The role of thiamine deficiency in alcoholic brain disease

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

ALCOHOL'S EFFECTS ON THIAMINE UPTAKE AND FUNCTION

As noted earlier, thiamine deficiency in affluent countries clearly is linked to alcoholism, occurring in up to 80 percent of alcoholics (e.g., Morgan 1982). However, only a subset of these alcoholics develop brain disorders such as WKS. Moreover, identical twins (who share all of their genetic information) show greater similarity with respect to alcohol-induced brain disease than do fraternal twins (who share on average 50 percent of their genetic information). These two observations have led to the conclusion that a genetic predis-position to thiamine deficiency and its effects may exist, as will be discussed in more detail in the section "Differential Sensitivity to Thiamine Deficiency."

Research over the past 30 years has identified several mechanisms through which alcoholism may contribute to thiamine deficiency. The most important of these mechanisms (as discussed in Hoyumpa 1980) include:

* Inadequate nutritional intake

* Decreased absorption of thiamine from the gastrointestinal tract and reduced uptake into cells

* Impaired utilization of thiamine in the cells.

Inadequate Nutritional Intake

Although most people require a minimum of 0.33 mg thiamine for each 1,000 kcal of energy they consume, alcoholics tend to consume less than 0.29 mg/1,000 kcal (Woodhill and Nobile 1972). In fact, in an early study of 3,000 alcoholics admitted to hospitals because of alcohol withdrawal symptoms or other alcohol-related illnesses, 40 percent exhibited periodic thiamine deficiency during drinking binges, 25 percent exhibited prolonged thiamine deficiency with some periods of normal intake, and 35 percent exhibited continuous thiamine deficiency (Leevy and Baker 1968). A later study found that alcoholic patients had significantly lower average levels of a thiamine compound containing one phosphate group (i.e., thiamine monophosphate), but the average levels of free thiamine and ThDP were similar in alcoholics and control subjects (Tallaksen et al. 1992). However, some of the alcoholics in that study had extremely high levels of free thiamine, suggesting that they may have had a problem in the steps that lead to the conversion of thiamine into its active, phosphate-containing form.

Decreased Uptake of Thiamine From the Gastrointestinal Tract

Animal studies have helped elucidate the mechanisms of normal and alcoholimpaired thiamine uptake from the gastrointestinal tract into the blood and cells. To be used by the body, thiamine must cross a number of barriers, first transferring across the membranes of the cells lining the gut (i.e., enterocytes), then entering those cells, and then crossing the membranes at the other end of the cells to enter the bloodstream. At low thiamine concentrations, such as those normally found in the human body, this transfer is achieved by a specific thiamine transporter molecule that requires energy. This is called an active transport process and seems to be associated with the rapid addition of two phosphate groups by the enzyme thiamine diphosphokinase (TPK) once the thiamine is inside the cell. At high thiamine concentrations, however, such as can be achieved after additional thiamine is administered, thiamine transport occurs through a passive process--that is, a mechanism that requires no energy.