Amygdalin

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Amygdalin
Identifiers
CAS number [29883-15-6]
PubChem 34751
MeSH Amygdalin
Properties
Molecular formula C20H27NO11
Molar mass 457.429
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Amygdalin (from Greek: ἀμυγδάλη, almond), C20H27NO11, also known as laevomandelonitrile or laetrile, is a glycoside initially isolated from the seeds of the tree Prunus dulcis, also known as bitter almonds, by Pierre-Jean Robiquet[1] and A. F. Boutron-Charlard in 1803, and subsequently investigated by Liebig and Wöhler in 1830, and others. Several other related species in the genus of Prunus, including apricot (Prunus armeniaca), also contain amygdalin. Some sources claim Ernst T. Krebs was the discoverer of the substance, and Krebs is generally credited with popularizing it as a purported cancer cure and as "Vitamin B17."

Contents

[edit] Chemistry

Amygdalin is extracted from almond or apricot kernel cake by boiling ethanol; on evaporation of the solution and the addition of diethyl ether, amygdalin is precipitated as white minute crystals. Liebig and Wöhler were already able to find three decomposition products of the newly discovered amygdalin: sugar, benzaldehyde, and prussic acid.[2] Later research showed that sulfuric acid decomposes it into d-glucose, benzaldehyde, and prussic acid (hydrogen cyanide); while hydrochloric acid gives mandelic acid, d-glucose, and ammonia.[3]

The decomposition induced by enzymes may occur in two ways. Maltase partially decomposes it, giving d-glucose and mandelic nitrile glucoside, C6H5CH(CN)O·C6H11O5; this compound is isomeric with sambunigrin, a glucoside found by E.E. Bourquelot and Danjou in the berries of the common elder, Sambucus nigra. Emulsin, on the other hand, decomposes it into benzaldehyde, cyanide, and two molecules of glucose; this enzyme occurs in the bitter almond, and consequently the seeds invariably contain free cyanide and benzaldehyde. An "amorphous amygdalin" is said to occur in the cherry-laurel. Closely related to these glucosides is dhurrin, C14H17O7N, isolated by W. Dunstan and T. A. Henry from the common sorghum or "great millet," Sorghum vulgare; this substance is decomposed by emulsin or hydrochloric acid into d-glucose, cyanide, and 4-hydroxybenzaldehyde.[citation needed]

[edit] Nomenclature

Amygdalin is also called laevomandelonitrile, or laetrile for short. Some claim that laetrile is derived from a Latin word meaning "joyfulness" as laetari is the Latin verb meaning "to rejoice or exult".[citation needed]

The National Cancer Institute explains that "the names Laetrile, laetrile, and amygdalin are often used in place of one another, but they are not the same product. The chemical make-up of Laetrile patented in the United States is different from the laetrile/amygdalin produced in Mexico. The patented laetrile is a partly synthetic (man-made) form of amygdalin, while the laetrile/amygdalin made in Mexico comes from crushed apricot pits."[4]

Though it is sometimes sold as "Vitamin B17", it meets none of the criteria of a vitamin. Amygdalin/laetrile was claimed to be a vitamin by Ernst Krebs, Jr in the hope that if classified as a nutritional supplement it would escape the federal legislation regarding the marketing of drugs. He could also capitalise on the public fad for vitamins at that time.[5]

[edit] Toxicity

Amygdalin contains 6% cyanide by weight. The enzyme, beta-glucosidase, required for release of the cyanide from the amygdalin molecule, is present in human small intestine and in a variety of common foods which leads to an unpredictable and potentially lethal toxicity when amygdalin or Laetrile is taken orally.[5][6]

[edit] Assessment as a Cancer Treatment

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Preclinical studies by the U.S. government's National Institutes of Health using laetrile alone and in combination with other substances showed little evidence that it is effective against cancer.[7] Several case studies were recorded involving laetrile and conventional treatments (e.g. radiation and chemotherapy) concurrently, and were therefore inconclusive. However positive results in one case series initiated two published uncontrolled clinical trials using amygdalin.[7] The Phase I study found that amygdalin caused minimal side effects, but the consumption of raw bitter almonds by two patients produced symptoms of cyanide poisoning. The Phase II study gave intravenous amygdalin combined with vitamins and pancreatic enzymes to 175 patients for 21 days followed by oral maintenance as part of a metabolic therapy program that also included dietary changes. Some patients reported improvements in symptoms, but all patients showed cancer progression 7 months after completing treatment, and improvements did not last after treatment.[8] No controlled or double-blind clinical trials have been reported.[7]

Another clinical trial was carried out in 1982 by the Mayo Clinic[9] and three other U.S. cancer centers under NCI sponsorship. Laetrile and "metabolic therapy" were administered as recommended by their promoters to 178 patients with advanced cancer for which there was no proven treatment. None were cured or stabilized or had any improvement of cancer-related symptoms. The median survival rate was about five months. In survivors after seven months, tumor size had increased. Several patients suffered from cyanide poisoning.

In 1974, the American Cancer Society officially labelled laetrile as "quackery," but advocates for laetrile dispute this label, asserting that financial motivations have tainted the published research.[10] As a result, some North American cancer patients have travelled to Mexico for treatment with the substance, allegedly under the auspices of Dr. Ernesto Contreras.[citation needed] One of these patients was actor Steve McQueen, who died in Mexico, while undergoing treatment for mesothelioma.

Reviews of available clinical evidence published in 2006 concluded that the claim that laetrile has beneficial effects for cancer patients is not supported by sound clinical data,[11] or by data from controlled clinical trials,[12] and that there is considerable doubt about its safety.[11]

Consequently, due to a lack of credible scientific evidence of its efficacy, and a high potential for toxicity, it has not been approved for this use by the United States' Food and Drug Administration.[4] Overall, a lack of peer reviewed information and the self-medication of patients with amygdalin can cause severe problems with cancer treatment.[13]

[edit] Supporters of amygdalin

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Laetrile advocates within the United States include a one-time chief chemist of the National Cancer Institute's cytochemistry laboratory,[14] Dean Burk Ph.D.[15], and G. Edward Griffin, author of "The Creature From Jekyll Island: A Second Look at the Federal Reserve".

Jason Vale, a national arm wrestling champion, was a leading spokesman for the legalization of laetrile after claiming to be cured of kidney, pancreatic and spleen cancer, purportedly by eating apricot seeds. However, in 2003 he was convicted of criminal contempt and in June 2004 was sentenced to 63 months in prison for marketing laetrile, for defrauding the U.S. government by claiming that he qualified for Legal Aid, and for ignoring a court order to stop distributing laetrile. Representatives of the Memorial Sloan-Kettering Cancer Center testified on the side of the prosecution during Vale's criminal trial.[16][17]

Phillip Day, businessman behind Credence Publications, publisher and supplier of alternate medical products, claims in a book published by his company that regular use provides complete protection for a healthy person from cancer, an 80% success (survival after 5 years) when used for treating a newly diagnosed cancer, and 15% success as treatment for a metastasizing cancer[18]. This opinion is based on the idea of cancer being a metabolic disease, a view not supported by current scientific knowledge.

[edit] Government regulation in the U.S.

Laetrile is a compound that has been used as an anticancer treatment in humans worldwide.[citation needed] It is not approved by the U.S. Food and Drug Administration (FDA) as a treatment for cancer or any other medical condition. The drug is made and used as a cancer treatment in Mexico.[19]

Since laetrile has not been approved as a treatment for cancer in the United States by the FDA,[19] doctors may not prescribe it specifically to treat cancer. However in certain US states the use of laetrile is authorized.[20] In Montana this "...does not prevent a physician from prescribing laetrile as a dietary supplement to a patient not suffering from any known malignancy, disease, illness, or physical condition."[21], while in Indiana a physician who has signed a written informed request can prescribe or administer amygdalin (laetrile) in place of, or as an adjunct to, accepted therapies for the "...treatment of a malignancy, a disease, an illness, or a physical condition of a patient".[22]

In the United States, the Food and Drug Administration continues to seek jail sentences for vendors selling laetrile for cancer treatment, calling it a "highly toxic product that has not shown any effect on treating cancer."[23]

Amygdalin is commonly manufactured in Mexico. Because of the lack of proven efficacy of amygdalin, it may be banned or difficult to locate in some locations.

[edit] References

 This article contain claims that needs additional citations for verification.
Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (October 2007)

This article incorporates text from the Encyclopædia Britannica Eleventh Edition, a publication now in the public domain.

  1. ^ A chronology of significant historical developments in the biological sciences. Botany Online Internet Hypertextbook. University of Hamburg, Department of Biology (2002-08-18). Retrieved on 2007-08-06.
  2. ^ F. Wöhler, J. Liebig (11837). "Ueber die Bildung des Bittermandelöls". Annalen der Pharmacie 22 (1): 1 - 24. doi:10.1002/jlac.18370220102. 
  3. ^ J. W. Walker, V. K. Krieble (1909). "The hydrolysis of amygdalin by acids. Part I". Journal of the Chemical Society 95 (11): 1369 - 1377. doi:10.1039/CT9099501369. 
  4. ^ a b What is laetrile?, National Cancer Institute, Retrieved on 14 January 2007
  5. ^ a b Laetrile: A Lesson in Cancer Quackery Ca Cancer J Clin 1981;31;91-95
  6. ^ Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc Natl Acad Sci U S A. 1981 October; 78(10): 6513–6516.
  7. ^ a b c Laetrile/Amygdalin - National Cancer Institute
  8. ^ NEJM - A clinical trial of amygdalin (Laetrile) in the treatment of human cancer
  9. ^ Moertel, C.G., (1982). "A clinical trial of amygdalin (laetrile) in the treatment of human cancer.". N. Engl. J. Med. (306): 201-206. 
  10. ^ Day, Phillip: Cancer: why we're still dying to know the truth, Credence Publications, Tonbridge, 1999, Pp. 43ff
  11. ^ a b Milazzo, Stefania; Stephane Lejeune, Edzard Ernst (2006-11-15). "Laetrile for cancer: a systematic review of the clinical evidence". Supportive Care in Cancer. doi:10.1007/s00520-006-0168-9. 
  12. ^ Milazzo S, Ernst E, Lejeune S, Schmidt K (2006). "Laetrile treatment for cancer". Cochrane Database Syst Rev (2): CD005476. doi:10.1002/14651858.CD005476.pub2. PMID 16625640. 
  13. ^ Schraub S. (2000). "Unproven methods in cancer: a worldwide problem". Supportive Care in Cancer 8: 10-15. doi:10.1007/s005209900057. 
  14. ^ Dean Burk, 84, Noted Chemist At National Cancer Institute, Dies, Washington Post, 9 October 1988
  15. ^ Dr Dean Burk, The Moss Reports
  16. ^ New York Man Sentenced to 63 Months for Selling Fake Cancer Cure, Medical News Today, 22 June 2004, Retrieved on 14 January 2007
  17. ^ McWilliams, Brian, The Spam Kings, O'Reilly, 2005 ISBN 0596007329
  18. ^ Day, Phillip: Cancer: Why we're still dying to know the truth, Tonbridge (UK): Credence Publications, 1999, P. 148;
  19. ^ a b Is laetrile approved by the FDA for use as a cancer treatment in the United States?, National Cancer Institute, Retrieved on 14 January 2007
  20. ^ Mennenga, Jerry (1978-04-02). Laetrile: Legal but undefined and unavailable. Illinois Issues. Retrieved on 2007-01-14.
  21. ^ Montana Code: Laetrile not endorsed -- permitted as a dietary supplement, Montana State Government, Montata Code Annotated 2005, Retrieved on 14 January 2007
  22. ^ Prescription or administration permitted with written informed request, Indiana State Government, Information Maintained by the Office of Code Revision Indiana Legislative Services Agency, Chapter 23. Drugs: Use of Amygdalin (Laetrile), Retrieved on 14 January 2007
  23. ^ US FDA (June 22, 2004). Lengthy Jail Sentence for Vendor of Laetrile—A Quack Medication to Treat Cancer Patients. FDA News

[edit] External links

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Types of Glycosides
Bond:
Geometry:
Glycone:
Aglycone:
Alcoholic glycoside | Anthraquinone glycoside | Coumarin glycoside | Cyanogenic glycoside | Flavonoid glycoside | Phenolic glycoside | Saponin | Cardiac glycoside | Steviol glycoside | Thioglycoside | Glycosylamine | Bufanolide | Cardenolide
Major families of biochemicals
Peptides | Amino acids | Nucleic acids | Carbohydrates | Nucleotide sugars | Lipids | Terpenes | Carotenoids | Tetrapyrroles | Enzyme cofactors | Steroids | Flavonoids | Alkaloids | Polyketides | Glycosides