Жеміс дәндің құрамындағы цианогенді гликозид

Cyanogenic glycoside present in kernels of fruit

Amygdalin (from Ancient Greek: ἀμυγδαλή amygdalē 'almond') is a naturally occurring chemical compound found in many plants, most notably in the seeds (kernels) 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. 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). 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 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). 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. 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. 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 which has a fatal oral dose range of 0.6–1.5 mg/kg of body weight.

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. A 500 mg laetrile tablet may contain between 2.5 and 25 mg of hydrogen cyanide. 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. Claims for laetrile were based on three different hypotheses: 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. 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. The term "vitamin B 17" is not recognized by Committee on Nomenclature of the American Institute of Nutrition Vitamins.

Amygdalin was first isolated in 1830 from bitter almond seeds (Prunus dulcis) by Pierre Jean Robiquet and Antoine Boutron Charlard. Liebig and Wöhler found three hydrolysis products of amygdalin: sugar, benzaldehyde, and prussic acid (hydrogen cyanide, HCN). 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. 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. and later marketed as laetrile for cancer treatment. Thereafter, 27 U. S. states legalized the use of amygdalin within those states.

In a 1977 controlled, blinded trial, laetrile showed no more activity than placebo. These mistakes were considered scientifically inconsequential, but Nicholas Wade in Science stated that "even the appearance of a departure from strict objectivity is unfortunate." The results from these studies were published all together. A 2015 systematic review from the Cochrane Collaboration found: quotation|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. For example, a 1982 trial by the Mayo Clinic of 175 patients found that tumor size had increased in all but one patient. 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." 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. Some American cancer patients have traveled to Mexico for treatment with the substance, for example at the Oasis of Hope Hospital in Tijuana. 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. Laetrile advocates in the United States include Dean Burk, a former chief chemist of the National Cancer Institute cytochemistry laboratory, 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. The court also found that Vale had made at least $500,000 from his fraudulent sales of laetrile. 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 which established that interstate transport of the compound was illegal, usage fell off dramatically. 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."

The Law & Order episode "Second Opinion" is about a nutritional counselor named "Doctor" Haas giving patients laetrile as a cancer treatment for breast cancer as an alternative to getting a mastectomy.