Written by Adele Stapf, Helen Cooke, Helen Seers and the CAM-Cancer Consortium.
Updated February 8, 2017

Amygdalin/Laetrile

Abstract and key points

  • Amygdalin is a naturally occurring plant compound primarily found in the seeds of apricots, peaches and bitter almonds. Laetrile is an acronym used to describe a purified, semi-synthetic form of amygdalin
  • There is no evidence for the effectiveness of drugs containing amygdalin in anti-cancer therapy
  • Laetrile is associated with considerable safety concerns

Amygdalin is a naturally occurring plant compound. It is primarily found in the seeds of apricots, peaches and bitter almonds and also in plants such as lima beans, clover and sorghum. Laetrile is an acronym (derived from LAEvorotatory and mandeloniTRILE) used to describe a purified, semi-synthetic form of amygdalin.

Laetrile is claimed to be an anti-cancer treatment or even cure, and cyanide is thought to be the active anti-cancer ingredient. It was at the height of its popularity in the U.S. in the 1970s and 1980s until the FDA considered it unsafe after a phase II controlled clinical trial in 1982 found no evidence for the efficacy of laetrile and highlighted considerable safety concerns including cyanide poisoning. According to current scientific understanding there is no evidence for the effectiveness of drugs containing amygdalin in anti-cancer therapy.  Based on this risk assessment and the lack of evidence for the effectiveness of amygdalin even after decades of clinical use, more recent reviews conclude that this substance should not be recommended for anti-cancer therapy.

What is Laetrile?

Description    

Amygdalin is a secondary plant compound belonging to the group of cyanogenic glycosides characterized by the release of cyanide upon enzymatic degradation.

Names

Amygdalin is also known as vitamin B17, mandelonitrile-beta-glucuronide (semi-synthetic), mandelonitrile beta-D-gentiobioside (natural product), amygdalina, and nitriloside. Laetrile is an acronym derived from ‘LAEvorotatory’ and ‘mandeloniTRILE’ and is used to describe a purified, semi-synthetic form of amygdalin.

Ingredients

Amygdalin is a secondary plant compound belonging to the group of cyanogenic glycosides, which are enzymatically degraded by beta-glucosidases to form cyanide. The compound is found in the seeds of apricots, peaches and bitter almonds and also in plants such as lima beans, clover and sorghum.  Minor amounts of amygdalin may be ingested when eating a balanced diet.

The chemistry of laetrile available in the United States is different from the one used in Mexico. The laetrile used in Mexico may be crushed apricot seeds rather than the semi-synthetic form of laetrile (mandelonitrile-beta-glucuronide) that is used in the US.1 Therefore it is conceivable that not all studies on laetrile have looked at the same compound.

Application and dosage

Amygdalin is usually taken orally in the form of bitter apricot seeds. Laetrile is available for oral administration as well as intravenous or intramuscular injection. Treatment is typically initiated intravenously for two to three weeks and then continued orally. Laetrile is also used as an enema form or applied directly to skin lesions.

History and providers

Amygdalin was first identified and isolated by French chemists in 1830 and was used as an anti-cancer agent in 1845 in Russia. By the 1920s amygdalin had reached the US, but the early pill form was considered to be too toxic and its use was discontinued. In the 1950s an apparently non-toxic, semi--synthetic intravenous form of amygdalin was developed by Ernst T Krebs in the U.S., and this became known as laetrile. In the 1970s laetrile gained popularity either as a single-agent treatment or as part of a metabolic treatment regimen that also included high-dose vitamin supplements and enzymes.2

Claims of efficacy/alleged indications/mechanisms of actions

Suppliers have postulated the use of amygdalin or laetrile as anti-cancer treatment. Proponents claim that amygdalin or laetrile has anti-cancer effects ascribing them to the cyanide released upon enzymatic degradation of the compound. They postulate that amygdalin is selectively effective against cancer cells only. This hypothesis involves an imbalance of the enzymes beta-glucosidases, beta-glucuronidase and rhodanase in cancer cells as compared to healthy cells. Malignant cells are claimed to be specifically vulnerable to cyanogenic glycosides because of two characteristics: firstly, a higher level of beta-glucosidases and beta-glucuronidase compared to healthy cells, which would lead to a more rapid intracellular release of cyanide from laetrile or amygdalin, and secondly, a deficiency in rhodanase, an enzyme that converts cyanide into the harmless compound thiocyanate.3 4

Many supporters of laetrile refer to anthropological evidence from epidemiological studies of secluded cultures consuming high levels of foods rich in amygdalin, e.g.  the Hunzakots of Pakistan, the Inuit of the Arctic or the indigenous Hopi and Navajo of North America.5 Expeditions have reported extraordinary longevity and the absence of cancer in these cultures, however the studies are often flawed due to language barriers, highly selected contacts and sometimes deliberate misinformation. They fail to provide clear evidence for a causal relationship between the uptake of amygdalin and the incidence of cancer.

According to a historical theory cancer develops as a result of a deficiency of a vitamin called "vitamin B17", which was the name the chemist E.T. Krebs gave to laetrile.6

Prevalence of use

The popularity of laetrile reached its peak in the United States in 1978 when it was reported that 70,000 people had been treated with it.2 Current prevalence data are not available.

Legal issues

In the US laetrile has had a long controversial history. This includes inaccurate theories of how it works, conspiracy theories of unpublished research studies supporting its use, banning of its use in the US by the Food and Drug Administration (FDA), and prison sentences for many proponents and suppliers (including ETKrebs himself). The controversy continues. In the United Kingdom the Medicines and Healthcare Products Regulatory Agency (MHRA) has assigned amygdalin/laetrile /B17 the status of a prescription-only medicine. The substance is not banned but it is unlicensed, and so access to it is subject to prescription by a medical doctor. This implies that doctors can supply it to a patient should they consider it an appropriate treatment, but do so at their own risk. There is no licensed product containing the substance laetrile/amygdalin/B17 in the UK. Drugs containing amygdalin are not approved by the regulatory authorities in Germany and are considered unsafe according to the German Drug Act.

Cost and expenditures

Drug preparations are available via the internet for approximately 100 US$ for 60-100 tablets. Since there are no clear guidelines on dosage and duration of treatment, it is not possible to provide the total cost of treatment.

Does it work?

Use as anti-cancer therapy

Systematic reviews

The authors of a 2015 Cochrane systematic review were unable to find any randomised controlled trials assessing the effectiveness of laetrile. They concluded that there was no evidence that laetrile was effective as an anti-cancer agent.6

Clinical trials

Two clinical trials have been conducted using amygdalin/laetrile:

In the first uncontrolled study (phase I;  n = 6) amygdalin was applied intravenously at a dosage of 4.5  g/m2 body surface followed by oral administration of  0.5 g three times daily.7 Additionally, patients took a combination of several vitamins and enzymes and followed a diet. Two of the six tumour patients studied developed symptoms of cyanide poisoning while they were taking oral amygdalin. No indications of clinical effectiveness were found.

The second clinical trial (phase II; n = 175) compared the above amygdalin dosage regimen versus a “high-dose group” (7 g/m2 body surface i.v. for 21 days followed by 0.5 g four times daily). Also the adjunct treatment programme comprising vitamins, dietary guidelines and enzymes differed in terms of the dosages used. One participant showed a decrease in tumour size.8

Observational studies and case series

No observational studies and case series allowing conclusions about the effectiveness and efficacy of amygdalin are available.

Is it safe ?

Adverse events

When taken orally amygdalin or laetrile may result in serious adverse events. The intestinal microflora contains enzymes that enhance the release of cyanide in the intestinal tract.14

The adverse events observed reflect the symptoms of cyanide poisoning. Headache, dizziness, nausea and vomiting, dermatitis or, in severe cases, disturbed consciousness, tachycardia, respiratory distress, liver damage, coma and death may occur following oral administration. Several fatalities were attributed to drug preparations containing amygdalin.9 10

The risk of cyanide poisoning with oral intake of laetrile is increased when vitamin C is taken additionally.11 A case of adverse drug reaction showing signs and symptoms of a serious, life-threatening inadvertent cyanide poisoning has been reported in Australia in 2005. The report suggests that a female patient increased the cyanide toxicity risk by taking amygdalin concomitantly with a high dose of vitamin C (4,800 mg).12 A case report of a 4-year-old boy with severe encephalopathy due to cyanide poisoning after oral and intravenous administration of amygdalin has been published in 2015.13

Since the tolerance of amygdalin may vary greatly, it is impossible to predict the risk for an individual patient. A review concluded that there is a high risk of cyanide poisoning when amygdalin is taken orally.15

As opposed to oral administration, there is no proof for toxicities associated with parenterally administered pure amygdalin.  However, amygdalin preparations contaminated with beta-glucosidases, seen particularly when the product is made from apricot seeds, may enhance the hydrolysis of amygdalin and thus considerably increase its toxicity. In the presence of such contaminants even parenteral application of amygdalin may cause cyanide poisoning.4

Contraindications

In addition to the risks mentioned above, products containing amygdalin may decrease liver function in patients with hepatic impairment.10  The use of amygdalin during pregnancy or breast-feeding is contraindicated.

Interactions

An experimental animal study showed no effect of amygdalin on the activity of the CYP2B isoenzymes; however there may be an effect on the subgroups CYP2A, 2C and 3A. There are no indications of any clinically relevant pharmacokinetic interactions.16

Warnings

Particularly oral ingestion may result in a dose-dependent severe, possibly fatal cyanide poisoning.

Additionally, cases of mislabeling have been observed and investigations of samples showed contamination with bacteria, toxins and other substances.

Citation Adele Stapf, Helen Cooke, Helen Seers, CAM-Cancer Consortium. Amygdalin/Laetrile [online document]. http://ws.cam-cancer.org/The-Summaries/Dietary-approaches/Amygdalin-Laetrile. February 8, 2017.

References

  1. Davignon, JP, Trissel, LA, & Kleinman, LM. Pharmaceutical assessment of amygdalin (Laetrile) products. Cancer Treatment Reports. 1978; 62 (1): 99-104.
  2. Chandler, RF, Phillipson, JD & Anderson, LA. Controversial Laetrile. Journal of Pharmacology. 1984; 232: 330-332
  3. Ellison, NM, Byar, DP, & Newell, GR. Special report on Laetrile: the NCI Laetrile Review. Results of the National Cancer Institute's retrospective Laetrile analysis.New England Journal of Medicine. 1978; 7;299 (10):549-52.
  4. Bulletin zur Arzneimittelsicherheit. Informationen aus BfArM und PEI. Ausgabe 3, September 2014. http://www.bfarm.de/bulletin, accessed 8th February 2017.
  5. McCarrison, SR. “Nutrition and National Health.” Journal of the Royal Society of Arts. 1936. lxxxiv, 1047, 1067, 1087.
  6. Milazzo S & Horneber M. Laetrile treatment for cancer. Cochrane Database Syst Rev. 2015 Apr 28;4:CD005476. doi: 0.1002/14651858.CD005476.pub4.
  7. Moertel, CG, Ames, MM, Kovach, JS, et al. A pharmacologic and toxicological study of amygdalin. Journal of the American Medical Association. 1981. 245 (6): 591-4.
  8. Moertel, CG, Fleming, TR, Rubin, J, et al. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. New England Journal of Medicine. 1982; 306 (4): 201-6.
  9. Braico, KT, Humbert, JR, Terplan, KL, & Lehotay, JM. Laetrile intoxication: report of a fatal case, New England Journal of Medicine. 1979; 1; 300 (5): 238-40.
  10. Sadoff, L, Fuchs, K, & Hollander, J, Rapid death associated with Laetrile ingestion, Journal of the American Medical Association. 1978; 14; 239 (15): 1532.
  11. Lee, M, Berger, HW, Givre, HL, et al. Near fatal Laetrile intoxication: Complete recovery with supportive treatment, Mount Sinai Journal of Medicine. 1982; 49 (4): 305-307.
  12. Bromley J, Hughes BG, Leong DC, Buckley NA. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Ann Pharmacother. 2005 Sep;39(9):1566-9.
  13. Sauer H, Wollny C, Oster I, Tutdibi E, Gortner L, Gottschling S, Meyer S. Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child. Wien Med Wochenschr. 2015 May;165(9-10):185-188.
  14. Newmark J, Brady, RO, Grimley, PM, Gal, AE, Waller, SG, & Thistlethwaite, JR. Amygdalin (Laetrile) and pruasin beta-glucosidases: Distribution in germ free rat and in human tumor tissue. Proceedings of the National Academy of Sciences of the United States of America. 1981; 78 (10): 6513-6.
  15. Milazzo S, Lejeune S, Ernst E. Laetrile for cancer: a systematic review of the clinical evidence. Support Care Cancer. 2007 Jun;15(6):583-95.
  16. Yamada H, Nakamura T, Oguri K. Induction of rat hepatic cytochromes P450 by toxic ingredients in plants: lack of correlation between toxicity and inductive activity. J Toxicol Sci. 1998 Dec;23(5):395-402.