tusílago

Butterbur (Petasites hybridus): A Comprehensive Reference

1. Identity and Botanical Classification

1.1 Taxonomy and Nomenclature

Common butterbur (Petasites hybridus (L.) G.Gaertn., B.Mey. & Scherb) is a perennial herbaceous flowering plant of the daisy (Asteraceae) family. It is also known as common butterbur, and it is native to all of Europe and northern and western Asia. The genus name, Petasites, is derived from the Greek word petasos, the felt hat worn by shepherds. The common name of butterbur is attributed to the large leaves being used to wrap butter during warm weather. Other common names include pestwurz (German), blatterdock, bog rhubarb, and butter-dock.

The names for this plant in some other languages translate as "rain hat" or "hat plant," reflecting another use of the large leaves.

1.2 Related Species

Petasites japonicus, known as bog rhubarb or giant butterbur, is an herbaceous perennial plant and has been used for its therapeutic effect on allergy and asthma in Korea and European countries, whereas Petasites tricholobus, distributed widely in southwest and northwest China, has been used for the treatment of palsy, hypertension, coughs, and snakebite. Petasites hybridus is medicinally the most widely used species due to its two sesquiterpenes, petasin and isopetasin. Butterbur is a member of the Asteraceae family of plants and grows in many parts of the world. So far 18 species of this genus have been identified, and traditional indications include the treatment of migraine and pain associated with tension headaches, stomach pain, allergic rhinitis, asthma, and spasms of the gastrointestinal tract.

1.3 Plant Parts Used and Common Preparations

Petasites hybridus is a plant native to Europe, and extracts are derived from its rhizomes and stems. Extracts of Petasites hybridus are prepared from the rhizomes, roots, and leaves. The plant parts used in herbal or dietary supplements are the leaves and the roots. While its leaf extract is used for hay fever, butterbur extract for migraines is typically made from the root of the plant.

Among the various butterbur extracts, Petadolex® is a well-established herbal remedy for the prevention of migraine attacks. It is produced from the rhizome of Petasites hybridus and is the only butterbur extract that has been extensively evaluated for safety and clinical efficacy in the preventive treatment of migraine. Petadolex® was introduced in 1972 in Germany and 1998 in the USA. A distinct leaf extract, Ze 339, has been the primary preparation studied in allergic rhinitis trials.

Butterbur extract is mostly available in capsule form. The most commonly available product is an extract of the rhizome of Petasites hybridus standardized to contain 7.5 mg of petasine per capsule.

2. Traditional and Historical Use

2.1 Ancient and Classical Antiquity

Butterbur has been used for health purposes for many centuries. Butterbur has a long history of traditional use stretching back at least 2,000 years. Its medicinal use was recorded by the famous botanist and physician Dioscorides in 65 AD, who recommended it for skin ulcers and gastrointestinal complaints. Ancient Greeks used it for fever and to alleviate spasms.

2.2 Medieval Europe

In the Middle Ages, the odor and smoke from burning butterbur roots were thought to fight plague. Butterbur extracts have been used for centuries in traditional medicine, and purported uses were for plague, asthma, gastrointestinal and respiratory illnesses, and cancer. In the Middle Ages, butterbur was used to fight the plague. It was dried as a powder and mixed with wine to prevent plague and other virulent diseases.

During the Middle Ages, butterbur leaves and roots were used to treat cough, plague, and fever. Later, physicians prescribed butterbur for coughs and asthma, then also for colic and migraines.

2.3 Broader Traditional Uses

The ethnopharmaceutic indications include improvement of gastrointestinal pain, treatment of lung diseases, whooping cough, spasms of the urogenital tract, cramps, fever, gastric ulcers, improvement of wound or skin healing, and treatment of headache.

The aerial parts of P. japonicus have been used in traditional Japanese folk medicine as an antipyretic, antitussive, or wound healing agent. P. japonicus is a common vegetable in Japan and Taiwan; the baked flower bud is used in traditional medicine as an expectorant or in the treatment of asthma. The leaves or stalks of P. japonicus are commonly consumed as vegetables in Korea and Japan.

3. Key Constituents and Active Compounds

3.1 Primary Active Compounds: Petasins

Petasins are the pharmacologically active ingredients of butterbur and are defined as sesquiterpenes, i.e., esters of petasol and angelic acid. The main active constituents are two sesquiterpenes, petasin and isopetasin. Pharmacological research identified petasins as active ingredients, but extracts differ in the amounts of petasins and their structural analogs, i.e., iso- and neopetasin as well as S-petasin, iso-S- and neo-S-petasin. To date more than 20 different eremophilanes (bicyclic sesquiterpenoids) have been reported.

Petadolex® contains a minimum of 15% petasins and isopetasins, the essential active ingredients shown to be effective in clinical studies.

3.2 Other Constituents

Chemical components of butterbur extracts include sesquiterpene alcohol esters (petasitine, neopetasitine, and isopetasitine), volatile oils, flavonoids, and tannins. Chemical analysis has also revealed essential oils and pyrrolizidine alkaloids (PAs) as additional constituents. Other constituents of butterbur include the flavonoid glycosides isoquercitrin and astragalin.

Isopetasin, a sesquiterpene found in plants of the genus Petasites, is known to have anti-inflammatory effects and is found in the rhizomes' essential oil. Sesquiterpene lactone concentrations are also high, likely contributing to antioxidant activity.

3.3 Pyrrolizidine Alkaloids (PAs)

Extracts from butterbur leaves and stems can contain pyrrolizidine alkaloids (senecionine, integerrimine), which are toxic molecules capable of causing sinusoidal obstruction syndrome in animals as well as humans. The toxic alkaloid content of the plant limits its direct usage. PA removal during manufacturing is therefore essential for safe oral use (discussed in detail in the Safety section).

4. Mechanisms of Action

4.1 Anti-inflammatory Activity

The anti-inflammatory activity of Petasites hybridus extracts is attributed to its sesquiterpene ester components, such as petasin and isopetasin. Butterbur decreases the production of the inflammatory mediators prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and cysteinyl-leukotrienes in animal and human cellular systems, as well as purified enzyme preparations.

Butterbur diminishes the production of inflammatory mediators by inhibiting activities of cyclooxygenases, lipoxygenases, and phospholipase A2, and desensitizes nociception by acting on TRPA1 and TRPV1 ion channels.

Petasins are responsible, at least in part, for the anti-inflammatory effects of butterbur, and are related to the ability to inhibit prostaglandin and leukotriene biosynthesis. Given the importance of inflammation to the pain of migraine, the anti-inflammatory properties of petasins provide a rationale for the use of butterbur in the treatment of migraine attacks.

4.2 Calcium Channel Antagonism

Petasin blocks intracellular calcium influx into neutrophils and eosinophils and inhibits leukotriene biosynthesis. Petasins inhibited L-type voltage-dependent Ca²⁺ channel (VDCC) activity in a concentration-dependent manner, and petasin-induced vasorelaxation was confirmed in blood vessels of spontaneous hypertensive rats.

4.3 CGRP Inhibition (Migraine-Relevant)

Butterbur inhibits the release of calcitonin gene-related peptide (CGRP) from meningeal afferents during migraine attacks. One of the primary ways Petadolex® functions is by inhibiting the release of calcitonin gene-related peptide (CGRP), a brain chemical closely linked to migraine symptoms. CGRP inhibition is also the mechanism by which the latest prescription drugs for migraine prevention operate.

4.4 Spasmolytic Activity

It has been shown experimentally that P. hybridus extract blocks degranulation of activated immune cell populations, reduces smooth muscle spasm, and has anti-inflammatory effects. This spasmolytic action underlies its traditional and studied uses in respiratory, gastrointestinal, and urological conditions.

4.5 Anti-allergic Activity

Ze339 and petasin, but not zileuton (a 5-lipoxygenase inhibitor), abrogated PAF- and C5a-induced increases in intracellular calcium concentrations. These data suggest that Ze339 and petasin may block, compared to zileuton, earlier signaling events initiated by G protein-coupled receptors in granulocytes, perhaps at the level of or proximal to phospholipase Cβ.

Petatewalide B, a derivative of Petasites, has also been found to exhibit anti-allergic activities. Specifically, the compound inhibits the activation of β-hexosaminidase in RBL-2H3 mast cells.

Petasites extract Ze 339 inhibited allergen-induced Th2 responses (IL-4, IL-5, and RANTES) and therefore airway inflammation in mice.

5. Scientific Evidence by Area of Use

5.1 Migraine Prevention

Migraine prophylaxis represents the most extensively researched and clinically supported application for butterbur. Petadolex® has been investigated in four studies, including one good quality clinical trial involving 202 patients, two randomized controlled trials with smaller cohorts including adults and children, and a large observational, open-label study.

First Placebo-Controlled Trial (2001): The first placebo-controlled, randomized clinical trial with Petadolex® was conducted in 2001. A group of 33 adult subjects given a dose of 50 mg twice daily demonstrated a decrease in migraine frequency from a baseline of 3.4 per month to 1.8 per month after 12 weeks of treatment (p=0.0024). No significant adverse effects, including elevation of liver function tests, were reported during the treatment period, and the authors noted burping as the only unique adverse effect.

Landmark Confirmatory Trial — Lipton et al. (2004): This larger trial was a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg twice daily, Petasites extract 50 mg twice daily, or placebo twice daily in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg twice daily (p=0.0012 vs. placebo), 36% for Petasites extract 50 mg twice daily (p=0.127 vs. placebo), and 26% for the placebo group. Petasites extract 75 mg twice daily was thus more effective than placebo and is well tolerated as a preventive therapy for migraine, while the 50 mg twice-daily dose was not significantly more effective than placebo on the primary study endpoints.

Guideline Recognition and Subsequent Withdrawal: These two studies were evaluated as part of the American Academy of Neurology evidence-based guideline update for NSAIDs and other complementary treatments for episodic migraine prevention in adults in 2012. The review categorized the studies as class I trials, and Petasites received a Level A classification, establishing it as effective for migraine prevention. However, the American Academy of Neurology stopped recommending butterbur in 2015 because of serious concerns about possible liver toxicity. The American Headache Society and the American Academy of Neurology: 2012 evidence-based guideline update indicated that Petasites (butterbur) demonstrates effectiveness for migraine prevention and is a valid option for patients with migraine to reduce both the severity and frequency of migraine attacks (Level A). The recommendation was questioned and then retracted in 2016.

More Recent Review (2022): A 2022 narrative review summarized the pharmacology, safety, and clinical efficacy of butterbur in the prevention of migraine attacks and presented new data on its mode of action. The review examined published literature and study reports on the safety and clinical efficacy of the butterbur root extract Petadolex® and reported new findings on petasins in dampening nociception by desensitizing calcium-conducting TRP ion channels of primary sensory neurons. In randomized, double-blinded, and placebo-controlled trials with Petadolex®, migraine attack frequency was reduced significantly at 150 mg/day, and no relevant abnormal liver function was reported. Notably, this review received funding from the Petadolex® manufacturer, which represents a potential conflict of interest that should be considered when interpreting its conclusions.

Pediatric Evidence: A butterbur root extract may reduce the frequency of migraines in adults and children when taken orally. Butterbur appears to help reduce the frequency of migraines in adults and children.

Evidence Strength: The migraine prophylaxis evidence is the strongest in the butterbur literature. The 2004 Lipton et al. randomized controlled trial was of sufficient quality to earn a Level A guideline rating, but this was subsequently withdrawn due to safety concerns. Critically, Petadolex® is the only butterbur extract investigated for migraine in clinical trials; due to lack of information it is not possible to compare it to other extracts such as Petasites hybridus leaf extracts or any other Petasites herbal preparations. The total volume of high-quality RCT data remains limited, and industry sponsorship of some trials is an additional caveat.

5.2 Allergic Rhinitis (Hay Fever)

The Ze 339 leaf extract (Tesalin, Zeller AG) is the preparation most studied for seasonal allergic rhinitis. Multiple randomized controlled trials and surveillance studies have been conducted.

Comparison with Cetirizine — BMJ Trial (2002): This was a randomized, double-blind, parallel-group comparison conducted at four outpatient general medicine and allergy clinics in Switzerland and Germany. One hundred thirty-one patients were screened and 125 were randomized. Butterbur (carbon dioxide extract tablets, Ze 339) was given one tablet four times daily, or cetirizine one tablet in the evening, both given for two consecutive weeks. Study medication consisted of butterbur (petasites carbon dioxide extract Ze 339 standardized to 8.0 mg of total petasine per tablet). Improvement in SF-36 score was similar in the two treatment groups for all items tested hierarchically. Butterbur and cetirizine were also similarly effective with regard to global improvement scores on the clinical global impression scale (median score 3 in both groups).

Dose-Dependent Efficacy Trial (2004): This study investigated whether the efficacy and safety of Butterbur extract Ze339 are related to dosage when administered to patients with intermittent allergic rhinitis. The design was a prospective, randomized, double-blind, placebo-controlled, parallel-group comparison, conducted at a multicenter setting including 6 outpatient general medicine and allergy clinics, and 186 patients were randomized. The high-dose group received one tablet three times daily and the low-dose group one tablet twice daily; all groups were treated for 2 consecutive weeks. Butterbur Ze339 was found to be an effective treatment for intermittent allergic rhinitis symptoms and was well tolerated. The effects of this herbal medicine were clear to patients and physicians in a double-blind evaluation against placebo.

Three-Arm Trial vs. Placebo and Antihistamine (2005): Both active treatments (butterbur and antihistamine) were individually significantly superior to placebo (p<0.001) in improving symptoms of intermittent allergic rhinitis, while there were no differences between the two active treatments (p=0.37).

Postmarketing Surveillance (2006): The efficacy and safety of the butterbur leaf extract Ze 339 (carbon dioxide extract from the leaves of Petasites hybridus L., 8 mg petasines per tablet) were tested in patients with seasonal allergic rhinitis. In an open postmarketing surveillance study, 580 patients were treated with an average of 2 tablets of Ze 339 daily for 2 weeks. Symptoms of seasonal allergic rhinitis improved in 90% of patients. Differences observed before and after therapy were significant and clinically relevant for all symptoms. Efficacy, tolerability, and improvement in quality of life were positively rated by 80%, 92%, and 80% of patients, respectively. Butterbur leaf special extract Ze 339 was confirmed by 3 GCP trials and 2 postmarketing surveillance trials to be safe and efficacious in the treatment of patients with seasonal allergic rhinitis.

Expert Consensus: According to consensus opinion among rhinology experts in 2020, butterbur is recommended as an option for adjunctive treatment for allergic rhinitis based on low- to moderate-level evidence of efficacy, low risk for adverse effects, and moderate cost.

Evidence Strength: The allergic rhinitis evidence is moderately robust, supported by multiple RCTs showing Ze 339 to be comparable to cetirizine in symptom control, and consistently superior to placebo. The postmarketing surveillance study was unblinded and therefore lower quality. Overall, evidence quality is rated as low to moderate.

5.3 Asthma and Respiratory Conditions

The efficacy and tolerability of a butterbur root extract (Petadolex®) for the treatment of asthma was analyzed in a prospective, non-randomized, open trial. Subjects included 64 adults and 16 children/adolescents treated for two months with the extract, followed by two months during which intake of the extract was optional. Concomitant asthma medication was permitted. The number, duration, and severity of asthma attacks decreased, while peak flow, forced expiratory volume (FEV1), and all measured symptoms improved during therapy. In addition, more than 40 percent of patients using asthma medications at baseline reduced intake of these medications by the end of the study.

Asthmatic patients were shown to benefit from butterbur's anti-inflammatory activity whilst on steroids.

Evidence Strength: Early research suggests that butterbur might be helpful for treating asthma and chronic bronchitis. The evidence in this area is preliminary — the key published study was open-label, non-randomized, and uncontrolled. No high-quality placebo-controlled RCTs have been published in asthma. Mechanistic data on leukotriene and prostaglandin inhibition offer biological plausibility, but the clinical evidence must be characterized as preliminary.

5.4 Gastrointestinal and Urological Applications

In rat gastric ulceration models, butterbur extract blocked the effects of ethanol and indomethacin. The spasmolytic properties of butterbur have led to its investigation in conditions associated with smooth-muscle cramping. It has also been used in treating patients with irritable bladder and urinary tract conditions. Ethnopharmaceutic indications include spasms of the urogenital tract, cramps, and gastric ulcers.

Evidence Strength: Although the list of historically claimed benefits of P. hybridus extracts in ethnomedicine is long, only limited evidence of therapeutic activity has been published for gastrointestinal and urological conditions. Evidence in these areas consists primarily of in vitro and animal studies, or small uncontrolled clinical observations. No robust clinical trials have been conducted. These uses remain speculative from an evidence-based standpoint.

6. Body Systems and Health Areas

• Neurological / Central Nervous System: Migraine prophylaxis — the best-supported clinical indication, via CGRP inhibition, calcium channel antagonism, and anti-inflammatory mechanisms.
• Immunological / Allergic: Seasonal allergic rhinitis (hay fever) — supported by multiple RCTs with Ze 339 leaf extract, demonstrating efficacy comparable to second-generation antihistamines.
• Respiratory: Asthma and chronic bronchitis — plausible mechanistically via leukotriene inhibition; clinical evidence is preliminary and non-randomized.
• Gastrointestinal: Gastric ulcer protection, antispasmodic for gastrointestinal cramping — evidence primarily preclinical.
• Urological: Irritable bladder, urinary tract spasms — traditional use supported by spasmolytic pharmacology; no published clinical trials.
• Dermatological: Topical wound healing — traditional use, no published controlled trials.

7. Dosage Forms and Dosages Reported in Studies

The most commonly available product is an extract of the rhizome of Petasites hybridus standardized to contain 7.5 mg of petasine per capsule. Intake in clinical practice is usually 1 to 2 capsules three times per day.

The following dosages have been reported specifically in clinical studies:

• Migraine prevention (Lipton et al., 2004): Three-arm randomized trial used Petasites extract 75 mg twice daily, Petasites extract 50 mg twice daily, or placebo twice daily over 4 months, in 245 patients. The 75 mg twice-daily dose produced the statistically significant reduction.
• Migraine prevention (first RCT, 2001): 33 adult subjects were given a dose of 50 mg twice daily for 12 weeks.
• Migraine prevention (pooled RCT data, narrative review): Migraine attack frequency was reduced significantly at 150 mg/day total dose in randomized, double-blinded, and placebo-controlled trials.
• Allergic rhinitis — Ze 339 (BMJ trial, 2002): One tablet of Ze 339 standardized to 8.0 mg of total petasine per tablet, four times daily, for two weeks.
• Allergic rhinitis — Ze 339 (dose-finding, 2004): High-dose group, one tablet three times daily; low-dose group, one tablet twice daily; all groups treated for 2 consecutive weeks.
• Allergic rhinitis — Ze 339 (postmarketing surveillance, 2006): 580 patients were treated with an average of 2 tablets of Ze 339 daily for 2 weeks.
• Asthma (open trial): The Petadolex® extract was used in 64 adults and 16 children/adolescents treated for two months. Specific dosing was not published in the PubMed abstract.
• General daily dose range across studies: Multiple studies recommend a daily dose of 50–150 mg.

8. Safety Considerations

8.1 Pyrrolizidine Alkaloids: The Primary Safety Concern

Butterbur contains unsaturated pyrrolizidine alkaloids that are known to be hepatotoxic in humans and in preclinical studies have been shown to be carcinogenic and mutagenic. One major area of concern regarding safety is with pyrrolizidine alkaloids which are commonly found in the butterbur plant. These substances can cause hepatotoxicity, lung toxicity, carcinogenesis, and thrombosis.

The butterbur plant contains substances called pyrrolizidine alkaloids (PAs). PAs can damage the liver and lungs and may cause cancer. Only butterbur products that have been processed to remove PAs and are labeled or certified as PA-free should be considered for use.

8.2 Product Quality and PA Removal

Butterbur herbal products for oral use must be specially processed to remove any traces of pyrrolizidine alkaloids. Certified extracts remove the pyrrolizidine alkaloids to avoid causing liver damage. However, the reality of commercial products is more complicated: in a review of 21 commercial butterbur products, 7 of the 21 products (33%) contained PAs. In addition, only 7 (33%) showed an amount of petasins consistent with each product's labeling.

8.3 Reported Cases of Hepatotoxicity

From the World Health Organization's Vigibase, one study reported 40 cases of hepatotoxicity, including two liver transplants associated with the use of Petasites formulations. However, these cases may be the result of the use of butterbur contaminated with alkaloids.

Cases of liver toxicity have been reported with extracts of butterbur where the pyrrolizidine alkaloids had reportedly been removed and only small amounts remained. A search of the WHO's pharmacovigilance database, VigiBase, revealed reports of adverse reactions involving the liver in association with products containing Petasites hybridus. VigiBase reports include nausea, anorexia, and pruritus to hepatic enzymes increased, hepatic necrosis, hepatocellular damage, jaundice, hepatitis, and hepatic failure.

Butterbur preparations processed to remove pyrrolizidine alkaloids do not appear to cause liver injury, either in the form of serum enzyme elevations during treatment or clinically apparent acute liver injury. However, recent cases of clinically apparent liver injury have been reported with use of several commercial preparations of butterbur, suspected to be due to residual pyrrolizidine alkaloid contamination.

The mechanism by which some preparations of butterbur might cause liver injury is not known but is likely due to a contaminant or mislabeling of the product.

8.4 Safety in Clinical Trials

Several studies, including studies of children and adolescents, have reported that PA-free butterbur products seem to be safe when taken by mouth for up to 16 weeks. Butterbur is generally well tolerated when taken orally. Side effects can include belching, diarrhea, drowsiness, rash, and stomach upset.

Few adverse reactions have been reported in clinical trials; however, these trials have been of short duration (maximum 16 weeks). GI symptoms, including nausea, flatulence, and belching, are the most common documented adverse reactions.

In the postmarketing surveillance study of Ze 339, adverse events occurred at a rate of 3.8%, and gastrointestinal complaints were predominantly nonspecific.

8.5 Preclinical Safety Studies

A butterbur root extract was evaluated in repeated-dose studies for up to 6 months. A no-observable-adverse-effect level at 15-fold of the maximal clinical dose (3 mg/kg/day MCD) was established for rats. At supratherapeutic doses (45–90-fold MCD), bile duct hyperplasia was observed, and mechanistic studies revealed regulations of solute carriers to likely account for bile duct proliferations. Additionally, liver function tests performed in cultures of primary human hepatocytes did not evidence hepatotoxicity at therapeutic butterbur levels and with migraine co-medications.

8.6 Guideline Withdrawal and Regulatory Context

Butterbur contains pyrrolizidine alkaloids (PA), which are hepatotoxic. The American Academy of Neurology stopped recommending butterbur in 2015 because of serious concerns about possible liver toxicity. The NCCIH notes that people should only consider butterbur products that have been processed to remove PAs and are labeled or certified as PA-free; some products may claim to be PA-free when they are not. The NCCIH also highlights that further research into the safety of long-term butterbur use is necessary.

8.7 Monitoring and Contraindications

Monitoring liver function (AST, ALT, ALP, GGT, bilirubin) is recommended due to potential hepatotoxicity from butterbur or drug contamination with pyrrolizidine alkaloids. Patients on butterbur who develop unexplained symptoms such as fatigue, nausea, abdominal pain, or dark urine should have routine liver tests drawn and discontinue use of the herb if there are any abnormalities.

Butterbur products that contain PAs may not be safe when applied to the skin, as PAs could be absorbed through cuts or scrapes.

8.8 Drug Interactions

Butterbur-drug interactions have not been formally defined. At the time of writing of one reference, there were no well-known supplement or food interactions with this supplement, and no reported interactions between this supplement and medicines were found. The absence of documented interactions reflects sparse pharmacokinetic research rather than confirmed safety with all co-administered agents.

8.9 Pregnancy, Lactation, and Pediatric Use

Butterbur is contraindicated in pregnancy and lactation due to the potential presence of pyrrolizidine alkaloids and the absence of safety data. Butterbur should only be given to children under the supervision of a qualified health practitioner. Several studies, including studies of children and adolescents, have reported that PA-free butterbur products seem to be safe when taken by mouth for up to 16 weeks in controlled research contexts.

References

• Giles M et al. Petasites hybridus (Butterbur). Alternative Medicine Review, 2001.
• Borlak J et al. Petasites for Migraine Prevention: New Data on Mode of Action, Pharmacology and Safety. A Narrative Review. Frontiers in Neurology, 2022.
• Din L, Lui F. Butterbur. StatPearls. National Library of Medicine / NCBI Bookshelf, updated 2023.
• Butterbur. LiverTox®. NCBI Bookshelf, NIH / National Institute of Diabetes and Digestive and Kidney Diseases.
• Butterbur: Usefulness and Safety. National Center for Complementary and Integrative Health (NCCIH), NIH.
• Headaches and Complementary Health Approaches: What the Science Says. NCCIH, NIH.
• Mihajilov-Krstev T et al. Phytochemistry, Toxicology and Therapeutic Value of Petasites hybridus Subsp. Ochroleucus (Common Butterbur) from the Balkans. Plants (Basel), 2020.
• Chemical Constituents of the Leaves of Butterbur (Petasites japonicus) and Their Anti-Inflammatory Effects. PMC/NCBI, 2020.
• Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ / PMC, 2002.
• Lipton RB et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology, 2004.
• Schapowal A; Petasites Study Group. Butterbur Ze339 for the treatment of intermittent allergic rhinitis: dose-dependent efficacy. Arch Otolaryngol Head Neck Surg, 2004.
• Käufeler R et al. Efficacy and safety of butterbur herbal extract Ze 339 in seasonal allergic rhinitis: postmarketing surveillance study. Advances in Therapy, 2006.
• Schapowal A. Treating intermittent allergic rhinitis: a prospective, randomized, placebo and antihistamine-controlled study of Butterbur extract Ze 339. Phytotherapy Research, 2005.
• Danesch U. Petasites hybridus (Butterbur root) extract in the treatment of asthma — an open trial. Altern Med Rev, 2004.
• Prieto JM. Update on the efficacy and safety of Petadolex®, a butterbur extract for migraine prophylaxis. Botanics: Targets and Therapy, 2014.
• Medsafe New Zealand. Complementary Corner: Butterbur and Liver Toxicity, 2012.
• NeurologyLive. Migraine Preventative Butterbur Has Safety Concerns.
• Aydın AA et al. The medical plant butterbur (Petasites): analytical and physiological (re)view. J Pharm Biomed Anal, 2013.
• Kälin M. The common butterbur (Petasites hybridus) – portrait of a medicinal herb. ResearchGate / Forsch Komplementarmed Klass Naturheilkd, 2003.
• Butterbur. U.S. Government / NCCIH Fact Sheet.