Table of Contents > Interactions & Depletions > American pennyroyal (Hedeoma pulegioides L.), European pennyroyal (Mentha pulegium L.) Print

American pennyroyal (Hedeoma pulegioides L.), European pennyroyal (Mentha pulegium L.)



Interactions

Pennyroyal/Drug Interactions:
  • AbortifacientsAbortifacients: Traditionally, pennyroyal is considered to be an abortifacient. Although pennyroyal oil has been historically used to induce abortions, it typically does so at lethal or near-lethal doses, making this action unpredictable, dangerous, and not recommended.
  • AntiandrogensAntiandrogens: Traditionally, pennyroyal is considered to be an abortifacient and emmenagogue. Theoretically, there may be an interaction with hormonal agents. However, clinical significance is unknown.
  • AntiestrogensAntiestrogens: Traditionally, pennyroyal is considered to be an abortifacient, and emmenagogue (menstrual flow stimulant). Theoretically, there may be an interaction with hormonal agents, however clinical significance is unknown.
  • Acetaminophen (Tylenol®)Acetaminophen (Tylenol®): The toxicity of pennyroyal may theoretically be increased when combined with acetaminophen. Acetaminophen may induce hepatotoxicity when glutathione stores are depleted, and there are data to suggest that pennyroyal may also deplete hepatic glutathione stores (31; 32). The similarity of the pathogenesis of pennyroyal-induced hepatic necrosis to that produced by acetaminophen, supported by case reports, suggests a possible role for N-acetylcysteine (NAC) in the treatment of pennyroyal or mixed pennyroyal-acetaminophen toxicity. However, one animal study found that NAC did not afford a significant survival benefit in pennyroyal oil toxicity (7).
  • Antidiabetic agentsAntidiabetic agents: Theoretically, pennyroyal may enhance the effects of hypoglycemic agents. There are two case reports of hypoglycemia in pediatric patients after ingesting pennyroyal (14).
  • AntihistaminesAntihistamines: Pulegone, a constituent of pennyroyal, has been shown to exert antihistamine effects on guinea-pig ileum (33).
  • Cytochrome P450 metabolized drugsCytochrome P450 metabolized drugs: Due to the suggested inhibition of the P450system by pennyroyal, concomitant use with drugs metabolized by the P450system may increase serum levels of those drugs. Similarly, pennyroyal levels may be affected by agents altering the P450 system. In vivo and in vitro studies suggest that the pennyroyal constituent pulegone diminishes the function of rat liver cytochrome P450 in an irreversible, time dependent fashion (34). In vitro and in vivo research suggests that the pulegone metabolite menthofuran is a potent inhibitor of human liver CYP2A6 (35) and may account for a significant degree of pennyroyal's hepatotoxic effects (36; 37). Pulegone and menthofuran may deplete cellular glutathione levels, leaving hepatocytes vulnerable to free radical damage (38).
  • Disulfiram (Antabuse®)Disulfiram (Antabuse®): Many tinctures contain high levels of alcohol and may cause nausea or vomiting when taken with metronidazole (Flagyl®) or disulfiram (Antabuse®).
  • Drugs that may lower seizure thresholdDrugs that may lower seizure threshold: Based on tradition, pennyroyal essential oil may have epileptogenic properties due to its constituents, namely its highly reactive monoterpene ketones (39).
  • Fertility agentsFertility agents: Traditionally, pennyroyal is considered to be an abortifacient, and it has been historically used to induce abortions. Therefore, pennyroyal oil may decrease the effectiveness of fertility agents.
  • Hepatotoxic agentsHepatotoxic agents: Pennyroyal may lead to hepatic failure and centrilobular necrosis, and may potentiate the effects of other hepatotoxic agents. An autopsy from an overdose found massive hepatic necrosis (23). Chemical hepatitis has been reported and is often detectable within 24 hours of ingestion of pennyroyal (23). Pulegone, a constituent of pennyroyal, has caused increased transaminases in humans (14) and increased plasma alkaline phosphatase and liver weight in rats after 28 days (160mg/kg) (27).
  • Hormonal agentsHormonal agents: Traditionally, pennyroyal is considered to be an abortifacient and emmenagogue. Theoretically, there may be an interaction with hormonal agents. However, clinical significance is unknown.
  • Metronidazole (Flagyl®)Metronidazole (Flagyl®): Many tinctures contain high levels of alcohol and may cause nausea or vomiting when taken with metronidazole (Flagyl®) or disulfiram (Antabuse®).

Pennyroyal/Herb/Supplement Interactions:
  • AbortifacientsAbortifacients: Traditionally, pennyroyal is considered to be an abortifacient. Although pennyroyal oil has been historically used to induce abortions, it typically does so at lethal or near-lethal doses, making this action unpredictable, dangerous, and not recommended.
  • AntiandrogensAntiandrogens: Traditionally, pennyroyal is considered to be an abortifacient, and emmenagogue (menstrual flow stimulant). Theoretically, there may be an interaction with hormonal agents, however clinical significance is unknown.
  • AntiestrogensAntiestrogens: Traditionally, pennyroyal is considered to be an abortifacient and emmenagogue. Theoretically, there may be an interaction with hormonal agents. However, clinical significance is unknown.
  • Black cohoshBlack cohosh: Pennyroyal and black cohosh (Cimicifuga racemosa) are sometimes taken together to induce abortion, although the use of these herbs together cannot be recommended due to the possibility of increased toxicity and death. There is a case report of a 24 year-old woman who took 48-56% of pennyroyal herb in an alcohol base and an unknown amount of black cohosh root for two weeks in an attempt to induce abortion (4). Following a single subsequent dose of this combination, the patient died within 48 hours.
  • Blue cohosh (Caulophyllum thalictroides)Blue cohosh (Caulophyllum thalictroides): Pennyroyal and blue cohosh (Caulophyllum thalictroides) have traditionally been taken together to normalize the menstrual cycle in women, and thus may act synergistically to increase menstrual flow. This use has not been scientifically investigated. Notably, blue cohosh may act as a vasoconstrictor and has been associated with multiple adverse outcomes.
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: Due to the suggested inhibition of the P450system by pennyroyal, concomitant use with drugs metabolized by the P450system may increase serum levels of those drugs. Similarly, pennyroyal levels may be affected by agents altering the P450 system. In vivo and in vitro studies suggest that the pennyroyal constituent pulegone diminishes the function of rat liver cytochrome P450 in an irreversible, time dependent fashion (34). In vitro and in vivo research suggests that the pulegone metabolite menthofuran is a potent inhibitor of human liver CYP2A6 (35) and may account for a significant degree of pennyroyal's hepatotoxic effects (36; 37). Pulegone and menthofuran may deplete cellular glutathione levels, leaving hepatocytes vulnerable to free radical damage (38).
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: Pennyroyal may lead to hepatic failure and centrilobular necrosis and may potentiate the effects of other hepatotoxic agents. An autopsy from an overdose found massive hepatic necrosis (23). Chemical hepatitis has been reported and is often detectable within 24 hours of ingestion of pennyroyal (23). Pulegone, a constituent of pennyroyal, has caused increased transaminases in humans (14) and increased plasma alkaline phosphatase and liver weight in rats after 28 days (160mg/kg) (27).
  • Herbs that lower seizure thresholdHerbs that lower seizure threshold: Based on tradition, pennyroyal essential oil may have epileptogenic properties due to its constituents, namely its highly reactive monoterpene ketones (39).
  • Hormonal herbs and supplementsHormonal herbs and supplements: Traditionally, pennyroyal is considered to be an abortifacient and emmenagogue. Theoretically, there may be an interaction with hormonal herbs and supplements. However, clinical significance is unknown.
  • Hormone replacement therapy (HRT)Hormone replacement therapy (HRT): Traditionally, pennyroyal is considered to be an abortifacient, and emmenagogue. Theoretically, there may be an interaction with hormonal herbs and supplements. However, clinical significance is unknown.
  • HypoglycemicsHypoglycemics: Theoretically, pennyroyal may enhance the effects of hypoglycemic agents. The available scientific literature reports two cases of hypoglycemia in pediatric patients after ingesting pennyroyal (14).
  • IronIron: Pennyroyal has been found to inhibit the absorption of iron in meals by up to 75% (40).
  • Licorice (Glycyrrhiza glabra)Licorice (Glycyrrhiza glabra): In a 1961 case report, a 23 year-old woman, six weeks pregnant, was noted to experience a severe psychotic episode and seizures after ingesting an unknown dose of pennyroyal 3-4 times daily and "Widow Welch's Female Pills," a combination of ferrous sulfate, sulfur, licorice (Glycyrrhiza glabra), and turmeric (Curcuma longa) (16). The patient recovered two days following hospital admission without recurrence, and she delivered a healthy child.
  • Turmeric (Curcuma longa)Turmeric (Curcuma longa): In a 1961 case report, a 23 year-old woman, six weeks pregnant, was noted to experience a severe psychotic episode and seizures after ingesting an unknown dose of pennyroyal 3-4 times daily and "Widow Welch's Female Pills," a combination of ferrous sulfate, sulfur, licorice (Glycyrrhiza glabra), and turmeric (Curcuma longa) (16). The patient recovered without recurrence two days after she was admitted to the hospital, and she delivered a healthy child.

Pennyroyal/Food Interactions:
  • Insufficient available evidence.

Pennyroyal/Lab Interactions:
  • Liver function tests (LFTs)Liver function tests (LFTs): Hepatic toxicity due to the pennyroyal constituent pulegone has been associated with elevations in transaminases in rats (27) and humans (23; 14).
  • Serum glucoseSerum glucose: Theoretically, pennyroyal may enhance the effects of hypoglycemic agents. The available scientific literature reports two cases of hypoglycemia in pediatric patients after ingesting pennyroyal (14).

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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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