Award details

DERIVE:Dev. of Riboflavin biomarkers to relate dietary sources with status, gene-nutrient interactions and validated health effects in adult cohorts

Reference	BB/P028241/1
Principal Investigator / Supervisor	Professor Mary Ward
Co-Investigators / Co-Supervisors	Professor Helene McNulty, Professor Kristina Pentieva, Professor Sean Strain
Institution	University of Ulster
Department	Sch of Biomedical Sciences
Funding type	Research
Value (£)	207,521
Status	Completed
Type	Research Grant
Start date	01/04/2017
End date	31/03/2020
Duration	36 months

Abstract

Riboflavin (vitamin B2) is essential for oxidation-reduction reactions, but 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. Elsewhere in the world (including Canada and US), riboflavin biomarkers are not measured in nutrition surveys because the existing biomarker EGRac requires very specific pre-analysis processing, unfeasible in most settings. DERIVE will develop accessible riboflavin biomarkers in plasma (FMN, FAD, riboflavin) and identify which most sensitively reflect dietary intakes and food sources of riboflavin in biobanked population based cohorts from Ireland (n=1136) and Canada (n=1200), and are in best agreement with EGRac. The functional significance of riboflavin will be evaluated using samples from previous placebo-controlled riboflavin interventions (n=537; UK cohorts) to test whether correcting low status is associated with a functional response related to a known metabolic role of riboflavin, the FMN-dependent generation of active vitamin B6 (i.e. PLP) in tissues. Finally we will demonstrate an important health effect of riboflavin by investigating its role in modulating blood pressure via a novel gene-nutrient interactive effect mediated through the FAD-dependent folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR).

Summary

Riboflavin (vitamin B2) is essential energy metabolism, but 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. Elsewhere in the world (including Canada and US), riboflavin biomarkers are not measured in nutrition surveys because the existing biomarker EGRac requires very specific pre-analysis processing, unfeasible in most settings. DERIVE will develop accessible riboflavin biomarkers in plasma (FMN, FAD, riboflavin) and identify which most sensitively reflect dietary intakes and food sources of riboflavin in biobanked population based cohorts from Ireland (n=1136) and Canada (n=1200), and are in best agreement with EGRac. The functional significance of riboflavin will be evaluated using samples from previous placebo-controlled riboflavin interventions (n=537; UK cohorts) to test whether correcting low status is associated with a functional response related to a known metabolic role of riboflavin, the FMN-dependent generation of active vitamin B6 (i.e. PLP) in tissues. Finally we will demonstrate an important health effect of riboflavin by investigating its role in modulating blood pressure via a novel gene-nutrient interactive effect mediated through the FAD-dependent folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR).

Impact Summary

Our proposal also aligns with the overall vision of the JPI HDHL initiative that by 2030 all citizens will have accessibility to a healthy diet and that the incidence of non-communicable diseases will have decreased significantly. The project focusses on riboflavin, its interaction with two closely related vitamins - vitamin B6 and folate - and a related gene-nutrient interaction, with important implications for health. In the context of the overall diet, milk and dairy foods - the only rich sources of dietary riboflavin - will be of particular relevance. Health Impact The proposed research is well aligned with the goal of promoting health and wellness in adults in Europe and Associated countries. Recent evidence suggests that low riboflavin status may be a much greater public health issue globally than is generally recognised. There are considerable implications for those most at risk of low intake and status of riboflavin, including adults generally who do not consume adequate intakes of milk and dairy foods, and particularly young women of reproductive age. Of note, riboflavin has an important role in one-carbon metabolism where it interacts with other relevant nutrients (i.e. folate and vitamin B6) and is required for normal functioning of the essential pathways dependent on these nutrients. Thus better riboflavin status is likely to have important roles in maintaining health throughout the lifecycle and in preventing disease including cancer, age-related cataracts and metabolic disorders leading to increased risk of cardiovascular disease. The contribution of riboflavin to health is however very much under-recognised at this time, and the evidence greatly lacking, due to the lack of an accessible biomarker to measure riboflavin status. The proposed project will addresses this gap, by validating riboflavin biomarkers for use in the current proposal and in future nutrition research internationally. Personalized nutrition: a novel role of riboflavin in health The project will bring together cross-sectional data on blood pressure with genetic, nutrient, blood biomarker and relevant clinical information in well-characterized cohorts. This new knowledge will provide important evidence to support a personalized nutritional strategy for preventing hypertension in genetically at-risk adults, with potential impacts on risk of disease in ageing (especially stroke), pregnancy outcomes, healthcare economics, and quality of life throughout the lifecycle. Societal and other impacts Leadership within Europe and Associated countries. The proposal brings together researchers with complementary expertise to engage in diet and health research at a pan-European and international level. Improving scientific capacity and capability within Europe and Internationally: The proposed project will establish a critical mass of expertise in this research area, allowing for excellent science and sharing of innovative approaches and infrastructures, and the data gathered willbe made available to the wider research community. It will also offer excellent experience and training to early career scientists and PhD students in nutrition, and thus contribute to strengthening the research base in the health and agri-food sectors. The scientific publications arising from this research will also provide important benefits to the wider research community by providing comprehensive data reporting important nutrition and health relationships in very well characterised observational cohorts, along with evidence of the potential benefits of improving micronutrient status for better health outcomes as demonstrated in intervention cohorts. Collaboration with industry and Enhanced competitiveness in the Agri-food sector: The new biomarkers of dietary riboflavin intake validated in the current project will be essential for substantiating Article 14 health claims for evaluation by the European Food Safety Authority.

Committee	Not funded via Committee
Research Topics	Diet and Health
Research Priority	X – Research Priority information not available
Research Initiative	ERA-HDHL Biomarkers for Nutrition and Health [2016]
Funding Scheme	X – not Funded via a specific Funding Scheme

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