Alcoholism and WK syndrome (WKS)
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Wernicke-Korsakoff syndrome {pronounced?vair-ni-kuh-kawr-suh-kawf,?(1)}?is a neurological disease caused by?vitamin B1 (Thiamine) deficiency. It occurs mostly in people with chronic alcoholism.
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Alcoholism is not the only cause of WKS; other factors that produce thiamine deficiency {malnutrition, genetic mutation, hyperthyroidism, anorexia, and liver diseases (2,3)}, also cause WKS .
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Wernick- Korsakoff (WK) syndrome consists of two different conditions (Wernicke encephalopathy and Korsakoff syndrome) that develop at the same time (4). Wernicke encephalopathy is characterized by?confusion, ataxia?(lack of muscle coordination),?and ophthalmoplegia?(weakness of the eye muscles) (3). Korsakoff Syndrome is irreversible and involves?memory loss?due to brain damage (in parts involved with memory).
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Another common milder disease caused by thiamine deficiency is beriberi –extreme thiamine deficiency can exacerbate beriberi into WK syndrome.
How important is thiamine to the body?
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Thiamine is a vitamin derived from food. It is also a component of the cofactor TPP (Thiamine pyrophosphate). This cofactor is important for mechanisms used by certain enzymes involved in carbohydrate metabolism. Examples (of these enzymes) are pyruvate dehydrogenase and transketolase involved in the conversion of pyruvate to acetyl-Co A and carbon transfers from ketose donors to aldose acceptors respectively. Since the affected biological pathways that require TPP are linked to several other pathways, the effect of its scarcity is massive. The nerves, neurotransmitters, heart, and muscle cells are affected.
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How can alcohol cause thiamine deficiency??
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The lining (mucosa) of the small intestine is where many nutrients are absorbed. Via the bloodstream, these nutrients are distributed to various organs. Chronic administration of ethanol impairs the absorption of thiamine in the intestine?(5) and destroys the intestinal lining (6). Alcohol inhibits/slows down the transport of thiamine from food in the small intestine. ??
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Again, aside from decreasing the activity of thiamine-metabolizing enzymes (involved in thiamine uptake), ethanol also increases the activity of thiamine pyrophosphate (TPP) degrading enzymes (phosphatases) (7).
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Even in the presence of sufficient food and thiamine supply, the combined result of the above actions of ethanol generates some manifestations of malnourishment (6).
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Finally, one of the signs of alcoholism is the switching of food for alcohol by an individual. When a person starts preferring alcohol over food, the body is deprived of needed nutrients (malnutrition). Since thiamine is gotten from food, not eating well will cause a thiamine deficit in the body.
This lack of feeding is also associated with another condition known as ketoacidosis. In the absence of carbohydrates, the body switches to fat stores for energy. Ketone bodies (acetoacetate and beta-hydroxybutyrate) are formed from (acetyl-CoA of) fat breakdown. If produced in excess (which is the case when alcohol replaces food for a long time), ketone bodies will decrease the blood’s pH and the blood becomes acidic).
Summary.
Alcoholism can cause WKS when:
(i)????????????????Ethanol interferes with thiamine metabolism
(ii)?????????????or?alcohol replaces food, the thiamine supply.
References:
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3. Vasan S, Kumar A. Wernicke Encephalopathy. Available from:?https://www.ncbi.nlm.nih.gov/books/NBK470344/?
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5. Gastaldi G, Casirola D, Ferrari G, Rindi G. Effect of chronic ethanol administration on thiamine transport in microvillous vesicles of rat small intestine. Alcohol Alcohol. 1989;24(2):83-9. doi: 10.1093/oxfordjournals.alcalc.a044888. PMID: 2719773.
6. Langlais PJ. Alcohol-Related Thiamine Deficiency: Impact on Cognitive and Memory Functioning.?Alcohol Health Res World. 1995;19(2):113-121.
7. Laforenza U, Patrini C, Gastaldi G, Rindi G. Effects of acute and chronic ethanol administration on thiamine metabolizing enzymes in some brain areas and in other organs of the rat. Alcohol Alcohol. 1990;25(6):591-603. doi: 10.1093/oxfordjournals.alcalc.a045055. PMID: 1964780.
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