Butterbur
Summary
Butterbur is a safety-first page. The raw plant contains liver-toxic pyrrolizidine alkaloids, and even certified PA-free root extract has been linked to rare severe liver injury, including two transplants. A PA-free root extract cut migraine frequency in trials (48% vs 26% on placebo, grade B), but neurologists withdrew their recommendation in 2015 over safety.
Key facts
- A daisy-family shrub; supplements use PA-free root extract (Petadolex) for migraine or leaf extract (Ze 339) for hay fever[1][3][5]
- Migraine attack frequency: reduced at 150 mg/day (B); hay fever symptoms: improved in most 2-week trials (C)[3][6][8]
- Root extract 100–150 mg/day for 12–16 weeks (migraine); leaf extract tablets 2–4 times daily for 2 weeks (hay fever)[3][4][5][7]
- Pyrrolizidine alkaloids can damage the liver and lungs and may cause cancer; use only certified PA-free products[1]
- 48 spontaneous reports with PA-free root extract, 9 severe and 2 requiring liver transplant[10]
- The American Academy of Neurology recommended it for migraine in 2012 and stopped in 2015 over safety concerns[1]
- 6 graded human outcomes on this page
- October 10, 2026
How it works
ProposedPetasins, the main active compounds, inhibit inflammatory mediators (cyclooxygenase, lipoxygenase and leukotriene pathways) and, in lab studies, blunt calcitonin gene-related peptide (CGRP) release from nerves involved in migraine. Leaf extracts are proposed to act through antileukotriene and antihistamine effects.[11][8]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Migraine | Grade B | Improved | RCT · n = 245 · 2004 | 3 rows |
| Hay fever | Grade C | Improved | RCT · n = 330 · 2005 | 3 rows |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Migraine attack frequency | Improved | Grade B | RCT · n = 245 · 2004 Adults aged 18–65 with 2–6 migraine attacks per month Form: PA-free Petasites root extract (Petadolex) · Dose: 75 mg twice daily (150 mg/day); 50 mg twice daily also tested · Duration: 4 months Attack frequency fell 48% on 150 mg/day versus 26% on placebo (p=0.0012); 68% versus 49% had at least a 50% reduction. The 100 mg/day dose was not significantly better than placebo. Mild burping was the most common side effect. | 15623680 (opens PubMed)Source [3] |
| Intermittent allergic rhinitis symptoms versus placebo and fexofenadine | Improved | Grade C | RCT · n = 330 · 2005 Adults with intermittent allergic rhinitis Form: Butterbur leaf extract Ze 339 (8 mg petasins per tablet) · Dose: 1 tablet three times daily · Duration: 2 weeks Butterbur and fexofenadine were each better than placebo (p<0.001) and did not differ from each other. | 16114089 (opens PubMed)Source [6] |
| Intermittent allergic rhinitis symptoms | Improved | Grade C | RCT · n = 186 · 2004 Adults with skin-test-confirmed intermittent allergic rhinitis Form: Butterbur leaf extract Ze 339 · Dose: 1 tablet twice or three times daily · Duration: 2 weeks Daytime symptoms improved more than placebo with a dose-response between the two doses; adverse events were similar to placebo. | 15611396 (opens PubMed)Source [5] |
| Migraine attack frequency | Improved | Grade C | RCT · n = 60 · 2000 Adults with migraine Form: PA-free Petasites root CO2 extract (Petadolex) · Dose: 50 mg twice daily (100 mg/day) · Duration: 12 weeks Attack frequency fell by up to 60% from baseline, significantly more than placebo; no adverse events were reported. | 11020030 (opens PubMed)Source [4] |
| Nasal airflow and symptoms during grass pollen season | No effect | Grade C | Crossover RCT · n = 35 · 2004 Adults with intermittent allergic rhinitis (Scotland) Form: Butterbur extract · Dose: 50 mg twice daily · Duration: 2 weeks per arm No significant effect on peak nasal inspiratory flow, nasal or eye symptoms, or quality of life versus placebo. | 15281472 (opens PubMed)Source [8] |
| Migraine frequency in children and adolescents | Improved | Grade D | Open-label trial · n = 108 · 2005 Children and adolescents aged 6–17 with migraine Form: PA-free Petasites root extract · Dose: 50–150 mg/day by age · Duration: 4 months 77% had at least a 50% drop in attack frequency; burping was the main side effect and no serious adverse events occurred. | 15836592 (opens PubMed)Source [9] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| PA-free butterbur root extract (e.g., Petadolex) | Varies[3][10] | No human absorption data in our sources.[10] | Mild burping common; rare severe liver injury reported even with PA-free product.[3][10] | Migraine trials (100–150 mg/day) |
| PA-free butterbur leaf extract (Ze 339) | Varies[5][6] | No human absorption data in our sources.[6] | Adverse events similar to placebo in 2-week trials.[5][6] | Hay fever trials |
| Raw butterbur plant, teas or uncertified products | Varies[1] | Contain pyrrolizidine alkaloids unless processed to remove them.[1] | Not safe: PAs can damage the liver and lungs and may cause cancer.[1] | Not used in clinical trials |
Studied doses
Doses studied in human trials ranged from 100 to 150 mg/day of PA-free root extract for migraine over 12–16 weeks, and leaf extract tablets two to four times daily for 2 weeks for hay fever. Only 150 mg/day beat placebo for migraine.[3][4][5][7]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Medicines
- Pain relievers and other drugs that can stress the liverCase reportIn a series of liver injury reports with butterbur root extract, 22 patients also took liver-toxic co-medications, and human liver-cell studies with ibuprofen, paracetamol and naratriptan showed enzyme changes. Avoid combining without medical supervision.[10]
- Medicines generallyNIH fact sheetNCCIH advises talking with your provider before combining butterbur with any medicine.[1]
Who should be careful
- Liver disease or heavy alcohol use
- Severe liver injury, including two transplants, has been reported with PA-free root extract.[10]
- Products not certified PA-free
- Pyrrolizidine alkaloids damage the liver and lungs and may cause cancer; uncertified products should not be used, including on broken skin.[1]
- Pregnancy and breastfeeding
- PA-containing butterbur may cause birth defects or liver damage; safety of PA-free products is not known.[1]
- Allergy to daisy-family plants
- People allergic to ragweed, chrysanthemums, marigolds or daisies may react to butterbur.[1]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
Liver safety
Liver toxicity is the main concern, from pyrrolizidine alkaloids in unprocessed plants and rare idiosyncratic injury with PA-free extract.
- Pyrrolizidine alkaloids
- Unprocessed butterbur contains PAs that can damage the liver and lungs and may cause cancer.[1]
- PA-free root extract
- A 2019 analysis of spontaneous reports found 48 liver injury cases, 9 severe, with 2 liver transplants; causality was likely in 3 and possible in 13, and many patients also took liver-toxic pain medicines.[10]
- Industry links in safety data
- That analysis and a 2022 review involve authors with funding, advisory or honoraria ties to the manufacturer, which also funded mechanistic safety studies.[10][11]
- Expert view
- A 2024 headache review summarizes butterbur as having strong efficacy evidence but a concern for liver toxicity, and defers to NCCIH guidance.[12]
How to read the label
- Label dose vs clinical doseMigraine trials used 75 mg of a specific root extract twice daily; 50 mg twice daily was not significantly better than placebo.[3]
- Look for "PA-free" certificationNCCIH advises using only products processed to remove PAs and labeled or certified PA-free.[1]
- Root vs leaf extractThe migraine evidence is for a root extract; the hay fever evidence is for a different leaf extract (Ze 339).[3][6]
Frequently asked questions
Does butterbur help migraines?
A PA-free root extract at 150 mg/day cut attack frequency 48% versus 26% on placebo in a 4-month trial, but liver safety concerns led neurologists to stop recommending it.[3][1]
Is butterbur safe?
Only products certified free of pyrrolizidine alkaloids should be considered, and even those have rare reports of severe liver injury.[1][10]
Does butterbur work for hay fever?
A leaf extract beat placebo and matched fexofenadine and cetirizine in 2-week trials, but an independent trial found no benefit.[6][7][8]
What does PA-free mean?
The extract has been processed to remove pyrrolizidine alkaloids, plant toxins that can damage the liver and lungs.[1]
Sources
- [1]Butterbur: Usefulness and Safety (last updated November 2024). NIH National Center for Complementary and Integrative Health, 2024. fact-sheet
- [2]Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: a systematic review.. Phytomedicine, 2006. systematic-review
- [3]Petasites hybridus root (butterbur) is an effective preventive treatment for migraine.. Neurology, 2004. RCT
- [4]An extract of Petasites hybridus is effective in the prophylaxis of migraine.. Int J Clin Pharmacol Ther, 2000. RCT
- [5]Butterbur Ze339 for the treatment of intermittent allergic rhinitis: dose-dependent efficacy in a prospective, randomized, double-blind, placebo-controlled study.. Arch Otolaryngol Head Neck Surg, 2004. RCT
- [6]Treating intermittent allergic rhinitis: a prospective, randomized, placebo and antihistamine-controlled study of Butterbur extract Ze 339.. Phytother Res, 2005. RCT
- [7]Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis.. BMJ, 2002. RCT
- [8]Effects of butterbur treatment in intermittent allergic rhinitis: a placebo-controlled evaluation.. Ann Allergy Asthma Immunol, 2004. crossover-RCT
- [9]Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract.. Headache, 2005. open-label
- [10]Hepatobiliary Events in Migraine Therapy with Herbs-The Case of Petadolex, A Petasites Hybridus Extract.. J Clin Med, 2019. observational
- [11]Petasites for Migraine Prevention: New Data on Mode of Action, Pharmacology and Safety. A Narrative Review.. Front Neurol, 2022. review
- [12]Nutraceuticals and Headache 2024: Riboflavin, Coenzyme Q10, Feverfew, Magnesium, Melatonin, and Butterbur.. Curr Pain Headache Rep, 2025. review
What changed
- First draft. Every PMID checked against NCBI E-utilities esummary (title and year taken from the record) and abstracts read for the cited rows.
- Adversarial review pass: every evidence row re-read against its PubMed abstract; the cetirizine comparison (no placebo arm) is cited only in the FAQ; the 2001 republication of the 60-patient migraine trial (PMID 11410074) was not double-counted. Industry ties: J. Borlak advisory role and manufacturer-funded mechanistic studies taken from the PubMed conflict statements of PMIDs 31083451 and 35585841. Safety, PA and guideline statements from the NCCIH fact sheet (opened 2026-10-10, updated November 2024). Retraction, expression-of-concern and erratum check run on all 11 PMIDs: none flagged. Safety-first page: no cost-per-dose block and no product links at launch. Page set indexable.