The significance of the plasma tocopherol concentration and of tocopherol tolerance tests in liver disease

Important relationships between vitamin E metabolism and the state of the liver have been recognized in experimental animals, and there is evidence to suggest that alterations in tocopherol metabolism may occur in humans with liver disease. Diversion of bile from the intestinal tract by chronic biliary fistula produces the typical muscu-lar dystrophy and testicular atrophy of vitamin E deficiency in dogs maintained on normal diets (1). Presumably these effects are due to faulty absorp-tion of the vitamin, since feeding bile results in improvement. Similar observations have been made in the rat (2). Massive necrosis of the liver, produced in rats by diets low in cystine and high in cod liver oil, or containing alkali-treated casein as the sole source of protein, can be prevented by tocopherol ad-ministration (37). The mechanism of this pro-tective action is not known, but it does not appear to be related to the usual vitamin E activity of tocopherol, since the protective dose is many times that required to prevent muscular dystrophy and testicular atrophy (4). Gy6rgy has sug-gested that tocopherol may protect the liver by neutralizing endogenous hepatotoxins which are normally detoxified by methionine and cystine (4). In this connection it is of interest that to-copherol also protects rats against carbon tetra-chloride poisoning (8), and recent work by Hove (9) suggests that the toxic action of carbon tetra-chloride on the liver and other tissues may be due to an induced vitamin ' E deficiency. Tocopherol may also have a bearing on hepatic function in connection with its recognized influence on pro-tein (10, 11), fat (7, 12, 13), carbohydrate (14) and vitamin A (15, 16) metabolism