DEvelopment of Riboflavin biomarkers to relate dietary sources with status, gene-nutrient Interactions and Validated health Effects in adult cohorts (DERiVE)

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
2020-03-31
Professor Mary Ward
Ulster University
Northern Ireland, UK

Consortium

Partner Organization Partner Country
University College CorkIreland
University of British ColumbiaCanada

1. Overall project description


1.1 Summary

Sub-optimal status of Riboflavin (vitamin-B2) may be more widespread than generally recognised because of reliance on dietary data only in many nutrition surveys and lack of reliable biomarker data. The DERiVE project aimed to address this by developing accessible riboflavin biomarkers and by demonstrating important functional, gene-nutrient and health effects of optimal riboflavin status in Canadian, Irish and UK cohorts. The objectives of the project were to:
 •.develop accessible biomarkers for assessment of riboflavin status and identify which most sensitively reflected dietary riboflavin intake in Irish (n=1136) and Canadian (1200) adults;
• determine which of the newly developed riboflavin-biomarkers were in best agreement with the gold-standard functional biomarker, erythrocyte glutathione reductase activation co-efficient (EGRac);
• investigate the functional significance of B2 by investigating whether low riboflavin status affects the riboflavin (FMN)-dependent generation of active vitamin B6;
• confirm the role of riboflavin in modulating blood pressure, via a novel gene-nutrient interactive effect, in UK, Irish and Canadian populations.



A summary of the main findings to date.
1. Using a newly validated high-throughput method for assessment of riboflavin status, results indicate that plasma riboflavin:
     • is the most promising measure of status (of three biomarkers investigated; plasma riboflavin, FMN and FAD). 
     • has the predictive power to identify individuals with low riboflavin (EGRac >1.3) or deficient riboflavin status (EGRac >1.4). Plasma FMN and FAD had no predictive capacity.
2. EGRac analysis found 56% of Canadians had optimal riboflavin status while 24% were deficient compared with 38% (optimal) v 35% (deficient) in NANS. Plasma riboflavin analysis further validated these findings in Canadians v NANS (19.0 v 13.9 vs nmol/L). 18% of Irish adults reported inadequate riboflavin intake while the main dietary sources of riboflavin were milk (20–24%), meat & meat products (14–18%) and ready-to-eat breakfast cereals (6–14%).
3. In UK and Irish cohorts those with optimal riboflavin status had significantly higher B6 status compared to those with deficient riboflavin status, confirming the metabolic dependency of vitamin B6 on riboflavin status. B6 status was significantly lower in Canadian women with riboflavin deficiency compared to adequacy. 
4. The role of riboflavin in modulating blood pressure, via a novel gene-nutrient interactive effect, was confirmed in UK and Irish cohorts; analysis of Canadian data is underway. 


Expected impacts: The findings have important public health implications. Suboptimal riboflavin status is more widespread than generally recognised and is associated with adverse health outcomes. The validation of a low-cost, high-throughput method for biomarker assessment of riboflavin will enable important data to be generated to inform future policies aimed at promoting better health globally.


1.2 Highlights

Published article, 2019: In conjunction with its sister project - ‘VALID’ (both funded under the same JPI ERA-HDHL 2017 co-funded call "Biomarkers for Nutrition and Health"), - an IMPACT article co-written by the two Project Coordinators, Prof Mary Ward and Prof Helene McNulty was published to profile the DERiVE and VALID projects. Impact 2018 (10): 1-4. doi: 10.21820/23987073.2018.10.83. This publication, highlighting both JPI HDHL projects, has been disseminated widely to a wide range of stakeholders internationally and through project websites: www.jpi-valid.com and www.derive-riboflavn.com.



Members of the DERiVE team attended the 12th International Conference on One Carbon Metabolism, B Vitamins and Homocysteine, Reus, Spain in June2019. Dr Liadhan McAnena’s presentation 'Is riboflavin deficiency in women of reproductive age a global problem?' was very well received by conference delegates and generated much 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. The health consequences of low and deficient riboflavin across different populations (particularly in relation to hypertension and cardiovascular disease) are the focus of ongoing analysis.


 



International Event, Dublin Ireland, 2019: The consortia for the DERiVE and VALID projects co-hosted a scientific symposium of both JPI HDHL projects at the Federation of European Nutrition Societies (FENS) 13th European Nutrition Conference, Dublin, Ireland, 15-18 October 2019, entitled 'Validating novel biomarkers of dietary exposure to Riboflavin and Polyphenols and associated health impacts: Transnational DERiVE and VALID projects'. At this joint symposium, Prof Mary Ward (DERIVE PI, Ulster University) presented The metabolic interaction of the B-vitamins riboflavin and vitamin B6 within one-carbon metabolismin European adult cohorts – The DERiVE project’. Observational data (>5000 adults aged 18-102) 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). Results confirmed a strong metabolic interdependency between riboflavin and vitamin B6 across adulthood and provided evidence that riboflavin is an important determinant of vitamin B6 status across the lifecycle. Work is ongoing to investigate the functional effects of changes in riboflavin status by measuring the response of vitamin B6 biomarker to interventions with riboflavin. Prof Yvonne Lamers (DERiVE project co-investigator and PI from University of British Columbia, Canada) presented ‘Validation of biomarkers to assess riboflavin status in Irish and Canadian population cohorts: the DERiVE project’ which confirmed plasma riboflavin as a reliable direct marker of riboflavin status for use in population studies. The symposium was very well received and generated a high degree of active participation from the scientific audience comprised of FENS conference delegates.


4. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPDoiPdf
McNulty H*, Strain JJ*, Hughes CF, Ward M*Riboflavin, MTHFR genotype and blood pressure: A personalized approach to prevention and treatment of blood pressure2017, 53, 2-910.1016/j.mam.2016.10.002
McNulty H, Ward M, Strain JJ, McAnena L, Pentieva KRiboflavin is an important determinant of vitamin B-6 status in healthy adults2020 In press
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 H*Blood 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
Ward M* and McNulty H*Dairy foods and cardiovascular health: a review of current evidence2019, 4(4), 29-30
Lamers Y*Approaches to improving micronutrient status assessment at the population level2019, 78(2), 170-17610.1017/S0029665118002781
Hughes CF and McNulty H*Assessing biomarker status of vitamin B in the laboratory: no simple solution2018, 55(2), 188-18910.1177/0004563217747907
Ward M* and McNulty H*Impact article on nutritional biomarkers for health2018, 10, 83-8510.21820/23987073.2018.10.83
Psara E, Moore K, Ward M*, Hughes CF, Strain JJ*, Molloy AM, ... McNulty M*Blood pressure profile and impact of MTHFR genotype in adults aged 60 to 102 years: preliminary findings.2018, 77(OCE3), E5910.1017/S0029665118000630
McNulty H*, Ward M*, Hoey L, Hughes CF, Pentieva K*Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges2019, 78 (3), 449-46210.1017/S0029665119000661
McNulty H*, Strain JJ*, Hughes CF, Pentieva K*, Ward M*Evidence of a role for one-carbon metabolism in blood pressure: can B vitamin intervention address the genetic risk of hypertension owing to a common folate polymorphism?2020, 4(1), nzz10210.1093/cdn/nzz102
Psara E, Pentieva K*, Ward M*, McNulty H*Critical review of nutrition, blood pressure and risk of hypertension through the lifecycle: do B vitamins play a role?2020, 173, 76-9010.1016/j.biochi.2020.03.016
Amenyah SD, McMahon A, Ward M*, Deane J, McNulty H*, Hughes CF, Strain JJ*, Horigan G, Purvis J, Walsh CP, Lees-Murdock DJRiboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR TT genotype2020, 173, 17-2610.1016/j.biochi.2020.04.007
Rooney M*, Bottiglieri T, Wasek-Patterson B, McMahon A, Hughes CF, McCann A, Horigan G, Strain JJ*, McNulty H*, Ward M*Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation2020, 173, 91-9910.1016/j.biochi.2020.04.004
Rooney M*, Hughes CF, McNulty H*, Clements M, Strain JJ*, Ward M*Measures of vascular health in a cohort of healthy adults stratified by MTHFR genotype2018, 32(1), S2310.1038/s41371-018-0109-3
Amenyah SD, Hughes CF, Ward M*, Rosborough S, Deane J, Thursby S-J, Walsh CP, Kok DEG, Strain JJ*, McNulty H*, Lees-Murdock DJInfluence of nutrients involved in one-carbon metabolism on DNA methylation in adults - a systematic review and meta-analysis2020, 20, 1-2010.1093/nutrit/nuz094
O'Sullivan E*, Kehoe L*, Walton J*, McNulty H*, Ward M*, McAnena L*, Hopkins S.M., McNulty B.A, Nugent A.P. and Flynn A*Intakes and status of riboflavin in a representative sample of Irish adults aged 18–90 years screened for MTHFR C677T polymorphism2020, E7110.1017/S0029665120000191
Tan A, Zubair M, Ho C-L, McAnena L, McNulty H, Ward M and Lamers YPlasma riboflavin concentration as novel indicator for vitamin-B2 status assessment: suggested cutoffs and its association with vitamin-B6 status in women2020, E65810.1017/S0029665120006072Download
Laura Kehoe (a1), Janette Walton (a2), Breige A. McNulty (a3), Anne P. Nugent (a4) and Albert FlynnThe role of fortified foods and nutritional supplements in the diets of older Irish adults2020, E45110.1017/S0029665120003997

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Scientific and Professional practitioners - October 2019Amy Tan (UBC), 'Plasma riboflavin concentration as novel indicator for vitamin-B2 assessment: suggested cutoffs and its association with vitamin-B6 status in women', FENS 13th European Nutrition Conference, Dublin, Ireland, 14-18 October 2019Poster presentation
Scientific and Professional practitioners - October 2019Prof Mary Ward (UU), DERiVE-VALID Symposium chairperson, 'The metabolic interaction of the B-vitamins riboflavin and vitamin B6 within one-carbon metabolism in European adult cohorts - The DERiVE Project', FENS 13th European Nutrition Conference, Dublin, Ireland, 14-18 October 2019Oral presentation
Scientific and Professional practitioners - October 2019Prof Yvonne Lamers (UBC), 'Validation of biomarkers to assess riboflavin status in Irish and Canadian population cohorts: The DERiVE Project', FENS 13th European Nutrition Conference, Dublin, Ireland, 14-18 October 2019Oral presentation
ScientificProf Mary Ward and Prof Sean JJ Strain, Members of the Organising Committee at the FENS 13th European Nutrition Conference, Dublin, Ireland, October 2019Organising committee
Scientific and Professional practitioners - October 2019Dr Emma O'Sullivan (UCC), 'Intakes and status of riboflavin in a representative sample of Irish adults aged 18-90 years screened for the MTHFR C677T polymorphism', FENS 13th European Nutrition Conference, Dublin, Ireland, 14-18 October 2019Oral presentation
Scientific and Professional practitioners - October 2019Dr Laura Kehoe (UCC), 'The role of fortified foods and nutritional supplements in the diets of older Irish adults', FENS 13th European Nutrition Conference, Dublin, Ireland, 14-18 October 2019Oral presentation
Scientific and Professional practitioners - October 2019Dr Laura Kehoe (UCC), 'Nutritional challenges for older adults in Europe: current status and future directions', FENS 13th European Nutrition Conference, Dublin, Ireland, 14-18 October 2019Oral presentation
Scientific and Professional practitioners - October 2019Larisse Melo (UBC), 'Development of novel vitamin B12 fortified yogurts using isolated and microencapsulated vitamin B12', FENS 13th European Nutrition Conference, Dublin, Ireland 14-18 October 2019Poster presentation
Scientific and students - February 2020Harry Jarrett (UU), 'The metabolic interaction between riboflavin & vitamin B6 in European adults', The Nutrition Society Irish Section Postgraduate Conference, Dublin, Ireland, 12-14 February 2020Oral presentation
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
General public - September 2019Prof Albert Flynn & Dr Janette Walton (UCC), 'National Children's Food Survey II: Launch of summary findings', Dublin, Ireland, 11 September 2019Oral presentation
Scientific - October 2019Prof Helene McNulty (UU), Co-chair of the Executive Committee, FENS 13th European Nutrition Conference, Dublin, Ireland, 14-18 October 2019Oral presentation at the Opening Ceremony
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
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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