Amygdalin

Amygdalin (from Ancient Greek: ἀμυγδαλή amygdálē 'almond') is a naturally occurring chemical compound best known for falsely being promoted as a cancer cure. It is found in many plants, but most notably in the seeds (kernels) of apricots, bitter almonds, apples, peaches, and plums. 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. Since the early 1950s, both amygdalin and a modified form named laetrile have been promoted as alternative cancer treatments, often under the misnomer vitamin B17 (neither amygdalin nor laetrile is a vitamin). Scientific study has found them to be clinically ineffective in treating cancer, as well as potentially toxic or lethal when taken by mouth due to cyanide poisoning. The promotion of laetrile to treat cancer has been described in the medical literature as a canonical example of quackery, and as 'the slickest, most sophisticated, and certainly the most remunerative cancer quack promotion in medical history'. 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 so that they will mix in response to tissue damage. This provides a natural defense system. Amygdalin is contained in stone fruit kernels, such as almonds, apricot (14,000 mg/kg), peach (6,800 mg/kg), and plum (4,000–17,500 mg/kg depending on variety), and also in the seeds of the apple (3,000 mg/kg). Benzaldehyde released from amygdalin provides a bitter flavor. Because of a difference in a recessive gene called Sweet kernal , less amygdalin is present in nonbitter (or sweet) almond than bitter almond. In one study, bitter almond amygdalin concentrations ranged from 33,000–54,000 mg/kg depending on variety; semibitter varieties averaged 994 mg/kg and sweet varieties averaged 63 mg/kg with significant variability based on variety and growing region. 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. 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. Amygdalin is hydrolyzed by intestinal β-glucosidase (emulsin) 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 (fatal oral dose: 0.6–1.5 mg/kg). 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 the portion of the molecule from which cyanide is released by decomposition.A 500 mg laetrile tablet may contain between 5–51 mg of hydrogen cyanide per gram.