Clinical trial NCT01741077: The Effect of Folic Acid Supplementation and Pregnancy on the Folate Forms in Red Blood Cells
Official title: The Effect of Folic Acid Supplementation and Pregnancy on the Folate Forms in Red Blood Cells
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy
Keywords: pregnancy
folic acid supplementation
reproduction
folate
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2012-12-04
Enrollment: 32
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: women of reproductive age

Brief summary: The purpose of this cross-sectional study was to examine whether or not physical changes or adaptations occur in response pregnancy or to the higher intakes of folic acid from supplementation typically consumed during the reproductive period.

Detailed description: Higher folate requirements during pregnancy to support growth and development are well established but it is unknown what metabolic changes occur in 1-carbon metabolism to provide sufficient nucleotides for DNA/RNA synthesis. Periconceptual folic acid (FA) supplementation and fortification of the food supply have been shown to reduce the risk of pregnancies with neural tube defects but conversely expose women to high FA intakes for extended periods of time. The purpose of this cross-sectional study is to establish if physiological adaptations occur in folate metabolism in response to pregnancy or higher intakes of FA typically consumed among women during the reproductive period. A convenience sample of thirty-two women (n=8/group) were recruited to compare the total concentrations and forms of folate (tetrahydrofolate \[THF\], 5-methylTHF, 5-formylTHF and 5, 10-methenylTHF) in red blood cells in four groups: a) pregnant women (PW, 30-36 weeks gestation) taking 1.0 mg of FA b) non-pregnant women (NPW) taking 0 mg of FA c) NPW taking 1.0 mg FA and d) NPW taking 5.0 mg FA. Blood samples were taken at a single time point and compared across groups. Total red blood cell concentrations were measured using both microbiological assay and liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. LC/MS/MS analysis was used to determine folate form concentrations.

Eligibility criteria: Inclusion Criteria:

1. pregnant women-

   * between 30 to 36 weeks gestation
   * taking 1 mg folic acid in a multisupplement
2. non-pregnant women-

   * not pregnant
   * taking either 0, 1 or 5 mg folic acid in a multisupplement

Exclusion Criteria:

* Taking any medications known to interfere with folate absorption at the time of sampling (ie. Antibiotics \[ can be enrolled into study if they will be off them at least two weeks prior to study commencement\], methotrexate, aminopterin)
* Those with a history of any disorders or conditions that could interfere with folate absorption or metabolism from either dietary or supplement sources such as the history/presence clinically significant gastrointestinal disease (chronic diarrhea, inflammatory bowel disease, partial gastrectomy), unresolved GI symptoms(diarrhea/vomiting), steatorrhea or other conditions that interfere with absorption, distribution, metabolism or excretion of folic acid.
* Those with preexisting conditions (pre-existing maternal diabetes; insulin-dependent diabetes; previous child with neural tube disorder (NTD), cleft-lip/palate or heart defect; epilepsy and/or seizure disorders) that can increase the risk of pregnancy complicated by NTD.

Primary outcomes:
measure: Red blood cell folate concentrations - tetrahydrofolate (THF)
timeFrame: At the point of participation (this is a single visit, single test study)
Secondary outcomes:
measure: Red blood cell folate concentrations - 5-methyltetrahydrofolate (5-methylTHF)
timeFrame: At the point of participation (this is a single visit, single test study)
measure: Red blood cell concentrations - 5-formyltetrahydrofolate (5-formylTHF)
timeFrame: At the point of participation (this is a single visit, single test study)
measure: Red blood cell folate concentrations - 5,10-Methenyltetrahydrofolate (5,10-methenylTHF)
timeFrame: At the point of participation (this is a single visit, single test study)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Deborah L O'Connor, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hartman BA, Fazili Z, Pfeiffer CM, O'Connor DL. Neither folic acid supplementation nor pregnancy affects the distribution of folate forms in the red blood cells of women. J Nutr. 2014 Sep;144(9):1364-9. doi: 10.3945/jn.113.189233. Epub 2014 Jul 2.