Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation
- Conditions
- One-carbon Metabolism in Healthy Individuals
- Interventions
- Dietary Supplement: Folic acidDietary Supplement: 5-methyltetrahydrofolate, calcium salt
- 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
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 25
- Generally healthy
- Body mass index of between 19-24 kg/m2
- Normal folate, vitamin B12, and B6 status
- 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
- Arm && Interventions
Group Intervention Description Folic acid supplementation Folic acid 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. 5-MTHF supplementation 5-methyltetrahydrofolate, calcium salt 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.
- 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
- Secondary Outcome Measures
Name Time Method
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