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Peppermint (Mentha x piperita)



Interactions

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, based on animal research (108).
  • AcyclovirAcyclovir: Peppermint has been found to enhance topical delivery of acyclovir in vitro and in animal experimentation (30).
  • AminophyllineAminophylline: Peppermint has been found to enhance permeation of aminophylline in vivo in human skin (97).
  • AnalgesicsAnalgesics: Based on a variety of studies (human, animal, and in vitro), menthol has been shown to exert a direct antinociceptive effect (187; 188; 189; 190; 191; 192; 105; 193; 194). Menthol has also been observed to improve the analgesic efficacy of tetracaine topical gel, partially through enhanced percutaneous permeation, in animal study (104).
  • AntacidsAntacids: According to secondary sources, agents that decrease stomach acid and increase gastric pH may cause premature dissolution of enteric-coated peppermint oil.
  • AntibioticsAntibiotics: Based on in vitro study, peppermint oil and menthol may have synergistic effects with some antibiotics like ciprofloxacin (9; 195; 196; 197; 198). These effects may be dependent on concentration, food pH, composition, storage temperature, and the nature of the microorganism (197).
  • Antidiabetic agentsAntidiabetic agents: According to in vitro study, the phenolic compounds and antioxidant activities found in peppermint tea may have hypoglycemic effects (199).
  • AntifungalsAntifungals: Synergistic effects against Candida albicans have been noted in vitro when peppermint essential oil was used with amphotericin B (198). Similarly, in laboratory study, menthol was found to enhance the efficacy of topical ketoconazole (103). In other laboratory work, peppermint displayed fungistatic and fungicidal activity against various fungi (200; 201). 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 (79; 202; 203; 204; 205; 206; 207); (208; 209; 210; 211).
  • AntihypertensivesAntihypertensives: Calcium channel-blocking activity of peppermint oil has been observed in animal models (212) 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 study (213).
  • AntiprotozoalsAntiprotozoals: In laboratory study, several peppermint extracts inhibited the growth and adherence of Giardia lamblia, the parasite that causes giardiasis (10).
  • Antispasmodic agentsAntispasmodic agents: Scientific review indicates that peppermint's principal action is a dose-dependent antispasmodic effect on the gastrointestinal tract (214).
  • Antiulcer agentsAntiulcer 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 (215).
  • AntitussivesAntitussives: Based on animal study and widespread anecdotal evidence, menthol may have antitussive effects (216).
  • Benzoic acidBenzoic acid: Based on in vitro study, dermal application of low concentrations of peppermint oil may reduce the absorption of benzoic acid via the skin (179).
  • CaffeineCaffeine: Menthol (100 mg) has been shown to delay caffeine absorption but not affect caffeine metabolism in human study (217).
  • Calcium channel blockersCalcium channel blockers: In vitro experimentation with animal tissue has indicated that peppermint oil may possess channel-blocking activity (212).
  • Cardiovascular agentsCardiovascular agents: A small cardioaccelerating effect has been observed following menthol administration in human study (90). 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 (92). Atrial fibrillation has also been noted in a case report (91).
  • CorticosteroidsCorticosteroids: Menthol, a constituent of peppermint, has been found to enhance the absorption of corticosteroids in animal study (102).
  • CyclosporineCyclosporine: Based on animal study (rats), peppermint oil may significantly increase the oral bioavailability of cyclosporine via the inhibition of liver enzyme cytochrome P450 3A4 (98).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Based on preclinical data, peppermint oil may (moderately) inhibit cytochromes P450 1A2, 2E, and 3A4, which may lead to increased blood levels of drugs metabolized by these isoenzymes (99; 98; 99; 100; 98).
  • DiclofenacDiclofenac: Menthol has been found to enhance the effects of transdermal diclofenac in animal experimentation (106; 218).
  • Hepatotoxic agentsHepatotoxic agents: Peppermint has been shown to cause dose-dependent hepatic damage and lipid peroxidation in animals (94).
  • Hormonal agentsHormonal agents: Peppermint has been shown to have antiandrogenic effects in rats and may be associated with diminished libido (26). In human study, peppermint tea was observed to reduce the level of free testosterone in the blood, without affecting the levels of total testosterone and DHEA (89; 26). Based on animal study, 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 (219).
  • ImmunosuppressantsImmunosuppressants: Based on lab study, the peppermint constituent alpha-humulene may increase interleukin-8 (IL-8) secretion (220).
  • InterleukinsInterleukins: Based on lab study, the peppermint constituent alpha-humulene may increase interleukin-8 (IL-8) secretion (220).
  • Iron saltsIron salts: Polyphenol-containing peppermint beverages have been found to dose-dependently inhibit iron absorption in both animal and human study (96; 221).
  • NeostigmineNeostigmine: Menthol has been shown to potentiate neostigmine stimulated colon activity in human study (222).
  • OndansetronOndansetron: Menthol has been found to enhance the effects of transdermal ondansetron in animal study (106).
  • OxytetracyclineOxytetracycline: Based on in vitro experimentation, peppermint oil and menthol may react synergistically with oxytetracycline (9).
  • PropranololPropranolol: In animal study, menthol has been found to enhance the absorption of topical propranolol, possibly through preferential distribution into intercellular spaces of the stratum corneum and reversible disruption of the intercellular lipid domain (223; 224).
  • SalicylatesSalicylates: Menthol has been found to enhance the absorption of salicylic acid in animal study (102). Peppermint has also been shown to contain salicylates (101)
  • TetracaineTetracaine: In animal study, menthol was shown to improve the analgesic efficacy of tetracaine topical gel, partially through enhanced percutaneous permeation (104; 105).
  • VenlafaxineVenlafaxine: Peppermint has been found to enhance the transdermal delivery of venlafaxine in vitro (107).
  • ZidovudineZidovudine: Menthol has been found to enhance transdermal permeation of zidovudine (AZT) in vitro (225).

Peppermint/Herb/Supplement Interactions:
  • AnalgesicsAnalgesics: Based on a variety of studies (human, animal, and in vitro), menthol has been shown to exert a direct antinociceptive effect (187; 188; 189; 190; 191; 192; 105; 193; 194). Menthol has also been observed to improve the analgesic efficacy of tetracaine topical gel, partially through enhanced percutaneous permeation, in animal study (104).
  • AntacidsAntacids: According to secondary sources, agents that decrease stomach acid and increase gastric pH may cause premature dissolution of enteric-coated peppermint oil.
  • AntibacterialsAntibacterials: Based on in vitro study, peppermint oil and menthol may have synergistic effects with some antibiotics like ciprofloxacin (9; 195; 196; 197; 198). These effects may be dependent on concentration, food pH, composition, storage temperature, and the nature of the microorganism (197).
  • AntifungalsAntifungals: Synergistic effects against Candida albicans have been noted in vitro when peppermint essential oil was used with amphotericin B (198). Similarly, in laboratory study, menthol was found to enhance the efficacy of topical ketoconazole (103). In other laboratory work, peppermint displayed fungistatic and fungicidal activity against various fungi (200; 201). 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 (79; 202; 203; 204; 205; 206; 207; 208; 209; 210; 211). Concomitant use of peppermint and basil oil has been found to have synergistic antifungal effects (226).
  • Anti-inflammatory herbsAnti-inflammatory herbs: Peppermint has been reported as exhibiting dose-dependent anti-inflammatory activity in animal study (213).
  • AntiparasiticsAntiparasitics: In in vitro study, several peppermint extracts inhibited the growth and adherence of Giardia lamblia, the parasite that causes giardiasis (10). Theoretically, concurrent use of peppermint with antiparasitic agents may have additive effects.
  • AntispasmodicsAntispasmodics: Scientific review indicates that peppermint's principal action is a dose-dependent antispasmodic effect on the gastrointestinal tract (214).
  • AntitussivesAntitussives: Based on animal study and widespread anecdotal evidence, menthol may have antitussive effects (216).
  • Antiulcer herbs and supplementsAntiulcer 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 (215).
  • BasilBasil: Concomitant use of peppermint and basil oil has been found to have synergistic antifungal effects in vitro (226).
  • Caffeine-containing herbsCaffeine-containing herbs: Menthol (100 mg) has been shown to delay caffeine absorption but not affect caffeine metabolism in human study (217).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: A small cardioaccelerating effect has been observed following menthol administration in human study (90). 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 (92). Atrial fibrillation has also been noted in a case report (91).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: Based on preclinical data, peppermint oil may (moderately) inhibit cytochromes P450 1A2, 2E, and 3A4, which may lead to increased blood levels of drugs metabolized by these isoenzymes (99; 98; 99; 100; 98).
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: Peppermint has been shown to cause dose-dependent hepatic damage and lipid peroxidation in animals (94).
  • Hormonal herbs and supplementsHormonal herbs and supplements: Peppermint has been shown to have antiandrogenic effects in rats and may be associated with diminished libido (26). In human study, peppermint tea was observed to reduce the level of free testosterone in the blood, without affecting the levels of total testosterone and DHEA (89; 26). Based on animal study, 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 (219).
  • HypoglycemicsHypoglycemics: According to in vitro study, the phenolic compounds and antioxidant activities found in peppermint tea may have hypoglycemic effects (199).
  • HypotensivesHypotensives: Calcium channel-blocking activity of peppermint oil has been observed in animal models (212) and, in theory, peppermint oil may add to the effects of agents that may also theoretically drop blood pressure.
  • ImmunosuppressantsImmunosuppressants: Based on lab study, the peppermint constituent alpha-humulene may increase interleukin-8 (IL-8) secretion (220).
  • IronIron: Polyphenol-containing peppermint beverages have been found to dose-dependently inhibit iron absorption in both animal and human study (96; 221).
  • QuercetinQuercetin: Based on animal study, menthol may enhance the absorption of topical quercetin (227).
  • Salicylate-containing herbsSalicylate-containing herbs: Menthol has been found to enhance the absorption of salicylic acid in animal study (102). Peppermint also contains salicylates, and concurrent use with other salicylates may have additive effects and increase salicylate levels (101).
  • Vitamin DVitamin D: Menthol has been found to enhance the antiproliferative activity of 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], an active form of vitamin D(3), in vitro (228).

Peppermint/Food Interactions:
  • Insufficient available evidence.

Peppermint/Lab Interactions:
  • Blood glucoseBlood glucose: According to in vitro study, the phenolic compounds and antioxidant activities found in peppermint tea may have hypoglycemic effects (199).
  • Heart rateHeart rate: A small cardioaccelerating effect has been observed following menthol administration in human study (90). 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 (92). Atrial fibrillation has also been noted in a case report (91).
  • 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 (26). In human study, peppermint tea was observed to reduce the level of free testosterone in the blood, without affecting the levels of total testosterone and DHEA (89; 26). Based on animal study, 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 (219).
  • Liver function testsLiver function tests: In animal study, peppermint was found to increase alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (94).

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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
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