Cyanogenic Compounds

Natural Sources

"In plants, cyanides are generally found in bound forms as cyanogenic glycosides and play an important role in plant defense against herbivory." "Overall, cyanogenic glycosides have been reported to occur in more than 3000 plant species (ca. from 130 families) and thus these species have a potential to produce HCN toxicity if ingested by animals and humans." ^{[Ashraf PAP]}

"The separation of cyanogenic glycosides and the degrading enzymes in the plant tissues prevents the formation of significant amounts of cyanide until the physical disruption of the plant compartments." ^{[Barceloux MTNS]}

"During the 1980s, U.S. interest in botanicals resurfaced under the guise of ‘‘complementary and alternative medicine’’ (CAM). By this time, botanicals had lost considerable credibility. Proponents of ‘‘Laetrile’’- a concoction of cyanogenic glycosides extracted from peach pits—drew media attention when the FDA began seizing the product as an ‘‘unapproved’’ drug and as ‘‘ineffective cancer treatment’’ (13). However, by 1991, in response to growing consumer interest, the U.S. Congress appropriated funds to the National Institutes of Health for the establishment of a federal research program for the scientific evaluation of CAM." ^{[LAM HSDI]}

"Laetrile (amygdalin) was a very popular cancer remedy in the 1980s despite clinical evidence of a lack of effect. Unfortunately, after pure amygdalin was banned, patients tried ingesting large amounts of apricot kernels, which led to several deaths because apricot kernels also contain an enzyme that hydrolyzes amygdalin and releases cyanide. Subsequent research showed that amygdalin alone can lead to cyanide poisoning." ^{[Mills HMPL]}

"In populations where cassava is a staple crop, care is taken to soak, grate, and ferment the cassava, allowing the release of HCN before consumption. Lima beans can be a problem if cooked at low temperature, which is insufficient to destroy toxic glycosides. As few as 12 bitter almonds can potentially kill a small child." ^{[Omaye FNT]}

"The genus Ximenia belongs to the Olacaceae and comprises about 8 species (Brasileiro et al., 2008): .... X. americana Linn. is the most common, being native to Australia and Asia where is commonly known as Yellow Plum or Sea Lemon. It is found mainly in tropical regions (Africa, India, New Zealand, Central America and south America), specially Africa and Brazil. In Asia, the young leaves are consumed as a vegetable, however, the leaves also contain cyanide and need to be thoroughly cooked, and should not be eaten in large amounts." ^{[Rao Phyt]}

Cassava

• "Cassava... is a staple in Africa and tropical areas in the Pacific Basin. Cassava contains cyanogenic glycosides, which are a source of cyanide. In cassava intended for animal food, the cyanide is removed by warming the chopped cassava in the sun. When cassava is intended for human consumption, the cyanide is removed by boiling it in water. If not adequately removed, the cyanide is released from the goitrogen either in the plant or in the body. In the body; it is converted to thiocyanate. Thiocyanate induces goiter by inhibiting uptake of iodine by the thyroid. Thiocyanate also inhibits the activity of thyroperoxidase." ^{[NB Brody]}


• Growol (Fermented Cassava Tubers)
  • Fermentation: "Owing to the content of cyanogenic glucosides, cassava tubers must be processed prior to consumption to lower the content of cyanide. During fermentation, the cyanide content of the roots is reduced by 90–100% and the texture changes from hard and brittle to soft and mushy, making it easier to extract the cassava starch. Using sieves locally fabricated, usually from bamboo, the coarse fibres are removed and discarded. The starch is then squeezed in the sieve to separate and remove the inner cortical cellulosic materials and the starch is washed 4–5 times and drained, or the material is put in a bag and squeezed to remove the liquid. After draining, the cassava pulp, composed mainly of starch, is steamed for 1 h. The product has a distinctive flavour due to the fermentation that occurs during soaking. The natural fermentation takes at least about 5 days to reach the required acidity (0.85% as lactic acid) at ambient temperatures of about 30^oC." ^{[Owens IFFSA]}
  • "As with all cassava products, the cyanide content of the roots is an important safety concern but there are no reports of cyanide levels in growol. It is well established that the detoxification of cassava is a consequence of the hydrolysis of the cyanogenic glycosides, liminarin and lotaustralin, to the corresponding cyanohydrins by endogenous linamarase, released by physical or enzymic tissue maceration, followed by spontaneous hydrolysis of the cyanohydrins and evaporation of the released HCN (Vasconcelos et al. 1990). Growol is traditionally made from sweet varieties of cassava that contain only low levels of cyanogenic glycosides and there is, therefore, little risk of cyanide poisoning. Certainly, there are no recently documented cases of acute poisoning due to growol consumption." ^{[Owens IFFSA]}
• Gari (West African food made from cassava tubers)
• "The bound cyanide is probably the major risk in the finished gari because the free cyanide is easily lost in the process of dehydration, boiling, or soaking in water. The processing method is therefore the determinant factor. For example, Pieris and Jansz (59) found that quick drying of cassava flour at a relatively high temperature prevents further enzyme reactions that could have broken up the bound cyanide. Thus, following moisturizing of the cassava flour, the enzyme system becomes reactivated. Unfortunately, they noted, that such flour was generally used for cooking purposes. They found this dangerous because of the possibility of the release of HCN in the stomach when consumed, leading to poisoning and nervous breakdown. For these reasons, grating, fermenting, and drying processes must be included in cassava for gari manufacture so as to reduce the poisonous cassava roots from about 350 mg HCN/kg in some varieties into a safer gari product having 20–30 ppm cyanide (10)." ^{[Steinkraus IIFF]}
• Other Notes
• "The roots are peeled and ground or pounded to release the glycosides and enzymes. The wet pulp is left to sit for twelve to twenty-four hours, during which time a portion of the volatile hydrogen cyanide gas escapes. Thorough cooking expels the remaining poisonous gas." [Brussell, 1997]

Bamboo

"Bamboo shoots are the newly emerged, edible shoots of several species of bamboo, in genera of the subfamily Bambusoideae, including Phyllostachys, Bambusa, and Dendrocalamus.... After removing the leaf sheaths, the stems are boiled for about half an hour to remove any bitterness (cyanogenic glycosides) but to retain their crisp texture. They are a particularly common food item in China, Japan, Korea, and Southeast Asia, and in many other countries..." ^{[Prance CHP]}

Forms

Degredation

"The leaves of various plants are also fermented to produce food products in parts of Africa. Ntoba mbodi is produced in Congo and central Africa from cassava (Manihot esculenta Crantz) leaves. This food is relatively rich in protein, despite a slight reduction in free nitrogen during fermentation, most likely due to liberation of hydrogen cyanide." ^{[Sarkar HIFIAF]}

"During the fermentation process, amines are produced by Bacillus spp., especially B. pumilus, which have the capacity to utilize cyanhydric acid for nutrition (Knowles, 1976). This invariably reduces the cyanide content of the fermenting cassava leaves during the fermentation. The decrease in the nitrogen content from 5.1% to 4.5% obtained during the fermentation was suggested to be due to the solubilization and volatilization of hydrogen cyanide (Kobawila et al., 2005)...". ^{[Sarkar HIFIAF]}

"The detoxification of cassava through fermentation includes an acid fermentation, during which the cyanogenic glycosides are hydrolyzed to liberate the toxic cyanide gas (Onabolu et al. 2002a,b). For example, cassava roots contain two cyanogenic glucosides, linamarin and lotaustralin (Ray and Ward 2006). When the roots are naturally fermented by a mixed population of yeasts (Saccharomyces cereviseae and Candida spp.) and LAB (Lactobacillus, Leuconostoc and Pediococcus), the cyanogen level is reduced drastically (Kostinek et al. 2005)." [Ray MFTF]

"...some classes of inorganic compounds such as cyanides and azides are toxic to many microbes [22]; however, these compounds may be degraded following a period of microbial adaption [112]. In this respect, certain studies have indeed shown the fungal biodégradation of cyanide and microbial adaption to such toxic compounds." ^{[Mohee BS]}

Examples

• "Gurbuz et al. [113] have examined cyanide effluent degradation by Scenedesmus obliquus. Gold mill effluents containing cyanide concentration of 77.9 mg/L was fed to batch unit to examine the ability of S. obliquus for degrading cyanide. Cyanide was reduced down to 6 mg/L in 77 h. Gurbuz et al. [113] reported that the cells had well adapted to high pH and the effluent contained cyanide and the metals." ^{[Mohee BS]}

Cyanide Exposure, Toxicity and Treatment

Toxicity

• Hydrocyanic acid — oral, human LD₅₀ 570 μg/kg ^{[Ling GMP]}
• "Hydrogen cyanide is known to cause gastrointestinal inflammation and inhibition of cellular respiration." ^{[Rao Phyt]}

"The clinical features associated with the ingestion of cyanogenic glycosides mimics cyanide poisoning, and the severity of the intoxication correlates to the dose of active cyanogenic compounds. The onset of vomiting, abdominal pain, weakness, dyspnea, diaphoresis, and lightheadedness followed by convulsions, stupor, disorientation, hypotension, metabolic acidosis, coma, respiratory failure, and cardiovascular collapse develops after exposure to high doses of cyanogenic glycoside - containing foods.... Symptoms typically start within one half hour after consumption and progress quickly. A case series associated the ingestion of wild apricot seed ingestions by Turkish children with the sudden onset of vomiting and crying followed by fainting, lethargy, and coma." ^{[Barceloux MTNS]}

An interaction of amygdalin with vitamin C has been suggested: "Vitamin C increases the in vitro conversion of amygdalin to cyanide and reduces body stores of cysteine, which detoxifies cyanide; the authors suggested that this was a plausible explanation for this adverse event." ^[SEHM]

Effect on Animals:

• "Summarizing, goats that suckle from mothers exposed to cyanogenic plants can be affected as thiocyanate and probably cyanide can be transferred from the maternal bloodstream to the offspring through milk. It is feasible to suppose that in this way kids can be indirectly intoxicated by cyanogenic plants." ^{[Acamovie PPRT]}

Treatment

"Local communities usually only have very small quantities of cyanide antidotes on hand due to their expense, short expiration dating, and rarity of use. However, some cities are stockpiling kits. The exhaled breath of cyanide exposure victims may smell like bitter almonds. Not everyone (only 40–60% of people) can detect this odor" ^{[Koehler PC]}

"Treatment of poisoning from exposure to cyanogenic plants is similar to the treatment of cyanide poisoning. Decontamination measures are not usually necessary because of the limited absorptive capacity of activated charcoal to cyanide. Mild to moderate ingestions usually require only supportive care. Indications for the use of an antidote... include alteration in mental status, severe acidosis, continuous seizures, and refractory hypotension. The administration of the cyanide antidote kit to children requires the appropriate adjustments for weight and hemoglobin content to avoid methemoglobinemia. Clinical features that suggest an appropriate response to nitrites and thiosulfate or hydroxocobalamin include the following: normalization of vital signs (blood pressure, pulse), normal mentation, cessation of seizure activity, spontaneous respirations, and resolution of metabolic acidosis.... The presence of persistent metabolic acidosis may require a continuous infusion of sodium thiosulfate (2 g/h) for 24 hours.... Survival has occurred in patients with cyanide poisoning including laetrile - induced, severe cyanide intoxication (coma, metabolic acidosis, profound hypotension requiring aggressive support with vasopressors) following only supportive care..." ^{[Barceloux MTNS]}

Some Treatment Options Include;

• "Cyanokit (hydroxocobalamin for injection) for the treatment of known or suspected cyanide poisoning. Dey, LP, Napa, CA, 2006." ^{[Koehler PC]}
• "Cyanide Antidote Kit (sodium nitrite injection, sodium thiosulfate injection, amyl nitrite inhalants) for the treatment of cyanide poisoning, Taylor Pharmaceuticals, Decatur, IL, 2006." ^{[Koehler PC]}
  • Synonyms "Amyl Nitrite,Sodium Thiosulfate, and Sodium Nitrite; Cyanide Antidote Kit; Sodium Thiosulfate, Sodium Nitrite, and Amyl Nitrite" ^[PTH]
  • Dosage "For cyanide poisoning, a 0.3 mL ampul of amyl nitrite is crushed every minute and vapor inhaled for 15-30 seconds until an I.V. sodium nitrite infusion is available. Following administration of 300 mg I.V. sodium nitrite, inject 12.5 g sodium thiosulfate I.V. (over10 minutes), if needed; injection of both may be repeated at 1/2 the original dose."^[PTH]
  • Administration "Sodium nitrite should be administered at a rate of 2.5-5 mL/minute." ^[PTH]
  • Contraindications "Hypersensitivity to amyl nitrite, sodium nitrite, nitrates, sodium thiosulfate, or any component of the formulation; severe anemia, pregnancy (amyl nitrite)" ^[PTH]
  • Warnings "When cyanide poisoning is related to smoke inhalation, if possible, the patient should be in a hyperbaric chamber before the kit is administered; the methemoglobin initially produced by sodium nitrite injection may otherwise exacerbate concomitant carbon monoxide poisoning that has already severely diminished oxygen-carrying capacity in red cells" ^[PTH]
  • Drug Interactions "Sodium nitrite antagonizes acetylcholine, epinephrine, and histamine effects; sodium nitrite potentiates hypotensive effects and/ or anticholinergic effects of tricyclic antidepressants, antihistamines, and meperidine and related CNS depressants; ethanol increases the toxicity of amyl nitrite" ^[PTH]
  • Amyl Nitrate: "Coronary vasodilator in angina pectoris; an adjunct in treatment of cyanide poisoning; also used to produce changes in the intensity of heart murmurs...Onset of action: Angina: Within 30 seconds Duration: 3-15 minutes...Dosage 1-6 inhalations from one capsule are usually sufficient to produce the desired effect...Contraindications Hypersensitivity to nitrates; severe anemia; head injury; angle-closure glaucoma; postural hypotension; head trauma or cerebral hemorrhage; pregnancy...Drug Interactions Ethanol taken with amyl nitrite may have additive side effects. Sildenafil: Avoid concurrent use of sildenafil; severe reactions may result." ^[PTH]
    

Journals of Interest

• Lussier, S.M., J.H. Gentile, and J. Walker. 1985. Acute and chronic effects of heavy metals and cyanide on Mysidopsis bahia (Crustacea: Mysidacea). Aquat. Toxicol. 7:25-35.
  
• Onabolu, A., Cassava processing, consumption and dietary cyanide exposure, Ph.D. Thesis, Karolinska Insitute, Stockholm, Sweden, 2001, pp. 7–19.

References

• Brussell, 1997 - Potions, Poisons, and Panaceas: An ethnobotanical Study of Montserrat, David E. Brussell, Southern Illinois University Press, 1997