It  is a water-soluble compound containing the thiazole and pyrimidine rings. It is readily destroyed by heat and considerable loss may occur in the preparation of food. Although thiamine is widely distributed in nature, rich sources are few, namely, peas, beans, lean pork, peanuts, oatmeal, whole wheat and enriched flour and bread. However, milk, vegetables and fruit contribute appreciable quantities to the diet.

Thiamine requirement is related to caloric intake, the minimal need being approximately 0.25 to 0.30 mg. per 1000 calories. The recommended allowance of this vita-min is 0.5 mg. per 1000 calories (Table 3). This large factor of safety seems desirable since bodily stores of thiamine are not large and may be exhausted rapidly in diseases associated with elevated metabolism and, perhaps, in other stress situations.

Thiamine functions in the body as a coenzyme, cocarboxylase, which is thiamine pyrophosphate and possibly also as a coenzyme in combination with lipoic acid, lipothiamide. Thiamine coenzymes are important in the decarboxylation of a-keto acids such as pyruvic acid. Sub-stances formed include acetic acid, acetyl phosphate and acetyl coenzyme A, the last being of great importance as it feeds into the tricarboxylic acid cycle to provide energy. In thiamine deficiency, pyruvate accumulates in the blood and tissues and there is a change in the lactate-pyruvate ratio. These findings are useful in the diagnosis of deficiency.

Thiamine Deficiency

The outstanding clinical findings in advanced thiamine deficiency are peripheral neuritis (dry beriberi) and heart disease with edema (wet beriberi). The diagnosis of thiamine deficiency is not easy, however, particularly in early stages since many findings are nonspecific and common to other pathologic states. In experimentally induced deficiency, early findings include anorexia, fatigability, apathy, epigastric pain, nausea and vomiting, and psychic and emotional disturbances such as irritability, moodiness, vague fears and depression (84). Daum and associates (84b) reported that the most sensitive physiologic indices of an inadequate supply of thiamine were decreases in maximum work output and in mechanical efficiency.

Early signs of polyneuritis are burning of the soles of the feet and numbness and tingling of the feet and legs. The first indication of heart disease may be abnormalities in the electrocardiogram. As polyneuritis becomes more severe, hyperesthesia and, later, an-. algesia develops beginning distally in the toes and progressing upward. Shooting pains in the legs, muscle cramps, tenderness of the calves, weakness, a decrease or absence of the Achilles and patellar reflexes and muscle atrophy may be observed. A test for neuritis which is widely used in the Orient is inability to rise from the squatting position. Complete flaccid paralysis with foot drop occurs in advanced deficiency. Changes in the upper extremity are rarely observed until involvement of the lower extremity has become severe. Edema may be present even in the absence of heart failure, the explanation for which is unknown.

The peripheral neuritis of chronic alcoholism is often due to thiamine deficiency. It is explicable by the poor dietary intake of thiamine and not by the ingestion of alcohol which actually requires less thiamine for utilization than does glucose. Neuritis in subjects with diabetes is only rarely due to thiamine deficiency. In some subjects with cirrhosis of the liver, peripheral neuritis improves following thiamine administration.

In beriberi heart disease, palpitation, precordial pain and dyspnea on exertion may be noted and cyanosis is common. Bradycardia at rest with tachycardia on exertion is seen early; subsequently, tachycardia may be persistent. The pulse pressure is wide, with a decrease in the diastolic pressure and occasionally a slight increase in systolic pressure. There is enlargement of both the right and left sides of the heart, the former predominating. Systolic murmurs and, rarely, diastolic murmurs may be heard over any of the valve areas. Gallop rhythm and embryocardia are common. Precordial and epigastric pulsations are observed frequently; the neck veins are dilated and may pulsate. The liver is enlarged and pulsations may be observed here as well. Edema is often massive and there may be transudation into serious cavities. Oliguria is a characteristic finding.

Roentgenographic examination of the heart shows an increase in the transverse diameter and, at times, enlargement of the pulmonary conus. Electrocardiographic abnormalities include lowering of QRS complexes, flattening of the T-waves, prolongation of the Q-T interval and deviations of the S-T segment. Occasionally, premature contractions, axis deviation or abnormalities of the P waves may be noted. The cardiac failure is of the high output type, circulation time being normal or decreased. Venous pressure is elevated. In severe cardiac beriberi, acute peripheral circulatory collapse and sudden death may occur.

The diagnosis of thiamine-deficiency heart disease is dependent on dietary history, elimination of other etiologic factors, the presence of a high output type of cardiac failure, coexistent peripheral neuritis and response to therapy with thiamine. Digitalis is of little value in the treatment of beriberi heart disease. On the other hand, administration of thiamine is followed by diuresis and gradual reversal of pathologic changes, the heart size and electrocardiographic findings returning to normal.

Infantile beriberi occurs in breast-fed infants of mothers who have thiamine deficiency. It has been observed rarely in the United States and has been studied largely in Japan and other Far Eastern countries (85). The earliest and most important symptoms are anorexia and vomiting. Urine becomes scant, the pulse and respiration labile and rapid. Cranial nerve involvement is common, particularly hoarseness due to vocal cord paralysis and ptosis of the eyelid. The child may whine in a plaintive manner and the “beriberi cry” is said to be characteristic. Diagnosis is made when acute symptoms supervene such as paroxysms of pain associated with rigidity of the body but not true convulsions. Cyanosis, engorgement of the neck veins and a small rapid pulse are frequent findings. Death often occurs within twelve to twenty-four hours. A less common chronic form of the disease has been de-scribed which is characterized by obstinate constipation, vomiting unrelated to meals, restlessness at night, enlargement of the heart, pallor and weakness.

Several laboratory tests have been developed which are useful in the diagnosis of thiamine deficiency (17). The urinary excretion of thiamine is linearly related to the intake except at low levels, although there is marked individual variation. Measurement of thiamine excretion in 24 hours is useful in reflecting dietary supply. In order to evaluate the extent of depletion of tissue stores, a test dose of thiamine may be given orally or intramuscularly and the excretion in the urine measured for a period of time thereafter. Well nourished subjects who are given 1.0 mg. of thiamine intramuscularly excrete 100-200 ug in the subsequent four hours. An excretion of less than 50 g with this test is usually considered evidence of deficiency.

In nutrition surveys, determination of excretion of thiamine in random specimens of urine in relation to excretion of creatinine may be used for an approximate estimate of the adequacy of thiamine nutrition.

Estimation of the concentration of thiamine in blood does not appear to be of much value in appraising nutritional status of individuals although it may reflect, to an extent, the intake of population groups (86). The concentration of pyruvic acid in blood rises as thiamine deficiency becomes evident but cannot be used as a nutritional index since other factors, such as activity and ingestion of glucose, influence blood levels of pyruvic acid. The ratio of lactic acid to pyruvic acid in blood was found by Stotz and Bessey (87) to be useful in determining thiamine adequacy. Horwitt (88) has proposed determination of a “carbohydrate index” for detecting early thiamine deficiency. In this test, glucose, lactic acid and pyruvic acid are measured in blood one hour after giving 1.8 gm. of glucose per kilogram body weight and 5 minutes after a standard exercise test.

cardiac index, L lactic acid, P pyruvic acid and G glucose. An index of more than 15 suggests thiamine deficiency.

Thiamine deficiency appears to be related to several syndromes other than peripheral neuritis and heart disease. A type of optic or retrobulbar neuritis, associated with paralysis of extra-ocular muscles, occurred in concentration camps in World War II and appeared to be due, at least in part, to thiamine deficiency. Wernicke’s encephalopathy, characterized by ophthalmoplegia, nystagmus, ataxia and mental disturbances is a syndrome due to deficiency of thiamine (89). Thiamine, and other vitamins of the B complex, have proved valuable in the treatment of delirium tremens and other acute alcoholic psychoses. The susceptibility of the nervous system to thiamine deficiency may be explained by its dependence on glucose metabolism.

Intolerance to large doses of thiamine has been reported and is presumably due to simple chemical toxicity, principally through the formation of excessive amounts of acetylcholine and histamine.