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

Human vitamin E (α-tocopherol) catabolism is a mechanism for regulating whole-body α-tocopherol. Objectives: To determine the roles of the intestine and liver on α-tocopherol catabolism as affected by fat or fasting, 2 deuterium-labeled (intravenous d6- and oral d3-) forms of α-tocopherol were used.

Differential catabolism of the intravenous d6-α-tocopherol and oral d3-α-tocopherol doses shows both liver and intestine have roles in α-tocopherol catabolism. During the 40% fat intervention, >90% of urinary d3-α-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 α-tocopherol catabolism while d3-α-tocopherol was retained in the intestine in the absence of adequate fat/food for α-tocopherol absorption.This trial was registered at clinicaltrials.gov as NCT00862433.

Healthy women received intravenous d6-α-tocopherol and consumed d3-α-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 α-tocopherol catabolites and α-carboxyethyl hydroxychromanol (α-CEHC) in urine, feces, and plasma that were catabolized from administered oral d3- and intravenous d6-α-tocopherols.

Urinary and plasma d3- and d6-α-CEHC concentrations varied differently with the interventions. Mean ± SEM cumulative urinary d6-α-CEHC derived from the intravenous dose excreted over 72 h during the 40% fat (2.50 ± 0.37 μmol/g creatinine) and 0% fat (2.37 ± 0.37 μmol/g creatinine) interventions were similar, but a ∼50% decrease was observed during the 0% fat-fast (1.05 ± 0.39 μmol/g creatinine) intervention (compared with 0% fat, P = 0.0005). Cumulative urinary d3-α-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 d6-α-tocopherol and oral d3-α-tocopherol doses shows both liver and intestine have roles in α-tocopherol catabolism. During the 40% fat intervention, >90% of urinary d3-α-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 α-tocopherol catabolism while d3-α-tocopherol was retained in the intestine in the absence of adequate fat/food for α-tocopherol absorption.This trial was registered at clinicaltrials.gov as NCT00862433.