Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00862433
First received: March 13, 2009
Last updated: August 22, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus Type II Non Insulin Dependent
Dietary Supplement: Vitamin E
Dietary Supplement: Vitamin C
Dietary Supplement: Lipid Oxidation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Vitamin E Pharmacokinetics and Biomarkers in Women

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Dose concentration relationship

Secondary Outcome Measures:
  • Lipid oxidative products

Estimated Enrollment: 128
Study Start Date: March 2009
Intervention Details:
    Dietary Supplement: Vitamin E
    N/A
    Dietary Supplement: Vitamin C
    N/A
    Dietary Supplement: Lipid Oxidation
    N/A
Detailed Description:

Vitamin E (a-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) a-tocopherols administered orally and intravenously to healthy lean (not overweight), 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 a-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 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 a-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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Subjects to be recruited for the study:

  • Healthy women
  • Ages 18 to 40 years old
  • Able to give informed consent
  • Blood pressure < 160/90 mm Hg
  • Not overweight (BMI < 27) without diabetes
  • Overweight (BMI greater than or equal to 27) without diabetes
  • Overweight (BMI greater than or equal to 27) with mild to moderate non-insulin dependent diabetes (Type 2 diabetes)

    • who are treated with diet alone or submaximal doses of oral hypoglycemic agents
    • whose fasting blood sugar is < 200mg/dl or HbA1C < 7.5
    • with no known target organ damage (End organ damage includes the following: proliferative retinopathy, serum creatinine < 1.8 m/dl, ischemic heart disease, congestive heart failure, peripheral vascular disease and peripheral neuropathy)
  • No regular medication other than aspirin (other than oral hypoglycemic agents and hormonal contraceptives).
  • Willingness to use effective contraceptive methods for the duration of the study

EXCLUSION CRITERIA:

Subjects with the following diseases or abnormalities will not be eligible for the study:

  • Digestive abnormalities, such as malabsorption or chronic diarrhea
  • Organ malfunction, including (but not limited to) liver disease, pulmonary disease, ischemic heart disease, heart failure, stroke, peripheral vascular disease
  • Hypertension (blood pressure > 160/90)
  • Anemia (hematocrit < 30)
  • Current or history of serious or chronic illness, including hyperlipidemia or hypercholesterolemia
  • Complications from diabetes such as kidney damage (renal insufficiency, serum creatinine > 1.8), eye damage (proliferative retinopathy), diabetic neuropathy, coronary artery disease, or peripheral vascular disease
  • Tobacco smoking
  • Use of medications (other than oral hypoglycemic agents and hormonal contraceptives).
  • Alcohol or drug abuse
  • Insulin treatment
  • Pregnancy or lactation (a urine pregnancy test will be performed on all women with reproductive age before each part of the study or monthly as necessary)
  • Positive HIV or hepatitis (b or c) screening tests
  • Food allergy, especially to soy or egg
  • Known coagulopathy
  • Unwillingness to use effective contraceptive methods such as barrier methods for the duration of the study.

Patients on antihypertensive medication are excluded even if blood pressure is well controlled because antihypertensive medication may affect vitamin E status, thus introducing a confounding variable. Whether antihypertensive medication interacts with vitamin E is not

known. Patients on oral contraceptive medication are excluded for similar reason that is to avoid the possible confounding effect of oral contraceptives on blood vitamin E. Patients on insulin treatment are excluded because Insulin treatment indicates a more severe form of diabetes than the mild to moderate type two diabetes that need only dietary treatment or treatment with submaximal doses of oral hypoglycemic agents for adequate blood sugar control. The effect of insulin administration on vitamin E is unknown, and is a confounding factor that will make data interpretation difficult.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00862433

Contacts
Contact: Sebastian J Padayatty, M.D. (301) 496-1069 sebastianp@intra.niddk.nih.gov
Contact: Mark A Levine, M.D. (301) 402-5588 markl@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Mark A Levine, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00862433     History of Changes
Other Study ID Numbers: 090097, 09-DK-0097
Study First Received: March 13, 2009
Last Updated: August 22, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Alpha-Tocopherol
Vitamin C
Antioxidant
Lipid Peroxidation
Oxidative Stress
Non-Insulin Requiring Diabetics
Health Volunteer
HV
Normal Weight
Overweight
Type 2 Diabetes

Additional relevant MeSH terms:
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamin E
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vitamins
Antioxidants
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 20, 2014