Editing Amygdalin (section)

=== History of laetrile ===

==== Early usage ====
Amygdalin was first isolated in 1830 from [[bitter almond]] seeds (''[[Prunus dulcis]]'') by [[Pierre-Jean Robiquet]] and [[Antoine François Boutron Charlard|Antoine Boutron-Charlard]].<ref>{{cite web | vauthors = von Sengbusch P |title=A chronology of significant historical developments in the biological sciences |work=Botany Online Internet Hypertextbook |publisher=[[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 }}</ref> [[Justus von Liebig|Liebig]] and [[Friedrich Woehler|Wöhler]] found three [[hydrolysis]] products of amygdalin: sugar, benzaldehyde, and [[hydrogen cyanide]].<ref>{{cite journal | title=Ueber die Bildung des Bittermandelöls | vauthors = Wöhler F, 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 [[sulfuric acid]] hydrolyzes it into [[D-glucose|<small>D</small>-glucose]], benzaldehyde, and hydrogen cyanide; while [[hydrochloric acid]] gives [[mandelic acid]], <small>D</small>-glucose, and [[ammonia]].<ref>{{cite journal | title=The hydrolysis of amygdalin by acids. Part I | vauthors = Walker JW, Krieble VK | journal=[[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 = Krebs Jr ET | pubdate = 23 May 1961 | title = Hexuronic acid derivatives | url = http://www.freepatentsonline.com/2985664.html | country = US | number = 2985664 | gdate = 23 May 1961 }}</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| vauthors = Carpenter D |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 | vauthors = Kennedy D |date= 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 | vauthors = <!-- Not listed --> | title = Unproven methods of cancer management. Laetrile | journal = CA: A Cancer Journal for Clinicians | publisher = American Cancer Society | volume = 41 | issue = 3 | pages = 187–192 |date= 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 W. Moss (science writer)|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| vauthors = Budiansky S |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 }}</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 = 1231–1234 | 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 = 81–88 |date= 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 |date= 1978 | pmid = 347176 | doi = 10.1002/jso.2930100203 | s2cid = 22185766 }}</ref>

A 2015 [[systematic review]] from the [[Cochrane Collaboration]] found: {{blockquote|<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 /> Subsequent research has confirmed the evidence of harm and lack of benefit.<ref>{{cite journal | vauthors = He XY, Wu LJ, Wang WX, Xie PJ, Chen YH, Wang F | title = Amygdalin – A pharmacological and toxicological review | journal = Journal of Ethnopharmacology | volume = 254 | pages = 112717 | date = May 2020 | pmid = 32114166 | doi = 10.1016/j.jep.2020.112717 }}</ref>

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. [[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|publisher=National Cancer Institute|date=23 September 2005}}</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) |website=CancerHelp.org.uk |date=30 August 2017 }}</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="EFSA 2016" />