View source for Chemistry:Amygdalin

{{short description|Cyanogenic glycoside present in kernels of fruit}}
{{Chembox
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| ImageFile = Amygdalin structure.svg
| ImageSize = 
| ImageFile2 = Amygdalin-from-xtal-3D-balls.png
| ImageSize2 = 220px
| IUPACName = (2''R'')-[β-<small>D</small>-Glucopyranosyl-(1→6)-β-<small>D</small>-glucopyranosyloxy]phenylacetonitrile
| SystematicName = (2''R'')-Phenyl{[(2''R'',3''R'',4''S'',5''S'',6''R'')-3,4,5-trihydroxy-6-({[(2''R'',3''R'',4''S'',5''S'',6''R'')-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl]oxy}acetonitrile
| OtherNames = 
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XUCIJNAGGSZNQT-JHSLDZJXSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 29883-15-6
| PubChem = 656516
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 214UUQ9N0H
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17019
| SMILES = O[C@@H]3[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]3OC[C@H]2O[C@@H](OC(C#N)c1ccccc1)[C@H](O)[C@@H](O)[C@@H]2O
| MeSHName = Amygdalin
  }}
|Section2={{Chembox Properties
| C=20 | H=27 | N=1 | O=11
| MolarMass=457.429
| Appearance=
| Density=
| MeltingPt= 223-226 °C(lit.)
| BoilingPt=
| Solubility= H2O: 0.1 g/mL hot, clear to very faintly turbid, colorless
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|Section3={{Chembox Hazards
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| NFPA-H = 1
| NFPA-F = 0
| NFPA-R = 0
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|Section8={{Chembox Related
| OtherAnions =
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| OtherFunction_label =
| OtherCompounds = [[Chemistry:Vicianin|Vicianin]], laetrile, [[Chemistry:Prunasin|prunasin]], sambunigrin }}
}}

'''Amygdalin''' (from [[Social:Ancient Greek|Ancient Greek]]: {{lang|grc|ἀμυγδαλή}} ''{{lang|grc-Latn|amygdalē}}'' 'almond') is a naturally occurring [[Chemistry:Chemical compound|chemical compound]] found in many plants, most notably in the seeds (kernels) of [[Biology:Apricot|apricot]]s, bitter almonds, [[Biology:Apple|apple]]s, [[Biology:Peach|peach]]es, cherries and [[Biology:Plum|plum]]s, and in the roots of manioc.

Amygdalin is classified as a cyanogenic glycoside, because each amygdalin molecule includes a [[Chemistry:Nitrile|nitrile]] group, which can be released as the toxic [[Chemistry:Cyanide|cyanide]] anion by the action of a [[Biology:Beta-glucosidase|beta-glucosidase]]. Eating amygdalin will cause it to release cyanide in the human body, and may lead to [[Medicine:Cyanide poisoning|cyanide poisoning]].<ref>{{cite web |url=https://www.efsa.europa.eu/en/press/news/160427 |publisher=European Food Safety Authority |title=Apricot kernels pose risk of cyanide poisoning |date=27 April 2016 |quote=A naturally-occurring compound called amygdalin is present in apricot kernels and converts to hydrogen cyanide after eating. Cyanide poisoning can cause nausea, fever, headaches, insomnia, thirst, lethargy, nervousness, joint and muscle various aches and pains, and falling blood pressure. In extreme cases it is fatal}}</ref>

Since the early 1950s, both amygdalin and a chemical derivative named '''''laetrile''''' have been promoted as [[Unsolved:Alternative cancer treatments|alternative cancer treatments]], often under the misnomer '''vitamin B<sub>17</sub>''' (neither amygdalin nor laetrile is a [[Chemistry:Vitamin|vitamin]]).<ref name=CaCancer/> Scientific study has found them to not only be clinically ineffective in treating cancer, but also potentially toxic or lethal when taken by mouth due to [[Medicine:Cyanide poisoning|cyanide poisoning]].<ref name=Milazzo2015>{{cite journal | vauthors = Milazzo S, Horneber M | title = Laetrile treatment for cancer | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD005476 | date = April 2015 | volume = 2018 | pmid = 25918920 | doi = 10.1002/14651858.CD005476.pub4 | pmc = 6513327 }}</ref> The promotion of laetrile to treat cancer has been described in the medical literature as a canonical example of [[Philosophy:Quackery|quackery]],<ref>{{cite journal | vauthors = Lerner IJ | title = The whys of cancer quackery | journal = Cancer | volume = 53 | issue = 3 Suppl | pages = 815–9 | date = February 1984 | pmid = 6362828 | doi = 10.1002/1097-0142(19840201)53:3+<815::AID-CNCR2820531334>3.0.CO;2-U | s2cid = 36332694 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Nightingale SL | title = Laetrile: the regulatory challenge of an unproven remedy | journal = Public Health Reports | volume = 99 | issue = 4 | pages = 333–8 | year = 1984 | pmid = 6431478 | pmc = 1424606 }}</ref> and as "the slickest, most sophisticated, and certainly the most [[Finance:Profit (accounting)|remunerative]] cancer quack promotion in medical history".<ref name=CaCancer/>

== Chemistry ==

Amygdalin is a cyanogenic glycoside derived from the aromatic amino acid [[Chemistry:Phenylalanine|phenylalanine]]. Amygdalin and [[Chemistry:Prunasin|prunasin]] are common among plants of the family [[Biology:Rosaceae|Rosaceae]], particularly the genus ''[[Biology:Prunus|Prunus]]'', [[Biology:Poaceae|Poaceae]] (grasses), [[Biology:Fabaceae|Fabaceae]] (legumes), and in other food plants, including flaxseed and manioc.  Within these plants, amygdalin and the enzymes necessary to hydrolyze it are stored in separate locations, and only mix as a result of tissue damage. This provides a natural defense system.<ref>{{cite journal | vauthors = Mora CA, Halter JG, Adler C, Hund A, Anders H, Yu K, Stark WJ | title = Application of the Prunus spp. Cyanide Seed Defense System onto Wheat: Reduced Insect Feeding and Field Growth Tests | journal = Journal of Agricultural and Food Chemistry | volume = 64 | issue = 18 | pages = 3501–7 | date = May 2016 | pmid = 27119432 | doi = 10.1021/acs.jafc.6b00438 }}</ref>

Amygdalin is contained in [[Biology:Drupe|stone fruit]] kernels, such as [[Biology:Almond|almond]]s, [[Biology:Apricot|apricot]] (14&nbsp;g/kg), [[Biology:Peach|peach]] (6.8&nbsp;g/kg), and [[Biology:Plum|plum]] (4–17.5&nbsp;g/kg depending on variety), and also in the seeds of the [[Biology:Apple|apple]] (3&nbsp;g/kg).<ref>{{Cite journal|last1=Bolarinwa|first1=Islamiyat F.|last2=Orfila|first2=Caroline|last3=Morgan|first3=Michael R.A.|date=2014|title=Amygdalin content of seeds, kernels and food products commercially-available in the UK|journal=Food Chemistry|language=en|volume=152|pages=133–139|doi=10.1016/j.foodchem.2013.11.002|pmid=24444917|url=http://eprints.whiterose.ac.uk/83873/2/Bolarinwa.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://eprints.whiterose.ac.uk/83873/2/Bolarinwa.pdf |archive-date=2022-10-09 |url-status=live}}</ref> [[Chemistry:Benzaldehyde|Benzaldehyde]] released from amygdalin provides a bitter flavor. Because of a difference in a recessive gene called ''Sweet kernal [Sk]'', much less amygdalin is present in nonbitter (or sweet) almond than [[Biology:Bitter almond|bitter almond]].<ref name="Sanchez-PerezJorgensen2008">{{cite journal|last1=Sanchez-Perez|first1=R.|last2=Jorgensen|first2=K.|last3=Olsen|first3=C. E.|last4=Dicenta|first4=F.|last5=Moller|first5=B. L.|title=Bitterness in Almonds|journal=Plant Physiology|volume=146|issue=3|year=2008|pages=1040–1052|doi=10.1104/pp.107.112979|pmid=18192442|pmc=2259050}}</ref> In one study, bitter almond amygdalin concentrations ranged from 33 to 54&nbsp;g/kg depending on variety; semibitter varieties averaged 1&nbsp;g/kg and sweet varieties averaged 0.063&nbsp;g/kg with significant variability based on variety and growing region.<ref name="LeeZhang2013">{{cite journal|last1=Lee|first1=Jihyun|last2=Zhang|first2=Gong|last3=Wood|first3=Elizabeth|last4=Rogel Castillo|first4=Cristian|last5=Mitchell|first5=Alyson E.|title=Quantification of Amygdalin in Nonbitter, Semibitter, and Bitter Almonds (Prunus dulcis) by UHPLC-(ESI)QqQ MS/MS|journal=Journal of Agricultural and Food Chemistry|volume=61|issue=32|year=2013|pages=7754–7759|doi=10.1021/jf402295u|pmid=23862656|s2cid=22497338 |url=https://escholarship.org/uc/item/9dw6c0v6}}</ref>

For one method of isolating amygdalin, the stones are removed from the fruit and cracked to obtain the kernels, which are dried in the sun or in ovens. The kernels are boiled in [[Chemistry:Ethanol|ethanol]]; on evaporation of the solution and the addition of [[Chemistry:Diethyl ether|diethyl ether]], amygdalin is precipitated as minute white crystals.<ref>{{Cite EB1911|wstitle=Amygdalin|volume=1|page=900}}</ref> Natural amygdalin has the (''R'')-configuration at the chiral phenyl center. Under mild basic conditions, this stereogenic center isomerizes; the (''S'')-epimer is called '''neoamygdalin'''. Although the synthesized version of amygdalin is the (''R'')-epimer, the stereogenic center attached to the nitrile and phenyl groups easily epimerizes if the manufacturer does not store the compound correctly.<ref>{{cite journal | vauthors = Wahab MF, Breitbach ZS, Armstrong DW, Strattan R, Berthod A | title = Problems and Pitfalls in the Analysis of Amygdalin and Its Epimer | journal = Journal of Agricultural and Food Chemistry | volume = 63 | issue = 40 | pages = 8966–73 | date = October 2015 | pmid = 26431391 | doi = 10.1021/acs.jafc.5b03120 }}</ref>

Amygdalin is [[Chemistry:Hydrolysis|hydrolyzed]] by intestinal β-glucosidase (emulsin)<ref>{{cite book|last1=George Mann|first1=Frederick|last2=Charles Saunders|first2=Bernard | name-list-style = vanc |title=Practical Organic Chemistry|date=1975|publisher=Longman|location=London|isbn=9788125013808|pages=509–517|edition=4th|url=http://www.sciencemadness.org/talk/files.php?pid=385854&aid=36353|access-date=1 February 2016}}</ref> and [[Biology:Amygdalin beta-glucosidase|amygdalin beta-glucosidase]] (amygdalase) to give [[Chemistry:Gentiobiose|gentiobiose]] and <small>L</small>-mandelonitrile. Gentiobiose is further hydrolyzed to give [[Chemistry:Glucose|glucose]], whereas mandelonitrile (the [[Chemistry:Cyanohydrin|cyanohydrin]] of [[Chemistry:Benzaldehyde|benzaldehyde]]) decomposes to give benzaldehyde and [[Chemistry:Hydrogen cyanide|hydrogen cyanide]]. Hydrogen cyanide in sufficient quantities ([[Chemistry:Acceptable daily intake|allowable daily intake]]: ~0.6&nbsp;mg) causes cyanide poisoning which has a fatal oral dose range of  0.6–1.5&nbsp;mg/kg of body weight.<ref name="ATSDR 2014">{{cite web | title=Medical Management Guidelines (MMGs): Hydrogen Cyanide (HCN) | website=ATSDR | date=2014-10-21 | url=https://www.atsdr.cdc.gov/MMG/MMG.asp?id=1141&tid=249 | access-date=2019-07-08}}</ref>

== Laetrile ==

{{Chembox
| Name = Laetrile
| ImageFile = Laetrile.svg
| ImageSize =
| ImageAlt =
| IUPACName = (2''S'',3''S'',4''S'',5''R'',6''R'')-6-[(''R'')-cyano(phenyl)methoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
| OtherNames = <small>L</small>-mandelonitrile-β-<small>D</small>-glucuronide, Vitamin B<sub>17</sub>
|Section1={{Chembox Identifiers
| CASNo = 1332-94-1
| PubChem = 5484354
|  ChemSpiderID = 4588479
|  SMILES = c1ccc(cc1)[C@H](C#N)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C(=O)O)O)O)O
|  StdInChI = 1S/C14H15NO7/c15-6-8(7-4-2-1-3-5-7)21-14-11(18)9(16)10(17)12(22-14)13(19)20/h1-5,8-12,14,16-18H,(H,19,20)/t8-,9-,10-,11+,12-,14+/m0/s1
|  StdInChIKey = XLSLFPQAPYONPW-WHUHBCJBSA-N
}}
|Section2={{Chembox Properties
| Formula =
| C=14 | H=15 | N=1 | O=7
| MolarMass = 309.2714
| Appearance =
| Density =
| MeltingPtC = 214 to 216
| BoilingPt =
| Solubility =
}}
|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}

Laetrile (patented 1961) is a simpler semisynthetic [[Chemistry:Derivative|derivative]] of amygdalin. Laetrile is synthesized from amygdalin by hydrolysis. The usual preferred commercial source is from apricot kernels (''[[Biology:Prunus armeniaca|Prunus armeniaca]]''). The name is derived from the separate words "laevorotatory" and "mandelonitrile". Laevorotatory describes the stereochemistry of the molecule, while mandelonitrile refers to the portion of the molecule from which cyanide is released by decomposition.<ref name="NCIpdq">{{cite journal | title = Laetrile/Amygdalin (PDQ®)–Health Professional Version: General Information | date = March 15, 2017 | pmid = 26389425 | url = https://www.cancer.gov/about-cancer/treatment/cam/hp/laetrile-pdq#section/_5 | website = cancer.gov | publisher = National Cancer Institute | series = Complementary and Alternative Medicine for Health Professionals | access-date = 2017-05-09 | last1 = Pdq Integrative | first1 = Alternative }}</ref>
A 500&nbsp;mg laetrile tablet may contain between 2.5 and 25&nbsp;mg of hydrogen cyanide.<ref>{{citation | editor=Jerrold B. Leikin | editor2=Frank P. Paloucek | entry=Laetrile | title=Poisoning and Toxicology Handbook | edition=4th | publisher=Informa | year=2008 | page=950 | isbn=978-1-4200-4479-9}}</ref>

Like amygdalin, laetrile is hydrolyzed in the duodenum (alkaline) and in the intestine (enzymatically) to <small>D</small>-[[Chemistry:Glucuronic acid|glucuronic acid]] and <small>L</small>-mandelonitrile; the latter hydrolyzes to benzaldehyde and hydrogen cyanide, that in sufficient quantities causes [[Medicine:Cyanide poisoning|cyanide poisoning]].<ref>{{cite journal | vauthors = Rietjens IM, Martena MJ, Boersma MG, Spiegelenberg W, Alink GM | title = Molecular mechanisms of toxicity of important food-borne phytotoxins | journal = Molecular Nutrition & Food Research | volume = 49 | issue = 2 | pages = 131–58 | date = February 2005 | pmid = 15635687 | doi = 10.1002/mnfr.200400078 }}</ref>

Claims for laetrile were based on three different hypotheses:<ref name=":0">{{cite book | first = James A. | last = Duke | name-list-style = vanc | title=CRC Handbook of Medicinal Spices | publisher=CRC Press | year=2003 | isbn=978-0-8493-1279-3 | pages=261–262}}</ref> The first hypothesis proposed that cancerous cells contained copious beta-glucosidases, which release HCN from laetrile via hydrolysis. Normal cells were reportedly unaffected, because they contained low concentrations of beta-glucosidases and high concentrations of [[Biology:Rhodanese|rhodanese]], which converts HCN to the less toxic [[Chemistry:Thiocyanate|thiocyanate]]. Later, however, it was shown that both cancerous and normal cells contain only trace amounts of beta-glucosidases and similar amounts of rhodanese.<ref name=":0" />

The second proposed that, after ingestion, amygdalin was hydrolyzed to mandelonitrile, transported intact to the liver and converted to a beta-glucuronide complex, which was then carried to the cancerous cells, hydrolyzed by beta-glucuronidases to release mandelonitrile and then HCN. Mandelonitrile, however, dissociates to benzaldehyde and hydrogen cyanide, and cannot be stabilized by glycosylation.<ref name="EFSA2016">{{cite journal|title=Acute health risks related to the presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot kernels|journal=EFSA Journal|volume=14|issue=4|year=2016|doi=10.2903/j.efsa.2016.4424|doi-access=free|hdl=2164/7789|hdl-access=free}}</ref>{{rp|9}}

Finally, the third asserted that laetrile is the discovered vitamin B-17, and further suggests that cancer is a result of "B-17 deficiency". It postulated that regular dietary administration of this form of laetrile would, therefore, actually prevent all incidences of cancer. There is no evidence supporting this conjecture in the form of a physiologic process, nutritional requirement, or identification of any deficiency syndrome.<ref name="pmid1154776">{{cite journal | vauthors = Greenberg DM | title = The vitamin fraud in cancer quackery | journal = The Western Journal of Medicine | volume = 122 | issue = 4 | pages = 345–8 | date = April 1975 | pmid = 1154776 | pmc = 1129741 }}</ref> The term "vitamin B-17" is not recognized by Committee on Nomenclature of the American Institute of Nutrition Vitamins.<ref name="NCIpdq" /> [[Unsolved:Ernst T. Krebs|Ernst T. Krebs]] (not to be confused with [[Biography:Hans Adolf Krebs|Hans Adolf Krebs]], the discoverer of the [[Biology:Citric acid cycle|citric acid cycle]]) branded laetrile as a vitamin in order to have it classified as a nutritional supplement rather than as a pharmaceutical.<ref name=CaCancer>{{cite journal | vauthors = Lerner IJ | title = Laetrile: a lesson in cancer quackery | journal = CA: A Cancer Journal for Clinicians | volume = 31 | issue = 2 | pages = 91–5 | year = 1981 | pmid = 6781723 | doi = 10.3322/canjclin.31.2.91 | s2cid = 28917628 | doi-access = free }}</ref>

=== History of laetrile ===
==== Early usage ====
Amygdalin was first isolated in 1830 from [[Biology:Bitter almond|bitter almond]] seeds (''[[Biology:Prunus dulcis|Prunus dulcis]]'') by Pierre-Jean Robiquet and Antoine Boutron-Charlard.<ref>{{cite web|title=A chronology of significant historical developments in the biological sciences |work=Botany Online Internet Hypertextbook |publisher=[[Organization:University of Hamburg|University of Hamburg]], Department of Biology |date=18 August 2002 |url=http://www.biologie.uni-hamburg.de/b-online/e01/geschichte.htm |access-date=6 August 2007 |archive-url=https://web.archive.org/web/20070820063617/http://www.biologie.uni-hamburg.de/b-online/e01/geschichte.htm |archive-date=20 August 2007 |url-status=dead |df=dmy }}</ref> Liebig and Wöhler found three [[Chemistry:Hydrolysis|hydrolysis]] products of amygdalin: sugar, benzaldehyde, and prussic acid (hydrogen cyanide, HCN).<ref>{{cite journal | title=Ueber die Bildung des Bittermandelöls |author1=Wöhler, F. |author2=Liebig, J. | journal=Annalen der Pharmacie | year=1837 | volume=22 | issue=1 | pages=1–24 | doi=10.1002/jlac.18370220102|s2cid=96869201 |url=https://zenodo.org/record/1426920 }}</ref> Later research showed that [[Chemistry:Sulfuric acid|sulfuric acid]] hydrolyzes it into <small>D</small>-glucose, benzaldehyde, and prussic acid; while [[Chemistry:Hydrochloric acid|hydrochloric acid]] gives [[Chemistry:Mandelic acid|mandelic acid]], <small>D</small>-glucose, and [[Chemistry:Ammonia|ammonia]].<ref>{{cite journal | title=The hydrolysis of amygdalin by acids. Part I |author1=Walker, J. W. |author2=Krieble, V. K. | journal=[[Organization:Journal of the Chemical Society|Journal of the Chemical Society]] | year=1909 | volume=95 | issue=11 | pages=1369–77 | doi=10.1039/CT9099501369}}</ref>

In 1845 amygdalin was used as a cancer treatment in Russia, and in the 1920s in the United States, but it was considered too poisonous.<ref name=CancerInstitute/> In the 1950s, a purportedly non-toxic, synthetic form was patented for use as a meat preservative,<ref name=patent>{{Cite patent| inventor-last = Krebs | inventor-first =Ernst T. | inventor2-last =Krebs, Jr. | inventor2-first =Ernst T. | pubdate = 23 May 1961 | title = Hexuronic acid derivatives | url = http://www.freepatentsonline.com/2985664.html | country = US | number = 2985664 | inventor =E Krebs}}</ref> and later marketed as laetrile for cancer treatment.<ref name=CancerInstitute/>

The U.S. Food and Drug Administration prohibited the interstate shipment of amygdalin and laetrile in 1977.<ref>{{cite book|last=Carpenter|first=Daniel | name-list-style = vanc |title= Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA. Princeton: Princeton University Press.|year=2010|publisher=Princeton University Press|location=Princeton|isbn=978-0-691-14180-0}}</ref><ref>{{cite journal | first = Donald | last = Kennedy | name-list-style = vanc | year = 1977 | url = http://www.cancertreatmentwatch.org/q/laetrile/commissioner.pdf | title = Laetrile: The Commissioner's Decision | journal = Federal Register | volume = Docket No. 77-22310}}</ref> Thereafter, 27 U.S. states legalized the use of amygdalin within those states.<ref>{{cite journal | author = American Cancer Society | title = Unproven methods of cancer management. Laetrile | journal = CA: A Cancer Journal for Clinicians | volume = 41 | issue = 3 | pages = 187–92 | year = 1991 | pmid = 1902140 | doi = 10.3322/canjclin.41.3.187 | s2cid = 5932239 | doi-access = free }}</ref>

==== Subsequent results ====
In a 1977 controlled, blinded trial, laetrile showed no more activity than placebo.<ref name="Wade1977"/>

Subsequently, laetrile was tested on 14 tumor systems without evidence of effectiveness. The Memorial Sloan&ndash;Kettering Cancer Center (MSKCC) concluded that "laetrile showed no beneficial effects."<ref name=Wade1977/> Mistakes in an earlier MSKCC press release were highlighted by a group of laetrile proponents led by Ralph Moss, former public affairs official of MSKCC who had been fired following his appearance at a press conference accusing the hospital of covering up the benefits of laetrile.<ref name="Budiansky1995">{{cite news|first=Stephen |last=Budiansky | name-list-style = vanc |title=Cures or Quackery: How Senator Harkin shaped federal research on alternative medicine |date=9 July 1995 |url=https://www.usnews.com/usnews/culture/articles/950717/archive_032434.htm |work=U.S. News & World Report |access-date=7 November 2009 |url-status=dead |archive-url=https://web.archive.org/web/20110903141336/http://www.usnews.com/usnews/culture/articles/950717/archive_032434.htm |archive-date=3 September 2011 |df=dmy }}</ref> These mistakes were considered scientifically inconsequential, but Nicholas Wade in ''Science'' stated that "even the appearance of a departure from strict objectivity is unfortunate."<ref name=Wade1977>{{cite journal | vauthors = Wade N | title = Laetrile at Sloan-Kettering: a question of ambiguity | journal = Science | volume = 198 | issue = 4323 | pages = 1231–4 | date = December 1977 | pmid = 17741690 | doi = 10.1126/science.198.4323.1231 | bibcode = 1977Sci...198.1231W }}</ref> The results from these studies were published all together.<ref>{{cite journal | vauthors = Stock CC, Tarnowski GS, Schmid FA, Hutchison DJ, Teller MN | title = Antitumor tests of amygdalin in transplantable animal tumor systems | journal = Journal of Surgical Oncology | volume = 10 | issue = 2 | pages = 81–8 | year = 1978 | pmid = 642516 | doi = 10.1002/jso.2930100202 | s2cid = 5896930 }}<br />
{{cite journal | vauthors = Stock CC, Martin DS, Sugiura K, Fugmann RA, Mountain IM, Stockert E, Schmid FA, Tarnowski GS | title = Antitumor tests of amygdalin in spontaneous animal tumor systems | journal = Journal of Surgical Oncology | volume = 10 | issue = 2 | pages = 89–123 | year = 1978 | pmid = 347176 | doi = 10.1002/jso.2930100203 | s2cid = 22185766 }}</ref>

A 2015 [[Systematic review|systematic review]] from the Cochrane Collaboration found: {{quotation|<nowiki>The claims that laetrile or amygdalin have beneficial effects for cancer patients are not currently supported by sound clinical data. There is a considerable risk of serious adverse effects from cyanide poisoning after laetrile or amygdalin, especially after oral ingestion. The risk–benefit balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously negative.</nowiki><ref name=Milazzo2015 />|sign=|source=}}

The authors also recommended, on ethical and scientific grounds, that no further clinical research into laetrile or amygdalin be conducted.<ref name=Milazzo2015 />

Given the lack of evidence, laetrile has not been approved by the U.S. Food and Drug Administration or the European Commission.

The U.S. [[Organization:National Institutes of Health|National Institutes of Health]] evaluated the evidence separately and concluded that clinical trials of amygdalin showed little or no effect against cancer.<ref name =CancerInstitute>{{cite web|url=http://www.cancer.gov/cancertopics/pdq/cam/laetrile/patient/allpages#Section_20|title=Laetrile/Amygdalin|work=National Cancer Institute|date=2005-09-23}}</ref> For example, a 1982 trial by the Mayo Clinic of 175 patients found that tumor size had increased in all but one patient.<ref>{{cite web|url=http://www.cancerhelp.org.uk/about-cancer/treatment/complementary-alternative/therapies/laetrile|title=Laetrile (amygdalin, vitamin B17)|work=cancerhelp.org.uk|date=2017-08-30}}</ref> The authors reported that "the hazards of amygdalin therapy were evidenced in several patients by symptoms of cyanide toxicity or by blood cyanide levels approaching the lethal range."

The study concluded "Patients exposed to this agent should be instructed about the danger of cyanide poisoning, and their blood cyanide levels should be carefully monitored. Amygdalin (Laetrile) is a toxic drug that is not effective as a cancer treatment".

Additionally,  "No controlled clinical trials (trials that compare groups of patients who receive the new treatment to groups who do not) of laetrile have been reported."<ref name =CancerInstitute />

The side effects of laetrile treatment are the symptoms of cyanide poisoning. These symptoms include: nausea and vomiting, headache, dizziness, cherry red skin color, liver damage, abnormally low blood pressure, droopy upper eyelid, trouble walking due to damaged nerves, fever, mental confusion, coma, and death.

The European Food Safety Agency's Panel on Contaminants in the Food Chain has studied the potential toxicity of the amygdalin in apricot kernels.  The Panel reported, "If consumers follow the recommendations of websites that promote consumption of apricot kernels, their exposure to cyanide will greatly exceed" the dose expected to be toxic.  The Panel also reported that acute cyanide toxicity had occurred in adults who had consumed 20 or more kernels and that in children "five or more kernels appear to be toxic".<ref name="EFSA2016" />

=== Advocacy and legality of laetrile ===
Advocates for laetrile assert that there is a [[Unsolved:Conspiracy theory|conspiracy]] between the US [[Organization:Food and Drug Administration|Food and Drug Administration]], the [[Medicine:Pharmaceutical industry|pharmaceutical industry]] and the medical community, including the American Medical Association and the American Cancer Society, to exploit the American people, and especially cancer patients.<ref name=ConsumerReports/>

Advocates of the use of laetrile have also changed the rationale for its use, first as a treatment of cancer, then as a vitamin, then as part of a "holistic" nutritional regimen, or as treatment for cancer pain, among others, none of which have any significant evidence supporting its use.<ref name=ConsumerReports/>

Despite the lack of evidence for its use, laetrile developed a significant following due to its wide promotion as a "pain-free" treatment of cancer as an alternative to [[Medicine:Surgery|surgery]] and [[Medicine:Chemotherapy|chemotherapy]] that have significant side effects. The use of laetrile led to a number of deaths.<ref name=ConsumerReports>{{Cite book | last = Editors of Consumer Reports Books | title = Health Quackery | place = Vernon, New York | publisher = Consumers Union | year = 1980 | chapter = Laetrile: the Political Success of a Scientific Failure | pages = [https://archive.org/details/healthquackeryco00cons/page/16 16–40] | isbn = 978-0-89043-014-9 | chapter-url-access = registration | chapter-url = https://archive.org/details/healthquackeryco00cons | url = https://archive.org/details/healthquackeryco00cons/page/16 }}</ref>
The FDA and AMA crackdown, begun in the 1970s, effectively escalated prices on the black market, played into the conspiracy narrative and enabled unscrupulous profiteers to foster multimillion-dollar smuggling empires.<ref>{{cite journal|last1=Herbert|first1=V|title=Laetrile: the cult of cyanide Promoting poison for profit|journal=The American Journal of Clinical Nutrition|volume=32|issue=5|year=1979|pages=1121–1158|doi=10.1093/ajcn/32.5.1121|pmid=219680|doi-access=free}}</ref>

Some American cancer patients have traveled to Mexico for treatment with the substance, for example at the [[Unsolved:Oasis of Hope Hospital|Oasis of Hope Hospital]] in Tijuana.<ref name=Moss2005>{{cite journal | vauthors = Moss RW | title = Patient perspectives: Tijuana cancer clinics in the post-NAFTA era | journal = Integrative Cancer Therapies | volume = 4 | issue = 1 | pages = 65–86 | date = March 2005 | pmid = 15695477 | doi = 10.1177/1534735404273918 | doi-access = free }}</ref> The actor Steve McQueen died in Mexico following surgery to remove a stomach tumor, having previously undergone extended treatment for pleural [[Medicine:Mesothelioma|mesothelioma]] (a cancer associated with asbestos exposure) under the care of William D. Kelley, a de-licensed dentist and orthodontist who claimed to have devised a cancer treatment involving pancreatic enzymes, 50 daily vitamins and minerals, frequent body shampoos, enemas, and a specific diet as well as laetrile.<ref>{{cite news|url=https://www.nytimes.com/2005/11/15/health/15essa.html?ex=1289710800&en=8059981c17deec5d&ei=5088|title=McQueen's Legacy of Laetrile|newspaper={{wipe|The New York Times}}|date=15 November 2005 | first=Barron H. | last=Lerner | name-list-style = vanc | access-date=23 April 2010}}</ref>

Laetrile advocates in the United States include [[Biography:Dean Burk|Dean Burk]], a former chief chemist of the [[Organization:National Cancer Institute|National Cancer Institute]] [[Biology:Cytochemistry|cytochemistry]] laboratory,<ref>{{cite news | url = http://www.highbeam.com/doc/1P2-1283487.html | title = Dean Burk, 84, Noted Chemist At National Cancer Institute, Dies | newspaper = {{wipe|The Washington Post}} | date = 9 October 1988 | access-date = 14 January 2007 | archive-url = https://web.archive.org/web/20121105073833/http://www.highbeam.com/doc/1P2-1283487.html | archive-date = 5 November 2012 | url-status = dead | df = dmy-all }}</ref> and national arm wrestling champion Jason Vale, who falsely claimed that his [[Medicine:Kidney cancer|kidney]] and [[Medicine:Pancreatic cancer|pancreatic]] cancers were cured by eating [[Biology:Apricot|apricot]] seeds. Vale was convicted in 2004 for, among other things, fraudulently marketing laetrile as a cancer cure.<ref>{{cite book | first = Brian S. | last = McWilliams | name-list-style = vanc |title=Spam kings: the real story behind the high-rolling hucksters pushing porn, pills and @*#?% enlargements |publisher=O'Reilly |location=Sebastopol, CA |year=2005 |isbn=978-0-596-00732-4 |url=https://archive.org/details/spamkingsrealsto00mcwi| url-access = registration | page = [https://archive.org/details/spamkingsrealsto00mcwi/page/237 237] | quote = Jason Vale. }}</ref> The court also found that Vale had made at least $500,000 from his fraudulent sales of laetrile.<ref>{{cite news |url=http://www.medicalnewstoday.com/articles/9825.php |title=New York Man Sentenced to 63 Months for Selling Fake Cancer Cure |date=22 June 2004 |work=Medical News Today |access-date=8 July 2010}}</ref>

In the  1970s, court cases in several states challenged the FDA's authority to restrict access to what they claimed are potentially lifesaving drugs. More than twenty states passed laws making the use of laetrile legal. After the unanimous Supreme Court ruling in ''United States v. Rutherford''<ref>{{cite court |litigants= United States v. Rutherford |vol= 442 |reporter= U.S. |opinion= 544 |court= United States Supreme Court |date= 1979 |url= http://caselaw.lp.findlaw.com/scripts/getcase.pl?navby=CASE&court=US&vol=442&page=544 }}</ref> which established that interstate transport of the compound was illegal, usage fell off dramatically.<ref name="NCIpdq" /><ref name="Curran1980">{{cite journal | vauthors = Curran WJ | title = Law-medicine notes. Laetrile for the terminally ill: Supreme Court stops the nonsense | journal = The New England Journal of Medicine | volume = 302 | issue = 11 | pages = 619–21 | date = March 1980 | pmid = 7351911 | doi = 10.1056/NEJM198003133021108 }}</ref> The US Food and Drug Administration continues to seek jail sentences for vendors marketing laetrile for cancer treatment, calling it a "highly toxic product that has not shown any effect on treating cancer."<ref name=usfda>{{cite web |publisher= FDA |date= June 22, 2004 |url= https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108314.htm |title= Lengthy Jail Sentence for Vendor of Laetrile – A Quack Medication to Treat Cancer Patients |archive-url= https://web.archive.org/web/20090710102512/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108314.htm |archive-date= 2009-07-10 }}</ref>

===In popular culture===

The ''Law & Order'' episode "Second Opinion" is about a nutritional counselor named "Doctor" Haas giving patients laetrile as a cancer treatment for breast cancer as an alternative to getting a mastectomy.

== See also ==


* List of ineffective cancer treatments
* [[Unsolved:Alternative cancer treatments|Alternative cancer treatments]]

== References ==

{{Reflist|30em}}

== External links ==

* [http://www.cancer.gov/cancertopics/pdq/cam/laetrile/patient/allpages Laetrile/Amygdalin information] from the [[Organization:National Cancer Institute|National Cancer Institute (U.S.A.)]]
* [http://www.cancertreatmentwatch.org/q/laetrile/commissioner.pdf Food and Drug Administration Commissioner's Decision on Laetrile]
* [http://www.quackwatch.com/01QuackeryRelatedTopics/Cancer/laetrile.html The Rise and Fall of Laetrile]

{{Glycosides}}

[[Category:Alternative cancer treatments]]
[[Category:Cyanogenic glycosides]]
[[Category:Plant toxins]]


{{Sourceattribution|Amygdalin}}