Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health-improvement strategies

Aoife Caffrey, Yvonne Lamers, Michelle M Murphy, Nicole Letourneau, Rachelle E Irwin, K. Pentieva, M Ward, Amy Tan, Alejandra Rojas-Gomez, Universitat Rovira i Virgili, Josefa Canals, Brenda MY Leung, Rhonda Bell, Gerald F Giesbrecht, Deborah Dewey, Catherine J Field, Michael Kobor, CP Walsh, H McNulty

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Suboptimal status of folate and/or interrelated B vitamins (B12, B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition–epigenome–brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition–epigenome–brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.
Original languageEnglish
Specialist publicationNutrition Bulletin
Publication statusPublished online - 21 Feb 2023

Bibliographical note

Funding Information:
The authors wish to acknowledge the JPI ERA‐HDHL call ‘Nutrition and the Epigenome’ ( https://healthydietforhealthylife.eu/index.php/joint‐actions/nutrition‐epigenome ) for selecting and recommending The EpiBrain Project for funding.

Publisher Copyright:
© 2023 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.


  • ageing
  • B vitamins
  • cognition
  • DNA methylation
  • folate one-carbon metabolism
  • folate
  • one‐carbon metabolism
  • one-carbon metabolism


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