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Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis

BMJ 2002; 324 doi: (Published 19 January 2002) Cite this as: BMJ 2002;324:144

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Toxicity of pyrrolizidine alkaloids

Many medicinal plants are used as treatment in traditional medicine,
often without any evidence of efficacy and sufficient safety. Butterbur
(Petasites hybridus L. or P. officinalis L.), Coltsfoot (Tussilago farfara
L.) , Common comfrey (Symphytum officinale L.), Borage (Borago
officinalis L.) , Crotalaria (Crotalaria retusa L.) and Common groundsel
(Senecio vulgaris L.) are only few samples of medicinal plants for which
there is a very old tradition of use, few clinical data on their
pharmacological efficacy, while enough data to state they toxic and
cancerogenic , because all these plants contain pyrrizolidine

In reference to the paper of Dr. A. Schapowal, we think the Author
did not deserve any attention to the main toxicological problematics of
Petasites hybridus. This plant in fact is known to contain PA: in rhizomes
they range from 5 to 90 ppm, whereas leaves contain between 0.02 to 1.50
ppm (1).

PA are usually concentrated in the metabolically active parts of the
complex rhizome which are the thickenings just below the leaves. They are
also present in flower stalks but are almost absent in leaf buds, the
petioles and the leaf blades (2). PA and PA-N-oxides induce tumors via a
genotoxic mechanism, and tumorigenicity is mediated by a set of eight
dehydroretronecine-derived DNA adducts. This mechanism may be general to
other carcinogenic PA and may also be responsible for the other
genotoxicities of PA, including mutagenicity and teratogenicity (3).
Besides the well known hepatotoxicty of PA, they have been associated with
potentially fatal hepatic veno-occlusive disease (Budd-Chiari Syndrome)
and fibrotic lung disease (4).

Papers dealing with herbal extract should report complete extractive
techniques, content of main constituents, presence or absence of toxic
substances, probable or demonstrated toxic effects, drugs interferences
and geographical area of production.

About Petasites hybridus the aim of future research should be the evidence
of clinical activity of preparations without PA content, especially for
chronic treatment and administration in gestational age and childhood.

We think should be improved vigilance of medical authorities on the use,
often as self-therapy, of over-the-counter herbal derivatives from which
toxic constituents have not been removed (5).


1. Wildi E, Langer T, Schaffner W, et al.: Quantitative analysis of
petasin and pyrrolizidine alkaloids in leaves and rhizomes of in situ
grown Petasites hybridus plants. Planta medica 1998;64:264-267.

2. Chizzola R, Ozelsberger B, Langer T.: Variability in chemical
constituents in Petasites hybridus from Austria. Bioch Syst Ecology 2000;
28: 421-432.

3. Fu PP, Chou MW, Xia Q, et al.: Genotoxic pyrrolizidine alkaloid N-
oxides. Mechanism leading to DNA adduct formation and tumorigenicity. J
Environ Sci Health 2001; 19/2: 353-385.

4. Pearson W.: Pyrrolizidine alkaloids in higher plants: Hepatic veno-
occlusive disease associated with chronic consumption. J Nutraceuticals
Funct Med Foods 2000; 3/1: 87-96.

5. Firenzuoli F, Gori L.: Herbal medicine. Minerva Med 2001; 92 (Suppl. 1
al N.3): 1-14.

Competing interests: No competing interests

22 January 2002
Firenzuoli Fabio
Department of Phytotherapy
Gori L
Via Paladini 1 , S. Giuseppe Hospital, 50053 Empoli (Italy)