Thiamine Deficiency
In humans the condition known as beriberi results from thiamine deficiency. The condition ~ rare in the Western world because of food habits and food enrichment. Anorexia (loss of ppetite), weight loss, fatigue, and gastrointestinal upsets are noted. Later in the disease cardiac impairment is seen. The administration of the vitamin or foods rich in it is usually llowed by dramatic disappearance of symptoms. Most thiamine deficiency states in humans are complicated by deficiencies of other B vitamins. A book by Williams is informative in relation to beriberi. In 1957 Brozek reported the results of a comprehensive study from Keys' laboratory.
Psychological changes and biochemical data are presented in human thiamine deprivation. :be study consisted of four experimental periods:
(a) a month for the standardization and llection of control values;
(b) partial restriction of the vitamin for 168 days, with daily intakes in three groups of men of 0.61, 1.01, or 1.81 mg, and energy expenditure of about 3300 Cal;
(c) an acute thiamine deprivation period of 15 to 27 days on "thiamine-free" diet; and
(d) a -l..:amine supplementation period, 5 mg daily for 9 to 21 days. Oral administration of thiamine .~ as started for each man when the investigators considered that the deficiency had progressed as far as was safe. At this time nausea and vomiting were present, general weakness was ronounced, anorexia was extreme, and blood pyruvic acid levels were elevated.
Thiamine supplementation restored appetites and resulted in a dramatic change in attitude of the subjects. Performance tests on intelligence were not affected adversely within limits of :he experimental conditions. Neurasthenia (nervous exhaustion with many symptoms), emotional deterioration, impaired coordination, and lowering of the pressure-pain threshold all responded dramatically to thiamine administration. During the period of partial restriction, with the other B vitamins supplied in adequate amounts, the intake of 0.2 mg thiamine per 1000 Cal was at the borderline of deficiency. Elevated blood pyruvic acid, especially after glucose ingestion, has been observed in advanced thiamine deficiency by various workers. This undoubtedly results from the diminished supply of thiamine pyrophosphate, required as coenzyme in a-keto acid decarboxylation. Blood pyruvic acid or the pyruvic-lactic ratio, following glucose administration, has been oflimited value in studying thiamine status.
Blood thiamine or thiamine pyrophosphate levels may prove to be more informative. On high-carbohydrate diet supplying only 0.11 to 0.18 mg of thiamine per day, eight growing men developed clinical thiamine-deficiency symptoms in 9 to 27 days. General malaise, headache, nausea, constipation, vomiting and generalized muscle ache were common symptoms. The urinary excretion of thiamine decreased to a point that it was undetectable by the eighteenth day. Transketolase activity of red cells also dropped as deficiency developed and increased during the repletion period.
The excretion of metabolites of the vitamin, the thiazole and pyrimidine moieties, increased above levels found when the vitamin intake was normal and was reduced after adding thiamine to the diet. The authors suggest that there is a body store of thiamine which can be used during insufficient intake. The proceedings of a conference on beriberi held in 1958 contain a great deal of information on the clinical, nutritional, and biochemical problems in this disease. Since the advent of synthetic diets capable of supporting good growth and reproduction in laboratory animals, the development of a thiamine deficiency has been followed closely from both the biochemical and neurological standpoint in a number of species. In pigeons on a severe thiamine deficiency early symptoms are loss of appetite, lassitude, and weight loss.
Paralysis and head retraction (opisthotonus) are followed by 'death in a matter of a few weeks. If the deficiency is less severe, the birds survive for long periods and develop many of the symptoms seen in humans. Rats lose their appetite after a short period on a deficient diet. If the diet contains small amounts of the vitamin, rather typical symptoms may ensue. A spasticity and stiffness of the hind legs is seen, and later the limbs may become paralyzed.· It is obvious that a large part of the symptomatology of thiamine deficiency is related to pathological changes in specific parts of the nervous system. It is impractical to discuss here detailed findings of experimental workers in this specialized field.
Rinehart, Greenberg, and Friedman made careful studies of the lesions of the nervous system of rhesus monkeys subjected to one or more periods of thiamine depletion. Outstanding were the lesions in the nuclear structures of the central nervous system. In the animals depleted two or more times the lesions were more severe and extensive. Certain myocardial changes were observed, and according to some investigators, they are similar to those of the human heart in beriberi. North and Sinclair, on the other hand, subjected rats to three to six successive periods of acute thiamine deficiency over an average survival period of 127 days. Other rats were subjected to a combined thiamine and pantothenic acid deficiency. In both studies there 'Yas no evidence of degenerative changes in the distal segments of the sciatic and posterior tibial nerves, in the lumbar dorsal-root ganglia, or in the lumbar cord.
