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📰Read the full Butterbur evidence review on GMJ News →Complete clinical article, references and updates on news.gmj.ge. This page is the structured safety summary.⚠ Patient buying non-PA-free butterbur — hepatotoxic/carcinogenic PAs [1]
⚠ Neurologist unaware of butterbur migraine evidence — Level A RCT data [2]
⚠ Patient told 'butterbur doesn't work for migraines' — AAN downgrade was safety-based, not efficacy-based [2]
⚠ Product without explicit PA-free certification — REJECT [1]
ℹ️ Not obtained from food. Not applicable — this is not obtained from food in meaningful amounts; supplementation is the practical route.
🔬 Lab interpreter
Recommended test
LFTs (ALT, AST)
LFTs (ALT, AST)
Reference range / target
Normal range
Normal range
To monitor for PA-related hepatotoxicity even in 'PA-free' products [1].
Full lab monitoring ↓⚕ For professionals — confirm ranges against your local laboratory.
Clinical verdict
Butterbur has Level A migraine prevention evidence (n=245 RCT: 48% reduction at 75 mg BID) — one of the strongest botanical evidence bases. The CRITICAL safety issue: raw plant PAs are hepatotoxic and carcinogenic. ONLY PA-free certified extracts are safe. Product availability is limited since the Petadolex® German withdrawal. If available and PA-free: one of the best natural migraine preventives. If PA status uncertain: do NOT use [1] [2].
1 How much do I need?
👤 Adults: Specific dosage data under clinical review
👴 Elderly: Specific dosage data under clinical review
🤰 Pregnancy: See guidance
AVOID. PA contamination risk even in 'PA-free' products. Insufficient pregnancy safety data [1].
👦 Pediatric: See guidance
Limited data. One study in children 6–17 years showed migraine reduction. PA-free extract essential. Use only under specialist guidance [1].
🏃 Athletes: Standard dose
⚖️ Obesity: Standard dose
Fat-soluble compounds may require dose adjustment in obesity.
🩺 Renal: Consult specialist
Dose adjustment may be needed in renal impairment.
🌱 Vegan: Standard dose
How to take
🍽 Timing: BID (morning and evening) [1].
💊 With food: With food to reduce GI irritation [1].
🚫 Avoid: ANY product without PA-free certification. Raw butterbur. During pregnancy [1].
2 Which form?
| Form | Bioavailability | Vegan | Cost |
|---|---|---|---|
| ['Petadolex® (PA-free butterbur extract)', 'gold standard', 'CO2-extracted, PA-free certified (<0.08 ppm PAs). 75 mg BID. Used in pivotal migraine RCT [1] [2].'] | Standard | Check label | |
| ['Generic PA-free butterbur extract', 'variable', 'Must verify PA-free certification. Without it, potentially hepatotoxic [1].'] | Standard | Check label | |
| ['Raw butterbur preparations', 'DANGEROUS', 'Contain hepatotoxic and carcinogenic pyrrolizidine alkaloids. NEVER use [1].', 'red'] | Standard | Check label |
3 Common questions
What are pyrrolizidine alkaloids and why are they dangerous? ▼
PAs are naturally occurring plant compounds that are metabolized by the liver into toxic pyrroles that cause hepatic veno-occlusive disease (sinusoidal obstruction syndrome) and are carcinogenic with chronic exposure. Many Asteraceae family plants contain PAs. Butterbur's raw leaves and rhizome contain significant PA levels. Only specialized CO2 extraction or other PA-removal processes make butterbur safe [1].
Why was Petadolex® withdrawn from Germany? ▼
In 2012, several hepatotoxicity case reports were associated with butterbur products in Germany, likely from products with inadequate PA removal. Petadolex® manufacturer (Weber & Weber) voluntarily withdrew pending re-evaluation. This was a manufacturing quality issue, not a failure of PA-free butterbur per se. The product remained available in other markets [1].
Is butterbur still recommended for migraines? ▼
The AAN/AHS initially gave butterbur Level A (effective) in 2012 but later downgraded to 'insufficient evidence to recommend' in 2015 — NOT because efficacy data changed (the RCT is excellent), but because of PA safety concerns and product availability. Many headache specialists still consider PA-free butterbur one of the best evidence-based natural migraine preventives [2].
How do I verify PA-free status? ▼
The product should state 'PA-free' or 'pyrrolizidine alkaloid-free' on the label, ideally with a COA showing PA levels <0.08 ppm. Petadolex® (if available) is the gold standard. Do NOT use any butterbur product that does not explicitly certify PA-free status [1].
4 Clinical evidence
Strong
Migraine prevention: a multicenter RCT (n=245) found Petadolex® 75 mg BID reduced migraine frequency by 48% over 4 months vs 26% placebo — statistically and clinically significant. The American Academy of Neurology and American Headache Society gave butterbur a Level A recommendation (effective) for migraine prevention in 2012, later downgraded due to PA safety concerns [2]. HIGH
Moderate
Allergic rhinitis: 2 RCTs found butterbur extract comparable to cetirizine and fexofenadine for seasonal allergy symptoms, without sedation [1]. Dose-response: 75 mg BID superior to 50 mg BID in the pivotal trial [2]. Asthma: 1 pilot study of butterbur for asthma prevention; insufficient [1]. MODERATE
Insufficient
5 Safety, toxicity & adverse events
Absolute contraindications
✕ Products that are NOT certified PA-free — raw butterbur's pyrrolizidine alkaloids are hepatotoxic and carcinogenic
✕ Liver disease
Relative
⚠ Ragweed/Asteraceae allergy
⚠ Use only standardized PA-free extracts
⚠ Anticholinergic/CYP interactions possible
⚠ Pregnancy and lactation — avoid
🚩 Red flags
● Patient using non-PA-free butterbur — hepatotoxicity risk [1]
● Jaundice in butterbur user — immediate LFTs, discontinue [1]
● Product sold as 'butterbur' without PA certification — reject [1]
6 Interactions
Drug interactions
CYP3A4 substrates Moderate
Mechanism: Petasin may inhibit CYP3A4 [1].
Effect: Increased drug levels [1].
Action: Monitor if on narrow-index CYP3A4 drugs [1].
Supplement synergies
Magnesium + Riboflavin (B2) + CoQ10 · 75 mg butterbur BID + 400 mg Mg + 400 mg B2 + 300 mg CoQ10
The 'migraine prevention quartet': butterbur + Mg + B2 + CoQ10. All have independent migraine RCT evidence [2].
The 'migraine prevention quartet': butterbur + Mg + B2 + CoQ10. All have independent migraine RCT evidence [2].
7 Regulatory
Germany (BfArM): Products without PA-free certification withdrawn. PA-free extracts were historically approved for migraine/allergy [1].
United States (FDA): Available as dietary supplement. FDA has not issued specific guidance on butterbur PAs [1].
AAN/AHS: 2012: Level A (effective) for migraine prevention. 2015: downgraded to 'insufficient evidence to recommend' due to PA safety concerns [2].
8 US supplement products
10
on-market products containing Butterbur (NIH DSLD)
Brands carrying Butterbur (7)
Click a brand to see its Butterbur products.
9 Frequently paired with
10 Cite this page
Vancouver: Pkhakadze G. Butterbur — safety profile [Internet]. Tbilisi: PHIG; 2026 [cited 2026 Jul 17]. Available from: https://supplement.ge/ingredients/butterbur/
APA 7th: Pkhakadze, G. (2026). Butterbur — Safety profile. Public Health Institute of Georgia. https://supplement.ge/ingredients/butterbur/
📋 Editorial information
Author: Prof. G. Pkhakadze, MD, MPH, PhD
Institution: Public Health Institute of Georgia (PHIG)
Affiliation: David Tvildiani Medical University (DTMU)
First published: January 2026
Last reviewed: 2026-05-29
Next review: January 2027
References: 4 cited sources
COI: SupplementIndex receives no funding from supplement manufacturers. All content independently authored by PHIG.
Process: Systematic literature review
📄 License & reuse
Published under Creative Commons Attribution 4.0 International (CC BY 4.0). You may share and adapt for any purpose with attribution.
Pkhakadze G. "Butterbur — Safety Profile." SupplementIndex, PHIG, 2026. https://supplement.ge/ingredients/butterbur/ CC BY 4.0.
GP
Prof. G. Pkhakadze, MD, MPH, PhD
Professor of Public Health · Head of Department, DTMU
Editor-in-Chief, Georgian Medical Journal (ISSN 3088-4322)
Chair, Public Health Institute of Georgia · UEMS Public Health Section
Educational and public health purposes. CC BY 4.0. Consult your healthcare provider before starting any supplement. Corrections: info@accreditation.ge. Publisher: PHIG