Scientific Name(s): Petasites frigidus (L.) Fr., Petasites hybridus (L.) G. Gaertner, Meyer and Scherb., Petasites japonicas Siebold & Zucc. Maxim.
Common Name(s): Arctic sweet coltsfoot (P. frigidus), Blatterdock, Bog rhubarb, Bogshorns, Butter-dock, Butterbur, Butterfly dock, Coltsfoot, Exwort, Fuki, Japanese sweet coltsfoot (P. japonicas), Pestilence-wort (P. hybridus), Pestwurz
Limited clinical trials of variable methodological quality suggest a possible place in therapy for asthma and the prophylaxis of migraines in adults and children, as well as in intermittent (seasonal) allergic rhinitis. However, recommendations are based on weak clinical efficacy information but with a low potential for side effects. Only commercial preparations that are certified not to contain toxic pyrrolizidine alkaloids should be used.
Migraine prophylaxis in adults: Butterbur extract 50 to 75 mg twice daily for 4 months.
Migraine prophylaxis in children 6 to 9 years: Butterbur extract 50 to 75 mg/day in 2 divided doses.
Migraine prophylaxis in children and adolescents 9 to 17 years: Butterbur extract 100 to 150 mg/day in 2 divided doses.
Avoid in hepatic impairment. Limited animal studies suggest butterbur's chemical constituents may exert cardiovascular effects.
Avoid use. Preparations may contain hepatotoxic pyrrolizidine alkaloids with carcinogenic and mutagenic activity.
None well documented.
GI symptoms, including nausea, flatulence, and belching, are the most common documented adverse reactions. Allergies, including anaphylaxis, have been reported.
Preparations may contain pyrrolizidine alkaloids with carcinogenic and mutagenic potential; commercial products typically are certified as pyrrolizidine free ("PA free"); however, levels of active petasins as well as toxic alkaloids have been found to be highly variable and incongruent with their labeling. Possible hepatotoxicity has been reported.
Butterbur is a perennial shrub native to Europe that commonly grows in wet, marshy ground or on sandbars near streams. Its distinctive pink-lilac flowers grow on large spikes that appear in spring before its large, downy leaves emerge. P. japonicas is commonly grown and consumed in Japan.1, 2
Although sometimes considered synonymous with Tussilago farfara, butterbur and coltsfoot are detailed separately (see Coltsfoot monograph).
The botanical name Petasites is derived from the Greek word petasos, a type of broad-brimmed hat worn by shepherds, referring to the plant's broad, downy leaves. The name butterbur relates to the use of the leaves to wrap butter during warm weather. During the Middle Ages, butterbur leaves and roots were used to treat cough, plague, and fever.
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. Other traditional uses include the treatment of gastric ulcer and bee stings.2, 3
Butterbur contains senecionine and other toxic pyrrolizidine alkaloids in the leaf and root; a competitive immunoassay has been developed for the determination of alkaloid content. High-performance liquid chromatography (HPLC) analyses of both plant parts indicate that, on average, alkaloid levels are lower in leaves than in roots.2, 3, 4
A large number of sesquiterpenes have been isolated from butterbur, with petasin and related eromophilanes being the most pharmacologically important. The sesquiterpene distribution varies according to plant part, growth season, and plant location. Use of HPLC methods for quantitative determination of petasin has been reported, and the existence of a distinct chemovar with furanoeremophilanes has been noted.2, 5
The petasin series of compounds are unstable in storage; rearrangements occur in dry plant materials and in stored extracts. The biosynthesis of petasin has been elucidated. Differences in the sesquiterpene profiles of various European Petasites species have been studied. Other constituents of butterbur include the flavonoid glycosides isoquercitrin and astralagin.5
Uses and Pharmacology
Only commercial preparations that are certified not to contain toxic pyrrolizidine alkaloids should be used.6
The availability of clinical trial data makes animal studies largely unwarranted.
Several clinical trials have been conducted on commercial preparations of butterbur to evaluate their efficacy in the management of allergic rhinitis. Subjective and objective data serve as end points and measures of efficacy. However, 3 of the larger trials were sponsored by manufacturers of butterbur extract and at least 1 study with negative results has been published.7
Mechanisms of action for butterbur in allergic rhinitis relate to a role in leukotriene activity rather than an antihistaminic effect. The Global Allergy and Asthma European Network Guidelines on Allergic Rhinitis and its Impact on Asthma (ARIA) (2010) conditionally recommend that butterbur not be used in patients with allergic rhinitis based on the very low-quality evidence of benefit and the high risk of adverse effects.6
The American Association of Otolaryngology-Head and Neck Surgery (AAOHNS) clinical practice guideline on allergic rhinitis (2015) states that too few data are available to make recommendations on the use of butterbur for managing symptoms of allergic rhinitis. Additionally, no recommendations could be made regarding use of herbal therapies, in general, based on the limited knowledge of herbal medicines by the panel and their concerns about quality of standardization and safety (low; uncertain).50
Studies of Petasites extracts in rodents have shown a decrease in airway hyperresponsiveness, including inhibition of eosinophil infiltration and mucus hypersecretion, as well as relaxation of tracheal tissues. Decreases in circulating levels of histamine and leukotrienes have been shown.8, 9, 10, 11, 12
There are limited clinical trials evaluating the efficacy of butterbur extracts in asthma. One small trial (N = 16) found improvement in the primary outcome of bronchial hyperresponsiveness with butterbur 50 mg/day taken for 1 week.13 A reduction in asthma attacks was reported in another open-design trial after subjects were administered 150 mg/day.14
Migraine prophylaxis, adults
Information is lacking; however, the widespread use of butterbur for the prevention of migraine and the availability of clinical trial data make animal studies largely irrelevant.
Earlier support for use of butterbur for prevention of episodic migraines in adults by the 2012 American Academy of Neurology and American Headache Society guidelines was withdrawn in 2015 subsequent to serious concerns over the safety of unregulated manufacturing processes that were not removing toxic pyrrolizidine alkaloids from commercially-available products. Additionally, levels of the active moiety, petasins, were found to be highly variable and even lacking in some products.15, 51, 52, 53
The Canadian Headache Society guidelines for migraine prophylaxis (2012) strongly recommend butterbur 75 mg twice daily for eligible patients for migraine prophylaxis based on moderate evidence (controlled trials), noting that the magnitude of benefit may be small, but side effects are minimal.16 Likewise, the European Federation of Neurological Societies guidelines on the treatment of migraines (2009) considers butterbur (petasites) as second line therapy for migraine prophylaxis based on moderate evidence.17 Meta-analysis suggests that butterbur 50 mg twice daily achieves a 50% reduction in migraine frequency at week 12 (odds ratio, 2.24; 95% confidence interval, 0.64 to 7.81; P = 0.2)15
The safety of long-term use of butterbur has not been established. The maximum duration studied in clinical trials for migraine was 16 weeks.15, 18
Migraine prophylaxis, children
Information is lacking; however, the widespread use of butterbur for the prevention of migraine and the availability of clinical trial data make animal studies largely irrelevant.
One open-label study has been conducted in children and adolescents 6 to 17 years of age.18 A second trial evaluated the per-protocol efficacy of music versus butterbur against placebo. A reduction in the primary outcome of migraine frequency was shown for butterbur but not for the secondary outcome responder rate. After 6 months, efficacy was equivalent to placebo.19 Reviews of the data have been published.20, 21, 22 The safety of long-term use of butterbur has not been established.
In rat gastric ulceration models, butterbur extract blocked the effects of ethanol and indomethacin.23, 24, 25
The active chemical components of butterbur in in vitro experiments have demonstrated the antioxidant effect of the active chemical components.26, 27, 28, 29, 30, 31
Methanol extracts of the leaves of P. japonicus were antimutagenic in human cancer and rat liver cell lines.32
The active chemical component petasin has been investigated for reported hypotensive effects. In in vitro experiments and in rat studies, both the S- and iso-S forms of petasin exerted a negative chronotropic effect on cardiac tissue. Reduced rates of atrial firing and a dose-dependent bradycardiac effect have been demonstrated. At the cellular level, blockade of the calcium channels was suggested, but the mechanism of action has not been established.33, 34, 35, 36, 37
The addition of butterbur extract to a 3-herb preparation increased its efficacy in a trial among patients with somatoform disorders.38
Petasin modulated glucose metabolism in mice.39
In vitro studies showed immunomodulatory effects of P. hybridus extracts.40
Decreased total cholesterol and low-density lipoproteins have been shown in mice fed high-fat diets and butterbur extracts.38, 41
Various commercial preparations are available. Only commercial preparations that do not contain hepatotoxic pyrrolizidine alkaloids should be used.6 Studies in special populations, such as in patients with renal or hepatic function impairment, are not available.
Migraine prophylaxis in adults
Butterbur extract 50 to 75 mg twice daily for 4 months.16
Migraine prophylaxis in children 6 to 9 years
Butterbur extract 50 to 75 mg/day in 2 divided doses has been studied.18, 19, 20
Migraine prophylaxis in children and adolescents 9 to 17 years
Butterbur extract 100 to 150 mg/day in 2 divided doses has been studied.18, 19, 20
Pregnancy / Lactation
Avoid use. Preparations may contain hepatotoxic pyrrolizidine alkaloids with carcinogenic and mutagenic potential.42, 43
None well documented.44, 45 Interactions could occur with calcium channel antagonists, inotropic and anticholinergic medicines, and inducers of CYP3A4 (eg, St. John's wort, carbamazepine, phenytoin, rifampin), which might result in increased production of toxic metabolites of the alkaloids.
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 of documented adverse reactions. Headache, dizziness, drowsiness, and fatigue have also been reported, as well as allergy to butterbur or other members of the Aster family.16, 46 Anaphylaxis has been documented in 2 cases with dyspnea, full-body urticaria, and itching occurring within minutes of consuming Japanese butterbur scape tempura.54 Clinical trials have reported mild elevation of liver enzymes with no clinical sequelae.18 (See Toxicology.)
Pyrrolizidine alkaloids have carcinogenic and mutagenic potential. 3, 42 Commercial butterbur preparations utilize an extraction process to remove the pyrrolizidine alkaloids content; these products should be labeled as "PA free." Concentrations greater than 37% petasin are toxic.18, 47 The German Federal Health Bureau established regulations that restrict oral exposure to pyrrolizidine alkaloids or their N-oxides to 1 mcg/day (not to exceed 6 weeks duration) or 0.1 mcg/day of any duration for non-pregnant, non-lactating adults. However, analysis of 21 commercially available dietary supplements in 2012 found 7 products to contain pyrrolizidine alkaloids; 6 solid formulations contained 0.1 to 4.48 mcg/dosage form and 1 liquid product was found to have 8.43 mcg/mL. Typically, doses are taken 2 to 3 times daily with meals. Additionally, 5 of the 7 products containing toxic alkaloids had no detectable level of the pharmacologically active petasins. Only 7 of the 21 dietary supplement products tested were found to have petasins within the limits claimed on the label plus no toxic pyrrolizidine alkaloids.53
Postmarketing pharmacovigilance between 1992 and 2006 revealed 40 cases of increased liver enzymes and possible hepatotoxicity with P. hybridus extracts, 9 as acute hepatitis and 2 as liver failure.48 Clinical trials have reported mild elevation of liver enzymes with no clinical sequelae.18
Acute toxicity studies in rats showed no hepatotoxicity. Dose-related bile duct hyperplasia and increased liver enzymes were found at 28 days and 6 months, returning to normal after cessation.48 Extracts of P. japonicus were not mutagenic in the Ames Salmonella typhimurium test.32 Inhibition of testosterone production has been reported in animal experiments.49
Mill. USDA, NRCS. 2014. The PLANTS Database (http://plants.usda.gov
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6. Brozek JL, Bousquet J, Baena-Cagnani CE, et al; Global Allergy and Asthma European Network; Grading of Recommendations Assessment, Development and Evaluation Working Group. Allergic rhinitis and its impact on asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol
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27. Oh SH, Sok DE, Kim MR. Neuroprotective effects of butterbur and rough aster against kainic Acid-induced oxidative stress in mice. J Med Food
28. Cui HS, Kim MR, Sok DE. Protection by petaslignolide A, a major neuroprotective compound in the butanol extract of Petasites japonicus
leaves, against oxidative damage in the brains of mice challenged with kainic acid. J Agric Food Chem
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