Amygdalin

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Amygdalin

Common Names

  • Apricot pits
  • vitamin B17
  • mandelonitrile-beta-glucuronide (semi-synthetic)
  • mandelonitrile beta-D-gentiobioside (natural product)
  • laevorotatory and mandelonitrile
  • prunasin

For Patients & Caregivers

How It Works

Amygdalin (Laetrile) has not been shown to treat or prevent cancer. It is associated with serious adverse effects.

Amygdalin (also called Laetrile®) is an extract derived from apricot pits and other plants. It can be broken down by enzymes in the intestine to produce cyanide, a known poison. It was first used in Europe and later in the United States as an alternative cancer therapy. Promoters claimed that the cyanide released from amygdalin selectively killed cancer cells, leaving normal tissue cells unharmed. When fed to laboratory animals that had cancer cells implanted in them, amygdalin did not reduce the tumor size or slow their growth. In a clinical study, cancer patients using amygdalin did not have any benefits but some showed cyanide toxicity.

There is renewed interest in studying amygdalin after the discovery of new anticancer mechanisms. However, cancer patients should not use this product in the current form until more is known about its safety and effectiveness.

Purported Uses
  • To prevent and treat cancer
    Although laboratory experiments suggest anticancer properties, clinical evidence does not support this use. Amygdalin (Laetrile®) has been linked to several cases of cyanide poisoning in cancer patients.
Patient Warnings
  • Cases of cyanide toxicity associated with the use of amygdalin have been reported.
  • There have been reports of contaminated and adulterated products of both injectable and oral forms.
Side Effects
  • Inflammation and redness of the skin.
  • Cyanide toxicity from high doses or prolonged use causing: nausea, vomiting, headaches, dizziness, mental confusion, bluish discoloration of the skin, low blood pressure, drooping eyelids, nerve dysfunction, coma, and death.
Special Point
  • The Food and Drug Administration has banned the sale and use of amygdalin (Laetrile®) due to the risk of cyanide poisoning. For this reason, Laetrile® is only offered at alternative medicine clinics outside the United States. Some clinics use it as a component of multi-modality metabolic therapies. Such therapies generally have not been found effective and are discussed at greater length in a separate monograph about metabolic therapies.
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For Healthcare Professionals

Brand Name
Laetrile®, Amigdalina, NovoDalin B17
Scientific Name
D-mandelonitrile-b-D-glucosido-6-b-D-glucoside
Clinical Summary

Amygdalin is a naturally occurring cyanogenic glycoside derived from nuts, plants, and the pits of certain fruits, primarily apricots. Bitter almonds containing amygdalin are used in Traditional Chinese Medicine to remove “blood stasis” and to treat abscesses (1). Amygdalin was first used to treat cancer more than a century ago in Russia and later in the United States. A purified form sold as Laetrile has been a popular alternative cancer therapy since the 1960s. Some claimed amygdalin to be a vitamin (B17) and that deficiencies could cause cancer, but this is not substantiated by scientific evidence (2). Amygdalin is banned in the United States but it is available in other countries and online.

Amygdalin is metabolized by the enzyme beta-glucosidase into benzaldehyde, glucose and cyanide in the intestine (3) (4). Cyanide is believed to be cytotoxic with actions selective against cancerous cells, but results from animal studies were mostly negative (4) (5) (6). Other preclinical data suggest that amygdalin has hepatoprotective effects (39); may help relieve pain due to its anti-inflammatory (7) and analgesic properties (8); and exerts protective effects by modulating epithelial-mesenchymal transitions following chronic obstructive pulmonary disease (COPD) (35). Amygdalin also inhibited tumor growth, but further studies are needed to confirm this finding (9).

A clinical trial in the late 1970s supported by the National Cancer Institute did not find amygdalin beneficial, and some patients in the study developed cyanide toxicity (10). A systematic review also concluded that amygdalin is ineffective against cancer (11). With the recent discovery of anticancer properties of amygdalin through previously unknown mechanisms (12) (13) (14) (15) (16) (32) (36) (37), there is renewed interest in whether this agent may have potential as an anticancer treatment.

However, amygdalin is not approved for use in the United States.

Purported Uses
  • Cancer prevention
  • Cancer treatment
Mechanism of Action

Amygdalin is metabolized by the enzyme beta-glucosidase, which removes the glucose molecules to form prunasin and mandelonitrile. This is further broken down to benzaldehyde and hydrocyanic acid (3) (4). When consumed orally, amygdalin is more likely to produce cyanide toxicity, compared with the injectable form (17), possibly due to the presence of enzymes from the microflora in the intestine (18). Cyanide from the hydrolysis of amygdalin is cytotoxic. It was postulated that this action is selective against cancerous cells because normal cells convert the cyanide to benign thiocyanate via rhodanese (19) (20) (21). This theory has not been proven in humans (22).

Amygdalin demonstrated anti-inflammatory effects by promoting the immunomodulating function of Treg cells (24). In animal studies, amygdalin suppressed prostaglandin E(2) synthesis and nitric oxide production through COX-2 and iNOS inhibition (7). It also reduced inflammation pain by inhibiting tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) (8), and exerts neurotrophic effects by activating the extracellular-signal-regulated kinase (ERK) 1/2 pathway (25).

Recent studies found amygdalin may have anticancer effects. In animal models, amygdalin inhibits the tumor-promoting effect of the Epstein-Barr virus (12). In human prostate cancer DU145 and LNCaP cells, it increased pro-apoptotic Bax protein expression and caspase-3 enzyme activity, while decreasing anti-apoptotic Bcl-2 protein expression (23). It also down regulates cell cycle-related genes in SNU-C4 human colon cancer cells (13). Amygdalin may inhibit growth and proliferation in bladder cancer cell lines by decreasing cell cycle regulatory proteins cdk2 and cyclin A (16). It also induces growth-regulating protein follistatin expression in human hepatocarcinoma HepG2 cells (15).

Warnings
  • Cases of cyanide toxicity associated with the use of amygdalin have been reported (10) (26) (27).
  • There have been reports of contaminated and adulterated products of both injectable and oral forms (28).
Adverse Reactions

Case reports
Oral: Dermatitis and cyanide toxicity including nausea, vomiting, headache, dizziness, mental obtundation, cyanosis, hypotension, ptosis, neuropathies, coma, and death (10) (17) (29) (27) (30).
Oral: Severe cyanide poisoning following ingestion of 3 grams of amygdalin with concurrent use of high doses of vitamin C (26).
Oral: Consumption of amygdalin caused peripheral neuropathy in a patient with vitamin B12 deficiency (31).
Oral and Intraveous: Administration of intravenous and oral amygdalin caused cyanide poisoning characterized by serious agitaion and encephalopathy in a 4-year-old (33).
Oral: Hypoxia from cyanide toxicity after consumption of apricot kernel extract (34).
Oral: Cyanide poisoning, involving respiratory distress and coma following tonic-clonic convulsions, after ingesting apricot kernels in a 3-year old. Symptoms improved after hemodialysis (38).
Oral: Cyanide poisoning, after ingesting apricot kernels in a 35-year-old woman. Symptoms improved after treatment with hydroxocobalamin (40).

 

 

Dosage (OneMSK Only)
References
  1. Chen JK, Chen TT. Chinese Medical Herbology and Pharmacology. California: Art of Medicine Press; 2004.

  2. Greenberg DM. The vitamin fraud in cancer quackery. West J Med. Apr 1975;122(4):345-348.

  3. Haisman DR, Knight DJ. The enzymic hydrolysis of amygdalin. Biochem J. May 1967;103(2):528-534.

  4. Hill GJ, 2nd, Shine TE, Hill HZ, et al. Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia. Cancer Res. Jun 1976;36(6):2102-2107.

  5. Yang HY, Chang HK, Lee JW, et al. Amygdalin suppresses lipopolysaccharide-induced expressions of cyclooxygenase-2 and inducible nitric oxide synthase in mouse BV2 microglial cells. Neurol Res. 2007;29 Suppl 1:S59-64. doi: 10.1179/016164107X172248

  6. Hwang HJ, Kim P, Kim CJ, et al. Antinociceptive effect of amygdalin isolated from Prunus armeniaca on formalin-induced pain in rats. Biol Pharm Bull. Aug 2008;31(8):1559-1564.

  7. Stock CC, Martin DS, Sugiura K, et al. Antitumor tests of amygdalin in spontaneous animal tumor systems. J Surg Oncol. 1978;10(2):89-123.

  8. Moertel CG, Fleming TR, Rubin J, et al. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N Engl J Med. Jan 28 1982;306(4):201-206. doi: 10.1056/NEJM198201283060403

  9. Milazzo S, Ernst E, Lejeune S, et al. Laetrile treatment for cancer. Cochrane Database Syst Rev. 2011(11):CD005476. doi: 10.1002/14651858.CD005476.pub3

  10. Fukuda T, Ito H, Mukainaka T, et al. Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biol Pharm Bull. Feb 2003;26(2):271-273.

  11. Park HJ, Yoon SH, Han LS, et al. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World J Gastroenterol. Sep 7 2005;11(33):5156-5161.

  12. Chen Y, Ma J, Wang F, et al. Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells. Immunopharmacol Immunotoxicol. Feb 2013;35(1):43-51. doi: 10.3109/08923973.2012.738688

  13. Makarevic J, Rutz J, Juengel E, et al. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2. PLoS One. 2014;9(8):e105590. doi: 10.1371/journal.pone.0105590

  14. Moertel CG, Ames MM, Kovach JS, et al. A pharmacologic and toxicological study of amygdalin. JAMA. Feb 13 1981;245(6):591-594.

  15. Carter JH, McLafferty MA, Goldman P. Role of the gastrointestinal microflora in amygdalin (laetrile)-induced cyanide toxicity. Biochem Pharmacol. Feb 1980;29(3):301-304.

  16. Ames MM, Moyer TP, Kovach JS, et al. Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol. 1981;6(1):51-57.

  17. Calabrese EJ. Possible adverse side effects from treatment with laetrile. Med Hypotheses. Sep 1979;5(9):1045-1049.

  18. Greenberg DM. The case against laetrile: the fraudulent cancer remedy. Cancer. Feb 15 1980;45(4):799-807.

  19. Jiagang D, Li C, Wang H, et al. Amygdalin mediates relieved atherosclerosis in apolipoprotein E deficient mice through the induction of regulatory T cells. Biochem Biophys Res Commun. Aug 5 2011;411(3):523-529. doi: 10.1016/j.bbrc.2011.06.162

  20. Yang C, Zhao J, Cheng Y, et al. Bioactivity-guided fractionation identifies amygdalin as a potent neurotrophic agent from herbal medicine Semen Persicae extract. Biomed Res Int. 2014;2014:306857. doi: 10.1155/2014/306857

  21. Bromley J, Hughes BG, Leong DC, et al. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Ann Pharmacother. Sep 2005;39(9):1566-1569. doi: 10.1345/aph.1E634

  22. Kalyanaraman UP, Kalyanaraman K, Cullinan SA, et al. Neuromyopathy of cyanide intoxication due to “laetrile” (amygdalin). A clinicopathologic study. Cancer. Jun 1 1983;51(11):2126-2133.

  23. Davignon JP, Trissel LA, Kleinman LM. Pharmaceutical assessment of amygdalin (Laetrile) products. Cancer Treat Rep. Jan 1978;62(1):99-104.

  24. Sadoff L, Fuchs K, Hollander J. Rapid death associated with laetrile ingestion. JAMA. Apr 14 1978;239(15):1532.

  25. O’Brien B, Quigg C, Leong T. Severe cyanide toxicity from ’vitamin supplements’. Eur J Emerg Med. Oct 2005;12(5):257-258.

  26. Makarević J, Rutz J, Juengel E, et al. Amygdalin influences bladder cancer cell adhesion and invasion in vitro. PLoS One. 2014 Oct 15;9(10):e110244.

  27. Sauer H, Wollny C, Oster I, et al. 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):185-8. doi: 10.1007/s10354-014-0340-7.

  28. Konstantatos A, Shiv Kumar M, Burrell A, et al.An unusual presentation of chronic cyanide toxicity from self-prescribed apricot kernel extract.  BMJ Case Rep. 2017 Sep 11;2017. pii: bcr-2017-220814.

  29. Wang Z, Fang K, Wang G, et al. Protective effect of amygdalin on epithelial-mesenchymal transformation in experimental chronic obstructive pulmonary disease mice. Phytother Res. 2019 Jan 30. doi: 10.1002/ptr.6274. [Epub ahead of print]

  30. Cassiem W, de Kock M. The anti-proliferative effect of apricot and peach kernel extracts on human colon cancer cells in vitro. BMC Complement Altern Med. 2019 Jan 29;19(1):32.

  31. Liczbiński P, Bukowska B. Molecular mechanism of amygdalin action in vitro: review of the latest research. Immunopharmacol Immunotoxicol. 2018 Jun;40(3):212-218.

  32. Dalkiran T, Kandur Y, Ozaslan M, Acipayam C, Olgar S. Role of Hemodialysis in the Management of Cyanide Intoxication From Apricot Kernels in a 3-Year-Old Child. Pediatr Emerg Care. 2018 Nov 5. doi: 10.1097/PEC.0000000000001644. [Epub ahead of print]

  33. Cigolini D, Ricci G, Zannoni M, et al. Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels. Emerg Med J. 2011 Sep;28(9):804-5.

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