Peppermint

Scientific Name(s): Mentha x piperita L. Peppermint is a hybrid of Mentha spicata L. (spearmint) and Mentha aquatica L. Family: Lamiaceae (mints)

Common Name(s): Peppermint , menthol

Uses

In addition to use as a seasoning and flavoring, peppermint is used to treat irritable bowel syndrome (IBS) and other GI conditions. Menthol is available in numerous commercial preparations used to treat respiratory tract infections and topically for its cooling and warming action to relieve pain. However, there is limited clinical information supporting its use for these conditions.

Dosing

Peppermint oil has been used as a carminative at doses of 0.1 to 0.24 mL. Up to 1,200 mg of the oil in enteric-coated tablets has been used to treat IBS. Peppermint oil (40 mL) has been added to barium suspensions and also administered intraluminally (8 mL) during colonoscopy.

Contraindications

Peppermint oil should not be administered to patients with gastroesophageal reflux or active gastric ulcers because the oil decreases esophageal sphincter pressure. Peppermint oil should not be applied to the face, especially under the nose of a child or infant. Enteric-coated preparations are not recommended for use in children younger than 8 years.

Pregnancy/Lactation

Documented adverse reactions. Avoid use because of emmenagogue effects.

Interactions

Peppermint oil may influence metabolism of certain drugs, including felodipine and simvastatin, via inhibition of the cytochrome P450 (CYP-450) enzyme system, increasing pharmacologic and adverse reactions. Absorption of caffeine may be delayed by menthol. Decreased cyclosporine levels have been reported with consumption of a tea containing peppermint and 8 other herbs.

Adverse Reactions

Peppermint oil may cause allergic reactions characterized by contact dermatitis, flushing, and headache and may worsen the symptoms of heartburn, hiatus hernias, and stomach ulcers.

Toxicology

Peppermint is GRAS (generally recognized as safe) in amounts used in seasoning or flavoring, although medicinal uses of the plant can cause adverse reactions. (See Adverse Reactions.)

Botany

This well-known perennial is a prototypical member of the mint family. 1 Like all mints, it has a square, purple-green stem with dark or light green leaves and purple- and lilac-colored flowers. The plant generally is sterile and spreads by means of runners. There are a variety of peppermint types cultivated worldwide. Pharmaceutical oil is derived from 2 varieties: white (light green leaves) and black (dark green leaves) peppermint. This is not to be confused with Japanese peppermint oil, which is similar in odor but derived from a different species. 2

History

First described in England in 1696, peppermint and its oil have been used in Eastern and Western traditional medicine as an antispasmodic, aromatic, and antiseptic in the treatment of cancers, colds, cramps, indigestion, nausea, sore throat, and toothaches. Today, the oil is used widely as a flavoring in chewing gum, cigarettes, mouthwash, pharmaceuticals, and toothpaste. It also is used as an ingredient in cough and cold preparations and as a carminative for IBS. As a menthol component, it is also found in numerous antipruritic, antiseptic, and local anesthetic preparations. 2

Chemistry

Peppermint oil is extracted from the plant by steam distillation. 2 The chemistry of peppermint oil is complex and highly variable, with more than 100 components isolated from the oil. The relative concentrations vary depending on climate, cultivar, and geographic location. 3 , 4 , 5 Peppermint yields 0.1% to 1% of volatile oil composed primarily of menthol (29% to 48%), menthone (20% to 31%), and menthyl acetate (3% to 10%). 6 Pulegone, contained in various forms of peppermint, should not exceed a concentration of 1% because it can be toxic. 7 The biosynthetic pathway of the terpenoids is well characterized, with pulegone being a branch point on the way to both menthol and menthofuran. 8 Peppermint harvest and drying have been thoroughly studied. 9 The profile of volatiles is affected by the presence of an endosymbiotic fungus. 10 Other pharmacologically active ingredients include bitter substances, caffeic acid, flavonoids, 3 and tannins. 11

Absorption of menthol is rapid following oral administration, and elimination is mainly via bile. 12 Menthol-glucuronide has been identified as the main metabolite, in addition to mono- or di-hydroxylated menthol derivatives. 13

Uses and Pharmacology

Several comprehensive reviews of peppermint's therapeutic activity have appeared in the literature. 14 , 15

GI use

The relative safety of peppermint and the availability of randomized clinical trials in humans render data from animal trials largely irrelevant. 2 , 16

Antiemetic

Animal models support the ability of peppermint oil to reduce nausea, but trials in humans have used poor methodology. 17 Trials have shown that menthol and peppermint oil are more effective than placebo, 18 , 19 but they are not more effective than standard treatments. 17 , 19 An allosteric effect of menthol and peppermint oil on the 5-HT 3 receptor may explain its antiemetic action; however, the effect was weak and may not be clinically relevant. 20

Biliary disorders

Peppermint oil has been used traditionally in the management of gallstones. A choleretic action of the oil has been described. 13

Dyspepsia

Peppermint oil alone and in combination with other herbs was more effective than placebo in reducing symptoms of dyspepsia in adults and children. 21 , 22 , 23 , 24 , 25 , 26 Gastric emptying was accelerated by peppermint oil added to a test meal. 27

Irritable bowel syndrome

Patients should be administered peppermint oil only after examination has definitely diagnosed IBS with no associated organic lesions and after other diagnoses have been eliminated. 20 Reviews of peppermint oil's role in IBS affirm its effectiveness compared with placebo and as standard treatment in patients with nonserious constipation or diarrhea to reduce global symptoms, pain, and bloating. 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 A comparison of 2 delayed-release preparations of peppermint oil found that Colpermin delivered the oil more effectively than Mintec . 39 Several studies of a combination product, Iberogast , which includes peppermint, have found effects on intestinal physiology in mice, 40 as well as antioxidant effects. 41

Smooth muscle spasm

Peppermint oil exerts an antispasmodic action on smooth muscle, considered to be caused by calcium channel blockade. 13 , 42 , 43 The oil has been useful in patients with colonic 16 , 43 , 44 , 45 and esophageal spasm 46 , 47 , 48 and in endoscopy. 43 , 48 , 49 , 50

Respiratory tract

Menthol is available in a variety of nonprescription products (eg, chest rubs, inhalations, lozenges, syrups) for the treatment of colds and related congestion and cough. A decrease in cough was demonstrated in children when inhalation of menthol was compared with placebo. 51 The mechanism by which menthol may act as an antitussive is still speculative 52 ; however, anion transporters in airway epithelial cells have been implicated. 53 Menthol inhalation can cause a subjective nasal decongestant effect without any objective decongestant action. 52 In lozenges, the main action of menthol appears to be a subjective sensation of improved nasal airflow. 52 No effect on forced expiratory volume was shown in patients with chronic mild asthma using nebulized menthol versus placebo. However, the menthol group used fewer bronchodilators and had fewer wheezing episodes. 54

Pain/Sensory effects

In low concentrations, topical application of menthol causes a cooling sensation, while in higher concentrations it causes local anesthesia and irritation. 52 , 55 , 56 These attributes of menthol have been used to construct pain models. 55 , 56 The irritant effect of menthol causes local vasodilation. 52 , 56 , 57 This effect has been used to aid penetration of topical drugs; higher diffusion of tetracaine has been demonstrated with menthol-enhanced gel. 57 Menthol's sensory effects are utilized in commercial topical musculoskeletal products. 52 , 58

The cooling effect of menthol has been explained by its direct effect on the “cold receptor” TRPM8, a distant relative of the vanilloid receptors that sense pain and noxious high temperatures. 59 , 60 , 61 , 62 Binding of menthol to TRPM8 induces calcium release from the endoplasmic reticulum and Golgi apparatus in the cell. 60 Menthol is an agonist of TRPM8. 59

Other effects
Antibacterial

Peppermint oil possesses antibacterial activity in vitro. Different commercial preparations exhibit various activities. 5 The essential oil and its constituents (eg, menthol, menthone) displayed activity against Escherichia coli , Helicobacter pylori , methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus , Pseudomonas species, Enterobacter aerogenes , and Salmonella enteritidis . 63 , 64 , 65 Weak antifungal activity also has been shown in vitro. 65 Biofilm development and growth of Listeria was inhibited by peppermint extracts, as well as those of rosemary and tea tree. 66

Antiviral

Aqueous extracts of peppermint and several other Lamiaceae inhibited HIV through interference with viral entry without altering cell viability. Several other enveloped viruses were similarly affected. 67

Cancer

Menthol was found to synergize with vitamin D in blocking the growth of prostate cancer cells by cooperatively modulating expression of bcl-2 and p21 proteins. 68 A reduction in incidence and multiplicity of induced lung cancer has been shown in mice. 69

CNS

Peppermint oil is being studied as aromatherapy for dementia by the Cochrane Dementia and Cognitive Improvement Group. 70 Peppermint oil in ethanol reduced pain sensitivity experienced with headaches. 71 Peppermint oil aroma has shown an antisoporific effect. 72 , 73 Memory performance was enhanced by peppermint oil, but not oil of ylang-ylang. 74 However, aromatherapy was no better than placebo in averting postoperative nausea. 19 Menthone promotes ambulation in mice; this effect is apparently mediated by the dopamine system, because it is additive with bupropion, which inhibits dopamine uptake, and is blocked by dopamine antagonists. 75 Neurochemical profiling of mint extracts in gamma–aminobutyric acid and antioxidant systems has been performed. 76

Liver

Peppermint oil protected mice against experimental hepatic injury by arsenic. 77

Other

Head lice were successfully treated with a lotion incorporating peppermint and eucalyptus oil. 78 Giardia trophozoites were inhibited by peppermint extracts. 79

Peppermint water has been studied for prevention of nipple cracks in breast-feeding women. 80

Dosage

Peppermint oil has been used as a carminative in clinical studies at doses of 0.1 to 0.24 mL. 16 , 81 , 82 , 83 Doses of peppermint oil of up to 1,200 mg in enteric-coated tablets have been used in treating IBS 45 , 46 ; 40 mL of peppermint oil has been added to barium suspension 23 ; and 8 mL of peppermint oil also has been administered intraluminally during colonoscopy. 22

Because of the oil's ability to relax GI smooth muscle, patients with hiatus hernia may experience worsening symptoms while ingesting peppermint-containing preparations. 42

Enteric-coated capsules should be swallowed whole and not crushed, broken, or chewed because peppermint oil can irritate the mouth, esophagus, and stomach. Tablets should be taken 30 to 60 minutes before meals on an empty stomach. 24 , 84

Pregnancy/Lactation

Documented adverse reactions. Avoid use because of emmenagogue effects. 85

Interactions

Caffeine

Absorption of a single dose of caffeine 200 mg was delayed by menthol 100 mg in healthy volunteers. 86

Felodipine

Peppermint oil may influence metabolism of felodipine via inhibition of CYP3A4, elevating felodipine plasma concentrations and increasing the pharmacologic effects and adverse reactions. Peppermint oil 600 mg in water increased the area under the curve (AUC) of felodipine 40%. 87 However, a study of the effect of menthol showed no effect on felodipine pharmacokinetics in healthy adults. 88

Simvastatin

Peppermint oil may influence metabolism of simvastatin via inhibition of CYP3A4, elevating simvastatin plasma concentrations and increasing the pharmacologic and adverse reactions. Peppermint oil 600 mg in water increased the AUC of simvastatin 30% in healthy volunteers. 87

Cyclosporine

Decreased cyclosporine levels were reported in a patient consuming herbal tea containing peppermint and 8 other herbs. 89

Adverse Reactions

Menthol, the major component of peppermint oil, may cause allergic reactions (eg, contact dermatitis, flushing, headache) in certain individuals. 6 , 90 , 91 , 92 Delayed patch-test reaction to menthol and peppermint oil may occur 6 to 14 days after application. 93 Symptoms of contact sensitivity and ulceration from oral menthol/peppermint-containing products improved with discontinuation and avoidance of these products. 94

Following ingestion of 40 drops of peppermint oil, a patient with no known allergies reported mucosal burns and edema of the tongue and oral cavity. 84 Excessive consumption of mint-flavored sweets caused stomatitis with oral papillary hypertrophy. 95 Vulval allergic contact dermatitis was documented in a patient who consumed large amounts of peppermint tea. 96 Likewise, a peppermint foot spray was linked to dermatitis in another patient. 97 Four cases of dermatitis of the lips were traced to peppermint-flavored lip balm. 98 Delayed-release peppermint oil capsules have caused a burning sensation during defecation because of unabsorbed menthol that reached the rectum. 24 Nonetheless, such peppermint allergies appear to be rare, with prospective patch testing finding no allergic or irritant reactions to either menthol or peppermint oil in 400 subjects. 99 Loss of libido in men following consumption of peppermint tea has been reported. 100

Toxicology

Like other mints from which menthol is derived as a plant extract, peppermint is GRAS for human consumption as a seasoning or flavoring. 7 , 15 Two comprehensive reports on peppermint safety have been published, 7 , 101 with pulegone and menthofuran being the constituents of toxicologic concern. Radiolabeled pulegone has been found to bind to rat kidney alpha2u-globulin, which may be a target of toxicity. 102

Rats fed peppermint oil in daily dosages of up to 100 mg/kg for 28 days developed dose-related brain lesions. A similar 90-day study demonstrated identical pathology, with no additional aggravation of the cyst-like spaces in the cerebellum. These were similar in nature to the neuropathy induced by hexachlorophene and attributed to the pulegone component of peppermint oil. 7 , 103 However, doses of this magnitude would be considered an overdosage with the oil. Current standards for peppermint oil limit pulegone concentration to 1% of the oil. 7

A case of delirium resulting from intoxication by oral ingestion of topical mentholatum required hospitalization in a woman with chronic alcoholism. 104 Delirium also was experienced in a man with chronic alcoholism after possible oral ingestion of a topical menthol/alcohol-containing analgesic. 105 Pulmonary edema and acute lung injury occurred in a patient following intravenous injection of peppermint oil. 106

Peppermint oil should not be administered to patients with heartburn or active gastric ulcers because symptoms may be exacerbated. The oil can decrease esophageal sphincter pressure and contribute to gastroesophageal reflux. 42 Peppermint oil should not be applied to the face, especially under the nose of a child or infant. 52 The application of menthol-containing ointment to the nostrils of an infant for the treatment of cold symptoms has caused instant collapse. 6 Enteric-coated preparations have not been studied in children younger than 8 years and are not recommended for use in very young children. No association was found between use of peppermint in the last 2 trimesters of pregnancy and premature birth. 107

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