Peppermint

Scientific Name(s): Mentha x piperita L.
Common Name(s): Menthol, Peppermint

Medically reviewed by Drugs.com. Last updated on Dec 9, 2024.

Clinical Overview

Use

Peppermint, peppermint oil, and its menthol extract have been evaluated for use in GI conditions, including nonserious constipation or diarrhea associated with irritable bowel syndrome (IBS) to reduce global symptoms of pain, and bloating; antispasmodic properties of the oil and menthol extract has led to use in endoscopic GI procedures. Quality clinical trials are lacking to recommend use for treatment of dyspepsia. Menthol, a component of peppermint oil, is often added to respiratory products to provide subjective decongestant action and is used as a vasodilatory agent to aid in penetration of topically applied anesthetic drugs. Limited or equivocal data are available for other uses.

Dosing

Up to 1,200 mg daily (180 to 400 mg 3 times daily) of peppermint oil in enteric-coated capsules has been used to treat nonserious constipation and diarrhea associated with IBS.

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

Adverse reactions, particularly with higher doses, have been documented with use of peppermint. Avoid internal use because of emmenagogue effects.

Interactions

Peppermint oil may inhibit cytochrome P450 (CYP-450) 3A4; use caution when administering with drugs metabolized by this enzyme.

Adverse Reactions

Peppermint oil may cause allergic reactions characterized by contact dermatitis, cutaneous burning, flushing, lacrimation, and headache, and may worsen the symptoms of heartburn, hiatus hernias, and stomach ulcers. Cutaneous and mucosal burns and skin necrosis have been reported with topical formulations.

Toxicology

Peppermint has generally recognized as safe (GRAS) status in amounts used in seasoning or flavoring, but medicinal use of the plant can cause adverse reactions. (See Adverse Reactions.)

Scientific Family

• Lamiaceae (mint)

Botany

Peppermint, a well-known perennial, is a prototypical member of the mint family.USDA 2018 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 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. Peppermint oil is not to be confused with Japanese peppermint oil, which is similar in odor but derived from a different species.Briggs 1993 Peppermint is a hybrid of Mentha spicata L. (spearmint) and Mentha aquatica L.

History

Peppermint and its oil were first described in England in 1696 and 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 widely used as a flavoring in chewing gum, cigarettes, mouthwash, pharmaceuticals, and toothpaste. It is also used as an ingredient in cough and cold preparations and as a carminative for IBS. Menthol, a component of peppermint oil, is also found in numerous antipruritic, antiseptic, and local anesthetic preparations.Briggs 1993

Chemistry

Peppermint oil is extracted from the plant by steam distillation.Briggs 1993 The chemistry of peppermint oil is complex and highly variable, with more than 100 components isolated. The relative concentrations vary depending on climate, cultivar, cycle stage, age, season, and geographic location.Ayaz 2017 Oxygenated monoterpenes (79.5%), monoterpene hydrocarbons (16.23%), and sesquiterpene hydrocarbons (2.44%) are the most abundant categories of chemicals. Peppermint yields 0.1% to 1% of volatile oil composed primarily of menthol (29% to 48%), menthone (18% to 33%), and menthyl acetate (3% to 10%), with lesser amounts of limonene (8%), pulegone (1.6% to 3.99%), piperitone (1.4% to 3.2%), 1,8-cineole (1.98% to 2.8%), linalool (2.64%), iso-pulegol (2.4%), and caryophyllene (1.44% to 1.95%).Abdellatief 2017, Bellassoued 2018, Leung 1980 Pulegone, contained in various forms of peppermint, should not exceed a concentration of 1% because it can be toxic.Nair 2001 The biosynthetic pathway of the terpenoids is well characterized, with pulegone being a branch point on the way to both menthol and menthofuran.Rios-Estepa 2008 Peppermint harvest and drying have been thoroughly studied.Zheljazkov 2010 The profile of volatiles is affected by the presence of an endosymbiotic fungus.Mucciarelli 2007 Major bioactive constituents of the essential oil of peppermint and other Lamiaceae species are hydroxycinnamic acids (ie, caffeic, chlorogenic, ferulic, and rosmarinic acids) and flavonoids. Peppermint leaf extract is characterized by a high hydroxycinnamic acid content (157.45 mg/g), comprised primarily of rosmarinic acid (61.05 mg/g), which is likely responsible for much of acetylcholinesterase inhibitory and antioxidant effects of the plant.Vladimir-Knezevic 2014

Uses and Pharmacology

Absorption of menthol is rapid following oral administration, and elimination is mainly via bile.(Yamaguchi 1994) Menthol-glucuronide has been identified as the main metabolite, in addition to mono- or dihydroxylated menthol derivatives.(Grigoleit 2005)

Aerobic capacity

Clinical data

The effect of peppermint essential oil on exercise and cardiorespiratory performance was investigated in 7 physically active young adults in a randomized, single-blind crossover study. In contrast to an earlier study, no significant beneficial effect on performance was observed.(Shepherd 2017) Similarly, a randomized, controlled, single-blind study in 106 healthy individuals revealed no significant changes in any of the spirometry measures following inhalation of peppermint, rosemary, or eucalyptus essential oils.(Koteles 2018)

Antibacterial activity

In vitro data

Peppermint oil possesses antibacterial activity in vitro. In one study, various commercial peppermint oil preparations exhibited a wide range of activity against different species of bacteria.(Lis-Balchin 1997) The essential oil and its constituents (eg, menthol, menthone) have displayed activity against Escherichia coli, Helicobacter pylori, methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus, Pseudomonas spp., Enterobacter aerogenes, and Salmonella enteritidis.(Imai 2001, Işcan 2002, Osawa 1999) Weak antifungal activity has also been shown in vitro.(Işcan 2002) Biofilm development and growth of Listeria was inhibited by peppermint extracts.(Sandasi 2010)

Antioxidant properties

Free radical scavenging and inhibition of lipid peroxidation appear to be the main mechanisms of peppermint's pharmacological actions.

Animal data

In rats, protection against chemically induced renal toxicity and hepatotoxicity has been demonstrated with a 40 mg/kg dose of peppermint oil, providing comparable antioxidant activity to that of silymarin 50 mg/kg.(Bellassoued 2018) In a study in rats with streptozotocin-nicotinamide–induced type 2 diabetes, free radical scavenging activity of peppermint essential oil was between that of ascorbic acid and butylated hydroxyanisole.(Abdellatief 2017)

Antiparasitic activity

Animal and in vitro data

In an in vitro study, Giardia lamblia trophozoites were inhibited by peppermint extracts.(Vidal 2007) In a mouse Schistosomiasis model, peppermint oil demonstrated antiparasitic and immunomodulatory effects that contributed to the pathophysiological control of the infection.(Zaia 2016)

Antiviral activity

In vitro and ex vivo data

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.(Geuenich 2008)

Cancer

Animal and in vitro data

In vitro, menthol enhanced vitamin D–mediated growth inhibition of prostate cancer cells by cooperatively modulating expression of bcl-2 and p21 proteins.(Park 2009) In mice with benzo[a]pyrene-induced lung carcinogenicity, an extract of M. piperita leaves reduced the incidence of lung tumors and tumor multiplicity.(Samarth 2006)

CNS

A study evaluating the mechanism by which menthone promotes ambulation in mice suggests the effect is mediated by the dopamine system; an additive effect on ambulation was observed when menthone was administered with bupropion, a dopamine uptake inhibitor; also, dopamine antagonists attenuated the effects of menthone. These findings suggest the mechanism underlying the ambulation-promoting effect of menthone could overlap with that of bupropion.(Umezu 2009) Neurochemical profiling of mint extracts in gamma–aminobutyric acid (GABA), acetylcholinesterase (AChE), and antioxidant systems has also been performed.(López 2010, Vladimir-Knezeic 2014) Extracts from peppermint exhibited potent, dose-dependent AChE inhibitory activity and potent, total antioxidant capacity.(Vladimir-Knezeic 2014)

Alertness

Clinical data

Peppermint oil aroma has shown an antisoporific effect.(Norrish 2005, Umezu 2001) In studies of healthy volunteers exposed to essential oil fragrances, odor pleasantness and subjective level of stress were factors significantly influencing cognitive performance,(Heuberger 2010) with an increase in attentional control demonstrated with an increase in attentional control demonstrated with peppermint oil compared to lavender oil.(Colzato 2014)

Anxiety

Clinical data

In patients who presented to the emergency department with acute coronary syndrome, administration of peppermint essential oil aromatherapy for 1 hour significantly reduced anxiety compared to patients who received placebo (P=0.02) in a randomized, controlled, unblinded study.(Soleimani 2022)

Dementia

Clinical data

In healthy volunteers, memory performance was enhanced with peppermint oil aroma, but not oil of ylang-ylang.(Moss 2008) Peppermint oil aromatherapy has been studied for use in dementia by the Cochrane Dementia and Cognitive Improvement Group, with results from only one identified trial showing benefit(Thorgrimsen 2003); an updated review of randomized controlled trials for dementia has been published, but no data regarding peppermint oil were identified for inclusion.(Forrester 2014)

Opioid withdrawal

Animal data

An extract of the aerial parts of peppermint (50, 100, 200, and 500 mg/kg) significantly reduced symptoms of morphine withdrawal in addicted animals.(Ebrahimie 2015)

Pain/Sensory effects

The cooling effect of menthol is explained by the direct effect of low doses on the "cold receptor" known as transient receptor potential melastatin type 8 (TRPM8), a distant relative of the vanilloid receptors that sense pain and noxious high temperatures.(Behrendt 2004, Mahieu 2007, McKemy 2002, Peier 2002, Renner 2012) Binding of menthol to TRPM8 induces calcium release from the endoplasmic reticulum and Golgi apparatus in the cell.(Mahieu 2007) Menthol is an agonist of TRPM8.(Behrendt 2004) Pain sensation effects have been shown to occur at higher menthol concentrations as a result of the activation of transient receptor potential ankyrin type 1 (TRPA1), which is activated by both menthol and nicotine in a reversible, nonreactive manner.(Renner 2012)

In vitro data

Nicotine-induced activation of TRPA1 was desensitized by the application of menthol in cell cultures.(Renner 2012)

Clinical data

Topical application of low concentrations of menthol causes a cooling sensation, while higher concentrations cause local anesthesia and irritation.(Eccles 1994, Hatem 2006, Wasner 2004) These attributes of menthol have been evaluated in constructed pain models.(Hatem 2006, Wasner 2004) The irritant effect of menthol causes local vasodilation,(Eccles 1994, Liu 2005, Wasner 2004) which can aid penetration of topical anaesthetic drugs; higher diffusion of tetracaine has been demonstrated with menthol-enhanced gel.(Liu 2005) Menthol's sensory effects are utilized in commercial topical musculoskeletal products.(Eccles 1994, Kraemer 2005)

Peppermint oil reduced pain sensitivity in patients with headaches(Göbel 1994), was an effective counter odor stimulant for the prevention of alliaceous migraines,(Roussos 2014) and significantly reduced pain scores during colonoscopy(Shavaki 2012) and after IV catheterization.(Akbari 2019) In a triple-blind, randomized, placebo-controlled crossover study of adults with a diagnosis of migraine headache (N=35 [intention-to-treat population]; 118 migraine attacks), cutaneously applied menthol provided a significant reduction in pain intensity within the first 2 hours of migraine compared to placebo (P=0.01). However, no significant difference in mean pain intensity was observed between groups at later time points. After 2 hours, the percentages of patients who were pain free (38.3% vs 12.1%; P=0.001), experienced pain relief (58.3% vs 17.2%; P=0), or had a pain-free response during the first 24 hours (33.3% vs 12.1%; P=0.008) and at 48 hours (28.3% vs 8.6%; P=0.008) were significantly higher with menthol. Rates of nausea/vomiting, photophobia, and phonophobia decreased significantly in both groups 2 hours after treatment, with lower incidences in the placebo group. Adverse events were reported in 15% and 7% in the menthol and placebo groups, respectively. Cutaneous burning sensation (8.3% of attacks), lacrimation (5% of attacks), and aggravation of headache (1.6% of attacks) were most common with menthol; 2 patients in the menthol group discontinued the study due to severe burning sensation and aggravation of headache.(Borhani Haghighi 2010)

Diabetes/Metabolic effects

Animal data

Glycemia was significantly lowered with 30-day administration of peppermint juice (0.29 g/kg/day; 70 kg human equivalent dose of 200 mL/day) in offspring of diabetic rat dams (P=0.0001) but not in controls. Additionally, offspring of control and diabetic rat dams treated with peppermint juice exhibited significantly improved cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) compared to control and diabetic dams receiving only vehicle (water). No significant differences were observed in lipid parameters between the offspring of nondiabetic and diabetic dams receiving peppermint juice, except for HDL values, which were observed to be significantly higher (P=0) in the nondiabetic offspring.(Barbalho 2011) In a diabetic rat model, peppermint essential oil significantly improved blood glucose, insulin, and C-peptide compared to controls (P<0.05 for all), with an 80 mg/kg dose providing an overall better effect than both a 40 mg/kg dose and positive control (the standard hypoglycemic agent glibenclamide). These results were supported by protective effects demonstrated in hepatic and pancreatic tissue, as well as by changes in hepatocyte and beta-cell immunology and insulin gene expression. Hematologic parameters (ie, total erythrocyte count, hemoglobin, hematocrit, white blood cell count, platelets) were also significantly increased in diabetic rats treated with either peppermint essential oil (40 mg/kg and 80 mg/kg) or positive control (glibenclamide) compared to diabetic controls (P<0.05).(Abdellatief 2017) In a study of adult Wistar rats, weight loss due to heat stress was mitigated with administration of peppermint extract, with 300 mg/kg and 600 mg/kg doses producing the greatest weight gains (+11 g and +16 g, respectively) compared to controls and compared to the 75 mg/kg and 150 mg/kg doses (P<0.05). Additionally, triglycerides, total cholesterol, and LDL were significantly lower with peppermint extract administration. However, administration of peppermint extract significantly increased glucose levels in a dose-dependent manner.(Mesbahzadeh 2015)

GI use

Menthol (the main component of peppermint oil) plasma levels exhibited dose proportionality in children 7 to 12 years of age with functional abdominal pain; indicative of linear pharmacokinetics. When corrected for the weight-adjusted dose, no difference was observed in total systemic exposure, C_max, or T_max for the 180, 360, or 540 mg dose of peppermint oil. The mean T_max ranged from 1.7 to 2.9 hours following administration of a delayed-release formulation. A possible dose-related difference in the mean elimination half-life was observed (2.1 hours for the low dose vs 4.6 hours for the high dose). High interindividual variability in dose-exposure relationship was observed among the 30 participants, possibly due to enterohepatic recycling with subsequent deconjugation in the intestinal lumen and drug reabsorption. Kinetics were unaffected by age, sex, race, ethnicity, demographic variables, or anthropometric values.(Shulman 2022)

Antiemetic activity

Animal and in vitro data

In vitro, an allosteric effect of menthol and peppermint oil on 5-HT₃ receptors may explain its antiemetic action; however, the effect was weak and may not be clinically relevant.(Heimes 2011) Animal models support the use of peppermint oil in reducing nausea.(Golembiewski 2005)

Clinical data

Clinical trials have shown that aromatherapy with menthol and peppermint oil may be more effective than placebo in treating postoperative nausea(Tate 1997) but is no more effective than standard treatments.(Anderson 2004, Golembiewski 2005)

In a small study (N=33), peppermint oil aromatherapy was no better than placebo in averting postoperative nausea.(Anderson 2004) Similar results were reported by an evidence-based review of aromatherapy for postoperative nausea and vomiting, which concluded there is no reliable evidence supporting use of peppermint oil for this indication.(Hines 2012) In contrast, another study supported decreased frequency and severity of postoperative nausea and vomiting (P=0.001 for each) with inhalation of peppermint oil compared to placebo in 60 patients who underwent open-heart surgery.(Maghami 2020)

Peppermint was identified as one of the 4 most common herbs used for pregnancy-related nausea/vomiting by certified or licensed midwives in state-wide surveys conducted in California, Texas, and North Carolina.(Dennehy 2010)

The effects of peppermint oil on chemotherapy-associated nausea, vomiting, and retching were explored in adult cancer patients in an open-label quasi-randomized controlled pilot study. Application of 3% peppermint oil between the upper lip and nose as aromatherapy 3 times daily for 5 days following chemotherapy led to statistically significant improvement in the nausea-vomiting-retching scores for peppermint compared to controls (no aromatherapy) on days 1, 2, 3, and 4 for 4 of the 5 chemotherapy regimens (ie, folfirinox, paclitaxel-trastuzumab, carboplatin AUC < 4-paclitaxel, cyclophosphamide-adriamycin) but not for the cisplatin regimen (P<0.001 to P=0.047).(Efe Erturk 2021)

The American Society of Enhanced Recovery and Society for Ambulatory Anesthesia's 2020 updated guideline for the management of postoperative nausea and vomiting (PONV) now recommends multimodal prophylaxis in adults with at least 1 risk factor. As a nonpharmacologic option, results from an updated meta-analysis for treatment of PONV determined that peppermint aromatherapy was no more effective than placebo in reducing nausea at 5 minutes (level A1). However, results from a small pilot study suggested that peppermint chewing gum was not inferior to ondansetron for PONV treatment in women who underwent laparoscopic or breast surgery under general anesthesia (level A3). Additionally, the guidelines highlight that the Enhanced Recovery After Surgery society recommendations include the liberal use of chewing gum as part of their enhanced recovery pathway to minimize PONV and postoperative ileus in patients who have undergone radical cystectomy for bladder cancer.(Darvall 2017, Gan 2020)

Biliary disorders

Animal and in vitro data

Choleretic action of peppermint oil has been described,(Grigoleit 2005, Zong 2011) with animal and in vitro studies demonstrating a significant increase in bile flow as well as changes in components of bile (eg, total cholesterol, bile acid, total bilirubin, direct bilirubin) after administration of peppermint oil. Gene expression related to bile acid synthesis was significantly upregulated in a time-dependent manner.(Zong 2011)

Dyspepsia

Clinical data

Gastric emptying was accelerated by peppermint oil when added to a test meal.(Inamori 2007) However, in a small randomized crossover study enrolling 10 healthy H. pylori-negative males, addition of peppermint oil to a histamine H₂ receptor antagonist (lafutidine) did not increase average intragastric pH or provide a longer duration of pH levels greater than 2, 3, 3.5, 4, 5, 6, and 7 compared to laftudine alone.(Iida 2011)

Functional abdominal pain

Clinical data

In 30 children 7 to 12 years of age with functional abdominal pain in the absence of a significant chronic medical condition, the pharmacokinetics of 3 doses of peppermint oil (180, 360, and 540 mg/day) and the relationship between systemic exposure and GI motility were investigated. Overall, mean pain severity was lower during the treatment period compared to baseline (P=0.004) and no adverse events were reported. No significant difference was observed in motility or gastric transit time after treatment compared to baseline. However, stomach contraction frequency increased significantly compared to baseline in the 540 mg group, whereas whole gut contraction was observed to decrease significantly in the 360 mg group (P=0.031 for each). Dose-pharmacodynamic relationships included a direct correlation between stomach as well as duodenal contraction frequency and dose (P=0.02 and 0.39, respectively), and between ileal mean contraction amplitude and dose (P=0.028). No correlation was found for dose and transit time.(Shulman 2022)

Irritable bowel syndrome

Clinical data

Administration of peppermint oil should be considered only after definite diagnosis of IBS with no associated organic lesions, and after other diagnoses have been eliminated.(Cash 2016) Reviews of peppermint oil and its role in IBS confirm its effectiveness compared with placebo and as standard treatment in patients with nonserious constipation or diarrhea to reduce global symptoms, pain, and bloating. Benefit may favor lower GI (eg, abdominal pain, bloating, stool consistency, stool frequency, flatulence) over upper GI symptoms (eg, belching, heartburn, nausea).(Cappello 2007, Ford 2008, Grigoleit 2005, Hadley 2005, Harris 2006, Huertas-Ceballos 2008, Jailwala 2000, Jones 2006, Kline 2001, Liu 1997, Merat 2010, Pittler 1998, van Zanten 2009) In contrast, no difference was reported between peppermint oil and placebo in IBS severity scores or secondary outcomes in a double-blind, randomized study that enrolled 133 patients with moderate to severe IBS symptoms. The majority of patients had IBS with diarrhea (mean, 39%) or mixed diarrhea/constipation (mean, 37%). Peppermint oil was administered as enteric-coated 180-mg capsules taken 30 minutes before meals 3 times daily for 6 weeks. Twice as many patients in the treatment group withdrew from the study (34.8%) compared to placebo (18.4%) with 17.4% vs 9.2% due to adverse events, respectively. The incidence of reflux/heartburn and belching were significantly higher for peppermint oil than placebo (26.1% vs 11.5% and 10.9% vs 2.3%, respectively).(Nee 2021)

A review of clinical trials investigating dosages of up to 1,200 mg/day of enteric-coated peppermint oil (capsules containing 180 to 200 mg of peppermint oil and administered as 1 to 2 capsules 3 times daily) over 2 to 4 weeks suggested peppermint oil may be a drug of first choice in patients with nonserious constipation and diarrhea associated with IBS to alleviate general symptoms and improve quality of life.(Grigoleit 2005) A 2014 systematic review and meta-analysis of 9 studies (N=726) evaluating peppermint oil for treatment of IBS symptoms support these observations.(Khanna 2014) In the Irritable Bowel Syndrome Reduction Evaluation and Safety Trial (IBSREST), which enrolled 72 patients with mixed- or diarrhea-type IBS, a novel capsule formulation incorporating triple-coated microspheres of peppermint oil (180 mg 3 times daily for 4 weeks) designed to provide sustained release in the small intestine was effective in providing rapid relief of IBS symptoms; at 24 hours and 4 weeks, Total IBS Symptom Score was significantly improved compared to placebo, and treatment was well tolerated.(Cash 2016) Similarly, abdominal pain (6 studies, N=556) and global IBS symptom improvement (7 studies, N=507) were found to be significantly improved with oral peppermint oil compared to placebo in another systematic review and meta-analyses of randomized, controlled trials. No heterogeneity was found among studies for either result.(Alammar 2019)

An American College of Gastroenterology monograph on the management of IBS and chronic idiopathic constipation (2014) states that peppermint oil is superior to placebo for improving IBS constipation symptoms. Limited data suggest it may attenuate visceral hypersensitivity and modulation of pain sensation (weak recommendation; moderate-quality evidence).(Ford 2014) The American College of Gastroenterology (ACG) clinical guideline for the management of irritable bowel syndrome (2021) suggests using peppermint/peppermint oil to provide relief of global IBS symptoms (conditional; low).(Lacy 2021) Likewise, the American Gastroenterology Association's updated clinical practice guidelines on the pharmacological management of IBS with diarrhea (2022) and with constipation (2022) continue to suggest using antispasmodics, including peppermint oil, in patients with IBS (conditional, low).(Chang 2022, Lembo 2022) The British Society of Gastroenterology's updated guidelines on the management of irritable bowel syndrome (2021) make a weak recommendation on the use of peppermint oil as an effective treatment for global symptoms and abdominal pain in IBS. Gastroesophageal reflux has been noted as a common side effect (very low).(Vasant 2021)

Smooth muscle spasm

Smooth muscle antispasmodic effects of peppermint appear to result from menthol inhibition of contractile response to acetylcholine, histamine, 5-HTP, and substance P via reduced calcium influx.(Asao 2001, Grigoleit 2005, Hills 1991, Khalaf 2019)

Clinical data

The oil or its l-menthol extract has been useful for colonic(Asao 2001, Grigoleit 2005, Somerville 1984, Sparks 1995) and esophageal spasm,(Hiki 2003, Massey 2001, Pimentel 2001) as well as to suppress peristalsis during colonoscopy(Inoue 2014, Shavaki 2012, Shah 2019) and other endoscopic procedures.(Asao 2001, Fujishiro 2014, Hiki 2012, Hiki 2003, Imagawa 2012, Mizuno 2006, Papathanasopoulos 2013, Yamamoto 2006)

In a double-blind, randomized placebo-controlled trial (N=66), times required for cecal intubation and total procedure were significantly reduced (P<0.001 each) with administration of enteric-coated peppermint oil capsules (ie, Colpermin; 187 mg of peppermint oil per capsule) as premedication for colonoscopy. Additionally, patient scores for colonic spasm, pain, and willingness to repeat the procedure (90% vs 19%, respectively), as well as endoscopist satisfaction scores were significantly better for the peppermint oil group compared to placebo (P<0.001 for each). Adverse effects reported in the treatment group (and not in the placebo group) included heartburn (n=1) and vomiting (n=1), with the latter leading to study discontinuation.(Shavaki 2012) Compared to placebo, l-menthol intracolonic spray led to significantly higher detection rates of adenomas (60.2% vs 42.6%; P=0.008), lower peristalsis scores (P<0.0001), and a higher proportion of patients with no peristalsis (71% vs 30.9%; P<0.0001).(Inoue 2014) Similar results were observed in a study of patients undergoing endoscopic gastric treatment; no or mild peristalsis was reported in 85.4% of patients receiving l-menthol compared to 39% of those receiving placebo (P<0.001), and higher sustained response rates were observed in the l-menthol group compared to placebo (P<0.001).(Fujishiro 2014) Sustained reduction in gastric phasic contractility resulting in a reduction in fasting intragastric pressure has also been documented following acute administration of peppermint oil.(Papathanasopoulos 2013) In another study of patients undergoing gastric endoscopy, sustained reduction in peristalsis with intragastric administration of l-menthol was dose dependent and significantly different than placebo. An adverse drug reaction occurring more often with menthol than placebo was mild headache; no abnormality in gastric mucosa was found at the antrum spray site in any subjects.(Hiki 2012) Mixed outcomes were reported with topical instillation of peppermint oil solution sprayed directly on the bowel wall at the time of a screening colonoscopy in a double-blind, randomized, placebo-controlled trial (N=48). Although average time to reach the cecum and the degree of colonic spasticity were significantly less in the peppermint oil group (P=0.04 and P=0.05, respectively), no significant differences were observed in total colonoscopy time, withdrawal time, extent of bowel wall visualization, severity of peristalsis, or perception of pain.(Shah 2019)

In a non-controlled retrospective study, data were assessed from patients with esophageal motility disorders who were treated with oral peppermint oil (11% via peppermint Altoids) for non-obstructive dysphagia (NOD) and/or non-cardiac chest pain (NCCP). Response rates were highest among those presenting with both NOD and NCCP (73%) and lowest among those with dysphagia only (53%). Significant response rates were observed in those presenting with esophagogastric junction outflow obstruction (100%) or distal esophageal spasm (83%) compared to other manometric diagnoses (P<0.01 for each), with parallel results seen in symptom relief scores (P=0.02 and P=0.002, respectively). The treatment was well tolerated.(Khalaf 2019)

Hepatoprotectant effects

Animal data

Peppermint oil protected against experimental hepatic injury by arsenic and other chemicals in mice and rats,(Bellassoued 2018, Ogaly 2018, Sharma 2007) with efficacy comparable to that of silymarin, a well-known antioxidant. Improvements were seen in liver enzymes, lipid parameters, lipid peroxidation biomarkers, and antioxidant enzymes; attenuation of histopathological hepatic lesions and fibrosis was also observed.(Bellassoued 2018, Ogaly 2018) Beneficial effects were dose dependent and were observed with a 40 mg/kg dose of M. piperita leaf essential oil but not with a 5 mg/kg dose.(Bellassoued 2018)

Nipple cracks

Clinical data

Topical peppermint water has been studied for prevention of nipple cracks in 196 primiparous breastfeeding women, with statistically significant favorable results observed in the peppermint water group.(Sayyah Melli 2007)

Polycystic ovary syndrome

Clinical data

A 2017 systematic review and meta-analysis of nutritional supplements and herbal medicines for polycystic ovary syndrome identified 1 randomized controlled trial evaluating the effects of M. spicata (N=41). Although no primary outcome data were reported, a significant effect was reported for peppermint compared to chamomile tea for reduction in total testosterone (P=0.03).(Arentz 2017)

Respiratory effects

Clinical data

Menthol is available in a variety of nonprescription products (eg, chest rubs, inhalants, lozenges, syrups) for the treatment of colds and related congestion and cough. A decrease in cough was demonstrated in children when menthol inhalation was compared with placebo.(Houghton 1998) The mechanism by which menthol may act as an antitussive is speculative(Eccles 1994); however, anion transporters (eg, TPRV1, TRPA1, ASICs) in airway epithelial cells have been implicated.(Morise 2010, Wise 2012) In a study of 12 healthy volunteers, a significant increase in cough threshold was observed via chemosensory stimulation using a sucrose mouth rinse followed by inhalation of menthol vapor. However, the effects demonstrated by l-menthol were lower than those following mouth rinse with the sucrose solution (25% vs 45%, respectively). High individual variability in sensitivity to menthol and sucrose pretreatment was observed.(Wise 2012) Antitussive effects were also demonstrated in adult patients with sensory hyper-reactivity and chronic cough (N=29) following pretreatment with a 1% (P<0.02) and 0.5% (P<0.05) nebulized menthol solution compared to placebo.(Millqvist 2013)

Menthol inhalation can cause a subjective nasal decongestant effect without any objective decongestant action. In lozenges, the main action of menthol appears to be a subjective sensation of improved nasal airflow.(Eccles 1994)

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.(Tamaoki 1995) Similarly, no significant differences were observed in upper airway resistance in healthy volunteers receiving inhaled menthol,(Pereira 2013) or in spirometry outcomes in patients with chronic cough and sensory hyper-reactivity receiving menthol pretreatment compared to placebo or healthy controls.(Millqvist 2013)

Smoking cessation/nicotine metabolism

Clinical data

In an open-label crossover study of adult smokers of nonmentholated cigarettes, the metabolic conversion of nicotine to cotinine was significantly reduced during what was referred to as a "mint drink period," during which peppermint tea was administered, compared to the "off-menthol" period, during which menthol-containing products and mint drinks were avoided (P<0.0001).(Ghazi 2011) However, other studies evaluating the effects of menthol on biomarkers of exposure in cigarette smokers show equivocal results regarding cotinine and nicotine levels.(Strasser 2013) Both nicotine and menthol activate the same somatosensory receptor (TRPA1) in a reversible manner, with desensitization of perceived nicotine irritation demonstrated after pretreatment with menthol. However, in a small crossover trial of 20 nonmenthol smokers, the perception of stinging pain from nicotine was decreased significantly more in a no-menthol condition compared with a menthol condition (P=0.0018).(Renner 2012) With the passing of the Family Smoking Prevention and Tobacco Control Act of 2009, the US Food and Drug Administration (FDA) gained authority to regulate tobacco products, including the power to ban associated flavors like clove but not menthol. To provide follow-up recommendations to the FDA, research has investigated the effect that a menthol ban might have on smokers. Findings have been mixed.(Rojewski 2014, Smith 2014, Strasser 2013)

In one open-label, randomized study of 60 adult smokers of menthol cigarettes, the effect of removing menthol from cigarettes was explored. Of the 32 smokers who completed the study, a worse taste, aftertaste, and less pleasant smoke smell were reported in the experimental group when transitioning from the menthol to the nonmenthol smoking period compared to the control group, consisting of smokers who continued to smoke their own brand cigarette across all periods. Additionally, smoking behavior outcomes such as puff volume and duration, but not number of puffs, increased from the menthol to the nonmenthol period. However, no change was observed in the number of cigarettes smoked per day between these 2 periods. No differences were observed in carbon monoxide, nicotine, or cotinine levels, or in the oxidative stress biomarker 8-oxo-dGuo between the menthol and nonmenthol sessions.(Strasser 2013) In a study assessing the relationship between menthol cigarette use and measures of cessation success, menthol cigarette smoking was associated with a lower abstinence rate compared to nonmenthol smoking after controlling for cessation treatment type. In a longitudinal secondary analysis of data from the Wisconsin Smokers Health Study (N=1,504 smokers), an estimated probability of abstinence success was reported as 37% for menthol smokers versus 45% for nonmenthol smokers. The magnitude of this effect decreased, as did the difference between abstinence probabilities when adjusted for the covariates of education, living with a smoker, proportion of friends smoking, and level of nicotine dependence. Statistical significance between menthol and nonmenthol cigarette smoking on cessation rates was lost when study site was included as an additional covariate to those previously listed. When race and gender covariates were combined, a significantly lower probability in abstinence was evident in females versus males who smoked menthol cigarettes, particularly black females compared with white females (17% vs 35%, respectively; P<0.0001).(Smith 2014) Similarly, a secondary analysis of data from a randomized controlled trial of low-dose naltrexone as an adjunct to nicotine replacement therapy reported significantly lower abstinence rates in menthol versus nonmenthol smokers at both 14 and 26 weeks (P=0.04 each). Weight gain was noted to be significantly higher in menthol smokers who quit than nonmenthol smokers who quit (P=0.03).(Rojewski 2014)

Other

Of 31 complementary and alternative medicine (CAM) remedies, peppermint oil was ranked in the bottom 10 and was the least recommended herbal remedy for dental issues (28%) made by German dentists and maxillofacial surgeons according to a prospective, cross-sectional survey (N=250). As one might expect, perceived effectiveness was rated higher among CAM proponents than opponents.(Baatsch 2017)

Dosing

Various dosages of peppermint oil in enteric-coated capsules have been evaluated for use in GI conditions and procedures.Cash 2016, Grigoleit 2005, Shavakhi 2012, Somerville 1984

Dosages of up to 1,200 mg/day of enteric-coated peppermint oil (capsules containing 180 to 200 mg of peppermint oil and administered as 1 to 2 capsules 3 times daily) over 2 to 4 weeks have been used in the treatment of nonserious constipation and diarrhea associated with IBS.Grigoleit 2005

In one study, a novel capsule formulation incorporating triple-coated microspheres of peppermint oil (180 mg 3 times daily for 4 weeks) was used for relief of IBS symptoms.Cash 2016

Enteric-coated peppermint oil capsules (Colpermin; 187 mg of peppermint oil per capsule) have also been used as antispasmodic premedication 4 hours prior to colonoscopy.Shavakhi 2012

Because of peppermint oil's ability to relax GI smooth muscle, patients with hiatus hernia may experience worsening symptoms while ingesting peppermint-containing preparations.Hills 1991

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

Pregnancy / Lactation

Adverse reactions, particularly with higher doses, have been documented with use of peppermint. Use in pregnancy should be avoided because of emmenagogue effects.Ernst 2002 Peppermint water applied topically has been studied for prevention of nipple cracks in breastfeeding women.Sayyah Melli 2007 Peppermint is reported to be one of the most commonly used herbal medicines by women in Asian countries and, in low doses, is considered safe during pregnancy, with no harmful effects observed to mother or fetus. However, consumption of high doses can trigger menstruation and abortion.Ahmed 2017

Interactions

In a small open-label study, peppermint tea (150 mL consumed 3 times daily for 7 days) significantly reduced the metabolism of nicotine to cotinine in adult smokers of nonmentholated cigarettes (P<0.0001). It is unknown whether peppermint inhibited the CYP2A6 or the aldehyde oxidase step of nicotine metabolism.(Ghazi 2011)

Aripiprazole: CYP3A4 inhibitors (weak) may increase the serum concentration of aripiprazole. Monitor therapy.(Abilify February 2011, Abilify Maintena February 2013, Aung 2010, Azuma 2012, Kubo 2005)

Caffeine: Absorption of a single dose of caffeine 200 mg was delayed by menthol 100 mg in healthy volunteers.(Gelal 2003)

Cyclosporine: Decreased cyclosporine levels were reported in a patient consuming herbal tea containing peppermint and 8 other herbs.(Nowack 2005)

Dofetilide: CYP3A4 inhibitors (weak) may increase the serum concentration of dofetilide. Monitor therapy.(Johnson 2001, Tikosyn February 2011, Walker 1996)

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%.(Dresser 2002) However, a study of the effect of menthol showed no effect on felodipine pharmacokinetics in healthy adults.(Gelal 2005) A class effect on other calcium channel blocking agents has been previously suggested.(Beesley 1996)

Flibanserin: CYP3A4 inhibitors (weak) may increase the serum concentration of flibanserin. Monitor therapy.(Addyi August 2015)

Lomitapide: CYP3A4 inhibitors (weak) may increase the serum concentration of lomitapide. Consider therapy modification.(Juxtapid March 2016, Patel 2016)

Nicotine: Peppermint may decrease the metabolism of nicotine. No action needed.(Ghazi 2011)

Nimodipine: CYP3A4 inhibitors (weak) may increase the serum concentration of nimodipine. Monitor therapy.(Nimodipine April 2015)

Pimozide: CYP3A4 inhibitors (weak) may increase the serum concentration of pimozide. Avoid combination.(Desta 1998, Desta 1999, Flockhart 1996, Orap August 2011)

Simvastatin: Peppermint oil may influence metabolism of simvastatin via inhibition of CYP3A4, elevating simvastatin plasma concentrations and increasing pharmacologic and adverse reactions. Peppermint oil 600 mg in water increased the AUC of simvastatin by 30% in healthy volunteers.(Dresser 2002)

Adverse Reactions

Menthol, the major component of peppermint oil, may cause allergic reactions (eg, contact dermatitis, flushing, headache).Herro 2010, Kawane 1996, Leung 1980, Posadzki 2012, Wilkinson 1994 Delayed patch-test reaction to menthol and peppermint oil may occur 6 to 14 days after application.Fleming 1998 Symptoms of contact sensitivity and ulceration from oral menthol/peppermint-containing products improved with discontinuation and avoidance of these products.Morton 1995 In a crossover study of migraine patients, cutaneous burning sensation (8.3% of migraine attacks), lacrimation (5% of attacks), and aggravation of headache (1.6% of attacks) were most common with menthol; 2 patients in the menthol group discontinued the study due to severe burning sensation and aggravation of headache.Borhani Haghighi 2010

Burns and skin necrosis following topical application of peppermint oil have been reported.Posadzki 2012 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.Tamir 2005 Excessive consumption of mint-flavored sweets caused stomatitis with oral papillary hypertrophy.Rogers 1995 Vulval allergic contact dermatitis was documented in a patient who consumed large amounts of peppermint tea.Vermaat 2008 A peppermint foot spray was linked to dermatitis in another patient,Kalavala 2007 and several cases of dermatitis of the lips and mouth were traced to peppermint flavored/menthol-containing lip balm, toothpaste, and throat spray.Bourgeois 2016, Tran 2010 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.Kanerva 2001 Loss of libido in men following consumption of peppermint tea has been reported.Akdogan 2004

Related/similar drugs

Toxicology

Like other mints from which menthol is derived as a plant extract, peppermint has GRAS status when consumed as a seasoning or flavoring.McKay 2006, Nair 2001 Two comprehensive reports on peppermint safety have been published,Nair 2001, SCF 2002 with pulegone and menthofuran being the constituents of toxicologic concern. Radiolabeled pulegone binds to rat kidney alpha-2u-globulin, which may be a target of toxicity.Ferguson 2007

Rats fed peppermint oil in dosages of up to 100 mg/kg/day 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, similar in nature to the neuropathy induced by hexachlorophene and attributed to the pulegone component of peppermint oil.Nair 2001, Olsen 1984 However, oil doses of this magnitude would be considered an overdosage with the oil. Standards for peppermint oil limit pulegone concentration to 1% of the oil.Nair 2001

A case of delirium resulting from intoxication by oral ingestion of topical mentholatum required hospitalization in a woman with chronic alcoholism.Huntimer 2000 A man with chronic alcoholism also experienced delirium after possible oral ingestion of a topical menthol/alcohol-containing analgesic.Weiss 2001 Pulmonary edema and acute lung injury occurred in a patient following intravenous injection of peppermint oil.Behrends 2005

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.Hills 1991 Peppermint oil should not be applied to the face, especially under the nose of a child or infant.Eccles 1994 The application of menthol-containing ointment to the nostrils of an infant for the treatment of cold symptoms has caused instant collapse.Leung 1980 Enteric-coated preparations have not been studied in children younger than 8 years and are not recommended for use in very young children.Kline 2001 No association between use of peppermint in the last 2 trimesters of pregnancy and premature birth has been identified, but use in pregnancy should be avoided.Moussally 2010

Index Terms

• Mentha aquatica L.
• Mentha spicata L.
• Spearmint

References

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