Evidence map›Paper›PMID 22163281›Full record

Trial reportPloS one2011

Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age.

Krista S Crider, Eoin P Quinlivan, Robert J Berry, Ling Hao, Zhu Li, David Maneval, Thomas P Yang, Sonja A Rasmussen, Quanhe Yang, Jiang-Hui Zhu and 2 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 54 citations in OpenAlex.

  1. Trial
  2. Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2017
    Trial
  3. Article
  4. Review
  5. Article
  6. Susceptibility to hypertension based onFrontiers in cardiovascular medicine · 2023
    Article
  7. Article
  8. Prenatal Multivitamin Use andInternational journal of environmental research and public health · 2020
    Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Krista S CriderDivision of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. kcrider@cdc.gov
Eoin P Quinlivan
Robert J Berry
Ling Hao
Zhu Li
David Maneval
Thomas P Yang
Sonja A Rasmussen
Quanhe Yang
Jiang-Hui Zhu
Dale J Hu
Lynn B Bailey
National Center on Birth Defects and Developmental Disabilities · USUniversity of Florida · USPeking University · CNCenters for Disease Control and Prevention · USFlorida College · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (-14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation.

Indexed as

Dietary SupplementsAdultBlood CoagulationDNA MethylationDouble-Blind MethodEpigenesis, GeneticFemaleFolic AcidGene Expression Regulation, NeoplasticGenetic VariationGenotypeHemoglobinsHumansMethylenetetrahydrofolate Dehydrogenase (NAD+)Odds RatioTime FactorsFolic AcidHemoglobinsMethylenetetrahydrofolate Dehydrogenase (NAD+)Vitamin B 12

Identifiers

PMID22163281
PMCPMC3233549
OpenAlexW2038449831

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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.