Vitamin B6 Effects for Women Taking Birth Control Pills

NCT01128244 | Completed Phase 2 Results

• 1 other identifier: 2RO1DKO72398-05
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Vitamin B6 Deficiency

Keywords

oral contraceptives; Vitamin B6; birth control pills; amino acids; Vitamin B6 deficiency; Vitamin B6 deficiency in women on oral contraceptives

Outcome Measures

Primary Outcomes (4)

• Total Remethylation of Homocysteine

  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.

  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

• Flux of Homocysteine Remethylation From Serine-derived Carbon

  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.

  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

• Fasting Plasma Pyridoxal Phosphate Concentration

  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 blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation.

• Fasting Plasma Cystathionine Concentration

  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.

  Fasting blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation.

Secondary Outcomes (1)

• Plasma 3-hydroxykynurenine Concentration

  April, 2010 - June, 2014

Study Arms (1)

Vitamin B6 Effects in OC Users

EXPERIMENTAL

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; Procedure: Infusion of labeled serine, methionine and leucine

Interventions

Vitamin B6 DIETARY_SUPPLEMENT

Subjects will receive vitamin B6 supplementation.

Also known as: pyridoxine HCl supplement, USP pyridoxine HCL

Vitamin B6 Effects in OC Users

Infusion of labeled serine, methionine and leucine PROCEDURE

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.

Vitamin B6 Effects in OC Users

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• history of gastrointestinal surgery
• chronic disease
• vitamin supplementation
• high protein diet
• progesterone
• no smoking
• chronic drug use
• alcoholism
• no vitamin supplementation

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida Clinical Research Center

Gainesville, Florida, 32610, United States

Location

Related Publications (3)

• Gregory JF, DeRatt BN, Rios-Avila L, Ralat M, Stacpoole PW. Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions. Biochimie. 2016 Jul;126:21-6. doi: 10.1016/j.biochi.2015.12.020. Epub 2016 Jan 4.

  PMID: 26765812 DERIVED

• Rios-Avila L, Coats B, Ralat M, Chi YY, Midttun O, Ueland PM, Stacpoole PW, Gregory JF 3rd. Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users. Am J Clin Nutr. 2015 Sep;102(3):616-25. doi: 10.3945/ajcn.115.113159. Epub 2015 Jul 22.

  PMID: 26201817 DERIVED

• Rios-Avila L, Coats B, Chi YY, Midttun O, Ueland PM, Stacpoole PW, Gregory JF 3rd. Metabolite profile analysis reveals association of vitamin B-6 with metabolites related to one-carbon metabolism and tryptophan catabolism but not with biomarkers of inflammation in oral contraceptive users and reveals the effects of oral contraceptives on these processes. J Nutr. 2015 Jan;145(1):87-95. doi: 10.3945/jn.114.201095. Epub 2014 Nov 19.

  PMID: 25527663 DERIVED

MeSH Terms

Conditions

Vitamin B 6 Deficiency

Interventions

Vitamin B 6; Methionine; Leucine

Condition Hierarchy (Ancestors)

Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids, Essential; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Neutral; Amino Acids, Branched-Chain

Limitations and Caveats

Secondary Outcome Measure(s): 5. Data Not Reported Exploratory Metabolite Profile and Metabolomics Analysis. The Analysis from the lab was delayed due to circumstance beyond our control.

Results Point of Contact

• Title: Dr. Jesse F. Gregory
• Organization: University of Florida

jfgy@ufl.edu

(352) 392-1991

Study Officials

• Jesse Gregory, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2010
• First Posted: May 21, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: February 7, 2017
• Results First Posted: December 17, 2014

Record last verified: 2016-12

Locations

US (1)