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.
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.
- 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.
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.