Aristolochiaceae

Aristolochia species

Plants belonging to the genus of Aristolochia are rich in aristolochic acids and aristolactams.

In the UK, the long-term (2 and 6 years) use of Aristolochia species in Chinese herbal mixtures, taken as an oral medication or herbal tea, resulted in Chinese-herb nephropathy with end-stage renal insufficiency [ ]. In reaction to these reports, the erstwhile Medicines Control Agency banned all Aristolochia species for medicinal use in the UK.

In June 2001, the FDA issued a nationwide alert, recalling 13 “Treasure of the East” herbal products containing aristolochic acid. Before this alert, the FDA had issued several warnings:

• On 4 April 2001 a “Dear Health Professional” letter was sent, drawing attention to serious renal disease associated with the use of aristolochic acid-containing dietary supplements or “traditional medicines.” Health professionals were urged to review patients who had had unexplained renal disease, especially those with urothelial tract tumors and interstitial nephritis with end-stage renal insufficiency, to determine if such products had been used.

• On 9 April 2001 a letter was sent to industry associations, detailing the reported cases of renal disease associated with aristolochic acid.

• On 11 April 2001 the FDA cautioned consumers to immediately discontinue any dietary supplements or “traditional medicines” that contain aristolochic acid, including products with “Aristolochia,” “Bragantia,” or “Asarum” listed as their ingredients.

In a related action, Health Canada first issued a warning on aristolochic acid in November 1999 that this ingredient posed a Class I Health Hazard with a potential to cause serious health effects or death [ ] and warned consumers not to use the pediatric product Tao Chih Pien. This Chinese product, sold in the form of tablets, is said to be a diuretic and a laxative. It is not labeled to contain aristolochic acid. However, the Chinese labeling says that it contains Mu Tong, a traditional term used to describe numerous herbs, including Aristolochia ; subsequent product analysis showed that Tao Chih Pien does indeed contain aristolochic acid. Health Canada advised individuals in possession of this product not to consume it and to return it to the place of purchase. It also issued a Customs Alert for the product to prevent the importation and sale of Tao Chih Pien and advised Canadians not to consume Longdan or Lung Tan Xi Gan products, since they may also contain aristolochic acid.

The product Longdan Qiegan Wan (“Wetness Heat” Pill) was removed from the Australian Register of Therapeutic Goods following the detection of aristolochic acid by laboratory testing by the Therapeutic Goods Administration [ ].

In 2002 the Medicines Safety Authority of the Ministry of Health in New Zealand (Medsafe) ordered the withdrawal of several traditional Chinese medicines sold as herbal remedies [ ]. The products included Guan Xin Su He capsules, Long Dan Xie Gan Wan Pills, and Zhiyuan Xinqinkeli sachets.

In 2004 the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), with the co-operation of Customs and Excise, seized a potentially illegal consignment of 90 000 traditional Chinese medicine tablets, Jingzhi Kesou Tanchuan, which reportedly contained Aristolochia .

In December 2004 the Hong Kong authorities warned the public not to take the product Shen yi Qian Lie Hui Chin, as laboratory tests showed that it contained aristolochic acid.

In 2004 China’s State FDA banned two commonly used herbs containing aristolochic acid, a toxin that is linked to renal insufficiency and cancer [ ]. Manufacturers were directed to replace Aristolochia fangchi and Aristolochia debilis with Staphania tetrandra and Inula helenium respectively in their traditional medicine formulations by 30 September 2004. The Provincial Drug Bureau was instructed to carry out inspections to ensure compliance with the ban by 31 October. Medicines found to contain either Aristolochia fangchi or Aristolochia debilis after 30 September were to be treated as fake under Chinese law. By a previous order, special restrictions were imposed on four other potentially harmful aristolochic acid-containing herbs in China ( Fructus aristolochiae , Aristolochia mollissima Hance , Herba aristolochiae , and Aristolochia tuberose ); however, there was no outright ban on these products. Several countries withdrew formulations containing aristolochic acid in 1981 after the demonstration of carcinogenicity in a 3-month toxicity study in rats. A consolidated list of products whose consumption and/or sale have been banned, withdrawn, severally restricted or not approved by governments has been published [ ].

Several review articles have covered the toxicology of Aristolochia [ ].