ERA-HDHL cofunded call “Biomarkers for Nutrition and Health” (BioNH 2016)

DEvelopment of Riboflavin biomarkers to relate dietary sources with status, gene-nutrient Interactions and Validated health Effects in adult cohorts (DERiVE)
DERiVE
2017-04-01
2019-08-13
Professor Mary Ward
Partner Organization Partner Country

1. Overall project description


1.1 Summary

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.


1.2 Highlights

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. 


4. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPDoiPdf
Jarrett H, Moore K, Hughes CF, Porter K, Hoey L, Ward M, Strain JJ, Molloy AM, Cunningham C, Casey M, Laird E, McCarroll K, Pentieva K, McNulty HBlood pressure and hypertension in relation to cognitive performance in older Irish adults from the TUDA cohort: Preliminary analysis.2018, 32, 693-721
Kehoe L, Walton J, Flynn A. Nutritional challenges for older adults in Europe: current status and future directions2019, 78 (2), 221-233https://doi.org/10.1017/S0029665118002744
Kehoe L, Walton J, Hopkins S, McNulty B, Nugent AP, McNulty H, Ward M, Flynn A. Association of key sources of riboflavin with EGRac status in a representative sample of Irish adults aged 18–90 years.2019, 78 (OCE1), E36https://doi.org/10.1017/S0029665119000405
Kehoe L, Walton J, Hopkins S, McNulty B, Nugent AP, McNulty H, Ward M, Flynn A.Intake, status and dietary sources of riboflavin in a representative sample of Irish adults aged 18-90 years.2018, 77(OCE3), E66https://doi.org/10.1017/S0029665118000708
Lamers Y.Approaches to improving micronutrient status assessment at the population level2019, 78(2), 170-17610.1017/S0029665118002781
Hughes CF, McNulty H.Assessing biomarker status of vitamin B in the laboratory: no simple solution2018, 55(2), 188-18910.1177/0004563217747907
Ward M and McNulty HImpact article on nutritional biomarkers for health2018, 2018(10), 83-8510.21820/23987073.2018.10.83
Psara E, Moore K, Ward M, Hughes C, Strain J, Molloy A, ... McNulty H.Blood pressure profile and impact of MTHFR genotype in adults aged 60 to 102 years: preliminary findings.2018, 77(OCE3), E5910.1017/S0029665118000630

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Industry - May 2019Mr Harry Jarrett (PhD Researcher) ‘The metabolic interaction between riboflavin & vitamin B6 in European adults’. DSM‐Ulster Symposium, Coleraine, Northern Ireland, 20th May 2019Oral presentation
Scientific - September 2018Mr Harry Jarrett (PhD Researcher) ‘Blood pressure and hypertension in relation to cognitive performance in older Irish adults from the TUDA cohort: Preliminary analysis.’ British and Irish Hypertension Society (BIHS) Annual Scientific Meeting, Univeristy of Cambridge, England 24-26th September 2018Poster presentation
Scientific - July 2018Mr Harry Jarrett (PhD Researcher) ‘Brain function response using magnetoencephalography (MEG) to a 2 year randomised trial with B-vitamins: a pilot study’. IACC Inauguration Symposium, Cellular coenzymes in health and disease, University College London, England 2nd-3rd July 2018Poster presentation
Scientific - June 2018Dr Laura Kehoe (PhD Researcher) ‘Intake, status and dietary sources of riboflavin in a representative sample of Irish adults aged 18-90 years’. Nutrition Society (Irish Section) Conference 2018: Targeted approaches to tackling current nutritional issues. Ulster University, 20-22nd June 2018Poster presentation
Scientific - December 2018Dr Laura Kehoe (PhD Researcher) 'Association of key sources of riboflavin with EGRac status in a representative sample of Irish adults aged 18–90 years'. Nutrition Society Winter Meeting, London, December 2018Oral presentation
Scientific - June 2018Dr Laura Kehoe (PhD Researcher) ‘Nutritional challenges for older adults in Europe: current status and future directions’. Nutrition Society (Irish Section) Conference 2018: Targeted approaches to tackling current nutritional issues. Ulster University, 20-22nd June 2018Oral presentation
Scientific - June 2018 Prof Yvonne Lamers 'Approaches to improving micronutrient status assessment at a population level'. Nutrition Society (Irish Section) Conference 2018: Targeted approaches to tackling current nutritional issues. Ulster University, 20-22nd June 2018Oral presentation
Scientific - June 2019Prof Yvonne Lamers 'From possible inadequacy to excess - discrepancy in folate status and folic acid intake of pregnant women across countries and supplementation guidelines'. 12th International conference on One Carbon Metabolism, B Vitamins and Homocysteine, Spain, 9th - 13th June 2019Oral presentation
Scientific - July 2018Prof JJ Strain 'DERiVE update: ERA-HDHL: Biomarkers in Nutrition and Health: ERA-HDHL mid-term symposium, The Hague, 4-5th July 2018Oral presentation
Industry - May 2019Dr Liadhan McAnena 'Is riboflavin deficiency in women of reproductive age a global problem?' DSM-Ulster Symposium, Coleraine, Northern Ireland, 20th May 2019Oral presentation
Scientific - June 2019Dr Liadhan McAnena ‘Is riboflavin deficiency in women of reproductive age a global problem?’ 12th International Conference on One Carbon Metabolism, B Vitamins and Homocysteine: Understanding their role in health and disease from the womb to old age, Southern Catalonia, Spain 9th-13th June 2019Poster presentation
Scientfic - June 2019Prof Helene McNulty 'Achieving optimal folate status for health: natural food folates versus folic acid', 12th International conference on One Carbon Metabolism, B Vitamins and Homocysteine, Spain, 9th - 13th June 2019Oral presentation
Scientific - August 2018Prof Helene McNulty 'Vitamins and Wellbeing from Tomb to Womb: Relationship between riboflavin MTHFR and hypertension'. 5th International Vitamin Conference, Sydney, Australia; 2018Oral presentation
Scientific, Industry - 2018Prof Helene McNulty: 'Role of nutrition throughout the lifespan: How to translate science into public health interventions at critical stages of the lifespan'. DSM symposium, Switzerland; 2018Oral presentation
Scientific - August 2018Prof Helene McNulty 'Riboflavin status, MTHFR and blood pressure'. Federation of American Societies for Experimental Biology (FASEB) Conference, Nova Scotia, Canada, August 2018Oral presentation
Scientific - June 2018Prof Helene McNulty 'Folate and related B vitamins through the lifecycle: public health priorities and challenges.' Nutrition Society (Irish Section) Conference 2018: Targeted approaches to tackling current nutritional issues. Ulster University, 20-22nd June 2018Oral presentation
Professional practitioners - 2018Prof Helene McNulty 'The role of riboflavin in reducing blood pressure in genetically at risk hypertensive adults'. EuroPrevent Satellite Symposium, 2018Oral presentation
Scientific - August 2018Dr Nadia Moran-Garcia 'Riboflavin, vitamin B6, and related metabolites detected in plasma in a single LC-MS/MS platform'. Federation of American Societies for Experimental Biology (FASEB) Conference, Nova Scotia, Canada; 2018 Oral presentation
ProfessionalsProf Mary Ward; Deputy Director of The Wellcome Trust-Wolfson Northern Ireland Clinical Research Facility (NICRF). Strategic role with the aim of facilitating research partnerships and collaborative between Ulster University, Queens University Belfast and The Belfast Trust. This also involves working closely with a range of other stakeholders including service users: 2017-presentA formal working group
Scientific - April 2019Prof Mary Ward 'Dairy foods and blood pressure: a review of current evidence', The Dairy Council for NI - Nutrition & Health What’s New ConferenceOral presentation
Study participants or study members - 2018Blood pressure update for RIBOGENE participants: 90 adults (participants and their family/friends) attended one of three public events held at venues across Northern Ireland (Belfast, Coleraine and Derry) to receive an update on research being conducted at the Nutrition Innovation Centre for Food and Health investigating the association between B-vitamins, blood pressure and a common genetic risk factor affecting 12% of the population. The event included 2 short presentations followed by a lively question and answer session. All those who attended provided very positive feedback following the event; 2018Oral presentation
Scientific - February 2019DERiVE scientific video log at the 5th International JPI HDHL conference: https://www.youtube.com/watch?v=YMPmjX4oh4oVideo log (vlog)
Professional Practitioners,Public/other audiences,Industry/Business,Supporters,Undergradua te students,Postgraduate students,Other audiences,Study participants or study members,Patients, carers and/or patient groups,Third sector organisations - ongoingDERiVE Project webpage derive-rivoflavin.com Website
Professional Practitioners,Public/other audiences,Industry/Business,Supporters,Undergradua te students,Postgraduate students,Other audiences,Study participants or study members,Patients, carers and/or patient groups,Third sector organisations - ongoingDERIVE Project twitter account: @derive_1Twitter website

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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