Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Oct 30;16(21):3703.
doi: 10.3390/nu16213703.

Response of One-Carbon Biomarkers in Maternal and Cord Blood to Folic Acid Dose During Pregnancy

Jennifer M Fleming  1 , Gisselle Rosa  1 , Victoria Bland  1 , Gail P A Kauwell  2 , Olga V Malysheva  3 , Alleigh Wettstein  1 , Dorothy B Hausman  1 , Lynn B Bailey  1 , Hea Jin Park  1
Affiliations
Randomized Controlled Trial

Response of One-Carbon Biomarkers in Maternal and Cord Blood to Folic Acid Dose During Pregnancy

Jennifer M Fleming et al. Nutrients. .

Abstract

Background/objectives: The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body's ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day).

Methods: Healthy pregnant women were randomized and provided supplements from their first prenatal visit (<12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery.

Results: A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations.

Conclusions: The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation.

Keywords: folate; supplementation; unmetabolized folic acid.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram for study participants.
Figure 2
Figure 2
Serum folate (a,b), 5MTHF (5-ethyltetrahydrofolate, (c,d)) and RBC (red blood cell) folate (e,f) concentration in maternal and cord blood in response to 400 or 800 μg/day folic acid supplementation during pregnancy. Mean ± sem, a two-tailed unpaired t-test between groups of infants, b two-tailed paired t-test between mother–infant pairs.
Figure 3
Figure 3
Unmetabolized folic acid concentration in maternal and cord blood in response to 400 or 800 μg/day folic acid supplementation during pregnancy. Mean ± sem, a two-tailed unpaired t-test between groups of mothers.
Figure 4
Figure 4
Choline (a,b), betaine (c,d), DMG (dimethylglycine, (e,f)) and TMAO (g,h) concentration in maternal and cord blood in response to 400 or 800 μg/day folic acid supplementation during pregnancy. Mean ± sem, a two-tailed unpaired t-test between groups of mothers or groups of infants, b two-tailed paired t-test between mother–infant pairs.
See this image and copyright information in PMC

References

    1. Zhao R., Matherly L.H., Goldman I.D. Membrane transporters and folate homeostasis: Intestinal absorption and transport into systemic compartments and tissues. Expert Rev. Mol. Med. 2009;11:e4. doi: 10.1017/S1462399409000969. - DOI - PMC - PubMed
    1. Stover P.J. Folate biochemical pathways and their regulation. In: Bailey L., editor. Folate in Health and Disease. 2nd ed. CRC Press; Boca Raton, FL, USA: 2010. pp. 50–70.
    1. Tamura T., Picciano M.F. Folate and human reproduction. Am. J. Clin. Nutr. 2006;83:993–1016. doi: 10.1093/ajcn/83.5.993. - DOI - PubMed
    1. Cunningham F.G., MacDonald P.C., Gant N.F., Leveno K.G., Gilstrap L.C. Williams Obstetrics. Appleton & Lange; Norwalk, CT, USA: 1989. Physiology in pregnancy; pp. 209–247.
    1. Institute of Medicine . Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academies Press (US) National Academy of Sciences; Washington, DC, USA: 1998. The National Academies Collection: Reports funded by National Institutes of Health. - DOI - PubMed

Publication types

LinkOut - more resources