TCM Herb Tainted with Kidney-Damaging Toxins

A traditional Chinese Medicine (TCM) herb labeled as Chaihu" (Bupleurum chinense root) was found to be adulterated with Aristolochia manshuriensis, which contains toxic compounds associated with kidney damage and urinary tract cancer, in a recent study  (Planta Med 2012; 78(3): 207-210). Researchers, who were studying drugs that modulate the GABA_A receptor, reported thin layer chromatography (HPTLC) analysis confirmed the presence of aristolochic acids, which are known to be in Aristolochia species, but this study showed the adulterants were in a sample of bupleurum roots that was imported from Germany to Switzerland.

The analysis showed the sample contained both a mixture of Aristolochia manshuriensis root and Bupleurum chinense root. "This case of adulteration with a highly nephrotoxic drug raises concerns about adequate quality control of TCM drugs commercialized in Europe," noted the study authors.

But the sample tested in the study was from 10 years ago, before more sophisticated monographs were developed for traditional Chinese herbs. Had researchers used the updated monographs when they obtained the sample in 2002, they would have been less likely to obtain an adulterated sample.

Steven Dentali, chief science officer, the American Herbal Products Association (AHPA), said he reached out to the study coauthor Matthias Hamburger, Ph.D., to find out why the sample was found to be adulterated when it originally passed a microscopic and macroscopic analysis prior to extraction in 2002. If the sample roots or pieces were large enough, a careful macroscopic analysis (observable by the naked eye) in 2002 should have uncovered the adulteration.

According to Dentali, Hamburger said in 2002, his researcher team did not have microscopic drawings or a thin layer chromatography (TLC) assay, so they made their determination on text descriptions from the German translation of the herbal monographs of the Chinese Pharmacopeia. Using the information they had, they determined the sample was pure, relying in part on the responsibility of the German supplier, the original importer from China, to have done a proper identification. In 2010, Hamburg and his team returned to check the original sample with updated assays and monographs, and the adulteration they found resulted in the recently published study.

This adulteration shouldn't scare consumers or product manufactures to think aristolochic acid contamination is widespread. "There are better monographs now," Dentaili noted, adding  the Chinese Pharmacopeia uses HPTLC. "In Germany, pharmacists are now required to verify the identify using the more up-to-date monographs to do that."

However, if consumers open their web browsers, they may not find that story represented. A recent USA Today article gives a good overview of the history of aristolochic acid and it's presence in TCM, but takes a turn to attack the Dietary Supplement Health and Education Act of 1994 (DHSEA) based on events that occurred 20 and 30 years ago. According to the article, aristolochic acid, a characteristic marker of birthwort (Aristolochia clematitis), may be responsible for increased levels of kidney failures in Taiwan, Croatia, Bulgaria, Romania and elsewhere.

The article noted how birthwort has been traditionally used to treat kidney stones among other illnesses, yet the places that use this medicine have a large incidence of kidney disease. The article explained that in 1969, a Croatian researcher first noted that Aristolochia poisoning may play a role in kidney failure and urinary tract cancer among farming villages along the Danube River valley in Croatia, Bulgaria, Romania and elsewhere in the region, and in 1991, the herb was behind the kidney failure of women who attending a "slimming" clinic in Brussels.

The Brussels case led to a 2000 New England Journal of Medicine report that found about 5 percent of 1,800 women given the Chinese herb, Aristolochia fangchi (another birthwort species), in a weight-loss treatment at the clinic had developed kidney failure.

In response, FDA issued alerts to consumers and warnings to the natural product industry in 2001 that aristolochic acids are associated with kidney damage, kidney failure and urinary tract cancer. Also in 2001, the American Herbal Products Association (AHPA) added information on aristolochic acid to its trade requirements, and aristolochic acid-containing plants to its list of known adulterants (in AHPA's Guidance Policies).

The USA Today article quoted Arthur Grollman of Stony Brook University, NY, who coauthored  a 2007 Proceedings of the National Academy of Sciences paper that showed the Balkan and Belgian cases were both caused by the aristolochic acid. The 2007 study found mutations of the plants' genes inactivated the tumor-suppressing gene p53.

This is an interesting finding, and any finding of an adulterated product should trigger alarm, but at the end of the USA Today article, the writerDan Verganounwarrantedly attacks the dietary supplement industry. I image this scenario: he turns in the article to his editors without the attack, and then they tell him to "spice it up." Can't say if that's true; just my daydreaming.

Anyway, the article takes the last two paragraphs to slam the American supplement industry (even thought the product was found in a European product). Vergano wrote, "But that doesn't mean there aren't other traditional remedies posing just as much concern as birthwort out there on health food store shelves, because under U.S. law, such dietary supplements aren't subject to the same safety testing that drugs and other medical treatments must undergo."

Then, Grollman is quoted as saying, "An important message for Americans is that Congress is inviting similar problems in our country by not holding dietary supplementswhich includes herbsto reasonable standards of safety and efficacy." He continued, "We simply don't know whether other herbal supplements like Aristolochia are being marketed right now."

Ouch. I can understand why USA Today would want to highlight the aristolochic acid issue, but why use the last few moments to scare consumers that the entire industry is unsafe and isn't up to snuff of safety?

A good way to combat this is for industry to showagain and again, like it's been doingthat good companies offer safe and effective products. Using good manufacturing practices (GMPs) and further quality control methods, the top tier companies offer safe products.

To make sure your company among that top tier with regard to monitoring the supply chain, attend the SupplySide MarketPlace education session, "Best Practices in Quality Assurance and Control: Monitoring Supply and Detecting Adulteration/Contamination," from 9 a.m. to noon, Thursday, May 10, Javits Center, New York. In this session, Mark Blumenthal, founder and executive director, American Botanical Council (ABC), and George M. Pontiakos, president and CEO, BI Nutraceuticals/Zuellig Group N.A., will discuss maintaining control over the supply chain. Or attend the SupplySide MarketPlace education session, "Supply Chain at a Crossroads: Protecting Yourself from Fraud and its Costs," on Thursday, May 10, 11:30 a.m. to 1:30 p.m., Javits Center, New York, where Cristian Barcan, head of S.E.T. InitiativeAmericas and Asia/Pacific, BASF Nutrition & Health; Mark A. LeDoux, J.D., founder, CEO and chairman, Natural Alternatives Intl. Inc.; and Marc S. Ullman, Esq., partner, Ullman, Shapiro & Ullman LLP, will discuss the telltale signs of manipulation in supply and how a company can be sure about its suppliers.

Or hear more from AHPA at SupplySide MarketPlace at the AHPA Botanical Congress, which will include presentations on topics such as global supply chain, legal and regulatory issues and an optional forum on botanical identification. The Botanical Congress will be held Tuesday, May 8, 8 a.m. to 5 p.m., Javits Center, New York.