Postprandial Vitamin E Plasma Enrichment and Second Meal Effect in Women with and without Metabolic Dysfunction-Associated Steatotic Liver Disease

Background The effect of meal fat sequence and excess body fat on post-prandial changes in vitamin E absorption is unclear. Objectives We investigated post-prandial changes in plasma vitamin E enrichment in response to (1) varied dietary fat sequences in healthy women and (2) excess body and liver fat in women with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Vitamin E (α-tocopherol, α-T) pharmacokinetics were assessed using deuterium (d)-labeled α-T administered orally (d 3 -α-T) and intravenously (d 6 -α-T). 13 healthy women received oral and IV α-T (30mg) with a liquid breakfast containing 40% or 0% fat, followed by 30% fat lunch and dinner at 4h and 8h, or a 12h fast (0% fat/fast). 6 women with MASLD and 10 normal weight controls received oral and IV α-T (2 mg) with similar meal sequence. Major outcomes were post-prandial plasma α-T %enrichment, Cmax, and AUCs at 4, 12, and 24h. Exploratory outcomes included the second meal effect (SME), defined as mean change in pre- vs post-2nd meal d 3 -α-T %enrichment at 4h and 12h respectively. Results At 4h oral d 3 -α-T %enrichment Cmax and AUC0-4h were not statistically different between 40% and 0%-fat groups. Following the 2nd meal at 4h, SME was 55% higher in the 0% group vs 40% group (15.8±1.1% vs 10.2±1.1%, p<0.009), resulting in greater Cmax and AUC in 0% group at 12h and 24h (p<0.04). Compared to the 0% group, the 0% fat/fast group showed reduced oral d 3 -α-T %enrichment, while no differences were seen with IV d 6 -α-T %enrichments. Compared with controls, the obese/MASLD cohort had 31% lower SME (0.87±0.1% vs 1.26±0.1%,p=0.047), resulting in reduced Cmax and AUC (p<0.04) at 24h. Conclusion The variation in the meal fat sequence (0%-to-30% vs 40%-to-30% fat) significantly enhanced SME and post-prandial d 3 -α-T %enrichment, while obesity/MASLD attenuated SME and post-prandial vitamin E %enrichment.