Chapter 10 Toxicity of herbal constituents

Most toxic effects of herbal medicines are due to the poor quality of the product. For example, herbal medicines may be adulterated with synthetic medicines and other compounds, or there may be problems in the production of such herbal medicines. However, some toxic compounds, including the pyrrolizidine alkaloids and aristolochic acids, still pose potential serious risks for a few plant-derived products.

This chapter is not about toxic plants as such (see Nelson et al 2006), but about those plants used as herbal medicines and in therapy. Most common herbal remedies are fairly safe in clinical use; not because they are ‘natural’, but because the long history of use has uncovered some of the adverse effects.

Traditional use is not always a reliable indication of safety, since toxicity which results only from chronic use, or manifests after a long interval between taking the medicine and the onset of a reaction, may make the connection difficult. Many patients do not consider phytomedicines to be ‘drugs’, therefore an association may not have been made between the remedy and an adverse reaction, so even though a herb has been used for hundreds of years there may remain cause for vigilance. Knowledge of the chemistry and metabolism of the constituents of a herb can help to predict toxicity problems.

As with all medicines, side effects and interactions with other drugs are possible; but these are a consequence of the therapeutic use of the herb and an assessment of the usual risk:benefit ratio should be made. Problems produced by misidentification, variations in composition, which may cause overdose or underdose, and contamination with microorganisms, pesticides or heavy metals are quality issues; however, there are a number of known toxic constituents, which confer no apparent health benefit, and herbs containing them should be avoided. Allergic reactions can be elicited by any drug, and idiosyncratic responses by definition cannot be foreseen; these are certainly not restricted to plant medicines, although some plant families (e.g. Asteraceae, Ranunculaceae) are notorious for their allergenicity.

Pyrrolizidine alkaloids

These have only been reported in the plant families Boraginaceae, Asteraceae, Leguminosae, Apocynaceae, Ranunculaceae and Scrophulariaceae, and not in all species. Medicinal herbs that may be affected include comfrey (Symphytum spp.), butterbur (Petasites hybridus (L.) P. Gaertn., B. Mey. & Scherb.), alkanet (Alkanna tinctoria Tausch, Boraginaceae), coltsfoot (Tussilago farfara) and hemp agrimony (Eupatorium cannabinum L., Asteraceae). Not all pyrrolizidine alkaloids are toxic, only those that are unsaturated at the 1,2-position (e.g. senecionine; Fig. 10.1). These are liver toxins and can produce veno-occlusive disease of the hepatic vein as well as being hepatocarcinogenic, and their effects are cumulative. Several documented clinical examples can be found in the literature. Although highly toxic, they are chemically rather labile and may, therefore, not present the serious risk originally thought, at least in herbal medicines that have undergone a lengthy process involving heat. For example, when six commercial samples of comfrey leaf were tested, none of these alkaloids were detectable. However, in fresh plant material, and also root samples, they may be present in significant amounts. The total recommended maximum dose of these alkaloids is less than 1 μg daily for less than 6 weeks per year. If herbal products, which may contain these, are to be employed (and some are very useful, e.g. butterbur and coltsfoot; see Chapter 16), the content must be estimated and, if necessary, the alkaloids should be removed before use.