Aristolochia

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 beyond) 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.
==History==
===Ancient times===
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.Ancient Medicinal Use of Aristolochia: Birthwort's Tradition and Toxicity by John Scarborough, Pharmacy in History, Vol. 53, No. 1, 2011.
 , a student of Aristotle, wrote the first botanic description and the first report on the pharmaceutical properties of birthwort in c. 300 BCE:
Other ancient writers who recommended birthwort for medical treatment included: , (3rd century BCE), , , , , and Pliny the Elder . Dioscorides wrote the first major book on herbal medicine between 50 and 100 CE, which was highly influential for over 1500 years.De Materia Medica by Dioscorides Pedanius, translated by T. A. Osbaldeston & R. P. A. Wood (2000) IBIDIS. ISBN 0620234350. Aristolochia appears on pp. 368-371 of the translation.
===Medieval era===
Aristolochia appeared in the (c. 400 CE), the foundational text for Ayurvedic medicine.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 by Arthur P. Grollman & Donald M. Marcus (2016) EMBO Reports 17(5):619-25. doi: 10.15252/embr.201642375.
Saint (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:
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.
===Post-Medieval era===
====Traditional Chinese medicine====
The (本草綱目) or Compendium of Materia Medica was first published in 1578 by (李時珍). Aristolochia appears in the Bencao Gangmu as "馬兜鈴" (mǎ dōu líng).本草綱目/草之七 Wikisource (Compendium of Materia Medica / Grass, Seven) Bernard Read's analysis of the Bencao Gangmu reported three species of Aristolochia (A. debilis, A. recurvilabra, and A. contorta),Chinese Medicinal Plants from the Pen Tsʻao Kang Mu 本草綱目 A.D. 1596 by Bernard E. Read (1936). Peking Natural History Bulletin, 3rd ed. but A. recurvilabra is now considered a synonym of A. debilis.Aristolochia recurvilabra Hance The Plant List: A Working List of All Plant Species.
G. A. Stuart reported that two species of Aristolochia were in use in China in 1911, A. kaempferi (馬兜鈴) and A. recurvilabra (A. debilis).Chinese Materia Medica. 1. Vegetable Kingdom by G. A. Stuart (1911). Presbyterian Mission Press, revised from F. Porter Smith. For A. kaempferi, Stuart stated:
For A. debilis, Stuart stated:
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.Health Department and National Chinese Medicine Management Office (ed.). Zhong Hua Ben Cao, 3–460–509. Shanghai Science Technology Publication. 1999. ISBN 7532351068. The species A. manshuriensis, A. fangchi, A. debilis, and A. contorta are included in the official Pharmacopoeia of the People's Republic of China.Pharmacopoeia of the People's Republic of China (2005). Chemical Industry Press, 2 volumes: ISBN 7502520627 and ISBN 7502520635.
====Western medicine====
In 1597, 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, , and Pliny the Elder.The Herball, or Generall Historie of Plantes by John Gerarde (1597). John Gerard The uses for "long birthwoorte" (A. longa) and "round birthwoorte" (A. rotunda) included:
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.Florida Ethnobotany by Daniel F. Austin (2004) CRC Press, pp. 109-110. ISBN 0849323320.
The 1931 book A Modern Herbal by reported the following on Aristolochia (note that no mention whatsoever is made of any possible side effects):
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…Reconfortatief of gezondheids en zeer versterkende pillen (Maandblad 15 juli 1881, jaargang 1, nummer 7) (9 jan 2009 | Van de Webredactie | Laatste wijziging: 10 jun 2009) KwakzalverijReconfortatief of gezondheids en zeer versterkende pillen (15 juli 1881) Nederlands Tijdschrift tegen de Kwakzalverij 1(7).
==Discovery of toxicity==
===Early reports===
William Cullen's Materia Medica reported in 1789 that an Aristolochia-containing substance called "Portland Powder" was effective in treating gout but,A Treatise of the Materia Medica by William Cullen (1789) Volume 2, page 54
In 1815, the father of modern toxicology, reported that Aristolochia was lethal to dogs.De l'Aristoloche (aristolochia clematitis) In Traité des poisons tiré des régnes minéral, vétal et animal; ou, Toxicologie génerale, considére sous les rapports de la physiologie de la pathologie et de la médécine légale by M. P. Orfila (1815) 3rd ed., volume 2, pp. 276-279.
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!"Beware of Nostrums (1888) The Peoria Medical Monthly volume 8, page 128.
===Modern research===
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.Chung-Hsin Chena, et al. "Aristolochic acid-associated urothelial cancer in Taiwan." Proceedings of the National Academy of Sciences. 2012 April 9. Aristolochic acid is one of the most potent carcinogens in the Carcinogenic Potency Database.Research and Publications on Herbal Products Known or Suspected to Contain Aristolochic Acid, a Human Carcinogen (archived from April 27, 2017).Aristolochic acid, sodium salt: Cancer Test Summary (archived from April28, 2017).
In Belgium, between 1990 and 1992, a weight-loss spa using TCM herbs thought they were giving their clients and 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.Aristolochic acid nephropathy: A worldwide problem by Frédéric D. Debelle et al. (2008) Kidney International 74:158–169; doi:10.1038/ki.2008.129.Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi) by J. L. Nortier et al. N. Engl. J. Med. 2000 Jun 8;342(23):1686-92. As epidemiologist Geoffrey Kabat noted:
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.Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 82 (2002) World Health Organization, International Agency for Research on Cancer. 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.Review of Human Carcinogens IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 100A (2012) World Health Organization, International Agency for Research on Cancer.
European birthwort (A. clematitis), which has also been used as a medicine, has been linked to (BEN), though this conclusion has taken decades to arrive at since the time that BEN was first diagnosed in the 1920s.Fifty years of Balkan endemic nephropathy: daunting questions, elusive answers by V. Batuman. Kidney International, Volume 69, Issue 4, 2 February 2006, Pages 644–646.Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, aristolochic acid nephropathy by Marc E. De Broe. Kidney International 81(6):513-5 · March 2012. 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.Uptake and Accumulation of Nephrotoxic and Carcinogenic Aristolochic Acids in Food Crops Grown in Aristolochia clematitis-Contaminated Soil and Water by W. Li et al. J. Agric. Food Chem. 2016 Jan 13;64(1):107-12. doi:10.1021/acs.jafc.5b05089.Quantitation of Aristolochic Acids in Corn, Wheat Grain, and Soil Samples Collected in Serbia: Identifying a Novel Exposure Pathway in the Etiology of Balkan Endemic Nephropathy by W. Chan et al. J. Agric. Food Chem. 2016 Jul 27;64(29):5928-34. doi:10.1021/acs.jafc.6b02203. Epub 2016 Jul 13. The widespread process of plants leaching chemicals into soil to promote or suppress other organisms is known as allelopathy, and is known to occur in other species of Aristolochia.Allelopathic effects of aqueous extracts of Artistolochia sic esperanzae O. Kuntze on development of Sesamum indicum L. seedlings by Ana Beatriz Gatti et al. (2010) Acta Botanica Brasilica 24(2): 454-461.
BEN has been found in northern Bosnia, eastern Croatia, Serbia, Kosovo, southwestern Romania, and northwestern Bulgaria.Organic compounds in water extracts of coal: Links to Balkan endemic nephropathy by S. V. M. Maharaj et al. (2013) Environmental Geochemistry and Health 36(1). doi:10.1007/s10653-013-9515-1 A 2016 study confirmed that AA-contaminated soil is a pathway to human exposure via bioaccumulation in food crops.Uptake and Accumulation of Nephrotoxic and Carcinogenic Aristolochic Acids in Food Crops Grown in Aristolochia clematitis-Contaminated Soil and Water by W. Li et al. (2016) J. Agric. Food Chem. 64(1):107-12. doi:10.1021/acs.jafc.5b05089. Epub 2015 Dec 22. A 2018 study further confirmed that AAs are long-lived soil contaminants, and AA soil contamination in the Balkans strongly correlated with BEN.Aristolochic Acids as Persistent Soil Pollutants: Determination of Risk for Human Exposure and Nephropathy from Plant Uptake by W. Li et al. (2018) J. Agric. Food Chem. 66(43):11468-11476. doi:10.1021/acs.jafc.8b04770.
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.Genetic loci that affect aristolochic acid-induced nephrotoxicity in the mouse by Thomas A. Rosenquist. (2011) Am. J. Physiol. Renal Physiol. 300(6):F1360–F1367.
Additionally, it is suspected that AA exposure is associated with liver cancer (hepatocellular carcinoma, HCC), particularly for people exposed to the hepatitis B virus.Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection by C. J. Chen et al. (2018) Int. J. Cancer. doi: 10.1002/ijc.31544. 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.Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia by A. W. T. Ng et al. (2017) Sci. Transl. Med. 9(412). pii: eaan6446. doi: 10.1126/scitranslmed.aan6446.
It is suspected that all species of Aristolochia contain some form of aristolochic acid (AA),Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2-A global assessment based on bibliographic sources by M. Heinrich et al. J. Ethnopharmacol. 2009 Aug 17;125(1):108-44. doi: 10.1016/j.jep.2009.05.028. Epub 2009 Jun 6. and dozens of species are known to contain either AA or AA analogs.Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinogenicity, and Underlying Mechanisms by Jiayin Han et al. (2019) Frontiers in Pharmacology 10. doi:10.3389/fphar.2019.00648.
===Asarum===
Asarum is a genus of plants used medicinally that are in the same family as the Aristolochia genus (Aristolochiaceae). Asarum species contain AAAristolochic Acid: FDA Warns Consumers to Discontinue Use of Botanical Products that Contain Aristolochic Acid (April 11, 2001) U.S. Food and Drug Administration (archived from July 10, 2009). and also contain AA analogs.Medicinally Used Asarum Species: High-Resolution LC-MS Analysis of Aristolochic Acid Analogs and In vitro Toxicity Screening in HK-2 Cells by Johanna Michl et al. (2017) Front. Pharmacol. 8:1-9. 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.Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines by E. J. Kim et al. (2013) J. Ethnopharmacol. 146(1):40-61. doi: 10.1016/j.jep.2012.12.027.
===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).Sequestration of aristolochic acids by the pipevine swallowtail, Battus philenor (L.): evidence and ecological implications by Karen R. Sime (2000) Chemoecology 10(4):169-178. doi:10.1007/PL00001819.The occurrence of aristolochic acids in neotropical troidine swallowtails (Lepidoptera: Papilionidae) by Clécio F. Klitzke & Keith S. Brown Jr. (2000) Chemoecology 10(2):99-102. doi.org/10.1007/s000490050013.
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.Conserving the Richmond Birdwing Butterfly over two decades: Where to next? by Don Sands (2008). Ecological Management & Restoration vol. 9 no. 1. doi: 10.1111/j.1442-8903.2008.00382.x."Notes on certain Lepidoptera ovipositing on plants which are toxic to their larvae" by R. Straatman (1962) Journal of the Lepidopterists Society 16:99–103. This suggests that the swallowtails and Aristolochia have been engaged in an evolutionary 
==Continuing usage==
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.Aristolochic Acid, an Herbal Carcinogen, Sold on the Web after FDA Alert by L. S. Gold & T. H. Slone (2003) New England Journal of Medicine 349:16 (archived from April 11, 2017). In 2018, it was reported that Aristolochia is still available for purchase on the internet.Aristolochia, a nephrotoxic herb, still surfs on the Web, 15 years later by V. Maggini et al. Intern. Emerg. Med. 2018 Mar 1. doi: 10.1007/s11739-018-1813-2.
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.Traditional Medicine Strategy 2014–2023 (2013) World Health Organization. ISBN 9789241506090. (archived from November 29, 2018).
A 2009 literature review found that 99 species of Aristolochia have been used ethnobotanically, but only 24 of these species have been studied phytochemically.Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2—a global assessment based on bibliographic sources by M. Heinrich et al. J. Ethnopharmacol. 2009 Aug 17;125(1):108-44. doi: 10.1016
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.Aristolochic acids in the roots of aristolochia chilensis, a dangerous Chilean medicinal plant by A. Urzua et al. Journal of the Chilean Chemical Society 58.4 (2013): 2089-2091. Needless to say, such claims of efficacy are never accompanied by any actual statistical evidence.
In 2016, it was estimated that ~100,000 people in the Balkans were at risk of BEN and that ~25,000 had BEN.Balkan endemic nephropathy: an update on its aetiology by M. Stiborová et al. Arch Toxicol. 2016 Aug 19 (Epub ahead of print).
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.Risk assessment of plant food supplements and other herbal products containing aristolochic acids using the Margin of Exposure (MOE) approach by R. Abdullah et al. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2016 Nov 28. [Epub ahead of print]. DOI:10.1080/19440049.2016.1266098.
A 2019 review found that AA was widespread in Chinese patent medicine.
===Algeria===
A. longa is widely used in traditional Algerian medicine. It is used to treat cancer,Oh, the irony! skin infections, and diabetes.Ethnobotanical study, antifungal activity, phytochemical screening and total phenolic content of Algerian Aristolochia longa by B. Benarba & B. Meddah J. Intercult. Ethnopharmacol. 2014 Oct-Dec;3(4):150-4. doi: 10.5455/jice.20140826030222.
===Bangladesh===
As of 2013, A. indica was in use among herbalists in Bangladesh. Knowledge of toxicity among herbalists was limited, and administered doses were often "very high".Is aristolochic acid nephropathy a widespread problem in developing countries? A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical-phytochemical approach by J. Michl et al. J. Ethnopharmacol. 2013 Aug 26;149(1):235-44. doi: 10.1016/j.jep.2013.06.028. Epub 2013 Jun 24.
===Brazil===
A 2015 ethnomedicinal study of Paraná, Brazil, in the vicinity of Parque Estadual da Cabeça do Cachorro found that A. triangularis was the second most frequently used herbal medicine.Ethno-medicinal study of plants used for treatment of human ailments, with residents of the surrounding region of forest fragments of Paraná, Brazil by M. Bolson et al. J. Ethnopharmacol. 2015 Feb 23;161:1-10. doi: 10.1016
===Bulgaria===
A. clematitis is used in Bulgarian herbal medicine for several indications, including as a diuretic.Повечето хора смятат, че хранителните добавки са безопасни. А дали е така?
===Chile===
A. chilensis is used in Chilean herbalism for various indications, including arthritis, hemorrhoids, gout, inflammation, weight loss, and overall health.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 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.
===China===
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.Analysis of potential risk factors for cancer incidence in patients with aristolochic acid nephropathy from Wenzhou, China by M. Sun et al. Ren. Fail. 2015 Mar;37(2):209-13. doi: 10.3109/0886022X.2014.990347. Epub 2014 Dec 26.
As of 2016, Chinese companies were still making A. debilis, A. manshuriensis, A. fangchi, and A. bracteolata available for export for medicinal purposes. — Aristolochia for sale on Alibaba in 2016
===Colombia===
A. anguicida was reported to be used in traditional medicine on the Atlantic Coast of Colombia. AA I was previously detected in A. anguicida.Folk medicine in the northern coast of Colombia: an overview by Harold Gómez-Estrada et al. J. Ethnobiol. Ethnomed. 2011; 7: 27. doi:10.1186/1746-4269-7-27.
===Ecuador===
The indigenous Awá people of Ecuador use several species of Aristolochia in their traditional medicine, including two that are ingested.Por el Camino Culebrero: Etnobotánica y Medicina de los indígenas Awá del Sábalo (Nariño) by Jaime Hernando Parra Rizo & Susan Virsano Bellow (1994) Ediciones ABYA-YALA. ISBN 9978990801.
===France===
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.Detection of aristolochic acids I and II in "Chiniy-trèf", a traditional medicinal preparation containing caterpillars feeding on Aristolochia trilobata L. in Martinique, French West Indies by X. Cachet et al. Toxicon. 2016 May;114:28-30. doi: 10.1016/j.toxicon.2016.02.013. Epub 2016 Feb 12.
===India===
thumb|right|100px|A. indica
A. indica, known as isvari, is used in Ayurvedic medicine. It is also found in Pakistan.Medicinal Plants of India and Pakistan: A Concise Work Describing Plants Used for Drugs and Remedies According to Ayurvedic, Unani, Tibbi Systems and Mentioned in British and American Pharmacopoeias by J. F. Dastur (1952) D. B. Taraporevala Sons & Co. 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.Ayurveda is well versed with the toxic effects of Aristolochia indica by Chandrakant Bhanushali (Published on Wednesday, 05 June 2013 18:21) Express Pharma. This should not be particularly comforting since AA is sequestered by blood albumin, which also restricts excretion.Physiological and Molecular Characterization of Aristolochic Acid Transport by the Kidney by Kathleen G. Dickman et al. J. Pharmacol. Exp. Ther. 2011 Aug; 338(2): 588–597. doi: 10.1124/jpet.111.180984. 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),Ayurvedic Medicine Information: Puga Khanda – Benefits, Dosage, Ingredients, Side Effects and gorochanadi contains the toxic heavy metal lead as an ingredient.Ayurvedic Medicine Information: Gorochanadi Gulika – Benefits, Dosage, Ingredients And Side Effects Isvari was included in a list of Ayurvedic herbs without comment in a 2010 WHO report on training Ayurvedic medicine practitioners.Benchmarks for training in traditional / complementary and alternative medicine: Benchmarks for Training in Ayurveda World Health Organization (2010). ISBN 9789241599627 (archived from June 13, 2018).
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.
In 2019, Indian researchers investigated whether A. krisagathra or A. bracteolata might be useful for male contraception."Antifertility Activity of Aristolochia krisagathra Sivarajan and Pradeep and Aristolochia bracteata Retz.: An in vivo evaluation" by P. S. Tresina et al. In: Ethnomedicinal Plants with Therapeutic Properties, edited by V. R. Mohan et al. (2019) CRC Press. ISBN 9781771887090. The researchers acknowledged that the plants contain AA but claimed that AA has many medicinal properties without acknowledging the danger of human use.
===Iran===
In Iran, Aristolochia species are known as zaravand or chopoghak (A. longa and A. olivieri) and are still used in herbal medicine as of 2015.Herbs and hazards: risk of aristolochic acid nephropathy in Iran by M. R. Ardalan et al. Iran J. Kidney Dis. 2015 Jan;9(1):14-7.Useful plants and drugs of Iran and Iraq / by David Hooper. With notes by Henry Field Field Museum of Natural History Botanical Series Vol. 9, no. 3, 1937.Ethnobotanical study of medicinal plants used by Kurd tribe in Dehloran and Abdanan Districts, Ilam Province, Iran by Ghasemi Pirbalouti et al. Afr. J. Tradit. Complement. Altern. Med. (2013) 10(2):368-000.
===Jamaica===
A. grandiflora is native in Jamaica and from Mexico to Ecuador.Aristolochia grandiflora Sw. Royal Botanic Gardens, Kew. It is known to be used medicinally in Jamaica and has been sold on Amazon as recently as 2024.Duck Flower Detox | 2 Whole Dried Blossoms | Aristolochia grandiflora plant | Wildharvested Herb of Jamaica Amazon.com (archived from 13 Mar 2024 17:11:45 UTC).
===Morocco===
thumb|right|100px|A. baetica
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".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.
===Pakistan===
A 2017 article on Pakistani folk medicine reported on four plant species widely used in folk medicine, including A. indica.Antimicrobial activity, toxicity and anti-inflammatory potential of methanolic extracts of four ethnomedicinal plant species from Punjab, Pakistan by Rabia Naz et al. (2017) BMC Complementary Medicine and Therapies 17:302. doi:10.1186/s12906-017-1815-z. 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.Traditional folk medicine from Pakistan studied to have great anti-inflammatory potential by Ralph Flores (January 29, 2019) NaturalNews (archied from March 5, 2019).Scientists examine the antimicrobial activity of four ethnomedicinal plants from Pakistan by Ralph Flores (07/02/2018) Science.News (archived from September 14, 2019).
===Papua New Guinea===
A. indica is used for malaria, abortion, and uterine inflammation in parts of Papua New Guinea.An ethnobotanical survey of medicinal plants used in the eastern highlands of Papua New Guinea by Ronald Y. Jorim et al. J Ethnobiol. Ethnomed. 2012; 8: 47.
===Paraguay===
A. triangularis was reportedly widely used in combination with yerba maté (Ilex paraguariensis) in Paraguayan folk medicine.Yerba Mate (Ilex paraguariensis) Beverage: Nutraceutical Ingredient or Conveyor for the Intake of Medicinal Plants? Evidence from Paraguayan Folk Medicine by Monika Kujawska (2018) Evidence-Based Complementary and Alternative Medicine doi: 10.1155/2018/6849317.
===Peru===
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."Rainer W. Bussmann & Douglas Sharon (2015) Plantas de Los Cuatro Vientos: Flora Magicá y Medicinal del Perú = Plants of the Four Winds: The Magic and Medicinal Flora of Peru (2007) Editorial Graficart. ISBN 0978996232.
===Romania===
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.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 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."Mărul lupului, planta care poate învinge cancerul Efemeride.
===South Korea===
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.Update of aristolochic acid nephropathy in Korea by Tae Hyun Ban et al. (2018) Korean J. Intern. Med. 33(5):961–969.
===Sri Lanka===
A. indica is used traditionally as a tonic, a stimulant, an emmenagogue (increasing pelvic blood flow), an emetic, and for fevers.Medicinal Resources and Ethnopharmacology in Sri Lanka and Nepal, edited by Tsuneo Nanba (1985) Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University.
===Taiwan===
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.Aristolochic Acid in the Etiology of Renal Cell Carcinoma by M. L. Hoang et al. Cancer Epidemiol. Biomarkers Prev. 2016 Dec;25(12):1600-1608. Epub 2016 Aug 23. A case-control study found that cumulative consumption of 250 mg of AA increased the risk of ccRCC by odds ratio (OR)=1.25.
===United States===
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.Quantification of aristolochic acids I and II in herbal dietary supplements by ultra-high-performance liquid chromatography-multistage fragmentation mass spectrometry by L. Vaclavik et al. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2014;31(5):784-91. doi: 10.1080/19440049.2014.892215. Epub 2014 Apr 8. 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,The Herb Book: The Most Complete Catalog of Herbs Ever Published by John B. Lust (2014). Dover. ISBN 0486781445. Reprint of the original 1974 edition. 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:
If you find a medical professional to supervise your consumption of A. clematitis, you're in more trouble than you think.
Since 2017, Hawaii Pharm has been selling a tincture containing A. clematitis, including on Amazon.com, that is intended for internal consumption.California Poppy and Kava Kava Liquid Extract, Organic California Poppy and Kava Kava Dried Root Tincture Hawaii Pharm (archived from March 2, 2017).California Poppy (Eschscholzia Californica) and Birthwort (Aristolochia Clematitis) Liquid Extract 4 oz by HawaiiPharm on Amazon.com (archived from January 1, 2019).
===Zimbabwe===
A. albida was reported to be used by traditional healers for treatment of malaria in Zimbabwe.Medicinal plants used by traditional healers to treat malaria in the Chipinge district in Zimbabwe by T. Ngarivhume et al. 'J. Ethnopharmacol. 2015 Jan 15;159:224-37. doi: 10.1016/j.jep.2014.11.011.
==External links==
*Common Herbal Supplement Linked to Cancer
==See also==
*Appeal to nature
*List of medicinal plants
*Herbal supplement
==Notes==
==References==
Category:Chinese medicine
Category:Herbal medicine
Category:Human carcinogens
Category:Indian medicine
Category:Plants
Category:Toxins