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Mentha pulegium L. Lamiaceae
SCN:
Standardized Common Name
 European pennyroyal,  Part: herb

QUICK REFERENCE SUMMARY

Safety Class:  2b, 2c, 2d
Interaction Class: A
Contraindications
Not for use during pregnancy or lactation (Anderson et al. 1996; Chadha 1988; Ciganda and Laborde 2003; Gordon et al. 1987; List and Hörhammer 1973).
Not for use by women with a heavy menstrual flow (Kuhn and Winston 2007).
Other Precautions
Not recommended for use in persons with liver or kidney disease (Brinker 2001; Gordon et al. 1987; Mizutani et al. 1987; Speijers 2001; Sztajnkrycer et al. 2003).
Not recommended for use in children or infants (Bakerink et al. 1996; Brinker 2001).
Drug and Supplement Interactions
None known.
Notice
Emmenagogue (Chadha 1988); see Appendix 2.
Editors’ Note
European pennyroyal leaf contains 1.0–2.0% essential oil consisting of 80.0–94.0% pulegone (List and Hörhammer 1973), a compound that causes severe liver toxicity when administered to rats in high doses (Gordon et al. 1987; Mizutani et al. 1987; Speijers 2001; Sztajnkrycer et al. 2003).
European pennyroyal and American pennyroyal (Hedeoma pulegioides) are historically interchangeable as the source for pennyroyal oil (De Smet 1992).

 
Adverse Events and Side Effects
Transient and generally mild adverse effects, including nausea, dizziness, and abdominal cramping, have been reported in association with the use of pennyroyal herb tea, even at doses as low as 1–3 cups. Much more serious side effects, including fatalities, are recorded with consumption of pennyroyal essential oil (see next entry) (Anderson et al. 1996).
Case reports also appear in the literature of significant adverse events with the use of incompletely described pennyroyal preparations to induce abortion. These include an epileptic event after use of 9–12 “pennyroyal tablets” daily for 4 days (Early 1961), and two deaths. One of the recorded deaths occurred after use of “a bottle of pennyroyal mixture” on two subsequent days (Vallance 1955). The other death was associated with ingestion of European pennyroyal herb extract in 48–56% alcohol by a 24-year-old diagnosed with a possibly ruptured ectopic pregnancy (Anderson et al. 1996). Two cases of coma associated with consumption of “essence of pennyroyal” are also reported (Anderson et al. 1996); the latter of these speculated that the material used was dilute pennyroyal oil (Braithwaite 1906).
Pharmacological Considerations
Coadministration of European pennyroyal tea and iron-fortified bread reduced absorption of the iron (Hurrell et al. 1999).
Pregnancy and Lactation
Pennyroyal essential oil (see next entry), has historically been used by women attempting to induce abortion (De Smet 1992; Williamson 2003). Although animal or other studies on the use of European pennyroyal herb during pregnancy and lactation are lacking, the content of the potentially toxic compound pulegone and traditional use of the oil suggest that European pennyroyal herb should not be used during pregnancy or when nursing.

 
REVIEW DETAILS

I. Drug and Supplement Interactions
Clinical Trials of Drug or Supplement Interactions
No clinical trials of drug or supplement interactions were identified.
Case Reports of Suspected Drug or Supplement Interactions
No case reports of suspected drug or supplement interactions were identified.
Animal Trials of Drug or Supplement Interactions
No animal trials of drug or supplement interactions were identified.
II. Adverse Events
Case Reports of Adverse Events
A review of pennyroyal toxicity identified 22 adverse events from 1883 to 1996, generally without differentiation between American pennyroyal (Hedeoma pulegioides) and European pennyroyal. Two of the identified events were associated with pennyroyal herb tea alone; two with use of pennyroyal herb tea and one or more additional preparations of pennyroyal herb; one with an alcohol extract of the herb; and the balance with pennyroyal essential oil (see next entry for further information on the case reports for essential oil). In women who drank pennyroyal tea, one or two cups of tea were associated with dizziness, weakness, and abdominal cramping. Consumption of the tea along with other preparations, including the essential oil, was associated with more severe symptoms including vomiting, stupor, and coma (Anderson et al. 1996). The case involving the extract, identified as “pennyroyal herb, 48% to 56% in an alcohol base” (probably an extract of the herb in 48–56% alcohol), was associated with the death of a 24-year-old woman with an undiagnosed ectopic pregnancy (Anderson et al. 1996; Young 1995).
Acute hepatic and neurological injury was observed in two Hispanic infants administered tea made from home-grown plants believed to be mint. An 8-week-old male developed fulminant liver failure with cerebral edema and necrosis, resulting in death, following a single dose of 120 ml of tea brewed from the plant’s leaves. A 6-month-old male experienced hepatic dysfunction and severe epileptic encephalopathy after thrice weekly ingestion of 90 ml of leaf tea. Upon examination of samples of the plants involved, it was suggested that the subspecies used contained pennyroyal oil, and serum analyses identified pulegone in one infant and its metabolite menthofuran in both. (Bakerink et al. 1996).
A case of contact dermatitis was reported in a woman who had recently picked European pennyroyal leaves (Roe et al. 2005).
III. Pharmacology and Pharmacokinetics
Human Pharmacological Studies
Coadministration of iron-fortified bread and European pennyroyal tea reduced absorption of the iron by 73%, an effect that was less pronounced than that of black tea or peppermint tea, but more inhibitory than cocoa or tea made with European vervain, linden flower, or chamomile (Hurrell et al. 1999).
Animal Pharmacological Studies
No relevant animal pharmacological studies were identified.
In Vitro Pharmacological Studies
Menthofuran, a metabolite of the compound pulegone, has been shown to be a significant inhibitor of the drug-metabolizing isoenzyme CYP2A6 (Khojasteh-Bakht et al. 1998).
IV. Pregnancy and Lactation
Pennyroyal oil has been traditionally used as an abortifacient (De Smet 1992; Gordon et al. 1987; Williamson 2003). Although animal or other studies on the use of pennyroyal herb during pregnancy and lactation are lacking, the content of the potentially toxic compound pulegone (see Toxicity Studies) and traditional use of the oil suggest that pennyroyal herb should not be taken during pregnancy or while nursing.
V. Toxicity Studies
Toxicity testing of pulegone in rats indicated that the no-observed-adverse-effect level (NOAEL) for the compound ranges between 20 mg/kg (administered by gavage) and 250 mg/kg (administered in food) daily (Imaizumi et al. 1985; Thorup et al. 1983).
The compound pulegone is metabolized to form menthofuran, a recognized hepatotoxin (Gordon et al. 1987; Mizutani et al. 1987; Speijers 2001; Sztajnkrycer et al. 2003).
Acute Toxicity
The LD50 of orally administered pennyroyal essential oil in rats is 220 to 580 mg/kg (Opdyke 1972).
Short-Term Toxicity
Rats administered pulegone at doses of 80 or 160 mg/kg daily had induced atonia, decreased blood creatinine content, lowered terminal body weight, and histopathological changes in the liver and in the white matter of the cerebellum. Rats administered 20 mg/kg daily did not exhibit these signs of toxicity (Thorup et al. 1983).
Genotoxicity
The compound pulegone tested negative for genotoxicity in a Salmonella typhimurium test and was weakly positive in the Drosophila melanogaster wing spot test (Franzios et al. 1997).
Immunotoxicity
In a screening study for immunotoxicity, mice treated orally with the compound isopulegol at doses up to 500 mg/kg daily for 5 days exhibited no signs of toxicity (Vollmuth et al. 1989).
Literature Cited
Anderson, I.B., W.H. Mullen, J.E. Meeker, et al. 1996. Pennyroyal toxicity: Measurement of toxic metabolite levels in two cases and review of the literature. Ann. Intern. Med. 124(8):726-734.
Bakerink, J.A., S.M. Gospe, Jr., R.J. Dimand, and M.W. Eldridge. 1996. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 98(5):944-947.
Braithwaite, P.F. 1906. A case of poisoning by pennyroyal: Recovery. Br. Med J. 2388:865.
Brinker, F. 2001. Herb contraindications and drug interactions. 3rd ed. Sandy, OR: Eclectic Medical Publications.
Chadha, Y. 1988. The wealth of India: A dictionary of Indian raw materials and industrial products. Delhi: Council of Scientific and Industrial Research.
Ciganda, C., and A. Laborde. 2003. Herbal infusions used for induced abortion. J. Toxicol. Clin. Toxicol. 41(3):235-239.
De Smet, P.A.G.M. 1992. Adverse effects of herbal drugs, Volume 1. Berlin: Springer.
Early, D.F. 1961. Pennyroyal: A rare case of epilepsy. Lancet 278:580-581.
Franzios, G., M. Mirotsou, E. Hatziapostolou, et al. 1997. Insecticidal and genotoxic activities of mint essential oils. J. Agric. Food Chem. 45(7):2690-2694.
Gordon, W.P., A.C. Huitric, C.L. Seth, R.H. McClanahan, and S.D. Nelson. 1987. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab. Dispos. 15(5):589-594.
Hurrell, R.F., M. Reddy, and J.D. Cook. 1999. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br. J. Nutr. 81(4):289-295.
Imaizumi, K., K. Hanada, K. Mawartari, and M. Sugano. 1985. Effect of essential oils on the concentration of serum lipids and apolipoproteins in rats. J. Agric. Biol. Chem. 49:2795-2796.
Khojasteh-Bakht, S.C., L.L. Koenigs, R.M. Peter, W.F. Trager, and S.D. Nelson. 1998. (R)-(+)-Menthofuran is a potent, mechanism-based inactivator of human liver cytochrome P450 2A6. Drug Metab. Dispos. 26(7):701-704.
Kuhn, M., and D. Winston. 2007. Herbal therapy & supplements. 2nd ed. St. Louis: Lippincott, Williams & Wilkins.
List, P.H., and H. Hörhammer. 1973. Hagers handbuch der pharmazeutischen praxis. Berlin: Springer.
Mizutani, T., H. Nomura, K. Nakanishi, and S. Fujita. 1987. Effects of drug metabolism modifiers on pulegone-induced hepatotoxicity in mice. Res. Commun. Chem. Pathol. Pharmacol. 58(1):75-83.
Opdyke, D. 1972. Monographs on fragrance raw materials. Food Cosmet. Toxicol. 12:949-950.
Roe, E., E. Serra-Baldrich, J. Dalmau, et al. 2005. Mentha pulegium contact dermatitis. Contact Dermat. 53(6):355.
Speijers, G. 2001. WHO Food Additives Series 46. Pulegone and related substances. Bilthoven, Netherlands: National Institute of Public Health and the Environment.
Sztajnkrycer, M.D., E.J. Otten, G.R. Bond, C.J. Lindsell, and R.J. Goetz. 2003. Mitigation of pennyroyal oil hepatotoxicity in the mouse. Acad. Emerg. Med. 10(10):1024-1028.
Thorup, I., G. Wurtzen, J. Carstensen, and P. Olsen. 1983. Short term toxicity study in rats dosed with pulegone and menthol. Toxicol. Lett. 19(3):207-210.
Vallance, W.B. 1955. Pennyroyal poisoning: A fatal case. Lancet 266:850-851.
Vollmuth, T.A., J.D. Heck, H.V. Ratajczak, and P.T. Thomas. 1989. Immunotoxicity assessment of flavoring ingredients using a rapid and economical screen. Toxicologist 9:206.
Williamson, E.M. 2003. Potter’s herbal cyclopedia. Saffron Walden, Essex: C.W. Daniel Co.
Young, G. 1995. Lifestyle on trial. Metro: Silicon Valley’s Weekly Newspaper. December 14-20, 1995 issue.