Protocol Number: 09-DK-0097

Title:

Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

Number:

09-DK-0097

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.

Sponsoring Institute:

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

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Children

Eligibility 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.

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

Special Instructions:

Currently Not Provided

Keywords:

Vitamin C

Antioxidant

Lipid Peroxidation

Oxidative Stress

Non-Insulin Requiring Diabetics

Alpha-Tocopherol

Recruitment Keyword(s):

Health Volunteer

HV

Normal Weight

Overweight

Type 2 Diabetes

Condition(s):

Diabetes Mellitus type II non insulin dependent

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Dietary Supplement: Vitamin E

Dietary Supplement: Vitamin C

Dietary Supplement: Lipid Oxidation

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

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.

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.

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.

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