MEASURING EFFECTS IN HUMANS OF DIETARY CYANIDE EXPOSURE FROM CASSAVA

To study whether the cyanogen content in cassava products causes a certain human disease it is necessary for the relevant form of cyanogen in food or metabolite in patients to be measured, to have a reliable analytical method of doing so, to know in which time period to measure the exposure and to find the patient, or patient to be, and control subjects in that time period. This is almost impossible; therefore medical investigations in this field must be based on a weaker study design. The advantages of the combined use of an ecological study design, a combination of qualitative and quantitative interview methods, chemical biomarkers to measure cyanide exposure, and community-based food chemistry experiments are demonstrated. Contrary to previously accepted terminology, there is no cyanide (HCN) of importance in cassava products. The separate determination of remaining glucosides and cyanohydrins in consumed products is relevant, since they are the main sources of dietary cyanide. Whereas HCN release is probably complete from consumed cyanohydrins the cyanogenic glucosides are only partly broken down to cyanide in the human body. The glucosides are partly absorbed and excreted unchanged in the urine as revealed by the use of a new analytical method. Absorbed HCN is reversible bound to the methaemoglobin fraction in the red cells, and blood levels reflect the balance between the rate of absorption and the rate of enzymatic detoxification to the main metabolite thiocyanate (SCN). Availability of sulfur is the rate limiting factor, but the body wisely gives priority to cyanide conversion even at low intakes of sulfur amino acids and some thiocyanate can always be formed. In spite of some limitations serum and urinary SCN remain the most useful biomarkers for estimation of cyanide intake. Due to a kidney threshold SCN levels reflect the load during the last few days; low loads are best measured by serum and high loads by urine levels. Estimation of the biological effective dose of HCN requires, however, determination of blood cyanide levels that unfortunately only reflect exposure during the last hours. The alternative HCN metabolites cyanate and amino-thiazoline carboxylic acid are promising biomarkers that may accumulate biological effective dose over a longer period. Criteria for defining safe levels of cyanogens in cassava products are discussed.