554 THE TOCOPHEROLS 



ing to Darby et al.,^""^ on the basis of differences in intestinal absorption or 

 differences in lipid-carrying power of the blood. 



The effectiveness of intestinal absorption of vitamin E has been meas- 

 ured by the tocopherol "absorption curve" (also termed "tolerance curve," 

 "tolerance test," "blood persistence curve"). Subjects are given a single, 

 large, oral dose of tocopherol (usually 5 to 20 mg. of a-tocopherol per kilo- 

 gram of body weight) and blood samples are taken at 0, 3, 6, 9, 12, and 

 24 hours. The curve obtained by plotting the tocopherol values, or the 

 planimeter measurement of the area under the curve, provides a basis for 

 comparing individual responses. Low response curves have been reported 

 in some, but not all, cases of liver disease,^'"' • ^"^ in primary fibrositis,-"* and 

 in sprue;^^^' ^^^- ^"^ low responses have been observed in cases of fibrocystic 

 disease of the pancreas, diarrhea and cirrhosis in infants, and in children 

 with celiac syndrome and lupus erythematosus, and rather high responses 

 in metabolic disorders with associated hypercholesteremia.^^^ 



Low response curves may not necessarily reflect impaired intestinal ab- 

 sorption. The fate of tocopherol, once it has passed the intestinal barrier, 

 may be influenced by inadequacy of a lipid or protein "carrier" to which 

 it may be bound either for purposes of transport or for functional activity^"^ 

 or by other biochemical alterations of the blood or tissues. Klatskin and 

 Molander,^^^ who have studied the combined picture of absorption and 

 fecal excretion in normal, convalescent, and cirrhotic individuals, feel that 

 the low plasma tocopherol level in cirrhotics is "more closely related to 

 tissue depletion than to an impairment of absorption or utilization." Their 

 observation that cirrhotics excrete a considerably smaller fraction of ad- 

 ministered tocopherol than do healthy adults suggests also the possibility 

 that in patients with impaired hepatic functions much less tocopherol is 

 re-excreted via the biliary tract. ^^^ Although bile from patients with opera- 

 tive biliary fistulas has about the same tocopherol content as blood,^^^- ^"^ 

 it is not known whether this represents a true excretion product or a phase 

 in an enterohepatic circulation of tocopherol. 



From what has been said, it appears that tendencies for plasma tocoph- 

 erol to reach different levels in a variety of diseases may reflect previous 

 dietary intake, effectiveness of absorption and excretion, state of tissue de- 

 pletion, or biochemical changes in the blood which influence its carrying 

 capacity for tocopherol. Low levels observed in diseases where a significant 

 and prolonged impairment of fat absorption is indicated may sometimes 

 reflect a low vitamin E status of the body as a whole, although they may 

 rarely represent degrees of depletion commensurate ^\dth typical biochemi- 

 cal or histopathologic manifestations of avitaminosis E. 



^M C. L. Steinl)erK, Med. Clin. N. Amer. 30, 221 (1946). 



206 K. C. D. Hickman and V. L. Harris, Advances in Enzymnl. 6, 409 (1946). 



