The role of thiamine deficiency in alcoholic brain disease

Alcohol Research & Health, Spring, 2003 by Peter R. Martin, Charles K. Singleton, Susanne Hiller-Sturmhofel

A deficiency in the essential nutrient thiamine resulting from chronic alcohol consumption is one factor underlying alcohol-induced brain damage. Thiamine is a helper molecule (i.e., a cofactor) required by three enzymes involved in two pathways of carbohydrate metabolism. Because intermediate products of these pathways are needed for the generation of other essential molecules in the cells (e.g., building blocks of proteins and DNA as well as brain chemicals), a reduction in thiamine can interfere with numerous cellular functions, leading to serious brain disorders, including Wernicke-Korsakoff syndrome, which is found predominantly in alcoholics. Chronic alcohol consumption can result in thiamine deficiency by causing inadequate nutritional thiamine intake, decreased absorption of thiamine from the gastrointestinal tract, and impaired thiamine utilization in the cells. People differ in their susceptibility to thiamine deficiency, however, and different brain regions also may be more or less sensitive to this condition. KEY WORDS: thiamine deficiency; alcoholic brain syndrome; chronic AODE (alcohol and other drug effects); Wernicke's encephalopathy; Wernicke-Korsakoff psychosis; alcoholic cerebellar degeneration; AODR (alcohol and other drug related) structural brain damage; malnutrition; disease susceptibility; survey of research

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Alcohol consumption can damage the brain through numerous mechanisms, many of which are discussed in the articles in this issue of Alcohol Research & Health. One of these mechanisms involves the reduced availability of an essential nutrient, thiamine, to the brain as a consequence of chronic alcohol consumption. This article describes the normal role of thiamine in brain functioning as well as the pathological consequences that result from thiamine deficiency. Specific actions of thiamine on a cellular level then are reviewed, followed by a discussion of how alcohol affects the body's processing and availability of thiamine as well as thiamine utilization by the cells. Finally, the article explores the hypothesis that people may differ in their sensitivity to thiamine deficiency and that different brain regions may be more or less sensitive to a deficiency in this important nutrient. Thiamine deficiency is particularly important because it can exacerbate many of the other processes by which alcohol induces brain injury, as described in other articles in this issue of Alcohol Research & Health.

WHAT IS THIAMINE AND WHAT ARE THE CONSEQUENCES OF THIAMINE DEFICIENCY?

Thiamine, also known as vitamin [B.sub.1], is an essential nutrient required by all tissues, including the brain. The human body itself cannot produce thiamine but must ingest it with the diet. Thiaminerich foods include meat (e.g., pork) and poultry; whole grain cereals (e.g., brown rice and bran); nuts; and dried beans, peas, and soybeans. In addition, many foods in the United States commonly are fortified with thiamine, including breads and cereals. Humans require a minimum of 0.33 milligrams (mg) thiamine for every 1,000 kilocalories (kcal) of energy they consume--in other words, people who consume a regular 2,000-kcal diet per day should ingest a minimum of 0.66 mg thiamine daily (Hoyumpa 1980). To provide a safety margin, a daily intake of 1.1 mg thiamine is currently recommended for adult women and 1.2 mg for adult men. (1) Studies have found that most healthy people typically consume 0.4 to 2.0 mg thiamine daily (Woodhill and Nobile 1972).

In the body, particularly high concentrations of thiamine are found in skeletal muscles and in the heart, liver, kidney, and brain (Singleton and Martin 2001). In the tissues, thiamine is required for the assembly and proper functioning of several enzymes that are important for the breakdown, or metabolism, of sugar molecules into other types of molecules (i.e., in carbohydrate catabolism). Proper functioning of these thiamine-using enzymes is required for numerous critical biochemical reactions in the body, including the synthesis of certain brain chemicals (i.e., neurotransmitters); production of the molecules making up the cells' genetic material (i.e., nucleic acids); and production of fatty acids, steroids, and certain complex sugar molecules. In addition, inadequate functioning of the thiamine-using enzymes can interfere with the body's defense against the damage (i.e., oxidative stress) caused by harmful, highly reactive oxygen molecules called free radicals. (For more information, see the section "Thiamine's Actions in the Cell.")

Because thiamine and the thiamine-using enzymes are present in all cells of the body, it would be plausible that inadequate thiamine affects all organ systems; however, the cells of the nervous system and heart seem particularly sensitive to the effects of thiamine deficiency. Therefore, the resulting impairment in the functioning of the thiamine-using enzymes primarily affects the cardiovascular and nervous systems. The classical manifestations of thiamine deficiency-related heart disease include increased blood flow through the vessels in the body, heart failure, and sodium and water retention in the blood. In the brain, thiamine is required both by the nerve cells (i.e., neurons) and by other supporting cells in the nervous system (i.e., glia cells). Thiamine deficiency is the established cause of an alcohollinked neurological disorder known as Wernicke-Korsakoff syndrome (WKS), but it also contributes significantly to other forms of alcohol-induced brain injury, such as various degrees of cognitive impairment, including the most severe, alcohol-induced persisting dementia (i.e., "alcoholic dementia"). These disorders are discussed in the following sections.