# Laetrile

Laetrile (patented 1961) is a 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.
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.$^{:9}$
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. The term "vitamin B-17" is not recognized by Committee on Nomenclature of the American Institute of Nutrition Vitamins. 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.

### 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. Liebig and Wöhler 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. In the 1950s, a purportedly non-toxic, synthetic form was patented for use as a meat preservative, and later marketed as laetrile for cancer treatment.
The U.S. Food and Drug Administration prohibited the interstate shipment of amygdalin and laetrile in 1977. 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.
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." 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. 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 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.
The authors also recommended, on ethical and scientific grounds, that no further clinical research into laetrile or amygdalin be conducted. Subsequent research has confirmed the evidence of harm and lack of benefit.
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. 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 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".

### 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.
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.
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. 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."