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| 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 |
| EC Number |
|
| MeSH | Amygdalin |
| UNII | |
| |
| |
| 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: | |
 | |
| Warning | |
| H302 | |
| P264,P270,P301+P312,P330,P501 | |
| NFPA 704 (fire diamond) | |
| Safety data sheet (SDS) | A6005 |
| Related compounds | |
Related compounds | Vicianin,laetrile,prunasin,sambunigrin |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Amygdalin (fromAncient Greek:ἀμυγδαλήamygdalē 'almond') is a naturally occurringchemical compound found in many plants, most notably in the seeds (kernels, pips or stones) ofapricots,bitter almonds,apples,peaches,cherries andplums, and in the roots ofmanioc.
Amygdalin is classified as acyanogenic glycoside, because each amygdalin molecule includes anitrile group, which can be released as the toxiccyanide anion by the action of abeta-glucosidase. Eating amygdalin will cause it to release cyanide in the human body, and may lead tocyanide poisoning.[1]
Since the early 1950s, both amygdalin and a chemical derivative namedlaetrile have been promoted asalternative cancer treatments, often under themisnomervitamin B17 (neither amygdalin nor laetrile is avitamin).[2] Scientific study has found them to not only be clinically ineffective in treating cancer but also dangerous due to the considerable poisoning risks.[3] The promotion of laetrile to treat cancer has been described in the medical literature as a canonical example ofquackery[4][5] and as "the slickest, most sophisticated, and certainly the mostremunerative cancer quack promotion in medical history".[2] Amygdalin has also been examined in the context oftraditional Chinese medicine.[6]
Amygdalin is contained inRosaceae plants[7]stone fruit kernels, such asalmonds,apricot (14 g/kg),red cherry (3.9 g/kg),black cherry (2.7 g/kg),peach (6.8 g/kg), andplum (4–17.5 g/kg depending on variety), and also in the seeds of theapple (3 g/kg).[8] 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.[9]
Amygdalin is a cyanogenic glycoside derived from the aromatic amino acidphenylalanine. Amygdalin andprunasin are common among plants of the familyRosaceae, particularly the genusPrunus,Poaceae (grasses),Fabaceae (legumes), and in other food plants, includingflaxseed andmanioc. 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.[10]
Benzaldehyde released from amygdalin provides a bitter flavor. Because of a difference in a recessive gene calledSweet kernel [Sk], much less amygdalin is present in nonbitter (or sweet) almond thanbitter almond.[11]
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 inethanol; on evaporation of the solution and the addition ofdiethyl ether, amygdalin is precipitated as minute white crystals.[12] Natural amygdalin has the (R)-configuration at the chiral phenyl center. Under mild basic conditions, this stereogenic center isomerizes; the (S)-epimer is calledneoamygdalin. Although the synthesized version of amygdalin is the (R)-epimer, the stereogenic center attached to the nitrile and phenyl groups easilyepimerizes if the manufacturer does not store the compound correctly.[13]
Amygdalin ishydrolyzed by intestinalβ-glucosidase (emulsin)[14] andamygdalin beta-glucosidase (amygdalase) to givegentiobiose andL-mandelonitrile. Gentiobiose is further hydrolyzed to giveglucose, whereas mandelonitrile (thecyanohydrin ofbenzaldehyde) decomposes to give benzaldehyde andhydrogen 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.[15]
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| 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 |
| |
| |
| 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 theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Laetrile (patented 1961) is a simpler semisyntheticderivative 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 words "laevorotatory" (referring to the molecule'sstereochemistry) and "mandelonitrile" (the portion of the molecule from which cyanide is released by decomposition).[16] A 500 mg laetrile tablet may contain between 2.5 and 25 mg of hydrogen cyanide.[17]
Like amygdalin, laetrile is hydrolyzed in the duodenum (alkaline) and the intestine (enzymatically) toD-glucuronic acid andL-mandelonitrile; the latter hydrolyzes to benzaldehyde and hydrogen cyanide, that in sufficient quantities causescyanide poisoning.[18]
Claims for laetrile were based on three different hypotheses.[19] One claimed that amygdalin was hydrolyzed tomandelonitrile, converted to a beta-glucuronide complex in the liver, then carried to cancer cells where it would release mandelonitrile and HCN. Mandelonitrile, however, dissociates to benzaldehyde and hydrogen cyanide, and cannot be stabilized by glycosylation.[20]: 9
Finally, the third asserted that laetrile is the discovered vitamin B-17, further suggesting that cancer results from "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.[21] The term "vitamin B-17" is not recognized by Committee on Nomenclature of the American Institute of Nutrition Vitamins.[16]Ernst T. Krebs (not to be confused withHans Adolf Krebs, the discoverer of thecitric acid cycle) branded laetrile as a vitamin in order to have it classified as anutritional supplement rather than as a pharmaceutical.[2]
Amygdalin was first isolated in 1830 frombitter almond seeds (Prunus dulcis) byPierre-Jean Robiquet andAntoine Boutron-Charlard.[22]Justus von Liebig andFriedrich Woehler found threehydrolysis products of amygdalin: sugar, benzaldehyde, andhydrogen cyanide.[23] Later research showed thatsulfuric acid hydrolyzes it intoD-glucose, benzaldehyde, and hydrogen cyanide; whilehydrochloric acid givesmandelic acid,D-glucose, andammonia.[24]
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.[25] In the 1950s, a purportedly non-toxic, synthetic form was patented for use as a meat preservative,[26] and later marketed as laetrile for cancer treatment.[25]
TheU.S. Food and Drug Administration prohibited the interstate shipment of amygdalin and laetrile in 1977.[27][28] Thereafter, 27 U.S. states legalized the use of amygdalin within those states.[29]
In a 1977 controlled, blinded trial, laetrile showed no more activity than placebo.[30] Subsequently, laetrile was tested on 14 tumor systems without evidence of effectiveness. TheMemorial Sloan–Kettering Cancer Center (MSKCC) concluded that "laetrile showed no beneficial effects."[30] Mistakes in an earlier MSKCC press release were highlighted by a group of laetrile proponents led byRalph Moss, a former public affairs official for MSKCC who had been fired following his appearance at a press conference accusing the hospital of covering up the benefits of laetrile.[31] These mistakes were considered scientifically inconsequential, butNicholas Wade, inScience, stated that "even the appearance of a departure from strict objectivity is unfortunate."[30] The results from these studies were published all together.[32]
A 2015systematic review from theCochrane 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.[33]
Given the lack of evidence, neither theU.S. Food and Drug Administration nor theEuropean Commission has approved laetrile. 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.[25] For example, a 1982 trial by theMayo Clinic of 175 patients found that tumor size had increased in all but one patient.[34] 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."[25]
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.
TheEuropean Food Safety Agency's Panel on Contaminants in the Food Chain has studied the potential toxicity of the amygdalin inapricot 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".[20]
Advocates for laetrile assert that there is aconspiracy between the USFood and Drug Administration, thepharmaceutical industry, and the medical community, including theAmerican Medical Association and theAmerican Cancer Society, to exploit the American people, and especially cancer patients.[35]
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.[35] 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 tosurgery andchemotherapy that have significant side effects. The use of laetrile led to a number of deaths.[35]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.[36]
Some American cancer patients have traveled toMexico for treatment with the substance, for example at theOasis of Hope Hospital inTijuana.[37] The actorSteve McQueen died in Mexico following surgery to remove astomach tumor, having previously undergone extended treatment forpleuralmesothelioma—a cancer associated withasbestos exposure—under the care ofWilliam Donald Kelley, a de-licensed dentist and orthodontist who claimed to have devised a cancer treatment involvingpancreatic enzymes, 50 daily vitamins and minerals, frequent body shampoos, enemas, a specific diet, and laetrile.[38]
Laetrile advocates in the United States includeDean Burk, a former chief chemist of theNational Cancer Institutecytochemistry laboratory,[39] and nationalarm wrestling champion Jason Vale, who falsely claimed that hiskidney andpancreatic cancers were cured by eatingapricot seeds. Vale was convicted in 2004 for, among other things, fraudulently marketing laetrile as a cancer cure.[40] The court also found that Vale had made at least $500,000 from his fraudulent sales of laetrile.[41]
In New Zealand, laetrile was among the purported treatments for cancer promoted byMilan Brych, who was later convicted of medical fraud.[42]
In the 1970s, court cases in several states challenged the FDA's authority to restrict access to what they claimed were potentially lifesaving drugs. More than twenty states passed laws making the use of laetrile legal. After the unanimous Supreme Court ruling inUnited States v. Rutherford,[43] which established that interstate transport of the compound was illegal, usage fell off dramatically.[16][44] The FDA 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."[45]
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
{{cite journal}}: CS1 maint: multiple names: authors list (link)Jason Vale.
| International | |
|---|---|
| National | |
| Other | |