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Chantal Bémeur, Jane A Montgomery, and Roger F Butterworth

Keywords Vitamins · Thiamine · Wernicke–Korsakoff syndrome · Pyridoxine ·

Niacin · Folic acid · Antioxidants

Contents

1 Introduction . 103

2 Thiamine (Vitamin B1) . 104

2.1 Thiamine Deficiency-Related Neurological Disorders . 105

2.2 Thiamine and Cell Metabolism/Function . 106

2.3 Neuronal Cell Death in Thiamine Deficiency . 108

3 Pyridoxine (Vitamin B6) . 110

4 Cobalamin (Vitamin B12) . 112

5 Niacin (Vitamin B3) . 114

6 Folic Acid (Vitamin B9) . 115

7 Antioxidant Vitamins . 116

7.1 α-Tocopherol (Vitamin E) . 116

7.2 Ascorbic Acid (Vitamin C) . 118

7.3 Carotenoids . 120

References . 120

1 Introduction

The consequences of malnutrition on the central nervous system are diverse and depend to a significant extent on the stage of development or maturity of the brain

as well as on the severity of the nutritional deficiency For example, vitamin deficien-cies result in a wide range of neuropathology and neuropsychiatric symptomatology

R.F Butterworth (B)

Neuroscience Research Unit, CHUM (Hôpital Saint-Luc), Montreal, QC, Canada H2X 3J4 e-mail: roger.butterworth@umontreal.ca

103

J.P Blass (ed.), Neurochemical Mechanisms in Disease,

Advances in Neurobiology 1, DOI 10.1007/978-1-4419-7104-3_4,

C

Springer Science+Business Media, LLC 2011

depending upon the nature and extent of the vitamin deficiency The most com-mon vitamin deficiency disorders are those associated with the group B vitamins, particularly thiamine (vitamin B1) The likelihood of multiple vitamin deficiencies should be borne in mind.

This review chapter summarizes current knowledge on vitamin deficiencies, examines the role of vitamins in cellular function, and reviews current mechanisms involved in the pathogenesis of brain dysfunction in vitamin deficiencies.

2 Thiamine (Vitamin B1)

Thiamine is a water-soluble vitamin and is also known as vitamin B1, or aneurin (Fig 1 ) Both the pyrimidine and thiazole moieties are necessary for biological activity, which is maximal when only one methylene group bridges the two moieties.

H3C N NH2 S

3

CH2 –– CH2 –– OH

+

2 3 5 6

4

4 5 2 3

Fig 1 Structure of thiamine

Thiamine status is influenced by the diet and by a variety of other factors, including its bioavailability in food products, ethanol consumption, the presence

of antithiamine factors in the diet as well as folate and protein status Ingested thi-amine is fairly well absorbed, rapidly converted to phosphorylated forms, stored poorly, and excreted in the urine in a variety of hydrolyzed and oxidized products (TanPhaichitr et al., 1999 ).

In developed countries, clinical thiamine deficiency occurs most commonly in alcoholics and in patients with grossly impaired nutritional status associated with, for example, gastrointestinal disease or AIDS (Butterworth, 2006 ) Thiamine defi-ciency may result from inadequate dietary intake of the vitamin Chronic alcohol consumption can result in thiamine deficiency by causing inadequate nutritional thiamine intake, decreased absorption from the gastrointestinal tract, and impaired thiamine utilization in the cells People differ in their susceptibility to thiamine defi-ciency and different brain regions may be more or less sensitive to this condition Thiamine deficiency is more common in developing countries where polished rice

is the staple diet Peripheral nerve damage (neuropathy) is a common consequence

of thiamine deficiency The neuropathy tends to be worse distally than proximally, involves myelin more than axons, and is often painful The neuropathy is linked to multiple deficiencies of water-soluble vitamins that often occur together in foods and are known as the vitamin B complex.