients with high cholesterol are not clear, with some studies finding cholesterol-lowering effects, and other research suggesting no benefits. At this time, there is not enough scientific evidence to support the use of guggul for any medical condition. Guggul may cause stomach discomfort or allergic rash as well as other serious side effects and interactions. It should be avoided in pregnant or breast-feeding women and in children. Safety of use beyond 4 months has not been well studied.

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    • "). A review of the use of guggul against hyperlipidaemia was published by the Natural Standard Collaboration in 2005 (Ulbricht et al., 2005). "
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    ABSTRACT: Oleo gum resin secreted by Commiphora mukul, also known as gum guggul, has been used widely as an ayurvedic drug. Commiphora mukul is a short thorny shrub that is native to the Indian subcontinent. Oleo gum resin extracted by incision of the bark is a very complex mixture of gum, minerals, essential oils, terpenes, sterols, ferrulates, flavanones and sterones. Its active constituents, the Z- and E-guggulsterones, have been demonstrated to exhibit their biological activities by binding to nuclear receptors and modulating the expression of proteins involved in carcinogenic activities. Guggulsterones have also been reported to regulate gene expression by exhibiting control over other molecular targets including transcription factors such as nuclear factor (NF)-κB, signal transducer and activator of transcription (STAT) and steroid receptors. Considerable scientific evidence indicates the use of gum guggul as a therapeutic agent in the treatment of inflammation, nervous disorders, hyperlipidaemia and associated cardiac disorders such as hypertension and ischaemia, skin disorders, cancer and urinary disorders. This review highlights the taxonomic details, phytochemical properties and pharmacological profile of gum guggul. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 11/2012; 26(11):1594-605. DOI:10.1002/ptr.4647 · 2.40 Impact Factor
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    • "ex Tschirch is used as an effective antimicrobial agent, as an herbal remedy for sore throats, canker sores and gingivitis. Myrrh is also used as a healing tonic, as a stimulant and as a hypolipidemic agent (Urizar et al. 2002; Wu et al. 2002; Ulbright et al. 2005). Traditionally , myrrh is used for the common cold, to relieve nasal congestion and coughing. "
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    ABSTRACT: Commiphora wightii (Arn.) Bhandari syn. C. mukul Engl. (Burseraceae) is an economically and pharmacologically important slow growing, dioecious, balsamiferous woody, multipurpose shrub heading towards extinction. Commonly known as “Guggul” due to the presence of steroidal compound guggulsterone in the oleo-gum resin, it has been used in treating various ailments and disorders since ancient times (2000 B.C.). Evaluation and confirmation of hypolipidemic effects of guggul based on Ayurvedic text in 1960s provided a new insight into its pharmacological applications. Two bioactive isomers of guggulsterone, E and Z, are responsible for lipid- and cholesterol-lowering activities. Recently, it has been shown to have anti-cancerous activity also. It is found in the dry regions of Indian subcontinent, namely India, Pakistan and Bangladesh. Ruthless and unscientific harvesting of oleo-gum resin from the wild, by local populations, for economic benefits with negligible conservation efforts has made this species endangered and has led to its inclusion in Red Data Book of IUCN. Although this plant has many excellent traits, adequate attention has not been focused on its conservation and improvement. Conventional propagation methods i.e., seeds, cuttings and air layering are in place but have many limitations. Therefore, application of modern biotechnological tools needs to be standardized for harnessing maximum benefits from this pharmaceutically important plant. An efficient regeneration system needs to be in place for improvement of this genus through genetic transformation and production of useful metabolites in cell cultures. Studies are in progress for micropropagation through shoot multiplication and somatic embryogenesis, as well as for secondary metabolite (guggulsterone) production in callus cultures and bioreactors. No selected germplasm is available for C. wightii since it is a wild plant. Breeding programs have not yet been started due to lack of systematic cultivation and conservation programs. Moreover, little information has been gathered regarding the genetic variability in this species using RAPD and ISSR markers. No details are available about genetic makeup and QTL linkage maps. Investigations are in progress to search sex linked markers in this dioecious species. Research is also in progress to decipher the molecular mechanisms underlying various pharmacological actions of guggul. Since the approval of use of guggul as a food supplement by United States Food and Drug Administration in 1994, an exponential increase in research publications on various aspects of research on guggul have been published. Present communication summarizes the problems, progress made and suggests some future directions of research for this important endangered medicinal plant.
    Genetic Resources and Crop Evolution 08/2012; 59(6). DOI:10.1007/s10722-012-9854-2 · 1.48 Impact Factor
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    • "For the subjects (45 participants) with high baseline levels of LDL (160 mg/dL or greater), gugulipid treatment significantly reduced serum triglyceride (14% and 10% decreases for the high-and low-dose groups, respectively), whereas triglyceride levels increased by 10% in subjects receiving placebo. The results from this study indeed raised a question regarding the hypocholesterolemic effect of the therapy (Szapary et al. 2003; Ulbricht et al. 2005). Several possible explanations were discussed for the discrepancy from prior trials. "
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    ABSTRACT: Oleogum resin (known as guggul) from the guggul tree, Commiphora mukul, found in India, Bangladesh, and Pakistan, has been used to treat various diseases including hyper-cholesterolemia, atherosclerosis, rheumatism, and obesity over several thousands of years. Guggulsterone isolated from guggul has been identified as the bioactive constituent responsible for guggul's therapeutic effects. Since the first study demonstrating the therapeutic effects of guggul in an animal model in 1966, numerous preclinical and clinical trails have been carried out. Although differences in study design, methodological quality, statistical analysis, sample size, and subject population result in certain inconsistencies in the response to therapy, the cumulative data from in vitro, preclinical, and clinical studies largely support the therapeutic claims for guggul described in the ancient Ayurvedic text. However, future clinical studies with much larger size and longer term are required to confirm these claims. The cardiovascular benefits of the therapy are derived from the multiple pharmacological activities associated with guggul or guggulsterone, notably its hypolipidemic, antioxidant, and antiinflammatory activities. It has been established that guggulsterone is an antagonist at farnesoid x receptor (FXR), a key transcriptional regulator for the maintenance of cholesterol and bile acid homeostasis. The FXR antagonism by guggulsterone has been proposed as a mechanism for its hypolipidemic effect. A recent study demonstrates that guggulsterone upregulates the bile salt export pump (BSEP), an efflux transporter responsible for removal of cholesterol metabolites, bile acids from the liver. Such upregulation of BSEP expression by guggulsterone favors cholesterol metabolism into bile acids, and thus represents another possible mechanism for its hypolipidemic activity. Guggulsterone has been found to potently inhibit the activation of nuclear factor-kappaB (NF-kappaB), a critical regulator of inflammatory responses. Such repression of NF-kappaB activation by guggulsterone has been proposed as a mechanism of the antiinflammatory effect of guggulsterone.
    Cardiovascular Drug Reviews 02/2007; 25(4):375-90. DOI:10.1111/j.1527-3466.2007.00023.x · 5.21 Impact Factor
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