ArticleClinical epigenetics2023
Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome.
Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Epigenetic Modulation of Exercise Adaptation: The Role of Dietary Supplementation in Athletic Performance.Genes · 2026Review
- Article
- A Scoping Review of Epigenetic Signatures of Diet and Diet-related Metabolites: Insights from Epigenome-Wide Association Studies and Their Implications for Cardiometabolic Health and Diseases.The Yale journal of biology and medicine · 2025Article
- Causality of genetically determined metabolites on susceptibility to prevalent urological cancers: a two-sample Mendelian randomization study and meta-analysis.Frontiers in genetics · 2024Article
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Authors and funding
25 authors at 6 institutions in 5 countries.
Funding
Abstract
backgroundB vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts. Associations between self-reported habitual daily B vitamin intakes and 756 metabolites (Metabolon Inc.) were assessed in serum samples from 1064 UK participants from the TwinsUK cohort. The identified B vitamin metabolomic biomarkers were then used in epigenome-wide association tests with fasting blood DNA methylation levels at 430,768 sites from the Infinium HumanMethylation450 BeadChip in blood samples from 2182 European participants from the TwinsUK and KORA cohorts. Candidate signals were explored for metabolite associations with gene expression levels in a subset of the TwinsUK sample (n = 297). Metabolomic biomarker epigenetic associations were also compared with epigenetic associations of self-reported habitual B vitamin intakes in samples from 2294 European participants.
resultsEighteen metabolites were associated with B vitamin intakes after correction for multiple testing (Bonferroni-adj. p < 0.05), of which 7 metabolites were available in both cohorts and tested for epigenome-wide association. Three metabolites - pipecolate (metabolomic biomarker of B6 and folate intakes), pyridoxate (marker of B6 and folate) and docosahexaenoate (DHA, marker of B6) - were associated with 10, 3 and 1 differentially methylated positions (DMPs), respectively. The strongest association was observed between DHA and DMP cg03440556 in the SCD gene (effect = 0.093 ± 0.016, p = 4.07E-09). Pyridoxate, a catabolic product of vitamin B6, was inversely associated with CpG methylation near the SLC1A5 gene promoter region (cg02711608 and cg22304262) and with SLC7A11 (cg06690548), but not with corresponding changes in gene expression levels. The self-reported intake of folate and vitamin B6 had consistent but non-significant associations with the epigenetic signals.
conclusionMetabolomic biomarkers are a valuable approach to investigate the effects of dietary B vitamin intake on the human epigenome.
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