What is peppermint oil good for?

Peppermint is a hybrid mint, a cross between two types of mint water mint [Mentha aquatica] and spearmint [Mentha spicata L.] also known as Mentha piperita. Indigenous to Europe and the Middle East, the plant is now widespread in cultivation in many regions of the world ¹. Peppermint has been used for health purposes for several thousand years. It is mentioned in records from ancient Greece, Rome, and Egypt. Peppermint oil is obtained by steam distillation from the fresh leaves of peppermint ². Both peppermint leaves and peppermint essential oil from peppermint have been used for health purposes. However, peppermint was not recognized as a distinct kind of mint until the 1700s. Essential oils are very concentrated oils containing substances that give a plant its characteristic odor or flavor. Peppermint is a common flavoring agent in foods, and peppermint oil is used to create a pleasant fragrance in soaps and cosmetics. Today, peppermint is promoted for irritable bowel syndrome (IBS), other digestive problems, the common cold, sinus infections, headaches, and other conditions. Peppermint oil is promoted for topical use (applied to the skin) for problems like headache, muscle aches, joint pain, and itching. In aromatherapy, peppermint oil is promoted for treating coughs and colds, reducing pain, improving mental function, and reducing stress.

Although results from clinical trials are mixed, the majority of evidence indicates that enteric-coated peppermint oil may be modestly effective in reducing some of the common symptoms of IBS. In combination with caraway oil, peppermint oil also may be effective in treating non-ulcer dyspepsia. Limited data show a modest effect at reducing colonic spasm during barium enema. Topical peppermint oil also may be helpful for treatment of tension headache. Peppermint oil should only be used at the recommended doses because significant toxicity can occur at higher doses. Even the recommended medicinal doses of peppermint oil should not be used in infants or very young children, or in women who are pregnant or lactating.

Peppermint oil contains a large number (> 80) of components including menthol (35–55%), l-menthone (20–31%), menthyl acetate (3–10%), cineol, and several other volatile oils (piperitenone carvone, menthofuran, isomenthone, isopulegol, 3-octanol, pulegone) ³. Peppermint oil major constituent and active ingredients appear to be menthol that in nature exists as a pure stereoisomer ⁴. Menthol activates cold-sensitive TRPM8 receptors in the skin and mucosal tissues, and is the primary source of the cooling sensation that follows the topical application of peppermint oil ⁵. Menthol is listed as generally regarded as safe (GRAS) by the US Food and Drug Administration ⁶. Peppermint oil has a high concentration of natural pesticides, mainly pulegone and menthone ⁷. It is known to repel some pest insects, including mosquitos, and has uses in organic gardening ⁷.

In addition, δ-cadinene, copaene, eugenol, methyl pivalate, menthomenthene, thujopsene, caryophyllene oxide also some of the compound identified in peppermint essential oil and demonstrated antifungal activity and antibacterial activity ⁸, ⁹. Peppermint essential oil have shown potent inhibitory activity against several microorganisms such as Penicillium digitatum, Aspergillus flavus, Aspergillus niger, Candida albicans, Saccharomyces cerevisiae Mucor spp., and Fusarium oxysporum ¹⁰. Peppermint oil has been reported as antifungal agent for several mycotoxigenic speceies by Silva et al. ¹¹; Aspergillus flavus and Aspergillus parasiticus, Freire et al. ¹², in 2012 reported against Aspergillus ochraceous, Colletotrichum gloeosporioides, Colletotrichum musae, F. oxysporum, Fusarium semitectum. Peppermint essential oil anti-inflammatory ¹³, antioxidant ¹⁴ and cytotoxic effects were reported by Sun et al. ¹⁵. Owing to the various constituents of peppermint, it has a variety uses, including topical application as an antiseptic and analgesic, inhalation as aromatherapy, and oral formulation for treatment of headache and various functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). Currently, peppermint essential oil has been widely used in cosmetic, food and pharmaceutical industries.

Peppermint leaves are aromatic perennial herb cultivated in most part of the world and it is used as folk medicine and frequently used in herbal tea and for culinary purpose to add flavor and aroma ¹⁶. Today, peppermint is used as a dietary supplement for irritable bowel syndrome (IBS), other digestive problems, the common cold, headaches, and other conditions. Peppermint oil is also used topically (applied to the skin) for headache, muscle aches, itching, and other problems. Peppermint leaf is available in teas, capsules, and as a liquid extract. Peppermint oil is available as liquid solutions and in capsules, including enteric-coated capsules.

Peppermint tea, which is made from peppermint leaves, appears to be safe. However, the long-term safety of consuming large amounts of peppermint leaf is unknown.

Peppermint oil appears to be safe when taken orally (by mouth) or applied topically in the doses commonly used. Peppermint oil has been safely used in many clinical trials. However, like many essential oils, peppermint oil can be toxic and even lethal at excessive dosages; it has been associated with interstitial nephritis and acute renal failure ¹⁷. It may have a choleretic effect and is contraindicated in patients with cholelithiasis or cholecystitis. Peppermint oil is relatively contraindicated in patients with hiatal hernia or significant gastroesophageal reflux disease, because its effect on the lower esophageal sphincter can lead to exacerbation of symptoms.

Peppermint oil has been used to trigger menstruation and should be avoided during pregnancy. Little is known about whether it’s safe to use peppermint oil during pregnancy or while breastfeeding. Peppermint oil should not be used internally or on or near the face in infants and young children because of its potential to cause bronchospasm, tongue spasms, and, possibly, respiratory arrest ¹⁸. However, the amount of peppermint in over-the-counter medications, topical preparations, and herbal teas is likely safe in pregnant and lactating women and in young children.

Possible side effects of peppermint oil taken orally include heartburn, nausea, and vomiting, abdominal pain, perianal burning, blurred vision and dry mouth ¹⁹. Rarely, peppermint oil can cause allergic reactions. Capsules containing peppermint oil are often enteric-coated to reduce the likelihood of heartburn. If enteric-coated peppermint oil capsules are taken at the same time as antacids, the coating can break down too quickly. Preliminary evidence from laboratory studies suggests that peppermint leaf and peppermint oil may inhibit the cytochrome P450 1A2 system ²⁰, which theoretically could lead to increased serum levels of drugs such as amitriptyline, cyclosporine (Sandimmune), and haloperidol (Haldol) in patients who regularly consume large amounts of peppermint leaf or peppermint oil. However, this interaction has not been proven to occur in humans. Peppermint oil has been reported to raise serum levels of simvastatin (Zocor) and felodipine (Plendil) in at least one case report ²¹.

Side effects of applying peppermint oil to the skin can include skin rashes and irritation. Peppermint oil should not be applied to the face of infants or young children because serious side effects may occur if they inhale the menthol in the oil.

Figure 1. Peppermint

Chemical Composition and Anti-Inflammatory, Cytotoxic and Antioxidant Activities of Peppermint Essential Oil from Leaves

51 volatile constituents in peppermint essential oil have been evaluated for their anti-inflammatory, cytotoxic and antioxidant activities ¹⁵. Test tube and animal studies showed that peppermint essential oil had a potent anti-inflammatory activity in the croton oil-induced mouse ear edema model, and the possible action mechanism might be attributed to its inhibitory effect on the production of nitric oxide (NO) and prostaglandin E2 (PGE2). Peppermint essential oil was also found to be active against SPC-A-1, K562 and SGC-7901 cancer cell lines. In addition, peppermint essential oil had a moderate antioxidant activity.

Peppermint antioxidant actions were previously suggested to be due to the presence of phenolic constituents in its leaves including rosmarinic acid and different flavonoids such as rutin, naringin, eriocitrin, luteolin, and hesperidin ²², ²³. High-performance liquid chromatography (HPLC) analysis of the peppermint leaf hydroalcoholic extract detected some peaks that coeluted with pure ursolic acid, epicatechin, caffeic acid, rutin, quercetin, naringenin, and kaempferol. These compounds were previously shown to act as anti-inflammatory and/or antioxidants ²⁴. In animal studies, it was clearly demonstrated in the Ames test that peppermint has antimutagenic effects once it significantly inhibited the shamma—a tobacco product—induced oral carcinogenesis in the hamster cheek pouch ²⁵. These results may serve as valuable research references for clinical research of medicines for treatment of inflammation and cancer in the future.

Table 1. Chemical composition of peppermint essential oil

	Molecular weight	Chemical constituents	(%)
1	136	α-Pinene	0.2
2	136	Sabinene	0.2
3	136	β-Pinene	0.46
4	136	β-Myrcene	0.52
5	134	Cymene	0.22
6	136	D-Limonene	1.76
7	154	Cineol	2.91
8	136	β-trans-Ocimene	0.07
9	154	Terpineol, cis-,β-	0.71
10	154	Linalool	0.42
11	154	2-Cyclohexen-1-ol, 1-methyl-4-(1-methylethyl)-, trans-	0.07
12	154	Isopulegol	0.15
13	154	Menthone	14.51
14	156	Neomenthol	9.26
15	156	Menthol	30.69
16	156	Cyclohexanol, 5-methyl-2-(1-methylethyl)-, (1α, 2α, 5α)-	0.45
17	154	Terpilenol	0.41
18	148	Estragole	0.3
19	138	Carane	0.07
20	152	Pulegone	4.36
21	152	Pipertone	2.31
22	198	Menthy acetate	12.86
23	198	Levomenthol	0.17
24	196	Isopuegyl acetate	0.08
25	204	Bicyclogermacrnene	0.06
26	164	Eugenol	0.11
27	204	α-Bourbonene	0.23
28	204	β-Elemene	0.29
29	164	Jasmone	0.09
30	204	Caryophyllene	2.52
31	204	β-Farnesene	0.54
32	204	Naphthalene, 1,2,4a,5,6,8a-hexahydro-4,7-dimethyl-1-(1-methylethyl)-	0.06
33	204	Germacrene	1.13
34	204	2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro-3,6-dimethyl-	1.69
35	204	Cadinene	0.18
36	154	β-(3-Thienyl)acrylic acid	2.09
37	220	Spathalenol	0.41
38	220	Caryophyllene oxide	1.37
39	222	Ledol	1.05
40	222	3-Hexadecyne	0.11
41	222	α-Cadinol	0.16
42	220	Aristolene epoxide	0.1
43	222	Eupiglobulol	0.35
44	236	Murolan-3,9(11)-diene-10-peroxy	0.06
45	212	Benzybenzoate	0.09
46	220	cis-Z-.α.-Bisabolene epoxide	0.2
47	268	Hexahydrofarnesgl acetone	0.15
48	238	Culmorin	0.08
49	296	Phytol	0.14
50	290	Grindelene	0.06
51	282	Eicosanel	0.06

Footnote:
^aRetention time (min).
^bKovats index relative to n-alkanes (C₉–C₂₅) on HP-1 capillary column.

[Source ¹⁵]

Peppermint essential oil benefits

In Eastern and Western traditional medicines, peppermint and its oil have been used in antispasmodics, aromatics, antiseptics or even medications for the treatment of colds, cramps, indigestions, nausea, sore throat, toothache or even cancer ²⁶. Modern pharmacology research has demonstrated that peppermint possesses antioxidant, antitumor, antiallergenic, antiviral and antibacterial activities ²⁷, ²⁸, ²⁹, ³⁰.

Peppermint oil for IBS (Irritable Bowel Syndrome)

Irritable bowel syndrome (IBS) is a common condition with a community prevalence of 10-15% of the general population ³¹. The annual incidence in primary care is around 0.8%, and the prevalence of patients diagnosed in primary care is about 3-4% ³². IBS has no single identified cause. It is not a pathological condition, i.e. there is no underlying disease process, but the bowel does not function properly, causing discomfort and inconvenience for sufferers. The pathophysiology of IBS is complex and involves an interaction of various factors, which includes, but is not limited to, genetic predisposition, gut-brain axis, visceral sensitivity, gastrointestinal motility, gut dysbiosis, neurotransmitters, food reactions, intestinal permeability, bile acids, inflammatory mediators, early-life stressors, psychosocial maladaptation, and somatization, among others ³³. IBS is difficult to treat, hence the wide range of treatments used—dietary exclusion, fiber supplements, and probiotics; antispasmodic drugs, antidiarrhoeal agents, and laxatives; antidepressants, hypnotherapy, and cognitive behavioral therapy. IBS patients with mild and intermittent symptoms usually benefit from lifestyle and dietary modification, which includes a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) ³⁴; and in some cases, lactose and gluten avoidance ³⁵. Smooth muscle relaxants and antispasmodics can also be used to help with IBS symptoms, especially abdominal pain and bloating ³⁶.

Although results of studies on the use of peppermint oil for the treatment of IBS symptoms have been mixed ³⁷, there seems to be a trend indicating mild effectiveness in the reduction of some IBS symptoms, especially flatulence and abdominal pain and distension.

In this systematic review and meta-analysis ³⁸, the researchers investigated the effectiveness of antispasmodics, fiber and peppermint oil in the treatment of IBS (irritable bowel syndrome). Individual trials on these treatments have been of variable quality with conflicting results, and previous systematic reviews have also resulted in different conclusions. This is a high quality systematic review that looked into all published research of peppermint oil, muscle relaxants (or antispasmodics) and fiber used in the treatment of IBS (irritable bowel syndrome). The three treatments were all found to reduce the risk of having persistent symptoms (such as abdominal pain and bloating) compared to placebo.

The researchers searched medical research databases to identify all randomized controlled trials (including foreign language studies) involving adults who met diagnostic criteria for IBS and who had received investigations, if necessary, to exclude an underlying cause. Studies had to compare antispasmodics, fibre or peppermint oil with an inactive placebo drug. They also had to include a follow-up of at least one week with an assessment of cure or improvement of symptoms. The researchers also hand-searched abstracts of conference proceedings for potential studies and looked at reference lists of all selected studies.

The main outcome that the researchers looked for was the efficacy of any of the three treatments compared to placebo on all IBS symptoms or just abdominal pain. The researchers assessed the quality of the trials and results were pooled to give the relative risk of symptoms persisting after treatment.

The search found 35 eligible studies for inclusion: 19 involving antispasmodics, nine of fibre, four of peppermint oil, and three involving antispasmodics or fibre.

The 12 trials of fiber had a total of 591 people with IBS. Treatments included bran (five studies), ispaghula husk (six studies) and, in one study, concentrated fiber. Overall, any fiber treatment reduced the risk of persistent symptoms by 13%, but this result was only of borderline significance. The only individual treatment that gave a significant reduction in symptoms was ispaghula.

The 22 trials of antispasmodics included 1,778 people with IBS and used a variety of drugs (12 in total) at different doses. Overall, antispasmodics significantly reduced the risk of persistent symptoms by 32% ³⁸. Of the individual drugs, only hyoscine, cimetropium, pinaverium and otilonium gave consistent significant evidence of benefit.

The four trials of peppermint oil, at different doses, included 392 people with IBS. Across these studies, 26% of those randomized to peppermint oil experienced persistent symptoms compared to 65% of those assigned to placebo. This gave an overall 57% reduction in risk of persistent symptoms when taking peppermint oil ³⁸.

The number of people that would need to be treated to prevent one person from having persistent abdominal symptoms was 2.5 for peppermint, five for antispasmodics and 11 for fiber ³⁸. This review provides evidence to support the use of symptomatic treatments such as peppermint oil ³⁸.

However, there are several points to bear in mind:

• The trials included in the review were of variable size, included slightly different patient groups, fulfilling different diagnostic criteria for IBS, different doses and treatment durations, were carried out in different settings (e.g. primary or secondary care), and used different criteria for symptom improvement. In the antispasmodic and peppermint oil trials, heterogeneity (diversity) was demonstrated to be statistically significant, i.e. different methods and results were obtained between trials, which may call into question the validity of combining results of the studies in this way.
• Although peppermint oil was highlighted in the review, as it demonstrated the greatest reduction in risk, it only included four trials with 392 people. This limits the strength of the conclusions that can be drawn from the combination of these studies. However, this is partly countered by the fact that three of the studies were of high quality and there was no statistical heterogeneity when they were combined. This increases the confidence in the finding.
• The authors report that none of the trials state whether the allocation of the treatments was concealed. This means that practitioners may have been aware of whether the active treatment or placebo was being given to participants. It has been found that this type of bias may give an overestimation of treatment effect.
• Adverse effects were not consistently reported across studies, so no firm conclusions can be made about the safety of any of the three treatments.
• The trials have only compared each treatment to inactive placebo, so it cannot be assumed that any one treatment is more effective than the others.

A prospective, double blind, placebo-controlled randomized trial with 57 patients with IBS by Rome II criteria showed that 64% of patients receiving enteric-coated peppermint oil and 34% of placebo users experienced a reduction in the total IBS symptom score at 4 weeks of ≥50% in the intention-to-treat population ³⁹. They also assessed the symptom score at 4 weeks after the end of treatment (8 weeks) and found a persisting beneficial effect at 8 weeks. Another randomized double-blind placebo-controlled study on 90 outpatients with IBS by Rome II criteria was conducted to demonstrate the efficacy of peppermint oil on quality of life ⁴⁰. Patients were randomly assigned to receive one capsule of Colpermin® (Tillotts Pharma, Ziefen, Switzerland) or a placebo three times daily for 8 weeks. They examined the effectiveness of peppermint oil in terms of relieving symptoms and improving quality of life using a questionnaire addressing six IBS symptoms and the 36-item Short Form Health Survey (SF-36) for quality of life. At week 8, 42.5% of patients receiving peppermint oil and 22.2% of patients receiving placebo were free from abdominal pain or discomfort ⁴⁰. However, there were no significant between-group differences detected in other IBS symptoms such as abdominal distension, flatulence, loose stool, hard stool, urgency, and incomplete evacuation. Although overall scores of 36-item Short Form Health Survey (SF-36) for the two groups were not significantly different, patients in the peppermint oil group showed improvements in the SF-36 domains of bodily pain, general health, social functioning, and role limitations due to emotional problems.

A recent 2016 study by Cash et al ⁴¹ reported the findings of a 4-week double blinded, placebo controlled randomized controlled trial which tested a novel formulation of peppermint oil designed for sustained release in the small intestine (IBgard®, IM HealthScience, Boca Raton, FL, USA) for its efficacy and tolerability in reducing IBS symptoms in 72 patients with mixed IBS (IBS-M) or IBS with diarrhea (IBS-D) by Rome III criteria. The specialized enteric-coating utilized in their trial consisted of a solid-state matrix that was triple-coated and designed to deliver peppermint oil with sustained release to the small intestine with fewer potential adverse effects. At trial completion, there was a 40% reduction in the total IBS symptom score in the peppermint oil group compared to baseline vs. 24.3% with placebo ⁴¹. Moreover, there was an increased improvement in both multiple and individual gastrointestinal symptoms, as well as in severe or unbearable symptoms compared to the placebo.

Similarly, some meta-analyses have shown peppermint oil to be effective in IBS, the number needed to treat ranged between 2 and 3 ⁴². In most recent meta-analysis of 12 randomized controlled trials with 835 patients with IBS, the risk ratio (RR) for the effect of peppermint oil (n = 253) versus placebo (n = 254) on global symptoms was 2.39 ⁴³. Overall, there were no differences in the reported adverse effects, peppermint oil (9.3%) versus placebo (6.1%). The number needed to treat with peppermint oil was three for global symptoms and four for abdominal pain.

Table 2. Summary of clinical trials of peppermint oil

Subject	Design	County	Comparison	Number	Outcome	Ref.	Jadad score
IBS based on symptoms	Single center, randomized, double-blind, placebo-controlled	Taiwan	Peppermint oil 137 mg three times a day or four times a day, before meal, 4 weeks vs. placebo	25:49:00	Symptom improvements after peppermint oil therapy were significantly better than after placebo.	Liu et al. 44	4
IBS by Rome II	Single center, randomized, double-blind, placebo-controlled	Italy	Peppermint oil 450 mg two times a day, before meal, 4 weeks vs. placebo	28:29:00	A 4-week treatment with peppermint oil is more effective than placebo in reducing abdominal symptoms related to IBS.	Cappello et al. 39	4
IBS by Rome II	Single center, randomized, double-blind, placebo-controlled	Iran	Peppermint oil 187 mg three times a day, before meal, 8 weeks vs. placebo	33:27:00	Severity of abdominal pain and discomfort were reduced significantly in the peppermint oil group. Peppermint oil significantly improved the quality of life.	Merat et al. 40	5
IBS by Rome III	Multicenter, randomized, double-blind, placebo-controlled	USA	Peppermint oil 180 mg three times a day, 4 weeks vs. placebo	35:37:00	Patients treated with peppermint oil experienced greater improvement in multiple individual gastrointestinal symptoms as well as in severe or unbearable symptoms, compared to placebo.	Cash et al. 41	5
Childhood IBS by Manning or Rome II	Multicenter, randomized, double-blind, placebo-controlled	USA	Peppermint oil 374 mg or 187 mg three times a day, 2 weeks vs. placebo	21:21:00	After 2 weeks, improvements in the change of symptom scale were reported in 71% of the patients receiving peppermint oil compared with 43% receiving placebo with statistical significance.	Kline et al. 45	3
Functional dyspepsia based on symptoms	Single center, randomized, double-blind, placebo-controlled	Germany	Peppermint oil 90 mg and caraway oil 50 mg two times a day, 4 weeks vs. placebo	48:48:00	For the major symptoms (intensity of pain, sensation of pressure, heaviness and fullness, and global improvement), the superiority of combination therapy of peppermint oil and caraway oil over placebo was statistically significant.	May et al. 46	5
Functional dyspepsia by Rome III	Multicenter, randomized, double-blind, placebo-controlled	Germany	Peppermint oil 90 mg and caraway oil 50 mg two times a day, 4 weeks vs. placebo	58:56:00	Compared to placebo, 4-week treatment with peppermint oil and caraway oil therapy significantly reduced symptoms of epigastric pain and postprandial distress and improved the participants’ quality of life.	Rich et al. 47	5

Footnote: The Jadad score ⁴⁸ is often used to assess the methodological quality of controlled trials. Studies are scored according to the presence of three key methodological features of clinical trials, specifically randomization, masking, and accountability of all patients, including withdrawals. One point is added for a “yes” answer to each of the first five items, and one point is subtracted for a “yes” answer to either of the last two items, for an overall score from 0–5. Its short length and ease of use remain as attractions; the 3 feature brevity gives the least responder burden ⁴⁹.

Reduction of colonic spasm during gastrointestinal procedures

As a consequence of peppermint oil’s relaxing properties on smooth muscle, peppermint oil given via enema has been examined in two trials as a means to reduce symptoms of gastrointestinal spasm during administration of barium enema and possibly during colonoscopy ⁵⁰, ⁵¹. In a randomized controlled trial of 383 patients undergoing barium enemas, 37 to 41 percent of those who received peppermint oil experienced a non-spasm examination, compared with 13.4 percent of those who received placebo ⁵⁰. In an randomized controlled trial of 141 patients undergoing barium enemas, no residual spasm was evident in 60 percent of the treated group, compared with 35 percent of the control group ⁵¹.

Non-ulcer dyspepsia (functional dyspepsia)

A combination of enteric-coated peppermint oil and caraway oil has been shown in several clinical trials to reduce symptoms of non-ulcer dyspepsia (e.g., fullness, bloating, gastrointestinal spasm), but the specific preparation used in these trials is not available in the U.S. ⁵², ⁵³. A meta-analysis of several trials of a preparation containing peppermint and caraway oils plus other herbal extracts (Iberogast) found it to be effective in the treatment of functional dyspepsia ⁵⁴. This benefit may be the result of the preparation’s relaxing effect on the lower esophageal sphincter, with concomitant equalization of pressure between stomach and esophagus and reduced sensation of bloating and abdominal pressure. However, this effect theoretically could result in reflux symptoms in patients predisposed to gastroesophageal reflux. Because multiple herbs were used in these trials, it is difficult to draw definitive conclusions about the specific effects of peppermint in this condition.

Recently, a randomized placebo-controlled trial with 114 outpatients with chronic or recurrent functional dyspepsia demonstrated that a fixed peppermint and caraway- oil combination (Menthacarin) treatment is effective for the relief of functional dyspepsia symptoms and improvement of disease-specific quality of life ⁴⁷. After 4 weeks of treatment, pain and discomfort scores improved by 7.6 ± 4.8 and 3.6 ± 2.5 points for Menthacarin and by 3.4 ± 4.3 and 1.3 ± 2.1 points for placebo, respectively ⁴⁷.

Tension headache

Two trials have shown that topical application of peppermint oil is effective in reducing symptoms of tension headache ⁵⁵, ⁵⁶. In one randomized controlled trial, 32 patients were tested using a variety of topical herbal preparations ⁵⁵. Compared with persons who received placebo, there was a significant analgesic effect in patients who applied a peppermint and ethanol preparation. A second randomized controlled trial that compared the effectiveness of topical peppermint oil and acetaminophen on 164 headaches in 41 patients found that a 10% peppermint oil preparation significantly reduced headache intensity after 15 minutes ⁵⁶. There was no significant difference in effectiveness between peppermint oil and acetaminophen, and no adverse effects were reported.

Peppermint oil dosage

The dosage of peppermint oil for the treatment of gastrointestinal diseases usually ranges from 0.2 to 0.4 ml, three times a day in enteric-coated capsules ⁵⁷. The dosage of peppermint oil used in the single clinical trial in children was 0.1 mL three times daily for children weighing less than 45 kg (99 lb, 3 oz) ⁵⁸. The oral dosage of peppermint oil range studied in most IBS trials was 187 to 500 mg (0.2–0.4 ml) administered two or three times daily for 2 to 8 weeks ⁴⁰. To secure the availability of unmetabolized peppermint oil at the target organ, a lower digestive tract in IBS, enteric-coated formation such as Colpermin® and Mintoil® (Cadigroup, Rome, Italy) capsules have been developed and have been widely used in clinical trials or real-world practice ³⁹. Each capsule of Colpermin® and Mintoil® contains 187 mg and 225 mg peppermint oil, respectively ⁵⁷. These formulated capsules are usually administered 30 to 60 minutes before meals in order to guarantee low gastric pH which prevents untimely capsule dissolution with premature release of peppermint oil into the stomach ³⁹.

In functional dyspepsia, most trials used a dose of 90 mg of peppermint oil in combination with 50 mg of caraway oil in a specific standardized preparation that is not currently available in the United States ⁴⁷.

Peppermint oil toxicity and safety

Peppermint oil has been used safely for various conditions in short-term clinical trials. In a randomized controlled trial with 90 patients with IBS, the most common adverse events of peppermint oil treatment group were heartburn, headache, and dizziness. However, these were not significantly different in the two groups ⁴⁰. However, peppermint oil is relatively contraindicated in patients with hiatal hernia or significant GERD, because its effects on the lower esophageal sphincter can lead to exacerbation of symptoms ³. Especially, when non-coated peppermint oil is taken orally, it can cause heartburn, nausea, and vomiting. The effective delivery method to the target organ by enteric coating is believed to prevent or reduce these upper gastrointestinal symptoms as well as improve peppermint oil efficacy ³. Even in the enteric coated formulation, heartburn could develop because of the premature rupture of capsules containing peppermint oil ⁵⁹. High concentrations of peppermint oil have been reported to cause anal burning ⁶⁰. Other minor adverse effects of peppermint oil reported in clinical trials include allergic reactions and blurred vision. Because peppermint oil may inhibit the cytochrome P450 system, it theoretically could lead to increased serum levels of drugs such as amitriptyline, haloperidol, and cyclosporine which are metabolized by this enzyme ⁶¹. However, this interaction has not been proven in humans.

Toxicology studies of peppermint oil and its components have been performed in animals. Histopathological changes in the white matter of the cerebellum were seen in rats (n = 20) given peppermint oil at doses of 40 and 100 mg/kg orally for 28 days, but no adverse effects were observed at 10 mg/kg ⁶². No adverse effects were observed at 10 mg/kg. In a comparable 90 day rat study (n = 28), cyst-like spaces in the white matter of the cerebellum and hyaline droplets in the proximal tubules of the kidneys were observed in the highest dose group only ⁶³. Interestingly, the extension of the cyst-like spaces was not aggravated with prolonged dosing in this study. Menthol administered to rats by gavage at 200, 400 and 800 mg/kg for 28 days significantly increased absolute and relative liver weights and the vacuolization of hepatocytes at all doses, although no sign of encephalopathy was observed ⁶⁴. At 80 and 160 mg/kg, pulegone administered for 28 days induced atonia, decreased blood creatinine levels, lowered body weight and caused histopathological changes in the liver and white matter of the cerebellum ⁶⁴. No adverse effects were observed with 20 mg/kg pulegone. Menthone given orally to rats (n = 20) at 200, 400 and 800 mg/kg for 28 days decreased creatinine and increased alkaline phosphatase in a dose-dependent manner, increased bilirubin and liver and spleen weights, and also caused histopathological changes in the white matter of the cerebellum in the two highest dose groups ⁶⁵. The accumulation of protein droplets containing α2μ-globulin in proximal tubular epithelial cells of rats (n = 10/group) was observed after the administration of either 500–1000 mg/kg 1,8-cineole or 800–1600 mg/kg limonene for 28 days, however, no histopathological changes were observed in the brain ⁶⁶.

• Although peppermint is commonly available as an herbal supplement, there are no established, consistent manufacturing standards for it, and some peppermint products may be contaminated with toxic metals or other substituted compounds.
• Peppermint oil appears to be safe when taken orally (by mouth) in the doses commonly used. Excessive doses of peppermint oil can be toxic.
• Short-term and sub-chronic peppermint oil oral studies reported cystlike lesions in the cerebellum in rats that were given doses of Peppermint Oil containing pulegone, pulegone alone, or large amounts (>200 mg/kg/day) of menthone. Pulegone is also a recognized hepatotoxin ⁶⁷.
• Possible side effects of peppermint oil include allergic reactions and heartburn. Capsules containing peppermint oil are often enteric-coated to reduce the likelihood of heartburn. If enteric-coated peppermint oil capsules are taken at the same time as antacids, the coating can break down too quickly.
• Like other essential oils, peppermint oil is highly concentrated. When the undiluted essential oil is used for health purposes, only a few drops are used.
• Side effects of applying peppermint oil to the skin can include skin rashes and irritation. Repeated intradermal dosing with Peppermint Oil produced moderate and severe reactions in rabbits, although Peppermint Oil did not appear to be phototoxic. Peppermint oil should not be applied to the face or chest of infants or young children because serious side effects may occur if they inhale the menthol in the oil.
• A study on diet and the development of gastroesophageal reflux disease (GERD) ⁶⁸ found that frequent consumption of peppermint tea was a risk factor for the development of gastroesophageal reflux disease (GERD). Gastroesophageal reflux disease (GERD) is a chronic gastrointestinal disease that significantly reduces quality of life and, in some patients, leads to serious complications, such as oesophageal stricture, gastrointestinal bleeding, or Barrett’s oesophagus. According to various sources, the typical symptoms of this disease (heartburn, discomfort in the upper abdomen, acid eructation) are experienced daily by 4–10%, and weekly by 10–30% of the adult population in Western countries ⁶⁹. Literature sources suggest that peppermint decreases lower esophageal sphincter (LES) tension; moreover, peppermint oil (studied in animal models) relaxes the smooth muscles of the alimentary tract ⁷⁰. Oliveria et al. ⁷¹ found that 8% of heartburn patients reported complaints after consuming peppermint. In contrast, Terry et al. ⁷² and Bulat et al. ⁷³ did not observe any effect of consuming products and beverages with peppermint on reflux episodes. This issue requires further research.
• The long-term safety of consuming large amounts of peppermint leaf is currently unknown.

A review on the use of peppermint oil, leaf extract, leaf and leaf water in cosmetic formulations by Nair ⁷⁴ concluded that each are considered safe, although the concentration of pulegone in products containing these ingredients should be limited to 1%. Although the toxicity of menthol is considered to be low, it has the ability to enhance the penetration and absorption of other agents contained in some formulations, thereby increasing the effective dose of these agents at the indicated intake. A few case study reports have described contact sensitivities to peppermint oil and its components in topical and oral preparations ⁷⁵, ⁷⁶, but a patch test study of 4000 patients by Kanerva et al. ⁷⁷ found that menthol and peppermint oil provoked neither allergic nor irritant reactions.

Akdogan et al. ⁷⁸ reported increased follicle stimulating hormone (FSH) and luteinizing hormone  (LH) levels and decreased testosterone levels in rats given 20 g/L peppermint tea in place of their drinking water. As opposed to spearmint tea, the only effect of peppermint on testicular tissue was segmental maturation arrest in the semniferous tubules. There are no chronic toxicity studies of peppermint in humans, although the German Commission E ⁷⁹ reports that the use of peppermint oil is contraindicated in patients with bile duct, gallbladder and liver disorders. Caution is also recommended for the use of peppermint oil capsules in patients with GI reflux, hiatal hernia or kidney stones.

Peppermint oil summary

• Peppermint oil has been studied most extensively for IBS. Results from several studies indicate that peppermint oil in enteric-coated capsules may improve IBS symptoms in adults.
• Peppermint oil was shown to be a safe and effective therapy for pain and global symptoms in adults with IBS.
• One small study suggests that peppermint oil in enteric-coated capsules may reduce abdominal pain in some children.
• A few studies have indicated that specific products containing peppermint oil plus caraway oil and specific combination products that include peppermint leaves may help relieve indigestion. But there isn’t any evidence showing that taking peppermint oil alone can help. In fact, peppermint oil taken alone may worsen indigestion in some people and cause unwanted side effects.
• A small amount of research suggests that peppermint oil might be helpful to reduce spasms during certain procedures, such as endoscopy or barium enema examination.
• Peppermint oil has been used topically for tension headaches and a limited amount of evidence suggests that it might be helpful for this purpose.
• Peppermint oil in a gel, water, or cream applied topically to the nipple area of breastfeeding women might be helpful for reducing pain and cracked skin. Menthol, which is in peppermint oil, should not be inhaled by or applied to the face of an infant or small child because it may negatively affect their breathing. Peppermint oil should therefore be used only after breastfeeding and then wiped off before the next breastfeeding session.
• There’s not enough evidence to allow any conclusions to be reached about whether peppermint oil is helpful for nausea, the common cold, or other conditions.
• There’s not enough evidence to show whether peppermint leaf is helpful for other conditions.

References

1. Sun Z, Wang H, Wang J, Zhou L, Yang P. Chemical Composition and Anti-Inflammatory, Cytotoxic and Antioxidant Activities of Essential Oil from Leaves of Mentha piperita Grown in China. Pizzo SV, ed. PLoS ONE. 2014;9(12):e114767. doi:10.1371/journal.pone.0114767. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262447/
2. Kearns GL, Chumpitazi BP, Abdel-Rahman SM, Garg U, Shulman RJ. Systemic exposure to menthol following administration of peppermint oil to paediatric patients. BMJ Open. 2015 Aug 12;5(8):e008375. doi: 10.1136/bmjopen-2015-008375
3. Haber SL, El-Ibiary SY. Peppermint oil for treatment of irritable bowel syndrome. Am J Health Syst Pharm. 2016 Jan 15;73(2):22, 24, 26 passim. doi: 10.2146/ajhp140801
4. Grigoleit HG, Grigoleit P. Pharmacology and preclinical pharmacokinetics of peppermint oil. Phytomedicine. 2005 Aug;12(8):612-6. doi: 10.1016/j.phymed.2004.10.007
5. Menthol and related cooling compounds. J Pharm Pharmacol. 1994 Aug;46(8):618-30. https://www.ncbi.nlm.nih.gov/pubmed/7529306
6. Food Additive Status List. https://www.fda.gov/food/food-additives-petitions/food-additive-status-list
7. Kumar S, Wahab N, Warikoo R. Bioefficacy of Mentha piperita essential oil against dengue fever mosquito Aedes aegypti L. Asian Pacific Journal of Tropical Biomedicine. 2011;1(2):85-88. doi:10.1016/S2221-1691(11)60001-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609176/
8. Samber N, Varma AL, Manzoor N. Evaluation of Mentha piperita essential oil and its major constituents for antifungal activity in Candida spp. Int J Innov Technol Exploring Eng. 2014;3:9404–11.
9. Derwich EL, Benziane ZI, Chabir RA, Taouil RA. In vitro antioxidant activity and GC/MS studies on the leaves of Mentha piperita (Lamiaceae) from Morocco. Int J Pharm Sci Drug Res. 2011;3:130–6.
10. Tyagi AK, Malik A. Antimicrobial potential and chemical composition of Mentha piperita oil in liquid and vapour phase against food spoiling microorganisms. Food Control. 2011;22:1707–14.
11. Silva FC, Chalfoun SM, Siqueira VM, Botelho DM, Lima N, Batista LR. Evaluation of antifungal activity of essential oils against potentially mycotoxigenic Aspergillus flavus and Aspergillus parasiticus. Rev Bras Farmacognosia. 2012;22:1002–10.
12. Freire MM, Jham GN, Dhingra OD, JARDIM C, Barcelos RC, VALENTE V, MOREIRA M. Composition, antifungal activity and main fungitoxic components of the essential oil of Mentha piperita L. J Food Saf. 2012;32:29–36.
13. Biochemical activities of Iranian Mentha piperita L. and Myrtus communis L. essential oils. Yadegarinia D, Gachkar L, Rezaei MB, Taghizadeh M, Astaneh SA, Rasooli I. Phytochemistry. 2006 Jun; 67(12):1249-55. https://www.ncbi.nlm.nih.gov/pubmed/16777154/
14. Antimicrobial and antioxidant activities of three Mentha species essential oils. Mimica-Dukić N, Bozin B, Soković M, Mihajlović B, Matavulj M. Planta Med. 2003 May; 69(5):413-9. https://www.ncbi.nlm.nih.gov/pubmed/12802721/
15. Chemical Composition and Anti-Inflammatory, Cytotoxic and Antioxidant Activities of Essential Oil from Leaves of Mentha piperita Grown in China. Sun Z, Wang H, Wang J, Zhou L, Yang P. PLoS One. 2014; 9(12):e114767. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262447/
16. Antimicrobial screening of Mentha piperita essential oils. Işcan G, Kirimer N, Kürkcüoğlu M, Başer KH, Demirci F. J Agric Food Chem. 2002 Jul 3; 50(14):3943-6. https://www.ncbi.nlm.nih.gov/pubmed/12083863/
17. Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine. 3rd ed. New York, N.Y. :Springer, 1998.
18. Blumenthal M. Herbal Medicine: Expanded Commission E Monographs. 1st ed. Newton, Mass.: Integrative Medicine Communications, 2000.
19. Pittler MH, Ernst E. Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. Am J Gastroenterol. 1998;93:1131–5.
20. Dresser GK, Wacher V, Wong S, et al. Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P4503A4 activity in vitro and in vivo. Clin Pharmacol Ther. 2002;72:247–55.
21. Dresser GK, Wacher V, Ramtoola Z, Cumming K, Bailey DG. Peppermint oil increases the oral bioavailability of felodipine and simvastatin. Amer Soc Clin Pharmacol Ther Ann Meeting. March 24–27, 2002;TPII-95.
22. Phenolic profile and antioxidant evaluation of Mentha x piperita L. (peppermint) extracts. Dorman HJ, Koşar M, Başer KH, Hiltunen R. Nat Prod Commun. 2009 Apr; 4(4):535-42. https://www.ncbi.nlm.nih.gov/pubmed/19476001/
23. Antiradical and anti-H2O2 properties of polyphenolic compounds from an aqueous peppermint extract. Sroka Z, Fecka I, Cisowski W. Z Naturforsch C. 2005 Nov-Dec; 60(11-12):826-32. https://www.ncbi.nlm.nih.gov/pubmed/16402541/
24. Guruvayoorappan C., Kuttan G. Rutin inhibits nitric oxide and tumor necrosis factor-alpha production in lipopolysaccharide and concanavalin-a stimulated macrophages. Drug Metabolism and Drug Interactions. 2007;22(4):263–278. https://www.ncbi.nlm.nih.gov/pubmed/18447002
25. Mint prevents shamma-induced carcinogenesis in hamster cheek pouch. Samman MA, Bowen ID, Taiba K, Antonius J, Hannan MA. Carcinogenesis. 1998 Oct; 19(10):1795-801. https://www.ncbi.nlm.nih.gov/pubmed/9806161/
26. A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.). McKay DL, Blumberg JB. Phytother Res. 2006 Aug; 20(8):619-33. https://www.ncbi.nlm.nih.gov/pubmed/16767798/
27. Zheng W., Wang S.Y. Antioxidant activity and phenolic compounds in selected herbs. J. Agric. Food Chem. 2001;49:5165–5170. doi: 10.1021/jf010697n.
28. Kim S., Cho Y., Park S. Cytotoxicity of methanol extracts of edible herbs against L1210 cells with the changes of antioxidant enzymes activities. Korean J. Pharm. 2002;33:376–383. [in Korean]
29. Inoue T., Sugimoto Y., Masuda H., Kamei C. Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L. Biol. Pharm. Bull. 2002;25:256–259. doi: 10.1248/bpb.25.256.
30. Herrmann E.C., Kucera L.S. Antiviral substances in plants of the mint family (Labiatae). III. Peppermint (Mentha piperita) and other mint plants. Proc. Soc. Exp. Biol. Med. 1967;124:874–878.
31. Tally NG, O. keele E.A, Zinsmeister A.R, Meton LV “ Prevalence of G .I symptoms in elderly- a population based study” Gastroenterology 102;895;1992
32. Emeran .A. Mayer” irritable bowel syndrome” N eng. J. Med 358:16; April 17;1692-99;2008.
33. Oswiecimska J, Szymlak A, Roczniak W, Girczys-Poledniok K, Kwiecien J. New insights into the pathogenesis and treatment of irritable bowel syndrome. Adv Med Sci. 2017;62(1):17–30. doi: 10.1016/j.advms.2016.11.001
34. Singh R, Salem A, Nanavati J, Mullin GE. The role of diet in the treatment of irritable bowel syndrome: a systematic review. Gastroenterol Clin N Am. 2018;47(1):107–137. doi: 10.1016/j.gtc.2017.10.003
35. Mullin GE, Shepherd SJ, Chander Roland B, Ireton-Jones C, Matarese LE. Irritable bowel syndrome: contemporary nutrition management strategies. JPEN J Parenter Enteral Nutr. 2014;38(7):781–799. doi: 10.1177/0148607114545329
36. Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;337:a2313. doi: 10.1136/bmj.a2313
37. Lawson MJ, Knight RE, Tran K, Walker G, Roberts-Thompson A. Failure of enteric-coated peppermint oil in the irritable bowel syndrome: a randomized, double-blind crossover study. J Gastroenterol Hepatol. 1988;3:235–8.
38. Ford AC, Talley NJ, Spiegel BMR, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 2008;337:a2313 https://doi.org/10.1136/bmj.a2313 (Published 14 November 2008) http://www.bmj.com/content/337/bmj.a2313.full
39. Cappello G, Spezzaferro M, Grossi L, Manzoli L, Marzio L. Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial. Dig Liver Dis. 2007 Jun;39(6):530-6. doi: 10.1016/j.dld.2007.02.006
40. Merat S, Khalili S, Mostajabi P, Ghorbani A, Ansari R, Malekzadeh R. The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome. Dig Dis Sci. 2010 May;55(5):1385-90. doi: 10.1007/s10620-009-0854-9
41. Cash BD, Epstein MS, Shah SM. A Novel Delivery System of Peppermint Oil Is an Effective Therapy for Irritable Bowel Syndrome Symptoms. Dig Dis Sci. 2016 Feb;61(2):560-71. doi: 10.1007/s10620-015-3858-7
42. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014 Jul;48(6):505-12. doi: 10.1097/MCG.0b013e3182a88357
43. Alammar, N., Wang, L., Saberi, B., Nanavati, J., Holtmann, G., Shinohara, R. T., & Mullin, G. E. (2019). The impact of peppermint oil on the irritable bowel syndrome: a meta-analysis of the pooled clinical data. BMC complementary and alternative medicine, 19(1), 21. https://doi.org/10.1186/s12906-018-2409-0
44. Liu JH, Chen GH, Yeh HZ, Huang CK, Poon SK. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol (1997) 32:765–8. 10.1007/BF02936952
45. Kline RM, Kline JJ, Di Palma J, Barbero GJ. Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children. J Pediatr (2001) 138:125–8. 10.1067/mpd.2001.109606
46. May B, Kohler S, Schneider B. Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia. Aliment Pharmacol Ther (2000) 14:1671–7. 10.1046/j.1365-2036.2000.00873.x
47. Rich G, Shah A, Koloski N, Funk P, Stracke B, Köhler S, Holtmann G. A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia. Neurogastroenterol Motil. 2017 Nov;29(11). doi: 10.1111/nmo.13132
48. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1-12. doi: 10.1016/0197-2456(95)00134-4
49. West S, King V, Carey TS, et al. Rockville, MD: Agency for Healthcare Research and Quality; 2002. Systems to rate the strength of scientific evidence. Evidence Report/Technology Assessment No. 47 (Prepared by the Research Triangle Institute-University of North Carolina Evidence-based Practice Center under Contract No. 290-97-0011) AHRQ Publication No. 02-E016.
50. Asao T, Kuwano H, Ide M, Hirayama I, Nakamura JI, Fujita KI, et al. Spasmolytic effect of peppermint oil in barium during double-contrast barium enema compared with Buscopan. Clin Radiol. 2003;58:301–5.
51. Sparks MJ, O’Sullivan P, Herrington AA, Morcos SK. Does peppermint oil relieve spasm during barium enema? Br J Radiol. 1995;68:841–3.
52. Holtmann G, Haag S, Adam B, Funk P, Wieland V, Heydenreich CJ. Effects of a fixed combination of peppermint oil and caraway oil on symptoms and quality of life in patients suffering from functional dyspepsia. Phytomedicine. 2003;10(suppl 4)56–7.
53. Madisch A, Holtmann G, Mayr G, Vinson B, Hotz J. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion. 2004;69:45–52.
54. Melzer J, Rosch W, Reichling J, Brignoli R, Saller R. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther. 2004;20:1279–87.
55. Gobel H, Schmidt G, Soyka D. Effect of peppermint and eucalyptus oil preparations on neurophysiological and experimental algesimetric headache parameters. Cephalalgia. 1994;14:228–34.
56. Gobel H, Fresenius J, Heinze A, Dworschak M, Soyka D. Effectiveness of oleum menthae piperitae and paracetamol in therapy of headache of the tension type [German]. Nervenarzt. 1996;67:672–81.
57. Kim, Y. S., Kim, J. W., Ha, N. Y., Kim, J., & Ryu, H. S. (2020). Herbal Therapies in Functional Gastrointestinal Disorders: A Narrative Review and Clinical Implication. Frontiers in psychiatry, 11, 601. https://doi.org/10.3389/fpsyt.2020.00601
58. Liu JH, Chen GH, Yeh HZ, Huang CK, Poon SK. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol. 1997;32:765–8.
59. Asao T, Mochiki E, Suzuki H, Nakamura J, Hirayama I, Morinaga N, Shoji H, Shitara Y, Kuwano H. An easy method for the intraluminal administration of peppermint oil before colonoscopy and its effectiveness in reducing colonic spasm. Gastrointest Endosc. 2001 Feb;53(2):172-7. doi: 10.1067/mge.2000.108477
60. Weston CF. Anal burning and peppermint oil. Postgrad Med J. 1987 Aug;63(742):717. doi: 10.1136/pgmj.63.742.717-a
61. Peppermint Oil. Am Fam Physician. 2007 Apr 1;75(7):1027-1030. https://www.aafp.org/afp/2007/0401/p1027.html
62. Thorup I, Wurtzen G, Carstensen J, Olsen P. 1983a. Short term toxicity study in rats dosed with peppermint oil. Toxicol Lett 19: 211–215.
63. Spindler P, Madsen C. 1992. Subchronic toxicity study of peppermint [Mentha piperita and Mentha arvensis] oil in rats. Toxicol Lett 62: 215–220.
64. Thorup I, Wurtzen G, Carstensen J, Olsen P. 1983b. Short term toxicity study in rats dosed with pulegone and menthol. Toxicol Lett 19: 207–210.
65. Madsen C, Wurtzen G, Carstensen J. 1986. Short-term toxicity study in rats dosed with menthone. Toxicol Lett 32: 147–152.
66. Kristiansen E, Madsen C. 1995. Induction of protein droplet (alpha 2 mu-globulin) nephropathy in male rats after short-term dosage with 1,8-cineole and l-limonene. Toxicol Lett 80: 147–152.
67. 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. https://www.ncbi.nlm.nih.gov/pubmed/11766133
68. Jarosz M, Taraszewska A. Risk factors for gastroesophageal reflux disease: the role of diet. Przegla̜d Gastroenterologiczny. 2014;9(5):297-301. doi:10.5114/pg.2014.46166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223119/
69. Gastroesophageal reflux among different racial groups in the United States. El-Serag HB, Petersen NJ, Carter J, Graham DY, Richardson P, Genta RM, Rabeneck L. Gastroenterology. 2004 Jun; 126(7):1692-9. https://www.ncbi.nlm.nih.gov/pubmed/15188164/
70. GERD pathogenesis, pathophysiology, and clinical manifestations. Kahrilas PJ. Cleve Clin J Med. 2003 Nov; 70 Suppl 5():S4-19. https://www.ncbi.nlm.nih.gov/pubmed/14705378/
71. Heartburn risk factors, knowledge, and prevention strategies: a population-based survey of individuals with heartburn. Oliveria SA, Christos PJ, Talley NJ, Dannenberg AJ. Arch Intern Med. 1999 Jul 26; 159(14):1592-8. https://www.ncbi.nlm.nih.gov/pubmed/10421282/
72. Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and gastric cardia. Terry P, Lagergren J, Wolk A, Nyrén O. Nutr Cancer. 2000; 38(2):186-91. https://www.ncbi.nlm.nih.gov/pubmed/11525596/
73. Lack of effect of spearmint on lower oesophageal sphincter function and acid reflux in healthy volunteers. Bulat R, Fachnie E, Chauhan U, Chen Y, Tougas G. Aliment Pharmacol Ther. 1999 Jun; 13(6):805-12. https://www.ncbi.nlm.nih.gov/pubmed/10383511/
74. Nair B. 2001. 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 20: 61–73
75. Morton CA, Garioch J, Todd P, Lamey PJ, Forsyth A. 1995. Contact sensitivity to menthol and peppermint in patients with intra-oral symptoms. Contact Dermatitis 32: 281–284.
76. Bonamonte D, Mundo L, Daddabbo M, Foti C. 2001. Allergic contact dermatitis from Mentha spicata (spearmint). Contact Dermatitis 45: 298.
77. Kanerva L, Rantanen T, Aalto-Korte K et al. 2001. A multicenter study of patch test reactions with dental screening series. Am J Contact Dermat 12: 83– 87.
78. Akdogan M, Ozguner M, Kocak A, Oncu M, Cicek E. 2004c. Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats. Urology 64: 394–398.
79. Blumenthal M, Busse WR, Goldberg A et al. (eds). 1998. The Complete German Commission E Monographs – Therapeutic Guide to Herbal Medicines. American Botanical Council: Austin.