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Standardized Butterbur Extract for Migraine Treatment: A Clinical Overview

The development of a standardized extract of the rhizome of purple butterbur (Petasites hybridus (L.) P. Gaertn., B. Mey. & Scherb., Asteraceae) has led to a new clinical approach to the management of migraine headache. Two clinical trials with a standardized CO2 extract have successfully demonstrated the extract’s ability to safely and effectively reduce the frequency and intensity of migraine headaches.

Purple butterbur is a perennial shrub native to Europe, northern Africa, and southwestern Asia that grows to about three feet tall.1 Although butterbur is frequently used as the common name, the species is also commonly known as purple butterbur and sweet coltsfoot.2 A related plant, P. frigidus (L.) Fries, is known as Arctic butterbur and Arctic sweet coltsfoot or western coltsfoot.

While both leaves and rhizomes have been used in traditional herbal medicine,3 only medicinal preparations of the rhizome are approved by the German Commission E for use in modern phytotherapy, for "supportive therapy for acute spastic pain in the urinary tract, particularly if stones exist."4

Active Constituents and Mechanism of Action

The leaves, rhizomes, and roots of butterbur contain a mixture of eremophilane-type sesquiterpenes consisting primarily of petasin (also known as petasine) and isopetasin.5 According to phytotherapy textbooks, petasin and isopetasin have both spasmolytic and analgesic actions.3 These active constituents also inhibit leukotriene synthesis, which may also contribute to butterbur’s antispasmodic and anti-inflammatory actions.6,7

Butterbur leaf and rhizome contain pyrrolizidine alkaloids (PAs), which are potentially hepatotoxic and carcinogenic constituents.8 Concern about the presence of PAs has led to the virtual demise of coltsfoot leaf (Tussilago farfara L., Asteraceae), comfrey root (Symphytum officinale L., Boraginaceae), and the groundsels (Senecio spp., Asteraceae) for oral use in herbal medicine and may be the primary explanation for the waning interest in the therapeutic use of butterbur in traditional herbal medicine. It is imperative that healthcare professionals recommend only butterbur products that are free of PAs or reduced to meet the limits set by the German Commission E. It should be noted that the Commission E monographs stipulate limits for PAs in approved herbal preparations that contain PAs, specifically 100 mcg per day in comfrey leaf or root, 1 mcg for extracts or pressed juice from fresh coltsfoot, and 1 mcg daily of petasites root. All limits refer to PAs with the 1,2 necine structure, including their N-oxides.4

Antispasmodic actions have led to the use of butterbur for urinary tract spasms due to kidney stones, digestive tract spasms, as well as lower back pain.3,9 It has also been used for whooping cough and bronchial asthma. A clinical trial found that a PA-free extract of the leaves (standardized to petasin content) was as effective as the antihistamine cetirizine in the treatment of allergic rhinitis.10 (Please see my review of this clinical trial in HerbalGram 56).

Migraine Prophylaxis

Two randomized, placebo-controlled, double-blind clinical trials tested the efficacy of the standardized butterbur extract (Petadolex®, Weber & Weber International GmbH & Co., Germany) in the treatment of migraines. In the first trial, 60 migraine patients (mean age 28.7 years) were randomized to receive either 50 mg of Petadolex or placebo two times per day for 12 weeks.11 Starting at the fourth week of treatment, the Petadolex group had a significant reduction in the number of migraine attacks compared to the placebo group (P < 0.05). Compared to the placebo group, those taking Petadolex had a 60 percent reduction in the number of migraines by week 12. The number of migraine days was also reduced significantly in the Petadolex group (3.4 ± 1.6 at baseline to 1.7 ± 0.9 days after 12 weeks) compared to placebo (3.0 ± 1.3 to 2.6 ± 1.2 days, P < 0.05). While the duration and intensity of migraines was significantly reduced at 8 weeks in the Petadolex group (P < 0.05), the difference compared to placebo was not significant at week 12. The mean number of accompanying symptoms (e.g., nausea, vomiting) was significantly reduced in the Petadolex group compared to placebo (P < 0.01). No adverse events were reported at the end of the 12-week trial.

The second trial randomized 202 migraine patients (ages 19—65 years) to receive either 50 mg of Petadolex, 75 mg of Petadolex, or placebo two times per day for 12 weeks following a four-week baseline run-in period.12 The primary endpoint, frequency of migraine attacks per four weeks, was reduced by 38 percent, 44 percent, 58 percent, and 51 percent in patients treated with 150 mg/day of Petadolex after 1 (baseline), 2, 3, and 4 months respectively. The 100 mg/day group had a reduction of 24 percent, 37 percent, 42 percent, and 40 percent, while the placebo group was 19 percent, 26 percent, 26 percent, and 32 percent, respectively. Treatment differences between those taking 100 mg/day of Petadolex were not significant compared to placebo. However, those taking 150 mg/day had a significant reduction in migraine count over 3 months of treatment compared to placebo (P < 0.001). The number of patients who had a 50 percent reduction in mean migraine attack frequency per month relative to baseline were considered therapy responders. The mean percent of responders in the 150 mg/day group (68 percent) was significantly greater than those taking placebo (49 percent) (P < 0.05). The mean three-month assessment of headache intensity also favored the Petadolex 150 mg/day group compared to placebo (P = 0.01). Eighty participants reported 131 adverse events – 23 patients in the placebo group and 29 patients and 28 patients in the 100 mg and 150 mg groups, respectively. The most frequently reported adverse events in patients taking Petadolex were gastrointestinal complaints with burping being the most common complaint (reported by approximately 20 percent of patients taking Petadolex).

Recommended Use

Petadolex is a CO2 extract of the butterbur rhizome (concentrated at a ratio of 28—44:1) standardized to 15 percent petasin and isopetasin with PAs reduced to < 0.08 ppm in the finished product (which represents the lower limit of detection). Adults and children over the age of 12 years may take 50 mg of the extract two to three times per day. Although clinical trials have only studied continuous use for up to 12 weeks, current product recommendation is for 4 to 6 months of continuous use of the product.

Side Effects/Contraindications

Side effects are rare with the use of the PA-free extract and have consisted primarily of mild gastrointestinal complaints (nausea, burping, and stomach pain) with rare reports of vomiting, diarrhea, and skin rash. In a recent safety report on standardized butterbur root extract, documentation of adverse events from 1976 to June 30, 2002 found a total of 75 reports of suspected adverse reactions from Germany and 18 spontaneous reports from other countries received by the manufacturer (Weber and Weber).13 Only 19 reports were determined to be possibly causally related to the administration of the medication and 8 reports to be probably causally related to the medication by thorough evaluation by German pharmacovigilance guidelines and standard operating procedures. One case of cholestatic hepatitis was diagnosed as a hypersensitivity reaction with a probable causal reaction to butterbur. Butterbur should not be used during pregnancy or lactation due to lack of safety studies, nor should it be used by those who have suffered from hepatitis or other liver ailments. There are no known drug interactions for butterbur rhizome extract.


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3. Weiss RF, Fintelmann V. Herbal Medicine. Stuttgart, Germany: Thieme; 2000:200-2.

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5. Bisset NG, Wichtl M. Herbal Drugs and Phytopharmaceuticals. Boca Raton, FL: CRC Press; 1994:366-8.

6. Bickel D, Röder T, Bestmann HJ, Brune K. Identification and characterization of inhibitors of peptido-leukotriene synthesis from Petasites hybridus. Planta Med 1994;60:318-22.

7. Thomet OAR, Wiesman UN, Schapowal A, et al. Role of petasine in the potential anti-inflammatory activity of a plant extract of Petasites hybridus. Biochem Pharmacol 2001;61:1041-7.

8. Gruenwald J, Brendler T, Jaenicke C, eds. PDR for Herbal Medicines. Montvale, NJ: Medical Economics; 2000:585-8.

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10. Schapowal A. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;321:1-4.

11. Grossmann M, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Inter J Clin Pharmacol Ther 2000;38:430-5.

12. Lipton RB, Gobel H, Wilkes K, Mauskop A. Efficacy of Petasites (an extract from Petasites rhizome) 50 and 75 mg for prophylaxis of migraine: Results of a randomized, double-blind, placebo-controlled study. Neurology 2002;58(suppl 3):A472 [Presented at the 44th Annual American Headache Society Meeting, June 22, 2002, Seattle, WA].

13. Danesch U, Rittinghausen R. Safety of a patented special butterbur root extract for migraine prevention. Headache 2003;43:76-8.