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Herbal Remedy Threatens Millions

By Ed Kang
May 2010

photo of the herb Aristolochia
The ancient Greeks describe Aristolochia as an antidote for poison, including snakebites; in Europe, they call it "birthwort," and women for 1000 years have used it to help expel the placenta after birth; in India, the herb is used in children to reduce fever; and in China, it's used for arthritis and for inflammation.  In April 2001, the U.S. Food and Drug Administration issued a warning(http://www.fda.gov/food/dietarysupplements/alerts/ucm096388.htm) Exit NIEHS to consumers to stop use of products containing aristolochic acid after women in Belgium developed serious and permanent kidney disease. (Photo courtesy of Arthur Grollman and Stony Brook University)

Arthur Grollman, M.D.
Arthur Grollman, M.D., whose primary interest is mechanisms of DNA repair and environmental carcinogenesis, is director of the Laboratory for Chemical Biology(http://www.lcb.stonybrook.edu/) Exit NIEHS at Stony Brook University. He is a member of NIEHS' Environmental Health Sciences Review Committee and a former member of the Board of Scientific Counselors. (Photo courtesy of Arthur Grollman and Stony Brook University)

Since the days of the ancient Greeks and Romans, people have turned to the ubiquitous plant Aristolochia - named after Aristotle - as an herbal medicine to treat a variety of symptoms and diseases, including arthritis and inflammation. Recently, this widely used herb has become a major topic of discussion because of its potent toxicity.

On April 21, NIEHS grantee(http://tools.niehs.nih.gov/portfolio/sc/detail.cfm?appl_id=7651416) and Stony Brook University Professor Arthur Grollman, M.D.(http://www.lcb.stonybrook.edu/node/116) Exit NIEHS, presented new findings from his ongoing research on the disease now known as aristolochic acid nephropathy at the American Association of Cancer Research (AACR)(http://www.aacr.org/home/scientists/meetings--workshops/aacr-101st-annual-meeting-2010.aspx) Exit NIEHS meeting in Washington, D.C. He hopes to convene a global conference to spark discussion of research and prevention of Aristolochia exposure.

"Aristolochia grows throughout the world," said Grollman, "and for millennia, every culture has used it for medicinal purposes. But it is such a potent and persistent toxin, one can't safely take even a small amount." In China and India especially, where herbal remedies play an important role in medicine, Aristolochia has emerged as a silent killer of those caught up in the claims of its healing power.

Decades-long latency

As Grollman explains, "It might take 20, 30, or more years for symptoms to appear, but ultimately people develop chronic kidney disease and urothelial cancer. We have detected the toxin in patients' tissues 50 years after the last exposure. I don't know of any other toxin that persists in tissues in an active form for half a century." The long delay between ingestion and disease appearance makes it difficult for traditional healers or those using the herb to make the connection between the two.

Grollman's investigations into the effects of Aristolochia began in the scattered, rural farm communities located in the Danube river basin where kidney disease and upper urinary tract cancer are prevalent. In these areas of Croatia, Serbia, and Bosnia, the Aristolochia plant grows freely in fields cultivated for wheat.

"About 50 percent of the local diet is comprised of bread from flour prepared in the old fashioned way - no effort is made to separate wheat grain from Aristolochia seeds. So residents of the endemic region are, in effect, ingesting on a daily basis low doses of this potent toxin from a very young age."

Fingerprint of a silent killer

The pathology of the renal disease - also called Balkan endemic nephropathy - is relatively unique and the associated cancer is found in an unusual location - the upper urinary tract.  In searching for its cause, Grollman analyzed mutations in the P53 gene - a tumor suppressor gene mutated in 50 percent of all cancers.

"Mutations in P53 are generally nonspecific, but with a handful of environmental agents, you can detect a definitive 'signature' mutation," said Grollman. "We have established the pattern of P53 mutations generated by aristolochic acid, which now joins aflatoxin and vinyl chloride as established human chemical carcinogens with distinct mutational signatures."

New findings point to significant global health impact

Grollman's newest findings shed light on the risk to the 80 percent of the world population that relies heavily on traditional herbal remedies to treat disease.

Epidemiologists from Taiwan National University recently examined Taiwan's national health care system records. The results indicated that one-third of the island's 25 million people have ingested herbs containing aristolochic acid for purported medicinal benefit. 

Grollman is blunt about the Taiwanese findings. "It's an enormous, well-documented exposure and undoubtedly connected to the high incidence of chronic kidney disease and upper urinary tract cancers in Taiwan."

If Aristolochia herbal use in mainland China mirrors that of Taiwan, as suspected by Grollman, the number of cases of aristolochic-acid induced renal disease and cancer could be staggering.

(Ed Kang is a public affairs specialist in the Office of Communications and Public Liaison and a regular contributor to the Environmental Factor.)



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