Low or imbalanced dietary and biomarker status of folate and interrelated B-vitamins (methyl donor nutrients) perturb 1-carbon metabolism, and adversely affect brain development in early life and brain function in later life. Human studies show that improved maternal folate status during pregnancy is associated with improved cognition in the offspring, whilst optimal folate and related B-vitamin status may prevent cognitive decline in later life. The biological mechanisms explaining these relationships are not clear but may involve DNA methylation of epigenetically-controlled genes related to brain development and function. A better understanding of the mechanisms linking relevant 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 will lead to improved understanding of the role of B vitamins, their epigenetic effects and brain function in childhood and older age, with expected results anticipated to provide scientific substantiation to support nutritional strategies for sustaining better brain health through the lifespan. The consortium, including partners from Ulster University, Northern Ireland (UU), Health Sciences Universitat Rovira i Virgili, Spain (URV), University of Calgary, Canada (UC) and University of British Columbia, Canada (UBC), has strong expertise in B vitamin nutrition and epigenetics and a track record of working together across our institutions in Canada, UK and Spain.

Since the start of the transnational EpiBrain project, and despite the COVID-related delays and research curtailments, the team has made excellent progress and can report on novel findings and the development of a new software for quantitative methylation analysis.  

The Folic Acid Supplementation during the Second and Third Trimesters (FASSTT) Trial from UU is the first study to test the effect of folic acid beyond the first trimester and has to date shared novel findings that find international interest and possible public health implications. Results from the FASSTT Trial showed that children of mothers who received folic acid supplementation in the second and third trimesters of pregnancy, compared to placebo, had higher overall cognition scores at 3 years of age and higher word reasoning scores at 7 years of age compared to the children of mothers in the placebo group. Follow-up of the children at 11 years also showed that language processing speed was higher in girls of mothers in the folic acid supplemented group compared to children of mothers in the placebo group. These findings have now been published, or are in press, in high-impact peer-reviewed medical and nutrition journals.

Further, Prof Colum Walsh and Dr Sara-Jayne Thursby from UU developed the user-friendly tool CandiMeth, which allows researchers with access to DNA methylation data from arrays to more easily look at specific genes and regions without having to write any code or use command line. The tool was developed particularly with colleagues such as those in nutrition in mind so they could try analysis of methylation themselves. The development and application of the tool has been published and the CandiMeth software is available publicly in the GitHub repository at https://github.com/sjthursby/CandiMeth. 

Highlights in regards to capacity building are the outstanding achievements of Dr Aoife Caffrey, Postdoctoral Researcher from UU. Dr Aoife Caffrey received the DSM Bright Science Award for Innovative PhD Research (€6,000) for her studies on "Maternal folate nutrition and offspring brain health", presented at the 13th Federation of European Nutrition Societies (FENS) conference, October 2019, in Dublin, Ireland. Dr Aoife Caffrey also received the University of Ulster Best PhD Thesis Award in 2020 (£250). For her virtual poster presentation at the FASEB Summer Research Conference on Folic Acid, Vitamin B12, and One-Carbon in August 2020, Dr Caffrey won the competitive FASEB Postdoctoral Poster Presentation Award (US $400). Congratulations, Aoife!

We are further pleased to report that Dr Sara-Jayne Thursby from UU has accepted a prestigious postdoc position at the Johns Hopkins Medical School in the US. Further, Dr Rachelle Irwin secured a Lecturer position in her field at UU, where she remains actively involved in her research program and has taken on core teaching roles.