542 THE TOCOPHEROLS 



controversial literature regarding the therapeutic efficacy of vitamin E 

 (a-tocopherol) in a variety of clinical disorders which often have little in 

 common with the deficiency syndrome in lower animals and which are not 

 associated with any known inadequacy of vitamin E in the diet or in body 

 tissues. If tocopherol actually does exert a V)eneficial effect in such disorders, 

 the high dosage levels reported as necessary suggest a true pharmacologic 

 action on particular tissues or local regions of the body, perhaps through 

 some influence upon deranged metabolic processes at the affected site. 



The distribution of vitamin E in various tissues and organs of man, at 

 a concentration quite similar to that in lower mammals, implies that it 

 serves some useful purpose. Depletion of body stores of vitamin E in lower 

 animals produces a varietj^ of symptoms and histopathologic changes which 

 sviggest that vitamin E functions as an important intracellular antioxidant; 

 whether it has other metabolic functions remains to be established. Regard- 

 less of how it participates in the metabolic economy of the animal organism, 

 it is a logical assumption that it functions in like manner in metabolic 

 processes of man, and that certain of the symptoms and lesions character- 

 izing the deficiency state in animals would also occur in man, provided 

 that comparable dietary conditions prevailed for a sufficiently long period 

 of time. On the basis of animal experimentation, where we have some notion 

 of the relations between previous tissue storage and rate of metabolic utili- 

 zation (or depletion) of tocopherol as a function of time, the possibility 

 that adult man ever reaches a state of uncomplicated avitaminosis E seems 

 rather remote. However, during early infancy, before tissue storage becomes 

 an important factor, there is real possibilit}^ of tocopherol inadequacy, as 

 will be discussed later. 



Deficiency states are of two general types: natural deficiency, due to 

 inadequate intake of a nutrient over prolonged periods of time which, in 

 the case of fat-soluble vitamins, are measured in terms of years, if previous 

 intake and body storage have been reasonably normal; and "conditioned" 

 deficiency, arising through factors which chronically diminish the absorp- 

 tion or storage or increase the rate of metabolic utilization of the vitamin. 

 Deficiency of a fat-soluble vitamin rarely appears as a true clinical syn- 

 drome in adult man; however, states of suboptimal nutrition with respect 

 to such vitamins are recognized, although they are usually complicated 

 by other dietary inadequacies. To establish whether suboptimal or marked 

 deficiency of vitamin E occurs in man there must be accjuisition of many 

 data on the vitamin E status of normal individuals and of others whose 

 status might be considered suboptimal on the basis of dietary habits or 

 organic disease. Such data must relate primarily to four major aspects of 

 vitamin E nutriture: (I) the dietary intake over a period of years, (2) the 

 extent of intestinal absorption and excretion, (3) capacity for tissue storage 



