Vitamin E catabolism in women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase, nonrandomized crossover study

Background: Human vitamin E (alpha-tocopherol) catabolism is a mechanism for regulating whole-body alpha-tocopherol. Objectives: To determine the roles of the intestine and liver on alpha-tocopherol catabolism as affected by fat or fasting, 2 deuteriumlabeled (intravenous d(6)- and oral d(3)-) forms of alpha-tocopherol were used.Methods: Healthy women received intravenous d(6)-alpha-tocopherol and consumed d(3)-alpha-tocopherol with a 600-kcal defined liquid meal (DLM; 40% or 0% fat, n = 10) followed by controlled meals; or the 0% fat DLM (n = 7) followed by a 12-h fast (0% fat-fast), then controlled meals <= 72 h. The order of the 3-phase crossover design was not randomized and there was no blinding. Samples were analyzed by LC/MS to determine the alpha-tocopherol catabolites and alpha-carboxyethyl hydroxychromanol (alpha-CEHC) in urine, feces, and plasma that were catabolized from administered oral d3- and intravenous d(6)-alpha-tocopherols.Results: Urinary and plasma d(3)- and d(6)-alpha-CEHC concentrations varied differently with the interventions. Mean +/- SEM cumulative urinary d(6)-alpha-CEHC derived from the intravenous dose excreted over 72 h during the 40% fat (2.50 +/- 0.37 mu mol/g creatinine) and 0% fat (2.37 +/- 0.37 mu mol/g creatinine) interventions were similar, but a similar to 50% decrease was observed during the 0% fat-fast (1.05 +/- 0.39 mu mol/g creatinine) intervention (compared with 0% fat, P = 0.0005). Cumulative urinary d(3)-alpha-CEHC excretion was not significantly changed by any intervention. Total urinary and fecal excretion of catabolites accounted for <5% of each of the administered doses.Conclusions: Differential catabolism of the intravenous d(6)-atocopherol and oral d(3)-alpha-tocopherol doses shows both liver and intestine have roles in alpha-tocopherol catabolism. During the 40% fat intervention, >90% of urinary d(3)-alpha-CEHC excretion was estimated to be liver-derived, whereas during fasting <50% was from the liver with the remainder from the intestine, suggesting that there was increased intestinal alpha-tocopherol catabolism while d(3)-alpha-tocopherol was retained in the intestine in the absence of adequate fat/food for alpha-tocopherol absorption.