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

NCT ID: NCT01687127

Last Updated: 2023-08-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-01

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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One-carbon Metabolism in Healthy Individuals

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Folic acid

Intervention Type DIETARY_SUPPLEMENT

Supplement

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.

Group Type EXPERIMENTAL

5-methyltetrahydrofolate, calcium salt

Intervention Type DIETARY_SUPPLEMENT

Supplement

Interventions

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Folic acid

Supplement

Intervention Type DIETARY_SUPPLEMENT

5-methyltetrahydrofolate, calcium salt

Supplement

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Pteroylmonoglutamic acid 5-MTHF Metafolin (brand name) Levomefolic acid

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Yvonne Lamers

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yvonne Lamers, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

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Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

Central Contacts

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Yvonne Lamers, PhD

Role: CONTACT

604-827-1776

Amy McMahon, PhD

Role: CONTACT

604-822-1250

Facility Contacts

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Yvonne Lamers, PhD

Role: primary

604-827-1776

Amy McMahon, PhD

Role: backup

604-822-1250

Other Identifiers

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CIHR Application Nr. 247226

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

H11-03009

Identifier Type: -

Identifier Source: org_study_id

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