The birthwort, also known as pipevine or Dutchman's Pipe vine, is a common name for plants in the genus Aristolochia. Birthwort is notable for its use in Western herbal medicine, traditional Chinese medicine (TCM), Ayurvedic medicine, and many indigenous herbal traditions. This is despite causing cancer and kidney failure. Home run for evidence-based medicine!
Given the long and well-documented history of medical usage (since 300 BCE) and the extreme toxicity of birthwort, it could be argued that this is one of the best cases against the "appeal to tradition" and against the related "appeal to ancient wisdom", "appeal to nature" and "argument from authority" fallacies.
Aristolochia has been used for thousands of years in various cultures worldwide as a panacea for numerous diseases. Birthwort was especially thought to be beneficial for women giving childbirth; the name Aristolochia derives from the Greek "άριστο λοχεία" for "noble birth" or "excellent birth". Aristolochia was commonly used in ancient Greek, Roman, and Byzantine pharmaceutical recipes for various conditions, including kidney ailments, peritonsillar abscess, bladder stones, edemas, gout, snakebite, and uterine complaints.
“”There are many uses of it for various purposes are enumerated; it is best for bruises on the head, good also for other wounds, against snake-bites, to produce sleep, for the womb as a pessary: for some purposes it is soaked with water and applied as a plaster, for others it is scraped into honey and olive-oil: against snake-bites it is drunk in sour wine and also sprinkled over the bite; to induce sleep it is given pounded up in black dry wine: in cases of prolapsus uteri it is used in water as a lotion. This plant then seems to have a surpassing variety of usefulness.
Other ancient writers who recommended birthwort for medical treatment included: Diocles of Carystus (c. 375–295 BCE), Philinus of Cos (3rd century BCE), Heraclides of Tarentum (c. 2nd–3rd century BCE), Aulus Cornelius Celsus (c. 25 BCE–c. 50 CE), Scribonius Largus (c. 1–c. 50 CE), Pedanius Dioscorides (c. 40–90 CE), and Pliny the Elder (23–79 CE). Dioscorides wrote the first major book on herbal medicine between 50 and 100 CE, De Materia Medica, which was highly influential for over 1500 years.
Saint Hildegard of Bingen (1098-1179 CE), a medieval polymath, wrote several books, including the 9-volume Physica. Physica was written between 1151-1158 CE and includes a description of plants and their medical uses. A modern English translation of the book includes this description of birthwort:
“”Birthwort (byverwurtz) is hot, and a bit cold. Therefore, pulverize its root and leaves and add half as much feverfew powder and one-fourth as much cinnamon powder. Mix them together and eat it daily, either with bread or with warm wine, or in broth. You will have no great or lasting infirmity until the time you die. No one should shun powder prepared this way. If a healthy person eats this powder daily, he will not be lying sick in bed a long time. If he is sick and eats it, he will be well. In order to conserve this powder safely throughout the year, it should be placed in a new, earthenware vessel, enclosed in the earth. It will retain its powers.
Hildegard's Physica was the foundation of Hildegardian medicine, a now-minor field of quackery that is mostly practiced in Germany and Switzerland; it is not clear whether modern practitioners of Hildegardian medicine have prescribed birthwort.
Traditional Chinese medicine
The Bencao Gangmu (本草綱目) or Compendium of Materia Medica was first published in 1578 by Li Shizhen (李時珍). Aristolochia appears in the Bencao Gangmu as "馬兜鈴" (mǎ dōu líng). Bernard Read's analysis of the Bencao Gangmu reported three species of Aristolochia (A. debilis, A. recurvilabra, and A. contorta), but A. recurvilabra is now considered a synonym of A. debilis.
“”As the open, cellular structure of these fruits is considered by the Chinese to resemble the human lung, they are strongly recommended in all forms of pulmonary affections. They have very little taste or smell and are not poisonous [emphasis added]. Other diseases for which they are prescribed are hemorrhoids and ascites. One of the fruits burned over a lamp, and the charred remains taken with wine, is considered a sure cure for heartburn.
For A. debilis, Stuart stated:
“”It is a highly valued remedy, being prescribed in combination with such drugs as ginseng and China root [Smilax china]. It is used in digestive disorders and chronic fluxes, especially those of women and children. It is regarded as being especially useful in summer diarrhoea and in chronic diarrhoea and dysentery… But in addition, this is regarded to be especially efficacious in expelling the 蠱 (Ku) poison. So highly is it valued for this purpose by the inhabitants of Lingnan that they have given it the name of 三百兩銀藥 (San-pai-liang-yin-yao) "three-hundred-taels-of-silver-drug." It is also considered to be a good remedy for snake-bite.
The Bencao Gangmu has remained in use continuously since its publication and was replaced in China by the 10-volume Zhong Hua Ben Cao (中华本草, Encyclopedia of Chinese Materia Medica) in 1999, which includes 23 species of Aristolochia, with little mention of toxicity. The species A. manshuriensis, A. fangchi, A. debilis, and A. contorta are included in the official Pharmacopoeia of the People's Republic of China.
In 1597, John Gerarde wrote what became a very popular book, called The Herball, or Generall Historie of Plantes. The book cited three ancient authorities on the uses of "birthwoorte": Pedanius Dioscorides, Galen (129–c. 200/c. 216 CE), and Pliny the Elder. The uses for "long birthwoorte" (A. longa) and "round birthwoorte" (A. rotunda) included:
- Dioscorides writeth, that a dram waight of long Birthwoort drunke with wine and also applied is good against serpents and deadly things: and that being drunk with myrrhe and pepper, it expelleth whatsoever is left in the matrix after the childe is delivered, the flowers also & dead children: and that being put up in a pessarie, it performeth the same.
- Round Birthwoorte serveth for all these things, and also the rest of the other poisons: it is likewise available against the stuffing of the lungs, the hicket, the shakings or shiverings of agues, hardness of the milt or spleene, burstings, cramps and convolutions, paines of the sides, if it be drunk with water.
- It plucketh out thornes, splinters, and shivers, and being mixed in plaisters, or pulteses, it draweth foorth scales or bones, removeth rottennesse and corruption, mundifieth and scoureth foule and filthie ulcers, and filleth them up with new flesh, if it be mixed with Ireos and honey.
- Galen saith, that branched Birthwoort is of a more sweete and pleasant smell: it therefore is used in ointments; but it is weaker in operations than the former ones.
- Birthwoort as Plinie writeth being drunk with water is a moste excellent remedie for crampes and convulsions, burses, and for such as have fallen from high places.
- It is good for them that are short winded, and troubled with falling sickness.
- The rounde Aristolochia doth beautifie, clense, and saften the teeth, if they be often frosted or rubbed with the powder thereof.
A. serpentaria is known to have been used medicinally by several Native American tribes (Koasati, Delaware, Osage, Choctaw, Náhuatl, Cherokee, Natchez, Alabama, Micmac, Mohegan, and Penobscot). Starting as early as the 1600s, European colonists, calling the plant "Virginia snakeroot", used it to treat snakebite.
“”Said to be useful as an aromatic stimulant in rheumatism and gout and for removing obstructions, etc., after childbirth. Dose, 1/2 to 1 drachm of the powdered root.
A. argentina root is used in that republic as a diuretic and diaphoretic, especially for rheumatism.
A. indica is used as an emmenagogue, antiarthritic, stomachic, purgative and vermifuge, and in the East Indies is used for similar purposes as the American and European species.
A. sempervirens is said to be used by the Arabians as a remedy against the poisonous effects of snake-bite.
A. foetida in Mexico is used as a stimulant to foul ulcers.A. serpentaria used in bilious, typhoid and typhus fevers, smallpox, pneumonia, amenorrhoea and fevers of a septicaemic type. It is often given in combination with Peruvian Bark [i.e., Cinchona spp.], rendering it more active and preventing ill effects on the stomach. It is also used in North America, as are several other varieties of the species, as an alexiteric and for the bites of mad dogs.
In 1881 the oldest skeptical organization in the world, Vereniging tegen de Kwakzalverij (VtdK, the Dutch Association Against Quackery), had already warned against pills with birthwort as a form of quackery and described them as "pills made of nothing", but added that they "contain nothing harmful". Well, the VtdK was half-right…
Discovery of toxicity
“”Soon after finishing the course of their medicine, they became valetudinary [sickly] In different shapes; and particularly were much affected with dyspeptic, and what are called nervous complaints, with lowness of spirits.
…In every one of them, before a year had passed after finishing the course of the powders, some hydropic symptoms appeared, which gradually increasing in the form of an ascites or hydrothorax, especially the latter joined with anasarca [swelling of the whole body], in less than two or at most three years proved fatal.
In 1888, a letter on the continuing usage of Portland Powder was published in The Peoria Medical Monthly, anecdotally stating that "every person treated by them died before the expiration of two years!"
As a result of scientific research conducted in the 20th century, it was discovered that birthwort can cause cancer and kidney failure because it contains aristolochic acid (AA), which is, in the amounts present in birthwort, a poison. Aristolochic acid is one of the most potent carcinogens in the Carcinogenic Potency Database.
In Belgium, between 1990 and 1992, a weight-loss spa using TCM herbs thought they were giving their clients Stephania tetrandra and Magnolia officinalis to help with weight loss. In reality, the herbal supplements contained Aristolochia fangchi; as a result, more than 100 out of its 1800 patients developed kidney failure. Several also developed urothelial and kidney cancers, and 39 had to undergo kidney transplants. Because TCM allows for the substitution of identically- or similarly-named plants, botanically unrelated plants may be substituted. In this case, the relatively safe Stephania tetrandra (漢防己, hàn fángjǐ) was intended for the clients, but the lethal Aristolochia fangchi (廣防己, guǎng fángjǐ) was given to the clients. As epidemiologist Geoffrey Kabat noted:
“”What is essential to realize is that the effects of Aristolochia [birthwort] were identified only thanks to the large cluster of cases of kidney failure occurring in young women who had attended the same spa. It is much more likely that isolated cases will go unnoticed, as happened with ephedra, and it could take years to identify a common cause.
People failed to recognize the nephrotoxic effects of Aristolochia in spite of its use in many cultures worldwide over thousands of years. In an interview, [Arthur P.] Grollman explained why: "The reason, of course, is quite simple. It's painless, and the damage happens much later, so you don't put together the fact that you took this medicine and four years later, you have kidney failure. It's been part of Ayurvedic, European, Chinese, and South American medicine for centuries. All of the great civilizations have used it. And not one reported its toxicity until the Belgians did 20 years ago. There are certain things that tradition can't tell you."
By 2002, the International Agency for Research on Cancer (IARC) had concluded that herbal remedies containing Aristolochia are carcinogenic to humans. This conclusion was based upon sufficient evidence of carcinogenicity of AA in animals and sufficient evidence of carcinogenicity of herbal remedies containing Aristolochia in humans. In 2012, IARC revised its evaluation to conclude that there was also sufficient evidence that AA itself is carcinogenic to humans. This conclusion was based on sufficient additional evidence showing that extracts of plants containing AA are carcinogenic to animals and limited evidence that AA itself is carcinogenic to humans.
European birthwort (A. clematitis), which has also been used as a medicine, has been linked to Balkan endemic nephropathy (BEN), though this conclusion has taken decades to arrive at since the time that BEN was first diagnosed in the 1920s. The source of BEN is likely wheat that is contaminated by seeds of A. clematitis and/or bioaccumulation in grain from soil and water where A. clematitis has grown. BEN has been found in northern Bosnia, eastern Croatia, Serbia, Kosovo, southwestern Romania, and northwestern Bulgaria. A 2016 study confirmed that AA-contaminated soil is a pathway to human exposure via bioaccumulation in food crops. A 2018 study further confirmed that AAs are long-lived soil contaminants, and AA soil contamination in the Balkans strongly correlated with BEN.
The actual number of aristolochic acid nephropathy (AAN) cases, which is usually fatal, is unknown and probably underestimated. "Approximately 5–10% of individuals exposed to AA develop renal insufficiency and/or cancer", suggesting that there may be a genetic component to AA nephropathy.
Additionally, it is suspected that AA exposure is associated with liver cancer (hepatocellular carcinoma, HCC), particularly for people exposed to the hepatitis B virus. A 2017 study found that large percentages of people with HCC were exposed to AA in some regions: 78% in Taiwan, 47% in mainland China, and 29% in southeast Asia.
Asarum is a genus of plants used medicinally that are in the same family as the Aristolochia genus (Aristolochiaceae). Asarum species contain AA and also contain AA analogs. Asarum species are used in TCM (xixin, 细辛) and are traditionally used by Native Americans. As of 2017, it is unclear how safe Asarum species are, and only 8 cases of AAN from Asarum ingestion have been reported in 45 years.
Caterpillars love it, birds hate it
Many species of Aristolochia are food for the larvae (caterpillars) of species of swallowtail butterflies (family Papilionidae). It has been demonstrated that AA is sequestered in the caterpillars and retained in the adult butterflies, making them unpalatable to most predators (mainly birds).
Not all species of Aristolochia plants are palatable to all species of swallowtails. It has been found that introduced South American Aristolochia elegans in Queensland, Australia, is lethal to the larvae of native swallowtails, the Richmond (Ornithoptera richmondia) and Cairns (Ornithoptera euphorion) birdwing butterflies. This suggests that the swallowtails and Aristolochia have been engaged in an evolutionary arms race.
In 2003, two years after the US FDA issued warnings about herbal remedies containing AA, it was reported that 19 herbal products were available over the internet with Aristolochia as a stated ingredient, and 95 additional products were suspected of containing AA. In 2018, it was reported that Aristolochia is still available for purchase on the internet.
In 2010, the World Health Organization (WHO) effectively encouraged the use of A. indica in a publication on Ayurvedic medicine. In doing so, they acted contrary to the information provided by one of their agencies, IARC. The WHO has continued to encourage the use of herbal medicine despite known problems with both efficacy and safety of herbal medicines.
The English-language portion of the internet regarding birthwort consists mainly of documents describing the presence of aristolochic acid in birthwort and the plant's use in traditional medicine, as well as scientific studies of the plant's composition and toxicity. In other languages, however, many herbalist sites actively recommend birthwort as a treatment for all sorts of things. Needless to say, such claims of efficacy are never accompanied by any actual statistical evidence.
A 2016 survey of plant food supplements of "botanicals of concern" (herbal medicines likely to contain AA) found that 3 of 18 samples (17%) contained AA and that a literature survey found that 206 of 573 samples (36%) contained AA.
A 2019 review found that AA was widespread in Chinese patent medicine.
A. chilensis is used in Chilean herbalism for various indications, including arthritis, hemorrhoids, gout, inflammation, weight loss, and overall health. It is also used in teas. According to researchers at Chile's Universidad de Santiago, consuming 1mg of the plant can cause harmful effects months after it was initially ingested.
In Wenzhou, China, 102 patients were reported with end-stage nephropathy between 2004 and 2013. These patients had an astoundingly high incidence of cancer, 41%, which is typical in populations of patients with AAN.
As of 2016, Chinese companies were still making A. debilis, A. manshuriensis, A. fangchi, and A. bracteolata available for export for medicinal purposes.
In 2016, it was reported that AA I and AA II were detected in traditional medicine known as chiniy-trèf, which is used in the overseas French region of Martinique. Chiniy-trèf is used for poisoning and hexes. It is prepared from caterpillars of the butterfly Battus polydamas, which feed on the leaves of A. trilobata.
A. indica, known as isvari, is used in Ayurvedic medicine. It is also found in Pakistan.:37-38 According to Chandrakant Bhanushali, General Secretary of the Ayurvedic Drug Manufacturers Association, the doses typically used are much lower (100× less) than the toxic doses in Belgium. This should not be particularly comforting since AA is sequestered by blood albumin, which also restricts excretion. According to Bhanushali, A. indica is found in two medicines used internally: poogakhanda and gorochanadi vati, but usage of these medicines is negligible. Also not particularly comforting is that the main ingredient of poogakhanda (or pooga khanda) is another human carcinogen, betelnut (Areca catechu), and gorochanadi contains the toxic heavy metal lead as an ingredient. Isvari was included in a list of Ayurvedic herbs without comment in a 2010 WHO report on training Ayurvedic medicine practitioners.
A. bracteolata (syn. A. bracteata) is also used in Indian traditional medicine. It is used to treat parasitic worms and snakebites, induce menstruation, and for childbirth.:36-37
In 2019, Indian researchers investigated whether A. krisagathra or A. bracteolata might be useful for male contraception.:305-324 The researchers acknowledged that the plants contain AA but claimed that AA has many medicinal properties without acknowledging the danger of human use.:308
In Morocco, A. baetica and A. longa were used among herbalists as of 2015, often substituted by the differently toxic and unrelated Bryonia dioica under the common name "bereztem".
A 2017 article on Pakistani folk medicine reported on four plant species widely used in folk medicine, including A. indica. The article analyzed the plants' antimicrobial, antioxidant, cytotoxic, and anti-inflammatory potential and concluded two of the non-Aristolochia species had the strongest effects. The authors did not study safety or mention the hazardousness of Aristolochia. Nonetheless, NaturalNews and its affiliate site 'Science.News' reported on this article, distorting its results and touting A. indica.
Papua New Guinea
It was reported in 2007 that A. ruiziana (known locally as bejuco de contra-aire) is used traditionally in the Amazonian part of Peru for "untangling a person who is confused or having trouble progressing in life."
A. clematitis is recommended by many herbalists in Romania, being used in tinctures, infusions, and creams, and used topically for a wide variety of diseases, including burns, varicose veins, eczema, psoriasis, acne, urticaria, hemorrhoids, skin cancer, genital herpes, and boils, among other things. It is also claimed that, in low doses, birthwort taken internally is not carcinogenic but is, in fact, effective treatment for several forms of cancer and many other diseases, and that birthwort "is one of the most powerful medicinal plants we have. It has so many possible applications that it would take entire tomes to describe them. It would not be amiss to say that the potency of birthwort's beneficial effects could be compared to that of an atomic bomb."
A study of Aristolochia in traditional Korean medicine found that AA is found in some Korean herbal remedies, that South Koreans have experienced AAN, and that there is a possibility that AAN is under-diagnosed in South Korea.
A. indica is used traditionally as a tonic, a stimulant, an emmenagogue (increasing pelvic blood flow), an emetic, and for fevers.:56
It has been estimated that about a third of Taiwan's herbal medicine prescriptions contain AA, and birthwort is considered a significant cause of kidney failure and upper urinary tract cancer in Taiwan. In Taiwan, 76% of clear cell renal cell carcinoma (ccRCC) cases had been exposed to AA based on an examination of DNA adducts. A case-control study found that cumulative consumption of 250 mg of AA increased the risk of ccRCC by odds ratio (OR)=1.25.
A limited (i.e., non-random) 2014 survey of 30 dietary supplements in the United States found that 20% of samples contained AA I and 7% contained AA II. Presumably, the sample was of supplements that were suspected of containing AA.
One of the more popular herbal medicine books, The Herb Book by John Lust, was reprinted in 2014 and has not been revised since its initial publication in 1974. Though there is a warning on the usage of A. clematitis in the book, it is far from sufficient, particularly because the full danger was not known in 1974 and because instruction for usage is still given. The warning states:
“”CAUTION: Birthwort contains a substance that acts similar to the poisonous alkaloid colchicine.[note 2] Use with care, preferably under medical direction.
If you find a medical professional to supervise your consumption of A. clematitis, you're in more trouble than you think.
- Portland Powder contained "equal parts of roots of round birthwort [A. rotunda] and gentian [Gentiana spp.], of the leaves of germander [Teucrium spp.] and ground pine, and of the tops of the lesser centaury [Centaurium pulchellum]…"
- As an aside, colchicine (extracted from plants of the genus Colchicum, "autumn crocus") is also a renal (kidney) toxin, but its mechanism of action is different than that of aristolochic acid. Lust was a naturopath and not a toxicologist, so his understanding of toxicology was superficial.
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- Повечето хора смятат, че хранителните добавки са безопасни. А дали е така?
- La maldición de las orejas de zorro, llega a su fin (25 de septiembre de 2013) Urbatorium.
- La planta medicinal chilena “Oreja de zorro” provoca cáncer. Septiembre 24, 2013 Info-natura
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- File:Alibaba Aristolochia.pdf — Aristolochia for sale on Alibaba in 2016
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- Ayurvedic Medicine Information: Puga Khanda – Benefits, Dosage, Ingredients, Side Effects
- Ayurvedic Medicine Information: Gorochanadi Gulika – Benefits, Dosage, Ingredients And Side Effects
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- Substitution between Aristolochia and Bryonia genus in North-Eastern Morocco: toxicological implications by A. Yamani et al. J. Ethnopharmacol. 2015 May 26;166:250-60. doi: 10.1016/j.jep.2015.03.036. Epub 2015 Mar 19.
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- Surpriza de pe lista celor 116 produse periculoase întocmită de OMS: Mărul lupului este cancerigen 02 noiembrie 2015 21:45 Libertatea.
- Ceaiuri care te pot îmbolnăvi Ziarul Ring
- Mărul lupului, planta care poate învinge cancerul Efemeride.
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