Health Care Professional Information

Scientific Name
D-mandelonitrile-b-D-glucosido-6-b-D-glucoside
Common Name

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

Brand Name

Laetrile®, Amigdalina, NovoDalin B17

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 through online outlets.

Amygdalin is metabolized by the enzyme beta-glucosidase into benzaldehyde, glucose and cyanide in the intestine (3) (4). Cyanide from the hydrolysis of amygdalin is believed to be cytotoxic with actions selective against cancerous cells, but results from animal studies were mostly negative (4) (5) (6). Other animal studies suggest it may help to relieve pain due to its anti-inflammatory (7) and analgesic effects (8). One study suggested amygdalin can inhibit tumor growth, but subsequent tests were unable to confirm this observation (9). A clinical trial in the late 1970s supported by the National Cancer Institute did not find amygdalin to be 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), there is renewed interest in developing this agent as an anticancer treatment.

Amygdalin has severe adverse effects. It should not be used as a cancer treatment in the current form.

Purported Uses
  • Cancer prevention
  • Cancer treatment
Constituents
  • D-mandelonitrile-b-D-glucosido-6-b-D-glucoside
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, as 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).

Recent studies found amygdalin may have anticancer effects through other mechanisms. In animals, amygdalin inhibits the tumor-promoting effect of the Epstein-Barr virus (12). In human prostate cancer DU145 and LNCaP cells, amygdalin increased pro-apoptotic Bax protein expression and caspase-3 enzyme activity, while decreasing anti-apoptotic Bcl-2 protein expression (23). It downregulates cell cycle-related genes in SNU-C4 human colon cancer cells (13). An in vitro study suggests 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).

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 reduced inflammation pain by inhibiting tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) (8).

Amygdalin exerts neurotrophic effects by activating the extracellular-signal-regulated kinase (ERK) 1/2 pathway (25).

Pharmacokinetics

Hydrocyanic acid, or cyanide, and benzaldehyde are formed from mandelonitrile when amygdalin is metabolized by beta-glucosidase enzymes in the cell. Administration of amygdalin 4.5 g/m2 intravenously to cancer patients displays two-compartment open model kinetics. Elimination half-life is approximately 2 hours with a mean clearance of 99 mL/min. No changes in whole blood levels of cyanide or thiocyanate were noted with parenteral administration (17). Repeated oral administration of amygdalin 500 mg tablets in cancer patients resulted in increased whole blood cyanide levels averaging approximately 1 mcg/mL (range 0–3 mcg/mL) (19).

Warnings

Amygdalin is not approved for use in the United States.
Cases of cyanide toxicity associated with the use of amygdalin have been reported (10) (26) (27).
Contaminated and adulterated products of both injectable and oral forms have been reported (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).

Literature Summary and Critique

Milazzo S, et al. Laetrile treatment for cancer. Cochrane Database Syst Rev. 2011 Nov 9;11:CD005476.
This review was conducted to assess the anticancer and possible adverse effects of laetrile and amygdalin. The databases CENTRAL (2011, Issue 1); MEDLINE (1951–2011); EMBASE (1980–2011); AMED; Scirus; CancerLit; CINAHL (all from 1982–2011); CAMbase (1998–2011); the MetaRegister; and the National Research Register were searched for the review. Sixty-nine studies were evaluated, but none met the inclusion criteria. Researchers concluded that the claims of beneficial effects made for laetrile or amygdalin are currently not supported by any clinical data. Further, there is a great risk of serious side effects from cyanide poisoning, especially following oral consumption of laetrile or amygdalin.

Moertel CG, et al. A clinical trial of amygdalin (laetrile) in the treatment of human cancer. New Eng J Med 1982;306:201-6.
A prospective, open-label evaluation of amygdalin plus “metabolic therapy” was conducted in 178 patients with various cancers. All patients were in generally good health and one-third had not received any prior treatment. Patients received 21 days of intravenous amygdalin 4.5 g/m2 followed by 500 mg amygdalin tablets three times daily. In addition, patients were placed on a metabolic therapy consisting of vitamins (A, C, E, B complex), minerals, and pancreatic enzyme supplementation. A diet restricting eggs, dairy, meats, and caffeinated and alcoholic beverages was also encouraged. Primary outcomes measured were tumor response and survival. Of 175 evaluable patients, there was one partial response, 79% had disease progression after 2 months, and 91% progressed by 3 months. Median survival based on all patients was 4.8 months from therapy initiation. Many adverse effects noted were related to cyanide toxicity, including headache, nausea, vomiting, dizziness, and mental obtundation. The results suggest that amygdalin is ineffective in the treatment of cancer.

Dosage (Inside MSKCC Only)
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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. Laster WR, Jr., Schabel FM, Jr. Experimental studies of the antitumor activity of amygdalin MF (NSC-15780) alone and in combination with beta-glucosidase (NSC-128056). Cancer Chemother Rep. Sep-Oct 1975;59(5):951-965.
  5. Wodinsky I, Swiniarski JK. Antitumor activity of amygdalin MF (NSC-15780) as a single agent and with beta-glucosidase (NSC-128056) on a spectrum of transplantable rodent tumors. Cancer Chemother Rep. Sep-Oct 1975;59(5):939-950.
  6. 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.
  7. 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
  8. 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.
  9. 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.
  10. 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
  11. 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
  12. 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.
  13. 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.
  14. 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
  15. Yang C, Li X, Rong J. Amygdalin isolated from Semen Persicae (Tao Ren) extracts induces the expression of follistatin in HepG2 and C2C12 cell lines. Chin Med. 2014;9:23. doi: 10.1186/1749-8546-9-23
  16. 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
  17. Moertel CG, Ames MM, Kovach JS, et al. A pharmacologic and toxicological study of amygdalin. JAMA. Feb 13 1981;245(6):591-594.
  18. 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.
  19. Ames MM, Moyer TP, Kovach JS, et al. Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol. 1981;6(1):51-57.
  20. Calabrese EJ. Possible adverse side effects from treatment with laetrile. Med Hypotheses. Sep 1979;5(9):1045-1049.
  21. Lea MA, Koch MR. Effects of cyanate, thiocyanate, and amygdalin on metabolite uptake in normal and neoplastic tissues of the rat. J Natl Cancer Inst. Nov 1979;63(5):1279-1283.
  22. Greenberg DM. The case against laetrile: the fraudulent cancer remedy. Cancer. Feb 15 1980;45(4):799-807.
  23. Chang HK, Shin MS, Yang HY, et al. Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. Biol Pharm Bull. Aug 2006;29(8):1597-1602.
  24. 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
  25. 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
  26. 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
  27. 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.
  28. Davignon JP, Trissel LA, Kleinman LM. Pharmaceutical assessment of amygdalin (Laetrile) products. Cancer Treat Rep. Jan 1978;62(1):99-104.
  29. Sadoff L, Fuchs K, Hollander J. Rapid death associated with laetrile ingestion. JAMA. Apr 14 1978;239(15):1532.
  30. O'Brien B, Quigg C, Leong T. Severe cyanide toxicity from 'vitamin supplements'. Eur J Emerg Med. Oct 2005;12(5):257-258.
  31. Chan TY. A probable case of amygdalin-induced peripheral neuropathy in a vegetarian with vitamin B12 deficiency. Ther Drug Monit. Feb 2006;28(1):140-141.

Consumer Information

How It Works

Bottom Line: Amygdalin (Laetrile) has toxic side effects and decreased survival in cancer patients.

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.
Research Evidence

Cancer treatment
A review was conducted to determine possible anticancer and adverse effects of laetrile and amygdalin. A total of 69 studies were evaluated. Researchers concluded that the claims of beneficial effects made for laetrile or amygdalin are currently not supported by any clinical data. Further, there is a great risk of serious side effects from cyanide poisoning, especially following oral consumption of laetrile or amygdalin.

A landmark study of amygdalin plus “metabolic therapy” on 178 patients with various cancers was conducted. All patients were in generally good health and one-third had not received any prior treatment. Patients received the study treatment for 3 weeks, which included both intravenous and oral amygdalin and a combination of vitamins, minerals, and enzyme supplements. A diet restricting eggs, dairy, meats, and caffeinated and alcoholic beverages was also encouraged. There was only 1 partial response to treatment among all participants and a majority of patients had disease progression after 2 months, with 91% progressing by 3 months. In addition, cyanide toxicity was identified as the cause of many adverse effects including headache, nausea, vomiting, dizziness, and mental confusion. Researchers determined that amygdalin was ineffective in the treatment of cancer.

Patient Warnings
  • Amygdalin is not an approved drug in the United States.
  • Laboratory analysis showed that some samples of amygdalin have been contaminated with microbes and substances that induce fever. This analysis also showed that both the injectable and oral forms contained less active product than was claimed on the label.
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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