The Neurotoxic Effects of Cycads and Metals: A Review

Abstract

The bioaccumulation of environmental toxins as possible risk factors in the etiology ofamyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) is studied inthree foci of the Western Pacific: Guam, the Kii Peninsula, and West Papua New Guinea. Theobjective of this study was to evaluate the best evidence on the exogenous causes of ALS/PDC, with emphasis on the role of cycads, iron, and manganese in the Western Pacific foci,by performing a systematic review of major electronic databases using predefined criteria, 68of which met the selection criteria. Two major environmental hypotheses are associated withthis enigmatic disease: the vegetal hypothesis, which focuses on the neurotoxic and genotoxicproperties of the cycad, and the mineral hypothesis, which focuses on the neurotoxic propertiesof metals. Although typically studied independently, environmental data suggests these twohypotheses may, in fact, converge. Epidemiologic research investigating the association betweenexposure to environmental toxins and ALS/PDC has proven inconclusive. Nevertheless,possible causal links indicate a need for more holistic research to not only better understandALS/PDC, but also glean new insights regarding the associated neurodegenerative diseases.