Vitamin E and Neurodegenerative Diseases

4 Vitamin E and Neurodegenerative Diseases There is evidence that Pcu kinson s disease is a result of oxidative radical dtimage, tmd there have 

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Carr AC, Zhu BZ, and Frei B (2000) Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha-tocopherol (vitamin E). Circulation Research 87,349-54. Diplock AT (2001) Antioxidants, nutrition and health. In Food and Nutritional Supplements Their Role in Health and Disease, IK Ransley, IK Donnelly, and NWRead (eds.), pp. 65-80. Berlin Springer. 

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Animal studies show some protective effects of tocopherol supplements against a variety of radical-generating chemical toxicants, and it has been assumed that vitamin E may similarly be protective against a variety of degenerative diseases that are associated with radical damage, including cancer, cardiovascular disease, cataracts, and neurodegenerative diseases. 

The scientific community has been discussing for quite some time now the relationship between oxidative stress, defined as the imbalance between oxidant and antioxidants [45], and the health-disease status. An impressive amount of information available in the literature deals with the effects of the classic antioxidants, ascorbic acid, a-tocopherol, and jS-carotene in a huge series of pathophysiological situations in experimental animals and humans. Concerning the effects of the classic antioxidants on mitochondrial function in situations of oxidative stress, the information is not so vast and most of the time it is not conclusive. However, substantial progress has been made in the description of the mitochondrial alterations in neurodegenerative diseases and in the a-tocopherol effects,both as prevention and as treatment [46]. We will briefly review some reports related to vitamin E and mitochondrial dysfunction in oxidative metaboHc disorders and in the neurodegenerative Alzheimer s and Parkinson s diseases. 

Prevention of Atherosclerosis, Cancer, Fibrosis, and Neurodegenerative Diseases by Vitamin E... 

Oxidative damage has been implicated in as many as one hundred disease states, including cardiovascular disease, cancer, stroke, neurodegenerative diseases, and chronic inflammatory diseases. The health-promoting effects of diets rich in fresh fruits and vegetables probably result in large part from their high content of antioxidant compounds, particularly vitamin C and vitamin E. 

Other studies have described preventive effects of vitamin E supplemmtation against certain types of cancer, fibrotic disease, or neurodegenerative diseases such as Alzheimer s - or Parkinson s disease (reviewed by J.M. Zingg and... 

Berman, K. and Brodaty, H., Tocopherol (vitamin E) in Alzheimer s disease and other neurodegenerative disorders, CNS Drugs 18 (12), 807-825, 2004. 

Oxidative stress is closely associated with the pathogenesis of ALS. Several antioxidants including vitamin E, acetylcysteine, methylcobalamin, and glutathione have been tested in clinical trials of ALS. Coenzyme QIO (CoQlO) is an antioxidant and mitochondrial cofactor (Fig. 9.12). It not only prevents lipid peroxidation but also stabilizes the Ca " channels. Its oral administration increases CoQlO levels in mitochondria. CoQlO produces promising effects in ALS transgenic mice and in clinical trials for neurodegenerative diseases other than ALS. Phase II clinical trial of CoQlO in ALS patients indicate that this dmg is ineffective in producing beneficial effects in ALS patients (Levy et al., 2006), and opinions on phase III trials have been controversial (Kaufmann et al., 2009). 

Vitamin E is often recommended and used in the therapy of AD [207,208] however, results of clinical studies are controversial [209]. In dietetics, there is the idea that a combination of extra- and intracellular antioxidant (ascorbic acid -I- vitamin E) provides adequate antioxidant status of the cells however, it seems that it does not meet at least in part. The interest in the field of toco-pherols moves to tocotrienols increasingly [210]. In addition, certain epoxides of tocotrienols proved as an effective elicitors of internal biosynthesis of coenzyme Q [211], which can enhance protection of mitochondrial metabolism. Reduced mitochondrial function is in terms of current views the first factor in the development of neurodegenerative diseases [212]. 

Vitamin E deficiency is seen rarely in humans. However, there may be a risk of vitamin E deficiency in premature infants because the placenta does not transfer a-tocopherol to the fetus in adequate amounts. When it occurs in older children and adults, it is usually a result of lipoprotein deficiencies or a lipid malabsorption syndrome. These include patients with abetalipoproteinemia or homozygous hypobeta-lipoproteinemia, those with cholestatic disease, and patients receiving total parenteral nutrition. There is also an extremely rare disorder in which primary vitamin E deficiency occurs in the absence of lipid malabsorption. This disorder is a rare autosomal recessive neurodegenerative disease caused by mutations in the gene for a-TTP. This disorder is known as ataxia with vitamin E deficiency (AVED). Patients with AVED have extraordinary low plasma vitamin E concentrations (<5pgml ) and have an onset between 4 and 18 years, with progressive development of peripheral neuropathy,... 

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