DIGESTION, ETC. OF FAT-SOLUBLE VITAMINS 321 



The mechanism by which tocopherols potentiate the action of vitamin 

 A is not entirely clear. Davies and Moore 334 concluded that the in- 

 creased storage of vitamin A accompanying the administration of toco- 

 pherol is probably to be ascribed to its antioxidant action. They state: 

 "The tocopherols are higher substituted members of the class of hydroxy- 

 aromatic substances, of which hydroquinone is a lower and less hydroxyl- 

 ated member. . . often used for stabilizing vitamin A in fats. The toco- 

 pherols may possibly have a similar action under physiological conditions." 

 Quackenbush and co-workers 339 believe that the protective action of 

 tocopherol toward carotene is due to its action "as an antioxidant in the 

 gastrointestinal tract rather than as a vitamin regulating some phase of 

 metabolism in the tissues." Finally, Hickman cl al. m arrived at the 

 same conclusion by showing that synergism is largely lost when vitamin A 

 and vitamin E are administered on alternate days. Moreover, it was 

 found that the co-vitamin E action was lost when the tocopherol was given 

 parenterally, while vitamin A was being introduced orally. This hy- 

 pothesis was further supported by the demonstration that antioxidants 

 other than tocopherol increased the growth-promoting action. 



One must conclude that the synergism of vitamin E toward vitamin A 

 also has another phase separate from the gastrointestinal effect. Hick- 

 man and collaborators 465 demonstrated this by showing that orally ad- 

 ministered tocopherols augmented the growth of rats receiving vitamin A 

 parenterally. This effect is ascribed to the protection of the vitamin A 

 circulating in the blood stream, since this "will be in danger of destruction 

 each time it passes through the vascular system connected with the in- 

 testinal wall." 342 The results of Lemley and her associates, 467 however, 

 are diametrically opposed to this concept of the intestinal action of the 

 tocopherols. In these latter tests, tocopherol exerted a synergism toward 

 vitamin A when the administration of vitamins A and E occurred on 

 alternate days; moreover, an aqueous solution of tocopherol, when ad- 

 ministered parenterally, was found to potentiate vitamin A action. More- 

 over, the prolongation of the depletion of young rats on a vitamin A-free 

 diet 465 must be a reflection of a vitamin E action taking place elsewhere 

 than in the gastrointestinal tract. 



a-Tocopherol, but not a-tocopherol acetate, has been shown to in- 

 crease the rate of gain-in-weight during the bioassay of vitamin A. 470 

 However, Miles et al. m reported that animals which received 1.5 mg. of 

 a-tocopherol daily did not gain as much as those receiving only 0.5 mg. 



470 M. C. Miles, E. M. Erickson, and H. A. Mattill, Proc. Son. Exptl. Biol. Med., 70, 

 1(32-105(1949). 



