Herb-Drug Interactions: Guggul

2011

Commiphora wightii (Am.) Bhandari (Burseraceae)

Synonym(s) and related species

Mukul myrrh.

Commiphora mukul Engl., Balsamodendrum wightii.

Constituents

The resinous sap, harvested from the tree bark by tapping, is extracted to produce guggul. Gugulipid is the purified standardised extract of crude gum guggul, and contains the active guggulsterone components Z-guggulsterone and E-guggulsterone, with cembrenoids, myrrhanone and myrrhanol derivatives.

Use and indications

Guggul is used mainly in Ayurvedic medicine and has been traditionally used to treat hypertension, osteoporosis, epilepsy, ulcers, cancer, obesity and rheumatoid arthritis. It is now often used for hyperlipidaemia, but clinical studies have found conflicting results for its lipid-lowering effects.

Pharmacokinetics

An in vitro study reported that gugulipid extract and purified guggulsterones may induce the expression of the cytochrome P450 isoenzyme CYP3A4. However, the clinical significance of this is unclear and further study is needed.

Interactions overview

In healthy subjects, the absorption of diltiazem and propranolol was modestly reduced by gugulipid. If the mechanism is confirmed, guggul might interact with a wide range of other drugs. A case of rhabdomyolysis has been attributed to the use of guggul alone, which should be borne in mind if it is combined with the statins, which also, rarely, cause this adverse effect.

Guggul + Diltiazem

Limited evidence suggests that guggul modestly reduces the absorption of single-dose diltiazem.

Clinical evidence

A crossover study in 7 fasting healthy subjects found that a single 1-g dose of gugulipid reduced the AUC and maximum concentration of a single 60-mg dose of diltiazem by 35% and 41%, respectively. This single dose of diltiazem did not have any effect on blood pressure or heart rate in these particular subjects, so it was not possible to assess the effect of the reduction in levels of diltiazem on its pharmacological effects. No details were given of the gugulipid or diltiazem preparations used.

Experimental evidence

No relevant data found.

Mechanism

Gugulipid is an oleoresin extracted from guggul. The authors of this study suggest that it might bind with drugs in the gut and reduce their absorption in a similar way to colestyramine and colestipol.

Importance and management

Gugulipid modestly reduced the absorption of diltiazem in this study, and this degree of reduction is probably unlikely to be clinically relevant. However, the formulation of diltiazem given was not stated and the effects of multiple dosing, or of larger doses of diltiazem, is unknown. Further study is needed. Bear in mind the potential for an interaction should a patient taking guggul have a reduced response to diltiazem.

Guggul + Food

No interactions found.

Guggul + Herbal medicines

No interactions found.

Guggul + Propranolol

Limited evidence suggests that guggul modestly reduces the absorption of single-dose propranolol.

Clinical evidence

A crossover study in 10 fasting healthy subjects found that a single 1-g dose of gugulipid reduced the AUC and maximum concentration of a single 40-mg dose of propranolol by 34% and 43%, respectively. This single dose of propranolol did not have any effect on blood pressure or heart rate in these particular subjects, so it was not possible to assess the effect of the reduction in levels of propranolol on its pharmacological effects. No details were given of the gugulipid or propranolol preparations used.

Experimental evidence

No relevant data found.

Mechanism

Gugulipid is an oleoresin extracted from guggul. The authors of this study suggest that it might bind with drugs in the gut and reduce their absorption in a similar way to colestyramine and colestipol.

Importance and management

Gugulipid modestly reduced the absorption of propranolol in this study. The clinical relevance of this reduction is not certain, but it is likely to be minor. Bear in mind the potential for an interaction should a patient taking guggul have a reduced response to propranolol.

Guggul + Statins

An isolated case suggests that guggul alone can cause rhabdomyolysis. If statins are also taken, the risk could be additive.

Clinical evidence

A case of rhabdomyolysis has been reported in a patient, 2 weeks after an extract of guggul 300 mg three times daily was started. The rhabdomyolysis resolved when the guggul preparation was stopped. The patient was not reported to be taking any other medication known to cause rhabdomyolysis and simvastatin had been stopped one year previously because of an increase in creatine kinase. The herbal product used was prepared by a local chemist using a standardised drug extract of the oleo gum resin without excipients.

Experimental evidence

No relevant data found.

Mechanism

Not known. The possibility that the resin used was adulterated was not investigated.

Importance and management

This appears to be the only case report of rhabdomyolysis occurring with a guggul-containing preparation. Guggul is widely used for cholesterol lowering, and the most commonly used conventional drugs for this condition are the statins, which are well recognised, rarely, to cause rhabdomyolysis. It is quite likely that guggul and statins are being used together, and the concern generated by this case report is that, if guggul alone can cause rhabdomyolysis, then combined use might increase the risk of rhabdomyolysis. However, this is only one case, and the mechanism (which could include adulteration) is uncertain. Bear the possibility of an additive effect in mind if myositis occurs with concurrent use. All patients taking statins should be warned about the symptoms of myopathy and told to report muscle pain or weakness. It would be prudent to reinforce this advice if they are known to be taking guggul.