People who have taken products containing aristolochia may develop cancer and the risk increases depending on how much they have taken, say researchers from Belgium.
Dr Joëlle Nortier (department of nephrology, Hôpital Erasme, Brussels) and colleagues detected urothelial carcinoma in 18 out of 39 patients who developed end-stage renal failure after taking Chinese herbal medicines containing aristolochia - 19 out of the remaining 21 had mild-to-moderate dysplasia.
The incidence of cancer in these patients appeared to increase with high cumulative total doses, as 10 of the 18 cases had taken more than 200g of Aristolochia fangchi (New England Journal of Medicine 2000;342:1686).
Commenting on the results in an editorial (ibid, p1742), Dr David Kessler (Yale university school of medicine, Connecticut, US) says: "The high prevalence of tumours in this group is striking - it is certainly higher than is commonly reported among patients with end-stage renal disease or transplant recipients. Combined with the known carcinogenicity of aristolochic acid in animals, the findings . . . are worrisome."
According to Dr Nortier and colleagues, aristolochic acid metabolites form DNA adducts in the kidney, which are specific markers of exposure to aristolochic acids and are directly involved in tumor development. All of the patients who had taken the herbal medicine had evidence of DNA adducts but none were found in kidney samples from patients who had not been exposed to aristolochia.
The patients had taken the Chinese herbal medicine as part of a weight loss programme that was intended to include Stephania tetranda and Magnolia officinalis but Aristolochia fangchi was accidentally substituted for the Stephania tetranda.
The programme had also included use of fenfluramine or dipropion, sometimes with other drugs, such as acetazolamide, which may have potentiated the toxicity of the aristolochia, they say.
Last year, the Committee on Safety of Medicines banned the sale of Chinese herbal medicines that contained aristolochia species following two reports of end-stage renal failure associated with these products (PJ, 1999;263:150).