title: Weak BMAA toxicity compares with that of the dietary supplement β-alanine.
abstract: β-N-methylamino-L-alanine (BMAA) is routinely described in the literature as a potent neurotoxin and as a possible cause of neurodegenerative disorders of aging such as Alzheimer's disease, amyotrophic lateral sclerosis, and the amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC) syndrome of Guam. To test for the toxicity of BMAA against human neurons, we chose 3 standard human neuronal cell lines for examination and compared the toxicity with the muscle-building nutritional supplement β-alanine, glutamic acid, and the established excitotoxins kainic acid, quisqualic acid, ibotenic acid, domoic acid, and quinolinic acid. Neurotoxicity was measured by the standard lactic dehydrogenase release assay after 5-day incubation of NT-2, SK-N-MC, and SH-SY5Y cells with BMAA and the comparative substances. The ED(50) of BMAA, corresponding to 50% death of neurons, varied from 1430 to 1604 μM while that of the nutritional supplement β-alanine was almost as low, varying from 1945 to 2134 μM. The ED(50) for glutamic acid and the 5 established excitotoxins was 200- to 360-fold lower, varying from 44 to 70 μM. These in vitro data are in accord with previously published in vivo data on BMAA toxicity in which mice showed no pathological effects from oral consumption of 500 mg/kg/day for more than 10 weeks. Because there are no known natural sources of BMAA that would make consumption of such amounts possible, and because the toxicity observed was in the same range as the nutritional supplement β-alanine, the hypothesis that BMAA is an environmental hazard and a contributor to degenerative neurological diseases becomes untenable.
authors.affiliation: Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Moonhee
authors.initials: M
authors.lastname: Lee
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D000087522:Cyanobacteria Toxins; D019587:Dietary Supplements / Q000633:toxicity*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D015091:beta-Alanine / Q000633:toxicity*
chemical_list: D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine; D015091:beta-Alanine