Laetrile for cancer: a systematic review of the clinical evidence

Abstract

Background

Many cancer patients treated with conventional therapies also try ‘alternative’ cancer treatments. Laetrile is one such ‘alternative’ that is claimed to be effective by many alternative therapists. Laetrile is also sometimes referred to as amygdalin, although the two are not the same.

Objective

The aim of this review is to summarize all types of clinical data related to the effectiveness or safety of laetrile interventions as a treatment of any type of cancer.

Materials and methods

All types of clinical studies containing original clinical data of laetrile interventions were included. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1951), EMBASE (from 1980), Allied and Complementary Medicine (AMED), Scirus, CancerLit, Cumulative Index to Nursing and Allied Health (CINAHL; all from 1982), CAMbase (from 1998), the MetaRegister, the National Research Register, and our own files. For reports on the safety of laetrile, we also searched the Uppsala database. No language restrictions were imposed.

Results

Thirty six reports met our inclusion criteria. No controlled clinical trials were found. Three articles were nonconsecutive case series, 2 were consecutive case series, 6 were best case series, and 25 were case reports. None of these publications proved the effectiveness of laetrile.

Conclusion

Therefore, the claim that laetrile has beneficial effects for cancer patients is not supported by sound clinical data.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    http://www.who.int/cancer/media/en/788.pdf

  2. 2.

    http://216.239.59.104/u/who?q=cache:Pqq2bFQPilgJ:www.euro.who.int/childhealthenv/Risks/CancerTop+children+cancer&hl=en&ie=UTF-8

  3. 3.

    http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_Introduction_7.asp?sitearea

  4. 4.

    Gibbs M (2004) Networking topics for palliative care. Pharm J 273(7320):539

    Google Scholar 

  5. 5.

    Schmidt K, Ernst E (2004) Assessing websites on complementary and alternative medicine for cancer. Ann Oncol 15:733–742

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Holland JC (1982) Why patients seek unproven cancer remedies: a psychological perspective. CA Cancer J Clin 32(1):10–14

    PubMed  CAS  Google Scholar 

  7. 7.

    Fenselau C, Pallante S, Batzinger RP, Benson WR, Barron RP, Sheinin EB, Maienthal M (1977) Mandelonitrile beta-glucuronide: synthesis and characterization. Science 198(4317):625–627

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Fukuda T, Ito H, Mukainaka T, Tokuda H, Nishino H, Yoshida T (2003) Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biol Pharm Bull 26(2):271–273

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Jean Bruneton (1999) Pharmacognosy, 2nd edn. Intercept, Paris

    Google Scholar 

  10. 10.

    Gurib-Fakim A, Brendler T (2004) Medicinal and aromatic plants of Indian Ocean islands. Medpharm, Stuttgart, Germany

  11. 11.

    Kwon HY, Hong SP, Hahn DH, Kim JH (2003) Apoptosis induction of Persicae Semen extract in human promyelocytic leukemia (HL-60) cells. Arch Pharm Res 26(2):157–161

    PubMed  CAS  Article  Google Scholar 

  12. 12.

    Turczan JW, Medwick T, Plank W (1978) Cyanogenetic glycosides. J Assoc Off Anal Chem 61:192–207

    CAS  Google Scholar 

  13. 13.

    Howard-Ruben J, Miller NJ (1984) Unproven methods of cancer management. Part II: current trends and implications for patient care. Oncol Nurs Forum 11(1):67–73

    PubMed  CAS  Google Scholar 

  14. 14.

    Dorr RT, Paxinos J (1978) The current status of laetrile. Ann Intern Med 89(3):389–397

    PubMed  CAS  Google Scholar 

  15. 15.

    Davignon JP, Trissel LA, Kleinman LM (1978) Pharmaceutical assessment of amygdalin (laetrile) products. Cancer Treat Rep 62(1):99–104

    PubMed  CAS  Google Scholar 

  16. 16.

    Ellison NM, Byar DP, Newell GR (1978) Special report on laetrile: NCI (National Cancer Institute) laetrile review. N Engl J Med 299:549–552

    PubMed  CAS  Article  Google Scholar 

  17. 17.

    David Shaffer (1979) The Associated Press (July 16)

  18. 18.

    Michael Putzel (1979) The Associated Press (June 19)

  19. 19.

    23 states have passed laetrile legislation (1980) The Associated Press (December 21)

  20. 20.

    Curran WJ (1980) Law-medicine notes. Laetrile for the terminally ill: Supreme Court stops the nonsense. N Engl J Med 302(11):619–621

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Meijer EL (2001) Sale over the Internet of substances for human consumption which are regarded as harmful in America. Off J (2001/C 151 E/071)

  22. 22.

    Questionable cancer practices in Tijuana and other Mexican border clinics (1991). CA Cancer J Clin 41(5):310–319

    Google Scholar 

  23. 23.

    Moertel CG, Fleming TR, Rubin J, Kvols LK, Sarna G, Koch R, Currie VE, Young CW, Jones SE, Davignon JP (1982) A clinical trial of amygdalin (laetrile) in the treatment of human cancer. N Engl J Med 306(4):201–206

    PubMed  CAS  Article  Google Scholar 

  24. 24.

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

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Newmark J, Brady RO, Grimley PM, Gal AE, Waller SG, Thistlethwaite JR (1981) Amygdalin (laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc Natl Acad Sci U S A 78(10):6513–6516

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Miller KW, Anderson JL, Stoewsand GS (1981) Amygdalin metabolism and effect on reproduction of rats fed apricot (Prunus armeniaca) kernels. J Toxicol Environ Health 7(3–4):457–468

    PubMed  CAS  Article  Google Scholar 

  27. 27.

    Biaglow JE, Durand RE (1978) The enhanced radiation response of an in vitro tumour model by cyanide released from hydrolysed amygdalin. Int J Radiat Biol Relat Stud Phys Chem Med 33(4):397–401

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Manner HW, Di Santi SJ, Maggio MI (1978) Amygdalin, vitamin A and enzyme induced regression of murine mammary adenocarcinomas. J Manip Physiol Ther 1(4):246–248

    Google Scholar 

  29. 29.

    Bhatti RA, Ablin RJ, Guinan PD (1981) Tumour-associated directed immunity in prostatic cancer: effect of amygdalin. IRCS Med Sci Clin Biochem 9(1):19

    Google Scholar 

  30. 30.

    Kousparou CA, Epenetos AA, Deonarain MP (2002) Antibody-guided enzyme therapy of cancer producing cyanide results in necrosis of targeted cells. Int J Cancer 99(1):138–148 (May 1)

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Syrigos KN, Rowlinson-Busza G, Epenetos AA (1998) In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. Int J Cancer 78(6):712–719

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Milazzo S, Ernst E, Lejeune S, Schmidt K (2006) Laetrile treatment for cancer. The Cochrane Database of Systematic Reviews, Issue 2, Art. No.: CD005476

  33. 33.

    Moertel CG, Ames MM, Kovach JS, Moyer TP, Rubin JR, Tinker JH (1981) Pharmacologic and toxicological study of amygdalin. JAMA 245(6):591–594 (Feb 13)

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Ames MM, Moyer TP, Kovach JS, Moertel CG, Rubin J (1981) Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol 6(1):51–57

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Schmidt ES, Newton GW, Sanders SM, Lewis JP, Conn EE (1978) Laetrile toxicity studies in dogs. JAMA 239(10):943–947 (Mar 6)

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    McAnalley BH, Gardiner TH, Garriott JC (1980) Cyanide concentrations in blood after amygdalin (laetrile) administration in rats. Vet Hum Toxicol 22(6):400–402 (Dec)

    PubMed  CAS  Google Scholar 

  37. 37.

    Treatment of cancer with laetriles; a report by the Cancer Commission of the California Medical Association (1953). Calif Med 78(4):320–326 (Apr)

    Google Scholar 

  38. 38.

    Guidetti Hector (1955) Observations preliminaries sur quelques cas de cancer traits par un glycuronosyde cyanogenetique. Acta XI(2):156–158

    Google Scholar 

  39. 39.

    Navarro MD (1957) The mechanism of action and therapeutic effects of laetrile in cancer. J Philipp Med Assoc 33(8):620–627

    PubMed  CAS  Google Scholar 

  40. 40.

    Tasca M (1959) Clinical observations on the therapeutic effects of a cyanogenetic glycuronoside in cases of human malignant neoplasms. Gazz Med Ital 118(4):153–159 (Apr)

    PubMed  CAS  Google Scholar 

  41. 41.

    Navarro MD (1964) Laetrile therapy in cancer. Acta Unio Contra Cancrum 20:392–394

    CAS  Google Scholar 

  42. 42.

    Navarro MD (1959) Five years experience with laetrile therapy in advanced cancer. Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contra Cancrum 15(Suppl 1):209–221

    PubMed  Google Scholar 

  43. 43.

    Morrone JA (1962) Chemotherapy of inoperable cancer: preliminary report of 10 cases treated with laetrile. Exp Med Surg 20:299–308

    Google Scholar 

  44. 44.

    Helvie CO, Cayce CT (1997) Alternative treatment for lung cancer and irregular heartbeat: two case studies. Alternate Health Pract 3(3):185–194

    Google Scholar 

  45. 45.

    Quackery PP (1992) South Med J 85(2):1264

    Google Scholar 

  46. 46.

    Mehta P (1980) Ineffectiveness of laetrile in the treatment of acute lymphoblastic leukemia. Clin Pediatr (Phila) 19(5):363–364 (May)

    CAS  Article  Google Scholar 

  47. 47.

    Perspective: resolving an ethical dilemma (1980). Nursing 10(5):39–43

  48. 48.

    Peterson RG, Rumack BH (1979) Laetrile and pregnancy. Clin Toxicol 15(2):181–184

    PubMed  CAS  Google Scholar 

  49. 49.

    Campbell DR, Mason WF, Standen JR (1978) Renal arteriography in von Hippel–Lindau disease. J Can Assoc Radiol 29(4):243–246 (Dec)

    PubMed  CAS  Google Scholar 

  50. 50.

    Ames MM, Kovach JS, Flora KP (1978) Initial pharmacologic studies of amygdalin (laetrile) in man. Res Commun Chem Pathol Pharmacol 22(1):175–185 (Oct)

    PubMed  CAS  Google Scholar 

  51. 51.

    Reactions to “laetrilomania” (1977). N Engl J Med 297(4):218–221 (Jul 28)

    Google Scholar 

  52. 52.

    Crippen DW, Veatch RM (1976) Laetrile: cancer cure or quack remedy? Hastings Cent Rep 6(6):18–20 (Dec)

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Leor R, Michaeli J, Brezis M, Stessman J (1986) Laetrile intoxication and hepatic necrosis: a possible association. South J Med 79(2):259–260 (Feb)

    CAS  Google Scholar 

  54. 54.

    Beamer WC, Shealy RM, Prough DS (1983) Acute cyanide poisoning from laetrile ingestion. Ann Emerg Med 12(7):449–451 (Jul)

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Kalyanaraman UP, Kalyanaraman K, Cullinan SA, McLean JM (1983) Neuromyopathy of cyanide intoxication due to “laetrile” (amygdalin). A clinicopathologic study. Cancer 51(11):2126–2133 (Jun 1)

    PubMed  Article  CAS  Google Scholar 

  56. 56.

    Shragg TA, Albertson TE, Fisher CJ Jr (1982) Cyanide poisoning after bitter almond ingestion. West J Med 136(1):65–69 (Jan)

    PubMed  CAS  Google Scholar 

  57. 57.

    Vogel SN, Sultan TR, Ten Eyck RP (1981) Cyanide poisoning. Clin Toxicol 18(3):367–383 (Mar)

    PubMed  CAS  Article  Google Scholar 

  58. 58.

    Liegner KB, Beck EM, Rosenberg A (1981) Laetrile-induced agranulocytosis. JAMA 246(24):2841–2842 (Dec 18)

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Rubino MJ, Davidoff F (1979) Cyanide poisoning from apricot seeds. JAMA 241(4):359 (Jan 26)

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    Horwitz ET (1979) Of love and laetrile: medical decision making in a child’s best interests. Am J Law Med 5(3):271–294

    PubMed  CAS  Google Scholar 

  61. 61.

    Morse DL, Boros L, Findley PA (1979) More on cyanide poisoning from laetrile. N Engl J Med 301(16):892 (Oct 18)

    PubMed  CAS  Google Scholar 

  62. 62.

    Maxwell DM (1978) Increased cyanide values in a laetrile user. Can Med Assoc J 119(1):18 (Jul 8)

    PubMed  CAS  Google Scholar 

  63. 63.

    Ortega JA, Creek JE (1978) Acute cyanide poisoning following administration of laetrile enemas. J Pediatr (6):1059 (Dec)

    Google Scholar 

  64. 64.

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

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Smith FP, Butler TP, Cohan S, Schein PS (1977) Laetrile toxicity: a report of two cases. JAMA 238(13):1361

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Navarro MD (1955) Metastatic pulmonary carcinoma treated with laetrile. Unitas 28:606–618

    Google Scholar 

  67. 67.

    Navarro MD, Lagman CL (1957) Breast carcinoma with lung and bone metastases treated with laetrile; case report. J Philipp Med Assoc 33(1):16–20 (Jan)

    PubMed  CAS  Google Scholar 

  68. 68.

    Bromley J, Hughes BG, Leong DC, Buckley NA (2005) Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Ann Pharmacother 39(9):1566–1569 (Sep)

    PubMed  Article  Google Scholar 

  69. 69.

    Bonati A (1991) How and why should we standardize phytopharmaceutical drugs for clinical validation? J Ethnopharmacol 32(1–3):195–197 (Apr)

    PubMed  Article  CAS  Google Scholar 

  70. 70.

    Calabrese EJ (1979) Conjoint use of laetrile and megadoses of ascorbic acid in cancer treatment: possible side effects. Med Hypotheses 5(9):995–997 (Sep)

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Calabrese EJ (1979) Possible side effects from treatment with laetrile. Med Hypotheses 5(9):1045–1049 (Sept)

    PubMed  Article  CAS  Google Scholar 

  72. 72.

    Hwang EY, Lee JH, Lee YM, Hong SP (2002) Reverse-phase HPLC separation of d-amygdalin and neoamygdalin and optimum conditions for inhibition of racemization of amygdalin. Chem Pharm Bull (Tokyo) 50(10):1373–1375 (Oct)

    Article  CAS  Google Scholar 

  73. 73.

    Hu S, Yuan D, Diao GF, Bi KS, Kano Y (2002) Studies on evaluation of Semen Armeniacae amarum. Zhongguo Zhong Yao Za Zhi 27(10):736–739 (Oct)

    PubMed  CAS  Google Scholar 

  74. 74.

    Krebs ET Jr, Krebs ET Sr, Beard HH (1950) The unitarian or trophoblastic thesis of cancer. Med Rec 163(7):149–174

    Google Scholar 

  75. 75.

    Gal EM, Fung FH, Greenberg DM (1952) Studies on the biological action of malononitriles, II: distribution of rhodanese (transulfurase) in the tissues of normal and tumor-bearing animals and the effect of malononitriles thereon. Cancer Res 12:574–579

    PubMed  CAS  Google Scholar 

  76. 76.

    Conchie J, Findlay J, Levvy GA (1959) Mammalian glycosidases: distribution in the body. Biochem J 71(2):318–325

    PubMed  CAS  Google Scholar 

  77. 77.

    Fishman WH (1955) Beta-glucoronidase. Adv Enzymol Relat Subj Bioch 16:361–409

    Article  CAS  Google Scholar 

  78. 78.

    Krebs ET Jr (1970) The nitrilosides (vitamin B17)—their nature, occurrence and metabolic significance antineoplastic vitamin B17. J Appl Nutr 22:75–86

    Google Scholar 

  79. 79.

    Donaldson MS (2004) Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr J 3(1):19 (Oct 20)

    PubMed  Article  CAS  Google Scholar 

  80. 80.

    Young VR, Newberne PM (1981) Vitamins and cancer prevention: issues and dilemmas. Cancer 47(Suppl 5):1226–1240 (Mar 1)

    PubMed  Article  CAS  Google Scholar 

  81. 81.

    Sakamoto S, Yoshino H, Shirahata Y, Shimodairo K, Okamoto R (1992) Pharmacotherapeutic effects of kuei-chih-fu-ling-wan (keishi-bukuryo-gan) on human uterine myomas. Am J Chin Med 20(3–4):313–317

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The authors thank Katja Schmidt for her valuable support and the European Commission for having funded the CAM-Cancer project within its fifth framework program.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Edzard Ernst.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Milazzo, S., Lejeune, S. & Ernst, E. Laetrile for cancer: a systematic review of the clinical evidence. Support Care Cancer 15, 583–595 (2007). https://doi.org/10.1007/s00520-006-0168-9

Download citation

Keywords

  • Laetrile
  • Amygdalin
  • Cancer
  • Systematic review