Health Care Professional Information
Scientific Name
Mentha pulegium, Hedeoma pulegioides
Common Name
Squaw mint, mosquito plant, American pennyroyal, European pennyroyal, mock pennyroyal, squaw balm, tickweed
Clinical Summary
An essential oil or tea derived from the leaves and flowering tops of the plant, pennyroyal is used in folklore medicine to induce abortion, alleviate menstrual symptoms, to treat inflammatory conditions, chronic bronchitis, minor ailments and colic in infants. Small amounts of the oil are approved by the Food and Drug Administration for use as a flavoring agent. Pennyroyal oil contains several monoterpenes, principally pulegone, which has known toxic effects on the liver and lungs. 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.
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
- Amenorrhea
- Asthma
- Bronchitis
- Cancer treatment
- Colic
- Common cold
- Headaches
- Induce abortion
- Inflammation
- Influenza
- Insect repel
- Premenstrual syndrome
- Stomach and intestinal gas
- Toothache
Constituents
- Volatile oils: Monoterpenes (e.g. pulegone, 3-octanone, 3-methylcyclohexanone, alpha-pinene, beta-pinene, p-cymene, limonene, p-mentha-1,4(8)-diene, pulegol, menthone, isomenthone, menthofuran, isopulegone, pulegone epoxides, piperitone, piperitenone)
- Monomeric flavonoids
- Others: 3-octylacetate, 3-octanol, 1-octen-3-ol, hedeomal, tannins, paraffins
(1) (2)
Mechanism of Action
The exact mechanism of action is unknown. Pennyroyal's abortifacient properties are thought 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).
Pharmacokinetics
Absorption
Studies in rats show a single 150 mg/kg intraperitoneal dose of pulegone produces peak plasma levels of 13.5 ± 3.0 mg/ml after about 15 minutes and a half-life of approximately one hour. Menthofuran levels peak at 7.0 ± 1.2 mg/ml one hour after pulegone administration, with a half-life of about 2 hours (10).
Distribution
Pulegone is oxidized by cytochrome P450 2E1, 1A2, and 2C19 to its proximate toxic metabolite menthofuran (about 50%), and other reactive metabolites (8). Menthofuran is thought responsible for less than half of the toxicity attributable to pennyroyal oil. Studies identify 2-Z-(2'-keto-4'-methylcyclohexylidene)propanal, an unsaturated keto aldehyde that forms adducts with cellular proteins, as the ultimate chemically reactive metabolite. Menthofuran also is metabolized to 4-hydroxy-4-methyl-2-cyclohexenone and p-cresol, a known liver and lung toxin (6). End products of cytochrome P450 oxidation of menthofuran include hydroxymenthofuran and its nontoxic tautomers mintlactone and isomintlactone (11). Pugelone may be metabolized by P450 via two other pathways to as yet unidentified electrophilic reactive species, which, together with pulegone, deplete glutathione (GSH) in liver and plasma by forming covalent adducts with its nucleophilic cysteinyl sulfhydryl group (7). Depletion of GSH further increases the hepatotoxicity induced by pulegone in rat models (9). Pennyroyal oil causes centrilobular liver necrosis in a dose-dependent manner (1).
Excretion
At least 14 pulegone metabolites, including menthofuran, are excreted in the urine (12) and at least 10 phase II metabolites are found conjugated to glutathione and glucuronide in bile.
Warnings
Analysis of commercially available pennyroyal leaves found contamination with low levels of bacteria, fungi, and yeast species.
(3)
Contraindications
Due to its abortifacient effects, pennyroyal should not be consumed by pregnant or breast-feeding women.
Adverse Reactions
Reported: 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 Report (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).
Case Report (Tea): An 8-week old boy, after ingesting 120 ml of homegrown pennyroyal mint tea to treat a suspected infection, 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. 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
Iron supplements: Monomeric flavonoids in pennyroyal may complex with iron in the intestinal lumen and reduce bioavailability by 50% or more.
(14)
Herb Lab Interactions
Elevated liver function tests
Metabolic acidosis
Increased PTT, PT, INR
Literature Summary and Critique
Clinical studies have not been performed.
Dosage (Inside MSKCC Only)
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References
- 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.
- Fetrow CW, et al. Professional's Handbook of Complementary and Alternative Medicines. Philadelphia: Springhouse; 1999.
- Martins HM, et al. Evaluation of microbiological quality of medicinal plants used in natural infusions. Int J Food Microbiol 2001;68:149-53.
- Bakerink JA, et al. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 1996;98:944-7.
- Sullivan JB, et al. Pennyroyal oil poisoning and hepatotoxicity. JAMA 1979;242:2873-4.
- Chen LJ, Lebetkin EH, Burka LT. Metabolism of (R)-(+)-pulegone in F344 rats. Drug Metab Dispos 2001;29:1567-77.
- 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.
- Gordon WP, et al. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab Dispos 1987;15:589-94.
- 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.
- 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.
- 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.
- Madyastha KM, Raj CP. Evidence for the formation of a known toxin, p-cresol, from menthofuran. Biochem Biophys Res Commun 1991;177:440-5.
- 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.
- 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.
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Dietz BM, Bolton JL. Biological reactive intermediates (BRIs) formed from botanical dietary supplements. Chem Biol Interact. 2010 Oct 21. [Epub ahead of print]
Consumer Information
How It Works
Bottom Line: 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 treat various minor ailments, including colic and bronchitis, but is better known for its abortion-inducing effects. Scientists are unsure exactly how pennyroyal exerts these effects (which, it should be noted, have not been consistently shown to occur), but it is thought that the herb causes irritation of the uterus, leading to contractions. However, lethal doses are necessary for this to occur, injuring or killing the mother as well as the fetus. The extensive toxicity of pennyroyal is due to a substance called pugelone, which is metabolized in the liver to highly toxic molecules that cause tissue damage in the internal organs. Studies in both animals and humans show that pulegone is directly toxic to the nervous system.
Purported Uses
Pennyroyal has not been studied in clinical trials. None of the claims below are backed by scientific evidence.
- To induce menstruation
- To treat lung conditions such as asthma and bronchitis
- To treat cancer
- To relieve stomach and intestinal gas (colic)
- To treat the common cold and the flu
- To treat headaches
- To induce abortion
- To reduce inflammation
- As an insect repellant
- To relieve the symptoms of premenstrual syndrome (PMS)
- To treat toothaches
Research Evidence
No clinical studies have examined the effectiveness of pennyroyal.
Patient Warnings
- Laboratory analysis of over-the-counter pennyroyal leaf products found contamination with low levels of bacteria, fungi, and yeast.
Do Not Take If
- You are pregnant or breast feeding (Pennyroyal can cause miscarriage and other toxic effects).
Side Effects
- Dizziness
- Weakness
- Hallucinations
- Abdominal cramps
- Nausea and stomach upset
- Liver toxicity
- Kidney toxicity
- Toxicity: At least 24 cases of pennyroyal toxicity are have been reported, including total liver failure, acute kidney failure, hypoglycemia (low blood sugar), blood clotting problems, metabolic acidosis (acidic pH of the blood), GI hemorrhage, lung congestion, mental status changes, cerebral edema, seizures, disseminated intravascular coagulation (blood clots forming in the blood vessels), and death. 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.
Last updated: February 22, 2011
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