Myrrh (Commiphora molmol) Clinical Summary Traditional usage Myrrh is perhaps best known for its historical role in many religion traditions as an ingredient in anointing oils, incense and an embalming ointment. It was also used as a highly valued perfume. Myrrh has a long history of use as an antiseptic and astringent and used to treat problems of the mouth, gum and throat and digestive tonic. Myrrh was a common ingredient in toothpowders and for parasites. Actions Anti-inflammatory, antioxidant, antiseptic, anaesthetic, astringent, anticancer, antiparasitic hypocholesterolaemic, hypoglycaemic/insulinaemic, hepatoprotective, thyroid modulator Indications • Hypercholesterolaemia & dyslipidaemia • Cancer • Toxin exposure, oxidative stress & liver disorders • Diabetes & obesity • Hypothyroid • Parasitic infections • Bacterial infections including acne, gum disease, gingivitis • Neuralgia Toxicity HUMAN Transient skin rashes, headaches and gastrointestinal disorders have been reported in some patients during studies with Myrrh. One case of rhabdomyolysis with hemoglobinuria has been reported that resolved when Myrrh was discontinued. ANIMAL Toxicity studies revealed a significant increase in weight of reproductive organs as well as elevated levels of RBC and Hb in mice. High doses of 1 or 5 g plant resin/kg/d caused salivation, soft faeces, jaundice, dyspnoea, ataxia and eventually death in goats. Lower doses were safe. Use in pregnancy Contraindicated due to possible emmenagogic action Contraindications and cautions None documented. Drug interactions None documented. Administration and dosage Dried resin: 200mg – 600mg daily Liquid extract (resin) 1:5 90% alcohol: 1.0-2.5mL 3 times daily. A full monograph is available on: www.herbalextracts.com.au Description Myrrh is a reddish-brown resinous material obtained from the dried sap of the Commiphora species of trees. A range of related shrubs from the Burseraceae family can be used to obtain the resin. Different species are native to different regions, for example Commiphora myrrha is native to Yemen, Somalia and Ethiopia while Commiphora gileadensis is native to Jordan. The bushes yielding the resin do not grow more than 2-3 metres in height. They are sturdy bushes, with knotted branches, and branchlets that stand out at right-angles, ending in a sharp spine. The trifoliate leaves are scanty, small and very unequal, oval and entire.1 There are ducts in the bark, and large cavities can form inside which fill with a granular secretion. The secretions are freely discharged as ‘tear drops’ when natural fissures occur or when the bark is cut. Myrrh initially flows as a pale yellow liquid, but hardens to a reddish-brown mass. Commercially the dried resinous ‘tears’ can be found in many sizes but average the size of a walnut. The surface is rough and powdered, and the pieces are brittle, semi-transparent, oily, and often show whitish marks. High quality myrrh can be identified through the darkness and clarity of the resin. The scent of raw myrrh resin and its essential oil is sharp and pleasant though slightly bitter. When burned, it produces a smoke that is heavy with the scent of vanilla and bitter overtones. Traditional usage Myrrh is perhaps best known for its historical role in many religion traditions. It was, and still is, a traditional ingredient in anointing oils in Christian, Jewish and Muslim religious ceremonies. Incense made from Myrrh was used in funerals and cremations. Myrrh has also been used historically in many cultures as a perfume and an embalming ointment and was highly valued - often worth more than its weight in gold. Hence, along with gold and frankincense, myrrh was one of the precious gifts that the three magi brought to Jesus. Myrrh has a long history of use as an antiseptic and astringent. In India as well as in the Middle East, Myrrh was traditionally used to treat problems of the mouth, gum and throat and was considered a tonic to the digestive system. Myrrh was a common ingredient in toothpowders and was considered excellent for ‘spongy gums’ and was also used to expel parasites. It was also used as a stimulating emmenagogue, an expectorant and mucous membrane stimulant in chronic respiratory and catarrhal states. Constituents Chemical analysis of myrrh has shown that it is composed on round 8-10% volatile oil, 25-40% resin and around 50-60 % gum. Broad assessment reveals ash, salts, sulphates, benzoates, malates, acetates of potassium, formic acid, acetic acid, tannins and a lignan.2 A further breakdown of the resins reveals commiphoric acids, heeraboresene, heerabomyrrhols, commiferin, novel triterpenes, epimansumbinol, progesterone and steroids such as guggulsterone.3, 4 The gum exudates of Myrrh have been determined to have acidic polysaccharides with galactose, 4-O-methyl-glucuronicacid, and rabinose along with furanosesquiterpenoids, 5 lindestrene, curzerene, and germacrone.6 The essential oil of myrrh contains sesquiterpenoid hydrocarbons, elemol, furanodiene, furanodienone, isofuranogermacrene, curzerenone and lindestrene.7 Pharmacological activities Cholesterol Lowering Activity The plant sterol guggulsterone (guggulipid) obtained from Myrrh resin has been shown to lower LDL (low-density lipoprotein) cholesterol and triglyceride levels and raise serum high density lipoprotein levels in both animal and human studies. Guggulsterone may act in more than one way to lower cholesterol. It has been shown to act as an antagonist to the bile acid receptor (BAR),8 and through lowering the enzyme, human pancreatic IB phospholipase , which controls gastrointestinal absorption of fat and cholesterol.9 Guggulsterone also acts by antagonising the farnesoid X receptor (FXR), a hormone receptor that is activated by bile acids and responsible for a range of actions. Guggulsterone was shown to be a selective bile acid receptor modulator that regulates expression of a subset of FXR targets.10 Guggulsterone treatment decreased hepatic cholesterol in mice fed a high-cholesterol diet but was not effective in FXR-null mice. Thus, researchers suggested that inhibition of FXR activation is a basis for the cholesterol-lowering activity of guggulsterone.11 A study found that the decrease in serum cholesterol in rats treated with guggulsterone was associated with enhanced uptake of LDL by the liver through receptor mediated endocytosis. Membranes prepared from the liver of guggulsterone treated rats exhibited up to an 87% increase in binding sites for LDL. Significant decreases in lipid levels in both serum and liver membrane were observed.12 Human studies have found mostly favourable results for Myrrh. One RCT examined 43 patients, with moderately increased cholesterol, for the effect of guggul or placebo for 12 weeks. After 12 weeks, mean levels of total cholesterol and HDL in the active group were significantly reduced compared with the placebo group.13 Another double-blind, RCT examined the use of guggulipid in healthy adults with hypercholesterolemia compared with placebo. However, this 8 week study did not find favourable results. There were no significant changes in levels of total cholesterol, HDL-C, triglycerides, or VLDL-C in response to treatment with guggulipid. Though it was generally well tolerated, 6 participants treated with guggulipid developed a hypersensitivity rash compared with none in the placebo group.14 Another compared gugulipid therapy with clofibrate therapy. With gugulipid the average fall in cholesterol and triglycerides was 11 and 16.8% respectively and with clofibrate 10 and 21% respectively. HDL-cholesterol was increased in 60% cases who responded to gugulipid therapy. Clofibrate had no effect on HDL-cholesterol. A significant decrease in LDL-cholesterol was observed in the responders to both drugs.15 The effects of guggulipid or placebo for 24 weeks were compared as adjuncts to a fruit- and vegetable-enriched diet in hypercholesterolaemic patients. Guggulipid decreased the total cholesterol level by 11.7%, the LDL cholesterol by 12.5%, triglycerides by 12.0%, and the total cholesterol/HDL cholesterol ratio by 11.1% from the post-diet levels, whereas the levels were unchanged in the placebo group. The HDL cholesterol level showed no changes in the two groups. The lipid peroxides, indicating oxidative stress, declined 33.3% in the guggulipid group without any decrease in the placebo group. The combined effect of diet and guggulipid at 36 weeks was as great as the reported lipid-lowering effect of modern drugs. The changes in blood lipoproteins were reversed in the guggulipid group during the washout period without such changes in the placebo group. Side effects of guggulipid were headache and digestive complaints in a few patients.16 A combination of Myrrh and Inula was studied in 200 patients with ischemic heart disease. A 39% decrease in total cholesterol, 51% decrease in triglycerides, and 32% decrease in total blood lipids were reported. At the end of the six-month study period, 26% of the subjects had a complete restoration of normal ECG, 59 % showed improvement in the ECG, 25% had no chest pain, and patients experiencing dyspnoea fell to 80% at baseline to 32%. Of those still experiencing chest pain and dyspnoea, the subjective levels of pain also improved after treatment. 17 There is accumulating evidence that LDL oxidation is essential for atherogenesis, and antioxidants may either slow down or prevent atherogenesis. Myrrh and guggulsterone, were shown to effectively inhibit LDL oxidation mediated by a range of substances.18 Regulation