Amygdalin

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Amygdalin
Amygdalin structure.svg
Amygdalin-from-xtal-3D-balls.png
Names
IUPAC name
[(6-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy](phenyl)acetonitrile
Identifiers
29883-15-6 N
ChEBI CHEBI:17019 YesY
ChEMBL ChEMBL461727 YesY
ChemSpider 570897 YesY
Jmol 3D model Interactive image
Interactive image
MeSH Amygdalin
PubChem 34751
UNII 214UUQ9N0H YesY
  • InChI=1S/C20H27NO11/c21-6-10(9-4-2-1-3-5-9)30-20-18(28)16(26)14(24)12(32-20)8-29-19-17(27)15(25)13(23)11(7-22)31-19/h1-5,10-20,22-28H,7-8H2/t10-,11+,12+,13+,14+,15-,16-,17+,18+,19+,20+/m0/s1 YesY
    Key: XUCIJNAGGSZNQT-JHSLDZJXSA-N YesY
  • InChI=1/C20H27NO11/c21-6-10(9-4-2-1-3-5-9)30-20-18(28)16(26)14(24)12(32-20)8-29-19-17(27)15(25)13(23)11(7-22)31-19/h1-5,10-20,22-28H,7-8H2/t10-,11+,12+,13+,14+,15-,16-,17+,18+,19+,20+/m0/s1
    Key: XUCIJNAGGSZNQT-JHSLDZJXBT
  • 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
  • N#C[C@H](O[C@@H]2O[C@H](CO[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)CO)[C@@H](O)[C@H](O)[C@H]2O)c3ccccc3
Properties
C20H27NO11
Molar mass 457.429
Vapor pressure {{{value}}}
Related compounds
Related compounds
 vicianin, laetrile, prunasin, sambunigrin
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Amygdalin (from Ancient Greek: ἀμυγδαλή amygdálē "almond"), is a poisonous cyanogenic glycoside found in many plants, but most notably in the seeds (kernels) of apricot, peach, bitter almond, 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 are vitamins.

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]

Chemistry

Amygdalin is a cyanogenic glycoside derived from the aromatic amino acid phenylalanine. Amygdalin and prunasin are very common among plants of the Rosaceae, particularly the Prunus genus, 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]

Amygdalin is contained in fruit kernels, such as apricot (8%), peach (6%), bitter almond (5%), and plum (2.5%)[citation needed]. 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 enantiomer is called neoamygdalin.

Amygdalin is hydrolyzed by intestinal β-glucosidase, emulsin, 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]

In small quantities these glycosides do exhibit expectorant, sedative and digestive properties. Wild cherry bark (Prunus serotina) is an excellent cough remedy and tonic, as well as a flavouring agent used in cough syrups. It is of benefit as a tea for bronchitis. The main antitussive principle is prunasin.[4] In Chinese medicine, apricot seeds (杏仁, xìngrén) are used against cough and constipation (4.5-9 g).[5]

Laetrile

Laetrile
Laetrile.svg
Names
IUPAC name
(2S,3S,4S,5R,6R)-6-[(R)-cyano(phenyl)methoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
Other names
L-mandelonitrile-β-D-glucuronide, Vitamin B₁₇
Identifiers
1332-94-1
PubChem 5484354
Properties
C14H15NO7
Molar mass 309.2714
Melting point 214 to 216 °C (417 to 421 °F; 487 to 489 K)
Vapor pressure {{{value}}}
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. It is synthesized from amygdalin by hydrolysis. The usual commercial source is from apricot kernels (Prunus armeniaca). A 500 mg laetrile tablet may contain between 5–51 mg of hydrogen cyanide per gram.[6]

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, which causes cyanide poisoning. Intravenous laetrile does not result in cyanide exposure.

Claims for laetrile were based on three different theories:[7]

  • Theory (1) claimed 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.[citation needed]
  • Theory (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 believed an untenable theory.
  • Theory (3) called laetrile vitamin B-17, suggesting that cancer is a result of B-17 deficiency. It postulated that chronic administration of laetrile would prevent cancer. No evidence was adduced to substantiate this hypothesis.

Ernst T. Krebs falsely branded laetrile as a vitamin in order to have it classified as a nutritional supplement rather than as a pharmaceutical. He would also capitalise on the public fad for vitamins at that time.[1]

History

Amygdalin was first isolated in 1830 from bitter almond seeds (Prunus dulcis) by Pierre-Jean Robiquet and Antoine Boutron-Charlard.[8] Liebig and Wöhler found three hydrolysis products of amygdalin: sugar, benzaldehyde, and prussic acid (hydrogen cyanide).[9] 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.[10]

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.[11] In the 1950s, a purportedly non-toxic, synthetic form was patented for use as a meat preservative,[12] and later marketed as laetrile for cancer treatment.[11]

The U.S. Food and Drug Administration prohibited the interstate shipment of amygdalin and laetrile in 1977.[13][14] Thereafter, 27 U.S. states legalized the use of amygdalin within those states.[15]

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. In a controlled, blinded follow-up experiment, laetrile showed no more activity than placebo.[16]

Subsequently, laetrile was tested on 14 tumor systems without evidence of effectiveness. MSKCC concluded that "laetrile showed no beneficial effects."[16] 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.[17] These mistakes were considered scientifically inconsequential, but Nicholas Wade in Science stated that "even the appearance of a departure from strict objectivity is unfortunate."[16] The results from these studies were published all together.[18]

A 2011 systematic review from the Cochrane Collaboration found: <templatestyles src="Template:Blockquote/styles.css" />

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.[19]

The authors also recommended, on ethical grounds, that no further clinical research into laetrile or amygdalin be conducted.[19]

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.[11] For example, a 1982 trial by the Mayo Clinic of 175 patients found that tumor size had increased in all but one patient.[20] 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." [21]

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

Advocates for laetrile assert that there is a conspiracy between the U.S. 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. 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. 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.[22] 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 foster multi-million dollar smuggling empires.[23]

Some North American cancer patients have traveled to Mexico for treatment with the substance, for example at the Oasis of Hope Hospital in Tijuana.[24] 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.[25]

Laetrile advocates in the United States include Dean Burk, a former chief chemist of the National Cancer Institute cytochemistry laboratory,[26] 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.[27] The court also found that Vale had made at least $500,000 from his fraudulent sales of laetrile.[28]

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."[29]

See also

References

  1. ↑ 1.0 1.1 1.2 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ 11.0 11.1 11.2 Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ US 2985664, Krebs, Ernst T. & Ernst T. Krebs, Jr., "Hexuronic acid derivatives" 
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ 16.0 16.1 16.2 Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  19. ↑ 19.0 19.1 Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Laetrile: The Cult of Cyanide Poisoning; Promoting Poison for Profit, American Journal of Clinical Nutrition, May, 1979, pp. 1121–1158. http://www.ajcn.org/content/32/5/1121.full.pdf retrieved: Jan. 2012.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  29. ↑ US FDA (June 22, 2004). Lengthy Jail Sentence for Vendor of Laetrile – A Quack Medication to Treat Cancer Patients. FDA News

External links

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