The Body's Affect on Vitamin C

Pharmacokinetics and Biodistribution of Ascorbic Acid in Healthy Human Subjects

Pharmacokinetics is the term used for how the body affects a drug once it is taken. Vitamin C, also known as ascorbic acid, is an essential water soluble vitamin. Meaning, the body does not make Vitamin C it must be taken in through the diet. In this study researchers will attempt to determine how the amount of water consumed affects the level of vitamin C in the blood (specifically the plasma component of the blood).

In this study researchers will take 13 subjects and place them on a Vitamin C restricted diet. Vitamin C levels will be measured twice a week on an outpatient basis until all subjects reach a desired low level of Vitamin C (12-15 micromolar plasma ascorbic acid concentration). Subjects will then be admitted and undergo 24 hour blood and urine collection. Following the collection of samples, subjects will then begin to receive Vitamin C orally (by mouth) and intravenously (injected into the vein). The dosage of Vitamin C will gradually increase from 30 mg-2500 mg divided into two daily doses. Blood and urine samples will be collected each time the dose is increased. The study will take approximately 18 weeks after which the subjects will be discharged in healthy condition.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Vitamin C (ascorbic acid, ascorbate) is an essential water soluble vitamin. Our studies at NIH were the first to demonstrate in healthy men and women how changes in a vitamin concentration in human plasma vary as a direct function of the amount ingested, over a wide range. ln the present study, we plan to achieve a prescorbutic vitamin C plasma concentration of approximately 5-10 micromolar in healthy human volunteers. We will gradually replete these subjects with incremental doses of vitamin C to measure how their plasma, red blood cell, and leukocyte concentrations will change as a function of the dose. We will also determine whether changes in vitamin C concentration result in changes in gene expression and metabolic profiles (metabolomics, lipidomics, proteomics).

Outpatient subjects will be encouraged to consume vitamin C in foods. As inpatients, vitamin C deficiency will be induced by placing subjects on a tightly restricted scorbutic diet. Plasma vitamin C will be monitored several times per week. When subjects have achieved a plasma ascorbate concentration of 5-10 micromolar, blood sampling and urine collection over 24 hours will be performed. After platelets and leukocytes are collected, ascorbate repletion will begin. Escalating doses of ascorbate will be administered orally and intravenously for the remainder of their inpatient admission. Total daily doses of 30mg, 60mg, 100mg, 200mg, 400mg, 1000mg and 2500mg will be given in two divided doses. Bioavailability of ascorbate will be determined at each dosage increment. When plasma ascorbate concentration reaches steady state for each dose, subjects will undergo 36 hr plasma sampling and a timed 48 hr urine collection. At steady state of each of 4 to 5 doses, an apheresis procedure will be performed for collection of platelets and leukocytes. lt is anticipated subjects will be discharged in healthy condition after 20-26 weeks.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

No

Description

  • INCLUSION CRITERIA:
  • 10 Males - ages 18 - 35 yrs
  • 10 Females - ages 18 - 35 yrs

No more than 4 subjects during any period will remain as inpatients on the endocrine/metabolic ward. These subjects will be normal volunteers selected from colleges/universities who will:

  1. Spend within a fall or spring semester (approximately 20-26 weeks) as an inpatient resident on the endocrine-metabolic ward at NIH.
  2. Be willing to adhere to an ascorbate restricted diet for the duration of the time spent in the study as an inpatient at NlH.
  3. Have veins adequate for venipunctures and be willing to undergo venipunctures approximately two to three times per week.
  4. Refrain from ingestion of any medication and cigarette smoking and ethanol.
  5. Be able to give informed consent.

EXCLUSION CRITERIA:

  1. Subject non-compliance with restricted diet.
  2. Pregnancy as determined by history, physical exam and urine b-HCG.
  3. History of diabetes mellitus, bleeding disorders, kidney stones, glucose-6- phosphate dehydrogenase deficiency, family history of hemochromatosis/iron overload.
  4. Platelet count <150,000/ul blood; prothrombin time/partial thromboplastin time (PT/PTT) > 1 second above normal upper limit.
  5. Positive test for exposure to human immunodeficiency virus.
  6. Positive tests for hepatitis B surface antigen, core antibody or surface antibody.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Pharmacokinetics and Biodistribution of Ascorbic Acid
Outpatient subjects will be encouraged to consume vitamin C in foods. As inpatients, vitamin C deficiency will be induced by placing subjects on a tightly restricted scorbutic diet. Plasma vitamin C will be monitored several times per week. When subjects have achieved a plasma ascorbate concentration of 5-10 micromolar, blood sampling and urine collection over 24 hours will be performed. After platelets and leukocytes are collected, ascorbate repletion will begin. Escalating doses of ascorbate will be administered orally and intravenously for the remainder of their inpatient admission. Total daily doses of 30mg, 60mg, 100mg, 200mg, 400mg, 1000mg and 2500mg will be given in two divided doses. Bioavailability of ascorbate will be determined at each dosage increment. When plasma ascorbate concentration reaches steady state for each dose, subjects will undergo 36 hr plasma sampling and a timed 48 hr urine collection.
Outpatient subjects will be encouraged to consume vitamin C in foods. As inpatients, vitamin C deficiency will be induced by placing subjects on a tightly restricted scorbutic diet. Plasma vitamin C will be monitored several times per week. When subjects have achieved a plasma ascorbate concentration of 5-10 micromolar, blood sampling and urine collection over 24 hours will be performed. After platelets and leukocytes are collected, ascorbate repletion will begin. Escalating doses of ascorbate will be administered orally and intravenously for the remainder of their inpatient admission. Total daily doses of 30mg, 60mg, 100mg, 200mg, 400mg, 1000mg and 2500mg will be given in two divided doses. Bioavailability of ascorbate will be determined at each dosage increment. When plasma ascorbate concentration reaches steady state for each dose, subjects will undergo 36 hr plasma sampling and a timed 48 hr urine collection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in ascorbic acid concentrations
Time Frame: 5 years
In this study researchers will attempt to determine how the amount of water consumed affects the level of vitamin C in the blood (specifically the plasma component of the blood).
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Mark A Levine, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 1997

Primary Completion (Actual)

August 25, 1999

Study Completion (Actual)

March 4, 2019

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

November 3, 1999

First Posted (Estimated)

November 4, 1999

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 21, 2024

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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