Last year, the US Food and Drug Administration issued a warning letter concerning the dangers associated with the use of herbal products containing aristolochic acid. The warning was prompted by reports from Belgium of a large number of patients from a weight loss clinic developing kidney failure and a rare form of cancer. The FDA sent a Letter to Health Professionals on April 4, 2001 (see: http://vm.cfsan.fda.gov/~dms/ds-botl3.html) advising of the problem and asking for reporting of all cases of renal disease associated with consumption of herbal products. On April 11, 2001, the FDA finally moved to warn consumers of the risks associated with consumption of products containing aristolochic acid.

The weight loss clinic in Belgium reported over 100 cases of severe renal dysfunction during the early 1990's. All patients were taking part in a weight loss program, which had recently added 2 herbal products as part of the regimen. Investigators concluded that one of the botanicals (Stephania tetrandra) had been inadvertently substituted with Aristolochia fangchi, a botanical which contains aristolochic acid. The confusion was the result, at least in part, of the similarity in the Chinese names of the plants. Seventy patients went on to kidney failure requiring dialysis or kidney transplants. Independent laboratory tests strongly suggested that exposure to aristolochic acid might predispose people to urothelial cancer. Because of the concern of cancer in these patients, 39 underwent exploratory surgery; 18 were diagnosed with urethelial cancer.

FDA laboratories analyzed a number of herbal products sold in the United States and identified that some indeed contained aristolochic acid. These products were either labeled as containing Aristolochia (also known as Virginia snakeroot) and, more disturbingly, those that were labeled to contain other herbs such as Stephania tetrandra, Clematis armandi and Akebia extract. The FDA issued warning letters and requests for product recalls. A listing of all of the products thus far identified as containing aristolochic acid can be found at: http://www.cfsan.fda.gov/~dms/ds-bot3.html.

It is important to note that these products are not subject to any meaningful FDA review. They are covered under the Dietary Supplement Health and Education Act (DSHEA). The reality of the legislation is that the consumer must exercise great caution when considering the use of dietary and nutritional supplements and herbal remedies. The usual and customary government oversight does not exist with these products. The FDA is powerless to remove a product unless it can clearly demonstrate that the product is harmful.

The regulatory situation that currently exists with products labeled as herbal remedies, dietary supplements and nutritional products has previously existed for prescription drugs. It would appear that we are destined to relive history. In 1937, Massengill marketed an elixir of sulfanilamide. That elixir was associated with 107 deaths in the United States, mostly in children. The cause of the deaths was the vehicle, diethylene glycol. The sulfanilamide disaster prompted the Congress to enact the Federal Food Drug and Cosmetic Act of 1938 establishing the requirement that companies show that their products were safe before they could be marketed. It took 107 deaths to produce more meaningful oversight of prescription drugs. Perhaps the 70 or so cases of kidney failure and the untold number of cases of urethelial cancer yet to be discovered will prompt the Congress to move toward more meaningful oversight of herbal remedies, dietary supplements and nutritional supplements.

Clinicians are urged to report any cases of renal dysfunction or failure associated with the use of herbal remedies to the FDA.