What are Guggulsterones?
Guggulsterones are the active components in an extract called gugulipid. Gugulipid is an extract of a gum resin from the tree Commiphora mukul. The term guggulsterones is used to collectively refer to two isomers, namely, E- and Z-guggulsterone. Gugulipid has been marketed in India as a hypolipidenic agent since 1988. In Ayurveda medicine, gugulipd is an anti-hyperlipdmic drug, characterized by cis (E)- and trans (Z)- stereoisomers. It was first isolated from the ethyl acetate fraction of gum resin of Commiphora mukul (known as Guggul) and considered as the active constituent of Guggul1-3. In 1986, with the proven efficacy and safety, the ethyl acetate extract of gum resin known as ‘Guggul’ was approved for marketing in India as an antihyperlipidemic drug and it is currently marketed in the USA and Western world as a dietary supplement4-6.
Where Does Guggulsterone Come From?
Known as the guggul tree, Commiphora mukul is a member of the Burseraceae family and is found in arid areas of India, Bangladesh, and Pakistan6. A small, bushy tree with thorny branches, it produces a yellowish gum resin in small ducts located throughout its bark. Each collecting season a guggul tree yields between 250–500 grams of dry resin, which is extracted from the bark through a process called tapping. In this process, an incision is made on the bark of the tree. The resin, which then seeps out, is allowed to harden before it is collected. The tree is tapped in the months of November to January and the resin is collected through May or June16.
In Ayurveda, the Indian traditional system of medicine, the gum resin from the tree Commiphora mukul has been used for thousands of years in the treatment of arthritis, inflammation, obesity, and disorders of lipid metabolism6. Multiple studies in animals and humans have shown that administration of guggulsterones can significantly lower both serum low-density lipoprotein (LDL) cholesterol and triglycerides. More specifically, the guggulsterones isomers act as antagonist ligands for the bile acid receptor termed, farnesoid X receptor (FXR). FXR is an important regulator of cholesterol homeostasis. Guggulsterones action on FXR is thought to account for its hypolipodemic activity16. Further, these isomers have also been shown to exhibited potential antioxidant, antiarthritic, anti-inflammatory, memory enhancing and anti-cancer pharmacological activities10-15.
Guggulsterones Negative Side Effects
Gugulipid, the ethyl acetate extract of gum guggul, is reported to be devoid of any adverse side effects on liver function, kidney function, or in hematological parameters when administered at a dose of 400 mg per day for four weeks17. From a medical perspective, guggulsterone is likely to interact with the many drugs whose metabolism is increased in response to pregnane X receptor (PXR) activation. PXR is a nuclear hormone receptor that regulates the expression of several key liver enzymes, called cytochrome P450. Therefore, gugulipid should be used only with caution in combination with other drugs.
Guggulsterones Recommended Dosages & Timing
The typical dosage used in studies depends on whether crude gum guggul or an extract of gum guggul is given. Studies using crude gum guggul typically use between 3 and 4 grams, whereas studies using the extract typically use between 0.5 and 1g gram.
Guggulsterones do not feature prominently in many sports nutrition products. However, when included, it is most often is a fat-loss type product due to its lipid lowering properties.
Guggulsterones are not commonly stacked with any other ingredient.
Studies have shown that guggulsterones in gugulipid have the potential to affect the bioavailability of other drugs. For instance administration of gugulipid at a single dose of one gram to 17 healthy volunteers significantly reduced peak plasma concentration of diltiazem and propranolol, which are used for the treatment of cardiovascular disease18. It is likely that this decrease is due to an increase in their metabolic rate, as it has been shown in rats that administration of guggulsterone significantly increases the expression of cytochrome P450 genes, which are responsible for metabolizing most of the drugs taken today19.1. Dev SA. Modern look at an age old Ayurvedic drug—guggul. Science Age. 1987; 13–18.
2. Satyavati GV, Dwarakanath C and Tripathi SN. Experimental studies on the hypocholesterolemic effect of Commiphora mukul. Engl. (Guggul). Indian Journal of Medical Research 1969; 57: 1950–1962.
3. Urizar NL & Moore DD. GUGULIPID: a natural cholesterol-lowering agent. Annual Review of Nutrition 2003; 23: 303–313.
4. Antarkar D, et al. Phase I tolerability study of Yogaraj-guggulu—a popular ayurvedic drug. Journal of Postgraduate Medicine. 1984;30:111–115.
5. Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovascular Drug Review. 2007;25:375–390.
6. Satyavati GV. Gum guggul (Commiphora mukul)—the success story of an ancient insight leading to a modern discovery. Indian Journal of Medical Research. 1988;87:327–335.
7. Cui J, et al. Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. Journal of Biological Chemistry 2003;278:10214–10220.
8. Mester L, et al. Inhibition of platelet aggregation by ‘guggulu’ steroids. Planta Medica. 1979;37:367–369.
9. Wu J, et al. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Molecular Endocrinology.2002;16:1590–1597.
10. Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovascular Drug Review. 2007;25:375–390.
11. Leeman N, et al. Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis. 2009;30:1848–1856.
12. Pratap R et al. Method of treating a cognitive memory dysfunction using Gugulipid. Patent no. 6896901, 2005.
13. Saxena G, et al. Gugulipid, anextract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice. Pharmacology and Biochemistry of Behaviour. 2007;86:797– 805.
14. Singh BB, et al. The effectiveness of Commiphoramukul for osteoartherisis of knee: an outcomes study. Alternative Therapies in Health and Medicine 2003;9:74–79.
15. Singh K, et al. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovascular Drugs Therapy 1997;8:659–664.
16. Urizar NL, Moore DD. GUGULIPID: a natural cholesterol-lowering agent. Annu Rev Nutr. 2003;23:303-31.
17. Agarwal RC, et al. Clinical trial of gugulipid—a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res.1986;84:626–634.
18. Dalvi SS, et al. Effect of gugulipid on bioavailability of diltiazem and propranolol. J. Assoc. PhysiciansIndia. 1994;42:454–455.
19. Kaul S & Kapoor NK. Cardiac sarcolemma enzymes and liver microsomal cytochrome P450 in isoproterenol treated rats. Indian J Med Res. 1989;90:62–68.