Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation

This study is not yet open for participant recruitment.
Verified November 2012 by University of British Columbia
Sponsor:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01687127
First received: September 13, 2012
Last updated: November 22, 2012
Last verified: November 2012
  Purpose

Periconceptional supplementation with folic acid - the synthetic form of the B-vitamin folate - reduces the occurrence of adverse pregnancy outcomes such as spina bifida. The underlying biochemical mechanisms for how folic acid affects health outcomes however are unknown. The naturally occurring form 5-methyltetrahydrofolate (5-MTHF) is now available and discussed as an adequate substitute to folic acid. This study aims to determine the effect of folic acid compared to 5-MTHF on cellular mechanisms. Stable isotope tracer protocols will be used that allow determining the effect of folic acid on the dynamics of metabolic pathways in the human body.

Hypothesis: Supplementation with high-dose folic acid alters the turnover rate of folate dependent pathways in healthy humans; but 5-MTHF does not. Genetic variations in a key enzyme of the folate metabolism will aggravate the effect of folic acid on the metabolic pathways.


Condition Intervention
One-carbon Metabolism in Healthy Individuals
Dietary Supplement: Folic acid
Dietary Supplement: 5-methyltetrahydrofolate, calcium salt

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: January 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Folic acid supplementation
Folic acid will be given orally in form of tablets. A supplement of 1 mg will be taken daily for 12 weeks. Thereafter, a supplement of 5 mg will be taken daily for 12 weeks (i.e., until Week 24). At baseline, Week 12, and Week 24, subjects will receive a 9-hour primed constant infusion of amino acids in saline solution for quantification of kinetics of one-carbon metabolism.
Dietary Supplement: Folic acid
Other Name: Pteroylmonoglutamic acid
Experimental: 5-MTHF supplementation
The calcium salt of 5-methyltetrahydrofolate (5-MTHF; Brand name "Metafolin") will be given orally in form of tablets. A supplement of 1 mg will be taken daily for 12 weeks. Thereafter, a supplement of 5 mg will be taken daily for 12 weeks (i.e., until Week 24). At baseline, Week 12, and Week 24, subjects will receive a 9-hour primed constant infusion of amino acids in saline solution for quantification of kinetics of one-carbon metabolism.
Dietary Supplement: 5-methyltetrahydrofolate, calcium salt
Other Names:
  • 5-MTHF
  • Metafolin (brand name)
  • Levomefolic acid

  Eligibility

Ages Eligible for Study:   20 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Generally healthy
  • Body mass index of between 19-24 kg/m2
  • Normal folate, vitamin B12, and B6 status

Exclusion Criteria:

  • Unable to swallow tablets
  • Unable to receive intravenous catheters
  • Use of vitamin supplements, amino acid or protein supplements for more than six months before study participation
  • Chronic consumption of a high-protein diet (e.g. Atkins Diet)
  • Medical conditions such as diabetes, asthma, cancer, cardiovascular disease, a history of neural tube defect (such as spina bifida) affected pregnancy, have had gastrointestinal surgery, abnormal kidney, thyroid function, or psychiatric illness, or any other chronic disease
  • Pregnancy or lactation
  • Smoking, use of recreational drugs, and/or consumption of more than one alcohol drink per day or more than seven per week.
  • Use of long-term prescription medication such as hormonal contraceptives, antidepressants, anticonvulsants, anticoagulants, or other chronic medication
  • Blood donation in the last three months prior to study start
  • Unable to provide informed consent, or unable to read and write English
  • Low compliance to intervention as determined by early steady-state or reduction in blood folate concentrations
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687127

Contacts
Contact: Theresa H Schroder, Dipl. 604-822-1250 schrod10@mail.ubc.ca
Contact: Yvonne Lamers, PhD 604-822-1490 yvonne.lamers@ubc.ca

Locations
Canada, British Columbia
Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 4H4
Contact: Theresa H Schroder, Dipl    604-822-1250    folate.study@ubc.ca   
Sub-Investigator: Jehannine C Austin, PhD         
Sub-Investigator: Amanda Skoll, MD, FRCSC         
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator: Yvonne Lamers, PhD University of British Columbia
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01687127     History of Changes
Other Study ID Numbers: H11-03009, CIHR Application Nr. 247226
Study First Received: September 13, 2012
Last Updated: November 22, 2012
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
folic acid
folate
5-methyltetrahydrofolate
supplements
women
one-carbon metabolism
methionine
DNA methylation
in vivo kinetics

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Hematinics
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014