Plasma Lipids-dependent Vitamin E Metabolism During Dynamic Hyperlipidemia

Summary

Study Description: A controlled interventional study of effects of postprandial hypertriglyceridemia from three consecutive high-fat vitamin E-stripped meals on the dynamics of plasma vitamin E concentrations in subjects with baseline normo- and hyperlipidemia, to explore the concept of vitamin E sequestration by fats in plasma. Objectives: Primary Objective: Compare effects of postprandial hypertriglyceridemia (PHTG) on plasma/lipoprotein vitamin E dynamics in subjects between baseline normo- and hyperlipidemia. Secondary Objectives: Compare effects of postprandial hypertriglyceridemia (PHTG) on other fat-soluble vitamins (gamma-tocopherol, phylloquinone \[K1\]; menaquinone \[K2\]; 25-OH vitamin D; retinol \[A\]) and related vitamers (beta-carotene, lycopene lutein/zeaxanthin) between subjects with baseline normo- and hyperlipidemia. Tertiary/Exploratory Objectives: 1. Compare effects of individual high-fat meals on the dynamics of vitamin E, gamma-tocopherol, phylloquinone \[K1\], menaquinone \[K2\], 25-OH vitamin D, retinol \[A\], and other carotenoids between subjects with baseline normo- and hyperlipidemia. 2. Compare effects of postprandial hypertriglyceridemia (PHTG) and resultant vitamin E dynamics on: red blood cell (RBC) membrane deformability, fluidity, and oxygen exchange capacity (p50); RBC vitamin E, plasma vitamin C, plasma dehydroascorbic acid; fasting glucose and insulin; oxidized LDL, coenzyme Q10, and plasma adipokine profile between subjects with baseline normo- and hyperlipidemia; 3. Explore effects of postprandial hypertriglyceridemia on small RNAs including microRNAs, tRNAs, and PIWI-interacting RNAs. 4. Explore the influence of genetic variance on the metabolism of vitamin E and other fat-soluble vitamins and related vitamers in subjects with baseline normo- and hyperlipidemia. Endpoints: Primary Endpoint: AUC (Area Under the Curve) of vitamin E plasma from hour 1 to hour 23, by cohort. Secondary Endpoints: AUC of gamma-tocopherol, phylloquinone \[K1\], menaquinone \[K2\], 25-OH vitamin D and retinol \[A\] from hour 1 to hour 23, by cohort. Tertiary/Exploratory Endpoints: 1. Between the timepoints that reflect consuming 3 high-fat meals, AUC of vitamin E, gamma-tocopherol, phylloquinone \[K1\], menaquinone \[K2\], 25-OH vitamin D, retinol \[A\], and other carotenoids will be separately calculated for each participant. 2. Over the course of inpatient visit, RBC membrane deformability/fluidity, p50, RBC vitamin E, plasma vitamin C, plasma dehydroascorbic acid, blood glucose, insulin, c-peptide, oxidized LDL, coenzyme Q10 and serum adipokine profiles in each subject. 3. Over the course of inpatient visit, small RNAs including microRNAs, tRNAs, and PIWI-interacting RNAs. 4. Genetic variance (single nucleotide polymorphisms, SNPs)- dependent change in lipid-soluble vitamin dynamics over the course of inpatient visit in each subject.