Selected for study fields were several distinct provincial regions of Japan which are noted to be stable in population composition, generally conservative in the mode of life, and distinguished by especially high figures in biometric statistics representing the Japanese characteristics of extraordinarily high incidence in death by cardiovascular diseases, stomach cancer, and hepatoma. From these regions, samples of popular fermented foodstuffs, consumed daily in quantity, were obtained as materials of study. They included “miso” or fermented soy bean paste, “katsuobushi” or fermented dry bonitos, and “starters” used for their fermentation processes. They were either commercial products from local plants or home-made ones. From 24 samples, 37 strains of fungi were isolated, of which 21 were found to produce toxic culture filtrates and extracts. Many of them produced kojic acid and β-nitropropionic acid. None, however, produced aflatoxin, although some strains produced blue and green fluorescent metabolites which have not yet been identified. Biologic tests carried out with the culture preparations revealed significant biologic activities in bacteriocidal effects, induction of bacteriophage, and influence on propagation of hamster cells in vitro. Moreover, short-term animal experiments showed development of miscellaneous remarkable pathologic changes, such as extensive hemorrhagic erosion in the glandular stomach, necrosis in the liver, and injuries in the kidneys, pancreas islets, and myocardium. The changes in the stomach and liver drew special attention in association with high incidence of chronic gastric and hepatic diseases in the biostatistics. Of the other changes, glomerulotubular nephritis, renal tubular oxalosis, pancreas-islet hemorrhage and degeneration, and myocardial hemorrhage and scar formation were impressive in relation to the high incidence of cardiovascular diseases. To prevent occurrence of toxic agents in fermented food, it was recommended to avoid the use of toxic strains of fungi and to eliminate contamination of undesirable strains of fungi.


This study was supported by NIH Contract No. PH43-65-1036.

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