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

核黄素(维生素B2)是必需的能量代谢，但生物标记状态很少被测量。英国和爱尔兰是世界上仅有的两个将核黄素生物标记物纳入国家膳食调查的国家。两国都存在一些担忧，即有很大比例的成年人表现出低核黄素状态，用红细胞谷胱甘肽还原酶激活系数(EGRac)(金标准标记物)来衡量，但这些发现的功能意义尚不清楚，因为总的来说，除年轻女性外，英国和爱尔兰成年人的饮食摄入量在饮食参考范围内。在世界其他地方(包括加拿大和美国)，核黄素生物标记物不在营养调查中测量，因为现有的生物标记物EGRac需要非常具体的分析前处理，这在大多数情况下是不可行的。派生将在血浆中开发可访问的核黄素生物标记物(FMN、FAD、核黄素)，并确定最敏感地反映来自爱尔兰(n=1136)和加拿大(n=1200)的生物库人群中核黄素的饮食摄入量和食物来源的核黄素生物标记物，并与EGRac最一致。核黄素的功能意义将使用以前安慰剂控制的核黄素干预(n=537；英国队列)的样本来评估，以测试纠正低状态是否与与核黄素的已知代谢作用有关的功能反应有关，核黄素是组织中依赖于FMN的活性维生素B6(即PLP)的生成。最后，我们将通过研究核黄素在调节血压中的作用来展示其重要的健康效应，这种作用是通过一种新的基因-营养交互作用来实现的，这种作用是通过FAD依赖的叶素代谢酶亚甲基四氢叶酸还原酶(MTHFR)介导的。

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).