Deprivation of folate and B12 increases neurodegeneration beyond that accompanying deprivation of either vitamin alone.

Increased homocysteine has in some cases been linked with an increased incidence of Alzheimer's disease and motor neuron disease. Folate or B12 deficiency increases homocysteine, but controversy exists as to whether their levels also correlate with either disorder. Since their presence within various dietary constituents may confound interpretation, we tested the impact of deprivation of either or both in the closed environment of neuronal cell cultures. Deprivation of either increased cytosolic calcium, reactive oxygen species, intracellular homocysteine, and apoptosis, but deprivation of both fostered substantially larger increases, supporting the notion that both are required for optimal neuroprotection.