Herbal acid: Poisonous remedy revealed

Herbal source for cancer epidemic

An informatics approach to toxic epidemiology has revealed that aristolochic acid (AA) leads to kidney failure and upper urinary tract cancer (UUC) in individuals exposed to the toxin. AA is found in some plant species that have been used in herbal medicine for centuries.

Incidence of UUC is relatively high in Taiwan. The use of herbal remedies based on Aristolochia is also commonplace. Now, a study of 151 UUC patients by Arthur Grollman of Stony Brook University School of Medicine and colleagues there and internationally has revealed that those two facts are not mere coincidence. Exposure to aristolochic acid from these remedies is, they say, a primary contributor to the incidence of this type of cancer in Taiwan.

Aristolochic acid, known systematically as 8-methoxy-6-nitrophenanthro[3,4-d][1,3]dioxole-5-carboxylic acid 8-methoxy-6-nitrophenanthro[3,4-d][1,3]dioxole-5-carboxylic acid, and its chemical cousins are known to be carcinogenic, mutagenic, and nephrotoxic. As such Chinese herbs such as Aristolochia fangchi and A. mandshurensis were banned in China and withdrawn from Chinese Pharmacopoea in 2005 because of the high concentration of this worrying compound. The US Department of Health and Human Services recognises the toxicity and health issues surrounding these compounds. Nevertheless, there are other related species that contain AA and its relatives and the new finding, as reported in Proceedings of the National Academy of Sciences (PNAS) has implications for the rise in so-called "alternative" medicine across the globe.

Given that many practitioners use herbal preparations with little thought to safety, or indeed efficacy, it is important that the risks associated with certain "remedies" are made known more widely. Anyone being offered preparations containing Aristolochia and its extracts may be at significant risk of developing chronic kidney disease or UUC regardless of the purported health benefits suggested by such practitioners. Moreover, in the West these species are touted as herbal weight loss agents and it was their use among a group of otherwise healthy Belgian women who subsequently developed kidney failure and UUC after taking Aristolochia herbs that first hinted at a problem with these herbs.

Belgium to the Balkans to Taiwan

Grollman and colleagues have also recently demonstrated that AA is behind an endemic nephropathy in the Balkans. Their work solved a medical mystery that had plagued doctors in the region for half a century. The women, it was found were ingesting Aristolochia clematitis, or birthwort, contained in wheat. The Balkans research then guided Grollman's team to other parts of the world where Aristolochia herbs are widely used and where there is a high incidence of kidney disease and UUC, which is how they reached Taiwan in their research travels.

"We believe our latest research highlights the importance of a long-overlooked disease that affects many individuals in Taiwan, and, by extension, in China and other countries worldwide, where Aristolochia herbal remedies traditionally have been used for medicinal purposes," explains Grollman.

Molecular epidemiology

The National Health Insurance data for Taiwan analysed for the years 1997-2003 indicated that herbal remedies known to contain AA were in widespread use during that period. Moreover, of 200,000 people randomly sampled from the entire insured population of the region, it was found that about one in three prescriptions led to the ingestion of these herbs. There is much to worry about in terms of cancer risk in terms of occupational exposure and ingestion of chemicals, but advocates of a natural approach to medicine repeatedly overlook the fact that herbal does not necessarily equate to safe and in this case AA exposure through the use of this particular class of herbal remedies has grown to a potentially global cancer epidemic.

In DNA from tumours found in 151 UUC patients, the team was able to identify a metabolite of AA bound to DNA [aristolactam(AL)-DNA adducts] in the kidney cortex of more than four out of five of the UUC patients. This was not the case with twenty-five patients with renal cell carcinomas acting as the control group. The AL-DNA adducts form through the reaction of AA with DNA. The phenanthrene core of the AAs perhaps giving them this particular ability to disturb the genetic code and trigger errant cell growth and tumour progression. Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) composed of three fused benzene, one of the very chemicals we are repeatedly warned to avoid for their carcinogenic properties.

The team also demonstrated that changes in the TP53 gene were observed. Alterations to this gene have been associated with several types of cancer and were present in the majority of the UUC patients, 84 (55.6%) of the 151 patients. "The findings provide a solid foundation for public health officials to develop strategies designed to eliminate aristolochic acid nephropathy and related upper urinary tract cancer," Grollman says.

"We attribute the progressive increase in the incidence of UUC in Taiwan over the past 25 years, especially among women, in part to the systematic replacement of traditionally used Mutong and Fangchi herbs with Aristolochia manchuriensis and Aristolochia fangchi, respectively," the team says. They point out that a similar rise in use occurred in mainland China from the 1930s until 2003 when the substitutions were banned. They point out that the presence of AA in Mutong and Fangchi exported to Taiwan between 1995 and 2003, as well as to other Asian countries, Great Britain, and The Netherlands, has been documented.