Aristolochia

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[[File:Aristolochia_californica_flower_2004-02-23.jpg|thumb|right|165px|The California pipevine (''Aristolochia californica'').]]{{altmed}}
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.<ref name=Scarborough>[http://www.jstor.org/stable/23645794?seq=1#page_scan_tab_contents Ancient Medicinal Use of ''Aristolochia'': Birthwort's Tradition and Toxicity] by John Scarborough, ''Pharmacy in History'', Vol. 53, No. 1, 2011.</ref>

{{wpl|Theophrastus}} {{lived|c. 371|c. 287 BCE}}, a student of [[Aristotle]], wrote the first botanic description and the first report on the pharmaceutical properties of birthwort in c. 300 BCE:

{{quotebox|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.<ref name=Scarborough/><ref>''Enquiry into Plants'', Book 6 by Theophrastus, Arthur F. Hort (Translator). Harvard University Press (1916). ISBN 0674990889.</ref>}}

Other ancient writers who recommended birthwort for medical treatment included: {{wpl|Diocles of Carystus}} {{lived|c. 375|295 BCE}}, {{wpl|Philinus of Cos}} (3<sup>rd</sup> century BCE), {{wpl|Heraclides of Tarentum}} {{lived|c. 2<sup>nd</sup>|3<sup>rd</sup> century BCE}}, {{wpl|Aulus Cornelius Celsus}} {{lived|c. 25 BCE|c. 50 CE}}, {{wpl|Scribonius Largus}} {{lived|c. 1|c. 50 CE}}, {{wpl|Pedanius Dioscorides}} {{lived|c. 40|90 CE}}, and [[Pliny the Elder]] {{lived|23|79 CE}}.<ref name=Scarborough/> Dioscorides wrote the first major book on herbal medicine between 50 and 100 CE, {{wpl|De Materia Medica|''De Materia Medica''|,}} which was highly influential for over 1500 years.<ref>[https://archive.org/details/de-materia-medica/ ''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.</ref>

===Medieval era===
''Aristolochia'' appeared in the {{wpl|Charaka Samhita|''Charaka Samhita''}} (c. 400 CE), the foundational text for [[Ayurvedic]] medicine.<ref name=grollman>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341512/pdf/EMBR-17-619.pdf 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.</ref>{{rp|620}}

[[Saint]] {{wpl|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:

{{quotebox|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.<ref>''Hildegard von Bingen's Physica: The Complete English Translation of Her Classic Work on Health and Healing'', translated by Priscilla Throop (1998). Healing Arts Press. ISBN 0892816619.</ref>}}

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====
{{main|Traditional Chinese medicine}}
The {{wpl|Bencao Gangmu|''Bencao Gangmu''}} (本草綱目) or ''Compendium of Materia Medica'' was first published in 1578 by {{wpl|Li Shizhen}} (李時珍). ''Aristolochia'' appears in the ''Bencao Gangmu'' as "馬兜鈴" (''mǎ dōu líng'').<ref>[https://zh.wikisource.org/wiki/%E6%9C%AC%E8%8D%89%E7%B6%B1%E7%9B%AE/%E8%8D%89%E4%B9%8B%E4%B8%83#.E9.A6.AC.E5.85.9C.E9.88.B4 本草綱目/草之七] Wikisource (''Compendium of Materia Medica'' / Grass, Seven)</ref> Bernard Read's analysis of the ''Bencao Gangmu'' reported three species of ''Aristolochia'' (''A. debilis'', ''A. recurvilabra'', and ''A. contorta''),<ref name=read>''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, 3<sup>rd</sup> ed.</ref> but ''A. recurvilabra'' is now considered a synonym of ''A. debilis''.<ref>[http://www.theplantlist.org/tpl1.1/record/kew-2651826?ref=tpl1 Aristolochia recurvilabra Hance] ''The Plant List: A Working List of All Plant Species''.</ref>

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'').<ref name=stuart>[https://archive.org/details/chinesemateriame00stuauoft ''Chinese Materia Medica. 1. Vegetable Kingdom''] by G. A. Stuart (1911). Presbyterian Mission Press, revised from F. Porter Smith.</ref> For ''A. kaempferi'', Stuart stated:

{{quotebox|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.<ref name=stuart/>}}

For ''A. debilis'', Stuart stated:

{{quotebox|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.<ref name=stuart/>}}

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.<ref>Health Department and National Chinese Medicine Management Office (ed.). ''Zhong Hua Ben Cao'', 3–460–509. Shanghai Science Technology Publication. 1999. ISBN 7532351068.</ref> The species ''A. manshuriensis'', ''A. fangchi'', ''A. debilis'', and ''A. contorta'' are included in the official ''Pharmacopoeia of the People's Republic of China''.<ref>''Pharmacopoeia of the People's Republic of China'' (2005). Chemical Industry Press, 2 volumes: ISBN 7502520627 and ISBN 7502520635.</ref>

====Western medicine====
{{main|Western medicine}}
In 1597, {{wpl|John Gerard|John Gerarde}} wrote what became a very popular book, called ''The Herball, or Generall Historie of Plantes''. The book cited three [[Appeal to ancient wisdom|ancient authorities]] on the uses of "birthwoorte": Pedanius Dioscorides, {{wpl|Galen}} {{lived|129|c. 200/c. 216 CE}}, and Pliny the Elder.<ref name=gerarde>[https://archive.org/details/herballorgeneral00gera/page/n5/mode/2up ''The Herball, or Generall Historie of Plantes''] by John Gerarde (1597). John Gerard</ref> The uses for "long birthwoorte" (''A. longa'') and "round birthwoorte" (''A. rotunda'') included:
{{quotebox|
*''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.<ref name=gerarde/>}}

''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.<ref>[https://books.google.com/books?id=7qgPCEiI4WMC&pg=PA110&lpg=PA110&dq=aristolochia+ethnobotany&source=bl&ots=uDkYez-tTR&sig=PCX-we2sJ2W3eOwhzDhemfpGC9Y&hl=en&sa=X&ved=0ahUKEwjp9aqL4YjNAhUO92MKHbd7CvwQ6AEIQDAF#v=onepage&q=aristolochia%20ethnobotany&f=false ''Florida Ethnobotany''] by Daniel F. Austin (2004) CRC Press, pp. 109-110. ISBN 0849323320.</ref>

The 1931 book ''[[A Modern Herbal]]'' by {{wpl|Maud Grieve}} {{lived|1858|1941}} reported the following on ''Aristolochia'' (note that no mention whatsoever is made of any possible side effects):

{{quotebox|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.

---Other Species---

''Aristolochia cymbifera'' from [[Brazil]] and [[Mexico]] is said to have medicinal properties similar to the official species. Butte affirms it is a depressant to the sensory nerve centres and is useful in neuralgia and pruritis; it was formerly considered alexiteric, antiparalytic, antiperiodic and aphrodisiac.

''A. argentina'' root is used in [[Argentina|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.<ref>[http://botanical.com/botanical/mgmh/b/birthw44.html Birthwort], ''A Modern Herbal'' by M. Grieve.</ref>}}

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…<ref>[http://www.kwakzalverij.nl/813/Maandblad_15_juli_1881_jaargang_1_nummer_7 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) ''Kwakzalverij''</ref><ref>[https://www.kwakzalverij.nl/tijdschrift/tijdschrift-archief-19e-eeuw/maandblad-15-juli-1881-jaargang-1-nummer-7/ Reconfortatief of gezondheids en zeer versterkende pillen] (15 juli 1881) ''Nederlands Tijdschrift tegen de Kwakzalverij '' 1(7).</ref>

==Discovery of toxicity==

[[File:Aristolochic-acids-I-and-II-2D-skeletal.png|thumb|right|200px|Structural formula of variations of Aristolochic acid (AA); the second variation contains a methoxy group (R = OCH<sub>3</sub>).]]

===Early reports===
William Cullen's ''Materia Medica'' reported in 1789 that an ''Aristolochia''-containing substance called "Portland Powder"{{efn|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'']…"<ref>[https://ia801409.us.archive.org/26/items/modernpracticep01thomgoog/modernpracticep01thomgoog.pdf ''The Modern Practice of Physic etc. etc.''] by Robert Thomas (1828) 9<sup>th</sup> ed., page 219</ref>}} was effective in treating gout but,<ref>[https://archive.org/details/treatiseofmateri02cull/ ''A Treatise of the Materia Medica''] by William Cullen (1789) Volume 2, page 54</ref>
{{cquote|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 1815, {{wpl|Mathieu Orfila||,}} the father of modern toxicology, reported that ''Aristolochia'' was lethal to dogs.<ref name=Scarborough/><ref>[https://ia902804.us.archive.org/33/items/BIUSante_38850x02x01/BIUSante_38850x02x01.pdf 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) 3<sup>rd</sup> ed., volume 2, pp. 276-279.</ref>

In 1888, a letter on the continuing usage of Portland Powder was published in ''The Peoria Medical Monthly'', [[anecdotal]]ly stating that "every person treated by them died before the expiration of two years!"<ref>[https://books.google.com/books?id=aEOgAAAAMAAJ&pg=PA128&dq=%22portland+powders%22&hl=en&sa=X&ved=0ahUKEwjUlcz3le7fAhVP1VkKHfTnD2UQ6AEINzAD#v=onepage&q=%22portland%20powders%22&f=false Beware of Nostrums] (1888) ''The Peoria Medical Monthly'' volume 8, page 128.</ref>

===Modern research===
[[File:Aristolochia clematitis.jpg|thumb|right|200px|Seeds of ''A. clematitis'', the European birthwort.]]
As a result of scientific research conducted in the 20<sup>th</sup> century, it was discovered that birthwort can cause cancer and kidney failure because it contains aristolochic acid (AA), which is, [[The dose makes the poison|in the amounts present in]] birthwort, a poison.<ref name=pnas>Chung-Hsin Chena, et al. "[http://www.pnas.org/content/early/2012/04/03/1119920109.full.pdf+html?sid=701744d3-ba01-4ef9-a78d-5d4802598329 Aristolochic acid-associated urothelial cancer in Taiwan]." ''Proceedings of the National Academy of Sciences''. 2012 April 9.</ref> Aristolochic acid is one of the most potent carcinogens in the Carcinogenic Potency Database.<ref name="herbal">[https://web.archive.org/web/20170427015831/http://toxnet.nlm.nih.gov/cpdb/aristolochicacid.html Research and Publications on Herbal Products Known or Suspected to Contain Aristolochic Acid, a Human Carcinogen] (archived from April 27, 2017).</ref><ref>[https://web.archive.org/web/20170428082442/https://toxnet.nlm.nih.gov/cpdb/pdfs/Aristolochicplot.pdf Aristolochic acid, sodium salt: Cancer Test Summary] (archived from April28, 2017).</ref>

In [[Belgium]], between 1990 and 1992, a weight-loss spa using TCM herbs thought they were giving their clients ''{{wpl|Stephania tetrandra}}'' and ''{{wpl|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.<ref name="worldwide">[https://www.kidney-international.org/article/S0085-2538(15)53279-1/fulltext Aristolochic acid nephropathy: A worldwide problem] by Frédéric D. Debelle et al. (2008) ''Kidney International'' 74:158–169; doi:10.1038/ki.2008.129.</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/10841870 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.</ref> As epidemiologist Geoffrey Kabat noted:

{{quotebox|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.<br />
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."<ref>[http://www.slate.com/articles/health_and_science/medical_examiner/2012/11/herbal_supplement_dangers_fda_does_not_regulate_supplements_and_they_can.single.html Natural Does Not Mean Safe: Herbal supplements are unregulated, overhyped, and potentially deadly.] by Geoffrey Kabat (Nov. 26 2012 3:36 PM) ''Slate''.</ref>}}

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.<ref name=iarc2002>[https://monographs.iarc.fr/ENG/Monographs/vol82/mono82.pdf ''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.</ref> 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.<ref name=iarc2012>[https://monographs.iarc.fr/ENG/Monographs/vol100A/mono100A-23.pdf 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.</ref>

European birthwort (''A. clematitis''), which has also been used as a medicine, has been linked to {{wpl|Balkan endemic nephropathy}} (BEN), though this conclusion has taken decades to arrive at since the time that BEN was first diagnosed in the 1920s.<ref>[http://www.sciencedirect.com/science/article/pii/S008525381551555X 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.</ref><ref>[https://www.researchgate.net/publication/221869702_Chinese_herbs_nephropathy_and_Balkan_endemic_nephropathy_Toward_a_single_entity_aristolochic_acid_nephropathy 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.</ref> The source of BEN is likely wheat that is contaminated by seeds of ''A. clematitis''<ref name="worldwide"/> and/or bioaccumulation in grain from soil and water where ''A. clematitis'' has grown.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/26654710 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.</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/27362729 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.</ref> 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''.<ref>[https://www.scielo.br/j/abb/a/vnn9DP6SLn8B4p74bLRHkrK/?lang=en&format=pdf Allelopathic effects of aqueous extracts of ''Artistolochia <small><sup>sic</sup></small> esperanzae'' O. Kuntze on development of ''Sesamum indicum'' L. seedlings] by Ana Beatriz Gatti et al. (2010) ''Acta Botanica Brasilica'' 24(2): 454-461.</ref>

BEN has been found in northern [[Bosnia and Herzegovina|Bosnia]], eastern [[Croatia]], [[Serbia]], Kosovo, southwestern [[Romania]], and northwestern [[Bulgaria]].<ref>[http://link.springer.com/article/10.1007%2Fs10653-013-9515-1 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</ref> A 2016 study confirmed that AA-contaminated soil is a pathway to human exposure via bioaccumulation in food crops.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/26654710 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.</ref> A 2018 study further confirmed that AAs are long-lived soil contaminants, and AA soil contamination in the Balkans strongly correlated with BEN.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/30286603 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.</ref>

[[File:Balkan endemic nephropathy map.svg|thumb|center|500px|Distribution of Balkan endemic nephropathy (BEN).]]

The actual number of aristolochic acid nephropathy (AAN) cases, which is usually fatal, is unknown and probably underestimated.<ref name="worldwide"/> "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.<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119144/ 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.</ref>

Additionally, it is suspected that AA exposure is associated with liver cancer (hepatocellular carcinoma, HCC), particularly for people exposed to the [[hepatitis B]] [[virus]].<ref>[https://www.ncbi.nlm.nih.gov/pubmed/29667191 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.</ref> 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.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/29046434 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.</ref>

It is suspected that all species of ''Aristolochia'' contain some form of aristolochic acid (AA),<ref>[https://www.researchgate.net/publication/26275286_Local_uses_of_Aristolochia_species_and_content_of_nephrotoxic_aristolochic_acid_1_and_2-A_global_assessment_based_on_bibliographic_sources 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.</ref> and dozens of species are known to contain either AA or AA analogs.<ref name=han>[https://www.researchgate.net/publication/333708825_Systematic_Overview_of_Aristolochic_Acids_Nephrotoxicity_Carcinogenicity_and_Underlying_Mechanisms 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.</ref>

===Asarum===

''Asarum'' is a genus of plants used medicinally that are in the same family as the ''Aristolochia'' genus (Aristolochiaceae). ''Asarum'' species contain AA<ref>[https://web.archive.org/web/20090710094540/https://www.fda.gov/Food/DietarySupplements/Alerts/ucm096388.htm Aristolochic 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).</ref><ref name=han/> and also contain AA analogs.<ref name=michl>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439001/ 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.</ref><ref name=han/> ''Asarum'' species are used in TCM (''xixin'', 细辛) and are traditionally used by Native Americans.<ref name=michl/> As of 2017, it is unclear how safe ''Asarum'' species are,<ref name=michl/> and only 8 cases of AAN from ''Asarum'' ingestion have been reported in 45 years.<ref name=michl/><ref>[https://www.ncbi.nlm.nih.gov/pubmed/23286904/ 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.</ref>

===Caterpillars love it, birds hate it===

[[File:AbbotV1Tab03AA.jpg|thumb|right|250px|Illustration from 1797 by John Abbot of the pipevine swallowtail (''Battus philenor'') and its caterpillar's host plant, the Virginia snakeroot (''Aristolochia serpentaria'').]]

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).<ref>[http://www.researchgate.net/publication/226452063_Sequestration_of_aristolochic_acids_by_the_pipevine_swallowtail_Battus_philenor_%28L.%29_evidence_and_ecological_implications 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.</ref><ref>[http://link.springer.com/article/10.1007/s000490050013#page-1 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.</ref>

Not all species of ''Aristolochia'' plants are palatable to all species of swallowtails. It has been found that introduced [[South America]]n ''Aristolochia elegans'' in Queensland, [[Australia]], is lethal to the larvae of native swallowtails, the Richmond (''Ornithoptera richmondia'') and Cairns (''Ornithoptera euphorion'') birdwing butterflies.<ref>[http://waingerlab.cbl.umces.edu/SupportingLiterature/LiteratureReviewDiagrams_Literature/Vines/Sands_2008.pdf 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.</ref><ref>"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.</ref> This suggests that the swallowtails and ''Aristolochia'' have been engaged in an [[evolutionary]] {{wpl|Evolutionary arms race|arms race.}}

==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.<ref>[https://web.archive.org/web/20170811201925/http://toxnet.nlm.nih.gov/cpdb/pdfs/NEJM.pdf 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).</ref> In 2018, it was reported that ''Aristolochia'' is still available for purchase on the internet.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/29498013 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.</ref>

In 2010, the World Health Organization (WHO) effectively encouraged the use of ''A. indica'' in a publication on Ayurvedic medicine.<ref name=who/> In doing so, they acted contrary to the information provided by one of their agencies, IARC.<ref name=iarc2002/><ref name=iarc2012/> The WHO has continued to encourage the use of herbal medicine despite known problems with both efficacy and safety of herbal medicines.<ref name=grollman/><ref>[https://web.archive.org/web/20181129215212/http://www.searo.who.int/entity/health_situation_trends/who_trm_strategy_2014-2023.pdf ''Traditional Medicine Strategy 2014–2023''] (2013) World Health Organization. ISBN 9789241506090. (archived from November 29, 2018).</ref>

A 2009 literature review found that 99 species of ''Aristolochia'' have been used ethnobotanically, but only 24 of these species have been studied phytochemically.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/19505558 Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2&mdash;a global assessment based on bibliographic sources] by M. Heinrich et al. ''J. Ethnopharmacol.'' 2009 Aug 17;125(1):108-44. doi: 10.1016</ref><ref name="herbal"/>

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.<ref>[https://scielo.conicyt.cl/scielo.php?pid=S0717-97072013000400041&script=sci_arttext&tlng=en 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.</ref> 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.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/27538407 Balkan endemic nephropathy: an update on its aetiology] by M. Stiborová et al. ''Arch'' Toxicol.'' 2016 Aug 19 (Epub ahead of print).</ref>

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.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/27892830 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.</ref>

A 2019 review found that AA was widespread in Chinese patent medicine.<ref name=han/> As of 2025, ''Aristolochia'' products intended for human consumption can be readily found on both Amazon<ref>[https://archive.ph/rx7RF Aristolochia Indica Dried Roots RAW (Karalakam) | Ayurvedic Wellness 50g, 1.76 Ounce (Pack of 1)] ''Amazon.com'' (archived from 27 Feb 2025 01:54:29 UTC).</ref><ref>[https://archive.ph/wip/5bgh1 Duck Flower Detox Tea (2 Duck Flowers), Aristolochia grandiflora, Wildharvested from Jamaica, All Natural Total Body Cleanse] ''Amazon.com'' (archived from 27 Feb 2025 01:56:28 UTC).</ref><ref>[https://archive.ph/wip/BEfq9 Aadu Thinna Paalai (Aristolochia Bracteata) Powder, 300g] ''Amazon.com'' (archived from 27 Feb 2025 02:00:52 UTC).</ref> and Ebay.<ref>[https://archive.ph/9R34d Jamaica Wildcraft Contribo 1oz Powder - Aristolochia Trilobata - Stomach Aches] ''Ebay'' (archived from 27 Feb 2025 02:11:35 UTC).</ref><ref>[https://archive.ph/6SyPL Jamaica Wildcraft Contribo 30 Capsules - Aristolochia Trilobata - Stomach Aches] ''Ebay (archived from 27 Feb 2025 02:13:12 UTC).</ref><ref>[https://archive.ph/Rm7sZ Jamaica Wildcraft Duck Flower- Aristolochia Grandiflora- 30 Capsules] ''Ebay'' (archived from 27 Feb 2025 02:14:28 UTC).</ref>

===Algeria===
''A. longa'' is widely used in traditional [[Algeria]]n medicine. It is used to treat cancer,<ref group=note>Oh, the irony!</ref> skin infections, and diabetes.<ref>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.</ref>

===Bangladesh===
[[File:Garudasalabhamlarva.jpg|thumb|right|100px|Larva of southern birdwing butterfly (''Troides minos'') eating leaves of ''A. indica'']]
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".<ref>[http://www.ncbi.nlm.nih.gov/pubmed/23806867 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.</ref>

===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.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/25482361 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</ref>

===Bulgaria===
[[File:Aristoloche.jpg|thumb|right|100px|''A. clematitis'']]
''A. clematitis'' is used in [[Bulgaria]]n herbal medicine for several indications, including as a diuretic.<ref>[http://gpnews.bg/повечето-хора-смятат-че-хранителните/ Повечето хора смятат, че хранителните добавки са безопасни. А дали е така?]</ref>

===Chile===
[[File:Aristolochia chilensis 03.jpg|thumb|right|100px|''A. chilensis'']]
''A. chilensis'' is used in [[Chile]]an herbalism for various indications, including arthritis, hemorrhoids, gout, inflammation, weight loss, and overall health.<ref name=chile>[http://urbatorium.blogspot.com/2013/09/la-maldicion-de-las-orejas-de-zorro.html La maldición de las orejas de zorro, llega a su fin] (25 de septiembre de 2013) ''Urbatorium''.</ref><ref name=chilenatura>[http://www.info-natura.com/blog/2013/09/24/la-planta-medicinal-chilena-oreja-de-zorro-provoca-cancer/ La planta medicinal chilena “Oreja de zorro” provoca cáncer.] Septiembre 24, 2013 Info-natura</ref> It is also used in teas.<ref name=chile/> According to researchers at Chile's Universidad de Santiago, consuming 1mg of the plant can cause harmful effects months after it was initially ingested.<ref name=chilenatura/>

===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.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/25540870 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.</ref>

As of 2016, Chinese companies were still making ''A. debilis'', ''A. manshuriensis'', ''A. fangchi'', and ''A. bracteolata'' available for export for medicinal purposes.<ref>[[File:Alibaba Aristolochia.pdf]] &mdash; Aristolochia for sale on Alibaba in 2016</ref>

===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''.<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224600/ 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.</ref>

===Ecuador===
The indigenous Awá people of [[Ecuador]] use several species of ''Aristolochia'' in their traditional medicine, including two that are ingested.<ref>''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.</ref>{{rp|67-68,230}}

===France===
[[File:Flore des serres v14 021a.jpg|thumb|right|100px|''A. trilobata'' painted by Louis van Houtte in 1861]]
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''.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/26879332 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.</ref>

===India===
[[File:Arsitolochia indica - flower.JPG|thumb|right|100px|''A. indica'']]
''A. indica'', known as ''isvari'', is used in [[Ayurvedic medicine]]. It is also found in Pakistan.<ref name=dastur>''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.</ref>{{rp|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.<ref name=expresspharma>[http://archivepharma.financialexpress.com/sections/market-section/2211-ayurveda-is-well-versed-with-the-toxic-effects-of-aristolochia-indica Ayurveda is well versed with the toxic effects of ''Aristolochia indica''] by Chandrakant Bhanushali (Published on Wednesday, 05 June 2013 18:21) ''Express Pharma''.</ref> This should not be particularly comforting since AA is sequestered by blood albumin, which also restricts excretion.<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141898/ 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.</ref> According to Bhanushali, ''A. indica'' is found in two medicines used internally: ''poogakhanda'' and ''gorochanadi vati'', but usage of these medicines is negligible.<ref name=expresspharma/> Also not particularly comforting is that the main ingredient of ''poogakhanda'' (or ''pooga khanda'') is another human carcinogen, [[betelnut]] (''Areca catechu''),<ref>[http://ayurmedinfo.com/2012/07/19/puga-khanda-benefits-dosage-ingredients-side-effects/ Ayurvedic Medicine Information: Puga Khanda – Benefits, Dosage, Ingredients, Side Effects]</ref> and ''gorochanadi'' contains the toxic heavy metal [[lead]] as an ingredient.<ref>[http://ayurmedinfo.com/2012/06/28/gorochanadi-gulika-benefits-dosage-ingredients-and-side-effects/ Ayurvedic Medicine Information: Gorochanadi Gulika – Benefits, Dosage, Ingredients And Side Effects]</ref> ''Isvari'' was included in a list of Ayurvedic herbs without comment in a 2010 WHO report on training Ayurvedic medicine practitioners.<ref name=who>[https://web.archive.org/web/20180613143835/https://apps.who.int/medicinedocs/documents/s17552en/s17552en.pdf 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).</ref>

''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.<ref name=dastur/>{{rp|36-37}}

In 2019, Indian researchers investigated whether ''A. krisagathra'' or ''A. bracteolata'' might be useful for male contraception.<ref name=tresina>"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.</ref>{{rp|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.<ref name=tresina/>{{rp|308}}

===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.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/25599730 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.</ref><ref>[https://archive.org/stream/usefulplantsdrugfihoop/usefulplantsdrugfihoop_djvu.txt 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.</ref><ref>[http://www.bioline.org.br/pdf?tc13046 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.</ref>

===Jamaica===
''A. grandiflora'' is native in [[Jamaica]] and from Mexico to Ecuador.<ref>[https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:92978-1/general-information#descriptions ''Aristolochia grandiflora'' Sw.] ''Royal Botanic Gardens, Kew''.</ref> It is known to be used medicinally in Jamaica and has been sold on Amazon as recently as 2024.<ref>[https://archive.ph/7XWGK 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).</ref>

===Morocco===
[[File:Aristolochia baetica - Cartagena - Espagne.JPG|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''".<ref>[http://www.ncbi.nlm.nih.gov/pubmed/25797117 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.</ref>

===Pakistan===
A 2017 article on [[Pakistan]]i folk medicine reported on four plant species widely used in folk medicine, including ''A. indica''.<ref name=naz>[https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-017-1815-z 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.</ref> The article analyzed the plants' antimicrobial, antioxidant, cytotoxic, and anti-inflammatory potential and concluded two of the non-''Aristolochia'' species had the strongest effects.<ref name=naz/> The authors did not study safety or mention the hazardousness of ''Aristolochia''. Nonetheless, [[NaturalNews]] and its affiliate site [[List of websites owned by Mike Adams|'Science.News']] reported on this article, distorting its results and touting ''A. indica''.<ref>[https://web.archive.org/web/20190305201041/https://www.naturalnews.com/2019-01-29-traditional-folk-medicine-from-pakistan-studied-to-have-great-anti-inflammatory-potential.html# Traditional folk medicine from Pakistan studied to have great anti-inflammatory potential] by Ralph Flores (January 29, 2019) ''NaturalNews'' (archied from March 5, 2019).</ref><ref>[https://web.archive.org/web/20190914150906/https://www.science.news/2018-07-02-scientists-examine-antimicrobial-activity-of-four-ethnomedicinal-plants-from-pakistan.html Scientists examine the antimicrobial activity of four ethnomedicinal plants from Pakistan] by Ralph Flores (07/02/2018) ''Science.News'' (archived from September 14, 2019).</ref>

===Papua New Guinea===
''A. indica'' is used for [[malaria]], [[abortion]], and uterine inflammation in parts of [[Papua New Guinea]].<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549922/ 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.</ref>

===Paraguay===
''A. triangularis'' was reportedly widely used in combination with [[List of medicinal plants#M|''yerba maté'']] (''Ilex paraguariensis'') in [[Paraguay]]an folk medicine.<ref>[https://www.hindawi.com/journals/ecam/2018/6849317/ 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.</ref>

===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."<ref>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.</ref>

===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.<ref name=surprise>[http://www.libertatea.ro/detalii/articol/surpriza-de-pe-lista-celor-116-produse-periculoase-intocmita-de-oms-marul-lupului-este-cancerigen-556843.html Surpriza de pe lista celor 116 produse periculoase întocmită de OMS: Mărul lupului este cancerigen] 02 noiembrie 2015 21:45 ''Libertatea''.</ref><ref name=teas>[http://www.ziarulring.ro/stiri/sanatate/220397/Ceaiuri-care-te-pot-imbolnavi Ceaiuri care te pot îmbolnăvi] ''Ziarul Ring''</ref> It is also claimed that, in low doses, birthwort taken internally is not carcinogenic but is, in fact, [[Bullshit|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."<ref name=surprise/><ref name=cure>[http://www.efemeride.ro/marul-lupului-planta-care-poate-invinge-cancerul Mărul lupului, planta care poate învinge cancerul] ''Efemeride''.</ref>

===South Korea===
A study of ''Aristolochia'' in [[traditional Korean medicine‎‎]] found that AA is found in some Korean herbal remedies, that [[South Korea]]ns have experienced AAN, and that there is a possibility that AAN is under-diagnosed in South Korea.<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129635/ Update of aristolochic acid nephropathy in Korea] by Tae Hyun Ban et al. (2018) ''Korean J. Intern. Med. 33(5):961–969.</ref>

===Sri Lanka===
''A. indica'' is used traditionally as a tonic, a stimulant, an emmenagogue (increasing pelvic blood flow), an emetic, and for fevers.<ref>''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.</ref>{{rp|56}}

===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.<ref name=pnas/> In Taiwan, 76% of clear cell renal cell carcinoma (ccRCC) cases had been exposed to AA based on an examination of [[DNA]] adducts.<ref name=RCC>[https://www.ncbi.nlm.nih.gov/pubmed/27555084 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.</ref> A [[case-control study]] found that cumulative consumption of 250 mg of AA increased the risk of ccRCC by odds ratio (OR)=1.25.<ref name=RCC/>

===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.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/24512293 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.</ref> 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,<ref name="theherbbook">''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.</ref> 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:
{{cquote|CAUTION: Birthwort contains a substance that acts similar to the poisonous alkaloid colchicine.<ref group=note>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.</ref> Use with care, preferably under medical direction.|||John Lust<ref name="theherbbook"/>}}

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.<ref>[https://web.archive.org/web/20170302182942/https://www.hawaiipharm.com/c-poppy-kava-alc-extract California Poppy and Kava Kava Liquid Extract, Organic California Poppy and Kava Kava Dried Root Tincture] Hawaii Pharm (archived from March 2, 2017).</ref><ref>[https://web.archive.org/web/20190101172253/https://www.amazon.com/California-Eschscholzia-Californica-Aristolochia-Clematitis/dp/B00J47J3TO?th=1 California Poppy (Eschscholzia Californica) and Birthwort (Aristolochia Clematitis) Liquid Extract 4 oz] by HawaiiPharm on Amazon.com (archived from January 1, 2019).</ref>

===Zimbabwe===
''A. albida'' was reported to be used by traditional healers for treatment of malaria in [[Zimbabwe]].<ref>[http://www.ncbi.nlm.nih.gov/pubmed/25449454 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.</ref>

==External links==
*[https://www.science.org/content/article/common-herbal-supplement-linked-cancer Common Herbal Supplement Linked to Cancer]

==See also==
*[[Appeal to nature]]
*[[List of medicinal plants]]
*[[Herbal supplement]]

==Notes==
{{reflist|2|group=note}}

==References==
{{reflist|2|80%}}

{{altmedbox}}

[[Category:Chinese medicine]]
[[Category:Herbal medicine]]
[[Category:Human carcinogens]]
[[Category:Indian medicine]]
[[Category:Plants]]
[[Category:Toxins]]

Categories: Chinese medicine, Herbal medicine, Human carcinogens, Indian medicine, Plants, Toxins