Clinical trial NCT01687127: Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation
Official title: Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: One-carbon Metabolism in Healthy Individuals
Keywords: folic acid
folate
5-methyltetrahydrofolate
supplements
women
one-carbon metabolism
methionine
DNA methylation
in vivo kinetics
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2012-09-18
Enrollment: 25
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Yvonne Lamers, PhD
role: PRINCIPAL_INVESTIGATOR
References: