Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

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.

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Conditions

• Diabetes
• Fatty Liver
• Obesity
• Healthy Volunteers

Interventions

DRUG

Alpha tocopherol

intravenous deuterated vitamin E at doses of 2mg, 5mg, 7.5mg, 10mg and 30mg.

OTHER

Vitamin E

Deuterated vitamin E, oral and intravenous, at doses of 2mg, 5mg, 7.5mg, 10mg and 30mg.

OTHER

Vitamin C

Oral vitamin C, one gram daily.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  lead NIH

Principal Investigators

• Mark A Levine, M.D. · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Design

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-10-10

Primary Completion

2016-10-21

Completion

2022-05-03

FDA Drug

Yes

Countries

• United States

Study Locations