Sub-optimal status of the B-vitamin Riboflavin may be more widespread than is generally recognised across the developed world, because of the reliance on dietary data only in nutrition surveys and lack of reliable biomarker data. The DERIVE project will address this gap by developing accessible riboflavin biomarkers for use in population surveys globally, and by demonstrating important functional, gene-nutrient and health effects of optimal riboflavin status in Canadian, Irish and UK cohorts. The study, which involves a trans-national collaboration, will access bio-banked blood samples and data from one of the most comprehensive dietary surveys in the EU, the Irish National Adult Nutrition Survey (www.iuna.net) as well as bio-banked specimen and data from the BC Generations Project (www.bcgenerationsproject.ca), part of the Canadian Partnership for Tomorrow Project, a major research platform for the study of disease causation. The newly developed biomarkers will be tested to identify which most sensitively reflect dietary intakes and food sources of riboflavin in the population-based cohorts from Ireland and Canada and which are in best agreement with the current functional biomarker, EGRac. Furthermore, and of note, the role of riboflavin in modulating blood pressure, via a novel gene-nutrient interactive effect, will be investigated in these populations. This will build considerably on recent findings from trials conducted by the UK partner showing significant blood pressure-lowering effects of riboflavin in adults with a genetic pre-disposition to increased blood pressure.

Riboflavin (vitamin B2), as FMN and FAD cofactors, is essential for energy metabolism although biomarker status is rarely measured. The UK and Ireland are the only countries worldwide to have included a riboflavin biomarker in national dietary surveys. Some concern exists in both countries regarding the large proportion of adults showing low riboflavin status, measured using erythrocyte glutathione reductase activation coefficient (EGRac) (the gold-standard marker), but the functional significance of such findings is unclear since in general, with the exception of younger women, dietary intakes of British and Irish adults are within dietary reference ranges. Among its metabolic roles, riboflavin is required (as FMN) to generate the active form of vitamin B6 in tissues. It has been shown previously that cells have a tendency to spare FAD at the expense of FMN therefore, in the condition of riboflavin deficiency, the FMN-dependent pathways would be expected to be primarily affected. Limited evidence indicates that riboflavin may act as the limiting nutrient for optimising vitamin B6 status among older adults deficient in vitamin B6, however, whether this effect is observed across adulthood is unknown. 

The transnational DERiVE project includes partners from Ulster University, Northern Ireland (UU), University of British Columbia, Canada (UBC) and University College Cork, Ireland (UCC). It has been a busy year for the DERiVE project, with all three centres exchanging samples for biomarker analysis. Early results were presented by Dr Liadhan McAnena from UU at the 12th International Conference on One Carbon Metabolism, B Vitamins and Homocysteine, Reus, Spain in June The presentation entitled 'Is riboflavin deficiency in women of reproductive age a global problem?' was very well received by conference delegates and generated interesting discussion The main findings were that sub-optimal riboflavin status in both developed and developing countries, appears to be a much greater problem that is generally recognised. Young women, particularly those in low-middle income countries, appear to be at greatest risk of riboflavin deficiency, Current work aims to further our understanding of the health consequences of low and deficient riboflavin across different populations (particularly in relation to hypertension and cardiovascular disease) and to investigate riboflavin status in a representative sample of the Canadian population from the BC generations cohort.

The metabolic interaction between riboflavin and vitamin B6 was also investigated in >5000 adults aged 18-102. Observational data were accessed from two large cohorts (the Trinity Ulster Department of Agriculture, TUDA study conducted in NI and ROI and the Irish National Adult and Nutrition, NANS Survey in ROI) and a randomised controlled trial previously conducted at UU. All biochemical analysis including the assessment of riboflavin (erythrocyte glutathione reductase activation coefficient) and vitamin B6 status (plasma pyridoxal phosphate (PLP) by HPLC) was completed at UU. Results indicated a strong metabolic interdependency between riboflavin and vitamin B6 across adulthood and suggest that riboflavin is an important determinant of vitamin B6 status across the lifecycle. These novel findings are currently being prepared for submission to a leading nutrition journal and will be presented at the 2019 FENS conference to be held in Dublin, Ireland 15-18th October 2019. Work is ongoing to investigate the functional effects of changes in riboflavin status by measuring the response of vitamin B6 biomarker to interventions with different doses of riboflavin.