One-carbon Metabolism in Healthy Individuals
Conditions
Keywords
folic acid, folate, 5-methyltetrahydrofolate, supplements, women, one-carbon metabolism, methionine, DNA methylation, in vivo kinetics
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.
Interventions
DIETARY_SUPPLEMENTFolic acid
Supplement
DIETARY_SUPPLEMENT5-methyltetrahydrofolate, calcium salt
Supplement
Sponsors
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways | 24 weeks |
Countries
Canada
Contacts
Primary ContactYvonne Lamers, PhD
Backup ContactAmy McMahon, PhD
Outcome results
None listed