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

August 14, 2023 updated by: Yvonne Lamers, University of British Columbia

Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4H4
        • Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Jehannine C Austin, PhD
        • Sub-Investigator:
          • Amanda Skoll, MD, FRCSC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Supplement
Other Names:
  • 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
Supplement
Other Names:
  • 5-MTHF
  • Metafolin (brand name)
  • Levomefolic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways
Time Frame: 24 weeks
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Investigators

  • Principal Investigator: Yvonne Lamers, PhD, University of British Columbia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

September 13, 2012

First Submitted That Met QC Criteria

September 17, 2012

First Posted (Estimated)

September 18, 2012

Study Record Updates

Last Update Posted (Actual)

August 15, 2023

Last Update Submitted That Met QC Criteria

August 14, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H11-03009
  • CIHR Application Nr. 247226 (Other Grant/Funding Number: Canadian Institutes of Health Research - Application Nr. 247226)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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