Vitamin B6 Deficiency Clinical Trial
Official title:
Vitamin B6 Effects on One-Carbon Metabolism
Chronically inadequate B6 nutritional status is associated with aberrant one-carbon (1C) metabolism and health. Plasma pyridoxal phosphate (PLP) >30 nmol/L often has been considered to be the cutoff indicative of nutritional adequacy, with 20-30 nmol/L considered marginal deficiency; however, the current Recommended Dietary Allowance (RDA) value was based on a more conservative cutoff of 20 nmol/L plasma PLP. As shown by in the investigators preliminary data, biochemical perturbations occur when humans have marginal B6 deficiency consistent with plasma PLP of 20-30 nmol/L. A prospective study also showed that plasma PLP <23.3 nmol/L is associated with 1.8-times higher risk of recurrent venous thromboembolism than those with PLP >23.3 nmol/L. The mechanism by which low B6 intake is associated with risk of vascular disease is not known. Since B6-deficiency has little tendency to raise fasting plasma total homocysteine (tHcy) but yields an elevated tHcy response following a methionine load, low B6 nutriture may lead to repeated transient mild hyperhomocysteinemia following meal consumption. Several reports of associations between elevated plasma C-reactive protein (CRP) and low B6 status have raised the hypothesis that systemic inflammation is prone to occur during B6 deficiency or contributes to low B6 status. The investigators previously found that healthy humans in low B6 status caused by dietary restriction exhibited normal plasma CRP levels. The investigators also postulate that oxidative stress associated with low B6 status, coupled with impaired glutathione synthesis, contributes to such risk. These questions indicate the need for a more thorough understanding of the metabolic changes occurring in low B6 status from marginal B6 intake and from drug interactions such as in women using oral contraceptives.
Potential subjects will undergo a prescreening visit to meet the inclusion criteria, have a
history, physical exam and routine labs drawn. The labs will verify the nutritional
eligibility of folate, vitamin B12 and vitamin B6. If the inclusion criteria is met then the
following will take place.
The subjects will come to the University of Florida (UF) Clinical and Translational Science
Institute (CTSI) Clinical Research Center (CRC) for a 9 hour infusion (with stable isotope
labeled serine, methionine and leucine) twice during the research study. Once at the start
of the study and again at day 29. Blood samples will be taken for metabolite analysis. The
infusion of nonradioactive, stable isotope labeled amino acids allows determination of the
rate of metabolic reactions in one-carbon metabolism. The results from all subjects' blood
analyses will provide us with information about rates of several parts of metabolism and
vitamin B6 status.
During the 2-days prior to the infusion a controlled diet will be required. The subjects
will be fed at the CTSI CRC. Dietary calculations and formulations will be conducted by
using Minnesota Nutrition Data Systems software. Subjects will come to the CRC twice per day
where they will meet with staff, consume morning and evening meals, and will be provided a
sack lunch and snacks (including weekends). Protein intake will be kept constant.
After the first infusion, all subjects will consume their self-selected usual diets for 28
days along with a commercial B6 supplement providing 10 mg/day. Weekly measurement of blood
will be used to verify compliance. All subjects will then consume a 2-day controlled diet at
the UF CRC to normalize protein intake, followed by an infusion procedure identical to the
first.
During the 4-week supplementation period, all subjects will come to the CRC weekly for
weighing, blood samples, and consultation with staff. Careful screening, close monitoring
and education of subjects, along with weekly monitoring of blood levels, all contribute to a
high degree of compliance.
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Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00877812 -
Vitamin B6 Dependence of One-Carbon Metabolism
|
N/A |