(OR18-07-23) Effects of Food and Fat on Plasma Vitamin E Over 24 Hours

Objectives: From studies of people with cholestatic liver disease or cystic fibrosis, fat is needed for α-tocopherol (α-T) absorption, but effects of fat and food ingestion on α-T absorption over time are not well understood. Here, we studied their roles on plasma α-T during the first 24h after α-T ingestion.

Methods: We analyzed α-T (RRR α-T) early pharmacokinetics (pk) using dual deuterium (d)-labeled α-T, given simultaneously as oral and intravenous (IV) doses to 10 healthy women. At T0 participants received 30 mg of IV d₆ α-T in a lipid emulsion resembling chylomicrons and 30 mg oral d₃ α-T in oil. Oral α-T was administered with a liquid meal containing either 40% or 0% fat. After dosing, participants had either controlled 30% fat meals (40% and 0% fat groups) or fasted for 12h (0% fat-12h fast group) followed by controlled 30% fat meals. Blood was drawn regularly; plasma d₃- α-T was measured by LC/MS/MS.

Results: Area under the curve (AUC) of plasma d₃ α-T concentrations over the first 4h (AUC_4h) was lower in the 0% fat group compared to the 40% group (1.7±0.7 vs 0.8±0.4 µM, mean±SEM, n=9, p< 0.05). Following 30% fat meals at 4 and 8 h, α-T AUC at 12h (AUC_12h) was similar in the 0% vs 40% fat groups (29.6±2.7 vs 28.1±2.7 µM, , n=9, p=0.33). Similarly, plasma d3-α-T concentrations at 12h (C α-T_12h) in the 0% vs 40% fat groups were similar (4.6±0.5 vs 3.7±0.4 µM, n=9, p=0.4). However, at 24h, AUC2_4h of the 0% fat group was higher compared to the 40% fat group (79.8±8.1 vs 69±5.7µM, n=9, p< 0.01). The AUC of the 0% fat 12h-fast group up to 24h was lower compared to the 0%fat (AUC_24h, 47.9±3.6 vs 78.9±9.3 µM, n=7, p< 0.05). Nonetheless, the C α-T24h of the 0% fat-12h-fast group was similar to the 0% fat group (4.1±0.3 vs 4.7±0.5, p=0.2).

Conclusions: Taken together, the findings show the importance of food intake following α-T ingestion rather than solely meal fat contents. Surprisingly, the absence of fat during acute α-T consumption did not increase α-T fecal excretion, as α-T AUC over 24h was actually increased after subsequent meals. Fasting after α-tocopherol did affect AUC over 24h, but after meal consumption, plasma d3 α-T concentrations were similar in all groups. These data suggest that α-T might be transiently stored in enterocytes with fasting until a meal with fat was consumed, with subsequent α-T secretion into lipoproteins.

Funding Sources: Office of dietary supplements (ODS), NIH, NIDDK