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

Not Applicable

Not yet recruiting

• Conditions: One-carbon Metabolism in Healthy Individuals

• Registration Number: NCT01687127
• Lead Sponsor: University of British Columbia

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-09-13
• Study First Submitted QC: 2012-09-17
• Study First Posted: 2012-09-18
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-14
• Last Update Posted: 2023-08-15
• Study Start: 2024-01-01
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 25

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways	24 weeks

Trial Locations

Locations (1)

Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute; 🇨🇦 Vancouver, British Columbia, Canada