Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women
| Status: | Recruiting |
|---|---|
| Conditions: | Healthy Studies, Obesity Weight Loss, Diabetes |
| Therapuetic Areas: | Endocrinology, Other |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 4/6/2019 |
| Start Date: | March 11, 2009 |
| End Date: | December 31, 2019 |
| Contact: | Sebastian J Padayatty, M.D. |
| Email: | sebastianp@intra.niddk.nih.gov |
| Phone: | (301) 496-1069 |
Vitamin E Pharmacokinetics and Biomarkers in Women
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.
- 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.
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 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 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 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 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.
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 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 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 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 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.
- 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
- Nonobese (BMI less than or equal to 29.9) 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,
hormonal contraceptives and medications taken only on an as-needed basis).
- 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, hormonal contraceptives and
medications taken only on an as-needed basis).
- 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, to soy or egg, milk protein (casein), or wheat/gluten
- 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 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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