Neurotoxic and neuromotor effects of cyanate, an oxidative byproduct of cyanide from linamarin in cassava: A systematic review
Article Sidebar
Submitted
July 10, 2024
Published
March 13, 2025
Keywords:
-
Cyanate, Neurotoxicity, Linamarin, Paralysis, Konzo, Cassava
Abstract
Background Linamarin-induced neurotoxicity manifests as either polyneuropathy, ataxia, and sensorineural deafness or as isolated symmetric spastic paraparesis of bilateral limbs, which are frequently observed in populations subsisting on a monotonous cassava-based diet. Attributable to the potential protein deficiency resulting from this dietary regimen, cyanide derived from linamarin may undergo oxidation to cyanate, a neurotoxin known to carbamoylate proteins and induce oxidative stress.
Aim: To synthesize preclinical and clinical evidence concerning cyanate-induced neurotoxicity, thereby identifying the predominant neurological adverse events following sodium cyanate exposure.
Methods: This study employed a systematic review methodology, utilizing four electronic databases (PubMed, Scopus, Cochrane Library, Google Scholar) to identify for publications on the neurotoxicity of cyanate from 1936 to 2024. A total of 1,089 articles were screened. Studies investigating non-neurotoxic effects and those lacking full-text availability were excluded, resulting in the selection of 10 for quality assessment and review. Preclinical studies were evaluated using the SYRCLE risk-of-bias tool, while non-randomized clinical studies were assessed using the Newcastle-Ottawa scale.
Results: The majority of studies were preclinical. One case-control study investigated the association between spastic paraparesis and protein carbamoylation. Rodents exposed to high-dose sodium cyanate (NaOCN) developed hindlimb spastic weakness or paralysis in 42.86% of animal studies, and ataxia, dysmetria, and cognitive impairment in 14.26%. Peptide carbamoylation was reported in 42.86%, while one study (14.26%) reported demyelination of the spinal cord. The sole case-control study reported a statistically significant (p = 0.01) association between severe konzo and carbamoylation of serum peptides.
Conclusion: Sodium cyanate administration at doses ranging from 60 to 200 mg/kg resulted in hindlimb weakness or spastic paralysis in rodents and spinal cord demyelination in primates, findings strikingly identical to the spastic paraparesis observed in konzo. Further investigations are required to determine the association between cyanate exposure and the development of spastic paraparesis resulting from monotonous cassava consumption.
Keywords: Cyanate, Neurotoxicity, Linamarin, Paralysis, Konzo, Cassava.
Full text article
Generated from XML file
References
Adamolekun B. (2010). Thiamine deficiency and the etiology of tropical ataxic neuropathy. International health, 2(1), 17–21. https://doi.org/10.1016/j.inhe.2009.12.004
Alter, B.P., Kan, Y.W., & Nathan, D.G. (1974). Alter, B. P., Kan, Y. W., & Nathan, D. G. (1974). Toxic effects of high-dose cyanate administration in rodents. Blood, 43(1), 69–77. https://doi.org/10.1182/blood.v43.1.69.69
Baguma, M., Nzabara, F., Maheshe Balemba, G., Malembaka, E. B., Migabo, C., Mudumbi, G., Bito, V., Cliff, J., Rigo, J. M., & Chabwine, J. N. (2021). Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review. Neurotoxicology, 85, 54–67. https://doi.org/10.1016/j.neuro.2021.05.001
Boivin, M. J., Okitundu, D., Makila-Mabe, B., Sombo, M. T., Mumba, D., Sikorskii, A., Mayambu, B., & Tshala-Katumbay, D. (2017). Cognitive and motor performance in Congolese children with konzo during 4 years of follow-up: a longitudinal analysis. The Lancet. Global health, 5(9), e936–e947. https://doi.org/10.1016/S2214-109X(17)30267-X
Cai, H., & Li, G. (2020). Efficacy of alginate-and chitosan-based scaffolds on the healing of diabetic skin wounds in animal experimental models and cell studies: A systematic review. Wound Repair and Regeneration: The International Journal of Tissue Repair and Regeneration, 28(6), 751–771. https://doi.org/10.1111/wrr.12857
Charache, S., Duffy, T. P., Jander, N., Scott, J. C., Bedine, M., & Morrell, R. (1975). Toxic-therapeutic ratio of sodium cyanate. Archives of Internal Medicine, 135(8), 1043–1047.
Chen, C., Kashala-Abotnes, E., Banea Mayambu, J. P., Mumba Ngoyi, D., Tshala-Katumbay, D., Mukeba, D., Kunyu, M., Boivin, M. J., & Wu, F. (2021). Cost-effectiveness of a wetting method intervention to reduce cassava cyanide-related cognitive impairment in children. Nature Food, 2(7), 469–472. https://doi.org/10.1038/s43016-021-00321-w
Chijioke, U., Madu, T., Okoye, B., Ogunka, A. P., Ejechi, M., Ofoeze, M., Ogbete, C., Njoku, D., Ewuziem, J., Kalu, C., Onyemauwa, N., Ukeje, B., Achonwa, O., Forsythe, L., Fliedel, G., & Egesi, C. (2021). Quality attributes of fufu in South-East Nigeria: guide for cassava breeders. International Journal of Food Science & Technology, 56(3), 1247–1257. https://doi.org/10.1111/ijfs.14875
Choi, H.-J. & Lee, S.-H. (2017). Cyanate Induces Apoptosis of Rat Glioma Cell Line. Journal of Life Science, 27(3), 267–274. http://dx.doi.org/10.5352/JLS.2017.27.3.267
Delporte, C., Zouaoui Boudjeltia, K., Furtmüller, P. G., Maki, R. A., Dieu, M., Noyon, C., Soudi, M., Dufour, D., Coremans, C., Nuyens, V., Reye, F., Rousseau, A., Raes, M., Moguilevsky, N., Vanhaeverbeek, M., Ducobu, J., Nève, J., Robaye, B., Vanhamme, L., Reynolds, W. F., … Van Antwerpen, P. (2018). Myeloperoxidase-catalyzed oxidation of cyanide to cyanate: A potential carbamylation route involved in the formation of atherosclerotic plaques? The Journal of Biological Chemistry, 293(17), 6374–6386. https://doi.org/10.1074/jbc.M117.801076
Harkness, D.R. (1976). Cyanate and sickle-cell anemia. Trends in Biochemical Sciences, 1(2), 73-76. https://doi.org/10.1016/0968-0004(76)90001-3
Haut, M. J., Toskes, P. P., Hildenbrandt, P. K., Glader, B. E., & Conrad, M. E. (1975). In vivo hepatic and intestinal toxicity of sodium cyanate in rats: cyanate-induced alterations in hepatic glycogen metabolism. The Journal of Laboratory and Clinical Medicine, 85(1), 140–154.
Hooijmans, C. R., Rovers, M. M., de Vries, R. B., Leenaars, M., Ritskes-Hoitinga, M., & Langendam, M. W. (2014). SYRCLE's risk of bias tool for animal studies. BMC Medical Research Methodology, 14, 43. https://doi.org/10.1186/1471-2288-14-43
Howlett, W.P. (1994). Konzo: A New Human Disease Entity. Acta Horticulturae, 375, 323-330. https://doi.org/10.17660/ActaHortic.1994.375.32
Hu, L., Tian, K., Zhang, T., Fan, C. H., Zhou, P., Zeng, D., Zhao, S., Li, L. S., Smith, H. S., Li, J., & Ran, J. H. (2019). Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1. Molecules (Basel, Switzerland), 24(18), 3231. https://doi.org/10.3390/molecules24183231
Huang, C. W., Huang, C. C., Huang, M. H., Wu, S. N., & Hsieh, Y. J. (2005). Sodium cyanate-induced opening of calcium-activated potassium currents in hippocampal neuron-derived H19-7 cells. Neuroscience letters, 377(2), 110–114. https://doi.org/10.1016/j.neulet.2004.11.081
Kambale, K. J., Ali, E. R., Sadiki, N. H., Kayembe, K. P., Mvumbi, L. G., Yandju, D. L., Boivin, M. J., Boss, G. R., Stadler, D. D., Lambert, W. E., Lasarev, M. R., Okitundu, L. A., Mumba Ngoyi, D., Banea, J. P., & Tshala-Katumbay, D. D. (2017). Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning. Neurotoxicology, 59, 256–262. https://doi.org/10.1016/j.neuro.2016.05.016
Kassa, R. M., Kasensa, N. L., Monterroso, V. H., Kayton, R. J., Klimek, J. E., David, L. L., Lunganza, K. R., Kayembe, K. T., Bentivoglio, M., Juliano, S. L., & Tshala-Katumbay, D. D. (2011). On the biomarkers and mechanisms of konzo, a distinct upper motor neuron disease associated with food (cassava) cyanogenic exposure. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 49(3), 571–578. https://doi.org/10.1016/j.fct.2010.05.080
Kimani, S., Moterroso, V., Lasarev, M., Kipruto, S., Bukachi, F., Maitai, C., David, L., & Tshala-Katumbay, D. (2013). Carbamoylation correlates of cyanate neuropathy and cyanide poisoning: relevance to the biomarkers of cassava cyanogenesis and motor system toxicity. SpringerPlus, 2, 647. https://doi.org/10.1186/2193-1801-2-647
Kimani, S., Sinei, K., Bukachi, F., Tshala-Katumbay, D., & Maitai, C. (2014a). Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents. Metabolic brain disease, 29(1), 105–112. https://doi.org/10.1007/s11011-013-9459-2
Kimani, S., Moterroso, V., Morales, P., Wagner, J., Kipruto, S., Bukachi, F., Maitai, C., & Tshala-Katumbay, D. (2014b). Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet. Food and Chemical Toxicology: An International Journal published for the British Industrial Biological Research Association, 66, 203–209. https://doi.org/10.1016/j.fct.2014.01.047
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Medicine, 6(7), e1000100. https://doi.org/10.1371/journal.pmed.1000100
Manning, J. M., & Acharya, A. S. (1984). The mechanism of action of two anti-sickling agents: sodium cyanate and glyceraldehyde. The American Journal of Pediatric Hematology/oncology, 6(1), 51–54. https://doi.org/10.1097/00043426-198423000-00024
Monekosso, G. L., Annan, W. G., & Ashby, P. H. (1964). Therapeutic effect of vitamin b complex on an ataxic syndrome in western Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 58(5), 432–436. https://doi.org/10.1016/0035-9203(64)90091-4
National Research Council (US) Panel on the Applications of Biotechnology to Traditional Fermented Foods. (1992). Applications of Biotechnology to Fermented Foods: Report of an Ad Hoc Panel of the Board on Science and Technology for International Development. National Academies Press (US).
Oluwole, O. S., Onabolu, A. O., Link, H., & Rosling, H. (2000). Persistence of tropical ataxic neuropathy in a Nigerian community. Journal of Neurology, Neurosurgery, and Psychiatry, 69(1), 96–101. https://doi.org/10.1136/jnnp.69.1.96
Osuntokun B. O. (1981). Cassava diet, chronic cyanide intoxication and neuropathy in the Nigerian Africans. World Review of Nutrition and Dietetics, 36, 141–173. https://doi.org/10.1159/000393156
Otubogun, F. M., Akinyemi, R. O., & Ogunniyi, A. O. (2019). Tropical ataxic neuropathy: Findings of a neuroepidemiological survey of Odeda, southwest Nigeria. Journal of the Neurological Sciences, 405, 116434. https://doi.org/10.1016/j.jns.2019.116434
Paul, L., Mudogo, C.N., Mtei, K.M., Machunda, R.L. & Ntie-Kang, F. (2020). A computer-based approach for developing linamarase inhibitory agents. Physical Sciences Reviews, 5(7), 1-13. https://doi.org/10.1515/psr-2019-0098
Precoppe, M., Komlaga, G. A., Chapuis, A., & Müller, J. (2020). Comparative Study between Current Practices on Cassava Drying by Small-Size Enterprises in Africa. Applied Sciences, 10(21), 7863. https://doi.org/10.3390/app10217863
Rwatambuga, F. A., Ali, E. R., Bramble, M. S., Gosschalk, J. E., Kim, M., Yandju, D. L., Okitundu, L. A., Boivin, M. J., Banea, J. P., Westaway, S. K., Larry, D., Vilain, E., Mumba Ngoyi, D., & Tshala-Katumbay, D. D. (2021). Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 148, 111917. https://doi.org/10.1016/j.fct.2020.111917
Siritunga, D., & Sayre, R. T. (2003). Generation of cyanogen-free transgenic cassava. Planta, 217(3), 367–373. https://doi.org/10.1007/s00425-003-1005-8
Tellez, I., Johnson, D., Nagel, R. L., & Cerami, A. (1979). Neurotoxicity of sodium cyanate. New pathological and ultrastructural observations in Maccaca nemestrina. Acta Neuropathologica, 47(1), 75–79. https://doi.org/10.1007/BF00698277
Tian, S., Li, Y., Zeng, H., Guan, W., Wang, Y., & Zhao, X. (2016). Cyanide oxidation by singlet oxygen generated via reaction between H2O2 from cathodic reduction and OCl(-) from anodic oxidation. Journal of colloid and interface science, 482, 205–211. https://doi.org/10.1016/j.jcis.2016.07.024
Tor-Agbidye, J., Palmer, V. S., Spencer, P. S., Craig, A. M., Blythe, L. L., & Sabri, M. I. (1999a). Sodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa. Brain Research, 820(1-2), 12–19. https://doi.org/10.1016/s0006-8993(98)01343-2
Tor-Agbidye, J., Palmer, V. S., Lasarev, M. R., Craig, A. M., Blythe, L. L., Sabri, M. I., & Spencer, P. S. (1999b). Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava. Toxicological sciences: an official journal of the Society of Toxicology, 50(2), 228–235. https://doi.org/10.1093/toxsci/50.2.228
Tylleskär, T., Banea, M., Bikangi, N., Cooke, R. D., Poulter, N. H., & Rosling, H. (1992). Cassava cyanogens and konzo, an upper motoneuron disease found in Africa. Lancet (London, England), 339(8787), 208–211. https://doi.org/10.1016/0140-6736(92)90006-o
Tylleskär, T., Légué, F. D., Peterson, S., Kpizingui, E., & Stecker, P. (1994). Konzo in the Central African Republic. Neurology, 44(5), 959–961. https://doi.org/10.1212/wnl.44.5.959
Wang, Z., Nicholls, S. J., Rodriguez, E. R., Kummu, O., Hörkkö, S., Barnard, J., Reynolds, W. F., Topol, E. J., DiDonato, J. A., & Hazen, S. L. (2007). Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nature medicine, 13(10), 1176–1184. https://doi.org/10.1038/nm1637
Wells, G.A., Shea, B., O’Connell, D., Peterson, J., Welch, V., Losos, M., & Tugwell, P. (2024). The Newcastle-Ottawa Scale (NOS) for assessing the quality of non randomised studies in meta-analyses. L’Hôpital d’Ottawa Institut de recherche. Retrieved from https://www.ohri.ca/programs/clinical_epidemiology/nosgen.pdf
Alter, B.P., Kan, Y.W., & Nathan, D.G. (1974). Alter, B. P., Kan, Y. W., & Nathan, D. G. (1974). Toxic effects of high-dose cyanate administration in rodents. Blood, 43(1), 69–77. https://doi.org/10.1182/blood.v43.1.69.69
Baguma, M., Nzabara, F., Maheshe Balemba, G., Malembaka, E. B., Migabo, C., Mudumbi, G., Bito, V., Cliff, J., Rigo, J. M., & Chabwine, J. N. (2021). Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review. Neurotoxicology, 85, 54–67. https://doi.org/10.1016/j.neuro.2021.05.001
Boivin, M. J., Okitundu, D., Makila-Mabe, B., Sombo, M. T., Mumba, D., Sikorskii, A., Mayambu, B., & Tshala-Katumbay, D. (2017). Cognitive and motor performance in Congolese children with konzo during 4 years of follow-up: a longitudinal analysis. The Lancet. Global health, 5(9), e936–e947. https://doi.org/10.1016/S2214-109X(17)30267-X
Cai, H., & Li, G. (2020). Efficacy of alginate-and chitosan-based scaffolds on the healing of diabetic skin wounds in animal experimental models and cell studies: A systematic review. Wound Repair and Regeneration: The International Journal of Tissue Repair and Regeneration, 28(6), 751–771. https://doi.org/10.1111/wrr.12857
Charache, S., Duffy, T. P., Jander, N., Scott, J. C., Bedine, M., & Morrell, R. (1975). Toxic-therapeutic ratio of sodium cyanate. Archives of Internal Medicine, 135(8), 1043–1047.
Chen, C., Kashala-Abotnes, E., Banea Mayambu, J. P., Mumba Ngoyi, D., Tshala-Katumbay, D., Mukeba, D., Kunyu, M., Boivin, M. J., & Wu, F. (2021). Cost-effectiveness of a wetting method intervention to reduce cassava cyanide-related cognitive impairment in children. Nature Food, 2(7), 469–472. https://doi.org/10.1038/s43016-021-00321-w
Chijioke, U., Madu, T., Okoye, B., Ogunka, A. P., Ejechi, M., Ofoeze, M., Ogbete, C., Njoku, D., Ewuziem, J., Kalu, C., Onyemauwa, N., Ukeje, B., Achonwa, O., Forsythe, L., Fliedel, G., & Egesi, C. (2021). Quality attributes of fufu in South-East Nigeria: guide for cassava breeders. International Journal of Food Science & Technology, 56(3), 1247–1257. https://doi.org/10.1111/ijfs.14875
Choi, H.-J. & Lee, S.-H. (2017). Cyanate Induces Apoptosis of Rat Glioma Cell Line. Journal of Life Science, 27(3), 267–274. http://dx.doi.org/10.5352/JLS.2017.27.3.267
Delporte, C., Zouaoui Boudjeltia, K., Furtmüller, P. G., Maki, R. A., Dieu, M., Noyon, C., Soudi, M., Dufour, D., Coremans, C., Nuyens, V., Reye, F., Rousseau, A., Raes, M., Moguilevsky, N., Vanhaeverbeek, M., Ducobu, J., Nève, J., Robaye, B., Vanhamme, L., Reynolds, W. F., … Van Antwerpen, P. (2018). Myeloperoxidase-catalyzed oxidation of cyanide to cyanate: A potential carbamylation route involved in the formation of atherosclerotic plaques? The Journal of Biological Chemistry, 293(17), 6374–6386. https://doi.org/10.1074/jbc.M117.801076
Harkness, D.R. (1976). Cyanate and sickle-cell anemia. Trends in Biochemical Sciences, 1(2), 73-76. https://doi.org/10.1016/0968-0004(76)90001-3
Haut, M. J., Toskes, P. P., Hildenbrandt, P. K., Glader, B. E., & Conrad, M. E. (1975). In vivo hepatic and intestinal toxicity of sodium cyanate in rats: cyanate-induced alterations in hepatic glycogen metabolism. The Journal of Laboratory and Clinical Medicine, 85(1), 140–154.
Hooijmans, C. R., Rovers, M. M., de Vries, R. B., Leenaars, M., Ritskes-Hoitinga, M., & Langendam, M. W. (2014). SYRCLE's risk of bias tool for animal studies. BMC Medical Research Methodology, 14, 43. https://doi.org/10.1186/1471-2288-14-43
Howlett, W.P. (1994). Konzo: A New Human Disease Entity. Acta Horticulturae, 375, 323-330. https://doi.org/10.17660/ActaHortic.1994.375.32
Hu, L., Tian, K., Zhang, T., Fan, C. H., Zhou, P., Zeng, D., Zhao, S., Li, L. S., Smith, H. S., Li, J., & Ran, J. H. (2019). Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1. Molecules (Basel, Switzerland), 24(18), 3231. https://doi.org/10.3390/molecules24183231
Huang, C. W., Huang, C. C., Huang, M. H., Wu, S. N., & Hsieh, Y. J. (2005). Sodium cyanate-induced opening of calcium-activated potassium currents in hippocampal neuron-derived H19-7 cells. Neuroscience letters, 377(2), 110–114. https://doi.org/10.1016/j.neulet.2004.11.081
Kambale, K. J., Ali, E. R., Sadiki, N. H., Kayembe, K. P., Mvumbi, L. G., Yandju, D. L., Boivin, M. J., Boss, G. R., Stadler, D. D., Lambert, W. E., Lasarev, M. R., Okitundu, L. A., Mumba Ngoyi, D., Banea, J. P., & Tshala-Katumbay, D. D. (2017). Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning. Neurotoxicology, 59, 256–262. https://doi.org/10.1016/j.neuro.2016.05.016
Kassa, R. M., Kasensa, N. L., Monterroso, V. H., Kayton, R. J., Klimek, J. E., David, L. L., Lunganza, K. R., Kayembe, K. T., Bentivoglio, M., Juliano, S. L., & Tshala-Katumbay, D. D. (2011). On the biomarkers and mechanisms of konzo, a distinct upper motor neuron disease associated with food (cassava) cyanogenic exposure. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 49(3), 571–578. https://doi.org/10.1016/j.fct.2010.05.080
Kimani, S., Moterroso, V., Lasarev, M., Kipruto, S., Bukachi, F., Maitai, C., David, L., & Tshala-Katumbay, D. (2013). Carbamoylation correlates of cyanate neuropathy and cyanide poisoning: relevance to the biomarkers of cassava cyanogenesis and motor system toxicity. SpringerPlus, 2, 647. https://doi.org/10.1186/2193-1801-2-647
Kimani, S., Sinei, K., Bukachi, F., Tshala-Katumbay, D., & Maitai, C. (2014a). Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents. Metabolic brain disease, 29(1), 105–112. https://doi.org/10.1007/s11011-013-9459-2
Kimani, S., Moterroso, V., Morales, P., Wagner, J., Kipruto, S., Bukachi, F., Maitai, C., & Tshala-Katumbay, D. (2014b). Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet. Food and Chemical Toxicology: An International Journal published for the British Industrial Biological Research Association, 66, 203–209. https://doi.org/10.1016/j.fct.2014.01.047
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Medicine, 6(7), e1000100. https://doi.org/10.1371/journal.pmed.1000100
Manning, J. M., & Acharya, A. S. (1984). The mechanism of action of two anti-sickling agents: sodium cyanate and glyceraldehyde. The American Journal of Pediatric Hematology/oncology, 6(1), 51–54. https://doi.org/10.1097/00043426-198423000-00024
Monekosso, G. L., Annan, W. G., & Ashby, P. H. (1964). Therapeutic effect of vitamin b complex on an ataxic syndrome in western Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 58(5), 432–436. https://doi.org/10.1016/0035-9203(64)90091-4
National Research Council (US) Panel on the Applications of Biotechnology to Traditional Fermented Foods. (1992). Applications of Biotechnology to Fermented Foods: Report of an Ad Hoc Panel of the Board on Science and Technology for International Development. National Academies Press (US).
Oluwole, O. S., Onabolu, A. O., Link, H., & Rosling, H. (2000). Persistence of tropical ataxic neuropathy in a Nigerian community. Journal of Neurology, Neurosurgery, and Psychiatry, 69(1), 96–101. https://doi.org/10.1136/jnnp.69.1.96
Osuntokun B. O. (1981). Cassava diet, chronic cyanide intoxication and neuropathy in the Nigerian Africans. World Review of Nutrition and Dietetics, 36, 141–173. https://doi.org/10.1159/000393156
Otubogun, F. M., Akinyemi, R. O., & Ogunniyi, A. O. (2019). Tropical ataxic neuropathy: Findings of a neuroepidemiological survey of Odeda, southwest Nigeria. Journal of the Neurological Sciences, 405, 116434. https://doi.org/10.1016/j.jns.2019.116434
Paul, L., Mudogo, C.N., Mtei, K.M., Machunda, R.L. & Ntie-Kang, F. (2020). A computer-based approach for developing linamarase inhibitory agents. Physical Sciences Reviews, 5(7), 1-13. https://doi.org/10.1515/psr-2019-0098
Precoppe, M., Komlaga, G. A., Chapuis, A., & Müller, J. (2020). Comparative Study between Current Practices on Cassava Drying by Small-Size Enterprises in Africa. Applied Sciences, 10(21), 7863. https://doi.org/10.3390/app10217863
Rwatambuga, F. A., Ali, E. R., Bramble, M. S., Gosschalk, J. E., Kim, M., Yandju, D. L., Okitundu, L. A., Boivin, M. J., Banea, J. P., Westaway, S. K., Larry, D., Vilain, E., Mumba Ngoyi, D., & Tshala-Katumbay, D. D. (2021). Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 148, 111917. https://doi.org/10.1016/j.fct.2020.111917
Siritunga, D., & Sayre, R. T. (2003). Generation of cyanogen-free transgenic cassava. Planta, 217(3), 367–373. https://doi.org/10.1007/s00425-003-1005-8
Tellez, I., Johnson, D., Nagel, R. L., & Cerami, A. (1979). Neurotoxicity of sodium cyanate. New pathological and ultrastructural observations in Maccaca nemestrina. Acta Neuropathologica, 47(1), 75–79. https://doi.org/10.1007/BF00698277
Tian, S., Li, Y., Zeng, H., Guan, W., Wang, Y., & Zhao, X. (2016). Cyanide oxidation by singlet oxygen generated via reaction between H2O2 from cathodic reduction and OCl(-) from anodic oxidation. Journal of colloid and interface science, 482, 205–211. https://doi.org/10.1016/j.jcis.2016.07.024
Tor-Agbidye, J., Palmer, V. S., Spencer, P. S., Craig, A. M., Blythe, L. L., & Sabri, M. I. (1999a). Sodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa. Brain Research, 820(1-2), 12–19. https://doi.org/10.1016/s0006-8993(98)01343-2
Tor-Agbidye, J., Palmer, V. S., Lasarev, M. R., Craig, A. M., Blythe, L. L., Sabri, M. I., & Spencer, P. S. (1999b). Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava. Toxicological sciences: an official journal of the Society of Toxicology, 50(2), 228–235. https://doi.org/10.1093/toxsci/50.2.228
Tylleskär, T., Banea, M., Bikangi, N., Cooke, R. D., Poulter, N. H., & Rosling, H. (1992). Cassava cyanogens and konzo, an upper motoneuron disease found in Africa. Lancet (London, England), 339(8787), 208–211. https://doi.org/10.1016/0140-6736(92)90006-o
Tylleskär, T., Légué, F. D., Peterson, S., Kpizingui, E., & Stecker, P. (1994). Konzo in the Central African Republic. Neurology, 44(5), 959–961. https://doi.org/10.1212/wnl.44.5.959
Wang, Z., Nicholls, S. J., Rodriguez, E. R., Kummu, O., Hörkkö, S., Barnard, J., Reynolds, W. F., Topol, E. J., DiDonato, J. A., & Hazen, S. L. (2007). Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nature medicine, 13(10), 1176–1184. https://doi.org/10.1038/nm1637
Wells, G.A., Shea, B., O’Connell, D., Peterson, J., Welch, V., Losos, M., & Tugwell, P. (2024). The Newcastle-Ottawa Scale (NOS) for assessing the quality of non randomised studies in meta-analyses. L’Hôpital d’Ottawa Institut de recherche. Retrieved from https://www.ohri.ca/programs/clinical_epidemiology/nosgen.pdf
Authors
Manalo, R. V., Ong, A. L., & Medina, P. M. (2025). Neurotoxic and neuromotor effects of cyanate, an oxidative byproduct of cyanide from linamarin in cassava: A systematic review. The North African Journal of Food and Nutrition Research, 9(19), 85–94. https://doi.org/10.51745/najfnr.9.19.85-94
Copyright (c) 2025 Rafael Vincent Manalo, Antonio Lorenzo Ong, Paul Mark Medina
This work is licensed under a Creative Commons Attribution 4.0 International License.
-
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
-
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
