Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

NCT00862433 | Completed Phase 1 FDA Drug

• 2 other identifiers: 09009709-DK-0097
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes; Fatty Liver; Obesity; Healthy Volunteers

Keywords

Non-Insulin Dependent Diabetes; Antioxidant; Lipid Peroxidation; Alpha-Tocopherol; Non-Alcoholic Fatty Liver Disease; Health Volunteer; HV; Normal Weight; Overweight; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Measure Vitamin E Kinetics

  Fractional vitamin E absorption and rates of plasma vitamin E disappearance after a single dose of oral and intravenous vitamin E

  q min, hrly, daily

Study Arms (4)

Arm 1

EXPERIMENTAL

Determine optimal fat content of meal for optimal absorption of vitamin E

Drug: Alpha tocopherol; Other: Vitamin E

Arm 2

EXPERIMENTAL

Determine optimal dose of vitamin E.

Drug: Alpha tocopherol; Other: Vitamin E

Arm 3

EXPERIMENTAL

Investigate the relationship between vitamin C status and vitamin E turnover

Drug: Alpha tocopherol; Other: Vitamin E; Other: Vitamin C

NAFLD sub-study

EXPERIMENTAL

Investigate the relationship between fatty liver disease and vitamin E turnover.

Drug: Alpha tocopherol; Other: Vitamin E

Interventions

Alpha tocopherol DRUG

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

Arm 1; Arm 2; Arm 3; NAFLD sub-study

Vitamin E OTHER

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

Arm 1; Arm 2; Arm 3; NAFLD sub-study

Vitamin C OTHER

Oral vitamin C, one gram daily.

Arm 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Traber MG, Ramakrishnan R, Kayden HJ. Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-alpha-tocopherol. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10005-8. doi: 10.1073/pnas.91.21.10005.

  PMID: 7937827 BACKGROUND

• Sowell J, Frei B, Stevens JF. Vitamin C conjugates of genotoxic lipid peroxidation products: structural characterization and detection in human plasma. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):17964-9. doi: 10.1073/pnas.0408433102. Epub 2004 Dec 17.

  PMID: 15608056 BACKGROUND

• Bruno RS, Ramakrishnan R, Montine TJ, Bray TM, Traber MG. alpha-Tocopherol disappearance is faster in cigarette smokers and is inversely related to their ascorbic acid status. Am J Clin Nutr. 2005 Jan;81(1):95-103. doi: 10.1093/ajcn/81.1.95.

  PMID: 15640466 BACKGROUND

• Traber MG, Leonard SW, Ebenuwa I, Violet PC, Niyyati M, Padayatty S, Smith S, Bobe G, Levine M. Vitamin E catabolism in women, as modulated by food and by fat, studied using 2 deuterium-labeled alpha-tocopherols in a 3-phase, nonrandomized crossover study. Am J Clin Nutr. 2021 Jan 4;113(1):92-103. doi: 10.1093/ajcn/nqaa298.

  PMID: 33184629 DERIVED

• Violet PC, Ebenuwa IC, Wang Y, Niyyati M, Padayatty SJ, Head B, Wilkins K, Chung S, Thakur V, Ulatowski L, Atkinson J, Ghelfi M, Smith S, Tu H, Bobe G, Liu CY, Herion DW, Shamburek RD, Manor D, Traber MG, Levine M. Vitamin E sequestration by liver fat in humans. JCI Insight. 2020 Jan 16;5(1):e133309. doi: 10.1172/jci.insight.133309.

  PMID: 31821172 DERIVED

• Traber MG, Leonard SW, Ebenuwa I, Violet PC, Wang Y, Niyyati M, Padayatty S, Tu H, Courville A, Bernstein S, Choi J, Shamburek R, Smith S, Head B, Bobe G, Ramakrishnan R, Levine M. Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled alpha-tocopherols in a 3-phase crossover design. Am J Clin Nutr. 2019 Nov 1;110(5):1148-1167. doi: 10.1093/ajcn/nqz172.

  PMID: 31495886 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Diabetes Mellitus; Fatty Liver; Obesity; Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Overweight

Interventions

alpha-Tocopherol; Vitamin E; Ascorbic Acid

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Digestive System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tocopherols; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Mark A Levine, M.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2009
• First Posted: March 16, 2009
• Study Start: October 10, 2014
• Primary Completion: October 21, 2016
• Study Completion: May 3, 2022
• Last Updated: April 24, 2026

Record last verified: 2025-12-09

Locations

US (1)