Clinical trial NCT01841658: Folic Acid Supplementation in Women of Child Bearing Age
Official title: Effect of Obesity and Folic Acid Supplementation on Gene-specific DNA Methylation in Women of Reproductive Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Folate Status
Folate Biomarkers
Lead sponsor: University of Georgia
Sponsor class: OTHER
Collaborators: name: University of Florida
name: Emory University
First posted: 2013-04-26
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of this study is to identify genes whose expression is potentially modifiable due to changes in folate intake and help delineate mechanisms accounting for the variability in individual response to folic acid supplementation. The study will be conducted in normal weight and obese women of childbearing age, supplemented for 8 weeks with 800 mcg/day folic acid.

It is hypothesized that (1) a change in folate status, induced by the supplementation, will influence the DNA methylation of specific genes and (2) the DNA methylation response to folic acid supplementation may differ between the normal weight and the obese women of childbearing age.

Detailed description: This study will be conducted in two phases. An initial screening study will be performed to determine folate status, MTHFR677 genotype and body composition of potential participants of the intervention study. Both folate status and MTHFR677 genotype are known independent predictors of response to folic acid supplementation. Blood samples will be collected, after an overnight fast, for determination of serum folate concentration and for MTHFR677 genotyping. Body composition and 24-hr dietary recalls will also be conducted during the screening visit.

The second phase is an eight week supplementation trial with 800 mcg/day folic acid. Screened individuals determined to have a serum folate \< 30 nmol/L (\< 50th percentile of NHANES 1999-2004) and of the CC or CT genotype (for MTHFR677) will be eligible for inclusion in the supplementation trial. Participants will be instructed to avoid dietary supplements, fortified ready-to-eat cereals, and other high folate content foods during intervention. Blood samples will be collected, after an overnight fast, at baseline and after 4 and 8 weeks of supplementation for determination of primary (DNA methylation profile) and secondary (nutritional, metabolic and health status biomarkers) outcome measures.

Eligibility criteria: Inclusion Criteria:

* Screening Phase:
* Female 18-40 yr
* Body Mass index 18.5 to 24.9 or \> 30 kg/m2
* Intervention Study:
* Serum folate \< 30 nmol/L
* MTHFR677CC or MTHFR677CT genotype

Exclusion Criteria:

* Currently pregnant, pregnancy within past 12 months
* Greater than 2 previous pregnancies
* Use of prescription drugs other than oral contraceptives
* Chronic disease (diabetes, hypertension,epilepsy,cancer, kidney disease, CVD)
* Acute illness (pneumonia, urinary tract infection, mononucleosis)
* Use of antibiotics in past 30 days
* Current smoker
* Use of dietary supplements including multivitamins in past 30 days
* Habitual consumption of fortified ready-to-eat cereals
* Significant weight change in past 12 months
* Typical alcohol consumption of 2 or more drinks per day
* INTERVENTION: all above plus serum folate \> 30 nmol/L; MTHFR677TT genotype

Primary outcomes:
measure: Cell-type-specific DNA methylation
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Gene-specific DNA methylation
timeFrame: Baseline, 4 weeks and 8 weeks
Secondary outcomes:
measure: Serum folate
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Red Blood Cell (RBC) Folate
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Body Composition
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: Athens
country: United States
facility: University of Georgia
state: Georgia
Study officials:
affiliation: University of Georgia
name: Lynn B Bailey, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Georgia
name: Dorothy Hausman, PhD
role: STUDY_DIRECTOR
References: