Amygdalin (D-mandelonitrile-β-gentiobioside) is a cyanogenic glycoside present in the pits of many fruits and in numerous plants belonging to the Rosaceae family, such as Prunus persica (peach), Prunus armeniaca (apricot) and Prunus amygdalus amara (bitter almond). Cyanogenic glycosides, also known as “nitrilosides,” are a large group of secondary metabolites that are widely distributed in the plant kingdom, including many plants that are commonly consumed by humans. The chemical properties of amygdalin from bitter almond seeds were first described by the German chemists Liebig and Wohler in 1837 after having been isolated 7 years earlier by the French chemists Pierre-Jean Robiquet and A. F. Boutron-Charlard.
Amygdalin was later "rediscovered" in 1920 by California physician Dr. Ernst Theodore Krebs, Sr. His son, Dr. Ernst Krebs, Jr. through further research, developed the compound into the injectable chemical known as “Laetrile or B17.” Both amygdalin, and its patented form Laetrile, have been promoted and sold as "vitamin B-17", although neither compound is technically considered a “vitamin.” Laetrile is structurally different from its mother compound, amygdalin, and is an acronym (LAEvo-rotatory mandeloniTRILE beta-diglucoside) for a purified, semi-synthetic form of amygdalin. The "LAEvo" part references a purified form of amygdalin that turns polarized light in a left-turning direction. Dr. Krebs Jr. discovered that only this left-turning form of Laetrile was effective against cancer.1 "Laetrile" (with a capital "L") usually refers to the Krebses' original product, whose purification process was patented by them; "laetrile" (with a lower case "l") refers to the commercial form of amygdalin which is most likely a mixture of the left and right-turning forms, which the Krebses believed to be much less effective as a therapy for cancer. Natural amygdalin with the right turning configuration can be racemized to the unnatural form, neoamygdaline, during inexperienced extraction, bad packing or storage.
It is alleged that the clinical research performed by the NCI (mentioned later in this article) did not use the laevo form of Laetrile used by Dr. Krebs, and consequently their results reported “Laetrile” to be ineffective for cancer. The subject of Laetrile is very complex and will be only briefly discussed in this paper. Furthermore, the politics of Laetrile have created a strong bias against amygdalin, hampering further human research of this beneficial compound.
Cyanogenic glycosides, such as amygdalin and prunasin, are found in over 1000 species of plants and consequently are present in the tissues of animals that eat those plants. Amygdalin and prunasin are common among plants of the family Rosaceae, particularly the genus Prunus, Poaceae (grasses), Fabaceae (legumes), and in other food plants, including flaxseed and manioc. Amygdalin is particularly found in:
Seeds of fruits or kernels: apricot, cherry, apple, peach, nectarine, plum, pear, prune
Nuts: macadamia, bitter almond, walnuts
Beans: Burma, broad (Vicia faba), lentils (sprouted), mung (sprouted), Lima, scarlet runner, Rangoon
Berries: Nearly all wild berries - blackberry, elderberry, raspberry, cranberry, strawberry, chokeberry, Christmas berry
Grasses: wheat grass, acacia, alfalfa (sprouted), milkweed, Sudan, white Dover
Seeds: flax, chia, sesame
Many plants that contain high amounts of amygdalin have been an important part of the traditional diet and food medicine of several cultures for millennia. For example, bitter almonds and apricot kernels, have been used in traditional Chinese medicine (TCM) for centuries. In TCM, apricot kernels are considered to benefit the large intestine and lungs, and are used to stop cough and wheezing, moistens the intestines, and unblock the bowels.2, 3 Apricot seed-oil has been used traditionally as a laxative. Additionally, in TCM bitter almonds have historically been employed to remove “blood stasis,” and to treat abscesses and tumors.4 Amygdalin from bitter almonds and apricot kernels was used to treat cancer more than a century ago in Russia and later in North America. Amygdalin was one of the most popular, non-conventional, anti-cancer treatments in the U.S. by 1970s. By 1978, an estimated 70,000 U.S. cancer patients had used amygdalin and its purified, semi-synthetic form Laetrile and to treat their cancer.5 However, Laetrile and amygdalin are not approved by the U.S. Food and Drug Administration as a treatment for cancer.
Most people take amygdalin in the form of apricot kernels. However, like an apricot, in the middle of a peach is a hard shell. If you break open the hard shell with a “nut cracker,” pliers or hammer, you will find a small seed/kernel in the middle that looks like an almond. This peach kernel, is much softer than an almond, does not taste like an almond, and is also rich in amygdalin. Generally, the bitterness of an apricot, almond or peach kernel is indicative of its amygdalin content. The more bitter, the more amygdalin it contains. Both sweet and bitter almond varieties contain quantities of amygdalin. However, there can be a significant range of amygdalin content of the apricot kernels being sold as “bitter” varieties. It is best to find a reputable source and always use the same source to assure consistency of amygdalin content.
As with so many other useful chemicals that we get from plants, the evolutionary utility of cyanogenic glycosides like amygdalin and prunasin is for defense of the plant. The cyanogenic glycosides contained in plants deters grazers, from eating the valuable seeds and dispensable fruit in the plants. Along with playing a role in deterring herbivores, in some plants they control germination, bud formation, carbon and nitrogen transport, and possibly act as antioxidants. The production of cyanogenic glycosides is an evolutionarily conserved function, appearing in species as old as ferns and as recent as angiosperms.
Verified cases of death from eating apricot kernels is extremely rare. I could find only three publications describing lethal consequences, all in children (these reports, however, are widely cited in anti-Laetrile publications). Sayre and Kaymakcalavu (1964) report that between 1957 and 1962, two children died of cyanide poisoning in a hospital in Central Turkey after eating apricot kernels. No information was provided on how many kernels were consumed. Lasch and Shawa (1981) report two more deaths of children in Gaza. One had been part of a group that had been “feasting on apricot kernels,” according to their parents, and another, again along with other children, had consumed a sweet prepared from apricot kernels. Once again, there was no information on how much was consumed. It was also reported, again from Turkey, that in 2011 a 28-month-old girl died from allegedly eating 10 apricot kernels. These anecdotal cases leave us with little idea of how many apricot kernels create a lethal dose. It is, however, remarkable that only these Turkey and Gaza cases are reported as fatalities in professional literature.
Plants containing cyanogenic glycosides have been consumed for millennia. The mystery remains that tens of thousands of people worldwide have purchased and presumably consumed apricot kernels over the last several decades. Particularly, in the 1970's when apricot kernels were in vogue, and even today as they are widely advertised on the internet. If apricot kernels are deadly toxic, why do reports of apricot kernel toxicity appear so rarely in the professional literature (check the dates of the reports), especially when the anti-Laetrile establishment is so eager to cite the few that do exist? Bear in mind that cytotoxic chemotherapy, such as alkylating agents, antimetabolite drugs, and anthracyclines, are well established as extremely toxic and potentially fatal, but are patented and sanctioned by the cancer industry as acceptably-toxic anticancerous compounds. The reality appears that the core issue is financial and more about patentably drugs than potential toxicity.
However, it is important to remember that too much of anything can be harmful. Eating more seeds or kernels than required may produce side effects, such as nausea, vomiting, headache, and feeling of malaise. For this reason, when consuming amygdalin-rich foods make sure it is in biologically reasonable amounts and monitored by a health care professional. Again, there is no guarantee of strength, purity or safety of Laetrile or amygdalin products, and effects may vary. You should always read product labels. If you have a medical condition, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Amygdalin chemistry is complicated but here is what is known so far. The glycone portion of the molecule consists of two sugars, gentiobiose and 2-D-glucose, attached glycosidically to the genin or aglycone, D-mandelonitrile. This can be further broken down to benzaldehyde and hydrocyanic acid. The beta-glycosidic linkage can be hydrolized specifically by emulsin (found in almonds) and 5-glucosidase. The small intestine normally contains beta-glucosidases, which are in part responsible for absorption and metabolism of dietary flavonoid glycosides in humans. The amygdalin compound contains several asymmetric carbons and therefore has optical activity in both the glycone and aglycone moieties. Hydrolysis of amygdalin by amgydalase, present in emulsin, yields the secondary glycoside prunasin and glucose. Prunasin can be further reduced by prunase to yield hydrocyanic acid, glucose, and benzaldehyde.6
Laetrile is produced by an extraction of ground apricot kernels. Most Laetrile produced in Mexico is obtained from the fruit kernels imported from California. The extraction process involves defatting the ground kernels, using ether or alcohol as solvents. It is estimated that 33 kernels are needed for each 500-mg tablet and 200 kernels for 3 g of the injectable form.
Several anticancer hypothesis mechanisms of amygdalin have been proposed. The first involves beta-glucosidase (β-glucosidase) activity. β-Glucosidases are enzymes that play essential roles in the removal of nonreducing terminal glucosyl residues from saccharides and glycosides. It is well established that β-glucosidase expression and activity is significantly upregulated in different types of solid tumors. Hence, cancerous cells express more beta-glucosidase than normal cells. Because amygdalin contains two glucose molecules, it is readily metabolized by cancer cells, yielding benzaldehyde and hydrocyanic acid. β-glucosidase is considered the unlocking enzyme for amygdalin molecules. It releases both the benzaldehyde and hydrocyanic acid, creating a toxic synergy that causes apoptosis, or cell death in cancer cells. In other words, a cancer cell`s β-glucosidase enzymes cause them to self-destruct by opening themselves to the hydrocyanic acid and benzaldehyde. This is a principal mechanism of how amygdalin targets cancer cells. Hence, when orally ingested, both Laetrile and amygdalin are metabolized by hydrolysis via the alkaline duodenal and intestinal juice enzymes forming D-glucuronic acid and L-mandelonitrile. L-mandelonitrile is further hydrolyzed to hydrogen cyanide and benzaldehyde. Cyanide detoxification is a function of the liver, and rhodanese is a key enzyme involved in sulfur metabolism in that detoxification. Hence, rhodanese in normal cells neutralizes free cyanide molecules and renders them harmless by combining them with sulfur. Binding the cyanide to sulfuric rhodanese creates thiocyanate, which is a neutral, nontoxic substance. Thiocyanate easily passes through the urine with no harm to the body. These two factors combine to affect a selective cyanide apoptosis of cancer cells, while normal cells remain undamaged.7 However, because of the small intestine’s increased beta-glucosidase activity, excess amygdalin has potential for intestinal toxicity. This theory has been criticized by certain “researchers” that contend both neoplastic and normal cells contain only traces of β-glucosidases and equal amounts of rhodanese. More research is needed to clarify β-glucosidase activity of cell types and its relationship to cyanogenic glycosides.
Another hypothesis has suggested that orally consumed amygdalin is metabolized to a mandelonitrile, which is then wholly transported to hepatic tissues to be transformed to a beta-glucuronide compound. This compound is in turn being conveyed to neoplastic cells to be further catabolized by β-glucuronidases to further liberate mandelonitrile and then hydrogen cyanide.
A third hypothesis suggested that a cancerous condition may be in part due to an amygdalin (also called vitamin B-17) deficiency. That B-17 is an essential compound from plants necessary for normal physiological function. This theory contends that steady dietary administration of B-17 as derived from certain fruit pits prevents the incidence of cancer. Hence, Ernst T. Krebs indicated that amygdalin and Laetrile is like an essential vitamin and should be categorized as a nutritional supplement rather than a drug.
Another proposed anticancerous mechanism involves glutathione metabolism. Aside from the direct apoptosis in cancer cells, the release of cyanide and benzaldehyde into tumors depletes their glutathione (GSH). GSH plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis. Disturbances in GSH levels are involved in the cause and progression of many human diseases, including cancer. However, elevated GSH levels are observed in various types of tumors, and this can make some tumors more resistant to cytotoxic chemotherapy.8, 9 Moreover, GSH content in some tumor cells is typically associated with higher levels of GSH-related enzymes, such as γ-glutamylcysteine ligase (GCL) and γ-glutamyl-transpeptidase (GGT) activities, as well as a higher expression of GSH-transporting export pumps.10 Therefore, it is not surprising that the GSH system has attracted pharmacological attention as a possible target for medical intervention against cancer progression and chemo-resistance. Tumor cell GSH depletion through cyanide and benzaldehyde release has an anticancerous effect. More research is needed to better clarify and delineate all the potential anticancerous mechanisms of amygdalin.
Amygdalin – Laetrile Controversy and Politics – Forbidden Fruits
If the cancer fighting potential of amygdalin and its purified, semi-synthetic form Laetrile was truly ineffective, there would be no controversy. Amygdalin is a tremendously valuable chemical discovery, but pharmaceutical companies, unlike other plant agents, have not been able to harness its anticancer powers into a patentable, profitable drug. Pacific yew tree (Taxus brevifolia) toxic taxine-alkaloids were patented to create the chemotherapy agents taxol and paxataxol. The Madagascan periwinkle’s (Catharanthus roseus) toxic vinca-alkaloids have been patented to create the chemotherapy agents vinblastine and vincristine. The May apple’s (Podophyllum peltatum) toxin podophyllotoxin has been patented to create the chemotherapy drugs, etoposide and teniposide. Trastuzumab emtansine (Kadcyla) is an antibody conjugated to a synthetic toxic derivative of the Ethiopian plant Maytenus ovatus. It is used to treat leukemia, breast and lung cancers.
All are very profitable, patented cytotoxic agents.
Its proponents consider amygdalin a natural cancer remedy for both prevention and treatment of cancer, while opponents warn that amygdalin and Laetrile is ineffective and toxic. This whole issue of amygdalin has been clouded by the forty-year-long Laetrile controversy. To fully appreciate the how Laetrile was blacklisted by the FDA, it is first necessary to understand the research trial that originally condemned it. Basically, the overall Laetrile controversy is not one of science, it is political, and involves big business. Only a few other areas of medicine, like stem cell research, has opinions been polarized as much as the pros and cons of Laetrile.
Because of cancer successes gained by doctors using amygdalin extracts, such as Laetrile, research on Laetrile began at Sloan-Kettering Institute. Between 1972 and 1973, the esteemed veteran cancer researcher Dr. Kanematsu Sugiura performed experiments to determine the effects of injectable extracts of amygdalin upon mice with mammary tumors. Dr. Sugiura reported that the mice treated with amygdalin had a 20 percent rate of metastases, while about 80 percent of the untreated controls developed metastases. Dr. Sugiura repeated studies several times with the same results of reduction of metastasis. Dr. Sugiura revealed his findings to his superiors at Sloan-Kettering Institute, but his studies were never published. After much debate, he was later fired. A book was written about Dr. Sugiura’s research on amygdalin at Sloan-Kettering entitled The Anatomy of A Cover-up.11 This book contains the statistical results of Dr. Sugiura's research work using different intraperitoneal injections of amygdalin on cancerous mice. These results do, indeed, show the benefit of amygdalin. Dr. Sugiura stated in this book, "The results clearly show that amygdalin significantly inhibits the appearance of lung metastases in mice bearing spontaneous mammary tumors and increases significantly the inhibition of the growth of the primary tumor over the appearance of inhibition in the untreated animals."
Dr. Kanematsu Sugiura, Laetrile Researcher - from a documentary about a cover-up involving what seemed to be a promising new cancer treatment in the 1970s.
In 1981, the NCI sponsored phase I and II clinical trials of “laetrile,” which were carried out at the Mayo Clinic. The phase I study gathered information about dosage and toxicity in preparation for the phase II study. In Phase II, one hundred seventy-eight patients with advanced cancers were treated with “laetrile.” The trial did not include a randomized control group and was not designed to determine if laetrile caused moderate increases in lifespan, improvements in well-being or pain control. The researchers concluded:
One hundred seventy-eight patients with cancer were treated with amygdalin (Laetrile) plus a 'metabolic therapy' program consisting of diet, enzymes, and vitamins. No substantive benefit was observed in terms of cure, improvement, or stabilization of cancer, improvement of symptoms related to cancer, or extension of life span... Amygdalin (laetrile) is a toxic drug that is not effective as a cancer treatment.12
This NCI trial and its conclusion was widely publicized and considered to be definitive and the final word about Laetrile. Over the next few years, several doctors and scientists challenged the validity of this trial. In a letter to the editor of the New England Journal of Medicine, journalist Michael L. Culbert, D.Sc., founding member of the Laetrile Advocacy Group Committee for Freedom of Choice in Cancer Therapy, Inc., asserted that the trial did not use pure amygdalin.13 He revealed that the “laetrile” used in the clinical trial was a degraded or decomposed form or a “RS-epimer racemic mixture.” The RS epimer racemic mixture is a mixture of natural amygdalin (R-amygdalin) and an isomer,14 an artificial form of amygdalin (referred to as the S-isomer, or isoamygdalin). Dr. Krebs Jr. strongly argued against this artificial form and maintained that this mixture is less than 50% as effective as the pure form. Krebs writes that the RS epimer racemic mixture “caused unpredictable, often severe, reactions in our patients” and that “all of our successful therapeutic studies were conducted using only pure natural amygdalin.15 It is important to be aware that the amygdalin molecule which naturally occurs in hundreds of edible seeds and plants, is considerably unstable during and after extraction from its natural source. Slight variations in the extracting procedure can cause the amygdalin molecules to change to a form unknown to nature. These are known as isomers. Such a conformation is called neo-amygdalin. A mixture of natural amygdalin molecules and neo-amygdalin molecules is called “iso-amygdalin.”
In his book Freedom from Cancer: the Amazing Story of Vitamin B-17, or Laetrile, Dr. Culbert wrote that “The (NCI) laetrile clinical trial wound up being, in essence, a U.S. government sponsored test of an uncertain laetrile product, whose application was in the hands of doctors and scientists known to be or assumed to be hostile to laetrile, whose patients were anonymous, and the test results of which, being coded, could not be individually released or cross-checked. Worse, the patients accepted for entry into the program were variously described as "terminal" or beyond hope of cure by conventional means."16
After the NCI trial was published, Time Magazine ran an article with titled “Laetrile flunks,” with the subtitle “Test shows cancer quackery.”17 The FDA subsequently placed sanctions against the sale of Laetrile stating that there was no evidence for its safety or effectiveness. Additionally, FDA regulation made amygdalin manufacture and extraction illegal. The U.S. government also banned the transport of Laetrile into the U.S. or across state lines, as well as the use of Laetrile in states without laws specifically allowing it. Since 2000, there have been several instances of prosecution because of Laetrile transport across state lines. Even Dr. Ernst Krebs, Jr. and his secretary served 6 months in the San Francisco County Jail in 1983 for their continued promotion of Laetrile. Today, it is still almost taboo to talk about Laetrile. According to the FDA the ban on Laetrile was due to risk of side effects. Interesting, that there does not exist the same controversy over the dangerous cytotoxic anthracyclines known to cause cardiac failure and fatalities every year. To understand politics is to understand finances.
Amygdalin and Laetrile Research
Fortunately, controversy has not stopped research and truth cannot be hidden indefinitely. Many subsequent foreign studies have confirmed Dr. Sugiura’s work, supporting his conclusion that Laetrile shows potential in reducing the metastatic potential of cancer, although it is not a cure. There have been numerous in vitro amygdalin studies over the last decade showing positive anticancer effects on many different cancer cell lines - human colon cancer cells,18 prostate cancer cells,19 liver cancer cells,20 cervical cancer cells,21 bladder cancer cells,22 and non-small cell lung cancer cells.23 A 2016, an in vitro study showed that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The researchers concluded that the results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially triple-negative breast cancer.24 From this in vitro research, it is only a matter of time before a well-managed, clinical trial will emerge. Despite contemporary positive research findings, you will find no retraction (or apology) by Sloan Kettering, and sadly, most of cancer information sites still claim that Laetrile is useless as a cancer treatment and dangerously toxic.
Here is a chronological listing of the more recent studies with web links that substantiate Dr. Sugiura’s work: