Plasma Lipids-dependent Vitamin E Metabolism During Dynamic Hyperlipidemia

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lipid Metabolism Disorders
• Intervention / Treatment: Dietary supplement: High fat liquid shake

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robert D Shamburek, M.D.; Phone Number: (301) 496-3460; Email: bobs@mail.nih.gov
• Study Contact Backup: Name: Katherine C Roskom, R.N.; Phone Number: (301) 451-7094; Email: katherine.roskom@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center
      • Contact: NIH Clinical Center Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 (800) 411-1222; Email: ccopr@nih.gov
      • Contact: Robert Shamburek, M.D.; Phone Number: 301-496-3460; Email: bobs@mail.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA

Cohort 1

1. Males and females between the ages of 18 to 65
2. BMI 18.5 - 26.9 kg/m^2
3. Subject understands the protocol and provides written, informed consent in addition to a willingness to comply with specified follow-up instructions and evaluations
4. Normotensive, not on medications for hypertension
5. Not on glucose-lowering or lipid-lowing medications
6. Screening labs with baseline HbA1c <5.7%, baseline fasting triglyceride < 150 mg/dL and LDL <100 mg/dL
7. Liver fat <2%

Cohort 2

1. Males and females between the ages of 18 to 65
2. BMI >26 kg/m^2 and <36 kg/m^2
3. Subject understands the protocol and provides written, informed consent in addition to a willingness to comply with specified follow-up instructions and evaluations.
4. Screening labs with baseline HbA1c <= 7.5%, agree to be off or stop oral glucose-lowering medications (metformin), baseline fasting triglyceride < 500 mg/dL and LDL <190 mg/dL, agree to be off or stop oral lipid-lowing medications for 4-10 weeks prior to the inpatient visit.
5. Liver fat <2%

EXCLUSION CRITERIA

1. For women: pregnancy or currently breastfeeding
2. Subjects <18-year-old. This age group has a broad spectrum of hormonal profiles, due to development and puberty, which significantly increases the heterogenicity of the study subjects.
3. Subjects >65-year-old. This age group has significantly increased risk of cardiovascular diseases. To minimize the risk from temporarily suspending lipid- and glucose-lowering medications and stress from serial blood draws, we exclude these individuals.
4. Heavy alcohol user (males with >2 drinks per day or >14 drinks per week; female with >1 drinks per day or >7 drinks per week)
5. Current smoker, or former smoker who quit smoking <15 years ago
6. Subjects with weight changes greater than 20% baseline body weight over the past 3 months
7. Subjects with lactose intolerance unwilling to take lactase
8. Subjects with type 1 diabetes
9. Subjects with hemoglobin <11 g/dL or hematocrit <33%
10. Subjects with abnormal liver function test results
11. Subjects with liver fat >= 2% on abdominal MRI
12. Subjects with a history of pancreatitis, diabetes ketoacidosis, hyperosmolar hyperglycemic state, advanced atherosclerosis, cardiovascular diseases, kidney diseases, or liver diseases
13. Subjects with fat malabsorption including: history of gastrointestinal surgery, pancreatic insufficiency, inflammatory bowel disease, celiac disease, moderate-to-severe irritable bowel syndrome, and pathologic mutations impacting lipoprotein metabolism
14. Subjects on glucocorticoids >1 week (not including topical glucocorticoids)
15. Subjects with HIV
16. Subjects with uncontrolled psychiatric and/or behavioral disorders
17. Subjects taking diabetes medications other than metformin
18. Anticipated surgery during the study period
19. Subjects with severe medication-resistant claustrophobia
20. Subjects who are unwilling to stop medications, vitamins and/or dietary supplements that investigators have requested to be held
21. Subjects participating in any other clinical study without informing investigators
22. Any other reason or clinical condition that the investigators judge would interfere with study participation and/or be unsafe for a participant or staff member

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy subjects; Three consecutive high-fat vitamin E-stripped meals	Dietary supplement: High fat liquid shake; Three consecutive high-fat vitamin E-stripped meals
Experimental: Subjects with hyperlipidemia; Three consecutive high-fat vitamin E-stripped meals	Dietary supplement: High fat liquid shake; Three consecutive high-fat vitamin E-stripped meals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (Area Under the Curve) of vitamin E plasma from hour 1 to hour 23 by cohort.	Compare the effects of postprandial hypertriglyceridemia on plasma vitamin E dynamics in subjects between baseline normo- and hyperlipidemia.	From hour 1 to hour 23

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of gamma-tocopherol, phylloquinone [K1]; menaquinone [K2]; 25-OH vitamin D; retinol [A] from hour 1 to hour 23 by cohort.	Compare the effects of postprandial hypertriglyceridemia 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) in subjects between baseline normo- and hyperlipidemia.	From hour 1 to hour 23

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Robert D Shamburek, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Traber MG, Leonard SW, Ebenuwa I, Violet PC, Wang Y, Niyyati M, Padayatty S, Tu H, Courville A, Bernstein S, Choi J, Shamburek R, Smith S, Head B, Bobe G, Ramakrishnan R, Levine M. Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled alpha-tocopherols in a 3-phase crossover design. Am J Clin Nutr. 2019 Nov 1;110(5):1148-1167. doi: 10.1093/ajcn/nqz172.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: July 18, 2026
• First Submitted That Met QC Criteria: July 18, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 18, 2026
• Last Verified: July 15, 2026

More Information

Terms related to this study

• Keywords: Vitamin D; Vitamin E; Vitamin C; Postprandial; Hypertriglyceridemia; Vitamin K; gamma tocopherol; Fat-Soluble Vitamins; Sequestration; Fat meal
• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Nutritional and Metabolic Diseases; Hypertriglyceridemia; Lipid Metabolism Disorders
• Other Study ID Numbers: 10002623; 002623-H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying results reported in publications may be shared. Depending on the sensitivity of the dataset and risk of re-identification, data may be made available through either an open-access repository or a controlled-access repository, consistent with informed consent, institutional review, and applicable policies.@@@@@@
• IPD Sharing Time Frame: Beginning following de-identification and publication of the primary results, or other prespecified time point, and continuing for as long as the repository or access mechanism remains available.
• IPD Sharing Access Criteria: Access to de-identified individual participant data will be determined based on the sensitivity of the data and disclosure risk. Data appropriate for broad sharing may be deposited in an open-access repository. Data requiring additional protections may be made available through a controlled-access mechanism subject to review and any applicable agreements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No