Purple Butterbur Root (Petasites hybridus): A Comprehensive Reference
1. Identity, Botanical Classification, and Common Names
Taxonomy and Scientific Nomenclature
Petasites hybridus, also known as the butterbur, is a herbaceous perennial flowering plant in the family Asteraceae that is native to Europe and northern Asia. Its full accepted scientific name is Petasites hybridus (L.) G.Gaertn., B.Mey. & Scherb., a perennial herbaceous flowering plant of the daisy (Asteraceae) family. The specific epithet hybridus is Latin for "hybrid," originating from Carl Linnaeus's 1753 description of the species as Tussilago hybrida in Species Plantarum, where he considered it a hybrid involving coltsfoot (Tussilago farfara). Confusingly, despite its specific epithet that suggests it is a cross between two different Petasites species, butterbur (Petasites hybridus) is accepted by botanical authorities as a distinct species.
Petasites hybridus is medicinally the most widely used species in the genus, due to its two sesquiterpenes, petasin and isopetasin. It is also known as common butterbur, and is native to all of Europe, and northern and western Asia. It should be distinguished from related species also called "butterbur": Petasites japonicus, known as bog rhubarb or giant butterbur, 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 snake-bite. The present article concerns Petasites hybridus specifically, the species most extensively studied in Western clinical contexts.
Etymology and Common Names
The genus name, Petasites, is derived from the Greek word petasos, which is 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 designation "purple butterbur root" found in commercial supplement contexts refers specifically to preparations derived from the rhizome and root of this plant, and reflects the plant's purplish flower spikes that emerge in early spring. Additional English names include devil's hat, evoking the expansive, hat-shaped foliage, and pestilence wort, stemming from its historical use during plague.
Morphology and Natural Habitat
The plant has long rhizomes and large leaves, which develop after flowering and can reach up to 60 cm in diameter, and it grows up to 3 feet in height. It is native to Europe, and is present as an introduced species in North America and West and North Asia. It is common on riverbanks, in wet meadows, and in other damp and shady locations. Common butterbur flowers are pink to purplish. Both this species and related species can spread by underground stems called rhizomes, allowing expansion of clumps of plants.
Commercial Preparations and Dosage Forms
Extracts of Petasites hybridus are prepared from the rhizomes, roots, and leaves. In the marketplace, the ingredient appears in several forms: standardized root or rhizome extract capsules or tablets (commonly labeled as "PA-free"), raw dried root powder, and carbon dioxide (CO₂) supercritical-fluid extracts. Raw and unprocessed butterbur extracts contain pyrrolizidine alkaloids, which are hepatotoxic and carcinogenic. Nonetheless, the patented CO₂-extract of butterbur is practically free of these toxic constituents (<0.088 ppm). The most clinically studied commercial preparation is Petadolex® (Weber & Weber GmbH, Germany). 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 was 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, and pharmacological research identified petasins as active ingredients. A separate leaf-based extract, ZE 339 (Zeller AG, Switzerland), has been evaluated primarily in the context of allergic rhinitis.
2. Traditional and Historical Use
Ancient and Medieval Traditions
Herbal preparations of P. hybridus have been practiced in traditional medicine in Europe for over 900 years, for the treatment of a broad spectrum of human ailments. Petasites (butterbur, Asteraceae) species have been used since ancient times in the traditional medicine of Asian and European countries to treat central nervous system (migraine), respiratory (asthma, allergic rhinitis, bronchitis, spastic cough), cardiovascular (hypertension), gastrointestinal (ulcers), and genitourinary (dysmenorrhea) disorders.
During the Middle Ages, butterbur was used to treat plague and fever; in the 17th century its use was noted in treating cough, asthma, and skin wounds. The plant can grow to a height of three feet and is usually found in wet, marshy ground, in damp forests, and adjacent to rivers or streams. In the Middle Ages, it earned the folk name "pestilence wort" due to its use against the plague and pestilential fevers, where the odor and smoke from burning roots were believed to ward off infection.
By the 17th century, as documented in Nicholas Culpeper's The English Physician (1652), the plant was applied for coughs, asthma, skin wounds, and fevers, often prepared as teas or poultices from leaves and rhizomes.
Austrian and Central European Folk Medicine
Petasites hybridus leaves were used in Austrian and Czech traditional medicine internally (as tea or cold maceration in ethanol) and externally (as compresses or maceration in vinegar) for treatment of infections, fever, flu, colds, hay-fever, and allergies. In Austrian and Czech folk practices, spanning centuries, leaves were used internally as teas or cold ethanol macerations for infections and influenza, and externally as compresses for wounds and contusions, reflecting its role in regional pharmacopoeias before standardized medicine.
Traditional Indications Across Cultures
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 gastro-intestinal tract. The aerial parts of the related P. japonicus have been used in traditional Japanese folk medicine as an antipyretic, antitussive, or wound-healing agent. In the European herbal tradition, the root specifically was associated with antispasmodic uses—particularly for urinary and gastrointestinal colic—and was considered to have diuretic properties.
3. Key Constituents and Active Compounds
Petasins (Sesquiterpene Esters)
The main active constituents are two sesquiterpenes, petasin and isopetasin. Also present are the sesquiterpene esters petasin, isopetasin, and neopetasin. Extracts are prepared from the rhizome and/or leaves of butterbur. Chemical analysis has revealed petasins (sesquiterpenes, i.e., esters of petasol and angelic acid) as major constituents, in addition to essential oils and pyrrolizidine alkaloids (PAs). Petasins are the pharmacologically active ingredients of butterbur and are defined as sesquiterpenes, i.e., esters of petasol and angelic acid.
Isopetasin, a sesquiterpene found in plants of the genus Petasites, is known to have anti-inflammatory effects; in rhizome essential oil, it has been found at approximately 3.9%, and sesquiterpene lactone concentrations are high, likely contributing to antioxidant activity. Commercial extracts used in clinical trials are typically standardized to a defined percentage of total petasins—commonly 15%—to ensure reproducibility of activity.
Pyrrolizidine Alkaloids (PAs)
Petasites hybridus contains senecionine and other toxic pyrrolizidine alkaloids in its leaves and roots. 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. P. hybridus contains pyrrolizidine alkaloids, which showed hepatotoxic, carcinogenic, and mutagenic properties. Hence, special extracts devoid of alkaloids obtained by sub- and super-critical carbon dioxide extraction were used in preclinical and clinical studies and phytotherapy.
Other Phytochemicals
The essential oil from the rhizome (yield approximately 0.067% v/w) contained 60 components (92.97% of total oil). Nine compounds had content higher than 3%, including (2E)-Nonenal (11.23%), 1-Nonene (8.57%), Germacrene D (5.01%), α-Eudesmol (4.52%), Isopetasin (3.93%), α-Bisabolol oxide (3.38%), epi-β-Santalene (3.45%), α-Santalene (3.36%), and β-Cubebene (3.13%). Constituents of P. japonicus (a closely related species) have been reported to include flavonoids, sesquiterpenes, triterpenes, and various types of phenolic compounds.
4. Mechanisms of Action
Anti-Inflammatory Pathways
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. Sesquiterpenes (petasin and isopetasin) have been found to exhibit anti-inflammatory effects through the inhibition of COX-2, leading to decreased leukotriene synthesis and prostaglandin E2 release.
In vitro cell studies have further characterized the anti-inflammatory mechanism: Researchers investigated the effects of a plant extract of Petasites hybridus (Ze339) and its isolated active sesquiterpene ester petasin in human eosinophil and neutrophil cell models. Zileuton, a 5-lipoxygenase inhibitor, was used as a positive control. All compounds inhibited both cysteinyl-LT synthesis in eosinophils and LTB4 synthesis in neutrophils. In contrast, only Ze339 and petasin, but not zileuton, 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 C(beta).
Petasin also inhibits phospholipase A2 activity and 5-lipoxygenase translocation from the cytosol to the nucleus in stimulated eosinophils, suggesting that petasins may block different intracellular signaling molecules. Petasites root extracts inhibited dose-dependently lipopolysaccharide (LPS)-induced PGE2 release and p42/44 MAPK activation in primary rat microglial cells. Repression of COX-2 expression was also confirmed at the mRNA and protein level.
Calcium-Channel Modulation
Petasins appear to have calcium-channel–blocking effects that may contribute to the mechanism of action of butterbur root. On the basis of laboratory studies, butterbur also has anti-inflammatory and vasodilatory effects on the cerebral arteries via inhibition of the lipoxygenase pathway and leukotriene synthesis.
CGRP Inhibition and Nociceptor Desensitization
Butterbur inhibits the release of calcitonin gene-related peptide (CGRP) of meningeal afferents during migraine attacks. Petasins and isopetasins act in migraine prophylaxis through several mechanisms. First, they have an antinociceptive effect by modulating the transient receptor potential ankyrin 1 (TRPA1) and the transient receptor potential vanilloid 1 (TRPV1), desensitizing TRP calcium channels. Secondly, they exhibit an anti-CGRP effect, because by inhibiting the TRPA1 and TRPV1 ion channels, there is a reduction in the release of calcitonin gene-related peptide (CGRP) in meningeal afferents during headache attacks.
Potential mechanisms accounting for therapeutic benefits in migraine include anti-inflammatory effects in addition to inhibition of calcitonin gene-related peptide (CGRP) release. Together, butterbur is considered effective in the prevention of migraine attacks by blocking CGRP signaling.
Antispasmodic Effects
The petasines, the main components of butterbur, inhibit the synthesis of leukotrienes and decrease the intracellular concentration of calcium, which explains their anti-inflammatory and antispasmodic properties. This dual mechanism — leukotriene inhibition and intracellular calcium reduction — is considered the pharmacological basis for butterbur's traditional use as an antispasmodic agent in smooth muscle, affecting the gastrointestinal tract, bile ducts, and urinary system.
5. Scientific Evidence by Area of Use
5.1 Migraine Prophylaxis
Summary of Evidence: This is the area with the strongest and most methodologically rigorous clinical evidence for butterbur root. Based on multiple clinical trials, the American Headache Society gave the herb a level A recommendation and declared it effective in preventing migraine headaches.
Key Randomized Controlled Trial (Lipton et al., 2004 — Neurology):
This study evaluated the clinical efficacy of a standardized special root extract from Petasites hybridus as a preventive therapy for migraine. It was a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period. Over 4 months, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs. placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs. placebo), and 26% for the placebo group. The investigators concluded that Petasites extract 75 mg twice daily was more effective than placebo and is a well-tolerated preventive therapy for migraine. No serious adverse effects were noted in this trial.
2022 Narrative Review of Randomized Controlled Trials (Petadolex®):
A 2022 narrative review of the literature examined the safety and clinical efficacy of the butterbur root extract Petadolex. The review of randomized, double-blinded, and placebo-controlled trials with Petadolex found that migraine attack frequency was reduced significantly at 150 mg/day, and no relevant abnormal liver function was reported. The reviewers concluded that butterbur is effective in the prevention of migraine attacks by blocking calcitonin gene-related peptide signaling.
Pediatric Evidence (Pothmann & Danesch, 2005 — Headache):
108 children and adolescents between the ages of 6 and 17 were included in a multicenter prospective open-label study. Participants suffered from migraines diagnosed according to IHS classifications for at least 1 year. A multicenter, prospective, open-label clinical study proved the potential of P. hybridus in migraine prophylaxis for children and teenagers; 108 patients with ages between 6 and 17 were treated with Petadolex® (50–150 mg extract daily, depending on age) over 4 months. At the end of 4 months of treatment with Petasites hybridus, the reduction in migraine attacks in the total sample was 63.2%, 67% for children aged 6 to 9 years, and 61.9% for adolescents aged 10 to 17 years. The overall response rate was 77.2%. This study was open-label and lacked a placebo control, which represents a significant methodological limitation.
Real-World Evidence (2026 Frontiers in Neurology):
In the last 25 years, butterbur has been more commonly used in the prophylaxis of migraine due to the action of petasins and isopetasins. It became a migraine prophylactic after several clinical studies proved its therapeutic efficacy.
Change in Guideline Status:
The American Academy of Neurology stopped recommending butterbur in 2015 because of serious concerns about possible liver toxicity. This withdrawal of formal guideline endorsement does not reflect new evidence of lack of efficacy, but reflects unresolved safety concerns (discussed below in Section 7).
Evidence Strength: For migraine prophylaxis, the evidence is moderately strong for the standardized PA-free Petadolex® extract at 75 mg twice daily (150 mg/day) in adults, supported by multiple randomized, double-blind, placebo-controlled trials. The pediatric evidence is encouraging but comes primarily from an open-label study and carries a higher risk of bias. The American Academy of Neurology's 2015 withdrawal of its level A guideline recommendation underscores that safety, not efficacy, is the central unresolved issue.
5.2 Allergic Rhinitis (Seasonal Hay Fever)
Summary of Evidence: Several randomized controlled trials have been conducted, primarily using the leaf extract ZE 339, though results are mixed. Results from studies on allergic diseases are mixed. Some suggest that butterbur is effective against allergic rhinitis and comparable to standard antihistamine drugs, but conflicting data indicate that it is no better than placebo for intermittent rhinitis or for allergic skin disease.
Key RCT: Butterbur vs. Cetirizine (Schapowal et al., 2002 — BMJ):
The study compared the efficacy and tolerability of butterbur (Petasites hybridus) with cetirizine in patients with seasonal allergic rhinitis (hay fever) in a randomized, double-blind, parallel-group comparison. Four outpatient general medicine and allergy clinics in Switzerland and Germany participated. 131 patients were screened and 125 were randomized (butterbur 61; cetirizine 64). Patients received butterbur (carbon dioxide extract tablets, ZE 339) one tablet four times daily, or cetirizine one tablet in the evening, for two consecutive weeks. 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). Because this trial lacked a placebo control arm, it cannot confirm that butterbur was superior to placebo—only that it performed comparably to cetirizine on the measures used.
Dose-Response and Placebo-Controlled Studies:
Schapowal also conducted a study on butterbur Ze339 for the treatment of intermittent allergic rhinitis documenting dose-dependent efficacy in a prospective, randomized, double-blind, placebo-controlled study, published in Archives of Otolaryngology — Head & Neck Surgery in December 2004.
Mechanistic Basis:
In the Schapowal 2002 study, the butterbur extract was standardized to 8.0 mg of total petasin per tablet (ZE 339, Zeller AG, Switzerland). The anti-allergic mechanism is consistent with leukotriene inhibition: In vitro studies suggested that an extract of Petasites hybridus (Ze339) blocks leukotriene synthesis in monocytes and granulocytes. Petasins are considered to be the pharmacologically active fraction within Ze339.
NCCIH Assessment:
Although there have been studies of butterbur root or leaf extracts as possible therapies for symptoms of hay fever (allergic rhinitis), the results were insufficient to determine effectiveness and safety.
Evidence Strength: Preliminary to moderate. There are positive signals from active-controlled trials (vs. cetirizine) and some placebo-controlled dose-finding data, but the NCCIH's assessment that results remain "insufficient to determine effectiveness and safety" is an accurate characterization of the current evidence base. Conflicting findings across studies and methodological limitations (absence of placebo arms in key trials) prevent firm conclusions.
5.3 Asthma and Chronic Bronchitis
Early research suggests that butterbur might be helpful for treating asthma and chronic bronchitis. Early research also suggests it might be helpful for treating chronic obstructive bronchitis. Limited evidence suggests butterbur may help reduce asthma symptoms by relaxing bronchial smooth muscles, though studies are preliminary.
A small clinical study by Ziolo and Samochowiec examined butterbur's properties in bronchial asthma and chronic obstructive bronchitis (Pharm Acta Helv 1998), referenced across the literature, but these studies are considered early-phase and have not been replicated in larger, well-controlled trials. The effects of butterbur as add-on therapy to inhaled corticosteroids in patients with atopic asthma had been evaluated in clinical research, investigating whether butterbur conferred complementary anti-inflammatory activity.
Evidence Strength: Weak and preliminary. Currently limited to small studies and mechanistic rationale (leukotriene inhibition, bronchial smooth muscle relaxation). No large, replicated placebo-controlled trials exist in asthma comparable to those in migraine.
5.4 Urinary Tract and Smooth Muscle Spasms
Some research indicates butterbur may help with urinary tract spasms due to its antispasmodic effects. Currently, the primary therapeutic uses for butterbur include prophylactic treatment of migraines and use as an antispasmodic agent for chronic cough or asthma. It has also been used in preventing gastric ulcers, and in treating patients with irritable bladder and urinary disorders. Modern indications include the prophylaxis of migraine, tension headache, spasms of the urogenital tract, gastro-intestinal tract, and bile duct.
Evidence Strength: Very limited. The biological rationale (antispasmodic through calcium modulation and leukotriene inhibition) is plausible, and there is historical and early clinical use, but no large, well-designed clinical trials in these indications have been published. The urinary tract evidence is essentially confined to preclinical pharmacology and small observational studies.
5.5 Gastrointestinal Applications
Butterbur has been used in preventing gastric ulcers. Uses also cited in clinical literature include stomach ulcers and upset stomach. More evidence is needed to rate the effectiveness of butterbur for these uses.
Evidence Strength: Very weak. Evidence in this area derives primarily from traditional use and animal pharmacology. No meaningful human clinical trial data are available to support butterbur as a treatment for gastrointestinal conditions.
6. Body Systems Associated with Butterbur Root
- Neurological system: Migraine prophylaxis, headache prevention; modulation of CGRP, TRPA1, and TRPV1 pathways implicated in nociception.
- Immune and allergic system: Allergic rhinitis, asthma; leukotriene inhibition providing anti-allergic effects.
- Respiratory system: Asthma, chronic bronchitis, spasmodic cough; bronchial smooth muscle relaxation via calcium antagonism.
- Genitourinary system: Urinary tract spasms, irritable bladder; antispasmodic activity via leukotriene and calcium modulation.
- Gastrointestinal system: Gastric ulcers, GI cramping and spasm; antispasmodic effects documented in traditional use and animal studies.
- Hepatic system (safety concern): Liver function is a monitored organ system due to the hepatotoxic potential of pyrrolizidine alkaloids found in non-PA-free preparations.
7. Dosage Forms and Doses Reported in Studies
The pivotal migraine trial used a three-arm comparison with Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients. The 75 mg twice-daily (150 mg/day) dose reached statistical significance; the 50 mg twice-daily arm did not achieve statistical significance versus placebo in that trial.
In randomized, double-blinded, and placebo-controlled trials with Petadolex®, migraine attack frequency was reduced significantly at 150 mg/day.
For pediatric migraine, 108 patients with ages between 6 and 17 were treated with Petadolex® (50–150 mg extract daily, depending on age) over 4 months.
For allergic rhinitis, the ZE 339 extract was standardized to 8.0 mg of total petasin per tablet, with patients receiving one tablet four times per day (i.e., four tablets daily).
Clinical studies have used the following doses for standardized, PA-free butterbur extracts: migraine prevention — 50–75 mg twice daily of an extract standardized to contain 15% petasins; allergic rhinitis — 50 mg twice daily of extract standardized to contain 7.5 mg of petasin per tablet; for children aged 6–17 for migraine — reduced dosages of 25–50 mg twice daily based on weight have been used in pediatric studies.
Most clinical trials have not evaluated doses significantly above these ranges. Limited pharmacokinetic studies suggest a plateau effect may occur at higher doses, but there are significant knowledge gaps regarding optimal dosing, particularly for long-term use.
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. Long-term use beyond this period has not been adequately studied in controlled settings. Researchers evaluated the safety of a butterbur root extract in repeated dose studies for up to 6 months. A no-observable-adverse-effect level (NOAEL) at 15-fold of the maximal clinical dose (3 mg/kg/day MCD) was established for rats.
8. Safety Considerations and Interactions
Pyrrolizidine Alkaloid Toxicity
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. Butterbur contains pyrrolizidine alkaloids (PAs), which are hepatotoxic. Some butterbur products contain chemicals called pyrrolizidine alkaloids (PAs). PAs can damage the liver, lungs, and blood circulation, and possibly cause cancer.
The commercial preparation process of butterbur typically removes these substances. It is therefore recommended that consumers of butterbur only buy brands that are free of alkaloids and other plant carcinogens.
Hepatotoxicity Cases and Regulatory Action
Severe hepatotoxicity may be associated with butterbur use, but the evidence is unclear. 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.
Acute and chronic toxicity studies of butterbur rootstock SFE-CO₂ extract in Wistar rats showed no adverse effects for the doses generally recommended in humans. However, post-marketing surveillance of the safety profile of Petadolex® indicated a potential risk for hepatotoxicity. Moreover, independent reports indicated several induced liver injuries after the use of Petadolex®; notwithstanding, those cases were rare and confounded by co-medications.
The American Academy of Neurology stopped recommending butterbur in 2015 because of serious concerns about possible liver toxicity. Some countries have withdrawn butterbur products from the market because of concerns about liver toxicity.
PA-Free Products and Residual Risk
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. However, there have been rare cases of liver injury associated with products that were reported to be PA-free. Some products claiming to be PA-free may not in fact be.
The cases of liver toxicity appear to have occurred with extracts of butterbur where the PAs had been removed and only small amounts remained. There is some evidence that other constituents found in butterbur, such as the sesquiterpene constituents — for example, petasin — may be implicated in the liver toxicity.
At supratherapeutic doses, i.e., 45–90-fold the maximal clinical dose, researchers observed bile duct hyperplasia, 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.
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. Despite this, the rare reported cases in the literature necessitate monitoring.
Contraindications and Special Populations
Butterbur products that contain PAs may not be safe when applied to the skin, as PAs could be absorbed through cuts or scrapes. Because Petasites hybridus belongs to the Asteraceae (daisy) family, individuals with documented hypersensitivity to related plants — such as ragweed (Ambrosia), chrysanthemums, marigolds, or daisies — may be at risk for cross-reactive allergic responses.
Safety data in pregnancy and lactation are absent from controlled clinical research. Adequate data on long-term use (beyond 16 weeks) in humans are also lacking. The NCCIH highlights that further research into the safety of long-term butterbur use is necessary.
Drug Interactions
Butterbur has no known moderate interactions with other drugs according to current drug interaction databases; however, given its inhibition of cytochrome P450-related inflammatory pathways and effects on vascular smooth muscle, caution is warranted with co-administration of other hepatically metabolized agents, anticoagulants, or antihypertensives. Formal interaction pharmacokinetic studies are limited.
Monitoring Recommendations
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.
9. Regulatory and Guideline Context
Although butterbur has been used over centuries in traditional medicine to treat various disorders, there are no approved medical uses, but it is sold as a dietary supplement. In the United States, it is regulated as a dietary supplement under DSHEA and is not approved by the FDA for any medical indication. Only butterbur products that have been processed to remove PAs and are labeled or certified as PA-free should be considered for use. The American Headache Society formerly granted a Level A evidence rating for migraine prophylaxis, which it subsequently upheld, while the American Academy of Neurology independently withdrew its guideline endorsement in 2015 over liver safety concerns.
References
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