Individuals and Populations Future Dietary Reference Intakes* Targeting Healthy and “non-Healthy” Individuals and Populations Future Dietary Reference Intakes* *EA Yetley, AJ MacFarlane,LS Greene-Finestone, C Garza, JD Ard, SA Atkinson, DM Bier, AL Carriquiry, WR Harlan D Hattis, JC King, D Krewski, DL O’Connor, RL Prentice, JV Rodricks, and GA Wells. Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: report from a joint US-/Canadian-sponsored working group. Am J Clin Nutr. 105:249S-285S, 2017.

Demographic Shift Source: U.S. Census Bureau, 

Changes in the Landscape of Nutrition and Health 1988 Surgeon General’s Report 1989 Diet and Health Report 1994 How Should the RDAs be Revised? “As problems of nutritional deficiency have diminished in the U.S., they have been replaced by problems of dietary imbalance and excess”. Prevalence of Obesity: 1986 2010 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29%

Stunting Rates by Region (UNICEF)

Challenges in Setting Future DRIs for Healthy and “non-Healthy” Individuals and Populations Outcomes of interest are unlikely to be nutrient-specific Absolute risks of targeted preventable conditions are not 100% in any population group Uncertainty in magnitude of risk reduction effectiveness remains difficult to estimate Multi-factorial nature of likely outcomes of interest

Growth Reference Study Prescriptive Approach: Reference v Standard Optimal Nutrition Breastfed infants Appropriate complementary feeding Optimal Environment No microbiological contamination No smoking Optimal Health Care Immunization Pediatric routines Optimal Growth

Parental Education (y)

Mothers' heights – Longitudinal study cm 8% difference in maternal length (based on Oman) Source: WHO Multicentre Growth Reference Study Group. Enrolment and baseline characteristics in the WHO Multicentre Growth Reference Study. Acta Paediatr Suppl 2006;450:7-15 .

Fathers' heights – Longitudinal study cm 7% difference expressed as delta between Oman and Norway expressed as percent of Norway’s value Source: WHO Multicentre Growth Reference Study Group. Enrolment and baseline characteristics in the WHO Multicentre Growth Reference Study. Acta Paediatr Suppl 2006;450:7-15 .

Length at Birth cm 3% difference in birth length (based on delta between India and Norway, and expressed as % of birth lengths in India Source: WHO Multicentre Growth Reference Study Group. Enrolment and baseline characteristics in the WHO Multicentre Growth Reference Study. Acta Paediatr Suppl 2006;450:7-15 .

Mean Lengths from Birth to 24 Months at Each of the MGRS Sites Age Mean of Length (cm) 200 400 600 50 60 70 80 Brazil Ghana India Norway Oman USA

Projected Adult Heights Means (points) and standard deviations (bars) of the difference between 2 times the height of the child at two years and the mid-parental height by site.

Key Messages Mid-parental height consistently explained a greater proportion of observed variability in attained child length than either paternal or maternal height alone Doubling a child’s height at two years matched mid parental height when parental stature was likeliest to reflect genetic potential and their children’s care approximated international recommendations Meeting international care recommendations also resulted in predicted adult statures of the children that approximate international norms notwithstanding shortfalls in parental heights.

Nutrient-environment interactions: Not New to DRI Discussions Smoking (vitamin C) Sun exposure (vitamin D) Epigenetics - phenotypic flexibility Secular trends in food supply such as: Fibre Salt Omega-3 fatty acids Fortificants Use of dietary supplements – nutrients and natural health products

Key Questions To Be Addressed in Deriving DRIs for Low and Middle Income Countries/Regions When are DRI’s for healthy populations/individuals appropriate baselines for estimating needs of unhealthy populations/ individuals? How and when does one account for undesirable characteristics such as the occurrence of LBW, excessive energy intakes, specific morbidities, poor baseline diets, polluted environments, etc? How and when does one consider other variables such as the non- continuous nature of human growth, simultaneous consideration of multiple factors many possibly having small effects (some synergistic; others antagonistic) on targeted outcomes? What are impacts of irregular periods of dietary excesses and want?

Estimating ULs for Free Living Populations In Low and Middle Income Countries The pathophysiology of macro- and micronutrient excesses in healthy individuals is usually understood poorly at all life stages, adding to extrapolation difficulties. Nutrients that are deficient but required to maintain homeostatic mechanisms that counter responses to other nutrient excess(es) often are inadequately considered.