On the basis of standard laboratory tests and animal models used to screen anticancer drugs, there is little evidence to support a specific cancer -killing ability for laetrile. These investigations used numerous cultured cell lines and tumor models, and they explored the following issues: (1) whether laetrile, given alone or in combination with other substances, exhibits anticancer activity of any kind; (2) the toxic effects associated with laetrile treatment; (3) the location of laetrile breakdown in the body and how this breakdown occurs; and (4) the route(s) of excretion for laetrile and its breakdown products.

Animal studies of laetrile have used rodents,[1-12] dogs,[13,14] Reviewed in [15] rabbits, Reviewed in [15] and a cat.[13] Early work led to the hypothesis that enzymes were necessary to release cyanide from amygdalin. When high levels of these enzymes were present, symptoms of cyanide poisoning were more pronounced.[1] Reviewed in [15] In two studies sponsored by the National Cancer Institute and published in 1975, various rodent cancers (osteogenic sarcoma, melanoma, carcinosarcoma, lung carcinoma, and leukemia) were transplanted into rats and mice.[2,3] In both studies, the animals were treated with intraperitoneal injections of amygdalin, with or without the enzyme beta-glucosidase. None of the solid tumors or leukemias investigated responded to amygdalin at any dose tested. No statistically significant increase in animal survival was observed in any of the treatment groups. Similar results were obtained in another study using human breast and colon cancer cells implanted into mice (xenograft models).[12] Amygdalin at every dose level tested produced no response either as a single agent or in combination with beta-glucosidase. It was discovered that animals experienced more side effects when beta-glucosidase was given concurrently (at the same time) with amygdalin, compared with amygdalin alone.[2,3]

Additional cell culture and animal studies involving more than a dozen other tumor models have been published.[1,4,5,7,8,10,11,16-20] In one study, preliminary findings by one of the principal investigators that amygdalin inhibited the growth of primary tumors and the incidence of lung metastases in mice bearing spontaneous (not treatment-induced) mammary adenocarcinomas could not be confirmed.[4] However, positive results were obtained in four studies.[11,17,18,20]

In the first of these studies, amygdalin enhanced the antitumor activity of a combination of enzymes and vitamin A in mice bearing spontaneous mammary adenocarcinomas.[11] The amygdalin was given by intramuscular injection, the vitamin A was administered orally through a feeding tube, and the enzymes were injected into and around tumor masses. No anticancer activity was observed when amygdalin was given alone.

In the second study, white blood cells and prostate cancer specimens were used to investigate the potential of amygdalin to stimulate the immune system.[18] The researchers found that amygdalin caused a statistically significant increase in the ability of a patient’s white blood cells to adhere to his own prostate cancer cells, suggesting some immune system boosting potential for amygdalin.

The third study investigated the ability of amygdalin and beta-glucosidase to indirectly sensitize the hypoxic (oxygen-starved) cells at the center of a tumor to the lethal effects of gamma irradiation.[17] Cells at the periphery (outer edge) of a tumor are more sensitive to gamma irradiation because they are not oxygen-deprived. Radiation kills cells, in part, by splitting molecules, including oxygen molecules, to form free radicals, which are highly reactive chemicals that can damage DNA and other important cellular components. It has been proposed that, by inhibiting oxygen uptake by peripheral tumor cells, more oxygen will diffuse to the hypoxic cells, thereby increasing their sensitivity to radiation. In this study, beta-glucosidase was used to break down amygdalin to release cyanide, with the cyanide inhibiting oxygen uptake by peripheral tumor cells. Presumably, cyanide uptake by interior tumor cells is less than that of cells located at a tumor’s periphery. Spheres of tumor cells created in the laboratory and tumor slices were used in the study. The investigators found that amygdalin and beta-glucosidase could act as indirect radiation sensitizers of hypoxic tumor cells. It should be noted, however, that independent confirmation of this positive finding has not been published in a peer-reviewed scientific journal. A major hurdle in the application of this technique to animals and humans is the development of a method for delivering a sufficient amount of cyanide to tumors without causing substantial systemic or regional toxicity.

In the fourth study, cultured human bladder cancer cells were treated with amygdalin alone or a combination of amygdalin and an antibody that was coupled (chemically) to beta-glucosidase.[20] The target for this antibody was the glycoprotein (a protein with sugar molecules attached) MUC1. Aberrant forms of MUC1 are produced and displayed at high levels on the outside of several types of cancer cells, including bladder cancer cells. In this study, amygdalin alone was not very effective in killing the bladder cancer cells, but its cell-killing ability was 36 times greater in the presence of the antibody-enzyme complex. There are two possible explanations for this increase in cell-killing ability. The first is that antibody-enzyme complexes bound via MUC1 produce high rates of amygdalin breakdown at the cell surface. This breakdown leads to high local production of cyanide, which is quickly taken up by the cells and kills them. The second explanation is that antibody-enzyme complexes bound to the cells are internalized, thereby increasing the intracellular concentration of beta-glucosidase. Increased beta-glucosidase activity inside a cell would result in increased breakdown of amygdalin taken up by it, and increased cyanide production and cell death. These two potential mechanisms are not mutually exclusive. In another experiment, the researchers cultured bladder cancer cells in the presence of human brain tumor cells, which do not express MUC1. When this coculture was treated with amygdalin and the antibody-enzyme complex, the bladder cancer cells were killed selectively. In view of the mechanisms proposed above, this result is not surprising, since the bladder cancer cells and the brain tumor cells in this coculture formed homogeneous colonies (colonies that contained exclusively bladder cancer cells or brain tumor cells). Conceivably, selective killing of some types of human cancer cells might be achievable through application of this method; however, these positive results must be confirmed independently, and the effectiveness of this approach in animal models must be demonstrated before its use in humans can be considered.

The toxicity of laetrile appears to be dependent on the route of administration. Oral administration is associated with much greater toxicity than intravenous, intraperitoneal, or intramuscular injection.[1,6,14,21] Reviewed in [9,10,22,23] As noted previously (refer to the History ¹ section of this summary for more information), most mammalian cells contain only trace amounts of the enzyme beta-glucosidase;[24] however, this enzyme is present in gastrointestinal tract bacteria and in many food plants. Reviewed in [6,9,15,25-27] Two studies have specifically examined the role of intestinal bacteria in the breakdown of orally administered amygdalin.[9,28] In one study, rats bred and raised under germ-free conditions and rats bred and raised under normal conditions were given oral amygdalin. The germ-free rats exhibited no side effects from the compound, and their blood concentrations of cyanide were indistinguishable from those of untreated rats. Many of the rats with normal quantities of intestinal bacteria showed signs of cyanide poisoning (e.g., lethargy and convulsions), and they had high levels of cyanide in their blood. In the second study, rats were either treated or not treated with the antibiotic neomycin before being given oral amygdalin.[6] In this study, urinary excretion of detoxified cyanide (i.e., thiocyanate) was measured. The amount of urinary thiocyanate was 40 times higher in rats that had not been given the antibiotic, indicating that more amygdalin had been broken down in animals with normal amounts of intestinal bacteria. In humans, as in rats, substantial breakdown of amygdalin occurs in the intestines; however, little breakdown of either intravenously or intramuscularly delivered amygdalin occurs in humans, with most of the intact compound eventually excreted in urine.[26,29]

References

1. Gostomski FE: The effects of amygdalin on the Krebs-2 carcinoma and adult and fetal DUB(ICR) mice. [Abstract] Diss Abstr Int B 39 (5): 2075-B, 1978. 
   
   
2. 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 59 (5): 939-50, 1975 Sep-Oct.  [PUBMED Abstract]
   
   
3. 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 59 (5): 951-65, 1975 Sep-Oct.  [PUBMED Abstract]
   
   
4. Stock CC, Tarnowski GS, Schmid FA, et al.: Antitumor tests of amygdalin in transplantable animal tumor systems. J Surg Oncol 10 (2): 81-8, 1978.  [PUBMED Abstract]
   
   
5. Menon MM, Bhide SV: Perinatal carcinogenicity of isoniazid (INH) in Swiss mice. J Cancer Res Clin Oncol 105 (3): 258-61, 1983.  [PUBMED Abstract]
   
   
6. Newton GW, Schmidt ES, Lewis JP, et al.: Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. West J Med 134 (2): 97-103, 1981.  [PUBMED Abstract]
   
   
7. Hill GJ 2nd, Shine TE, Hill HZ, et al.: Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia. Cancer Res 36 (6): 2102-7, 1976.  [PUBMED Abstract]
   
   
8. 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 63 (5): 1279-83, 1979.  [PUBMED Abstract]
   
   
9. Carter JH, McLafferty MA, Goldman P: Role of the gastrointestinal microflora in amygdalin (laetrile)-induced cyanide toxicity. Biochem Pharmacol 29 (3): 301-4, 1980.  [PUBMED Abstract]
   
   
10. Khandekar JD, Edelman H: Studies of amygdalin (laetrile) toxicity in rodents. JAMA 242 (2): 169-71, 1979.  [PUBMED Abstract]
    
    
11. Manner HW, DiSanti SJ, Maggio MI, et al.: Amygdalin, vitamin A and enzyme induced regression of murine mammary adenocarcinomas. J Manipulative Physiol Ther 1 (4): 246-8, 1978. 
    
    
12. Ovejera AA, Houchens DP, Barker AD, et al.: Inactivity of DL-amygdalin against human breast and colon tumor xenografts in athymic (nude) mice. Cancer Treat Rep 62 (4): 576-8, 1978.  [PUBMED Abstract]
    
    
13. Lewis JP: Laetrile. West J Med 127 (1): 55-62, 1977.  [PUBMED Abstract]
    
    
14. Schmidt ES, Newton GW, Sanders SM, et al.: Laetrile toxicity studies in dogs. JAMA 239 (10): 943-7, 1978.  [PUBMED Abstract]
    
    
15. Dorr RT, Paxinos J: The current status of laetrile. Ann Intern Med 89 (3): 389-97, 1978.  [PUBMED Abstract]
    
    
16. Levi L, French WN, Bickis IJ, et al.: Laetrile: a study of its physicochemical and biochemical properties. Can Med Assoc J 92: 1057-61, 1965. 
    
    
17. 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 33 (4): 397-401, 1978.  [PUBMED Abstract]
    
    
18. Bhatti RA, Ablin RJ, Guinan PD: Tumour-associated directed immunity in prostatic cancer: effect of amygdalin. IRCS Med Sci Biochem 9 (1): 19, 1981. 
    
    
19. 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 64 (1): 105-9, 1980.  [PUBMED Abstract]
    
    
20. 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 78 (6): 712-9, 1998.  [PUBMED Abstract]
    
    
21. Moertel CG, Ames MM, Kovach JS, et al.: A pharmacologic and toxicological study of amygdalin. JAMA 245 (6): 591-4, 1981.  [PUBMED Abstract]
    
    
22. Newmark J, Brady RO, Grimley PM, et al.: 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): 6513-6, 1981.  [PUBMED Abstract]
    
    
23. Navarro MD: Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contr Cancrum 15(suppl 1): 209-21, 1959. 
    
    
24. Conchie J, Findlay J, Levvy GA: Mammalian glycosidases: distribution in the body. Biochem J 71: 318-25, 1959. 
    
    
25. Herbert V: Laetrile: the cult of cyanide. Promoting poison for profit. Am J Clin Nutr 32 (5): 1121-58, 1979.  [PUBMED Abstract]
    
    
26. Ames MM, Moyer TP, Kovach JS, et al.: Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol 6 (1): 51-7, 1981.  [PUBMED Abstract]
    
    
27. Unproven methods of cancer management. Laetrile. CA Cancer J Clin 22 (4): 245-50, 1972 Jul-Aug.  [PUBMED Abstract]
    
    
28. Shils ME, Hermann MG: Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 58 (3): 323-40, 1982.  [PUBMED Abstract]
    
    
29. Ames MM, Kovach JS, Flora KP: Initial pharmacologic studies of amygdalin (laetrile) in man. Res Commun Chem Pathol Pharmacol 22 (1): 175-85, 1978.  [PUBMED Abstract]
    
    

Glossary Terms

Cancer that begins in cells that line certain internal organs and that have gland-like (secretory) properties.

A substance found in the pits of many fruits such as apricots and papayas, and in other foods. It has been tried in some countries as a treatment for cancer, but it has not been shown to work in clinical studies. Amygdalin is not approved for use in the United States. Also called laetrile.

An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models.

A laboratory experiment using animals to study the development and progression of diseases. Animal studies also test how safe and effective new treatments are before they are tested in people.

A drug used to treat infections caused by bacteria and other microorganisms.

A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

Having to do with stopping abnormal cell growth.

A large group of single-cell microorganisms. Some cause infections and disease in animals and humans. The singular of bacteria is bacterium.

The organ that stores urine.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Cancer that begins in the skin or in tissues that line or cover internal organs.

A malignant tumor that is a mixture of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat).

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

Cells of a single type (human, animal, or plant) that have been adapted to grow continuously in the laboratory and are used in research.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called DNA.

The amount of medicine taken, or radiation given, at one time.

A protein that speeds up chemical reactions in the body.

A highly reactive chemical that often contains oxygen and is produced when molecules are split to give products that have unpaired electrons (a process called oxidation). Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

A type of radiation therapy that uses gamma radiation. Gamma radiation is a type of high-energy radiation that is different from x-rays.

The stomach and intestines. The gastrointestinal tract is part of the digestive system, which also includes the salivary glands, mouth, esophagus, liver, pancreas, gallbladder, and rectum.

Free of bacteria, viruses, and other microorganisms that can cause infection and disease.

A protein that has sugar molecules attached to it.

Having too little oxygen.

The complex group of organs and cells that defends the body against infections and other diseases.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

The long, tube-shaped organ in the abdomen that completes the process of digestion. The intestine has two parts, the small intestine and the large intestine. Also called bowel.

Inside a cell.

Injection into muscle.

Within the peritoneal cavity (the area that contains the abdominal organs). Also called IP.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called IV.

A researcher in a clinical trial or clinical study.

A substance found in the pits of many fruits such as apricots and papayas, and in other foods. It has been tried in some countries as a treatment for cancer, but it has not been shown to work in clinical studies. Laetrile is not approved for use in the United States. Also called amygdalin.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

Having to do with the breast.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

By or having to do with the mouth.

A cancer of the bone that usually affects the large bones of the arm or leg. It occurs most commonly in young people and affects more males than females. Also called osteosarcoma.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

The original tumor.

Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.

In oncology, describes the body area right around a tumor.

In medicine, an improvement related to treatment.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Affecting the entire body.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

A surgical procedure in which tissue or an organ is transferred from one area of a person’s body to another area, or from one person (the donor) to another person (the recipient).

Cells, tissues, or animals used to study the development and progression of cancer, and to test new treatments before they are given to humans. Animals with transplanted human tumors or other tissues are called xenograft models.

Having to do with urine or the organs of the body that produce and get rid of urine.

A nutrient that the body needs in small amounts to function and stay healthy. Vitamin A helps in vision, bone growth, reproduction, growth of epithelium (cells that line the internal and external surfaces of the body), and fighting infections. It is fat-soluble (can dissolve in fats and oils). Vitamin A is found in liver, egg yolks, and whole milk dairy products from animals and in fish oils. It can also be made in the body from a substance found in some fruits and vegetables, such as cantaloupes, carrots, spinach, and sweet potatoes. Vitamin A is being studied in the prevention and treatment of some types of cancer. Also called retinol.

A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.

The transplant of an organ, tissue, or cells to an individual of another species.