Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation
Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism
2 other identifiers
interventional
25
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Jan 2024
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 13, 2012
CompletedFirst Posted
Study publicly available on registry
September 18, 2012
CompletedStudy Start
First participant enrolled
January 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
August 15, 2023
August 1, 2023
3 years
September 13, 2012
August 14, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways
24 weeks
Study Arms (2)
Folic acid supplementation
EXPERIMENTALFolic 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.
5-MTHF supplementation
EXPERIMENTALThe 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.
Interventions
Supplement
Supplement
Eligibility Criteria
You may qualify if:
- Generally healthy
- Body mass index of between 19-24 kg/m2
- Normal folate, vitamin B12, and B6 status
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute
Vancouver, British Columbia, V5Z 4H4, Canada
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yvonne Lamers, PhD
University of British Columbia
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 13, 2012
First Posted
September 18, 2012
Study Start
January 1, 2024
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
August 15, 2023
Record last verified: 2023-08