A patient has unexplained abnormal liver enzymes. You suspect drug induced liver injury (DILI). Further inquiry yields a history of migraine headaches for which the patient takes an herbal product. What could be the cause of DILI in this patient?
Butterbur extract from Petasites hybridus.
Butterbur contains petasins including petasin, isopetasin, and neopetasin. These are the presumed active ingredients to reduce the frequency of migraine headaches by various proposed mechanisms. The American Academy of Neurology suggested butterbur in a 2012 guideline but retired the guideline in 2015 “due to serious safety concerns”.
P. hybridus is in the Asteraceae family. Raw plant material from P. hybridus also contains some pyrrolizidine alkaloids (PA), which are hepatotoxic. Various plants (mainly from Asteraceae, Boraginaceae, and Leguminosae families) contain hepatotoxic PAs.
Makers of a proprietary European naturopathic product, Petadolex® (Weber and Weber GmbH and Co, KG, Inning, Germany and marketed in the US as an unregulated dietary supplement by Linpharma Inc., Tampa, FL) describe it as “virtually free of pyrrolizidine alkaloids”. Although Petadolex® lost its marketing approval in Germany, Switzerland, and the UK, a manufacturer-supported review suggested that hepatotoxicity was infrequent and reversible while citing their own early trials of Petadolex with a 4% incidence of elevated liver enzymes among study subjects.
Contributor: Michael Mullins, MD on behalf of Herbs & Dietary Supplements Section
Holland S., Silberstein SD et al.: Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults, Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012, Apr 24; 78(17): 1346-1353 [RETIRED 2015] https://doi.org/10.1212/WNL.0b013e3182535d0c
Diener HC, Freitag FG, Danesch U. Safety profile of a special butterbur extract from Petasites hybridus in migraine prevention with emphasis on the liver. Cephalalgia Reports 2018; https://doi.org/10.1177%2F2515816318759304