Pennyroyal

• How It Works

  Pennyroyal is an extremely toxic herb that has caused multi-organ failure and death in several people.

  Pennyroyal is a flowering plant that was used in folk medicine to induce abortion, alleviate menstrual symptoms, and to treat inflammatory conditions and minor ailments. The oil itself is highly toxic, and is not recommended for internal use. A substance called pugelone in pennyroyal is thought to be responsible for its toxic effects and tissue damage. Studies in both animals and humans show that pulegone is also directly toxic to the nervous system. There have been a number of case reports and also several deaths attributed to the use of this botanical.

• Purported Uses

  There is no scientific evidence for use of pennyroyal in the following conditions:

  • To induce menstruation
  • To treat lung conditions
  • To treat cancer
  • To treat colds or flu
  • To treat headaches
  • To induce abortion
  • To reduce inflammation
  • As an insect repellant
  • To relieve PMS symptoms
  • To treat toothaches
• Patient Warnings
  • This botanical contains compounds that are toxic to both animals and humans.
• Do Not Take If

  In general, pennyroyal oil is highly toxic and is not recommended for internal use.

  • You are pregnant or breast feeding: Pennyroyal can cause miscarriage and other toxic effects.
  • You are taking iron supplements: Pennyroyal may reduce bioavailability by 50% or more.
  • You are taking cytochrome P450 substrate drugs: A case report of acute liver failure was possibly caused by drug interactions with pennyroyal tea.
• Side Effects
  • Dizziness
  • Weakness
  • Hallucinations
  • Nausea, cramps, and stomach upset
  • Liver and kidney toxicities

  Case Reports of Toxicity and Death

  • At least 24 cases of pennyroyal toxicity, including liver and kidney failure, low blood sugar, blood clotting problems, acidic blood pH, GI hemorrhage, lung congestion, mental status changes, brain swelling, seizures, and death. 
  • A 76-year-old woman experienced acute liver failure, possibly caused by drug interactions with pennyroyal tea.
  • There are several reports of young women who took pennyroyal oil for its abortion-inducing effects and died of multi-organ failure.
  • One infant given pennyroyal tea for respiratory infections died from organ failure.
• Scientific Name

  Mentha pulegium, Hedeoma pulegioides

• Clinical Summary

  An essential oil or tea derived from the leaves and flowering tops of the plant, pennyroyal was used in folk medicine to induce abortion, alleviate menstrual symptoms, and to treat inflammatory conditions, chronic bronchitis, and minor ailments. The oil itself is highly toxic, and is not recommended for internal use.

  Pennyroyal oil contains several monoterpenes, principally pulegone, to which toxic effects on the liver and lungs are attributed. Oxidative metabolites of pugelone such as menthofuran are oxidized further by cytochrome P450 to reactive intermediates that form adducts with cellular proteins and cause organ damage ⁽⁴⁾.

  Ingestion of pennyroyal oil in adults or tea in children causes severe toxicity ^(4) (5), including hepatic failure, acute renal failure, coagulopathies, metabolic acidosis, GI hemorrhage, pulmonary congestion with consolidation, cerebral edema, seizures, disseminated intravascular coagulation, and death.

• Purported Uses
  • Cancer treatment
  • Inflammation
  • Insect repellent
  • Lung conditions
  • Menstrual symptoms
• Mechanism of Action

  Pennyroyal’s abortifacient properties are thought to be due to irritation of the uterus, causing contractions, but lethal doses are necessary for this to occur and the effect is inconsistent. Pennyroyal’s mint properties, attributable to the menthol component, theoretically may act in dilating respiratory passages in bronchitis or asthma when consumed as a tea ⁽⁵⁾. European and American pennyroyal oil consist of 80-90% and 16-30% (R)-(+)-pulegone, respectively, which is oxidized by cytochrome P450 to menthofuran (about 50%) and other toxic metabolites ⁽⁴⁾. The menthofuran is further oxidized to an epoxide which is likely the ultimate toxic biological reactive intermediate ⁽¹⁵⁾ that causes liver damage. Animal and human studies also show that pulegone is neurotoxic. Menthofuran is known to decrease glucose-6-phosphatase activity in rat models, causing hypoglycemia ⁽¹⁾.

• Warnings

  This botanical contains compounds that are toxic to both animals and humans.

• Contraindications
  • In general, pennyroyal oil is highly toxic and is not recommended for internal use.
  • Due to its abortifacient effects, pennyroyal should not be consumed by pregnant or breast-feeding women.
• Adverse Reactions

  Dizziness, weakness, syncope, hallucinations, abdominal cramps, nausea, GI upset, pupillary changes, hepatotoxicity, renal injury.

  Toxicity: At least 24 cases of pennyroyal toxicity are in the literature, reporting fulminant hepatic failure, acute renal failure, hypoglycemia, coagulopathy, metabolic acidosis, GI hemorrhage, pulmonary congestion with consolidation, mental status changes, cerebral edema, seizures, disseminated intravascular coagulation, and death. Pennyroyal oil ingestion is treated with gastric lavage, activated charcoal, and N-acetylcysteine in patients evaluated soon after ingestion.

  Case Reports

  Acute liver failure: In 76-year-old woman possibly caused by drug interactions with pennyroyal tea, which makes use of 1A2, 2E1, and 2C19 as substrates ⁽¹⁶⁾.

  Multiorgan failure leading to coma and death with pennyroyal oil: A 24-year-old woman ingested pennyroyal extract for over 2 weeks and, after acute ingestion, developed abdominal cramps, chills, vomiting, syncope, cardiopulmonary arrest and multiorgan failure leading to coma and death. Exploratory laparotomy showed a hemorrhagic ectopic pregnancy ⁽¹³⁾. An 18-year old ingested 30 ml of pennyroyal oil and developed abdominal pain, vomiting, coagulopathy, and died one week later from cardiopulmonary arrest and multiple organ failure ⁽⁵⁾.

  Infant death with use of pennyroyal tea:  After ingesting 120 ml of homegrown pennyroyal mint tea to treat a suspected infection, an 8-week old boy experienced multiple organ failure including confluent hepatocellular necrosis, kidney hemorrhage and necrosis, bilateral lung consolidation with diffuse alveolar damage and hemorrhage, and diffuse cerebral edema with acute ischemic necrosis and isolated vacuolation of the midbrain. The infant died 4 days after admission.

  Infant hepatic injury, seizures, and bleeding: A 6-month old boy developed acute hepatic injury, seizures, and sinus hemorrhage after regular consumption of pennyroyal tea, and recovered after 2 months of hospitalization ⁽⁴⁾.

• Herb-Drug Interactions

  Cytochrome P450 substrate drugs: A case report of acute liver failure was possibly caused by drug interactions with pennyroyal tea, which makes use of 1A2, 2E1, and 2C19 as substrates ⁽¹⁶⁾. CYP2E1 in particular has been determined to be the major metabolizing enzyme for pulegone, the key toxic constituent of pennyroyal ⁽¹⁷⁾.

  Iron supplements: Monomeric flavonoids in pennyroyal may complex with iron in the intestinal lumen and reduce bioavailability by 50% or more ⁽¹⁴⁾.

• References

  1. Gordon WP, et al. Hepatotoxicity and pulmonary toxicity of pennyroyal oil and its constituent terpenes in the mouse. Toxicol Appl Pharmacol 1982;65:413-24.

  2. Fetrow CW, et al. Professional’s Handbook of Complementary and Alternative Medicines. Philadelphia: Springhouse; 1999.

  3. Martins HM, et al. Evaluation of microbiological quality of medicinal plants used in natural infusions. Int J Food Microbiol 2001;68:149-53.

  4. Bakerink JA, et al. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 1996;98:944-7.

  5. Sullivan JB, et al. Pennyroyal oil poisoning and hepatotoxicity. JAMA 1979;242:2873-4.

  6. Chen LJ, Lebetkin EH, Burka LT. Metabolism of (R)-(+)-pulegone in F344 rats. Drug Metab Dispos 2001;29:1567-77.

  7. Khojasteh-Bakht SC, Nelson SD, Atkins WM. Glutathione S-transferase catalyzes the isomerization of (R)-2-Hydroxymenthofuran to mintlactones. Arch Biochem Biophys 1999;370:59-65.

  8. Gordon WP, et al. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab Dispos 1987;15:589-94.

  9. Thomassen D, Slattery JT, Nelson SD. Menthofuran-dependent and independent aspects of pulegone hepatotoxicity: roles of glutathione. J Pharmacol Exp Ther 1990;253:567-72.

  10. Thomassen D, Slattery JT, Nelson SD. Contribution of menthofuran to the hepatotoxicity of pulegone: assessment based on matched area under the curve and on matched time course. J Pharmacol Exp Ther 1988;244:825-9.

  11. Khojasteh-Bakht SC, et al. Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran by human liver cytochrome P-450s: evidence for formation of a furan epoxide. Drug Metab Dispos 1999;27:574-80.

  12. Madyastha KM, Raj CP. Evidence for the formation of a known toxin, p-cresol, from menthofuran. Biochem Biophys Res Commun 1991;177:440-5.

  13. Anderson IB, et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 1996;124:726-34.

  14. Hurrell RF, Reddy M, Cook JD. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr 1999;81:289-95.

  15. Dietz BM, Bolton JL. Biological reactive intermediates (BRIs) formed from botanical dietary supplements. Chem Biol Interact. 2011 Jun 30;192(1-2):72-80.

  16. Fozard J, Hieger M. Hepatic Failure From Pennyroyal Tea Interaction With Medications Metabolized by the Cytochrome P450 Enzymes. Am J Ther. Aug 13 2019.

  17. Gordon P, Khojasteh SC. A decades-long investigation of acute metabolism-based hepatotoxicity by herbal constituents: a case study of pennyroyal oil. Drug Metab Rev. Feb 2015;47(1):12-20.