Manihot esculenta consumption and pancreatitis: A critical review of epidemiological, mechanistic, and toxicological evidence

Chronic pancreatitis has long been recorded commonly in Kerala, India, where tapioca has traditionally been a staple food. Tapioca has been proposed as a probable cause of tropical chronic pancreatitis, as it contains natural cyanogenic glycosides, which release cyanide if not adequately processed. This review critically examines the evidence by evaluating epidemiological studies, biological mechanisms and toxicological findings pertaining to tapioca consumption and pancreatic damage and other confounding factors. A systematic literature review was conducted using PubMed, Scopus, Web of Science and Google Scholar. Included for the compilation were 42 important studies and peer-reviewed articles published between 2010 and 2025. Existing literature suggests that cyanogenic glycosides in tapioca causing cyanide exposure can produce oxidative stress, mitochondrial dysfunction and cellular damage. These findings are mostly based on experimental studies and neurological disease such as konzo rather than studies regarding normal dietary consumption of tapioca. Currently there is scanty and inconclusive epidemiological or clinical evidence suggesting tapioca consumption to be an etiological factor of chronic pancreatitis. It has been reported that soaking, fermenting, boiling and drying easily eliminate cyanide and well-cooked tapioca is safe to consume on a regular basis. The review findings also suggest that chronic pancreatitis is a multifactorial disease influenced by genetic susceptibility, nutritional status, environmental exposures, micronutrient deficiencies and socioeconomic factors. Its development therefore cannot be due to a single dietary component. Further long-term studies using advanced methods may establish the relation between tapioca consumption and chronic pancreatitis.