Feverfew and butterbur

What it is

Feverfew (Tanacetum parthenium) is a herb whose extracts have been used to prevent migraine [1]. Butterbur (Petasites hybridus) is a root whose standardised extract, Petadolex, has been tested in migraine trials [2].

How it might work

Proposed mechanism for butterbur: its petasins may block inflammatory mediators and calcium signalling in pain-sensing nerves, and may reduce release of CGRP during migraine attacks. These are proposals from laboratory and review work [3]. Feverfew has been proposed to block serotonin receptors, but this is not established in human trials [4].

What the research says

Butterbur: in a 245-person trial, 75 mg twice a day cut attacks by 48% against 26% on placebo (per-protocol) [5]. A reanalysis of a 60-person trial found 45% of people on the extract had at least a 50% drop in attacks, against 15% on placebo [6]. A 2006 review found moderate evidence for 150 mg a day of Petadolex [2]. A 2020 systematic review rated the evidence as positive but limited [7].

Feverfew: a 2004 Cochrane review of five trials (343 people) found mixed results [1]. A 2015 Cochrane update of six trials (561 people) found one larger trial with a difference of 0.6 attacks a month against placebo, but the review rated the evidence as low quality [8]. A 147-person trial found no overall benefit, and a 170-person trial found attacks fell by 1.9 a month against 1.3 on placebo [9][10].

Doses used in studies

Butterbur: 75 mg twice a day (positive in the largest trial) and 50 mg twice a day (not significant) [5]; 150 mg a day was the dose with the best results in the 2006 review [2]. Children were given butterbur in a 12-week trial [11]. Feverfew: a stable extract at 6.25 mg three times a day [10]; the dose-response trial tested 2.08, 6.25 and 18.75 mg three times a day [9].

Safety and interactions

Feverfew: trials reported only mild, short-lived side effects, most often gastrointestinal complaints and mouth ulcers [8]. Butterbur: trials reported mild gastrointestinal effects, mostly burping [5]. Liver injury is the main safety concern. Four probable cases of reversible cholestatic hepatitis were linked to long-term butterbur use, about one in 175,000 people [12]. A 2019 review of spontaneous reports counted nine severe cases on Petadolex, two requiring transplant, and noted that 22 patients reported other liver-affecting medicines, especially during painful periods [13]. Rat studies gave a no-adverse-effect level at 15 times the maximum clinical dose, and bile duct changes appeared only at very high doses [3]. Pregnancy, breastfeeding, and interactions with specific medicines were not reported in the studies read for this page, so this page cannot give a safe-use answer for these groups [5][8][13]. People with liver disease or taking other liver-affecting medicines should ask a doctor before using butterbur [13]. No upper intake limit was found in the studies read [1][5].

Caveats and open questions

Butterbur trials are small, mostly of one brand (Petadolex), and some safety reviews are written by people with ties to its maker [2][13][3]. The feverfew evidence is low quality and mixed, with the most positive trial needing confirmation in larger studies [8]. No ongoing trials of either herb alone were found in ClinicalTrials.gov; the completed combination trials did not settle the question [1].