Influence of Nutrients involved in One-Carbon Metabolism on DNA Methylation in Adults: A Systematic Review and Meta-Analysis

Research output: Contribution to journalArticle


Context: Aberrant DNA methylation is linked to various diseases. The supply of methyl groups for methylation reactions is mediated via S-adenosylmethionine which depends on the availability of folate and related B-vitamins.
Objectives: To investigate the influence of key nutrients involved in one-carbon metabolism on DNA methylation in adults.
Data sources: Systematic literature searches were conducted in the Cochrane library, Medline, Embase, CINAHL Plus, Scopus and Web of Science databases. Studies that met the inclusion criteria and were published in English were included.
Data extraction: The first author, study design, sample size, population characteristics, type of intervention and duration, tissue type or cells analyzed, molecular techniques and DNA methylation outcomes.
Data synthesis: A meta-analysis of RCTs was conducted to investigate the effect of one-carbon metabolism nutrients on global DNA methylation. Functional analysis and visualization was performed using BioVenn software.
Results: From a total of 2620 papers screened by title, 53 studies met the inclusion criteria. Qualitative analysis indicates significant associations between one-carbon metabolism nutrients and DNA methylation. In meta-analysis of RCTs stratified by method of laboratory analysis, supplementation with folic acid alone or in combination with vitamin B-12 significantly increased global DNA methylation in studies employing LC-MS, which had markedly lower heterogeneity (n = 3, Z = 3.31, P = 0.0009; I2 = 0%) in comparison to other methods. Functional analysis highlighted a subset of 12 differentially methylated regions that were significantly related to both folate and vitamin B-12 biomarkers.
Conclusions: This study supports significant associations between one-carbon metabolism nutrients and DNA methylation. However, standardization of DNA methylation techniques is recommended to reduce heterogeneity and facilitate comparison across studies.
Original languageEnglish
Article numbernuz094
Pages (from-to)1-20
Number of pages20
JournalNutrition Reviews
Early online date23 Dec 2019
Publication statusPublished - 23 Jan 2020



  • DNA methylation
  • B-vitamins
  • folate
  • epigenetics
  • one-carbon metabolism
  • nutrients
  • adults
  • global DNA methylation

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