Leading with the inflammatory headline – “Herbal Remedies Are An Overlooked Global Hazard” – a commentary in the European Molecular Biology Organization reports expresses alarm over the use of herbal remedies, by focusing the danger of Aristolochia. Rather surprising the report arrives 16 years after the U.S. Food and Drug Administration cautioned manufacturers of herb products to avoid using herbs that contain a compound known as aristolochic acid (AA).
The authors, Dr. Donald M. Marcus and Dr. Arthur P. Grollman, suggest that while millions of people around the world use herbal health remedies, long-term use of herbal remedies is no guarantee of their safety.
Dr. Marcus, professor emeritus of medicine and immunology at Baylor College of Medicine, and Dr. Grollman, professor of pharmacological sciences at Stony Brook University, discuss the scientific evidence showing that the plant Aristolochia can cause aristolochic acid nephropathy (AAN). People with this condition experience interstitial nephritis, renal failure and cancers of the urinary track.
The authors remark that in Taiwan, according to the national prescription database, between 1997 and 2003, 8 million people were exposed to herbals containing Aristolochia. Studies of patients with renal failure and cancer in Taiwan and China show that tens of millions of people in those countries are at risk of AAN.
In genetically susceptible people, consuming Aristolochia can lead to the formation of complexes between aristolactam, a compound in Aristolachia, and DNA in renal tissues. These complexes lead to mutations in the TP53 tumor suppressor gene, which in turn initiate the process toward kidney cancer. Additional studies have shown that this process may also lead to the development of cancer in the liver and the bladder.
Marcus and Grollman indicate that other herbals and traditional medicines are responsible for severe adverse events in Africa and Asia, but in these cases epidemiological data are lacking.
Although Aristolochia has been used as a herbal remedy for more than 2000 years, “the intrinsic toxicities were not recognized, owing, in large part, to the latency period between exposure and the onset of symptomatic disease, and, in part, to genetic determinants that confer susceptibility to only approximately 5 percent of those exposed to this herb,” said the authors. The long-term scientific study of AAN revealed the association of the disease with Aristolochia.
Almost all carcinogens and many toxins require a long period of time before symptoms appear. This makes it very difficult for a layman or a professional to identify a particular compound as the cause of an illness when it was taken months or years earlier.
“The history of Aristolachia indicates that other herbs that have been used for a long time may also have toxic and/or carcinogenic compounds,” said the authors, adding the absurd statement – “It is prudent to assume that many herbs may contain toxic or carcinogenic substances that can cause subsequent health problems for humans.”
The recognition of Aristolochia‘s profound toxicity and carcinogenicity in humans began in the early 1990s, when about 100 otherwise healthy Belgian women developed a rapidly progressing chronic kidney disease that ultimately required dialysis or renal transplantation.
Marcus and Grollman disagree with the World Health Organization’s endorsement of the use of traditional herbal remedies on the premise that traditional medicine is of proven quality, without mentioning the lack of scientific evidence supporting the efficacy of herbal remedies or their demonstrated hazards, as in the case of Aristolochia.
The authors emphasize that their primary concern is “the prevention of toxicities associated with herbal medicine and not a categorical rejection of traditional healing practices. Herbal remedies pose a global hazard. We encourage the global health community to take actions that will evaluate both long- and short-term safety, as well as the efficacy of botanical products in widespread use.”
The American Council on Science & Health reprinted the report adding the headline – “Sometimes Herbal Remedies Can Kill You.”
No surprise that Dr. Marcus is a leading critic of alternative medicine, especially herbal medicine. An article on complementary and alternative therapies (CAT) for lupus, included a review of all research conducted on CAT by the Cochrane Library, a clearinghouse of research publications, and found only 0.8 percent of CAT therapies were found to be harmful, compared with 8.1 percent of conventional treatments.
This led Dr. Marcus to complain: “Don’t ignore that 0.8 percent harm. Chiropractic treatment can tear a blood vessel at the base of the brain, or even cause a stroke in rare instances. Herbal medications are unregulated, meaning you don’t really know what you’re getting. And those therapies that aren’t harmful may be useful only because they trigger a placebo effect.”
Marcus has also criticized Consumer Reports. “Consumer Reports and its Health Newsletter provide sound advice about nutrition and medicine, with one exception: their recommendations concerning alternative therapies, especially dietary supplements.”
He continues: “In the absence of sound evidence about the efficacy of herbals beyond a placebo effect, uncertainty about their activity and purity, and growing information about their adverse effects, their use should be discouraged.”
After the FDA’s warning in 2000 about Aristolochia, Dr. Subhuti Dharmananda, of the Institute for Traditional Medicine, Portland, Oregon, addressed the issue of the herb’s toxicity and the renal failure situation in Belgium. “The way that they were used in the Belgian clinic did not mirror any traditional practices in China,” he writes. “The combination of Western drugs and Western herbs, mesotherapy, and other techniques that were applied over an extended period at the clinic is not congruent with the traditional use of the herbs in China.
In modern practice in the West, herbal remedies are often recommended by health professionals for long-term use, at least so long as they continue to provide symptomatic relief or are believed to be of continuing benefit on some other basis. In at least one case of renal failure in England claimed to be associated with Aristolochia, a woman had been taking a decoction intended to treat eczema that included mutong for two years. In one case presented in Japan, a woman had been taking what was described as a “health food” product that was a “traditional remedy” for atopic dermatitis for three years; presumably it contained mutong derived from Aristolochia.
The role of modern drugs might also be critical to the development of renal problems when taking herbs containing AA. In the U.S., it was recently reported that half of all adults now take an average of two prescription drugs a year and that more than a quarter of all adults take four or more prescription drugs (after age 65, the number of prescribed drugs rises further). Dozens of approved drugs have the potential for causing adverse renal effects. These figures for drug use do not include the myriad over the counter drugs that people may use, including some, such as analgesics, that can contribute to renal failure. It is possible that use of the herb medicines derived from Aristolochia plants when used alone rarely, if ever, cause renal failure, but that when combined with certain drugs, the toxicity develops.
While Aristolochia plants may have been used with considerable freedom of adverse effects for centuries, and although there may exist safe ways to utilize plants that contain AA today, it remains unclear what those ways are or how to enforce sticking to the safe regimen when using the herbs. A halt to their use remains one of the only safeguards, and the FDA action is justified. Most of the Aristolochia herbs used in China are not critical to herbal therapeutics in the West. Indeed, it appears that the majority of Aristolochia plants that have been used in the West during the past three decades were imported as substitutes for other non-Aristolochia plant materials that may have equally well served the purposes of the herbalists.”
On average Americans spend $300 billion per year on prescription drugs, and $20 billion on herbs and other dietary supplements. U.S. annual spending on prescription medicines is expected to climb as high as $400 billion by 2020.
Grollman, D. M. Marcus. Global hazards of herbal remedies: lessons from Aristolochia: The lesson from the health hazards of Aristolochia should lead to more research into the safety and efficacy of medicinal plants. EMBO reports, 2016; 17 (5): 619 DOI: 10.15252/embr.201642375