Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

Phase 1

Completed

• Conditions: Diabetes; Fatty Liver; Obesity; Healthy Volunteers
• Interventions: Drug: Alpha tocopherol; Other: Vitamin E; Other: Vitamin C

• Registration Number: NCT00862433
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary

Background:

* Vitamin E is an antioxidant that reduces the damaging effects of oxygen in the body. Most American men (90%) and women (96%) do not get enough vitamin E from their diets; however, the amount of vitamin E needed by the body has been studied only in men, not women. In addition, it is unknown whether another antioxidant, vitamin C, helps vitamin E in protecting the body. Because vitamin E is a fat-soluble vitamin, how much body fat a person has could affect the amount of vitamin E needed for protection.

Objectives: This study has three arms to examine vitamin E requirements:

* To determine the amount of fat required to get the best vitamin E absorption from a meal.

* To determine the amount (i.e., best dose) of vitamin E that must be consumed before it can be measured in the blood.

* To examine how vitamin E and vitamin C work together in the body, in conjunction with diet and vitamin supplements.

Eligibility:

* Arms 1 and 2: Women between the ages of 18 and 40 years who have a normal weight and body mass index (BMI) of 27 or less.

* Arm 3: Women between the ages of 18 and 40 years who have a normal weight (BMI 27), who are overweight (BMI \> 27), or who are overweight (BMI \> 27) and have non insulin-dependent diabetes.

Design:

* Arm 1: Five studies, each lasting 1 month with 1 month off between studies (total study = 10 months). Participants will take 500 1,000 mg of vitamin C twice daily for 2 weeks before admission to the clinical center for 1 week.

* Study 1: Participants will eat breakfast containing a known amount of fat, after which they will take a vitamin E pill as well as receive an IV injection of vitamin E. Other foods contain only negligible amounts of vitamin E. Blood and urine samples will measure levels of vitamin E and other substances.

* Studies 2 5: Outpatient visits will consist of the same tests as in Study 1; however, the amount of fat in the breakfast will range from 0% to 40% in random order. During one of the studies, an adipose tissue biopsy will be collected to determine how much vitamin E is in the tissues.

* Arm 2: Five studies, each lasting 1 month with 1 month off between studies (total study = 10 months). Preparation for Arm 2 is the same as in Arm 1. The proportion of fat, muscle, and water in the body will also be measured.

* Study 1: Participants will eat breakfast containing 30% fat, after which they will take a vitamin E pill as well as receive an IV injection of vitamin E. Conditions and procedures are the same as in Arm 1.

* Studies 2 5: Outpatient visits will consist of the same tests as in Study 1; however, the amount of vitamin E in the breakfast will range from 2 to 30 mg in random order.

* Arm 3: Outpatient (2 to 6 weeks) and inpatient studies (4 to 6 weeks).

* Outpatient study: Participants will take 500 1,000 mg of vitamin C daily and provide blood and urine samples, as well as an adipose tissue sample.

* Inpatient studies: Two vitamin E inpatient studies. Before these begin, participants vitamin C blood levels will be reduced by means of a diet low in vitamin C. Blood tests will determine how quickly vitamin C leaves the body. Once the vitamin C level is reduced, the first vitamin E study will begin.

Study A: The procedure for this study is the same as in Arm 2, Study 1.

Study B: The procedure for this study is the same as in Study A, except that the participants blood vitamin C levels will be higher.

Detailed Description

Vitamin E (alpha-tocopherol) is essential for humans but determining human dietary requirements has proved difficult. The recommended dietary allowance (RDA) for vitamin E is not met by 96% of American women, without apparent harm. Because vitamin E is an antioxidant, optimum consumption of vitamin E may improve the health of obese women who experience high levels of inflammation and oxidative stress. We hypothesize that vitamin E functions as an antioxidant is related to its tissue stores, and that delivery to tissue stores can be calculated from plasma vitamin E turnover kinetics from slow release pools. We propose turnover kinetics as a new means to estimate vitamin E recommended dietary allowance. We will study vitamin E pharmacokinetics using dual stable-isotope labeled (deuterium) alpha-tocopherols administered orally and intravenously to healthy nonobese, overweight and overweight non-insulin requiring diabetic women. Blood samples will be collected at intervals and vitamin E measured by mass spectrometry. Because ascorbic acid (vitamin C) concentrations may alter alpha-tocopherol pharmacokinetics, subjects will be studied first at low and then high steady state plasma vitamin C concentrations. Before this main study, two preliminary trials will be performed. In preliminary trial 1, fat content for optimal absorption will be assessed because fat-content of a meal may alter vitamin E absorption. The fat content in preliminary trial 1 will be 0 - 40% of calories in the breakfast meal during which vitamin E will be administered. In preliminary trial 2, optimal fat content from preliminary trial 1 will be used, and the vitamin E dose will be varied. Vitamin E dose amount could non-specifically alter vitamin E kinetics. We will therefore determine the largest dose (2-30 mg) that does not non-specifically increase vitamin E turnover, with fat held constant. Additionally, we will measure vitamin E pharmacokinetics as a function of lipid peroxidation biomarkers to provide direct data that can be used to predict vitamin E requirements for women, and to set new recommendations for vitamin E intakes. We will explore new alpha-tocopherol functions, specifically whether gene transcription in human subjects is regulated by vitamin E status in relation to vitamin C status. Because vitamin E turnover may be affected by vitamin C concentrations, we will use a vitamin C depletion-repletion study design to investigate the relationship between vitamin C status and vitamin E turnover.

Study Timeline

• Study First Submitted: 2009-03-13
• Study First Submitted QC: 2009-03-13
• Study First Posted: 2009-03-16
• Study Start: 2014-10-10
• Primary Completion: 2016-10-21
• Study Completion: 2022-05-03
• Status Verified: 2025-01-02
• Last Update Submitted: 2025-01-03
• Last Update Posted: 2025-01-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 50

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Arm 1	Alpha tocopherol	Determine optimal fat content of meal for optimal absorption of vitamin E
Arm 1	Vitamin E	Determine optimal fat content of meal for optimal absorption of vitamin E
Arm 2	Alpha tocopherol	Determine optimal dose of vitamin E.
Arm 2	Vitamin E	Determine optimal dose of vitamin E.
Arm 3	Alpha tocopherol	Investigate the relationship between vitamin C status and vitamin E turnover
Arm 3	Vitamin E	Investigate the relationship between vitamin C status and vitamin E turnover
Arm 3	Vitamin C	Investigate the relationship between vitamin C status and vitamin E turnover
NAFLD sub-study	Alpha tocopherol	Investigate the relationship between fatty liver disease and vitamin E turnover.
NAFLD sub-study	Vitamin E	Investigate the relationship between fatty liver disease and vitamin E turnover.

Primary Outcome Measures

Name	Time	Method
Measure Vitamin E Kinetics	q min, hrly, daily	Fractional vitamin E absorption and rates of plasma vitamin E disappearance after a single dose of oral and intravenous vitamin E

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States