Thiamine Deficiency and Alcoholic Brain Disease

by National Institute of Health

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 (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 (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.

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 B1, 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. Thiamine-rich foods include meat (pork) and poultry; whole grain cereals (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 thiamine for every 1,000 kilocalories 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. 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 (1 Lower levels are recommended for children, and slightly higher levels are recommended for pregnant and breast-feeding women.) Studies have found that most healthy people typically consume 0.4 to 2.0 mg thiamine daily.

In the body, particularly high concentrations of thiamine are found in skeletal muscles and in the heart, liver, kidney, and brain. 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 (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 (neurotransmitters); production of the molecules making up the cells' genetic material (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 (oxidative stress) caused by harmful, highly reactive oxygen molecules called free radicals.

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 (neurons) and by other supporting cells in the nervous system (glia cells). Thiamine deficiency is the established cause of an alcohol-linked 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 ("alcoholic dementia"). These disorders are discussed in the following sections.

Wernicke's Encephalopathy and Korsakoff's Psychosis

WKS typically consists of two components, a short-lived and severe condition called Wernicke's encephalopathy (WE) and a long-lasting and debilitating condition known as Korsakoff's psychosis. WE is an acute life-threatening neurologic disorder caused by thiamine deficiency. In affluent countries, where people normally receive adequate thiamine from their diets, thiamine deficiency is most commonly caused by alcoholism; accordingly, in these countries WE is primarily found in alcoholics. The symptoms of WE include mental confusion, paralysis of the nerves that move the eyes (oculomotor disturbances), and an impaired ability to coordinate movements, particularly of the lower extremities (ataxia). For example, patients with WE may be too confused to find their way out of a room or may not even be able to walk. Many WE patients, however, do not exhibit all three of these signs and symptoms, and clinicians working with alcoholics must be aware that WE may be present even if the patient presents with only one or two of them. In fact, neuropathological studies after death indicate that many cases of thiamine deficiency-related encephalopathy may not be diagnosed in life because not all the "classic" signs and symptoms are present or recognized.

Approximately 80 to 90 percent of alcoholics with WE develop Korsakoff's psychosis, a chronic neuropsychiatric syndrome characterized by behavioral abnormalities and memory impairments. Although these patients have problems remembering old information (retrograde amnesia), it is the disturbance in acquisition of new information (anterograde amnesia) that is most striking. For example, these patients can engage in a detailed discussion of events in their lives but cannot remember ever having had that conversation an hour later. Because of these characteristic memory deficits, Korsakoff's psychosis also is called alcohol amnestic disorder. It is still somewhat controversial, however, whether Korsakoff's psychosis always is preceded by WE or whether it develops in fits and starts, without an overt episode of WE.

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