124 VITAMINS A AND CAROTENES 



to the injury of the nerve roots, the nerve fibers responded })y regeneration 

 and exhibited all the details described by Cajal in his classic studies of 

 degeneration and regeneration produced experimentally by crushing in- 

 juries. 



C. HYPERVITAMINOSIS A 

 1. Pathologic Physiology 



Vitamin A, when given in excessive amounts, causes severe untoward 

 results usually referred to as toxic. Instances of severe illness in adults, 

 prompt onset of headache, vomiting, diarrhea, and giddiness, and, about 

 a week later, desquamation of the skin and some loss of hair are on record 

 as the result of ingesting 300 to 500 g. of polar bear liver, the vitamin A 

 content of which may be as high as 18,000 I.U. per gram.^" 



Numerous instances (eighteen) of the deleterious effects of long-continued 

 administration of vitamin A in the form of fish liver oil concentrates have 

 been described in infants and young children, and but one instance in an 

 adult who received a vitamin A preparation free from vitamin D. Symp- 

 toms and signs common to all these patients were scaly dermatitis, patchy 

 loss of hair, fissured lips, irritability, anorexia, and skeletal pain. Nothing 

 is known of the biologic properties of vitamin A that will explain the physio- 

 logic disturbances responsible for the "toxic" effects of hypervitaminosis A. 



Laboratory studies of human patients to date have not given consistent 

 results. With but one exception the source of vitamin A has been fish liver 

 concentrates with a high vitamin D content, and therefore a new appraisal 

 is necessary of the reported instances of lowered serum proteins, elevated 

 alkaline phosphatase, and elevated serum lipids. On the whole, no definitive 

 information has been obtained from laboratory animals given excessive 

 amounts of vitamin A preparations free of vitamin D. There are no sig- 

 nificant changes in calcium, phosphorus, and phosphatase values, which is 

 not surprising because the skeletal effects to be described are those of 

 increased tempo of growth processes in which resportion of bone is balanced 

 by new bone formation. Cholesterol and phospholipid studies likewise have 

 not been informative.* 



Excessive doses of pure vitamin A in the rat increase the prothrombin 

 time^^ and, although rats synthesize vitamin K in their intestinal tracts, 

 will cause death from hemorrhage in about 90 % of rats on a vitamin K-free 

 diet.^- Discovery that excessive amounts of vitamin A cause prompt repara- 

 tive changes in the rachitic metaphysis of the rat"''^ led to metabolism studies 



30 K. Rodahl, Norsk Pularinslilult. Skrifter 92, (1949). 



31 S. E. Walker, E. Eylenburg, and T. Moore, Biochem. J. 41, 575 (1947). 



32 C. L. Maddock, S. B. Wolbach, and D. Jensen, Federation Proc. 7, 275 (1948). 



33 S. B. Wolbach and C. L. IVIaddock, Federation Proc. 8, 376 (1949). 



