The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety

Research both in the United States and abroad suggests that significant numbers of people are involved with various forms of alternative medicine. However, the reasons for such use are, at present, poorly understood. To investigate possible predictors of alternative health care use. Three primary hypotheses were tested. People seek out these alternatives because (1) they are dissatisfied in some way with conventional treatment; (2) they see alternative treatments as offering more personal autonomy and control over health care decisions; and (3) the alternatives are seen as more compatible with the patients' values, worldview, or beliefs regarding the nature and meaning of health and illness. Additional predictor variables explored included demographics and health status. A written survey examining use of alternative health care, health status, values, and attitudes toward conventional medicine. Multiple logistic regression analyses were used in an effort to identify predictors of alternative health care use. A total of 1035 individuals randomly selected from a panel who had agreed to participate in mail surveys and who live throughout the United States. Use of alternative medicine within the previous year. The response rate was 69%. The following variables emerged as predictors of alternative health care use: more education (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.1-1.3); poorer health status (OR, 1.3; 95% CI, 1.1-1.5); a holistic orientation to health (OR, 1.4; 95% CI, 1.1-1.9); having had a transformational experience that changed the person's worldview (OR, 1 .8; 95% CI, 1 .3-2.5); any of the following health problems: anxiety (OR, 3.1; 95% CI, 1.6-6.0); back problems (OR, 2.3; 95% CI, 1 .7-3.2); chronic pain (OR, 2.0; 95% CI, 1.1 -3.5); urinarytract problems (OR, 2.2; 95% CI, 1.3-3.5); and classification in a cultural group identifiable by their commitment to environmentalism, commitment to feminism, and interest in spirituality and personal growth psychology (OR, 2.0; 95% CI, 1.4-2.7). Dissatisfaction with conventional medicine did not predict use of alternative medicine. Only 4.4% of those surveyed reported relying primarily on alternative therapies. Along with being more educated and reporting poorer health status, the majority of alternative medicine users appear to be doing so not so much as a result of being dissatisfied with conventional medicine but largely because they find these health care alternatives to be more congruent with their own values, beliefs, and philosophical orientations toward health and life.

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 Chinese-herb weight-reducing compounds during the period of exposure (1990 to 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 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 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 a high.

Aristolochic acid, a potent human carcinogen produced by Aristolochia plants, is associated with urothelial carcinoma of the upper urinary tract (UUC). Following metabolic activation, aristolochic acid reacts with DNA to form aristolactam (AL)-DNA adducts. These lesions concentrate in the renal cortex, where they serve as a sensitive and specific biomarker of exposure, and are found also in the urothelium, where they give rise to a unique mutational signature in the TP53 tumor-suppressor gene. Using AL-DNA adducts and TP53 mutation spectra as biomarkers, we conducted a molecular epidemiologic study of UUC in Taiwan, where the incidence of UUC is the highest reported anywhere in the world and where Aristolochia herbal remedies have been used extensively for many years. Our study involves 151 UUC patients, with 25 patients with renal cell carcinomas serving as a control group. The TP53 mutational signature in patients with UUC, dominated by otherwise rare A:T to T:A transversions, is identical to that observed in UUC associated with Balkan endemic nephropathy, an environmental disease. Prominent TP53 mutational hotspots include the adenine bases of (5')AG (acceptor) splice sites located almost exclusively on the nontranscribed strand. A:T to T:A mutations also were detected at activating positions in the FGFR3 and HRAS oncogenes. AL-DNA adducts were present in the renal cortex of 83% of patients with A:T to T:A mutations in TP53, FGFR3, or HRAS. We conclude that exposure to aristolochic acid contributes significantly to the incidence of UUC in Taiwan, a finding with significant implications for global public health.