Amygdalin

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Amygdalin
Amygdalin structure.svg
Amygdalin-from-xtal-3D-balls.png
Names
IUPAC name
(2R)-[β-D-Glucopyranosyl-(1→6)-β-D-glucopyranosyloxy]phenylacetonitrile
Systematic IUPAC name
(2R)-Phenyl{[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl]oxy}acetonitrile
Identifiers
3D model (JSmol)
66856
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.045.372 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 249-925-3
MeSH Amygdalin
PubChem CID
UNII
  • 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 Yes check.svgY
    Key: XUCIJNAGGSZNQT-JHSLDZJXSA-N Yes check.svgY
  • 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
Melting point 223–226 °C (433–439 °F; 496–499 K)
H2O: 0.1 g/mL hot, clear to very faintly turbid, colorless
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H302
P264, P270, P301+P312, P330, P501
NFPA 704 (fire diamond)
NFPA 704.svgHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 0: Will not burn. E.g. waterInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
0
0
Safety data sheet (SDS) A6005
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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Amygdalin (from Ancient Greek: ἀμυγδαλήamygdalē 'almond') is a naturally occurring chemical compound found in many plants, most notably in the seeds (kernels, pips or stones) of apricots, bitter almonds, apples, peaches, cherries and plums, and in the roots of manioc.

Amygdalin is classified as a cyanogenic glycoside, because each amygdalin molecule includes a nitrile group, which can be released as the toxic cyanide anion by the action of a beta-glucosidase. Eating amygdalin will cause it to release cyanide in the human body, and may lead to cyanide poisoning. [1]

Since the early 1950s, both amygdalin and a chemical derivative named laetrile have been promoted as alternative cancer treatments, often under the misnomer vitamin B17 (neither amygdalin nor laetrile is a vitamin). [2] 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 cyanide poisoning. [3] The promotion of laetrile to treat cancer has been described in the medical literature as a canonical example of quackery [4] [5] and as "the slickest, most sophisticated, and certainly the most remunerative cancer quack promotion in medical history". [2] It has also been described as traditional Chinese medicine. [6]

Chemistry

Amygdalin is a cyanogenic glycoside derived from the aromatic amino acid phenylalanine. Amygdalin and prunasin are common among plants of the family Rosaceae, particularly the genus Prunus , Poaceae (grasses), 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. [7]

Amygdalin is contained in stone fruit kernels, such as almonds, apricot (14 g/kg), peach (6.8 g/kg), and plum (4–17.5 g/kg depending on variety), and also in the seeds of the apple (3 g/kg). [8] 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 bitter almond. [9] In one study, bitter almond amygdalin concentrations ranged from 33 to 54 g/kg depending on variety; semibitter varieties averaged 1 g/kg and sweet varieties averaged 0.063 g/kg with significant variability based on variety and growing region. [10]

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 ethanol; on evaporation of the solution and the addition of diethyl ether, amygdalin is precipitated as minute white crystals. [11] 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. [12]

Amygdalin is hydrolyzed by intestinal β-glucosidase (emulsin) [13] and amygdalin beta-glucosidase (amygdalase) to give gentiobiose and L-mandelonitrile. Gentiobiose is further hydrolyzed to give glucose, whereas mandelonitrile (the cyanohydrin of benzaldehyde) decomposes to give benzaldehyde and hydrogen cyanide. Hydrogen cyanide in sufficient quantities (allowable daily intake: ~0.6 mg) causes cyanide poisoning which has a fatal oral dose range of 0.6–1.5 mg/kg of body weight. [14]

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
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.045.372 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
  • InChI=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
    Key: XLSLFPQAPYONPW-WHUHBCJBSA-N
  • 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
Properties
C14H15NO7
Molar mass 309.2714
Melting point 214 to 216 °C (417 to 421 °F; 487 to 489 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Laetrile (patented 1961) is a simpler semisynthetic derivative 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 "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. [15] A 500 mg laetrile tablet may contain between 2.5 and 25 mg of hydrogen cyanide. [16]

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. [17]

Claims for laetrile were based on three different hypotheses: [18] 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 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. [18]

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. [19] : 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. [20] The term "vitamin B-17" is not recognized by Committee on Nomenclature of the American Institute of Nutrition Vitamins. [15] Ernst T. Krebs (not to be confused with Hans Adolf Krebs, the discoverer of the citric acid cycle) branded laetrile as a vitamin in order to have it classified as a nutritional supplement rather than as a pharmaceutical. [2]

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. [21] Liebig and Wöhler found three hydrolysis products of amygdalin: sugar, benzaldehyde, and hydrogen cyanide. [22] Later research showed that sulfuric acid hydrolyzes it into D-glucose, benzaldehyde, and hydrogen cyanide; while hydrochloric acid gives mandelic acid, D-glucose, and ammonia. [23]

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. [24] In the 1950s, a purportedly non-toxic, synthetic form was patented for use as a meat preservative, [25] and later marketed as laetrile for cancer treatment. [24]

The U.S. Food and Drug Administration prohibited the interstate shipment of amygdalin and laetrile in 1977. [26] [27] Thereafter, 27 U.S. states legalized the use of amygdalin within those states. [28]

Subsequent results

In a 1977 controlled, blinded trial, laetrile showed no more activity than placebo. [29]

Subsequently, laetrile was tested on 14 tumor systems without evidence of effectiveness. The Memorial Sloan–Kettering Cancer Center (MSKCC) concluded that "laetrile showed no beneficial effects." [29] 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. [30] These mistakes were considered scientifically inconsequential, but Nicholas Wade in Science stated that "even the appearance of a departure from strict objectivity is unfortunate." [29] The results from these studies were published all together. [31]

A 2015 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 risk–benefit balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously negative. [3]

The authors also recommended, on ethical and scientific grounds, that no further clinical research into laetrile or amygdalin be conducted. [3] Subsequent research has confirmed the evidence of harm and lack of benefit. [32]

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. [24] For example, a 1982 trial by the Mayo Clinic of 175 patients found that tumor size had increased in all but one patient. [33] 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." [24]

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". [19]

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. [34]

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. [34]

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. [34] 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. [35]

Some American cancer patients have traveled to Mexico for treatment with the substance, for example at the Oasis of Hope Hospital in Tijuana. [36] 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. [37]

Laetrile advocates in the United States include Dean Burk, a former chief chemist of the National Cancer Institute cytochemistry laboratory, [38] and national arm wrestling champion Jason Vale, who falsely 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. [39] The court also found that Vale had made at least $500,000 from his fraudulent sales of laetrile. [40]

In New Zealand, laetrile was among the purported treatments for cancer promoted by Milan Brych, who was later convicted of medical fraud. [41]

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 [42] which established that interstate transport of the compound was illegal, usage fell off dramatically. [15] [43] 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." [44]

See also

Related Research Articles

<span class="mw-page-title-main">Almond</span> Species of nut

The almond is a species of tree from the genus Prunus. Along with the peach, it is classified in the subgenus Amygdalus, distinguished from the other subgenera by corrugations on the shell (endocarp) surrounding the seed.

<span class="mw-page-title-main">Cyanide</span> Any molecule with a cyano group (–C≡N)

In chemistry, cyanide is a chemical compound that contains a C≡N functional group. This group, known as the cyano group, consists of a carbon atom triple-bonded to a nitrogen atom.

<span class="mw-page-title-main">Hydrogen cyanide</span> Highly toxic chemical with the formula HCN

Hydrogen cyanide is a chemical compound with the formula HCN and structural formula H−C≡N. It is a highly toxic and flammable liquid that boils slightly above room temperature, at 25.6 °C (78.1 °F). HCN is produced on an industrial scale and is a highly valued precursor to many chemical compounds ranging from polymers to pharmaceuticals. Large-scale applications are for the production of potassium cyanide and adiponitrile, used in mining and plastics, respectively. It is more toxic than solid cyanide compounds due to its volatile nature. A solution of hydrogen cyanide in water, represented as HCN, is called hydrocyanic acid. The salts of the cyanide anion are known as cyanides.

<span class="mw-page-title-main">Apricot</span> Cultivated fruit

An apricot is a fruit, or the tree that bears the fruit, of several species in the genus Prunus.

<i>Prunus</i> Genus of trees and shrubs

Prunus is a genus of trees and shrubs in the flowering plant family Rosaceae that includes plums, cherries, peaches, nectarines, apricots and almonds. The genus has a cosmopolitan distribution, being native to the temperate regions of North America, the neotropics of South America, and temperate and tropical regions of Eurasia and Africa, There are about 340 accepted species as of March 2024.

<i>Prunus laurocerasus</i> Species of plant

Prunus laurocerasus, also known as cherry laurel, common laurel and sometimes English laurel in North America, is an evergreen species of cherry (Prunus), native to regions bordering the Black Sea in southwestern Asia and southeastern Europe, from Albania and Bulgaria east through Turkey to the Caucasus Mountains and northern Iran.

B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. They are a chemically diverse class of compounds.

<span class="mw-page-title-main">Glycoside</span> Molecule in which a sugar is bound to another functional group

In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme hydrolysis, which causes the sugar part to be broken off, making the chemical available for use. Many such plant glycosides are used as medications. Several species of Heliconius butterfly are capable of incorporating these plant compounds as a form of chemical defense against predators. In animals and humans, poisons are often bound to sugar molecules as part of their elimination from the body.

<span class="mw-page-title-main">Cyanohydrin</span> Functional group in organic chemistry

In organic chemistry, a cyanohydrin or hydroxynitrile is a functional group found in organic compounds in which a cyano and a hydroxy group are attached to the same carbon atom. The general formula is R2C(OH)CN, where R is H, alkyl, or aryl. Cyanohydrins are industrially important precursors to carboxylic acids and some amino acids. Cyanohydrins can be formed by the cyanohydrin reaction, which involves treating a ketone or an aldehyde with hydrogen cyanide (HCN) in the presence of excess amounts of sodium cyanide (NaCN) as a catalyst:

<i>Prunus serotina</i> Species of tree

Prunus serotina, commonly called black cherry, wild black cherry, rum cherry, or mountain black cherry, is a deciduous tree or shrub in the rose family Rosaceae. Despite its common names, it is not very closely related to commonly cultivated cherries. It is found in the Americas.

<span class="mw-page-title-main">Ernst T. Krebs</span> Promoter of the quack cancer treatment laetrile

Ernst Theodore Krebs Jr. was an American promoter of various substances as alternative cures for cancer, including pangamic acid and amygdalin. He also co-patented the semi-synthetic chemical compound closely related to amygdalin called laetrile, which was also promoted as a cancer preventative and cure. His medical claims about these compounds are not supported by scientific evidence and are widely considered quackery.

<span class="mw-page-title-main">Apricot kernel</span> Toxic seed of the apricot

An apricot kernel is the apricot seed located within the fruit endocarp, which forms a hard shell around the seed called the pyrena.

<span class="mw-page-title-main">Mandelic acid</span> Chemical compound

Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. The racemic mixture is known as paramandelic acid.

Ernesto Contreras (1915–2003) served as a Mexican medical doctor. He operated the Oasis of Hope Hospital in Tijuana for over 30 years, claiming to "treat" cancer patients with amygdalin (also called "laetrile" or, erroneously, "vitamin B17") which has been found completely ineffective. His practices have been widely condemned.

<span class="mw-page-title-main">Apricot oil</span>

Apricot oil or apricot kernel oil is pressed from the kernels of the Prunus armeniaca (apricot). Apricot kernels have an oil content of 40-50%. The oil is similar to almond oil and peach oil, both of which are also extracted from the kernels of the respective fruit.

<span class="mw-page-title-main">Cyanide poisoning</span> Broad-spectrum poisoning

Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest. Onset of symptoms usually occurs within a few minutes. Some survivors have long-term neurological problems.

<span class="mw-page-title-main">Mandelonitrile lyase</span> Class of enzymes

The enzyme (R)-mandelonitrile lyase (EC 4.1.2.10, (R)-HNL, (R)-oxynitrilase, (R)-hydroxynitrile lyase) catalyzes the chemical reaction

Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is among the simplest aromatic aldehydes and one of the most industrially useful.

<span class="mw-page-title-main">Prunasin</span> Chemical compound

(R)-prunasin is a cyanogenic glycoside related to amygdalin. Chemically, it is the glucoside of (R)-mandelonitrile.

The Oasis of Hope Hospital is a clinic in Tijuana, Mexico providing alternative cancer treatments to its customers. The clinic was founded by the physician Ernesto Contreras. After his death in 2003, the management of the hospital was taken over by his son, Francisco Contreras, and nephew, Daniel Kennedy.

References

  1. ↑ "Apricot kernels pose risk of cyanide poisoning". European Food Safety Authority. 27 April 2016. 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
  2. 1 2 3 Lerner IJ (1981). "Laetrile: a lesson in cancer quackery". CA: A Cancer Journal for Clinicians. 31 (2): 91–95. doi: 10.3322/canjclin.31.2.91 . PMID   6781723. S2CID   28917628.
  3. 1 2 3 Milazzo S, Horneber M (April 2015). "Laetrile treatment for cancer". The Cochrane Database of Systematic Reviews. 2015 (4): CD005476. doi:10.1002/14651858.CD005476.pub4. PMC   6513327 . PMID   25918920.
  4. ↑ Lerner IJ (February 1984). "The whys of cancer quackery". Cancer. 53 (3 Suppl): 815–819. doi: 10.1002/1097-0142(19840201)53:3+<815::AID-CNCR2820531334>3.0.CO;2-U . PMID   6362828. S2CID   36332694.
  5. ↑ Nightingale SL (1984). "Laetrile: the regulatory challenge of an unproven remedy". Public Health Reports. 99 (4): 333–338. PMC   1424606 . PMID   6431478.
  6. ↑ Shi J, Chen Q, Xu M, Xia Q, Zheng T, Teng J, et al. (June 2019). "Recent updates and future perspectives about amygdalin as a potential anticancer agent: A review". Cancer Medicine. 8 (6): 3004–3011. doi:10.1002/cam4.2197. PMC   6558459 . PMID   31066207.
  7. ↑ Mora CA, Halter JG, Adler C, Hund A, Anders H, Yu K, et al. (May 2016). "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): 3501–3507. doi:10.1021/acs.jafc.6b00438. PMID   27119432.
  8. ↑ Bolarinwa IF, Orfila C, Morgan MR (2014). "Amygdalin content of seeds, kernels and food products commercially-available in the UK" (PDF). Food Chemistry. 152: 133–139. doi:10.1016/j.foodchem.2013.11.002. PMID   24444917. Archived (PDF) from the original on 9 October 2022.
  9. ↑ Sánchez-Pérez R, Jørgensen K, Olsen CE, Dicenta F, Møller BL (March 2008). "Bitterness in almonds". Plant Physiology. 146 (3): 1040–1052. doi:10.1104/pp.107.112979. PMC   2259050 . PMID   18192442.
  10. ↑ Lee J, Zhang G, Wood E, Rogel Castillo C, Mitchell AE (August 2013). "Quantification of amygdalin in nonbitter, semibitter, and bitter almonds (Prunus dulcis) by UHPLC-(ESI)QqQ MS/MS". Journal of Agricultural and Food Chemistry. 61 (32): 7754–7759. doi:10.1021/jf402295u. PMID   23862656. S2CID   22497338.
  11. ↑ Chisholm H, ed. (1911). "Amygdalin"  . Encyclopædia Britannica . Vol. 1 (11th ed.). Cambridge University Press. p. 900.
  12. ↑ Wahab MF, Breitbach ZS, Armstrong DW, Strattan R, Berthod A (October 2015). "Problems and Pitfalls in the Analysis of Amygdalin and Its Epimer". Journal of Agricultural and Food Chemistry. 63 (40): 8966–8973. doi:10.1021/acs.jafc.5b03120. PMID   26431391.
  13. ↑ Mann FG, Saunders BC (1975). Practical Organic Chemistry (4th ed.). London: Longman. pp. 509–517. ISBN   9788125013808.
  14. ↑ "Medical Management Guidelines (MMGs): Hydrogen Cyanide (HCN)". ATSDR. 21 October 2014. Retrieved 8 July 2019.
  15. 1 2 3 PDQ Integrative, Alternative, and Complementary Therapies Editorial Board (15 March 2017). "Laetrile/Amygdalin (PDQ®)–Health Professional Version: General Information". cancer.gov. Complementary and Alternative Medicine for Health Professionals. National Cancer Institute. PMID   26389425 . Retrieved 9 May 2017.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ↑ Leikin JB, Paloucek FP, eds. (2008). "Laetrile". Poisoning and Toxicology Handbook (4th ed.). Informa. p. 950. ISBN   978-1-4200-4479-9.
  17. ↑ Rietjens IM, Martena MJ, Boersma MG, Spiegelenberg W, Alink GM (February 2005). "Molecular mechanisms of toxicity of important food-borne phytotoxins". Molecular Nutrition & Food Research. 49 (2): 131–158. doi:10.1002/mnfr.200400078. PMID   15635687.
  18. 1 2 Duke JA (2003). CRC Handbook of Medicinal Spices. CRC Press. pp. 261–262. ISBN   978-0-8493-1279-3.
  19. 1 2 EFSA Panel on Contaminants in the Food Chain (CONTAM) (2016). "Acute health risks related to the presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot kernels". EFSA Journal. 14 (4). doi: 10.2903/j.efsa.2016.4424 . hdl: 2164/7789 .
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