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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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Commiphora mukul, Commiphora Wightii, Guggulsterones, pregna-4,17-diene-3,16-dione
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.
The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Guggul has in your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
|Level of Evidence ||Effect||Change||Magnitude of Effect Size ||Scientific Consensus||Comments|
Possible decrease in total cholesterol, but this is unreliable (and paired with a possible increase in LDL-C, this is likely to be not desirable)
Either no significant change associated with Guggul supplementation or a small decrease is observed
Although unreliable, there is a possible increase in LDL cholesterol from Guggul supplementation
See 2 studies
No significant influence of Guggul on triglycerides is detectable
No significant influence on vLDL cholesterol levels
|D||Symptoms of Osteoarthritis|
Possible reductions in the symptoms associated with osteoarthritis
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).
Guggulsterones may be able to suppress carcinogenic growth in head and neck cells from smokeless (chewing) tobacco, according to preliminary in vitro results. Guggulsterones seem to have special mechanisms for head and neck anti-carcinogenesis.
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.
(Common misspellings for Guggul include gugglesterone, googlesterone, gugglusterone, google, guggle)
(Common phrases used by users for this page include guggulsterone reviews, guggulsterone pharmacokinetics anti obesity mechanisms, guggulsterone 25mg, guggul supplements thyroid, guggul breast cancer, commiphora mukul review article)