Reviewed:Brattström A. A newly developed extract (Ze 339) from butterbur (Petasites hybridus L.) is clinically efficient in allergic rhinitis (hay fever). Phytomedicine. 2003;10(suppl IV):50–52.

Butterbur (Petasites hybridus [L.] P. Gaertn. et al., Asteraceae) is a perennial herb native to northern temperate regions that exists in two chemo-varieties: those containing petasins and those with furano-petasins. In terms of safety and efficacy, the petasin chemo-variety appears to be superior to the furano-petasin chemo-variety. Therefore, leaves from one selected petasin chemo-variety (PETZEL) are cultivated and dried to produce the extract Ze 339 (Tesalin^®; Zeller Medical AG, Switzerland). This extract has anti-inflammatory properties and is composed primarily of petasins and fatty acids; aromatic compounds and phytosterols are also present. Petasins are bioavailable and have a half-life of 4–6 hours (half-life: the time required for the concentration of petasins in the blood to be metabolized and reduced to half the original level, thereby reducing or terminating its pharmacological activity).

A tablet containing extract Ze 339, equivalent to 8 mg petasins, has been developed by the Zeller company for use in clinical trials. According to a company official, Ze 339 is virtually free of hepatotoxic pyrrolizidine alkaloids (PAs), which are found in fresh or dried butterbur roots and to a much lesser degree in leaves. The proprietary extract is manufactured according to a patented method to reduce even the smallest traces of PAs during the extraction process; however, the company can only claim that the PAs are under the analytical detection limit (as low as 35 ppb [parts per billion]) (G. Boonen [georg.boonen@zellerag.ch], e-mail, July 1, 2004). This level would be considered relatively insignificant from a toxicological perspective, since using oral administration of 1 mcg daily is accepted as non-toxic, according to the German Commission E Monograph on Petasites Root.¹

In a “proof of principle” trial,² Ze 339 was shown to down-regulate inflammation mediators such as histamine and leukotriene (agents promoting inflammation and mucous secretions and other symptoms associated with allergic rhinitis) in nasal lavage and to increase airflow in patients with allergic rhinitis. In vitro data on this extract support a dual mechanism of action comprising the immobilization of intracellular calcium and the leucotriene synthesis inhibition.^3,4

This article reports on two recent clinical trials that were conducted to determine the clinical efficacy of Ze 339 in patients with allergic rhinitis.

In the first trial,⁵ conducted in 2000, the efficacy of Ze 339 was compared with that of cetirizine (Zyrtec^®; Pfizer, Morris Plains, NJ). The Ze 339 group contained 65 patients; the cetirizine contained 66. Improvement in quality of life was the main efficacy variable. “Both treatments came out as equivalent (non-inferior)” after 2 weeks of treatment. Efficacy was determined by using a validated questionnaire with various quality of life determinants for both trials.⁶

In the second trial, conducted during 2001 and 2002, the severity of symptoms was measured following the guidelines established by the U.S. Food and Drug Administration.⁷ For 2 weeks, one group of patients was treated with a high dose (3 tablets; equivalent to 24 mg petasins) of Ze 339 (n = 60), one group was treated with a low dose (2 tablets; 16 mg petasins) of Ze 339 (n = 65), and one group was treated with placebo (n = 61). The patients and the clinicians rated Ze 339 as being “significantly superior” to placebo on the basis of improvements in the severity of symptoms (e.g., sneezing, nasal congestion, runny nose, itchy nose, and itchy eyes). The type and incidence of adverse events was not significantly different among the groups.

Based on the design of these studies, butterbur extract Ze 339 demonstrated efficacy for treating seasonal allergic rhinitis symptoms. The researchers concluded that “The effects of this herbal medicine are clear to both patients and doctors when evaluated against placebo, double-blindly.”

These trials add more evidence to the benefit of butterbur in treating symptoms of allergic rhinitis. A previous trial⁵ published in the British Medical Journal also showed efficacy in rhinitis (reviewed in Dr. Don Brown’s Clinical Update in HerbalGram 56⁸). A totally different butterbur preparation from Germany has been the subject of another previous article by Dr. Brown in HerbalGram.⁹ This product is made of a standardized extract of the butterbur rhizome and has been the subject of positive clinical trials for migraine prophylaxis.

—Brenda Milot, ELS

References:

1. Blumenthal M, Busse WR, Goldberg A, Hall T, Riggins CW, Rister RS, ed; Klein S, Rister RS, trans. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council;1998.

2. Thomet OAR, Wiesmann UN, Schapowal A, Bizer C, Simon HU. Role of petasin in the potential anti-inflammatory activity of a plant extract of Petasites hybridus. Biochem Pharmacol. 2001;61:1041-1047.

3. Thomet OAR, Wiesmann UN, Blaser K, Simon HU. Differential inhibition of inflammatory effector function by petasin, isopetsin and neopetasin in human eosinophils. Clin Exp Allergy. 2001;31:1310-20.

4. Thomet OAR, Schapowal A, Heinisch IVWM, Wiesmann UN, Simon UH. Anti-inflammatory activity of an extract of Petasites hybridus in allergic rhinitis. Int Immunopharmacol. 2002;2: 997-1006.

5. Schapowal A. Petasites Study Group. Randomized controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. Br Med J. 2002;324:144-146.

6. Bousquet J, Duchateau J, Pignat JC, et al. Improvement of quality of life by treatment with cetirizine in patients with perennial allergic rhinitis as determined by a French version of the SF-36 questionnaire. J Allergy Clin Immunol. 1996;99:309–316.

7. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for industry: Allergic rhinitis clinical development programs for drug products. Available at: www.fda.gov/cder/guidance/index.htm.

8. Brown D. Treating seasonal allergic rhinitis with butterbur extract. HerbalGram. 2002;56:26-27.

9. Brown D. Standardized butterbur extract for migraine treatment: A clinical overview. HerbalGram. 2003;58:18-19.