Summary of Guggul
Primary Information, Benefits, Effects, and Important Facts
Guggul is a plant which is known for its active ingredients, the guggulsterones. It has been traditionally used for combatting ailments such as high blood lipids, liver dysfunction and obesity.
Its most well marketed effect, that of being able to increase thyroid activity, does not occur with doses commonly found in supplements. It does, however, exert an anti-cholesterolemic effect (lowers blood cholesterol levels) and is also an anti-inflammatory and anti-oxidant compound.
It is a healthy compound, but not effective for the main means it is marketed for (fat loss).
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Things To Know & Note
The plant guggul had both water soluble and fat soluble fragments; the active guggulsterones are fat soluble.
'Dermatological Hypersensitivity' (adverse skin reactions) have been associated with Guggul and Guggulipid consumption
How to Take Guggul
Recommended dosage, active amounts, other details
A standard dose of guggul (plant extract) is 400-500mg taken thrice daily with meals, totaling 1,200-1,500mg daily (although doses up to 2,000mg have been used before) If using the guggulsterones in isolation, a dose of 25mg taken thrice a day with meals is used.
Sometimes 'gum guggul' is used in doses of 2-4.5g a day (total), and while it is not sure if guggul needs to be consumed with meals it still tends to be recommended out of prudency.
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Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects guggul has on your body, and how strong these effects are.
|Grade||Level of Evidence [show legend]|
|Robust research conducted with repeated double-blind clinical trials|
|Multiple studies where at least two are double-blind and placebo controlled|
|Single double-blind study or multiple cohort studies|
|Uncontrolled or observational studies only|
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
|Minor||Moderate See 2 studies|
|Minor||Moderate See 2 studies|
|Minor||Moderate See 2 studies|
|-||Very High See 2 studies|
|-||- See study|
|Minor||- See study|
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Research Breakdown on Guggul
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Guggul is also known as the plant Commiphora Mukul, an medicine from Ayurveda once touted to cure a myriad of diseases and ailments such as obesity, liver dysfunction, tumors, urinary dysfunction, sinus, edema, and sudden paralytic seizures.
The 'guggul' is isolated from the bark of the guggul tree and is a mixture of various diterpenes, sterols, flavanones and steroid esters. It is most well known for a fat soluble mixture called 'guggulsterones', which are two sterols (Guggulsterone E and Z) with high human bioactivity.
As a herbal supplement, Guggul contains a variety of molecules including:
Using the whole plant, approximately 45% of the compound is classified as ethyl-acetate soluble (fat soluble) whereas 55% of the compound is insoluble in ethyl-acetate ( and thus water soluble). Guggulsterones appear to be fat-soluble, and the fat soluble portion is patented as Guggulipid when standardized to 2.5% Guggulsterones. Another fragment of the Guggul plant also appears to be patented for anti-diabetic purposes.
There appears to be high variability in active guggulsterone (E and Z) content between various plants due to growing conditions and cross-pollination, thus when using the whole plant one batch may differ from others.
One rat study showed the Guggulsterone Z, at a dose of 10mg/kg bodyweight, increased iodine uptake and metabolic activity of the thyroid gland.
The mechanisms of action of guggulsterone Z in this regard is unlike Thyroid-Stimulating Hormone and is not pituitary mediated. It was shown (again, at 10mg/kg bodyweight) to increase serum T3 and T4 levels. (It should be noted that this dose is much higher than what is customarily used in herbal supplements).
Guggulsterones have been noted to reduce hepatic (liver) cholesterol in mice via antagonism of the Farnesoid X (FXR) receptor when the cholesterol is introduced in the diet.
The mechanism of action seems to be through decreasing bile acid secretion and synthesis (via inhibiting the rate limiting enzyme of bile acid synthesis from cholesterol, cholesterol 7alpha-hydroxylase, via Pregnasane X Receptor (PXR) activation) and uptaking less cholesterol from the diet due to less bile acids. In this particular scenario, the lack of degradation of cholesterol into bile salts also causes a hepatic increase in cholesterol, although serum decreases are noted. In other situations (in which bile salts agonism the Bile Salt export Pump) guggulsterones seem to actually act synergistically with bile acts. Guggulsterones seem to be a highly regulator bile acid and cholesterol compound via modulation of FXR and BSEP.
Guggulsterones may also lower serum cholesterol by enhancing hepatic reuptake of cholesterol by stimulating hepatic LDL receptors.
The hypolipidemic effects of Guggul are the effects of guggul most supported by the literature, as they have extended past preclinical rodent and vitro studies. According to Shishodia et al. most clinical human trials show on average a 20% decrease in serum TGs and cholesterol, with positive benefits being seen in 70-80% of patients. A high inter-individual variation was noted at the recommended dosage of either 400-500mg plant extract or 25mg guggulsterones, both 2-3 times a day with meals. The effects of the patented extract 'Gugulipid' are more ambiguous.
Through inhibition of P-glycoprotein efflux in breast cancer cells, guggulsterones have been implicated at increasing chemosensitivity to doxorubicin in drug-resistant breast cancer cells. The 11.48-fold improvement seen at 10uM was similar in potency to 10uM of the pharmaceutical standard verapamil, which displayed 13.23-fold improvement, and 10uM guggulsterones paired with 10uM doxorubicin increased the cytotoxicity of the latter by 6.15-fold despite not demonstrating anti-cancer effects on its own.
Guggul is able to suppress the activation of NF-kB via interfereing with various activators such as hydrogen peroxide, TNF-a, phorbol ester and cigarette smoke. NF-kB, a transcription factor, is known as a significant pro-inflammatory and pro-carcinogenic metabolic lever in cells, and its inhibition of activation is typically associated with reduced risks of various forms of cancers.
Guggulsterones also appear to reduce circulating levels of pro-inflammatory cytokines and markers such as IL-1b, IL-2, and TNF-a. Guggulsterones are also able to reduce CycloOxygenase-2 (COX2) mRNA levels and suppress its TNFa mediated induction (activation).
One human intervention noted that, out of 22 persons receiving 2160mg Guggul daily for 12 weeks, that 10 (45%) experienced some manner of side effect. Most (7) were gastrointestinal distress while 2 reported adverse interactions with either their Thyroxin medication or their state of hypothyroidism as these 2 persons reported fatigue; the last instance was a skin rash. These 2 instances of thyroid interaction were hypothesized to be either due to more rapid metabolism of thyroid hormones, which Guggul has been shown to do or through interacting with bioavailability like it has been demonstrated with the drugs propanolol and diltiazem. This study, however, used a supplement containing Guggul alongside Ginger (25mg), Black Pepper (25mg), and parts of both Terminalia chebula and Terminalia belerica.
Skin rashes have been reported in other trials using 1-2g Guggulipid (ethyl acetate fraction standardized to 2.5% Guggulsterones) daily for a month, but this particular trial did not note intestinal distress.
- Shishodia S, et al. The guggul for chronic diseases: ancient medicine, modern targets. Anticancer Res. (2008)
- Zhu N, et al. Bioactive constituents from gum guggul (Commiphora wightii). Phytochemistry. (2001)
- Hanus LO, et al. Myrrh--Commiphora chemistry. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. (2005)
- Development of Biotechnology for Commiphora wightii : A Potent Source of Natural Hypolipidemic and Hypocholesterolemic Drug.
- Tonkal AM, Morsy TA. An update review on Commiphora molmol and related species. J Egypt Soc Parasitol. (2008)
- Method of treating a cognitive memory dysfunction using Gugulipid.
- Food compositions for reducing insulin resistance.
- Apomixis and Polyembryony in the Guggul Plant, Commiphora wightii.
- Tripathi YB, Malhotra OP, Tripathi SN. Thyroid Stimulating Action of Z-Guggulsterone Obtained from Commiphora mukul. Planta Med. (1984)
- Tripathi YB, et al. Thyroid stimulatory action of (Z)-guggulsterone: mechanism of action. Planta Med. (1988)
- Urizar NL, et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science. (2002)
- Owsley E, Chiang JY. Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene. Biochem Biophys Res Commun. (2003)
- The Hypolipidemic Agent Guggulsterone Regulates the Expression of Human Bile Salt Export Pump: Dominance of Transactivation over Farsenoid X Receptor-Mediated Antagonism.
- Stimulation of low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats.
- Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev. (2007)
- Guggul: An excellent herbal panacea.
- Hypolipidemic and antioxidant effects of commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia.
- Ulbricht C, et al. Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration. Complement Ther Med. (2005)
- Xu HB, Li L, Liu GQ. Reversal of multidrug resistance by guggulsterone in drug-resistant MCF-7 cell lines. Chemotherapy. (2011)
- Shishodia S, Aggarwal BB. Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J Biol Chem. (2004)
- Ichikawa H, Aggarwal BB. Guggulsterone inhibits osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand and by tumor cells by suppressing nuclear factor-kappaB activation. Clin Cancer Res. (2006)
- Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. (2004)
- Manjula N, et al. Inhibition of MAP kinases by crude extract and pure compound isolated from Commiphora mukul leads to down regulation of TNF-alpha, IL-1beta and IL-2. Int Immunopharmacol. (2006)
- Lv N, et al. Guggulsterone, a plant sterol, inhibits NF-kappaB activation and protects pancreatic beta cells from cytokine toxicity. Mol Cell Endocrinol. (2008)
- Macha MA, et al. Guggulsterone targets smokeless tobacco induced PI3K/Akt pathway in head and neck cancer cells. PLoS One. (2011)
- Macha MA, et al. 14-3-3 zeta is a molecular target in guggulsterone induced apoptosis in head and neck cancer cells. BMC Cancer. (2010)
- Leeman-Neill RJ, et al. Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis. (2009)
- 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. (2009)
- Dalvi SS, et al. Effect of gugulipid on bioavailability of diltiazem and propranolol. J Assoc Physicians India. (1994)
- Szapary PO, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. (2003)
- Singh BB, et al. The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther Health Med. (2003)