How It Works
Bottom Line: Guggul may be able to lower blood cholesterol levels, but the long-term health effects of this botanical are not known. There is no evidence that guggul can treat any other medical conditions.
Guggul is a tree resin extract that has been used in Ayurvedic medicine for centuries. Scientists do not know exactly how guggul works, and little research has been performed with this botanical. In laboratory experiments, a chemical in guggul called guggulsterone affects the production cholesterol by the liver. Mice that are fed guggul have reduced levels of cholesterol synthesis by the liver compared to mice fed normal diets. A handful of clinical trials have suggested that dietary guggul can reduce blood cholesterol levels in humans.
Purported Uses
- To treat acne
No scientific evidence supports this use for guggul alone. See the Ayurveda monograph for more information on the treatment of acne with botanical combinations.
- To treat osteoarthritis and rheumatoid arthritis
No scientific evidence supports this use.
- To treat hemorrhoids
No scientific evidence supports this use.
- To reduce high cholesterol
Results are mixed.
- To treat urinary tract disorders
No scientific evidence supports this use.
- To lose weight
No scientific evidence supports this use.
Research Evidence
Most clinical trials with guggul have been performed at hospitals in India:
High cholesterol:
A randomized controlled trial studied the effects of a low-cholesterol diet with or without guggul on lowering high cholesterol (>200 mg/dl). For six months, 61 patients were randomly assigned to take 50 mg of guggulipid two times a day, while the other hald took a placebo pill two times a day. It was found that the diet alone caused a significant decrease in LDL ("bad") and total cholesterol and triglycerides in both groups, but those treated with the guggulipid adjunct had an even greater reduction, nearly twice as much as with the diet alone.
One hundred and twenty obese, hypercholesterolemic or hyperlipemic patients were randomly split into the following four groups: (1) 2 grams three times a day 'purified' guggulu (according to Ayurvedic texts), (2) 500 mg twice a day of Fraction 'A' of petroleum ether extract of gum guggulu, (3) a placebo pill or (4) 500 mg three times a day of clofibrate (a drug to lower cholesterol). Patients with high cholesterol who took Fraction 'A' had a significant decrease in blood cholesterol and triglyceride levels, the same as that acheived with clofibrate.
One hundred and three adults with hypercholesterolemia in the Philadelphia, PA metropolitan area participated in a trail of guggul. Subjects were randomly assigned to receive either standard dose guggulipid, high-dose guggulipid or placebo for eight weeks. Total cholesterol levels did not change significantly for adults treated with guggulipid. Furthermore, levels of LDL ("bad") cholesterol increased significantly in the groups treated with guggulipid when compared with those in the placebo group. Researchers suggest that prior trials done India did not measure LDL cholesterol levels accurately. Other possible areas of discrepency include differing diet or genetic makeup of subjects in Indian trials.
Warnings
- This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. The product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
Do Not Take If
- You are taking warfarin, aspirin, NSAIDs or other blood thinners (In theory, guggul may increase the risk of bleeding. Take with caution and ask your doctor).
- You are taking thyroid supplements, have hyperthyroidism or hypothyroidism (Guggul may stimulate the thyroid gland).
Side Effects
- Headache
- Mild nausea
- Belching
- Hiccoughs
- Loose stools
- Rash
Scientific Name
Commiphora mukul
Common Name
Gum guggal, gum guggulu, Guggal
Clinical Summary
Derived from resins of the tree. Guggul is the English name for a medicinal plant that has been used for thousands of years in Ayurveda. Extracts of the plant are traditionally used alone and in combination with other botanicals to treat various clinical disorders including rheumatism, arthritis, neurological diseases, hemorrhoids, urinary disorders and skin diseases. Recent interest has arisen regarding the ability of guggul to treat obesity and related disorders of lipid metabolism. A handful of clinical trials suggest comparable effectiveness to clofibrate in reducing cholesterol and total lipid count
(4) (5), however, one trial suggests that guggul may actually raise cholesterol levels
(9). This herb has received little attention outside of India, where nearly all of the studies have been conducted and reported. Guggul appears to be relatively safe, although minor side effects, mainly gastrointestinal, are reported. A recent study showed that guggulsterone activates nuclear receptors such as pregnane receptor which leads to expression of
CYP3A genes. Since
CYP3A4 encodes cytochrome P450 that is involved in metabolizing 60% of drugs, patients taking guggulsterone should be cautious while taking medications that are metabolized by the CYP3A proteins
(10).
Purported uses
- Acne
- Arthritis
- Hemorrhoids
- High cholesterol
- Rheumatoid arthritis
- Urinary tract disorders
- Weight loss
Constituents
Some pharmacologically active components have been identified, including guggulsterone and gugulipid.
(7)
Mechanism of Action
Exact mechanism is unknown. In vitro studies point to the effect of guggulsterone on the biosynthesis of cholesterol in the liver
(5). Another recent study proposes that the cholesterol-lowering activity of guggulsterone in mice comes from its inhibition of FXR, a nuclear hormone receptor that is activated by bile acids. FXR mediates a negative feedback loop that decreases the rate of bile acid production by the liver. This loop is an important component in the regulation of cholesterol metabolism
(8). According to a recent study, guggulsterone activates nuclear receptors such as estrogen receptor a, pregnane X receptor, and progesterone receptor. The study also showed that activation of pregnane receptor by guggulsterone led to induction of CYP3A genes in vitro
(10).
Adverse Reactions
Reported: Headache, mild nausea, eructation, hiccough, and loose stools
(5). Hypersensitivity rash
(9).
Herb-Drug Interactions
Anticoagulants/Antiplatelets: Due to potential anticoagulant and antiplatelet effects, guggul theoretically may potentiate the effects of aspirin, NSAIDs and warfarin.
Thyroid supplements: Guggul may have thyroid stimulating activities.
(5)Guggul can induce CYP3A4 activity and may interact with substances metabolized by the same enzyme.
(10)
Lab Interactions
Reduced serum cholesterol
Reduced serum triglycerides
(5)Elevated TSH, T3 and T4
(7)
Literature Summary and Critique
Singh RB, et al. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia.
Cardiovasc Drugs Ther 1994;8:659-64.
This randomized, double-blind study divided 61 patients aged 25-65 years with serum cholesterol levels >200 mg/dl into two groups. Throughout the study, both groups were advised to eat at least 400 g/day of fruits and vegetables and had other dietary restrictions aimed to lower their cholesterol levels. One group was given 50 mg guggulipid BID for 24 weeks followed by a 12 week washout period. The second group was given a placebo in place of the guggulipid. While the diet alone caused a significant decrease in total cholesterol, LDL and triglycerides in both groups, those treated with the guggulipid adjunct had significant further reduction of nearly twice as much as with the diet alone. The washout period results further pointed to guggulipid as the producer of the noted effect.
Kuppurajan K, et al. Effect of guggulu (Commiphora mukul—Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases.
J Assoc Physicians India 1978;26:367-73.
This clinical trial divided 120 patients into obese, hypercholesterolemic or hyperlipemic groups, which were further divided into 21-day treatment arms of: (1) 2 g three TID 'purified' guggulu (according to Ayurvedic texts), (2) 500 mg BID Fraction 'A' of petroleum ether extract of gum guggulu, (3) placebo or (4) 500 mg TID clofibrate. Significant reduction in serum cholesterol and total lipids were seen in the Fraction 'A' treatment arm in the hypercholesterolemic group. The reduction was comparable to that seen with clofibrate. Other significant reductions occurred in other treatment arms, but larger, focused studies are needed to replicate this data.
Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, DerMarderosian AH, Cirigliano MD et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290:765-72. A clinical trial of 103 patients with hypercholesterolemia. Patients were randomly chosen to receive either 1 gram guggulipid, 2 grams guggulipid or placebo three times daily for eight weeks. Patients in both of the guggulipid groups failed to show any lowering of total cholesterol, HDL cholesterol, triglycerides or VLDL cholesterol. Furthermore, patients treated with guggulipid were found to have statistically significant increases in LDL cholesterol levels when compared with those in the placebo group. Researchers suggest that the diet or genetic makeup of patients in previous Indian trials of guggulipid may have accounted for some of the perceived cholesterol-lowering effects. Researchers also suggest that previous studies did not use the standard ultaracentrifugation technique to directly measure levels of LDL cholesterol.
References
- 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.
- Satyavati GV, Dwarakanath C, Tripathi SN. Experimental studies on the hypocholesterolemic effect of Commiphora mukul. Engl. (Guggul). Indian J Med Res 1969;57:1950-62.
- Malhotra SC, Ahuja MM, Sundaram KR. Long term clinical studies on the hypolipidaemic effect of Commiphora mukul (Guggulu) and clofibrate. Indian J Med Res 1977;65:390-5.
- Kuppurajan K, et al. Effect of guggulu (Commiphora mukul--Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India 1978;26:367-73.
- 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;8:659-64.
- Scartezzini P, Speroni E. Review on some plants of Indian traditional medicine with antioxidant activity. J Ethnopharmacol 2000;71:23-43.
- DerMarderosian A, editor. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999.
- Urizar NL, et. al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 2002 May 31;296(5573):1703-6.
- Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, DerMarderosian AH, Cirigliano MD et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290:765-72.
- Dan E, et al. Guggulsterone activates multiple nuclear receptors and induces CYP3A gene expression through the pregnane X receptor. JPET 2004;310:528-535.
