Results 1 to 2 of 2

Thread: Guan Mu Tong, Guang Fangchi and Urinary Tract Cancers

  1. #1

    Guan Mu Tong, Guang Fangchi and Urinary Tract Cancers

    A well done study out of Taiwan that explores the relationship between various TCM Chinese herbs that contain aristolochic acid, and the increased incidence of different urinary tract cancers.

    Background Consumption of Chinese herbs that contain aristolochic acid (eg, Mu Tong) has been associated with an increased risk of urinary tract cancer.

    Methods

    We conducted a population-based case–control study in Taiwan to examine the association between prescribed Chinese herbal products that contain aristolochic acid and urinary tract cancer. All patients newly diagnosed with urinary tract cancer (case subjects) from January 1, 2001, to December 31, 2002, and a random sample of the entire insured population from January 1, 1997, to December 31, 2002 (control subjects), were selected from the National Health Insurance reimbursement database. Subjects who were ever prescribed more than 500 pills of nonsteroidal anti-inflammatory drugs and/or acetaminophen were excluded, leaving 4594 case patients and 174 701 control subjects in the final analysis. Adjusted odds ratios and 95% confidence intervals were estimated by using multivariable logistic regression models for the association between prescribed Chinese herbs containing aristolochic acid and the occurrence of urinary tract cancer. Models were adjusted for age, sex, residence in a township where black foot disease was endemic (an indicator of chronic arsenic exposure from drinking water [a risk factor for urinary tract cancer]), and history of chronic urinary tract infection.

    Introduction

    Aristolochic acid nephropathy—a progressive form of renal interstitial fibrosis—was first reported in a group of young Belgian patients with end-stage renal disease in 1993 and was thought to be caused by the use of Chinese herbal medicines that contained aristolochic acid. Aristolochic acid has been shown to be associated with urothelial cancer in studies of clinical cases around the world, in animal models, and by the detection of aristolochic acid–DNA adducts in kidney and ureteral tissues. In 2002, the International Agency for Research on Cancer classified herbal remedies that contain plant species of the genus Aristolochia, which contain a high level of aristolochic acid, as carcinogenic in humans. Consequently, many countries have since banned the use of herbs containing aristolochic acid, including Taiwan, in November of 2003. Before this time, however, products containing these herbs were widely prescribed in Taiwan.

    In Taiwan, there have been case reports of renal failure associated with the use of Chinese herbal products and herbs that contain aristolochic acid. However, to our knowledge, there have been no reports of urinary tract cancer associated with the use of herbs or herbal products containing aristolochic acid. In March of 1995, Taiwan established the National Health Insurance (NHI) program, which covers more than 96% of Taiwanese residents. The NHI routinely reimburses enrollees for the cost of prescribed medicines, including Chinese herbal products containing aristolochic acid, which were widely prescribed before the ban in 2003. We used the NHI reimbursement database to conduct a population-based case–control study to examine the association between having been prescribed Chinese herbal products that contain substantial amounts of aristolochic acid, including Guan Mu Tong and Guang Fangchi, and the risk of urinary tract cancer. In addition to smoking, chronic exposure to arsenic in drinking water, which causes an endemic peripheral vascular disease called black foot disease in specific areas of Taiwan, has been documented to be associated with an increased incidence of bladder cancer. We conducted this case–control study in Taiwan to examine the association between urinary tract cancers and having been prescribed Chinese herbal products that contain aristolochic acid and a potential dose–response relationship. In particular, we controlled for the potential confounding effect of arsenic exposure.


    Exposure Assessment

    According to standard prescriptions recommended by the Committee on Chinese Medicine and Pharmacy in Taiwan, Chinese herbal products produced before new regulations were promulgated in November of 2003 might include the following herbs containing aristolochic acid: Ma Dou Ling (Fructus Aristolochiae), Tian Xian Teng (Caulis Aristolochiae), Xi Xin (Asarum heterotropoides), Guan Mu Tong (Aristolochia manshuriensis), Guang Fangchi (Aristolochia fangchi), and Qing Mu Xiang (Radix Aristolochiae). Of these, Guan Mu Tong and Guang Fangchi were once sold under the names of Mu Tong (Akebia species) and Fangchi (Stephania species), respectively. Several studies revealed that 89.2%–100% of Fangchi preparations contained Guang Fangchi, and more than 84% of Mu Tong preparations contained Guan Mu Tong. These herbs were taken as single products or were components of mixed herbal formulas that are recommended by ancient Chinese medicine books (eg, Mu Tong in the Long Dan Xie Gan mixture). Because the prescription data from the NHI database can be linked directly to the actual drug(s) prescribed by means of the product number, we were able to identify all subjects who had taken these Chinese herbal products. In addition, each pharmaceutical company in Taiwan has published and submitted the detailed composition of each of its products to the Committee on Chinese Medicine and Pharmacy to be approved for registration. By using this information, we determined the original amounts of herbs, in grams, for each mixture of Chinese herbal products, and the total dose of each aristolochic acid–containing herb (eg, Mu Tong, Fangchi, and Xi Xin) during the exposure period from January 1, 1997, to the date of diagnosis of urinary tract cancer or December 31, 2002, if censored, was summed for each subject included in this study. To allow a minimal induction time for an exposed subject to develop urinary tract cancer, we calculated the cumulative dose for each herb prescribed to an individual up to 1 year before the diagnosis of urinary tract cancer.

    According to the Committee on Chinese Medicine and Pharmacy, Mu Tong is usually prescribed for the treatment of hepatitis, urinary tract infection, rhinitis, dysmenorrhea, and eczema.

    Black foot disease is a peripheral vascular disease that has been endemic to the coastal region of Taiwan for the past 60 years, is related to the water derived from artesian wells containing arsenic, and has been documented to be associated with an increased incidence of bladder cancer. In addition, comparison of clinical features of patients with these cancers indicated that no patients with urinary tract cancer associated with black foot disease (or arsenic exposure) developed end-stage renal disease before the occurrence of cancer. In fact, there were only two cases of urinary tract cancer who were simultaneously associated with having been prescribed more than 60 g of Mu Tong and with living in a township endemic for black foot disease. Hence, these findings indicate that exposure to more than 60 g of Mu Tong and to arsenic are two independent risk factors for urinary tract cancer.

    In this study, the association between the cumulative doses of aristolochic acid–containing herbs and the risk of occurrence of urinary tract cancer seemed to be dose-dependent. According to the annual reports of National Laboratory of Food and Drug in Taiwan, 1 g of Guan Mu Tong and Guang Fangchi was estimated to contain 2.59 and 2.04 mg of aristolochic acid, respectively. Thus, a cumulative dose of 60 g of Mu Tong and of 100 g of Fangchi in Chinese herbal products contains approximately 155 and 204 mg, respectively, of aristolochic acid, which is slightly higher than the 147-mg aristolochic acid dose reported in the Belgian reports. In this study, we observed a consistent dose–response relationship between the estimated intake of aristolochic acid (or prescribed dose of aristolochic acid–containing Mu Tong) and urinary tract cancer, which suggests that aristolochic acid may be the agent responsible for carcinogenicity. In this study, more than 100 g of Fangchi was statistically significantly associated with an increased crude odds ratio for urinary tract cancer; however, the association did not reach statistical significance after adjustment for other risk factors, probably because of the small number of case subjects. By contrast, Xi Xin contains only minute amounts of aristolochic acid, or approximately 0.009–0.042 mg aristolochic acid per g, which is approximately 1:50 to 1:200 of the amount in Aristolochia fangchi. At the prescribed median daily dose of 0.9 g for Xi Xin in this study, exposure to more than 155 mg of aristolochic acid would take longer than 10 years. Thus, we were unable to detect any association between prescription of Chinese herbal products containing Xi Xin (Asarum heterotropoides) and urinary tract cancer. However, careful attention should still be paid regarding the use of Chinese herbal products containing Xi Xin, and long-term follow-up should be provided for subjects who regularly consume these products.

    In this study, 43% of urinary tract cancer cases were upper urinary tract cancer, which is similar to rates reported by the National Cancer Registry and in a previous clinical report of pathology-confirmed urinary tract cancer cases in Taiwan. These rates are much higher than those in other countries, in which less than 10% of all urinary tract cancer cases are upper urinary tract cancer. In this study, prescription of Chinese herbal products was associated with urothelial cancers that occurred in all parts of the urinary tract, similar to what was reported in a recent case series of Belgian women who received kidney transplants for end-stage aristolochic acid nephropathy in which 44.7% had upper urinary tract cancer and 39.5% had bladder cancer. Thus, we suggest that aristolochic acid induces urothelial cancers in the upper urinary tract and bladder with approximately equal tendency.

    In conclusion, having been prescribed more than 60 g of Mu Tong or more than 150 mg aristolochic acid from Chinese herbal products was associated with an increased risk of developing urinary tract cancer. The linear dose–response relationship between the estimated level of aristolochic acid and urinary tract cancer might be useful for considering a complete ban, or for establishing limits, on the consumption of herbal products and/or herbs that contain low amounts of aristolochic acid. Care must still be taken for prescribing doses less than 60 g of Mu Tong or 150 mg of aristolochic acid because there might be no threshold dose under a linear dose–response relationship and given recent evidence for an increased risk of chronic kidney disease associated with a prescribed dose of 30–60 g of Mu Tong. In this study, from 2001 to 2002, there were 118 new cases of urinary tract cancer in Taiwan associated with the ingestion of more than 60 g of the Chinese herb Mu Tong, which represents 3% of all new patients with urinary tract cancer. In addition to a ban on products that contain any amount of aristolochic acid, we also recommend continued surveillance of herbs or Chinese herbal products that might be adulterated with aristolochic acid–containing herbs. Finally, patients with a history of aristolochic acid nephropathy or consumption of Mu Tong or Fangchi before they were banned should be monitored regularly for urinary cancer.
    Experienced Community organizer. Yeah, let's choose him to run the free world. It will be historic. What could possibly go wrong...

    "You're just a jaded cynical mother****er...." Jeffpeg

    (more comments in my User Profile)
    russbo.com



  2. #2
    Join Date
    Mar 2012
    Posts
    2
    God bless you, Guan Mu Tong ! Yesterday I got up from my bed and my bladder area started to hurt and I was just thinking I have to go pee and later it still hurt... today as I get to college my bladder area starts to hurt again and I'm just ignoring it, but every time I get up it hurts and when I start walking it hurts too, but the symptom's I researched doesn't go with what I'm feeling... and I'm 27 years old and I'm scared what the doctor will do if I go, What will he do??? Now I'm using ADULT DIAPERS to safe.
    Last edited by doc; 03-09-2012 at 06:13 AM. Reason: removed spam hyperlink; imaginative attempt however.

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •