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

University of British Columbia

Status: Not yet enrolling

Conditions: One-carbon Metabolism in Healthy Individuals

Treatments: Dietary Supplement: Folic acid; Dietary Supplement: 5-methyltetrahydrofolate, calcium salt

Study type: Interventional

Funder types: Other

Identifiers

NCT01687127

CIHR Application Nr. 247226 (Other Grant/Funding Number)

H11-03009

Details and patient eligibility

About

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.

Enrollment: 25 estimated patients

Sex: Female

Ages: 20 to 35 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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25 participants in 2 patient groups

Folic acid supplementation

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Folic acid

5-MTHF supplementation

Experimental group

Description:

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.

Treatment:

Dietary Supplement: 5-methyltetrahydrofolate, calcium salt