Can butterbur cause liver toxicity?

There is a small risk that butterbur can cause liver toxicity, especially when used with hepatotoxic (toxic to the liver) medications, like acetaminophen, or in people with pre-existing liver conditions. Liver toxicity is likely caused by the known hepatotoxins pyrrolizidine alkaloids (PAs), which are supposed to be removed when the herb is processed for commercial dietary supplement use.^[1] However, a 2012 study that tested 21 commercial butterbur supplements found that only 7 of the supplements contained no PAs, while another 7 contained toxic levels of PAs.^[2] This might explain why there have been reports of hepatotoxicity in people taking commercial butterbur supplements that are supposed to be free of PAs. For example, there are 48 reports of mild to severe liver injury in people taking 50 to 225 mg of a commercially available butterbur extract daily for 4 to 730 days. Of these cases, 22 people were also taking other medications that can increase the risk of liver toxicity (such as acetaminophen). Severe liver toxicity seems to be more likely with long-term use and was reported in people who took butterbur for an average of 103 days.^[3]