The Effect of Thiamin Deficiency Produced by Oxythiamin, by Neopyrithiamin, and by Diet, on the Metabolism of Alcohol

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Abstract
In animals alcohol is first oxidized to acetaldehyde (Stage I); the acetaldehyde is further oxidized to acetate and the acetate then metabolized in the same manner as acetate from other sources (Stage II). It is generally held that thiamin plays no part in alcohol metabolism. Indirect evidence is accumulating which might indicate that thiamin may be necessary for some phase of alcohol metabolism. The present work attempted to discover thiamin effect. Severe thiamin deficiency was produced in dogs by oxythiamin, neopyrithiamin and diet The symptoms observed after oxythiamin differed from those produced by neopyrithiamin or diet. This supports the theory of Woolley and Merrifield (Fed. Proc. 11: 548, 1952) that oxythiamin diminishes tissue cocarboxylase and that neopyrithiamin interferes with a function of thiamin distinct from the one involving cocarboxylase. Doses of ethyl alcohol which normally produced only mild intoxication resulted in severe symptoms or death in dogs pretreated with oxythiamin. Increased toxicity was accompanied by a marked fall in blood glucose. A slow intraven. infusion of acetaldehyde also produced a fall of blood glucose in the oxythiamin-treated animals but did not change the blood glucose of normal animals. Dogs treated with neopyrithiamin or made deficient by diet responded to alcohol in the same way as normal controls., Pretreatment with disulfiram resulted in an increase of blood acetaldehyde following alcohol admn. This did not occur in thiamin deficient or normal dogs. The rate at which alcohol disappeared from the blood in all the treated dogs was unchanged from that found in the same animals without treatment. These results are interpreted as evidence that thiamin plays some role in the usual pathway for metabolism of acetaldehyde (Stage II of alcohol metabolism) and that this role is beyond the first step in metabolism of acetaldehyde.