Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase crossover design

Abstract

Background Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed. Objective We hypothesized that the dual-isotope technique, using 2 deuterium-labeled [intravenous (IV) d6- and oral d3-] α-T, would be effective in determining α-T fractional absorption. Further, defined liquid meal (DLM) fat or fasting would modulate α-T fractional absorption and lipoprotein transport. Methods A 3-phase cr ossover design was used. At 0 h, participants received IV d6-α-T and consumed d3-α-T with a 600-kcal DLM (40% or 0% fat) followed by controlled meals or by the 0% fat DLM, a 12-h fast, and then controlled meals. Blood samples and fecal samples were collected at intervals and analyzed by LC-MS. Pharmacokinetic parameters were calculated from plasma tracer concentrations and enrichments. Fractional absorption was calculated from d3- to d6-α-T areas under the curve, from a novel mathematical model, and from the balance method (oral d3-α-T minus fecal d3-α-T excreted). Results Estimated α-T fractional absorption during the 40% fat intervention was 55% ± 3% (mean ± SEM; n = 10), which was 9% less than during the 0% fat intervention (64% ± 3%, n = 10; P < 0.02). Fasting had no apparent effect (56% ± 3%, n = 7), except it slowed plasma oral d3-α-T appearance. Both balance data and model outcomes confirmed that the DLM fat did not potentiate d3-α-T absorption. During the IV emulsion clearance, HDL rapidly acquired d6-α-T (21 ± 2 nmol/L plasma per minute). During the first 8 h postdosing, triglyceride-rich lipoproteins (TRLs) were preferentially d3-α-T enriched relative to LDL or HDL, showing the TRL precursor role. Conclusions Quantitatively, α-T absorption is not limited by fat absence or by fasting. However, α-T leaves the intestine by a process that is prolonged during fasting and potentiated by eating, suggesting that α-T absorption is highly dependent on chylomicron assembly processes. This trial was registered at clinicaltrials.gov as NCT00862433.

Vitamin E sequestration by liver fat in humans

“…Taken together, our findings suggest that a body fat compartment, possibly intestinal fat, additionally modulates d 3 -α-tocopherol. The lack of statistical significance in d 3 -α-tocopherol bioavailability for healthy versus HS subjects may be explained by the variability in percentage body fat in our cohort (33%-57%) as well as effects of subsequent food ingestion on α-tocopherol trafficking (18,29). Future studies focusing on subjects with similar percentage of body fat, with and without HS, as well as controlled fasting and postprandial studies can address these possibilities.…”

“…To further evaluate the effect of body (i.e., intestinal) fat on d 3 -α-tocopherol physiology, we compared fractional absorption in HS versus healthy subjects, using the dual-isotope technique (18). Given the additional contribution that intestinal fat could have to modulate d 3 -α-tocopherol but not d 6 -α-tocopherol, we had anticipated a reduction in the d 3 /d 6 AUC ratio that would indicate reduced fractional absorption in the HS group.…”

“…All 10 healthy subjects participated in the 2-mg intervention, while 6 out of the 10 also participated in the 5-mg intervention. Half-lives for d 6 -and d 3 -α-tocopherol were less than 40 hours (18), and the washout period used was more than 1400 hours (>2 months; >30 × half-life) between interventions. All HS subjects received the 2-mg intervention.…”

Neuroprotective Potentials of Natural Vitamin E for Cerebral Small Vessel Disease

“…The general understanding of vitamin E absorption and trafficking is that orally administered vitamin E undergoes intestinal luminal processing, where it accumulates in lipid droplets, which then coalesce with nascent chylomicrons [32]. The vitamin E isoforms are not discriminated during the intestinal absorption or incorporation into chylomicrons.…”

“…Recently, Traber and colleagues, which lead as one of the most prolific research groups in vitamin E tocopherol, suggested novel approaches to assess α-tocopherol absorption and trafficking in order to establish human vitamin E requirements [32]. Their study observed that the absorption of α-tocopherol is not necessarily limited by the absence of fat or fasting and that the absorption is highly dependent on chylomicron assembly processes.…”