138 VITAMINS A AND CAROTENES 



merit. In the case of infants and young children, where prior storage of the 

 vitamin is more hmited, outright vitamin A deficiency is more common 

 but is not often a simple deficiency state. Much of what we know regarding 

 symptoms and pathologic changes in tissues resulting from vitamin A 

 deficiency in human beings is based upon clinical observations on infants 

 and young children. 



Uncomplicated vitamin A deficiency in laboratory animals leads to three 

 primary dysfunctions: (1) defective vision in dim light, due to needs for 

 vitamin A as a precursor of visual purple in rod cells of the retina; (2) 

 atrophy and keratinizing metaplasia of many epithelia of the body; and 

 (3) disturbances in the appositional growth and remodeling of bone. These 

 dysfunctions and lesions are most readily induced by deprivation of vitamin 

 A and carotene during early life and require much more prolonged periods 

 of depletion in older animals with appreciable body stores of the vitamins. 

 In fact, alterations of bone growth occur only in young, rapidly growing 

 animals and have been demonstrated only in laboratory animals. This 

 leaves for our consideration the visual dysfunctions, which are primarily 

 physiologic, and the epithelial alterations, which represent the major histo- 

 pathologic manifestations of the deficiency state. Before discussing the 

 nature of these phenomena in man, it may be pertinent to consider the 

 types and sources of evidence on which the clinical findings, and our ulti- 

 mate conclusions, are based. 



2. Deficiency in Human Volunteers 



One approach to an evaluation of the effects of vitamin A depletion in 

 man is the maintenance of human volunteers on a diet deficient in vitamin 

 A but otherwise adequate until the appearance of specific symptoms which 

 can be carefully studied and then shown to disappear following vitamin A 

 therapy. Even then, information regarding pathologic changes in tissues 

 is limited to material obtained through biopsy. Between the years 1937 

 and 1943 eight experiments of this type were reported, largely in an effort 

 to evaluate photometric measurements of dark dysadaptation (night blind- 

 ness) as a criterion of suboptimal intake of vitamin A. The depletion 

 periods varied from 1 to 73^ months. The results were far from conclusive, 

 and indicated the need for a more exacting investigation extending over a 

 much longer period. 



A study of this type was undertaken in 1942 at the Sorbey Research 

 Institute in Sheffield, England, because of need for more accurate data on 

 human requirements for vitamin A.^ Twenty-three conscientious objectors 



1 E. M. Hume and H. A. Krebs, Vitamin A Requirement of Human Adults; An 

 Experimental Study of Vitamin A Deprivation in Man (A Report of the Vitamin 

 A Sub-Committee of the Accessory Food Factors Committee), Med. Research 

 Council (Brit.) Spec. Kept. Ser. 264, (1949). 



