Mentha x piperita

Peppermint/Drug Interactions:

  • GeneralGeneral: Menthol has been found to enhance the percutaneous transfer and transdermal delivery of various drugs.
  • 5-fluorouracil (5-FU)5-fluorouracil (5-FU): Peppermint oil may enhance skin absorption of topical 5-fluorouracil, according to animal research (140).
  • Acetylcholinesterase inhibitorsAcetylcholinesterase inhibitors: Peppermint has been found to have high inhibitory activity against acetylcholinesterase (AChE) in laboratory research (224).
  • AcyclovirAcyclovir: Peppermint has been found to enhance topical delivery of acyclovir in vitro and in animal experimentation (41).
  • Alzheimer's agentsAlzheimer's agents: According to secondary sources, peppermint may interact with Alzheimer's agents.
  • AminophyllineAminophylline: Peppermint has been found to enhance permeation of aminophylline in vivo in human skin (128).
  • AnalgesicsAnalgesics: Based on a variety of research (human, animal, and in vitro), menthol has been shown to exert a direct antinociceptive effect (225; 226; 227; 228; 229; 230; 137; 231; 232; 233). Menthol has also been observed to improve the analgesic efficacy of tetracaine topical gel, partially through enhanced percutaneous permeation, in animal study (136).
  • AntacidsAntacids: According to secondary sources, agents that decrease stomach acid and increase gastric pH may cause premature dissolution of enteric-coated peppermint oil.
  • AntiarrhythmicsAntiarrhythmics: In human research, patients using peppermint oil reported cardiac disorders, including abnormal ECG such as supraventricular premature beats, ST segment depression, and premature ventricular contractions (117).
  • AntibioticsAntibiotics: Based on in vitro research, peppermint oil and menthol may have synergistic effects with some antibiotics like ciprofloxacin (11; 234; 235; 236; 237). These effects may be dependent on concentration, food pH, composition, storage temperature, and the nature of the microorganism (236). In human research, peppermint had synergistic effects with TMS forte (160mg trimethoprim and 800mg sulfamethoxazole) (238).
  • Antidiabetic agentsAntidiabetic agents: According to in vitro research, the phenolic compounds and antioxidant activities found in peppermint tea may have hypoglycemic effects (141).
  • Antiemetic agentsAntiemetic agents: In human research, peppermint oil reduced the incidence of nausea (176) and peppermint has also been reported to relieve pregnancy-induced nausea and vomiting (63).
  • AntifungalsAntifungals: Synergistic effects against Candida albicans have been noted in vitro when peppermint essential oil was used with amphotericin B (237). Similarly, in laboratory study, menthol was found to enhance the efficacy of topical ketoconazole (135). In other laboratory work, peppermint displayed fungistatic and fungicidal activity against various fungi (239; 21). Based on animal study, peppermint oil and menthol may be effective against Candida albicans, Fusarium oxysporum, Fusarium verticillioides, Trichophyton mentagrophytes, Trichophytonrubrum, Trichophytontonsurans, Penicillium chrysogenum, Aspergillus niger, A. flavus, A. fumigatus, A. sulphureus, Mucor fragilis, and Rhizopus stolonifer (101; 240; 241; 242; 243; 244; 245; 246; 247; 248; 249).
  • AntihistaminesAntihistamines: In animal research, 50% EtOH extract of peppermint inhibited histamine release at a concentration of 1mcg/mL (250).
  • AntihypertensivesAntihypertensives: Calcium channel-blocking activity of peppermint oil has been observed in animal models (251) and, in theory, peppermint oil may add to the effects of agents that may also theoretically drop blood pressure.
  • Anti-inflammatory agentsAnti-inflammatory agents: Peppermint has been reported as exhibiting dose-dependent anti-inflammatory activity in animal research (252). In human research, a mixture of naturally-occurring plant oils, containing peppermint, exhibited marked anti-inflammatory activity in epithelial cells of the upper respiratory system (253).
  • Antineoplastic agentsAntineoplastic agents: In vitro research demonstrated that peppermint oil can revert tumor cells back to a differentiated state (254). Based on animal research, oral administration of Mentha extract may have chemopreventive and antimutagenic effects, possibly due to its antioxidative and radical-scavenging properties (34; 255).
  • AntiprotozoalsAntiprotozoals: In laboratory research, several peppermint extracts inhibited the growth and adherence of Giardia lamblia, the parasite that causes giardiasis (12).
  • Antispasmodic agentsAntispasmodic agents: Scientific review indicates that peppermint's principal action is a dose-dependent antispasmodic effect on the gastrointestinal tract (256; 257; 258; 157; 259).
  • AntitussivesAntitussives: Based on animal research and widespread anecdotal evidence, menthol may have antitussive effects (260).
  • Antiulcer and gastric acid-reducing agentsAntiulcer and gastric acid-reducing agents: The commercial combination product STW-5 (Iberogast?), which contains extracts of peppermint leaf, as well as other herbal components, has been demonstrated to exert a dose-dependent antiulcerogenic effect associated with reduced acid output, increased mucin secretion, increased prostaglandin E2 release, and a decrease in leukotrienes (261).
  • Antiviral agentsAntiviral agents: An antiviral substance was detected in peppermint oil with activity against the Newcastle disease virus (NDV), herpes simplex, vaccinia, Semliki forest, influenza A virus, and West Nile virus (262). In laboratory research, peppermint exhibited high virucidal activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) (40; 263). Additionally, it has been found to have activity against the acyclovir-resistant strain of HSV-1 (263).
  • AnxiolyticsAnxiolytics: According to secondary sources, peppermint may interact with anxiolytics.
  • Benzoic acidBenzoic acid: Based on in vitro research, dermal application of low concentrations of peppermint oil may reduce the absorption of benzoic acid via the skin (216).
  • CaffeineCaffeine: Menthol (100 mg) delayed caffeine absorption but did not affect caffeine metabolism in human research (264).
  • Calcium channel blockersCalcium channel blockers: In vitro research with animal tissue has indicated that peppermint oil may possess channel-blocking activity (251).
  • Cardiovascular agentsCardiovascular agents: A small cardioaccelerating effect has been observed following menthol administration in human research (114). In a case-control study assessing peppermint oil as an antispasmodic, one patient (N=40) experienced bradycardia and one experienced a sympathovagal response, which was on par with the adverse effect rate seen in historical controls using glucagons (116). Atrial fibrillation has also been noted in a case report (115).
  • CorticosteroidsCorticosteroids: Menthol, a constituent of peppermint, has been found to enhance the absorption of corticosteroids in animal research (134).
  • CyclosporineCyclosporine: Based on animal research in rats, peppermint oil may significantly increase the oral bioavailability of cyclosporine via the inhibition of liver enzyme cytochrome P450 3A4 (129).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: In preclinical data, peppermint oil may modify cytochromes P450 1A2, 2B, 2E, and 3A4 activity (130; 129; 130; 131; 129; 265). According to secondary sources, peppermint may also interact with cytochrome P450 3A5 and 3A7 inhibitors.
  • Dermatologic agentsDermatologic agents: Skin rashes and irritation from the topical use of peppermint oil and its derivatives have been noted (105; 172; 56).
  • DiclofenacDiclofenac: In animal research, menthol enhanced the effects of transdermal diclofenac (138; 266).
  • ExpectorantsExpectorants: According to secondary sources, peppermint may interact with expectorants.
  • Gastrointestinal agentsGastrointestinal agents: In human research, gastrointestinal upset, including diarrhea (117), nausea and vomiting (110; 112), and abdominal pain (105; 112) have been reported.
  • Hepatotoxic agentsHepatotoxic agents: In animal research, peppermint caused dose-dependent hepatic damage and lipid peroxidation (120).
  • Hormonal agentsHormonal agents: Peppermint has been shown to have antiandrogenic effects in rats and may be associated with diminished libido (38). In human research, peppermint tea was observed to reduce the level of free testosterone in the blood, without affecting the levels of total testosterone and DHEA (113; 38). Based on animal research, the mechanism may involve spearmint-induced oxidative stress in the hypothalamus as well as testicular antiandrogenicity (altered levels of gene expression, enzymes, and hormones) resulting in decreased synthesis of LH and FSH, which in turn downregulate the production of testicular testosterone through the disruption of a number of intermediate cascades (267).
  • ImmunosuppressantsImmunosuppressants: Based on laboratory research, the peppermint constituent alpha-humulene may increase interleukin-8 (IL-8) secretion (268).
  • InsecticidesInsecticides: In human research, a product called Terminix(?) ALLCLEAR(?) Sidekick Mosquito Repeller (containing cinnamon oil 10.5%; eugenol 13%; geranium oil 21%; peppermint 5.3%; and lemongrass oil 2.6%) provided significant protection against mosquitoes; however, the mechanism of this protection is unclear (59).
  • InterleukinsInterleukins: Based on laboratory research, the peppermint constituent alpha-humulene may increase interleukin-8 (IL-8) secretion (268).
  • Iron saltsIron salts: Polyphenol-containing peppermint beverages dose-dependently inhibited iron absorption in both animal and human research (127; 269).
  • Neurologic agentsNeurologic agents: In human research, headaches (117) and worsening of headache (118) have been reported.
  • NeostigmineNeostigmine: Menthol potentiated neostigmine stimulated colon activity in human research (270; 224).
  • NicotineNicotine: In human research, mean concentrations of nicotine/cotinine ratio was higher in urine samples when consuming a drink containing menthol; therefore, reducing the conversion of nicotine to cotinine (271).
  • OndansetronOndansetron: Menthol enhanced the effects of transdermal ondansetron in animal research (138).
  • Osteoporosis agentsOsteoporosis agents: Metabolites of (-)-menthol inhibited bone resorption in vitro (60).
  • OxytetracyclineOxytetracycline: Based on in vitro research, peppermint oil and menthol may react synergistically with oxytetracycline (11).
  • Performance-enhancing herbs and supplementsPerformance-enhancing herbs and supplements: According to human research, peppermint aroma may have beneficial effects on cognition, attention, and alertness and improve tactile performance (272; 273; 177; 274).
  • PropranololPropranolol: In animal research, menthol enhanced the absorption of topical propranolol, possibly through preferential distribution into intercellular spaces of the stratum corneum and reversible disruption of the intercellular lipid domain (275; 276).
  • SalicylatesSalicylates: In animal research, menthol enhanced the absorption of salicylic acid (134). Peppermint has also been shown to contain salicylates (133).
  • TetracaineTetracaine: In animal research, menthol improved the analgesic efficacy of tetracaine topical gel, partially through enhanced percutaneous permeation (136; 137).
  • VenlafaxineVenlafaxine: Peppermint enhanced the transdermal delivery of venlafaxine in vitro (139).
  • ZidovudineZidovudine: Menthol enhanced transdermal permeation of zidovudine (AZT) in vitro (277).

    • Peppermint/Herb/Supplement Interactions:

  • Alzheimer's herbs and supplementsAlzheimer's herbs and supplements: According to secondary sources, peppermint may interact with Alzheimer's herbs and supplements.
  • AnalgesicsAnalgesics: Based on a variety of research (human, animal, and in vitro), menthol has been shown to exert a direct antinociceptive effect (225; 226; 227; 228; 229; 230; 137; 231; 232; 233). Menthol has also been observed to improve the analgesic efficacy of tetracaine topical gel, partially through enhanced percutaneous permeation, in animal study (136).
  • AntacidsAntacids: According to secondary sources, agents that decrease stomach acid and increase gastric pH may cause premature dissolution of enteric-coated peppermint oil.
  • AntiarrhythmicsAntiarrhythmics: In human research, patients using peppermint oil reported cardiac disorders, including abnormal ECG such as supraventricular premature beats, ST segment depression, and premature ventricular contractions (117).
  • AntibacterialsAntibacterials: Based on in vitro research, peppermint oil and menthol may have synergistic effects with some antibiotics like ciprofloxacin (11; 234; 235; 236; 237). These effects may be dependent on concentration, food pH, composition, storage temperature, and the nature of the microorganism (236). In human research, peppermint had synergistic effects with TMS forte (160mg trimethoprim and 800mg sulfamethoxazole) (238).
  • Antiemetic agentsAntiemetic agents: In human research, peppermint oil reduced the incidence of nausea (176) and peppermint has also been reported to relieve pregnancy-induced nausea and vomiting (63).
  • AntifungalsAntifungals: Synergistic effects against Candida albicans have been noted in vitro when peppermint essential oil was used with amphotericin B (237). Similarly, in laboratory study, menthol was found to enhance the efficacy of topical ketoconazole (135). In other laboratory work, peppermint displayed fungistatic and fungicidal activity against various fungi (239; 21). Based on animal study, peppermint oil and menthol may be effective against Candida albicans, Fusarium oxysporum, Fusarium verticillioides, Trichophyton mentagrophytes, Trichophytonrubrum, Trichophytontonsurans, Penicillium chrysogenum, Aspergillus niger, A. flavus, A. fumigatus, A. sulphureus, Mucor fragilis, and Rhizopus stolonifer (101; 240; 241; 242; 243; 244; 245; 246; 247; 248; 249).
  • AntihistaminesAntihistamines: In animal research, 50% EtOH extract of peppermint inhibited histamine release at a concentration of 1mcg/mL (250).
  • Anti-inflammatory herbsAnti-inflammatory herbs: Peppermint has been reported as exhibiting dose-dependent anti-inflammatory activity in animal research (252). In human research, a mixture of naturally-occurring plant oils, containing peppermint, exhibited marked anti-inflammatory activity in epithelial cells of the upper respiratory system (253).
  • Antineoplastic herbs and supplementsAntineoplastic herbs and supplements: In vitro research demonstrated that peppermint oil can revert tumor cells back to a differentiated state (254). Based on animal research, oral administration of Mentha extract may have chemopreventive and antimutagenic effects, possibly due to its antioxidative and radical-scavenging properties (34; 255).
  • AntioxidantsAntioxidants: Peppermint exhibited antioxidant activity (15; 16; 17; 18; 19; 20; 21; 22; 23; 24). It has been shown to act as a radical scavenger and inhibit lipid peroxidation (24). In other experiments, peppermint essential oil demonstrated antioxidant activity in a linoleic acid emulsion system by inhibiting conjugated dienes formation by 52.4% and linoleic acid secondary oxidized product generation by 76.9% (at 0.1% concentration) (23). In vitro research reported that Mentha piperita L. had the lowest thiobarbituric acid reactive substance (TBARS) (278).
  • AntiparasiticsAntiparasitics: In vitro, several peppermint extracts inhibited the growth and adherence of Giardia lamblia, the parasite that causes giardiasis (12).
  • AntispasmodicsAntispasmodics: Scientific review indicates that peppermint's principal action is a dose-dependent antispasmodic effect on the gastrointestinal tract (256; 257; 258; 157; 259).
  • AntitussivesAntitussives: Based on animal research and widespread anecdotal evidence, menthol may have antitussive effects (260).
  • Antiulcer and gastric acid-reducing herbs and supplementsAntiulcer and gastric acid-reducing herbs and supplements: The commercial combination product STW-5 (Iberogast?), which contains extracts of peppermint leaf, as well as other herbal components, has been demonstrated to exert a dose-dependent antiulcerogenic effect associated with reduced acid output, increased mucin secretion, increased prostaglandin E2 release, and a decrease in leukotrienes (261).
  • Antiviral agentsAntiviral agents: An antiviral substance was detected in peppermint oil with activity against the Newcastle disease virus (NDV), herpes simplex, vaccinia, Semliki forest, influenza A virus, and West Nile virus (262). In laboratory research, peppermint exhibited high virucidal activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) (40; 263). Additionally, it has been found to have activity against the acyclovir-resistant strain of HSV-1 (263).
  • AnxiolyticsAnxiolytics: According to secondary sources, peppermint may interact with anxiolytics.
  • BasilBasil: Concomitant use of peppermint and basil oil has been found to have synergistic antifungal effects in vitro (279).
  • Caffeine-containing herbs and supplementsCaffeine-containing herbs and supplements: Menthol (100 mg) delayed caffeine absorption but did not affect caffeine metabolism in human research (264).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: A small cardioaccelerating effect has been observed following menthol administration in human research (114). In a case-control study assessing peppermint oil as an antispasmodic, one patient (N=40) experienced bradycardia and one experienced a sympathovagal response, which was on par with the adverse effect rate seen in historical controls using glucagons (116). Atrial fibrillation has also been noted in a case report (115).
  • Cytochrome P450-modifying herbs and supplementsCytochrome P450-modifying herbs and supplements: In preclinical data, peppermint oil may modify cytochromes P450 1A2, 2B, 2E, and 3A4 activity (130; 129; 130; 131; 129; 265). According to secondary sources, peppermint may also interact with cytochrome P450 3A5 and 3A7 inhibitors.
  • ExpectorantsExpectorants: According to secondary sources, peppermint may interact with expectorants.
  • Gastrointestinal agentsGastrointestinal agents: In human research, gastrointestinal upset, including diarrhea (117), nausea and vomiting (110; 112), and abdominal pain (105; 112) have been reported.
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: In animal research, peppermint caused dose-dependent hepatic damage and lipid peroxidation (120).
  • Hormonal herbs and supplementsHormonal herbs and supplements: Peppermint has been shown to have antiandrogenic effects in rats and may be associated with diminished libido (38). In human research, peppermint tea was observed to reduce the level of free testosterone in the blood, without affecting the levels of total testosterone and DHEA (113; 38). Based on animal research, the mechanism may involve spearmint-induced oxidative stress in the hypothalamus as well as testicular antiandrogenicity (altered levels of gene expression, enzymes, and hormones) resulting in decreased synthesis of LH and FSH, which in turn downregulate the production of testicular testosterone through the disruption of a number of intermediate cascades (267).
  • HypoglycemicsHypoglycemics: According to in vitro research, the phenolic compounds and antioxidant activities found in peppermint tea may have hypoglycemic effects (141).
  • HypotensivesHypotensives: Calcium channel-blocking activity of peppermint oil has been observed in animal models (251) and, in theory, peppermint oil may add to the effects of agents that may also theoretically drop blood pressure.
  • ImmunosuppressantsImmunosuppressants: Based on laboratory research, the peppermint constituent alpha-humulene may increase interleukin-8 (IL-8) secretion (268).
  • InsecticidesInsecticides: In human research, a product called Terminix(?) ALLCLEAR(?) Sidekick Mosquito Repeller (containing cinnamon oil 10.5%; eugenol 13%; geranium oil 21%; peppermint 5.3%; and lemongrass oil 2.6%) provided significant protection against mosquitoes; however, the mechanism of this protection is unclear (59).
  • IronIron: Polyphenol-containing peppermint beverages dose-dependently inhibited iron absorption in both animal and human research (127; 269).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: In human research, headaches (117) and worsening of headache (118) have been reported.
  • Osteoporosis agentsOsteoporosis agents: Metabolites of (-)-menthol inhibited bone resorption in vitro (60).
  • Perillyl alcohol-containing herbs and supplementsPerillyl alcohol-containing herbs and supplements: Additional identified components of peppermint include polymerized polyphenols, perillyl alcohol (254), flavonoids, carotene, tocopherols, betaine, rosmarinic acid, eriocitrin, luteolin, hesperidin, choline, caffeic acid, and alpha-humulene (7; 280).
  • Performance-enhancing herbs and supplementsPerformance-enhancing herbs and supplements: According to human research, peppermint aroma may have beneficial effects on cognition, attention, and alertness and improve tactile performance (272; 273; 177; 274).
  • Radioprotective herbs and supplementsRadioprotective herbs and supplements: Peppermint has been shown to have protective effects against irradiation in animal research (66; 67; 68; 69; 70; 71; 72; 73; 74).
  • QuercetinQuercetin: Based on animal research, menthol may enhance the absorption of topical quercetin (281).
  • Salicylate-containing herbsSalicylate-containing herbs: In animal research, menthol enhanced the absorption of salicylic acid (134). Peppermint has also been shown to contain salicylates (133).
  • Vitamin DVitamin D: Menthol enhanced the antiproliferative activity of 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], an active form of vitamin D(3), in vitro (282).

    • Peppermint/Food Interactions:

  • Caffeinecontaining foodsCaffeine-containing foods: Menthol (100 mg) delayed caffeine absorption but did not affect caffeine metabolism in human research (264).
  • Iron-containing foodsIron-containing foods: Polyphenol-containing peppermint beverages dose-dependently inhibited iron absorption in both animal and human research (127; 269).

    • Peppermint/Lab Interactions:

  • Blood glucoseBlood glucose: According to in vitro research, the phenolic compounds and antioxidant activities found in peppermint tea may have hypoglycemic effects (141).
  • Heart rateHeart rate: In human research, a small cardioaccelerating effect (114), bradycardia, a sympathovagal response (116), and atrial fibrillation (115) have been reported.
  • Hormone panel (LH, FSH, and estradiol levels)Hormone panel (LH, FSH, and estradiol levels): Peppermint has been shown to have antiandrogenic effects in rats and may be associated with diminished libido (38). In human research, peppermint tea was observed to reduce the level of free testosterone in the blood, without affecting the levels of total testosterone and DHEA (113; 38). Based on animal research, the mechanism may involve spearmint-induced oxidative stress in the hypothalamus as well as testicular antiandrogenicity (altered levels of gene expression, enzymes and hormones) resulting in decreased synthesis of LH and FSH, which in turn downregulate the production of testicular testosterone through the disruption of a number of intermediate cascades (267).
  • Kidney function testsKidney function tests: In animal research in rats, oral menthone decreased creatinine (191).
  • Liver function testsLiver function tests: In animal research, peppermint was found to increase alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (120). In other animal research in rats, menthone increased alkaline phosphatase and bilirubin (191).