Folic Acid Supplementation in Women of Child Bearing Age

University of Georgia50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Obesity

Interventions

Folic acidDIETARY_SUPPLEMENT

Participants will be instructed to consume 2 tablets per day, a total of 800 micrograms folic acid. To facilitate compliance, participants will be instructed in the use of a compliance calendar and will receive frequent telephone and 'text' reminders from project staff. Additionally, compliance will be determined by return pill count.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

University of Georgia

Athens, Georgia, United States

Outcomes

Primary Outcomes

Cell-type-specific DNA methylation

Change in DNA methylation in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined in DNA isolated from specific white blood cell types. Microarray analysis will be used to assess changes in multiple methylation sites within regulatory pathways for folate metabolism and/or development. Each subject will serve as her own control.

Time frame: Baseline, 4 weeks and 8 weeks

Gene-specific DNA methylation

Change in DNA methylation in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined in DNA isolated from whole blood . Microarray analysis will be used to assess changes in multiple methylation sites of specific genes within regulatory pathways for folate metabolism and/or development. Each subject will serve as her own control.

Time frame: Baseline, 4 weeks and 8 weeks

Secondary Outcomes

Serum folate

Change in serum folate concentrations in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus. Each subject will serve as her own control.

Time frame: Baseline, 4 weeks and 8 weeks

Red Blood Cell (RBC) Folate

Change in red blood cell (RBC) folate in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus.

Time frame: Baseline, 4 weeks and 8 weeks

Body Composition

Body composition in terms of fat mass (g), lean mass (g) and % body fat will be determined using the BODPOD instrument and verified by dual-energy X-ray absorptiometry (DXA). The DXA analysis will also provide an indication of regional fat distribution, and total bone area, bone mineral content and bone density.

Data from ClinicalTrials.gov

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