Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women
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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 |
- Dose concentration relationship
- Lipid oxidative products
| Estimated Enrollment: | 128 |
| Study Start Date: | March 2009 |
-
Dietary Supplement: Vitamin E
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. We will also study whether single nucleotide polymorphisms (SNPs) exist in relevant genes and account for inter-individual differences in vitamin E metabolism and pharmacokinetics. 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 |
- 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.
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 > 2), eye damage (proliferative retinopathy), diabetic neuropathy, coronary artery disease, or peripheral vascular disease
- Tobacco smoking
- Use of medications (other than oral hypoglycemic agents or aspirin)
- Alcohol or drug abuse
- Insulin treatment
- Pregnancy (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
- Oral contraceptives
- Patients on antihypertensive medication
- Patients on oral contraceptive medication
- Patients on insulin treatment
Contacts and Locations| Contact: Sebastian J Padayatty, M.D. | (301) 496-1069 | sebastianp@intra.niddk.nih.gov |
| Contact: Mark A Levine, M.D. | (301) 402-5588 | markl@intra.niddk.nih.gov |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Not yet 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 | |
| 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: | May 11, 2013 |
| 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:
|
Vitamin E Alpha-Tocopherol Tocopherols Tocotrienols Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases |
Ascorbic Acid Vitamins Antioxidants Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protective Agents Physiological Effects of Drugs Micronutrients Growth Substances |
ClinicalTrials.gov processed this record on June 17, 2013