ArticleNutrients2020
Moderate Folic Acid Supplementation in Pregnant Mice Results in Behavioral Alterations in Offspring with Sex-Specific Changes in Methyl Metabolism.
Article in Nutrients, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Using 6S-5-methyltetrahydrofolate instead of folic acid in prenatal multivitamin reduces unmetabolized folic acid concentrations in the mother-fetus dyad: a 24-week randomized controlled trial.Frontiers in nutrition · 2026Trial
- Fortification with folic acid and early human embryo development: lessons from assisted reproduction.Journal of assisted reproduction and genetics · 2025Article
- The relationship between folic acid deficiency and preeclampsia-like phenotypes in rats.BMC pregnancy and childbirth · 2025Article
- Timing of standard chow exposure determines the variability of mouse phenotypic outcomes and gut microbiota profile.Lab animal · 2025Article
- The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.EMBO reports · 2025Article
- Folic Acid and Methyltetrahydrofolate Supplementation in theNutrients · 2024Article
- Epigenetic regulation by TET1 in gene-environmental interactions influencing susceptibility to congenital malformations.bioRxiv : the preprint server for biology · 2024Article
- Timing of standard chow exposure determines the variability of mouse phenotypic outcomes and gut microbiota profile.bioRxiv : the preprint server for biology · 2024Article
- Risk of Excess Maternal Folic Acid Supplementation in Offspring.Nutrients · 2024Review
- Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review.Nutrients · 2023Review
- Article
- Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution.Nutrients · 2023Article
- High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults.Nutrients · 2022Observational
- Review
- Early Life Stage Folic Acid Deficiency Delays the Neurobehavioral Development and Cognitive Function of Rat Offspring by Hindering De Novo Telomere Synthesis.International journal of molecular sciences · 2022Article
- Absorption and Tissue Distribution of Folate Forms in Rats: Indications for Specific Folate Form Supplementation during Pregnancy.Nutrients · 2022Article
- Excessive Folic Acid Mimics Folate Deficiency in Human Lymphocytes.Current issues in molecular biology · 2022Article
- Moderate Folic Acid Supplementation in Pregnant Mice Results in Altered Sex-Specific Gene Expression in Brain of Young Mice and Embryos.Nutrients · 2022Article
- Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles.Biomolecules · 2022Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Fifteen to 20% of pregnant women may exceed the recommended intake of folic acid (FA) by more than four-fold. This excess could compromise neurocognitive and motor development in offspring. Here, we explored the impact of an FA-supplemented diet (5× FASD, containing five-fold higher FA than recommended) during pregnancy on brain function in murine offspring, and elucidated mechanistic changes. We placed female C57BL/6 mice for one month on control diets or 5× FASD before mating. Diets were maintained throughout pregnancy and lactation. Behavioural tests were conducted on 3-week-old pups. Pups and mothers were sacrificed at weaning. Brains and livers were collected to examine choline/methyl metabolites and immunoreactive methylenetetrahydrofolate reductase (MTHFR). 5× FASD led to hyperactivity-like behavior and memory impairment in 3-week-old pups of both sexes. Reduced MTHFR protein in the livers of FASD mothers and male pups resulted in choline/methyl metabolite disruptions in offspring liver (decreased betaine) and brain (decreased glycerophosphocholine and sphingomyelin in male pups, and decreased phosphatidylcholine in both sexes). These results indicate that moderate folate supplementation downregulates MTHFR and alters choline/methyl metabolism, contributing to neurobehavioral alterations. Our findings support the negative impact of high FA on brain development, and may lead to improved guidelines on optimal folate levels during pregnancy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.