Subscribe to RSS
DOI: 10.1055/s-0035-1547584
Amygdalin: Nutzen oder Risiko?
Publication History
Publication Date:
21 December 2015 (online)
![](https://www.thieme-connect.de/media/dzo/201504/lookinside/thumbnails/bla_10-1055-s-0035-1547584-1.jpg)
Zusammenfassung
Die Komplementär- und Alternativmedizin (CAM) ist oftmals in die Behandlung von Tumorerkrankungen eingebunden. Tatsächlich ist ihre Popularität in den letzten Jahrzehnten stetig angestiegen. 80 % der amerikanischen und 50 % der europäischen Tumorpatienten wenden CAM begleitend oder anstelle der konventionellen Therapie an. Dennoch ist das Wissen über die Wirkeffektivität von CAM dürftig. Die Diskrepanz zwischen Anwendung und tatsächlichem Benefit wird insbesondere beim cyanogenen Diglucosid Amygdalin deutlich, das in den Kernen der Spezies Rosaceae angereichert vorliegt. In den 1970er-Jahren repräsentierte Amygdalin eines der populärsten nicht-konventionellen Antitumor-Verfahren. Alleine im Jahr 1978 konsumierten 70.000 amerikanische Krebspatienten diese Substanz. Ob Amygdalin aber überhaupt als antitumorales Agens angesprochen werden kann, ist unklar. Befürworter betrachten Amygdalin als natürliches Heilmittel, Gegner hingegen verneinen diese Eigenschaft und warnen vor toxischen Nebeneffekten. Der Übersichtsartikel fasst das Wissen um diese Substanz zusammen.
Summary
Battling cancer, for many, includes the use of complementary and alternative medicine (CAM). CAM popularity has steadily increased over the past decades and up to 80 % of American and more than 50 % of European cancer patients use CAM together with, or in place of, conventional therapy. However, information about the therapeutic efficacy of CAM is meager. The discrepancy between use and factual benefit is particularly apparent with respect to the cyanogenic diglucoside amygdalin, present in the fruit kernels of the Rosaceae species. Amygdalin was one of the most popular, non-conventional, anti-cancer treatments in the 1970s and by 1978 70,000 US cancer patients had used amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Proponents consider amygdalin a natural cancer cure, whereas opponents warn that amygdalin is ineffective and even toxic. The review article summarizes current knowledge of this compound.
-
Literatur
- 1 Akıl M, Kaya A, Ustyol L, Aktar F, Akbayram S. Acute cyanide intoxication due to apricot seed ingestion. J Emerg Med 2013; 44: e285-e286
- 2 Allfrey VG, Boffa LC, Vidali G. Selective inhibition with sodium cyanate of protein synthesis in colon cancer cells. Cancer 1977; 40: 2692-2698
- 3 American Cancer Society Unproven methods of cancer management: Contreras methods. CA Cancer J Clin 1971; 21: 317-321
- 4 Ames MM, Moyer TP, Kovach JS, Moertel CG, Rubin J. Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol 1981; 6: 51-57
- 5 Arafa HM. Possible contribution of beta-glucosidase and caspases in the cytotoxicity of glufosfamide in colon cancer cells. Eur J Pharmacol 2009; 616: 58-63
- 6 Ardenne M, Reitnauer PG. Tumour hyperacidulation through intravenous glucose infusion enhanced by amygdalin and beta-glucosidase application. Arch Geschwulstforsch 1975; 45: 135-145
- 7 Barnett RC, Pointer J, Nimtz J, Beers R. Subacute laetrile intoxication. West J Med 1981; 134: 170-172
- 8 Barwina M, Wiergowski M, Sein Anand J. Accidental poisoning with peach seeds used as anticancer therapy--report of two cases. Przegl Lek 2013; 70: 687-689
- 9 Basu TK. High-dose ascorbic acid decreases detoxification of cyanide derived from amygdalin (laetrile): studies in guinea pigs. Can J Physiol Pharmacol 1983; 61: 1426-1430
- 10 Beamer WC, Shealy RM, Prough DS. Acute cyanide poisoning from laetrile ingestion. Ann Emerg Med 1983; 12: 449-451
- 11 Biaglow JE, Durand RE. 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 1978; 33: 397-401
- 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; 39: 1566-1569
- 13 Calabrese EJ. Conjoint use of laetrile and megadoses of ascorbic acid in cancer treatment: possible side effects. Med Hypotheses 1979; 5: 995-997
- 14 Chang HK, Shin MS, Yang HY, Lee JW, Kim YS, Lee MH, Kim J, Kim KH, Kim CJ. Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. Biol Pharm Bull 2006; 29: 1597-1602
- 15 Chaouali N, Gana I, Dorra A, Khelifi F, Nouioui A, Masri W, Belwaer I, Ghorbel H, Hedhili A. Potential Toxic Levels of Cyanide in Almonds (Prunus amygdalus), Apricot Kernels (Prunus armeniaca), and Almond Syrup. ISRN Toxicol 2013; 2013: 610648
- 16 Chen Y, Ma J, Wang F, Hu J, Cui A, Wei C, Yang Q, Li F. Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells. Immunopharmacol Immunotoxicol 2013; 35: 43-51
- 17 Chitnis MP, Adwankar MK, Amonkar AJ. Studies on high-dose chemotherapy of amygdalin in murine P388 lymphocytic leukaemia and P815 mast cell leukaemia. J Cancer Res Clin Oncol 1985; 109: 208-209
- 18 Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment Statement on cyanogenic glycosides in bitter apricot kernels. http://cot.food.gov.uk/sites/default/files/cot/cotstatementapricot200615.pdf Zugriff 17. 06. 2015
- 19 Curran WJ. Law-medicine notes. Laetrile for the terminally ill: Supreme Court stops the nonsense. N Engl J Med 1980; 302: 619-621
- 20 Curt GA. Unsound methods of cancer treatment. Princ Pract Oncol Updates 1990; 4: 1-10
- 21 Davignon JP, Trissel LA, Kleinman LM. Pharmaceutical assessment of amygdalin (Laetrile) products. Cancer Treat Rep 1978; 62: 99-104
- 22 Dorr RT, Paxinos J. The current status of laetrile. Ann Intern Med 1978; 89: 389-397
- 23 Ellison NM, Byar DP, Newell GR. Special report on Laetrile: the NCI Laetrile Review. Results of the National Cancer Institute’s retrospective Laetrile analysis. N Engl J Med 1978; 299: 549-552
- 24 Frakes RA, Sharma RP, Willhite CC. Comparative metabolism of linamarin and amygdalin in hamsters. Food Chem Toxicol 1986; 24: 417-420
- 25 Freese A, Brady RO, Gal AE. A beta-glucosidase in feline kidney that hydrolyzes amygdalin (laetrile). Arch Biochem Biophys 1980; 201: 363-368
- 26 Fukuda T, Ito H, Mukainaka T, Tokuda H, Nishino H, Yoshida T. Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biol Pharm Bull 2003; 26: 271-273
- 27 Guo J, Wu W, Sheng M, Yang S, Tan J. Amygdalin inhibits renal fibrosis in chronic kidney disease. Mol Med Rep 2013; 7: 1453-1457
- 28 Hall AH, Linden CH, Kulig KW, Rumack BH. Cyanide poisoning from laetrile ingestion: role of nitrite therapy. Pediatrics 1986; 78: 269-272
- 29 Hall AH, Rumack BH. Clinical toxicology of cyanide. Ann Emerg Med 1986; 15: 1067-1074
- 30 Hill GJ, 2nd. Shine TE, Hill HZ, Miller C. Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia. Cancer Res 1976; 36: 2102-2107
- 31 Hill HZ, Backer R, Hill GJ 2nd. Blood cyanide levels in mice after administration of amygdalin. Biopharm Drug Dispos 1980; 1: 211-220
- 32 http://www.bfarm.de/DE/Home/home_node.html Zugriff 07.02.2015
- 33 http://www.cancer.gov/cancertopics/pdq/cam/laetrile/HealthProfessional/page1/AllPages/Print Zugriff 09.05.2015
- 34 http://www.cancer.gov/cancertopics/pdq/cam/laetrile/patient/page2 Zugriff 09.05.2015
- 35 http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/laetrile Zugriff 09.05.2015
- 36 Humbert JR, Tress JH, Braico KT. Fatal cyanide poisoning: accidental ingestion of amygdalin. JAMA 1977; 238: 482
- 37 Koeffler HP, Lowe L, Golde DW. Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow. Cancer Treat Rep 1980; 64: 105-109
- 38 Kwon HY, Hong SP, Hahn DH, Kim JH. Apoptosis induction of Persicae Semen extract in human promyelocytic leukemia (HL-60) cells. Arch Pharm Res 2003; 26: 157-161
- 39 Laetrile. N Engl J Med 1982; 307: 118-120 http://www.nejm.org/doi/full/10.1056/NEJM198207083070213
- 40 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 1975; 59: 951-965
- 41 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 1979; 63: 1279-1283
- 42 Li XB, Liu CH, Zhang R, Huang XT, Li YY, Han L, Xu ML, Mi SQ, Wang NS. Determination and pharmacokinetics of amygdalin in rats by LC-MS-MS. J Chromatogr Sci 2014; 52: 476-481
- 43 Makarević J, Rutz J, Juengel E, Kaulfuss S, Reiter M, Tsaur I, Bartsch G, Haferkamp A, Blaheta RA. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2. PLoS One 2014; 9: e105590-
- 44 Makarević J, Rutz J, Juengel E, Kaulfuss S, Tsaur I, Nelson K, Pfitzenmaier J, Haferkamp A, Blaheta RA. Amygdalin influences bladder cancer cell adhesion and invasion in vitro. PLoS One 2014; 9: e110244-
- 45 Maxwell DM. Increased cyanide values in a laetrile user. Can Med Assoc J 1978; 119: 18
- 46 Milazzo S, Lejeune S, Ernst E. Laetrile for cancer: a systematic review of the clinical evidence. Support Care Cancer 2007; 15: 583-595
- 47 Miller KW, Anderson JL, Stoewsand GS. Amygdalin metabolism and effect on reproduction of rats fed apricot kernels. J Toxicol Environ Health 1981; 7: 457-467
- 48 Moertel CG, Ames MM, Kovach JS, Moyer TP, Rubin JR, Tinker JH. A pharmacologic and toxicological study of amygdalin. JAMA 1981; 245: 591-594
- 49 Moertel CG, Fleming TR, Rubin J, Kvols LK, Sarna G, Koch R, Currie VE, Young CW, Jones SE, Davignon JP. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N Engl J Med 1982; 306: 201-206
- 50 Morrone JA. Chemotherapy of inoperable cancer. Preliminary report of 10 cases treated with laetrile. Exp Med Surg 1962; 20: 299-308
- 51 Moss M, Khalil N, Gray J. Deliberate self-poisoning with Laetrile. Can Med Assoc J 1981; 125: 1126-1128
- 52 Moss RW. The Laetrile Controversy. In: Moss RW. The Cancer Industry: The Classic Expose on the Cancer Establishment. Brooklyn, NY: First Equinox Press; 1996: 131-52
- 53 Moss RW. Patient perspectives: Tijuana cancer clinics in the post-NAFTA era. Integr Cancer Ther 2005; 4: 65-86
- 54 Nagahara N, Ito T, Minami M. Mercaptopyruvate sulfurtransferase as a defense against cyanide toxication: molecular properties and mode of detoxification. Histol Histopathol 1999; 14: 1277-1286
- 55 Nahin RL. Use of the best case series to evaluate complementary and alternative therapies for cancer: a systematic review. Semin Oncol 2002; 29: 552-562
- 56 Navarro MD. Five years’ experience with Laetrile therapy in advanced cancer. Acta Unio Int Contra Cancrum 1959; 15: 209-221
- 57 Navarro MD. Laetrile therapy in cancer. Acta Unio Int Contra Cancrum 1964; 20: 392-394
- 58 Newmark J, Brady RO, Grimley PM, Gal AE, Waller SG, Thistlethwaite JR. Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc Natl Acad Sci USA 1981; 78: 6513-6516
- 59 Newton GW, Schmidt ES, Lewis JP, Conn E, Lawrence R. Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. West J Med 1981; 134: 97-103
- 60 Oliveri V, Viale M, Caron G, Aiello C, Gangemi R, Vecchio G. Glycosylated copper(II) ionophores as prodrugs for β-glucosidase activation in targeted cancer therapy. Dalton Trans 2013; 42: 2023-2034
- 61 Ortega JA, Creek JE. Acute cyanide poisoning following administration of Laetrile enemas. J Pediatr 1978; 93: 1059
- 62 Ovejera AA, Houchens DP, Barker AD, Venditti JM. Inactivity of DL-amygdalin against human breast and colon tumor xenografts in athymic (nude) mice. Cancer Treat Rep 1978; 62: 576-578
- 63 Park HJ, Yoon SH, Han LS, Zheng LT, Jung KH, Uhm YK, Lee JH, Jeong JS, Joo WS, Yim SV, Chung JH, Hong SP. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World J Gastroenterol 2005; 11: 5156-5161
- 64 Rauws AG, Olling M, Timmerman A. The pharmacokinetics of prunasin, a metabolite of amygdalin. J Toxicol Clin Toxicol 1982; 19: 851-856
- 65 Relman AS. Closing the books on Laetrile. N Engl J Med 1982; 306: 236
- 66 Riecke VA. Amygdalin. In: Riecke VA. Die neuern Arzneimittel, ihre physischen und chemischen Eigenschaften. 2. Aufl. Stuttgart: Hoffman’sche Verlags-Buchhaltung; 1840: 34-37
- 67 Rossi B, Guidetti E, Deckers C. A Clinical Trial of Chemotherapeutic Treatment of Advanced Cancers with L- Mandelonitrile β- Diglucoside (abstract). 9th International Cancer Congress, Tokyo, Japan, 1966
- 68 Sadoff L, Fuchs K, Hollander J. Rapid death associated with laetrile ingestion. JAMA 1978; 239: 1532
- 69 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; 165: 185-188
- 70 Shim SM, Kwon H. Metabolites of amygdalin under simulated human digestive fluids. Int J Food Sci Nutr 2010; 61: 770-779
- 71 Shragg TA, Albertson TE, Fisher CJ Jr.. Cyanide poisoning after bitter almond ingestion. West J Med 1982; 136: 65-69
- 72 Singh P, Rao P, Bhattacharya R. Dose and time-dependent effects of cyanide on thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine λ-lyase activities. J Biochem Mol Toxicol 2013; 27: 499-507
- 73 Speijers G. Cyanogenic glycosides. National Institute of Public Health and Environmental Protection. http://www.inchem.org/documents/jecfa/jecmono/v30je18.htm Zugriff 20.07.2015
- 74 Stock CC, Tarnowski GS, Schmid FA, Hutchison DJ, Teller MN. Antitumor tests of amygdalin in transplantable animal tumor systems. J Surg Oncol 1978; 10: 81-88
- 75 Stock CC, Martin DS, Sugiura K, Fugmann RA, Mountain IM, Stockert E, Schmid FA, Tarnowski GS. Antitumor tests of amygdalin in spontaneous animal tumor systems. J Surg Oncol 1978; 10: 89-123
- 76 Strugala GJ, Rauws AG, Elbers R. Intestinal first pass metabolism of amygdalin in the rat in vitro. Biochem Pharmacol 1986; 35: 2123-2128
- 77 Strugala GJ, Stahl R, Elsenhans B, Rauws AG, Forth W. Small-intestinal transfer mechanism of prunasin, the primary metabolite of the cyanogenic glycoside amygdalin. Hum Exp Toxicol 1995; 14: 895-901
- 78 Suchard JR, Wallace KL, Gerkin RD. Acute cyanide toxicity caused by apricot kernel ingestion. Ann Emerg Med 1998; 32: 742-744
- 79 Syrigos KN, Rowlinson-Busza G, Epenetos AA. In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. Int J Cancer 1998; 78: 712-719
- 80 Wagner B, Galey WR. Kinetic analysis of hexose transport to determine the mechanism of amygdalin and prunasin absorption in the intestine. J Appl Toxicol 2003; 23: 371-375
- 81 Weber P. Influence of amygdalin treatment on clinical progress and tumor relevant serum enzymes in 29 cancer patients. Doctoral thesis. Medical faculty of the Georg August-University Göttingen, Germany, 1975
- 82 Widtmann HJ, Denk J. Zur Kenntnis des Amygdalins. Pharmaceutisches Central-Blatt. 1833. 2. 758-759
- 83 Wisniak J, Robiquet P-J. Emergent topics on chemistry education. Educ quím 2013; 24: 139-149
- 84 32. 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 1975; 59: 939-950
- 85 Zagrobelny M, Bak S, Rasmussen AV, Jørgensen B, Naumann CM, Lindberg Møller B. Cyanogenic glucosides and plant-insect interactions. Phytochemistry 2004; 65: 293-306