Amygdalin

From Wikipedia, the free encyclopedia

Amygdalin

Names
IUPAC name
[(6-O--D-Glucopyranosyl--D-
glucopyranosyl)oxy](phenyl)acetonitrile
Identifiers
29883-15-6
CAS Number
Interactive image
3D model (Jmol) Interactive image

CHEBI:17019
ChEBI
570897
ChemSpider
ECHA InfoCard 100.045.372
MeSH Amygdalin
34751
PubChem CID
214UUQ9N0H
UNII
InChI[show]
SMILES[show]
Properties
Chemical formula C20H27NO11
Molar mass 457.429
Melting point 223-226 C(lit.)
H2O: 0.1 g/mL hot, clear to
Solubility in water
very faintly turbid, colorless
Hazards
Safety data sheet A6005

GHS pictograms

GHS signal word Warning

GHS hazard
H302
statements
GHS precautionary P264, P270, P301+312, P330,
statements P501

NFPA 704
0
1
0
Related compounds
Vicianin, laetrile, prunasin,
Related compounds
sambunigrin
Except where otherwise noted, data are given for
materials in their standard state (at 25 C [77 F],
100 kPa).
verify (what is ?)
Infobox references

Amygdalin (from Ancient Greek: amygdl "almond") is a poisonous cyanogenic

glycoside found in many plants, but most notably in the seeds (kernels) of apricot, bitter
almonds, apple, peach, and plum.

Since the early 1950s, both amygdalin and a modified form named laetrile have been promoted
as alternative cancer treatments, often using the misnomer Vitamin B17.[1] But studies have
found them to be clinically ineffective in the treatment of cancer, as well as potentially toxic or
lethal when taken by mouth, due to cyanide poisoning. Neither amygdalin nor laetrile is a
vitamin.
The promotion of laetrile to treat cancer has been described in the medical literature as a
canonical example of quackery,[2][3] and as "the slickest, most sophisticated, and certainly the
most remunerative cancer quack promotion in medical history."[1]

Contents
1 Chemistry
2 Laetrile
o 2.1 History of laetrile
2.1.1 Early usage
2.1.2 Initial positive results
2.1.3 Subsequent results
o 2.2 Advocacy and legality of laetrile
3 See also
4 References
5 External links

Chemistry
Amygdalin is a cyanogenic glycoside derived from the aromatic amino acid phenylalanine.
Amygdalin and prunasin are very common among plants of the Rosaceae family, particularly the
genus Prunus, Poaceae (grasses), Fabaceae (legumes), and in other food plants, including linseed
and manioc. Sambunigrin, obtained from leaves of the elder tree (Sambucus nigra), is isomeric
to prunasin.[4] Within these plants, amygdalin and the enzymes necessary to hydrolyze them are
stored in separate locations so that they will mix in response to tissue damage. This provides a
natural defense system[5]

Amygdalin is contained in stone fruit kernels, such as apricot (8%), peach (6%), bitter almond
(5%), and plum (2.5%); amygdalin is also found in the seeds of the apple.[6] The stones are taken
out of the fruit and cracked to obtain the kernels, which are dried in the sun or in ovens. The
kernels are boiled in ethanol; on evaporation of the solution and the addition of diethyl ether,
amygdalin is precipitated as white minute crystals. 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.[7]

Amygdalin is hydrolyzed by intestinal -glucosidase, emulsin,[8] and amygdalase to gentiobiose

and L-mandelonitrile. Gentiobiose is further hydrolyzed to glucose, whereas mandelonitrile is
hydrolyzed to benzaldehyde and hydrogen cyanide. Hydrogen cyanide in sufficient quantities
(allowable daily intake: ~0.6 mg)[citation needed] causes cyanide poisoning (fatal oral dose: 0.6-
1.5 mg/kg)[citation needed]. Apricot pits contain 89-2,170 mg/kg hydrogen cyanide (wet
weight).[citation needed]

Laetrile
 Laetrile

Names
IUPAC name
(2S,3S,4S,5R,6R)-6-[(R)-cyano(phenyl)methoxy]-
3,4,5-trihydroxyoxane-2-carboxylic acid
Other names
L-mandelonitrile--D-glucuronide, Vitamin B
Identifiers
1332-94-1
CAS Number
Interactive image
3D model (Jmol)
4588479
ChemSpider
ECHA InfoCard 100.045.372
5484354
PubChem CID
InChI[show]
SMILES[show]
Properties
Chemical formula C14H15NO7
Molar mass 309.2714
214 to 216 C (417 to 421 F;
Melting point
487 to 489 K)
Except where otherwise noted, data are given for
materials in their standard state (at 25 C [77 F],
100 kPa).
Infobox references

Laetrile (patented 1961) is a simpler semisynthetic version of amygdalin. Laetrile is synthesized

from amygdalin by hydrolysis. The usual preferred commercial source is from apricot kernels
(Prunus armeniaca). The name is derived from the separate words "laevarotatory" and
"mandelonitrile". Laevarotatory describes the stereochemistry of the molecule, while
mandelonitrile refers to its chemical identity[9]

A 500 mg laetrile tablet may contain between 551 mg of hydrogen cyanide per gram.[10]
Like amygdalin, laetrile is hydrolyzed in the duodenum (alkaline) and in the intestine
(enzymatically) to D-glucuronic acid and L-mandelonitrile; the latter hydrolyzes to benzaldehyde
and hydrogen cyanide, that in sufficient quantities causes cyanide poisoning. Intravenous laetrile
does not result in cyanide exposure. This is due to the fact that the necessary enzymes are
released either upon chewing the plant material or are provided by bacteria residing in the human
gastrointestinal system.[11]

Claims for laetrile were based on three different hypotheses:[12]

Hypothesis (1) 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 rhodanese, which converts HCN to the less toxic thiocyanate. Later, however, it was
shown that both cancerous and normal cells contain only trace amounts of beta-
glucosidases and similar amounts of rhodanese.[12]
Hypothesis (2) 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. This was considered untenable.
Hypothesis (3) 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 incidence of
cancer. There is no credible evidence supporting this conjecture.

Ernst T. Krebs branded laetrile as a vitamin in order to have it classified as a nutritional

supplement rather than as a pharmaceutical.[1]

History of laetrile

Early usage

Amygdalin was first isolated in 1830 from bitter almond seeds (Prunus dulcis) by Pierre-Jean
Robiquet and Antoine Boutron-Charlard.[13] Liebig and Whler found three hydrolysis products
of amygdalin: sugar, benzaldehyde, and prussic acid (hydrogen cyanide).[14] Later research
showed that sulfuric acid hydrolyzes it into D-glucose, benzaldehyde, and prussic acid; while
hydrochloric acid gives mandelic acid, D-glucose, and ammonia.[15]

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.[16] In the 1950s, a purportedly non-toxic, synthetic
form was patented for use as a meat preservative,[17] and later marketed as laetrile for cancer
treatment.[16]

The U.S. Food and Drug Administration prohibited the interstate shipment of amygdalin and
laetrile in 1977.[18][19] Thereafter, 27 U.S. states legalized the use of amygdalin within those
states.[20]
Initial positive results

In 1972, Memorial Sloan-Kettering Cancer Center (MSKCC) board member Benno C. Schmidt,
Sr. convinced the hospital to test laetrile. Kanematsu Sugiura, the scientist who performed the
tests, found that laetrile inhibited secondary tumors in mice, though it did not destroy the primary
tumors. He repeated the experiment several times with the same results. However, three other
researchers were unable to confirm Sugiura's results. Sugiura's results were leaked to laetrile
advocates, resulting in significant public attention.

Subsequent results

In 1977 a controlled, blinded follow-up experiment, laetrile showed no more activity than
placebo.[21]

Subsequently, laetrile was tested on 14 tumor systems without evidence of effectiveness.

MSKCC concluded that "laetrile showed no beneficial effects."[21] Mistakes in the MSKCC press
release were highlighted by a group of laetrile proponents led by Ralph Moss, former public
affairs official of MSKCC who was fired following his appearance at a press conference
accusing the hospital of covering up the benefits of laetrile.[22] These mistakes were considered
scientifically inconsequential, but Nicholas Wade in Science stated that "even the appearance of
a departure from strict objectivity is unfortunate."[21] The results from these studies were
published all together.[23]

A 2011 systematic review from the Cochrane Collaboration found:

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 riskbenefit
balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously
negative.[24][needs update]

The authors also recommended, on ethical grounds, that no further clinical research into laetrile
or amygdalin be conducted.[24]

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

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.[16] For example, a 1982 trial
by the Mayo Clinic of 175 patients found that tumor size had increased in all but one patient.[25]
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." [26]

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.

Advocacy and legality of laetrile

Advocates for laetrile assert that there is a conspiracy between the US Food and Drug
Administration, the 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.[27]

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.[27]

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 surgery and chemotherapy that
have significant side effects. The use of laetrile led to a number of deaths.[27] 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.[28]

Some North American cancer patients have traveled to Mexico for treatment with the substance,
for example at the Oasis of Hope Hospital in Tijuana.[29] The actor Steve McQueen died in
Mexico following surgery to remove a stomach tumor having previously undergone extended
treatment for pleural 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.[30]

Laetrile advocates in the United States include Dean Burk, a former chief chemist of the National
Cancer Institute cytochemistry laboratory,[31] and national arm wrestling champion Jason Vale,
who claimed that his kidney and pancreatic cancers were cured by eating apricot seeds. Vale was
convicted in 2004 for, among other things, fraudulently marketing laetrile as a cancer cure.[32]
The court also found that Vale had made at least $500,000 from his fraudulent sales of laetrile.[33]

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."[34]

See also
 Medicine portal

List of ineffective cancer treatments

Alternative cancer treatments
Amygdalin beta-glucosidase
Beta-glucosidase

References
1.

Lerner IJ (1981). "Laetrile: a lesson in cancer quackery". CA Cancer J Clin. 31 (2): 915.
doi:10.3322/canjclin.31.2.91. PMID 6781723.
Lerner IJ (February 1984). "The whys of cancer quackery". Cancer. 53 (3 Suppl): 8159.
doi:10.1002/1097-0142(19840201)53:3+<815::AID-CNCR2820531334>3.0.CO;2-U.
PMID 6362828.
Nightingale SL (1984). "Laetrile: the regulatory challenge of an unproven remedy". Public
Health Rep. 99 (4): 3338. PMC 1424606 . PMID 6431478.
Andrew Pengelly (2004), The Constituents of Medicinal Plants (2nd ed.), Allen & Unwin,
pp. 4445, ISBN 1-74114-052-8
Mora, Carlos A.; Halter, Jonas G.; Adler, Cornel; Hund, Andreas; Anders, Heidrun; Yu,
Kang; Stark, Wendelin J. (2016-05-11). "Application of the Prunus spp. Cyanide Seed Defense
System onto Wheat: Reduced Insect Feeding and Field Growth Tests". Journal of Agricultural
and Food Chemistry. 64 (18): 35013507. doi:10.1021/acs.jafc.6b00438. ISSN 0021-8561.
PMID 27119432.
Bolarinwa, Islamiyat F.; Orfila, Caroline; Morgan, Michael R.A. (2014). "Amygdalin
content of seeds, kernels and food products commercially-available in the UK". Food Chemistry.
152: 133139. doi:10.1016/j.foodchem.2013.11.002.
Wahab, Farooq (2015). "Problems and Pitfalls in the Analysis of Amygdalin and its
Epimer". Journal of Agricultural and Food Chemistry. 63: 89668973.
doi:10.1021/acs.jafc.5b03120.
George Mann, Frederick; Charles Saunders, Bernard (1975). Practical Organic Chemistry
(4th ed.). London: Longman. pp. 509517. ISBN 9788125013808. Retrieved 1 February 2016.
"Laetrile/Amygdalin". National Cancer Institute. Retrieved 2016-11-16.
Jerrold B. Leikin; Frank P. Paloucek, eds. (2008), "Laetrile", Poisoning and Toxicology
Handbook (4th ed.), Informa, p. 950, ISBN 978-1-4200-4479-9
Rietjens, Ivonne M. C. M.; Martena, Martijn J.; Boersma, Marelle G.; Spiegelenberg, Wim;
Alink, Gerrit M. (2005-02-01). "Molecular mechanisms of toxicity of important food-borne
phytotoxins". Molecular Nutrition & Food Research. 49 (2): 131158.
doi:10.1002/mnfr.200400078. ISSN 1613-4133.
James A. Duke (2003), CRC Handbook of Medicinal Spices, CRC Press, pp. 261262,
ISBN 0-8493-1279-5
 "A chronology of significant historical developments in the biological sciences". Botany
Online Internet Hypertextbook. University of Hamburg, Department of Biology. 18 August 2002.
Archived from the original on 20 August 2007. Retrieved 6 August 2007.
F. Whler; J. Liebig (1837). "Ueber die Bildung des Bittermandells". Annalen der
Pharmacie. 22 (1): 124. doi:10.1002/jlac.18370220102.
J. W. Walker; V. K. Krieble (1909). "The hydrolysis of amygdalin by acids. Part I". Journal
of the Chemical Society. 95 (11): 136977. doi:10.1039/CT9099501369.
"Laetrile/Amygdalin". National Cancer Institute.
US 2985664, Krebs, Ernst T. & Ernst T. Krebs, Jr., "Hexuronic acid derivatives"
Carpenter, Daniel (2010). Reputation and Power: Organizational Image and
Pharmaceutical Regulation at the FDA. Princeton: Princeton University Press. Princeton:
Princeton University Press. ISBN 0-691-14180-0.
Kennedy, Donald (1977). "Laetrile: The Commissioner's Decision" (PDF). Federal Register.
Docket No. 77-22310.
American Cancer Society (1991). "Unproven methods of cancer management. Laetrile". CA
Cancer J Clin. 41 (3): 18792. doi:10.3322/canjclin.41.3.187. PMID 1902140.
Wade N (December 1977). "Laetrile at Sloan-Kettering: A Question of Ambiguity". Science.
198 (4323): 12314. doi:10.1126/science.198.4323.1231. PMID 17741690.
Budiansky, Stephen (9 July 1995). "Cures or Quackery: How Senator Harkin shaped federal
research on alternative medicine". U.S. News & World Report. Archived from the original on 3
September 2011. Retrieved 7 November 2009.
Stock CC, Tarnowski GS, Schmid FA, Hutchison DJ, Teller MN (1978). "Antitumor tests of
amygdalin in transplantable animal tumor systems". J Surg Oncol. 10 (2): 818.
doi:10.1002/jso.2930100202. PMID 642516.
Stock CC, Martin DS, Sugiura K (1978). "Antitumor tests of amygdalin in spontaneous animal
tumor systems". J Surg Oncol. 10 (2): 89123. doi:10.1002/jso.2930100203. PMID 347176.
Milazzo S, Ernst E, Lejeune S, Boehm K, Horneber M (2011). "Laetrile treatment for
cancer". Cochrane Database Syst Rev (Systematic review) (11): CD005476.
doi:10.1002/14651858.CD005476.pub3. PMID 22071824.
"Laetrile (amygdalin, vitamin B17)". cancerhelp.org.uk.
"Laetrile/Amygdalin". National Cancer Institute.
Editors of Consumer Reports Books (1980). "Laetrile: the Political Success of a Scientific
Failure". Health Quackery. Vernon, New York: Consumers Union. pp. 1640. ISBN 0-89043-
014-4
Laetrile: The Cult of Cyanide Poisoning; Promoting Poison for Profit, American Journal of
Clinical Nutrition, May 1979, pp. 11211158. http://www.ajcn.org/content/32/5/1121.full.pdf
retrieved: Jan. 2012.
Moss RW (March 2005). "Patient perspectives: Tijuana cancer clinics in the post-NAFTA
era". Integr Cancer Ther. 4 (1): 6586. doi:10.1177/1534735404273918. PMID 15695477.
Lerner, Barron H. (15 November 2005). "McQueen's Legacy of Laetrile". New York Times.
Retrieved 23 April 2010.
"Dean Burk, 84, Noted Chemist At National Cancer Institute, Dies". Washington Post. 9
October 1988.
Brian S. McWilliams (2005). Spam kings: the real story behind the high-rolling hucksters
pushing porn, pills and @*#?% enlargements. Sebastopol, CA: O'Reilly. ISBN 0-596-00732-9.
 "New York Man Sentenced to 63 Months for Selling Fake Cancer Cure". Medical News
Today. 22 June 2004. Retrieved 8 July 2010.

34. US FDA (22 June 2004). Lengthy Jail Sentence for Vendor of Laetrile A Quack
Medication to Treat Cancer Patients. FDA News

External links
Laetrile/Amygdalin information from the National Cancer Institute (U.S.A.)
Food and Drug Administration Commissioner's Decision on Laetrile
The Rise and Fall of Laetrile

[hide]

v
t
e

Glycosides
O-glycosidic bond
N-glycosidic bond
Bond S-glycosidic bond
C-glycosidic bond

-Glycoside
-Glycoside
Geometry 1,4-Glycoside
1,6-Glycoside

Fructoside
Galactoside
Glucoside
Glycone Glucuronide
Rhamnoside
Riboside

Alcoholic glycoside
Cardiac glycoside
o Bufadienolide
Aglycone o Cardenolide
Cyanogenic glycoside
Glycosylamine
Phenolic glycoside
 o Anthraquinone glycoside
o Coumarin glycoside
o Flavonoid glycoside
Saponin
Steviol glycoside
Thioglycoside

Categories:

Alternative cancer treatments

Cyanogenic glycosides
Plant toxins

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Amygdalin
From Wikipedia, the free encyclopedia
Amygdalin
 Names
IUPAC name
[(6-O--D-Glucopyranosyl--D-
glucopyranosyl)oxy](phenyl)acetonitrile
Identifiers
29883-15-6
CAS Number
Interactive image
3D model (Jmol) Interactive image

CHEBI:17019
ChEBI
570897
ChemSpider
ECHA InfoCard 100.045.372
MeSH Amygdalin
34751
PubChem CID
214UUQ9N0H
UNII
InChI[show]
SMILES[show]
Properties
Chemical formula C20H27NO11
Molar mass 457.429
Melting point 223-226 C(lit.)
H2O: 0.1 g/mL hot, clear to
Solubility in water
very faintly turbid, colorless
Hazards
Safety data sheet A6005

GHS pictograms

GHS signal word Warning

GHS hazard
H302
statements
GHS precautionary P264, P270, P301+312, P330,
statements P501

NFPA 704

0
 1
0
Related compounds
Vicianin, laetrile, prunasin,
Related compounds
sambunigrin
Except where otherwise noted, data are given for
materials in their standard state (at 25 C [77 F],
100 kPa).
verify (what is ?)
Infobox references

Amygdalin (from Ancient Greek: amygdl "almond") is a poisonous cyanogenic

glycoside found in many plants, but most notably in the seeds (kernels) of apricot, bitter
almonds, apple, peach, and plum.

Since the early 1950s, both amygdalin and a modified form named laetrile have been promoted
as alternative cancer treatments, often using the misnomer Vitamin B17.[1] But studies have
found them to be clinically ineffective in the treatment of cancer, as well as potentially toxic or
lethal when taken by mouth, due to cyanide poisoning. Neither amygdalin nor laetrile is a
vitamin.

The promotion of laetrile to treat cancer has been described in the medical literature as a
canonical example of quackery,[2][3] and as "the slickest, most sophisticated, and certainly the
most remunerative cancer quack promotion in medical history."[1]

Contents
1 Chemistry
2 Laetrile
o 2.1 History of laetrile
2.1.1 Early usage
2.1.2 Initial positive results
2.1.3 Subsequent results
o 2.2 Advocacy and legality of laetrile
3 See also
4 References
5 External links

Chemistry
Amygdalin is a cyanogenic glycoside derived from the aromatic amino acid phenylalanine.
Amygdalin and prunasin are very common among plants of the Rosaceae family, particularly the
genus Prunus, Poaceae (grasses), Fabaceae (legumes), and in other food plants, including linseed
and manioc. Sambunigrin, obtained from leaves of the elder tree (Sambucus nigra), is isomeric
to prunasin.[4] Within these plants, amygdalin and the enzymes necessary to hydrolyze them are
stored in separate locations so that they will mix in response to tissue damage. This provides a
natural defense system[5]

Amygdalin is contained in stone fruit kernels, such as apricot (8%), peach (6%), bitter almond
(5%), and plum (2.5%); amygdalin is also found in the seeds of the apple.[6] The stones are taken
out of the fruit and cracked to obtain the kernels, which are dried in the sun or in ovens. The
kernels are boiled in ethanol; on evaporation of the solution and the addition of diethyl ether,
amygdalin is precipitated as white minute crystals. 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.[7]

Amygdalin is hydrolyzed by intestinal -glucosidase, emulsin,[8] and amygdalase to gentiobiose

and L-mandelonitrile. Gentiobiose is further hydrolyzed to glucose, whereas mandelonitrile is
hydrolyzed to benzaldehyde and hydrogen cyanide. Hydrogen cyanide in sufficient quantities
(allowable daily intake: ~0.6 mg)[citation needed] causes cyanide poisoning (fatal oral dose: 0.6-
1.5 mg/kg)[citation needed]. Apricot pits contain 89-2,170 mg/kg hydrogen cyanide (wet
weight).[citation needed]

Laetrile
Laetrile

Names
IUPAC name
(2S,3S,4S,5R,6R)-6-[(R)-cyano(phenyl)methoxy]-
3,4,5-trihydroxyoxane-2-carboxylic acid
Other names
L-mandelonitrile--D-glucuronide, Vitamin B
Identifiers
1332-94-1
CAS Number
Interactive image
3D model (Jmol)
4588479
ChemSpider
ECHA InfoCard 100.045.372
 5484354
PubChem CID
InChI[show]
SMILES[show]
Properties
Chemical formula C14H15NO7
Molar mass 309.2714
214 to 216 C (417 to 421 F;
Melting point
487 to 489 K)
Except where otherwise noted, data are given for
materials in their standard state (at 25 C [77 F],
100 kPa).
Infobox references

Laetrile (patented 1961) is a simpler semisynthetic version of amygdalin. Laetrile is synthesized

from amygdalin by hydrolysis. The usual preferred commercial source is from apricot kernels
(Prunus armeniaca). The name is derived from the separate words "laevarotatory" and
"mandelonitrile". Laevarotatory describes the stereochemistry of the molecule, while
mandelonitrile refers to its chemical identity[9]

A 500 mg laetrile tablet may contain between 551 mg of hydrogen cyanide per gram.[10]

Like amygdalin, laetrile is hydrolyzed in the duodenum (alkaline) and in the intestine
(enzymatically) to D-glucuronic acid and L-mandelonitrile; the latter hydrolyzes to benzaldehyde
and hydrogen cyanide, that in sufficient quantities causes cyanide poisoning. Intravenous laetrile
does not result in cyanide exposure. This is due to the fact that the necessary enzymes are
released either upon chewing the plant material or are provided by bacteria residing in the human
gastrointestinal system.[11]

Claims for laetrile were based on three different hypotheses:[12]

Hypothesis (1) 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 rhodanese, which converts HCN to the less toxic thiocyanate. Later, however, it was
shown that both cancerous and normal cells contain only trace amounts of beta-
glucosidases and similar amounts of rhodanese.[12]
Hypothesis (2) 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. This was considered untenable.
Hypothesis (3) 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 incidence of
cancer. There is no credible evidence supporting this conjecture.
Ernst T. Krebs branded laetrile as a vitamin in order to have it classified as a nutritional
supplement rather than as a pharmaceutical.[1]

History of laetrile

Early usage

Amygdalin was first isolated in 1830 from bitter almond seeds (Prunus dulcis) by Pierre-Jean
Robiquet and Antoine Boutron-Charlard.[13] Liebig and Whler found three hydrolysis products
of amygdalin: sugar, benzaldehyde, and prussic acid (hydrogen cyanide).[14] Later research
showed that sulfuric acid hydrolyzes it into D-glucose, benzaldehyde, and prussic acid; while
hydrochloric acid gives mandelic acid, D-glucose, and ammonia.[15]

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.[16] In the 1950s, a purportedly non-toxic, synthetic
form was patented for use as a meat preservative,[17] and later marketed as laetrile for cancer
treatment.[16]

The U.S. Food and Drug Administration prohibited the interstate shipment of amygdalin and
laetrile in 1977.[18][19] Thereafter, 27 U.S. states legalized the use of amygdalin within those
states.[20]

Initial positive results

In 1972, Memorial Sloan-Kettering Cancer Center (MSKCC) board member Benno C. Schmidt,
Sr. convinced the hospital to test laetrile. Kanematsu Sugiura, the scientist who performed the
tests, found that laetrile inhibited secondary tumors in mice, though it did not destroy the primary
tumors. He repeated the experiment several times with the same results. However, three other
researchers were unable to confirm Sugiura's results. Sugiura's results were leaked to laetrile
advocates, resulting in significant public attention.

Subsequent results

In 1977 a controlled, blinded follow-up experiment, laetrile showed no more activity than
placebo.[21]

Subsequently, laetrile was tested on 14 tumor systems without evidence of effectiveness.

MSKCC concluded that "laetrile showed no beneficial effects."[21] Mistakes in the MSKCC press
release were highlighted by a group of laetrile proponents led by Ralph Moss, former public
affairs official of MSKCC who was fired following his appearance at a press conference
accusing the hospital of covering up the benefits of laetrile.[22] These mistakes were considered
scientifically inconsequential, but Nicholas Wade in Science stated that "even the appearance of
a departure from strict objectivity is unfortunate."[21] The results from these studies were
published all together.[23]

A 2011 systematic review from the Cochrane Collaboration found:

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 riskbenefit
balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously
negative.[24][needs update]

The authors also recommended, on ethical grounds, that no further clinical research into laetrile
or amygdalin be conducted.[24]

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

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.[16] For example, a 1982 trial
by the Mayo Clinic of 175 patients found that tumor size had increased in all but one patient.[25]
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." [26]

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.

Advocacy and legality of laetrile

Advocates for laetrile assert that there is a conspiracy between the US Food and Drug
Administration, the 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.[27]

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.[27]

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 surgery and chemotherapy that
have significant side effects. The use of laetrile led to a number of deaths.[27] 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.[28]

Some North American cancer patients have traveled to Mexico for treatment with the substance,
for example at the Oasis of Hope Hospital in Tijuana.[29] The actor Steve McQueen died in
Mexico following surgery to remove a stomach tumor having previously undergone extended
treatment for pleural 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.[30]

Laetrile advocates in the United States include Dean Burk, a former chief chemist of the National
Cancer Institute cytochemistry laboratory,[31] and national arm wrestling champion Jason Vale,
who claimed that his kidney and pancreatic cancers were cured by eating apricot seeds. Vale was
convicted in 2004 for, among other things, fraudulently marketing laetrile as a cancer cure.[32]
The court also found that Vale had made at least $500,000 from his fraudulent sales of laetrile.[33]

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."[34]

See also

Medicine portal

List of ineffective cancer treatments

Alternative cancer treatments
Amygdalin beta-glucosidase
Beta-glucosidase

References
1.

Lerner IJ (1981). "Laetrile: a lesson in cancer quackery". CA Cancer J Clin. 31 (2): 915.
doi:10.3322/canjclin.31.2.91. PMID 6781723.
Lerner IJ (February 1984). "The whys of cancer quackery". Cancer. 53 (3 Suppl): 8159.
doi:10.1002/1097-0142(19840201)53:3+<815::AID-CNCR2820531334>3.0.CO;2-U.
PMID 6362828.
Nightingale SL (1984). "Laetrile: the regulatory challenge of an unproven remedy". Public
Health Rep. 99 (4): 3338. PMC 1424606 . PMID 6431478.
Andrew Pengelly (2004), The Constituents of Medicinal Plants (2nd ed.), Allen & Unwin,
pp. 4445, ISBN 1-74114-052-8
 Mora, Carlos A.; Halter, Jonas G.; Adler, Cornel; Hund, Andreas; Anders, Heidrun; Yu,
Kang; Stark, Wendelin J. (2016-05-11). "Application of the Prunus spp. Cyanide Seed Defense
System onto Wheat: Reduced Insect Feeding and Field Growth Tests". Journal of Agricultural
and Food Chemistry. 64 (18): 35013507. doi:10.1021/acs.jafc.6b00438. ISSN 0021-8561.
PMID 27119432.
Bolarinwa, Islamiyat F.; Orfila, Caroline; Morgan, Michael R.A. (2014). "Amygdalin
content of seeds, kernels and food products commercially-available in the UK". Food Chemistry.
152: 133139. doi:10.1016/j.foodchem.2013.11.002.
Wahab, Farooq (2015). "Problems and Pitfalls in the Analysis of Amygdalin and its
Epimer". Journal of Agricultural and Food Chemistry. 63: 89668973.
doi:10.1021/acs.jafc.5b03120.
George Mann, Frederick; Charles Saunders, Bernard (1975). Practical Organic Chemistry
(4th ed.). London: Longman. pp. 509517. ISBN 9788125013808. Retrieved 1 February 2016.
"Laetrile/Amygdalin". National Cancer Institute. Retrieved 2016-11-16.
Jerrold B. Leikin; Frank P. Paloucek, eds. (2008), "Laetrile", Poisoning and Toxicology
Handbook (4th ed.), Informa, p. 950, ISBN 978-1-4200-4479-9
Rietjens, Ivonne M. C. M.; Martena, Martijn J.; Boersma, Marelle G.; Spiegelenberg, Wim;
Alink, Gerrit M. (2005-02-01). "Molecular mechanisms of toxicity of important food-borne
phytotoxins". Molecular Nutrition & Food Research. 49 (2): 131158.
doi:10.1002/mnfr.200400078. ISSN 1613-4133.
James A. Duke (2003), CRC Handbook of Medicinal Spices, CRC Press, pp. 261262,
ISBN 0-8493-1279-5
"A chronology of significant historical developments in the biological sciences". Botany
Online Internet Hypertextbook. University of Hamburg, Department of Biology. 18 August 2002.
Archived from the original on 20 August 2007. Retrieved 6 August 2007.
F. Whler; J. Liebig (1837). "Ueber die Bildung des Bittermandells". Annalen der
Pharmacie. 22 (1): 124. doi:10.1002/jlac.18370220102.
J. W. Walker; V. K. Krieble (1909). "The hydrolysis of amygdalin by acids. Part I". Journal
of the Chemical Society. 95 (11): 136977. doi:10.1039/CT9099501369.
"Laetrile/Amygdalin". National Cancer Institute.
US 2985664, Krebs, Ernst T. & Ernst T. Krebs, Jr., "Hexuronic acid derivatives"
Carpenter, Daniel (2010). Reputation and Power: Organizational Image and
Pharmaceutical Regulation at the FDA. Princeton: Princeton University Press. Princeton:
Princeton University Press. ISBN 0-691-14180-0.
Kennedy, Donald (1977). "Laetrile: The Commissioner's Decision" (PDF). Federal Register.
Docket No. 77-22310.
American Cancer Society (1991). "Unproven methods of cancer management. Laetrile". CA
Cancer J Clin. 41 (3): 18792. doi:10.3322/canjclin.41.3.187. PMID 1902140.
Wade N (December 1977). "Laetrile at Sloan-Kettering: A Question of Ambiguity". Science.
198 (4323): 12314. doi:10.1126/science.198.4323.1231. PMID 17741690.
Budiansky, Stephen (9 July 1995). "Cures or Quackery: How Senator Harkin shaped federal
research on alternative medicine". U.S. News & World Report. Archived from the original on 3
September 2011. Retrieved 7 November 2009.
Stock CC, Tarnowski GS, Schmid FA, Hutchison DJ, Teller MN (1978). "Antitumor tests of
amygdalin in transplantable animal tumor systems". J Surg Oncol. 10 (2): 818.
doi:10.1002/jso.2930100202. PMID 642516.
Stock CC, Martin DS, Sugiura K (1978). "Antitumor tests of amygdalin in spontaneous animal
tumor systems". J Surg Oncol. 10 (2): 89123. doi:10.1002/jso.2930100203. PMID 347176.
Milazzo S, Ernst E, Lejeune S, Boehm K, Horneber M (2011). "Laetrile treatment for
cancer". Cochrane Database Syst Rev (Systematic review) (11): CD005476.
doi:10.1002/14651858.CD005476.pub3. PMID 22071824.
"Laetrile (amygdalin, vitamin B17)". cancerhelp.org.uk.
"Laetrile/Amygdalin". National Cancer Institute.
Editors of Consumer Reports Books (1980). "Laetrile: the Political Success of a Scientific
Failure". Health Quackery. Vernon, New York: Consumers Union. pp. 1640. ISBN 0-89043-
014-4
Laetrile: The Cult of Cyanide Poisoning; Promoting Poison for Profit, American Journal of
Clinical Nutrition, May 1979, pp. 11211158. http://www.ajcn.org/content/32/5/1121.full.pdf
retrieved: Jan. 2012.
Moss RW (March 2005). "Patient perspectives: Tijuana cancer clinics in the post-NAFTA
era". Integr Cancer Ther. 4 (1): 6586. doi:10.1177/1534735404273918. PMID 15695477.
Lerner, Barron H. (15 November 2005). "McQueen's Legacy of Laetrile". New York Times.
Retrieved 23 April 2010.
"Dean Burk, 84, Noted Chemist At National Cancer Institute, Dies". Washington Post. 9
October 1988.
Brian S. McWilliams (2005). Spam kings: the real story behind the high-rolling hucksters
pushing porn, pills and @*#?% enlargements. Sebastopol, CA: O'Reilly. ISBN 0-596-00732-9.
"New York Man Sentenced to 63 Months for Selling Fake Cancer Cure". Medical News
Today. 22 June 2004. Retrieved 8 July 2010.

34. US FDA (22 June 2004). Lengthy Jail Sentence for Vendor of Laetrile A Quack
Medication to Treat Cancer Patients. FDA News

External links
Laetrile/Amygdalin information from the National Cancer Institute (U.S.A.)
Food and Drug Administration Commissioner's Decision on Laetrile
The Rise and Fall of Laetrile

[hide]

v
t
e

Glycosides
O-glycosidic bond
Bond N-glycosidic bond
S-glycosidic bond
 C-glycosidic bond

-Glycoside
-Glycoside
Geometry 1,4-Glycoside
1,6-Glycoside

Fructoside
Galactoside
Glucoside
Glycone Glucuronide
Rhamnoside
Riboside

Alcoholic glycoside
Cardiac glycoside
o Bufadienolide
o Cardenolide
Cyanogenic glycoside
Glycosylamine
Phenolic glycoside
Aglycone
o Anthraquinone glycoside
o Coumarin glycoside
o Flavonoid glycoside
Saponin
Steviol glycoside
Thioglycoside

Categories:

Alternative cancer treatments

Cyanogenic glycosides
Plant toxins

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