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

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Riboflavin (vitamin B2) is essential energy metabolism, but biomarkerstatus is rarely measured. The UK and Ireland are the only countries worldwide to have included a riboflavinbiomarker in national dietary surveys. Some concern exists in both countries regarding the large proportion ofadults 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 referenceranges. Elsewhere in the world (including Canada and US), riboflavin biomarkers are not measured in nutritionsurveys because the existing biomarker EGRac requires very specific pre-analysis processing, unfeasible in mostsettings. DERIVE will develop accessible riboflavin biomarkers in plasma (FMN, FAD, riboflavin) and identifywhich most sensitively reflect dietary intakes and food sources of riboflavin in biobanked population basedcohorts from Ireland (n=1136) and Canada (n=1200), and are in best agreement with EGRac. The functionalsignificance of riboflavin will be evaluated using samples from previous placebo-controlled riboflavininterventions (n=537; UK cohorts) to test whether correcting low status is associated with a functional responserelated to a known metabolic role of riboflavin, the FMN-dependent generation of active vitamin B6 (i.e. PLP) intissues. Finally we will demonstrate an important health effect of riboflavin by investigating its role in modulatingblood pressure via a novel gene-nutrient interactive effect mediated through the FAD-dependent folatemetabolising enzyme methylenetetrahydrofolate reductase (MTHFR).