Vitamin B6 Effects for Women Taking Birth Control Pills

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01128244
First received: May 20, 2010
Last updated: March 10, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Vitamin B6 Deficiency
Dietary Supplement: Vitamin B6
Procedure: Infusion of labeled serine, methionine and leucine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vitamin B6 Effects on One-Carbon Metabolism

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Total Remethylation of Homocysteine [ Time Frame: Blood samples will be taken prior to infusion and at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7.5, and 9h. Infusions will be conducted at baseline and after 28 days ] [ Designated as safety issue: No ]
    Data from analysis of serine, methionine and leucine in the timed blood samples of all subjects will provide a measurement of the metabolic rate of total remethylation of homocysteine before and after vitamin B6 supplementation.

  • Flux of Homocysteine Remethylation From Serine-derived Carbon [ Time Frame: Blood samples will be taken prior to infusion and at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7.5, and 9h. Infusions will be conducted at baseline and after 28 days ] [ Designated as safety issue: No ]
    Data from analysis of serine, methionine and leucine in the timed blood samples of all subjects will provide a measurement of the metabolic rate of homocysteine remethylation from serine-derived carbon before and after vitamin B6 supplementation. These flux values may be slightly higher than flux of total homocysteine remethylation in Outcome Measure 1 because of the small contribution of methionine salvage to the flux measured in Outcome Measure 2.

  • Fasting Plasma Pyridoxal Phosphate Concentration [ Time Frame: Fasting blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation. ] [ Designated as safety issue: No ]
    For all subjects, the concentration of plasma pyridoxal phosphate in fasting blood samples taken before and after the supplementation period will provide a direct measure of vitamin B6 nutritional status.

  • Fasting Plasma Cystathionine Concentration [ Time Frame: Fasting blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation. ] [ Designated as safety issue: No ]
    For all subjects, the concentration of plasma cystathionine in fasting blood samples taken before and after the supplementation period will provide a functional measure of vitamin B6 nutritional status.


Secondary Outcome Measures:
  • Exploratory Metabolite Profile and Metabolomics Analysis. [ Time Frame: 2013-2015 ] [ Designated as safety issue: No ]
    For all subjects, analysis of blood samples before and after vitamin B6 supplementation will allow evaluation of discriminating biomarkers using targeted metabolite profile analysis of one-carbon metabolism and tryptophan catabolism constituents. Also, we will conduct exploratory evaluation and potential identification of new biomarkers using metabolomics analysis on subjects before and after vitamin B6 supplementation.


Enrollment: 13
Study Start Date: April 2010
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin B6 Effects in OC Users

All subjects will be given an infusion of labeled serine, methionine and leucine prior to vitamin B6 supplementation and after 28 days of treatment. In addition, they will receive a special diet 2 days prior to the infusion and will have weekly weight, blood, and visits to the clinic.

The results from analysis of vitamin B6 and these amino acids in blood will provide us with specific measurements of the rates of two aspects of metabolism (Primary Outcomes 1 and 2) and specific measurements of vitamin B6 nutritional status (Primary Outcomes 3 and 4).

Dietary Supplement: Vitamin B6
Subjects will receive vitamin B6 supplementation.
Other Names:
  • pyridoxine HCl supplement
  • USP pyridoxine HCL
Procedure: Infusion of labeled serine, methionine and leucine
Subjects will be given an infusion of the stable isotope labeled amino acids, serine, methionine and leucine prior to vitamin B6 supplementation and after 28 days of B6 treatment. In addition, they will receive a special diet 2 days prior to the infusion and will have weekly weight, blood, and visits to the clinic.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy female subjects
  • normal screening labs
  • normal body weight
  • nonpregnant
  • Plasma PLP<30nmol/L

Exclusion Criteria:

  • history of gastrointestinal surgery
  • chronic disease
  • vitamin supplementation
  • high protein diet
  • progesterone
  • no smoking
  • chronic drug use
  • alcoholism
  • no vitamin supplementation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01128244

Locations
United States, Florida
University of Florida Clinical Research Center
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Jesse Gregory, PhD University of Florida
  More Information

No publications provided by University of Florida

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01128244     History of Changes
Other Study ID Numbers: 2RO1DKO72398-05
Study First Received: May 20, 2010
Results First Received: December 9, 2014
Last Updated: March 10, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
oral contraceptives
Vitamin B6
birth control pills
amino acids
Vitamin B6 deficiency
Vitamin B6 deficiency in women on oral contraceptives

Additional relevant MeSH terms:
Vitamin B 6 Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamin B Deficiency
Contraceptives, Oral
Contraceptives, Oral, Combined
Pyridoxal
Pyridoxine
Vitamin B 6
Vitamin B Complex
Vitamins
Contraceptive Agents
Contraceptive Agents, Female
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 26, 2015