MarketAmygdalin
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Amygdalin

Amygdalin is a naturally occurring chemical compound found in many plants, most notably in the seeds of apricots, bitter almonds, apples, peaches, cherries and plums, and in the roots of manioc.

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. Benzaldehyde released from amygdalin provides a bitter flavor. Because of a difference in a recessive gene called Sweet kernel [Sk], much less amygdalin is present in nonbitter (or sweet) almond than bitter almond. 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 ==
Laetrile
}} }} 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 words "laevorotatory" (referring to the molecule's stereochemistry) and "mandelonitrile" (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 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. One claimed that amygdalin was hydrolyzed to mandelonitrile, converted to a beta-glucuronide complex in the liver, then carried to cancer cells where it would release mandelonitrile and hydrogen cyanide. Mandelonitrile, however, dissociates to benzaldehyde and hydrogen cyanide, and cannot be stabilized by glycosylation. 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. The term "vitamin B-17" is not recognized as a valid vitamin or micronutrient. 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. Justus von Liebig and Friedrich Woehler found three hydrolysis products of amygdalin: sugar, benzaldehyde, and hydrogen cyanide. 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. 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. Subsequent results 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: The authors also recommended, on ethical and scientific grounds, that no further clinical research into laetrile or amygdalin be conducted. Given the lack of evidence, neither the U.S. Food and Drug Administration nor the European 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. 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 Donald 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, a specific diet, and 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 New Zealand, laetrile was among the purported treatments for cancer promoted by Milan Brych, who was later convicted of medical fraud. 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 in United States v. Rutherford, which established that interstate transport of the compound was illegal, usage fell off dramatically. 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." == See also ==
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