Vitamin E may be helpful in Alzheimer’s disease prevention The results of research reported in the October 2004 issue of the Journal of Alzheimer’s Disease identifies a culprit in Alzheimer’s disease and shows vitamin E may help slow the destruction of brain cells that occurs as a result.
In a study funded by the National Institutes of Health, University of Kentucky chemistry professor Allan Butterfield and colleagues compared rat and human forms of amyloid beta peptide, a compound that forms the plaques in the brains of Alzheimer’s patients which are believed to be responsible for the damage incurred by this disease. They found that amyloid beta peptide from both rats and humans caused DNA fragmentation in neurons, a loss of neuron connections, and lowered cell viability.
It had previously been proposed that copper binding sites in human amyloid beta contributed to the disease. In the current study, Dr Butterfield’s findings show that rat amyloid beta, which lacks copper binding sites, still causes damage, and that it is the methionine residue in beta amyloid that damages brain cells.
Methionine is an amino acid that occurs in relatively high amounts in animal-derived proteins and contributes to the formation of homocysteine, another amino acid that when elevated has been determined to double the risk of developing Alzheimer’s disease. Earlier research had revealed that methionine was involved in the neurotoxicity and oxidative stress caused by amyloid beta in humans.
Protein oxidation and lipid peroxidation were similar in both animal and human amyloid beta and were both inhibited by vitamin E, an antioxidant vitamin. Studies have found an association between vitamin E intake and reduced cognitive decline and Alzheimer’s disease, adding evidence to the suggestion that it may help retard the disease in humans.
The findings indicate that that reactive oxygen species play a role in the toxicity of amyloid beta peptide, and that the oxidative stress it causes may be due to methionine rather than copper.
Alzheimer’s disease The most characteristic features of Alzheimer's disease are senile plaques of beta-amyloid peptide, neurofibrillary tangles involving tau protein, loss of synapses, and (ultimately) the death of neurons. Although neurofibrillary tangles are more closely associated with neuronal death than beta-amyloid, the evidence is becoming convincing that beta-amyloid is the factor most responsible for starting the degenerative processes of Alzheimer's disease.
Researchers have shown that cultured cells are prevented from beta-amyloid toxicity with the addition of vitamin E (Grundman 2000). Researchers at the University of Kentucky published a ground-breaking article showing that vitamin E prevented the increase of polyamine metabolism in response to free-radical mediated oxidative stress caused by the addition of beta-amyloid to the rat neurons (Yatin et al. 1999).
Research conducted in Germany showed that both natural and synthetic vitamin E were more effective than estrogen (17-beta estradiol) in protecting neurons against oxidative death caused by beta-amyloid, hydrogen peroxide, and the excitatory amino acid glutamate (Behl 2000).
Research conducted at the University of California, San Diego, School of Medicine studied the protective effects of vitamin E in apolipoprotein E-deficient mice. Those treated with vitamin E displayed a significantly improved behavioral performance in the Morris water maze. Also, the untreated mice displayed increased levels of lipid peroxidation and glutathione, whereas the vitamin E-treated mice showed near normal levels of both lipid peroxidation and glutathione (Veinbergs et al. 2000).
A study of 44 patients with Alzheimer's disease and 37 matched controls showed that vitamin E levels in the cerebrospinal fluid (CSF) and serum were significantly lower in Alzheimer's patients (Jimenez-Jimenez et al. 1997).
In the Alzheimer's Disease Cooperative Study, 2000 mg of vitamin E were given to Alzheimer's disease patients. This slowed the functional deterioration leading to nursing home placement (Grundman 2000).
An article by Sano et al. (1997) described a double-blind, placebo-controlled, randomized, multicenter trial of patients with Alzheimer's disease of moderate severity. A total of 341 patients received the selective monoamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (vitamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or placebo for two years. The baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups. Both vitamin E and selegeline delayed the progression of the disease with vitamin E acting slightly better than selegeline (median time 670 vs. 655 days, respectively).
Memantine is an N-methyl- D-aspartate (NMDA) receptor antagonist that is neuroprotective by blocking glutamate, which can cause overstimulation of the nerves and become toxic to the nervous system. Memantine may benefit individuals with Alzheimer’s disease by improving cognition and overall functioning.