Benefits
Migraine prevention
Butterbur has been studied in people who already get migraines, not in healthy people, and the research is on one specific extract called Petadolex. In a placebo-controlled trial in 60 people over 12 weeks, using 2 capsules of 25 mg twice daily, migraine frequency fell by up to 60 percent from each person's own starting point, significantly more than with placebo. A systematic review of Petasites preparations reached a similar conclusion, though it rests on those same small trials. Two things need saying plainly. The American Academy of Neurology did give butterbur a Level A rating for migraine prevention in 2012, but it retired that guideline in 2015 over safety concerns that unregulated manufacturing was not reliably removing the toxic pyrrolizidine alkaloids, so it is not current evidence. And the exact product tested in that trial was later pulled from the German market.
Allergic rhinitis symptom relief
The strongest study here is a multicentre placebo-controlled trial in 186 people with intermittent allergic rhinitis, randomised for 2 weeks to a high dose of the Ze 339 extract (one tablet three times daily, 60 people), a low dose (one tablet twice daily, 65 people) or placebo (61 people). Both active doses beat placebo, with a significant dose relationship, and side effects were no different from placebo. An earlier 2-week trial compared Ze 339 with the antihistamine cetirizine in 125 people and found the two similar, but it had no placebo group, so it cannot show that either one actually worked. Both of those trials were run by the same investigator. The one trial by an independent group, a 35-person crossover study in Scotland during grass pollen season, found no significant difference from placebo. So the picture is genuinely mixed, and what evidence exists applies to the Ze 339 extract in people with a diagnosed pollen allergy.
Laboratory work on inflammation pathways
In laboratory work, the petasins in butterbur reduce the activity of an enzyme called 5-lipoxygenase and lower production of leukotriene B4, an inflammatory messenger. That is the proposed reason the Ze 339 extract was tested in hay fever. No study cited on this page looked at asthma, breathing tests or airway symptoms, and butterbur should never be used in place of prescribed asthma treatment or a rescue inhaler.
Mechanism of action
5-LOX and leukotriene B4 inhibition
In laboratory studies, petasin and isopetasin reduce the activity of the 5-lipoxygenase enzyme and lower production of leukotriene B4, an inflammatory messenger thought to play a part in allergic inflammation and possibly in migraine. This is a proposed explanation, not something that was measured in any of the human trials cited here. This targeted anti-leukotriene mechanism is distinct from COX inhibition and explains the non-NSAID anti-inflammatory profile.
Calcium channel blockade and smooth muscle relaxation
In laboratory work, petasins block calcium channels in the smooth muscle of blood vessels, which relaxes them. Researchers have suggested this as one reason the extract was tested for migraine, but no study cited here measured blood vessel activity in people, so treat it as a hypothesis rather than a demonstrated mechanism.
Mast cell stabilization and histamine reduction
In laboratory studies, butterbur extract reduces the release of histamine from mast cells, the immune cells involved in allergic reactions. Because it does not block H1 receptors the way antihistamine drugs do, researchers have proposed this as the reason it did not cause drowsiness in the one trial that compared it directly with cetirizine.
Clinical trials
Randomised, double-blind, placebo-controlled trial of a special Petasites hybridus extract (Petadolex), 2 capsules of 25 mg twice daily, versus placebo in 60 people who already had migraine, over 12 weeks. Main outcome: how often migraine attacks occurred. (Grossmann and Schmidramsl 2000, Int J Clin Pharmacol Ther)
60 people with migraine. 12-week intervention.
Migraine frequency fell by up to 60 percent from each person's own starting point, and the reduction was significantly greater than with placebo. This was a small trial, and the extract tested is the one that was discontinued in Germany in 2009 after the federal regulator refused to reauthorise it. The 2012 Level A rating from the American Academy of Neurology is often quoted for butterbur, but the academy retired that guideline in 2015 because unregulated manufacturing was not reliably removing the liver-toxic pyrrolizidine alkaloids, so it should not be treated as current evidence.
Randomised, double-blind, parallel-group trial comparing the butterbur extract Ze 339 with the antihistamine cetirizine over 2 weeks in 125 people with intermittent allergic rhinitis (61 on butterbur, 64 on cetirizine). There was no placebo group. (Schapowal et al. 2002, BMJ)
125 people with intermittent allergic rhinitis randomised. 2-week intervention.
The two groups improved to a similar degree: quality-of-life scores on the SF-36 improved similarly and the clinical global impression score was a median of 3 in both groups. Because there was no placebo group, this does not show that either treatment worked, since both groups could have improved simply as the pollen season changed. The sedation difference is real and worth knowing: 8 of the 12 side effects reported in the cetirizine group were sedative in nature.