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How to Develop Dietary Reference Intakes Based on Chronic Disease Endpoints

The Omega-3’s EPA & DHA, A Case Study Workshop

By Invitation Only

Hilton Garden Inn Downtown, Ottawa ON
08:30 - 09:00   Registration: Coffee and Light Breakfast
09:00 - 09:15   Welcome and overview of conference aims
Speakers: David Ma, PhD - University of Guelph and Richard Bazinet, PhD - University of Toronto
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About the speakers:

Dr. David W.L. Ma
Professor and Director, Guelph Family Health Study

Dr. Ma is a Full Professor and Director of the Guelph Family Health Study at the University of Guelph. He is also the Past-President for the Canadian Nutrition Society. Dr. Ma’s research encompasses investigations to better understand the role of fats in human health and disease.  Studies seek to enhance our understanding of the role of fats through the lifecycle and how various fats support health, prevent and treat chronic diseases. Dr. Ma has published more than 100 peer-reviewed papers in areas related to diet and cancer, nutrigenomics, and the role of omega-3 and omega-6 fatty acids in health and disease. As the Director of the Guelph Family Health Study (GFHS), a longitudinal cohort study of families with young children, he leads a multidisciplinary team of investigators and trainees to better understand determinants of health in young families. The goal of the GFHS is to develop tools and new approaches to support healthy habits and behaviours that will have lasting benefits for the prevention of chronic disease.


Dr. Richard Bazinet
Dr. Bazinet received his BSc from the University of Western Ontario and completed his PhD under the supervision of Dr. Stephen Cunnane at the University of Toronto in 2003.  Dr. Bazinet then completed a postdoctoral fellowship in Dr. Stanley Rapoport’s Brain Physiology and Metabolism Section at the National Institute on Aging, National Institutes of Health.   Dr. Bazinet joined the University of Toronto in 2006, where he is currently an Associate Professor and Canada Research Chair in Brain Lipid Metabolism.  Dr. Bazinet is the recipient of several awards, including the Early Career Award from the International Society for the Study of Fatty Acids and Lipids; the Jordi-Folch-Pi Memorial Award from the American Society for Neurochemistry; the Future Leaders Award from the International Life Sciences Institute,  the Young Scientist Award for the American Oil Chemists’ Society and the Early Researcher Award from the Canadian Society for Nutrition.   Dr. Bazinet sits on several editorial boards and is currently Editor-in-Chief of Prostaglandins, Leukotrienes and Essential Fatty Acids as well as a Senior Associate Editor of Lipids.  The overall goal of Dr. Bazinet’s research program is to identify the mechanisms that regulate brain lipid metabolism (signaling) and to identify the role of brain lipid metabolism in the pathogenesis of neurodegenerative diseases and neuropsychiatric disorders.  Dr. Bazinet has published over 150 papers, largely in the field of brain fatty acid metabolism and is co-author of the joint WHO/FAO joint expert consultation on dietary fats and the central nervous system during aging and disease.  Dr. Bazinet is currently the president of the International Society for the Study of Fatty Acids and Lipids (ISSFAL). 


Morning Segment: Moderated by David Ma
09:15 - 10:00   The Dietary Reference Intakes Process and Guiding Principles for using Chronic Disease Endpoints
Speaker: Amanda J. MacFarlane - Nutrition Research Division, Health Canada
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In 1994, the governments of Canada and the US jointly supported the Food and Nutrition Board (National Academies of Sciences, Engineering and Medicine) to develop harmonized nutrient reference values. A risk assessment framework was established that included an explicit statistical construct for intake and requirement distributions and concepts of risk at both the low and high end of intakes. The resulting Dietary Reference Intakes (DRIs) included the Estimated Average Requirement (EAR) and a Tolerable Upper Intake Level (UL). Given the growing recognition that nutrients contribute to chronic disease risk, reduction in the risk of chronic diseases was to be included in the formulation of the DRIs where sufficient data for efficacy and safety existed. While new reference values such as the Adequate Intake (AI) value were developed, incorporating chronic disease indicators proved challenging for establishing EARs and ULs; only a limited number of nutrients had values set based on chronic disease indicators. To address the scientific and evidentiary limitations, guiding principles for developing DRIs based on chronic disease endpoints were established recently and included the creation of a new DRI value, the Chronic Disease Risk Reduction (CDRR) value. I will present an overview of the basic risk assessment principles that underpin the DRIs, including the identification of appropriate biomarkers of status and health outcome, establishment of a causal relationship between the intake of a nutrient and health outcome, modelling the intake-response relationship between them, and the type of evidence required to substantiate these relationships, with a focus on chronic disease endpoints. 

About the Speaker:

Amanda MacFarlane, Ph.D. is a Research Scientist and Head of the Micronutrient Research Section in the Nutrition Research Division at Health Canada. She is an Adjunct Professor in the Dept. of Biochemistry, Microbiology and Immunology at the University of Ottawa and the Dept. of Biology at Carleton University. She has a Ph.D. in Biochemistry from the University of Ottawa (2004) and did her Post-Doctoral training in the Division of Nutritional Sciences at Cornell University (2004-2008). She joined Health Canada in 2008 where she examines the effect of folate intake on genotoxicity in somatic cells, as well as the impact of maternal and paternal folate intake on germline and offspring genomic and epigenomic stability. She also uses national health survey and cohort data to identify the socioeconomic, dietary and genetic determinants of folate and B vitamin status of Canadians. She was a Steering Committee member for the 2015 expert panel convened by the US National Toxicology Program and the NIH Office of Dietary Supplements for Identifying Research Needs for Assessing Safe Use of High Intakes of Folic Acid. She has been the Chair of the Joint Canada-US Dietary Reference Intakes Working Group since 2013. She was the Project Co-Director (2014-2017) for the expert panel and workshop “Options for Addressing Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs)” for which she won the Health Canada 2017 Deputy Minister’s Award for Excellence in Science. She is currently an Associate Editor for The American Journal of Clinical Nutrition.

10:00 - 10:30   Omega-3s and development: Structure and function
Speaker: Susan E. Carlson, PhD University of Kansas Medical Center
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DHA is a structural fatty acid in membranes that has been consistently shown to increase when DHA consumption is increased.   The DHA in erythrocyte phospholipids is a frequently used indicator of DHA status that reflects change in membrane DHA of other organs and brain regions. The presentation will address the balance of DHA and ARA in infant formulas fed during the first year of life on age-appropriate cognitive outcomes, behavior, EEG and fMRI out to 9 years of age.  Prenatal studies of DHA supplementation conducted since 2002, when US and Canadian infants began to receive DHA and ARA postnatally,  have measured similar outcomes out to age 6. While these studies don’t find convincing evidence of improved cognitive function with DHA supplementation, they also show that early structural changes in membrane DHA have long term effects on brain function and possibly function of other organs.

About the Speaker:

Susan E. Carlson is the AJ Rice Professor of Nutrition and University Distinguished Professor at the University of Kansas Medical Center in the Department of Dietetics and Nutrition and Director of the PhD Program in Medical Nutrition Science. She received her BS in Home Economics from Washington State University and her PhD in Nutrition (Biochemistry and Physiology) from Iowa State University.  She was an NIHLB Postdoctoral Fellow in the Department of Pathology at the University of Wisconsin–Madison and in the Department of Pediatrics at the University of South Florida, where she served on the Faculty in Pediatrics. She was a faculty member in  the Division of Newborn Medicine at the University of Mississippi Medical Center and in the Newborn Center at the University of Tennessee, Memphis, rising to the rank of Professor in the Departmens of Pediatrics, Obstetrics and Gynecology and Biochemisty.  She is an honorary member of the American Dietetic Association (2002) for pioneering work on the role of DHA in infant development, received the March of Dimes Agnes Higgins Award (2008) for pioneering research benefiting women and children, and is a Distinguished Alumna of Iowa State University (2017). She is a charter member of ISSFAL and served as President-elect, President and Past President (2009-2018).  She has delivered >180 invited international and national lectures, published >150 original reports and written 36 book chapters.  She works with an interdisciplinary team that includes a cognitive neuroscientist, electrophysiologist, and biostatistician doing large randomized clinical trials that seek to define the role of LCPUFA during the first 1000 days of development. Her research has been funded by the NICHD, NIHLB, and NEI.

10:30 - 11:00   Health Break
11:00 - 11:30   Evidence for CVD
Speaker: Ken Stark, PhD - University of Waterloo
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Evidence for potential cardiovascular benefits from the dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were initially driven by epidemiological observations from Greenland and Japan indicating that populations consuming high amounts of seafood and EPA + DHA such as Japan had a lower risk of cardiovascular disease.  Early clinical trials supported these observations with various cardiovascular benefits including antithrombotic, blood pressure lowering, heart rate lowering and antiarrhythmic effects.  A potent effect of EPA + DHA supplements reducing sudden cardiac death in the GISSI-Prevenzione trial would be a catalyst for dietary recommendations from various expert groups and societies.  While results from observational studies supported a beneficial effect of EPA + DHA on cardiovascular disease risk, the results from intervention studies were inconsistent.  In the past 15 years, numerous meta-analyses have been completed that have provided inconsistent conclusions.  The use of blood biomarkers of EPA + DHA status in clinical trials and their proper interpretation could resolve some of this heterogeneity.  The most recent meta-analysis that included three recent clinical trials (VITAL, ASCEND and REDUCE-IT) and considered dose levels indicates that EPA + DHA intake can reduce the risk of on coronary heart disease and will be examined in more detail.  

About the Speaker:

Ken Stark is a Canada Research Chair in Nutritional Lipidomics and a Full Professor in the Department of Kinesiology at the University of Waterloo.  He received his B.Sc. (Honours) from the University of Toronto and his Ph.D. from the University of Guelph and he completed a post-doctoral fellowship at the National Institute on Alcohol Abuse and Alcoholism of Health.  Dr. Stark has over 100 peer reviewed publications and he is known as a leader in the areas of fatty acid and lipid analytical methodology and the impact of diet on fatty acid metabolism.  He was a member of the ILSI-North America Fatty Acid Best Practices panel and currently serves on the Board of Directors of the International Society for the Study of Fatty Acids and Lipids.  His insights on the use of blood biomarkers to assess the intake of omega-3 polyunsaturated fatty acids have led to international collaborations resulting publications in high impact journals such as the New England Journal of Medicine, Progress in Lipid Research and Cell Stem Cell.

11:30- 12:00  Evidence for brain health and aging
Speaker: Melanie Plourde, PhD - Université de Sherbrooke
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Aging and carrying an epsilon 4 allele of apolipoprotein E (E4) are two prominent Alzheimer’s disease (AD) risk and both are associated with anomalies in lipid metabolism. Recent strong evidence links blood docosahexaenoic acid (DHA), an omega-3 (OM3) fatty acid in fish, with better cognitive scores and lower risk of AD [1]. There is, however, skepticism about this link and this is largely because there is a disconnect between epidemiological, molecular and animal studies which generally favor a link between higher DHA intake and neuroprotection whereas results of clinical DHA and fish oil are mixed. In this conference, we will briefly summarize these evidences. There are several knowledge gaps in this field that might explain the mixed results such as poor fundamental knowledge on: 1) OM3 fatty acid metabolism, 2) the blood-to-brain DHA link 3) the timing to which OM3 should be provided: before or after onset on AD, 4) duration of the OM3 intake and 5) whether DHA should be provided alone or combined with eicosapentaenoic acid (EPA). This conference will also review the evidence on the OM3 fatty acid levels during aging pre and post-supplementation and how this may affect brain health and dietary recommendation index. 

About the Speaker:

Prof Plourde obtained her PhD in 2006 from Université de Bourgogne and Université Laval. She completed 3 years of postdoctoral fellow in the group of Prof Cunnane at Université de Sherbrooke and she worked on lipid metabolism and ketone production. She then completed a one year postdoctoral fellow in genetics and nutrigenomics with Marie-Claude Vohl and Louis Pérusse at Université Laval. She is now Associate Professor at Université de Sherbrooke. Her research program is focussed on the hypothesis that docosahexaenoic acid (DHA), an omega-3 fatty acid, plays a role in human brain functions and cognition but this is conditional to how DHA is esterified on the glycerol backbone. She has shown that DHA metabolism is modified by aging and in carriers of the epsilon 4 allele of the apolipoprotein E (E4), the highest genetics risk for developing late-onset Alzheimer’s disease (AD). She has a multidisciplinary expertise that includes lipid nutrition, physiology, aging, cognition, genetics and obesity, with lipid metabolism as the central theme. Her research program includes experiments in humans and in knock-in mice for human E4. Since 2016, she received two competitive salary awards (CIHR and FRQ-S), one international (ILSI), one national (CIHR/CNS) and one institutional prize. She also received the first institutional Research Chair on lipid metabolism during aging donated by the Medical Research Center of Université de Sherbrooke. She has an h-index of 24. 

12:00 - 13:00 
Lunch / Networking
Afternoon Segment: Moderated by Dr. Richard Bazinet
13:00 - 13:30 Omega 3s – Immunity and Inflammation
Speaker: Catherine J. Field, PhD RD - University of Alberta
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An immune system that responds both effectively and efficiently to challenges in the environment and within the body is essential for health.  Altered and/or dysregulated immune function, particularly evidence of inflammation, has been identified as contributing to both the etiology and pathology of almost all of the chronic diseases. It is well established that consumption of the n-3 long-chain polyunsaturated fatty acids can regulate both immune development and immune function in animal models and humans.  To date the majority of the evidence in humans has come from observational studies of ‘healthy’ individuals or clinical trials conducted in individuals/patients with chronic diseases.  This has made translation to a DRI somewhat problematic.  This presentation will review the current evidence for the essentiality of the n-3 long chain polyunsaturated fatty acids, eicosapentaenoic and docosahexaenoic acid, for both immune development and function and the risk for chronic diseases. The knowledge gaps will be identified for further discussion. 

About the speaker:

Catherine Field’s research program centers on the effect of nutrition on the immune system. Current research includes: establishing the role of polyunsaturated fats on immune development, the use of fatty acids in the prevention and treatment of breast cancer and identifying the association between nutritional status and maternal mental health and infant neuro-physical development.  She has published more than 250 peer reviewed publications and trained over a 100 students in research.  Dr. Field received the McCalla and Killam Professorships from the University of Alberta, the Earl Willard McHenry Award for Leadership in Nutrition from the Canadian Nutrition Society and the Mary Mitchell Award for service to the Dietetic Profession in Alberta. Dr. Field is Past-President of the American Society for Nutrition, serves on the International Life Sciences Board of Trustees, is Vice Chair of the CIHR advisory board for INMD and an Associate Editor for Advances in Nutrition. 

13:30 - 14:00 A framework for developing recommended intakes of bioactive dietary substances
Speaker: Allison A. Yates, PhD, RD
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Since the first release of Dietary Reference Intakes for the U.S. and Canada in 1997 that included evaluating evidence for establishing intake recommendations for nutrients and other food components beyond the deficiency paradigm, advances in both how to approach consideration of research findings as well burgeoning research on many aspects of the diet have driven the need to more carefully approach the development of intake recommendations. To this end, the recent introduction of a new category of DRIs, Chronic Disease Risk Reduction intakes (CDRR) in 2017 by the Food and Nutrition Board, focused on chronic disease relationships, due to the many specific considerations that must be reviewed when evaluating risk which is influenced by both diet and other factors. Other food components, or dietary bioactives, now need to be considered in a framework or construct.  How to consider food components or bioactives in the food supply that play a role in maintaining health, but for which a deficiency state is not obvious, and for which a chronic disease relationship may not be causal, is needed.  This session will focus on the  developing step-wise process to evaluate safety and effectiveness of dietary bioactives, and develop recommended intakes where warranted.  A prototype example of such a process will be presented.   

About the speaker:

Allison A. Yates holds Bachelor’s and Master’s degrees from UCLA in public health and dietetics, a PhD from the University of California at Berkeley in nutrition, and is a registered dietitian. She served on the faculties of the University of Texas Health Science Center in Houston, Emory University School of Medicine in Atlanta, and was the founding Dean of the College of Health and Human Sciences at the University of Southern Mississippi in Hattiesburg.  Her research focused on human protein and energy requirements.  In 1994 she was named Director of the Food and Nutrition Board (FNB) of the Institute of Medicine, now the U.S. National Academy of Medicine, where, over a 10-year period through 2004, she led the expanded approach to establishing human requirements and recommendations for nutrients (RDAs), termed Dietary Reference Intakes (DRIs), for the United States and Canada. While at the FNB, she directed the 2002-2004 study for the U.S. FDA to design a framework for evaluating the safety of dietary supplements.  In 2006, she joined the U.S. Department of Agriculture, Agricultural Research Service (ARS), as Director of the Beltsville Human Nutrition Research Center; where she subsequently was appointed Associate Director for the Beltsville Area region of ARS, retiring in October 2014.  While at USDA, she served as the alternate delegate for the United States to the WHO/FAO Codex Committee on Nutrition and Foods for Special Dietary Uses. She was selected a Fellow of the American Society for Nutrition in 2014 and currently serves as an editor for the 11th edition of Present Knowledge in Nutrition as well as the chair of the ILSI-North America Standing Committee to Guide Development of Recommendations for Bioactive Dietary Substances. 

14:00 - 14:30 Health Break
14:30 - 15:15 Systematic reviews for nutrition studies using chronic disease endpoints
Speaker: George A. Wells, MSc, PhD - University of Ottawa Heart Institute
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Coming Soon

About the speaker:

George A. Wells, MSc, PhD
Professor, School of Epidemiology and Public Health, University of Ottawa
Professor, Department of Medicine, University of Ottawa
Principal Investigator, Cardiovascular Research Methods Centre, University of Ottawa
Heart Institute

Dr. Wells is a Professor in the School of Epidemiology and Public Health at the University of Ottawa and Principal Investigator of the Cardiovascular Research Methods Centre at the University of Ottawa Heart Institute. He is also a Professor in the Department of Medicine and a Senior Investigator at the Ottawa Hospital Research Institute at the Ottawa Hospital. His research interests are in the design and analysis of clinical trials, health technology assessment, statistical methodology related to health care delivery, systematic reviews andmeta-analysis, economic evaluations and the development and assessment of decision support technologies for patients and practitioners. Dr. Wells is the author or co-author of over 900 published articles and over 1050 scientific abstracts. He has been the principal investigator or co-investigator on over 270 research projects. His H-index score in Google Scholar is 174 and Scopus 134 and Web of Science 152. He has taught at the University graduate and undergraduate level for 40 years and has supervised over 100 graduate students.

Dr. Wells has worked extensively with national and international government and nongovernment research organizations, as well as private pharmaceutical and biotechnology industries. He has been on the executive and steering committees of national and international research programs, external safety and efficacy monitoring committees, scientific grant review committees, editorial committees and, scientific advisory committees. He is currently an Associate Editor of the Journal of Clinical Epidemiology and on the Editorial Committee of the Canadian Medical Association Journal.

15:15 - 16:00 Q #1 - Working discussion: How does the evidence map onto the guidelines for weight/strength of evidence?
16:00 - 16:45 Q #2Working discussion: What do we need for inclusion criteria for future research – which critical studies are lacking?
16:45 - 17:00 Closing Remarks
Speakers: David Ma and Richard Richard Bazinet
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