A perennial plant found in Europe, southwestern Asia, and north Africa, butterbur is also referred to as exwort, butter dock, and bog rhubarb.1 For decades the commercial use of butterbur in the United States was strongly discouraged due to many of the available formulations containing excessive toxic pyrrolizidine alkaloids (PAs), which can cause lethal liver damage.1 However, a European product known as Petadolex has recently been introduced into the market. This product is free of toxic PAs and is considered safe for routine use.2

Mechanism of action

The leaf and roots of this herb are the components used to treat allergies, asthma, and migraine.1 The active ingredients are thought to be petasins (which are sesquiterpene compounds) and isopetasin, both of which reduce muscle spasms and inflammation. Butterbur has also shown dose-dependent inhibition on cyclooxygenase and prostaglandin E2 in vitro, which appears to be independent of the petasin action.3 Both actions would obviously have mitigating effects on any acute, inflammatory-mediated condition.

Science

Allergy researchers conducted a head-to-head placebo-controlled trial of butterbur and fexofenadine to determine subjective effects on perennial allergic rhinitis. In this trial, patients were randomized to butterbur, fexofenadine, or placebo. The findings showed that butterbur was equally effective as fexofenadine at relieving nasal symptoms.4 Another trial involving butterbur and the well-known branded antihistamine cetirizine (Zyrtec) was conducted using 125 patients with seasonal allergic rhinitis. Again, the effects of butterbur extract were equal to or greater than those of cetirizine. Butterbur also seemed to be somewhat superior in patients who experienced sedation with the branded antihistamines.5 As an antihistamine, butterbur also has been found to decrease the priming of the mast cells in response to contact with allergens.6

Perhaps an even more exciting potential for butterbur is its use for combating and preventing migraine headaches. Migraines affect 18% of women and 6.5% of men in the United States, with a total financial burden on the U.S. economy of more than $11 billion annually.7,8 Some studies have documented a reduction in migraine frequency and intensity by as much as 60% when butterbur extract is used over an extended period of time.9 In addition to the spasmolytic and anti-inflammatory actions of butterbur that would help mitigate migraine, a calcium-channel-blocking effect has also been noted.10 This is thought to be one of the mechanisms that aids in migraine prophylaxis.

Safety, interactions, and side effects

Butterbur is metabolized through the Cytochrome P450 3A4 pathway.11 Since this enzyme pathway is also highly utilized by a wide variety of common medications and herbals, avoid use of butterbur with other therapies that might be enhanced or limited by this interaction. All usage and safety indications should be prefaced with the caution to use products certified as free from the hepatotoxic PAs.

Butterbur is considered “likely safe” in adults without major organ dysfunction.11 Patients with known liver dysfunction should avoid butterbur, and those with known allergies to members of the ragweed family should proceed cautiously with initial use.1 Usage in children is less studied but is considered “possibly safe.”11 Usage in pregnancy and lactation is discouraged.11

Dosage, cost, and how supplied

The usual dose for migraine prophylaxis and treatment is 50-75 mg twice daily.7 In studies, maximum response required daily use for two to three months. If a lengthy period passes in which the patient is migraine-free, a tapering and discontinuation may be attempted.7 The cost averages $30 for a month’s supply of capsules.2

For allergic rhinitis, the typical daily dose is 50 mg twice daily either throughout the duration of the allergy season or continuously, depending on the patient’s symptoms.7

Summary

The primary safety concern with this treatment is the potential for hepatotoxicity with nonpurified formulations. Considering the sizeable side-effect profile of prescription migraine medications, butterbur is a reasonable option. While most branded medications for allergic rhinitis are now available OTC, they are still relatively costly and carry the usual side-effect profile. Overall, the cost of butterbur is reasonable and far superior to that of the current pharmaceutical anti-migraine medications and allergy products. Butterbur can be recommended with reasonable assurance of the presence of adequate safety and efficacy data.

References

  1. Memorial Sloan-Kettering Cancer Center. Butterbur.
  2. Danesch UC. Petasites hybridus (Butterbur root) extract in the treatment of asthma—an open trial. Altern Med Rev. 2004;9:54-62.
  3. Fiebich BL, Grozdeva M, Hess S, et al. Petasites hybridus extracts in vitro inhibit COX-2 and PGE2 release by direct interaction with the enzyme and by preventing p42/44 MAP kinase activation in rat primary microglial cells. Planta Med. 2005;71:12-19.
  4. Lee DK, Gray RD, Robb FM, et al. A placebo-controlled evaluation of butterbur and fexofenadine on objective and subjective outcomes in perennial allergic rhinitis. Clin Exp Allergy. 2004;34:646-649.
  5. Schapowal A; Petasites Study Group. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ. 2002;324:144-146.
  6. Lee DK, Carstairs IJ, Haggart K, et al. Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis. Clin Exp Allergy. 2003;33:882-886.
  7. Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137:840-849.
  8. Hazard E, Munakata J, Bigal ME, et al. The burden of migraine in the United States: current and emerging perspectives on disease management and economic analysis. Value Health. 2009;12:55-64.
  9. Lipton RB, Göbel H, Einhäupl KM, et al. Petasites hybrid root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240-2244.
  10. Sheykhzade M, Smajilovic S, Issa A, et al. S-petasin and butterbur lactones dilate vessels through blockage of voltage gated calcium channels and block DNA synthesis. Eur J Pharmacol. 2008;593:79-86.
  11. Natural Medicines Comprehensive Database. Butterbur.

All electronic documents accessed August 16, 2010.

By Sherril Sego, FNP-C, DNP. Ms. Sego is a staff clinician at the VA Hospital in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas.