564 THE TOCOPHEROLS 



Be, and essential fatty acids), and the toxic or otherwise detrimental effects 

 of such substances as alloxan, silver nitrate, o-cresyl phosphate and carbon 

 tetrachloride. In many instances, additional tocopherol means the difference 

 between death of the animal or continued survi^'al in good health. Pre- 

 sumably these beneficial effects relate to the antioxidant functions of to- 

 copherol, operating sometimes in the intestinal tract and at other times at 

 sites where local tissue injury would otherwise occur. Furthermore, tocoph- 

 erol can enhance the curative action of critical amounts of vitamin A 

 and essentially fatty acids, possibly by protecting them up to the point 

 of intestinal absorption. 



D. THERAPEUTIC USE 



There exists an extensive but rather controversial literature dealing with 

 the therapeutic efficacy of tocopherol in a wide variety of disease states, 

 many of which have little or nothing in common with experimentally in- 

 duced manifestations of vitamin E deficiency and are not associated with 

 any evidence of a significant inadequacy of tocopherol in the patient. Fur- 

 thermore, the effects reported are usually obtained only with relatively 

 high doses over a period of many weeks or months. As expressed by Hick- 

 man^ in an interesting review of this subject, "The discrepancy between 

 the few milligrams a day that suffice to maintain the majority of people 

 in health and the hundreds of milligrams being used clinically gives cause 

 for serious thought. . . . Only time and continued study can resolve the 

 dosage paradox with this ^^tamin . . .." 



Those who report benefit in certain clinical disorders usually stress the 

 importance of sustained, high daily dosage, generally amounting to between 

 200 and 600 mg. of a-tocopherol; this represents about twelve to thirty-six 

 times the average daily intake from diet. There is also the common obser- 

 vation that only in a certain proportion of patients suffering from a spe- 

 cified disorder is there a significant remission of symptoms, the remainder 

 showing no benefit other than perhaps an improved sense of well-being and 

 physical \agor. Observations such as these suggest that in certain instances 

 high tocopherol dosage may, through its capacity to regulate and enhance 

 intracellular oxidations, greatly improAC states of lowered or otherwise 

 altered metabolism at various localized sites in tissues and organs of the 

 body. The location of the latter, and their relation to the etiology and se- 

 quelae of the disease entity under consideiation would, of course, vary 

 widely from patient to patient. In other words, as in its i)rotective effect 

 in enabling the experimental animal to resist and overcome the effects of a 

 varietj' of metabolic stresses, \ho clinical value of tocopherol may lie in 

 large part in its ability to counteract localized metal)oli(' and toxic stresses 



5K. C. D. Hickman, Record Chem. Progr. 9, 104 (194S). 



I 



