The Body's Affect on Vitamin C
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): Vitamin C
Intervention type(s): Other
Intervention description(s): 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Pharmacokinetics; Biodistribution; Ascorbic Acid