536 THE TOCOPHEROLS 



(4) Influence of Variations in Diet. According to Dam,^"* exudative dia- 

 thesis is rare and encephalomalacia never occurs in chicks fed purified 

 E-deficient diets containing no added fats; furthermore, dietary unsatur- 

 rated fats accentuate both manifestations, and by varying the type and 

 proportion of fats and other components of the diet it is possible to produce 

 these two manifestations separately or concomitantly. Essentially the same 

 diet may give a very different incidence of the two symptoms in the hands 

 of different investigators.^"^ The presence of substances such as ascorbic 

 acid,^"^ xanthophyll,"" or redox substances of various types,"^ by virtue 

 of their capacity to replace tocopherol as an antioxidant in the gastrointesti- 

 nal tract or elsewhere, may confer considerable protection against the symp- 

 toms. Thus it appears that in addition to lack of vitamin E there is a delicate 

 balance of dietary factors which operate to determine the onset and severity 

 of the vascular dysfunctions and the anatomic site at which they occur. 

 In this connection reference may be made to the lymphoblastoma-like 

 growths observed by Adamstone"^ in the liver, the intestine, and other 

 visceral organs of the chick, sometimes leading to hemorrhage by invasion 

 of blood vessels, when cod liver oil or sardine oil, but not halibut liver oil, 

 was added to diets previously treated with ferric chloride to destroy traces 

 of vitamin E. On the other hand, additions of halibut liver oil led to an 

 anemia-like condition presumably resulting from extensive erythrophag- 

 ocytosis in the liver. ^^^ These findings have not been confirmed or satis- 

 factorily explained. 



b. Mammals 



(1) Hemorrhage. The vascular stasis and hemorrhage occurring in the 

 rat fetus, as described in an earlier section (p. 520), bears a certain resem- 

 blance to the vascular dysfunctions in chicks. So also do the interfascial, 

 subcutaneous, and thymic hemorrhages observed during the second month 

 of life in rats reared from birth on low-E diets high in total unsaturated 

 fatty acids of cod liver oil,^^'* and also the hemorrhages into cranial and 

 visceral cavities, lungs, and intestine ol)served by Elvehjem et al.^^^ in 

 puppies born of mothers fed mineralized milk diets low in vitamin E. As 

 in the chick studies just discussed, there are again the three factors to be 



i"9 L. Zacharias, P. Goldhaber, and V. E. Kinsey, J. Nutrition 42, 359 (1950). 

 "0 P. Goldhaber, L. Zacharias, and V. E. Kinsey, J. Nutrition 42, 453 (1950). 

 "1 H. Dam, I. Kruse, I. Prange, and E. Sondergaard, Acta Physiol. Scand. 22, 299 



(1951). 

 "2 F. B. Adamstone, Am. J. Cancer 28, 540 (1936); Arch. Pathol. 31, 717 (1941). 

 "» F. B. Adamstone, Arch. Pathol. 31, 613 (1941). 

 "* R. E. Rumery, Thesis, Histological and biochemical reactions of the immature 



rat to diets low in tocopherols (vitamin E) and high in unsaturated fatty acids. 



University of Rochester, 1952. 

 "6 C. A. Elvehjem, J. E. Gonce, Jr., and G. W. Newell, J. Pediat. 24, 436 (1944). 



