Cycasin

Cycasin is a plant toxin produced by cycads, primarily found in the seeds and developing tissues of species in the genus Cycas, such as Cycas revoluta and Cycas circinalis. Chemically, it is methylazoxymethanol beta-D-glucoside, a glycoside of methylazoxymethanol (MAM). It occurs in relatively high concentrations in seeds, which have historically been used as food in some cultures after processing.

When ingested, cycasin is hydrolyzed by intestinal glycosidases to methylazoxymethanol (MAM), the compound responsible for much of its toxicity. MAM is a reactive methylating agent that can damage DNA and promote carcinogenesis; it is considered the principal active metabolite. In animal studies, exposure to cycasin or MAM induces tumors in the liver and gastrointestinal tract and can cause neurotoxic effects. The toxicology of cycasin is the subject of ongoing research, particularly regarding its role in neurodegenerative disease pathways.

Occurrence and human relevance: Cycasin content is highest in cycad seeds, which have been used in some traditional foods after processing. In the mid-20th century, concerns about neurodegenerative disease and cancer linked to cycad-derived diets arose in populations such as those studied in Guam, associated with ALS-PDC, though the exact contribution of cycasin remains debated. Modern guidance generally discourages using cycad seeds for food, as processing decreases but does not reliably eliminate the toxin.

Safety and research uses: Cycasin is handled in toxicology and carcinogenesis research to study the effects of the active metabolite MAM. It is not used as a medicinal agent and poses genotoxic and carcinogenic risks.