The Influence of Thiamine Deficiency on Citric Acid Excretion

According to current views on the intermediary metabolism of carbohydrate, both thiamine and citric acid are significant factors in the oxidation of this foodstuff, Thiamine in its phosphorylated form has been shown (Banga, Ochoa, and Peters, 1939) to be required for the oxidative removal of the pyruvic acid produced in the course of carbohydrate breakdown. Likewise, according to Krebs and Johnson (1937), some product (probably pyruvic acid) of carbohydrate metabolism reacts with oxalacetic acid to form citric acid which in turn yields carbon dioxide and a series of simpler dicarboxylic acids before the cycle is repeated. It might be expected, therefore, that the metabolic disturbance characteristic of thiamine deficiency would, in part, make itself felt in an alteration of the “citric acid cycle” and thus possibly in a change in the rate of excretion of citric acid in the urine, inasmuch as it has been shown that even with an adequate allowance of thiamine, dietary carbohydrate exerts a definite influence on the urinary citric acid (Smith and Meyer, 1939). Studies have been carried out to determine whether or not a relationship between thiamine deficiency and the excretion of citric acid can be demonstrated. A marked increase in citric acid output in the urine of rats has been reported by Krusius and Simola (1938) and also by Krebs (1938). On the other hand Sober, Lipton, and Elvehjem (1940) indicate that severe thiamine deficiency is accompanied by a decrease in urinary citric acid, with a prompt rise of considerable magnitude when the experimental animals (rats) were realimented with thiamine. The data given in the present report have a bearing on this problem.