Date of Award
Doctor of Philosophy
John T. Smith
Samuel R. Tipton, Frances A. Schofield, Jane R. Savage
(From the Introduction)
Several clinical workers in the later 1930's reported that vitamin E was of positive therapeutic value in the treatment of primary fibrositis. At that time a role for vitamin E in connective tissue metabolism was proposed. This role was never substantiated because of the failure of other groups to repeat the original work. It was subseqently realized that the original experiments were very poorly controlled and there was no real way of knowing whether or not the results obtained were due only to chance. Since that time the idea of a vitamin E, collagen relationship has been generally discredited.
In more recent years, knowledge has been expanded both in the areas of collagen biogenesis and the physiological role of vitamin E. Contained in this expanded knowledge are several isolated facts which -- indicate some role for vitamin E in collagen metabolism.
It has been found that the synthesis of the subunits of the triple-stranded collagen molecule proceeds by the same route as that of the soluble proteins. It was found by different groups that vitamin E deficiency results in an increase in desoxyribonucleic acid (DNA) in several tissues. It was also shown that there was an increase in the uptake of glycine by muscle tissue in avitaminosis E.
It is known that the synthesis of collagen in certain tissues is very sensitive to vitamin C deficiency. Avitaminotic C animals do not synthesize as much collagen as do their controls. The possibility of avitaminoic E animals exhibiting a secondary vitamin C deficiency was indicated by the finding that liver homogenates derived from vitamin E deficient rats did not convert glucuronic acid to ascorbic acid as readily as did those from their controls. The secondary vitamin C deficiency could result in a decreased collagen synthesis.
More recent advances in the knowledge of the mode of action of vitamin E have indicated that vitamin E deficiency results in a decrease in the rate of sulfate uptake by sulfomucopolysaccharides. Decreasing the amount of dietary sulfate causes an intensification of vitamin E related changes in mucopolysaccharide metabolism with a concurrent reduction in the amount of hexosamine present in cellular lipoproteins. It was shown that treatment of an animal with cortisone caused a failure of sulfomucopolysaccharides to be sulfated and also of mature collagen fibrils to be formed. Lathyrism, a condition which produces a failure in sulfomucopolysaccharide sulfation, also results in failure of collagen fibrils to mature. This raises the possibility that there may be a failure on the part of collagen in avitaminoic E animals to mature.
It appears from the aforegoing that avitaminosis E could either cause a qualitative or quantitative change in collagen metabolism and that the level of dietary inorganic sulfate may exert some influence.
It is the purpose of this study to determine if a relationship could be demonstrated between collagen and vitamin E.
Brown, Robert Glenn, "Some Aspects of Vitamin E and Collagen Relationships. " PhD diss., University of Tennessee, 1964.