Aristolochia fangchi and Urothelial Carcinoma
Clinical Briefs
With Comments from John La Puma, MD, FACP
Aristolochia fangchi and Urothelial Carcinoma
August 2000; Volume 3; 95-96
Source: Nortier JL, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 2000;342:1686-1692.
"Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic.
"The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for weight-reducing compounds during the period of exposure (1990-1992) in these patients were obtained, and the cumulative doses were calculated.
"Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46%; 95% confidence interval, 29-62%): 17 cases of carcinoma of the ureter, renal pelvis, or both, and one papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma. The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by Aristolochia species) is high."
COMMENT
Though the FDA indicates that it will pursue "regulatory action," and it’s possible that these particular supplements may even be pulled, there’s no real possibility under DSHEA that FDA can be more than reactive in the regulation of dietary supplements. Popular demand for supplement availability is too strong, and people want to try new medicines in the form of herbs. It’s entirely sensible that people do so: Ethical pharmaceuticals are often expensive, hard to access, and may be toxic.
Herbs, though, can be toxic, too. These results, and a subsequent FDA Letter to Health Care Professionals about supplements, show that persuasively.
Which Chinese herbs cause cancer? The list is long, and the details are posted in three attachments to the FDA letter on its Web site. The named botanicals include Aristolochia spp., Asarum spp., Bragantia spp., Stephania spp., Clematis spp., Akebia spp., Cocculus spp., Diploclisia spp., Menispernum spp., Sinomenium spp., Mu tong, Fang ji, Guang fang ji, Fang chi, Kan-Mokutsu (Japanese), and Mokutsu (Japanese). Aristolochic acid-containing herbs have been banned in the United Kingdom, Canada, Germany, and Australia.
Chinese herbs are coming to light in American medicine in an unhappy way. Sure, they’re sold by the ton in traditional Chinese medicine; certainly there is beneficial, therapeutic effect to some. But compounded patent medicines have been contaminated with heavy metals. Compounded creams have been laced with corticosteroids. And Chinese herb nephropathy is well-described, as is a series of more than 100 Belgians with end-stage renal disease, some of whom were unlucky enough also to receive anorexigenic agents popular in the early 1990s. Aristolochic acid joins this dark group, and should be taken off the open market immediately.
Recommendation
Aristolochic acid is carcinogenic. Find out if your patients are taking it. If so, advise them to discontinue it and see a urologist immediately.
August 2000; Volume 3; 95-96
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