The Body's Affect on Vitamin C
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 35 |
| Updated: | 4/6/2019 |
| Start Date: | October 25, 1991 |
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.
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.
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.
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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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