Evidence supports peppermint oil for irritable bowel syndrome (IBS), spasm during barium enema, and, topically, for headache. It should not be used in babies or small children.

[LFODPKM ] Letter Key

Latin Name

Mentha × piperita L.

Family

Labiatae/Lamiaceae

Other Common Names

Brandy mint, curled mint, and balm mint

Description

• Peppermint is a hybrid of water mint (Mentha aquatica) and spearmint (Mentha × spicata). The latter is a hybrid of two other species, M. longifolia and M. suaveolens.

Part Used

Essential oil, leaf (dried)

Known Active Constituents

• Volatile oil (1% to 3%), containing principally (—)-menthol (35% to 55%) and its stereoisomers menthone (10% to 40%), (+)-neomenthol (about 3%), and (+) isomenthol (3%). The oil also contains cineol (2% to 13%), limonene (0.2% to 6%), carvone, monoterpenes, and sesquiterpenes (1). Pulegone, the toxic component of pennyroyal, occurs in young plants and may be detected in inferior quality oils; commercial oils do not usually contain pulegone (2).
• Peppermint leaf also contains flavonoids including luteolin, rutin, and hesperidin, as well as phenolic acids and triterpenes (1). Peppermint leaves are high in beta-carotene; retinal equivalents/100 g were found to be 940 by high-pressure liquid chromatography (HPLC) or 1,016 by open-column chromatography (3).

Mechanism/Pharmacokinetics

• In animal models, peppermint oil inhibits muscle contraction induced by serotonin or substance P. Peppermint oil topically applied to the forehead increases skin blood flow (measured by Doppler) (4). Menthol is fat-soluble and quickly absorbed from the small intestine. Peak menthol levels are lower and excretion of menthol metabolites delayed with delayed-release preparations; total urinary excretion of menthol is similar with immediate and delayed-release preparations (1).

[Outline]

• LLatin Name
• FFamily
• OOther Common Names
• DDescription
• PPart Used
• KKnown Active Constituents
• MMechanism/Pharmacokinetics

[CAO ] Letter Key

Clinical Trials

• Irritable bowel syndrome (IBS)
  • A meta-analysis of peppermint oil for IBS identified eight randomized controlled trials (RCTs) (two parallel group trials and six crossover trials); treatment was administered for 2 weeks to 6 months. Three trials were excluded (two because of insufficient data, one was neither double-blind nor placebo-controlled) (5). The meta-analysis showed that peppermint oil, compared with placebo, significantly improved global symptoms.
  • A recent placebo-controlled double-blind RCT (not included in the previous meta-analysis) tested an enteric-coated peppermint oil formulation in 110 patients with IBS (6). Symptoms of abdominal pain, abdominal distension, stool frequency, flatulence, and borborygmi were significantly reduced in the peppermint group, compared with placebo. A double-blind, 2-week RCT in 42 children with IBS found a benefit for enteric-coated peppermint oil capsules (76% improved, compared with 19% of placebo-treated patients) (7).
• Spasm after barium enema
  • In one study, 141 patients were randomized either to standard barium suspension or to peppermint oil mixed into the barium suspension (30 mL of a 1 in 125 aqueous solution emulsified with Tween 80) (8). Significantly more of the peppermint-treated patients (60%) experienced no residual spasm compared with 35% of controls. No adverse events were noted. The authors point out that this inexpensive, simple treatment may decrease the need for intravenous spasmolytics.
• Headache
  • A crossover RCT compared topical peppermint oil (10% peppermint oil in ethanol) to peppermint-scented placebo for tension headaches in 41 patients; patients also received acetaminophen 1,000 mg or placebo. Each person tried every combination (9). A total of 164 headaches were recorded. The oil was spread across forehead and temples every 15 minutes for 45 minutes; pain intensity was recorded every 15 minutes for 1 hour. Compared with placebo, topical peppermint significantly reduced headache intensity after 15 minutes and throughout the hour. There was no significant difference between acetaminophen and topical peppermint oil; simultaneous administration did not result in a significantly better result than either treatment alone.
  • A double-blind placebo-controlled crossover study in 32 healthy men examined topical applications of ethanol and peppermint oil, eucalyptus oil, both oils, and placebo (traces of essential oils were added to some preparations to maintain blinding) (10). Both peppermint preparations significantly reduced electromyographic (EMG) activity of the temporalis muscle; eucalyptus or ethanol caused no change. Induced pain was generally not different among groups; peppermint reduced pain from ischemic or heat stimulus, but not pressure stimulus; ethanol alone significantly increased pain from heat stimulus. Performance-related activity (a measure of mood state) increased significantly only in the combination group; irritability significantly decreased in both peppermint groups.
• Aromatherapy for postoperative nausea
  • In one study, 18 patients who had undergone major gynecologic surgery were assigned to no treatment, inhaled vapors of peppermint oil, or inhaled vapors of peppermint essence (as a placebo) (11). The results did not clearly favor peppermint oil.
• Dyspepsia
  • A combination product (peppermint oil 90 mg and caraway oil 50 mg × 4 weeks) was tested against cisapride in 118 patients with functional dyspepsia (12). The primary outcome measure was pain score by visual analog scale. The treatments were similar in reducing frequency of pain and the dyspeptic discomfort score and in improving clinical global impression.
  • Another double-blind, placebo-controlled trial in 45 dyspepsia patients (39 completed) tested three enteric-coated capsules daily (each contained 90 mg peppermint oil and 50 mg caraway oil) (13). After 4 weeks, 63.2% of treated patients and 25% of controls were pain-free. Improvement in pain intensity occurred in 89.9% of those treated compared with 45% of controls.
  • A commercial combination product containing ethanol-aqueous extracts of peppermint and other herbs [100 mL contained caraway (3.7 g), fennel (8.13 g), peppermint (9.26 g), and wormwood (1.92 g)] was compared with metoclopramide (about 24 mg/day) in 60 participants with upper abdominal complaints (including pain, nausea, heartburn, retching, and gastric cramping) (14). Patients took 25 drops 20 minutes before meals three times daily for their assigned treatment. After 2 weeks, significant differences favoring the herb treatment were seen in epigastric pain, nausea, heartburn, and gastrospasm.
• Decongestant activity
  • In 62 volunteers with colds, 30 received a lozenge with 11 mg menthol; in another experiment, 29 healthy participants used an inhaler with 125 mg menthol dissolved in 1 mL paraffin; and in a third experiment, 31 participants inhaled mentholated air for 5 minutes. All of these studies showed a subjective enhancement of nasal air flow; however, none showed any change in nasal airway resistance by rhinomanometry (1).
• Cough
  • Inhaled menthol with eucalyptus oil reduced citric acid-induced cough in an experiment involving 20 participants who inhaled air, placebo (pine oil), or menthol dissolved in eucalyptus oil in a 3:1 ratio (15). Because eucalyptus oil is also used to treat cough, it is not possible to separate the effect of menthol from eucalyptus in this experiment.

Animal/In Vitro

• Peppermint oil inhibits contraction of smooth muscle in vitro and reduces morphine-induced spasm in Oddi’s sphincter in anesthetized guinea pigs and enhances bile production in dogs. Menthol enhances bile production in rats and dogs (1).
• Peppermint tea (0.4 g/kg body weight) increased bile secretion in cannulated dogs; mixed flavonoids (2 mg/kg) also increased bile secretion in dogs. Intravenous injection of 0.5 mL peppermint tea increased bile acids in cannulated rats. Weak sedative and weak diuretic effects were noted in mice after a single dose (300 mg/kg and 1,000 mg/kg) dried aqueous extract. Menthol inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase (1).

Other Claimed Benefits/Actions

• Dyspepsia, flatulence, gastritis, colic, biliary disorders, and sedation

[Outline]

• CClinical Trials
  • Irritable bowel syndrome (IBS)
  • Spasm after barium enema
  • Headache
  • Aromatherapy for postoperative nausea
  • Dyspepsia
  • Decongestant activity
  • Cough
• AAnimal/In Vitro
• OOther Claimed Benefits/Actions

[ADT ] Letter Key

Adverse Reactions

• Menthol:
  • Doses of menthol greater than 2 g could be lethal, but individuals have survived doses as high as 9 g. A review of menthol reactions noted cases of urticaria, allergic cheilitis, and stomatitis; allergic reactions are rare.
  • Two cases of fibrillation caused by heavy ingestion of peppermint candy have been reported (no details are reported) (16).
  • Mentholated cigarettes have been associated with a case of psychosis and of nonthrombocytopenic purpura (17).
  • Bradycardia, ataxia, confusion, and irritability were reported in a 58-year-old woman who smoked 80 mentholated cigarettes daily; electrocardiogram (EKG) showed nonspecific ischemic changes. Discontinuing the cigarettes normalized all symptoms and signs. A rechallenge with menthol (1 g menthol t.i.d. × 1 week) caused anorexia, exhaustion, difficulty concentrating, and bradycardia (17).
  • Jaundice in newborns [especially those with glucose-6-phosphate dehydrogenase (G6PD) deficiency] has been associated with menthol (1).
• Essential oil, ingested: Heartburn (non-enteric-coated), recurrent muscle pain, gastrointestinal effects include stomatitis, esophagitis, gastritis, diarrhea, and pancreatitis (2)
• Essential oil (topical): Skin burns
  • A 62-year-old man developed severe necrosis involving deep fasciae and underlying muscle after using a heating pad after topically applying a preparation containing menthol and methyl salicylate (oil of wintergreen) (18). Fever, leucocytosis, metabolic acidosis, abnormal liver and renal function tests, and lung infiltrate were also noted. The authors note that this picture is consistent with chemical and electrical burns with toxic effects from absorption of menthol and methyl salicylate. He was hospitalized for almost a year and received skin grafts; residual renal dysfunction persisted.
  • Chemical burns of the hand were reported in a pharmaceutical factory worker exposed to peppermint oil (2).
• Respiratory effects
  • Laryngeal and bronchial spasms may occur in babies or small children if peppermint oil is applied to the chest or nasal area (1). Inhalation of menthol may cause apnea or laryngospasm in some individuals (1).

Drug Interactions

• None reported. Peppermint oil enhances cyclosporine oral bioavailability in rats (19).
• Patients taking acid blockers or those with achlorhydria should probably use only enteric-coated preparations.

Animal Toxicity

• Acute oral studies show minimal toxicity of peppermint oil.
• Subchronic and short-term toxicity studies in rats given pulegone, peppermint oil with pulegone, or large doses of menthone found cyst-like cerebellar lesions (20). In rats, 100 mg/kg diluted peppermint oil for 90 days caused nephropathy (1). Pulegone is hepatotoxic (20). In rats, menthofuran (250 mg/kg × 3 days) caused hepatotoxicity (1).
• Peppermint leaf dried aqueous extract given orally to 12 mice (4,000 mg/kg) over 7 days caused no macroscopic signs of toxicity (1).

[Outline]

• AAdverse Reactions
  • Menthol:
  • Essential oil (topical): Skin burns
  • Respiratory effects
• DDrug Interactions
• TAnimal Toxicity

Common Dosage Forms

• Dried leaf: 2 to 3 g t.i.d.
• Tea: 1.5 to 3 g t.i.d.
• Tincture: (1:5, 45% ethanol) 2 to 3 mL t.i.d.
• Oil (for internal use, pulegone should be limited to less than 1%): Daily dose, 6 to 12 drops
• As an inhalation, 3 to 4 drops in hot water
• For IBS, 0.2 to 0.4 mL t.i.d. in enteric-coated capsules
• External use: Dilute preparations, semisolid and oily preparations 5% to 20%, aqueous-ethanol preparations 5% to 10%, nasal ointments 1% to 5% essential oil
  • Children 4 to 12 years: Proportion of adult dosage according to body weight or age (see risks).

1. European Scientific Cooperative on Phytotherapy (ESCOP). Monographs on the medicinal uses of plant drugs. Menthae piperitae folium (peppermint leaf) and Menthae piperitae aetheroliun (peppermint oil). Fascicule 3. Exeter, UK, 1997.
2. Bowen IH, Cubbin IJ. Mentha piperita and Mentha spicata. In: De Smet PAGM, Keller K, Hänsel R, Chandler RF (eds.) Adverse effects of herbal drugs, vol 1. Berlin: Springer-Verlag, 1992:170–178.
3. De Almeida-Muradian LB, Rios MD, Sasaki R. Determination of provitamin A of green leafy vegetables by high performance liquid chromatography and open column chromatography. Bollettino Chimico Farmaceutico 1998;137:290–294.
4. Göbel H, Schmidt G, Dworschak M, et al. Essential plant oils and headache mechanisms. Phytomedicine 1995;2:93–102.
5. Pittler MH, Ernst E. Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. Am J Gastroenterol 1998;93:1131–1135.
6. Liu JH, Chen GH, Yeh HZ et al. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol 1997;32:765–768.
7. Kline RM, Kline JJ, Di Palma J et al. Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children. J Pediatr 2001;138:125–128.
8. Sparks MJ, O’Sullivan P, Herrington AA et al. Does peppermint oil relieve spasm during barium enema? Br J Radiol 1995;68:841–843.
9. Göbel H, Fresenius J, Heinze A et al. [Effectiveness of Oleum menthae piperitae and paracetamol in therapy of headache of the tension type]. Nervenarzt 1996;67:672–681.
10. Göbel H, Schmidt G, Soyka D. Effect of peppermint and eucalyptus oil preparations on neurophysiological and experimental algesimetric headache parameters. Cephalalgia 1994;14:228–234.
11. Tate S. Peppermint oil: a treatment for postoperative nausea. J Adv Nursing 1997;26:543–549.
12. Madisch A, Heydenreich C-J, Wieland V et al. Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride: a multicenter, reference-controlled, double-blind equivalence study. Arzneim-Forsch/Drug Res 1999;49:925–932.
13. May B, Kuntz HD, Kieser M et al. Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia. Arzneim-Forsch/Drug Res 1996;46:1149–1153.
14. Westphal J, Horning M, Leonhardt K. Phytotherapy in functional upper abdominal complaints. Phytomedicine 1996;2:285–291.
15. Morice AH, Marshall AE, Higgins KS et al. Effect of inhaled menthol on citric acid induced cough in normal subjects. Thorax 1994;49:1024–1026.
16. Thomas JG. Peppermint fibrillation [Letter]. Lancet 1962;1:222.
17. Luke E. Addiction to mentholated cigarettes [Letter]. Lancet 1962;1:110–111.
18. Heng MCY. Local necrosis and interstitial nephritis due to topical methyl salicylate and menthol. Cutis 1987;39:442–444.
19. Wacher VJ, Wong S, Wong HT. Peppermint oil enhances cyclosporine oral bioavailability in rats: comparison with D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) and ketoconazole. J Pharm Sci 2002;91:77–90.
20. Nair B. Final report on the safety assessment of Mentha Piperita (peppermint) oil, Mentha Piperita (peppermint) leaf extract, Mentha Piperita (peppermint) leaf, and Mentha Piperita (peppermint) leaf water. Int J Toxicol 2001;20 (Suppl 3):61–73.