Slow toxins, biologic markers, and long-latency neurodegenerative disease in the western Pacific region

The inhabitants of several small islands in the Pacific Ocean, including Guam, have an especially high rate of Parkinson's disease. This high incidence has particularly intrigued researchers, because the Parkinson's disease occurs within a complex of disorders including amyotrophic lateral sclerosis, with pathological features similar to Alzheimer's disease. Over 25 years ago, this parkinsonism dementia/amyotrophic lateral sclerosis complex (P-D/ALS) was hypothesized to result from the ingestion of food products made from seeds indigenous to the area. This hypothesis later lost support, but has recently been reconsidered. The seeds, which come from a type of Cycad plant, contain a neurotoxic compound called cycasin and are used to make flour in traditional recipes. The relationship between cycasin and P-D/ALS is strengthened by the observation that on islands where different cycad flour, not containing cycasin, is used, P-D/ALS is unknown. However, the hypothesis fell into disfavor as researchers were unable to produce a similar syndrome in animals by feeding them cycad flour. Cycasin and its primary metabolite methylazoxymethanol (MAM) is a potent carcinogen, and animals injected with MAM are very likely to develop cancer. MAM can also produce birth defects in developing animals. The possibility has now been raised that some of the toxic effects responsible for causing cancer may result in other long-term effects in people. MAM is a member of a class of cancer-causing substances called alkylating agents, which exert their influence by permanently changing DNA. It is possible that the slow accumulation of such changes may set the stage for the onset of neurological disease later in life. Furthermore, it may also be possible that cycasin could induce changes in DNA which affect fetal development and set the stage for neurological disease decades later. Curiously, however, the rate of cancer among the western Pacific residents who use flour containing cycasin, although greater than average, is less than would be predicted on the basis of the powerful cancer-causing properties of this substance. The incidence of P-D/ALS is declining on Guam and other islands; it is tempting to speculate that this may be due to the decline in the use of traditional cycad flour in cooking. (Consumer Summary produced by Reliance Medical Information, Inc.)