Dietary Reference Intakes

DIETARY REFERENCE INTAKES (DRIs): 10 Years Later Korean Nutrition Society November, 2004 Allison A. Yates Director, Nutritional Sciences ENVIRON Health Sciences Institute Funding for the DRIs has been provided by the U.S. DHHS (Office of Disease Prevention and Health Promotion, Food and Drug Administration, Centers for Disease Control and Prevention, and NIH); USDA; U.S. Army; Health Canada; the Dannon Institute;International Life Sciences Institute-North America, and the DRI Corporate Donors Fund (contributors include Roche Vitamins, Kemin Foods; M&M/Mars; Mead Johnson Nutritionals; and Nabisco Foods Group) 121-03 DRIs Dietary Reference Intakes Food and Nutrition Board 119-02 Recommended Dietary Allowances 1941 Energy Protein 2 minerals (Ca, Fe) 6 vitamins (A, C, D, thiamin, riboflavin, niacin) 159-02 402-01 Recommended Dietary Allowances 1989 Energy Protein 7 minerals (Ca, Fe, P, Mg, Zn, I, Se) 11 vitamins (A, C, D, thiamin, riboflavin, niacin, E, K, B 6, B 12, folate) Safe and adequate daily dietary intakes (biotin, pantothenate, Cu, Mn, F, Cr, Mo) 160-02 Definition of RDAs... levels of intake of essential nutrients considered, in the judgment of the Food and Nutrition Board on the basis of available scientific knowledge, to be adequate to meet the known nutritional needs of practically all healthy persons. NRC, 1974, 1980, 1989 181-01

FNB 1994 Concept Paper Focused on Need to Include Recommendations to meet variety of uses Concepts of reduction of risk to chronic disease Review of other food components Rationale for functional end points used Open dialog with interested groups Estimates of upper limits of intakes 401-01 126-01 Process for Setting DRIs Committee of experts Literature review Solicitation of advice Workshops Scientific Meetings Correspondence NRC review 147-01 Upper Reference Levels Subcommittee Risk Assessment Model Dietary Reference Intakes Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Panels Ca, Vitamin D, Phosphorus, Mg, F Folate, B 12, B Vitamins, Choline Vitamins C and E, Se, ß-carotene and Other Carotenoids Vitamins A and K, As, B, Cr, Cu, Fe, I 2, Mn, Mo, Ni, Si, V, Zn Energy, CHO, Lipids, Amino Acids, Protein, Fiber, Physical Activity Other Food Components? Electrolytes, Water Alcohol? Uses of DRIs Subcommittee Assessment Planning 149-05 Top 10 DRI Questions What s wrong with the old RDAs? Can t you just update the numbers? Is DRI the new term for RDA? What s the difference between an RDA and an AI? 142-02

Top 10 DRI Questions Why are some of the ULs less than the new RDAs for the same nutrients? Why were DFEs developed? Why were REs changed to RAEs? How can the UL for sodium be so low? No one eats such a small amount (2,300 mg) Top 10 DRI Questions Should I be concerned that the current food label in the U.S. uses 15 mg of zinc as the DV, and this is more than the new RDA for adults (11 mg), and twice the UL for children 1-3 years (7)? Which DRI should I use to plan diets with? Why aren t there different ULs for men and women? 142-02 Why DRIs? Conceptual Approach Quantitative dietary recommendations need to address multiple users and meet multiple needs Labeling Limits for fortification Assessing adequacy of diets of population groups One number can t do it all 142-02 Criteria for Establishing RDAs Scientific Database Observed intakes in healthy populations Epidemiological observations Balance studies Depletion/repletion studies Animal experiments Biochemical measurements 130-01 Dietary Reference Intakes (DRIs) DRI is a collective term that includes nutrientbased dietary reference values: Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) Acceptable Macronutrient Distribution Range (AMDR) 199-01 Dietary Reference Intakes (DRIs) DRI is a collective term that includes nutrient-based dietary reference values: Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) 199-01

Dietary Reference Intakes Frequency Distribution of Individual Requirements Dietary Reference Intakes Risk of inadequacy EAR UL RDA AI 0.5 0.5 Risk of excess Observed level of intake Increase 196-02 2 s.d. EAR 2 s.d. Increasing Intake 194-01 Model for Dietary Reference Values Frequency Distribution of Individual Requirements Increasing Intake 3 ab 6 ay 9 10 EAR - Based on Indicator of Adequacy RDA 195-02 Probability of Inadequacy Probability That Specified Usual Iron Intake Would Be Inadequate to Meet the Needs of a Randomly Selected Menstruating Woman 1 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Hb > 11.0 g/dl Maintain Biochemical Function Maintain Stores 6 8 10 12 14 16 18 20 G. Beaton, 1994 Usual level of iron intake (mg/day) 216-03 It Depends on the Criterion Chosen Why an EAR? Risk of inadequacy EAR 1 EAR 2 UL 0.5 0.5 Risk of excess To establish the recommendation for an individual To assess adequacy of population intakes RDA 1 RDA 2 Increasing Intake 217-03

Dietary Reference Intakes (DRIs) Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) 199-01 Relationship of EAR and RDA Estimated Average Requirement (EAR) = requirement for 50% of the population Recommended Dietary Allowance (RDA) = requirement for 97.5% of the population, so plan diets for individuals using this DRI RDA = EAR + 2 SD (if symmetrically distributed) 205-02 Model for Dietary Reference Values Frequency Distribution of Individual Requirements Dietary Reference Intakes (DRIs) Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) Increasing Intake 3 ab 6 ay 9 10 EAR - Based on Indicator of Adequacy RDA 195-02 199-01 AI Adequate Intake Based on observed or experimentally determined approximations of the nutrient intake by a defined population or subgroup that appear to sustain a defined nutritional state Used as a guide to nutrient intake for the individual 207-01 Risk of inadequacy Dietary Reference Intakes EAR RDA AI 0.5 0.5 UL Observed level of intake Risk of excess Increase 196-02

Dietary Reference Intakes (DRIs) UL Tolerable Upper Intake Level Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) The highest level of daily nutrient intake that is likely to pose no risks of adverse health effects to almost all individuals in the general population Not a recommended level of intake Not a level that is desirable to attain 199-01 211-02 Why a UL? To identify when it s s possible to have adverse effects or toxicity when consuming too much of a nutrient Unique Characteristics of Nutrients vs. Food Contaminants Absence of dose-response data Few available human or animal chronic studies Few surveillance studies to establish NOAEL (No Observed Adverse Effect Level) Available databases often concentrate on supplement intake, not total intake Significant differences in bioavailability 227-01 Risk Assessment for Nutrients Effect of Uncertainty Assessment on UL Hazard Identification Dose-Response Assessment Exposure Assessment Risk Characterization (UF) Risk Management (FDA) Risk of Adverse Effects Risk of Adverse Effects 100% 50% 100% 50% RDA UL NOAEL LOAEL RDA NOAEL UL LOAEL 231-01 Increasing Intake 230-03

Why an EAR? Population Prevalence of Inadequate Intakes To establish the recommendation for an individual To assess adequacy of population intakes Frequency EAR Area estimates prevalence of inadequacy Intakes Usual Intake (amount/day) 246-03 Vitamin C Intake for Men and Women Who Don t t Smoke (Food and Supplements) Vitamin C Intake for Men and Women Who Do Smoke (Food and Supplements) EAR = 60 mg for Women 75 mg for Men women below EAR = 10% men below EAR = 21% Adjusted EAR = 95 mg for Women 110 mg for Men women below EAR = 30% men below EAR = 52% 479-01 480-01 New Units of Expression Folate Folate Vitamin E Vitamin A Dietary Folate Equivalents α - Tocopherol Retinol Activity Equivalents Folate is generic term that includes food folates (pteroylpolyglutamates) and synthetic folic acid (pteroylmonoglutamic acid). Food folates must be hydrolyzed in the intestine prior to absorption, and are therefore less bioavailable than synthetic folic acid.

Dietary Folate Equivalents: Food Folate: 50% 1 µg DFE = 1.0 µg naturally present folate (DFE = 1 x weight) Folate from Fortified Food: 85% 1 µg DFE = 0.6 µg added to foods (DFE = 1.7 x weight) Folate from Supplements w/ water: >90% 1 µg DFE = 0.5 µg from supplements (DFE = 2 x weight) 364-02 Folate in Foods, Supplements Serving Size Folate µg DFE µg Orange juice 120 g 100 100 Ready-to-eat cereals Highly fortified 30 g 400 667 Mod. Fortified 1/2 cup 100 167 Noodles, rice, pasta (cooked) 1 cup 60 100 Bread 25 g 20 33 Supplement 1 pill 400 800 B 12 RDA for Adults Ages 51+ Years 10-30% adults >50 years: atrophic gastritis absorption of dietary B12 Bioavailability of food-bound B12 for elderly may be very low for some EAR, RDA: no change with age but foods fortified with B12 (such as fortified cereals) or B12-containing supplements should meet most of the RDA of 2.4 µg of B12 Vitamin A Required for normal vision, reproduction, gene expression, embryonic development, growth, and immune function Provitamin A carotenoids: β-carotene β-cryptoxanthin α-carotene Comparison of 1989 and 2001 Interconversion of Vitamin A and Carotenoid Units NRC, 1989 1 retinol equivalent (RE) = 1 µg all-trans-retinol = 2 µg all-trans-β-carotene in oil = 6 µg all-trans-βcarotene = 12 µg other dietary provit. A carotenoids IOM, 2001 1 retinol activity equivalent (RAE) = 1 µg all-trans-retinol = 2 µg all-trans-β-carotene in oil = 12 µg all-trans-β- carotene = 24 µg other dietary provitamin A carotenoids 1 µg all-trans-retinol = 3.33 IU vitamin A activity from retinol (WHO, 1966) Derivation of Retinol Equivalents NRC, 1989 Old RE for dietary β-carotene: supplemental β- carotene in oil well absorbed, converts to 1/2 vitamin A by weight; other food β-carotene only 1/3 absorbed, so conversion of food β-carotene is 1/3 x 1/2 = 1/6 Vitamin A activity of β-cryptoxanthin and α- carotene is 1/2 relative to β-carotene 1/12

Derivation of New Retinol Activity Equivalents IOM, 2001 RAE for dietary β-carotene: 1/6 (not 1/3) relative to absorption of supplemental β-carotene (in oil) conversion of absorbed β-carotene to vitamin A (1/2) = 1/12 Vitamin A activity of β-cryptoxanthin and α- carotene still 1/2 relative to β-carotene 1/24 Indicators Considered for Estimating the Average Requirement for Vitamin A Dark adaptation Serum/plasma retinol concentration Isotope dilution Relative dose-response/modified relative dose-response Conjunctival impression cytology Immune function Adequate liver stores Adverse Effects Considered in Setting the Upper Level for Vitamin A Bone mineral density Liver toxicity Teratogenicity (women of reproductive age) Bulging fontanel (infants) Upper Levels for Vitamin A Women of reproductive age NOAEL (teratogenicity) = 4,500 μg/day = 3,000 μg/day* UF 1.5 All other adults LOAEL (liver toxicity) = 14,000 μg/day = 3,000 μg/day* UF 5 * From pre-formed vitamin A sources only Tolerable Upper Intake Levels for Vitamin A (µg/day) Life Stage UL 0 6 mo 600 7 12 mo 600 1 3 y 600 4 8 y 900 9 13 y 1,700 14 18 y 2,800 19 y 3,000 Preg, Lact See age group Vitamin K Required as a coenzyme for the synthesis of proteins active in blood coagulation and bone metabolism

Special Considerations Vitamin K Coumadin interaction Patients undergoing anticoagulant therapy are advised to keep their daily vitamin K intake constant Vitamin K vitamin E interaction Adverse Effects Considered in Setting the Upper Level for Vitamin K No adverse effects of vitamin K from food were identified so no UL was set Probably of little consequence in healthy individuals; patients undergoing anticoagulant therapy should avoid large intakes of vitamin E (> 400 IU/day) Iron Component of a number of proteins including enzymes and hemoglobin Indicators Considered for Estimating the Average Requirement for Iron Serum ferritin concentration Plasma total iron binding capacity Serum transferrin saturation Erythrocyte protoporphyrin Soluble serum transferrin receptor Hemoglobin concentration and hematocrit Erythrocyte indexes Balance studies Factorial modeling Setting the EAR for Iron for Infants and Children (1 8 8 years) Factorial modeling Obligatory fecal, urinary, and dermal (basal) losses Increase in hemoglobin mass Increase in tissue (nonstorage) iron Increase in storage iron Setting the EAR for Iron for Children and Adolescents (9 18 years) Factorial modeling Basal losses Increase in hemoglobin mass Increase in tissue (nonstorage) iron Menstrual iron losses for girls (14 18 years)

Setting the EAR for Iron for Adults Factorial modeling Basal losses Menstrual losses (premenopausal women) Setting the EAR for Iron for Pregnancy Basal losses Fetal and placental iron deposition Increase in hemoglobin mass Adverse Effects Considered for Setting the Upper Level for Iron* Gastrointestinal distress Impaired zinc absorption Cardiovascular disease Cancer UL = LOAEL (gastrointestinal = 70 mg/day 45 mg/day* UF distress) 1.5 Zinc Major roles: Catalytic Structural Regulatory *May not protect individuals with hemochromatosis Adverse Effects Considered in Setting the Upper Level for Zinc Immunological response Serum lipoprotein and cholesterol concentration Reduced copper status Reduced iron absorption Leukocyte copper concentration UL = LOAEL (reduced copper = 60 mg/day = 40 mg/day UF status) 1.5 Conceptual Framework: Uses of Dietary Reference Intakes NUTRIENT REQT S PLANNING DIETS NUTRIENT INTAKES ASSESSING DIETS Group Indiv. Group Indiv. From: Beaton, 1994

What are the Goals of Dietary Planning? Optimize prevalence of diets that are nutritionally adequate without being excessive Meet nutrient requirements/recommendations for individuals, low risk for groups, low prevalence Avoid potential risks of excessive intakes for individuals, low risk for groups, low prevalence Goals are for Intakes Traditionally, planning has been for foods offered or served The actual goal, however, relates to intakes This is challenging, as planners can t control intakes Planning for Individuals Are there special considerations? No Plan to meet RDA/AI Remain below UL Meet EER Stay within AMDR other nutrients Yes (e.g., smoker - Vitamin C) Plan appropriate intakes based on special considerations Planning for Individuals Pyramid not yet assessed to determine whether it requires revision to DRI recommended intakes Still the most useful way to begin planning individual diets Assessment and Planning are Linked Planning for Homogeneous Groups Assess Plan Energy: Monitor body weight over time Nutrients: To be confident intakes meet RDA/AI, need many days of records Revise plan as necessary Select goals for each nutrient of interest Estimate target usual intake distribution Plan menus to achieve target usual intake distributions Assess results

Step 1: Selecting Goals Acceptable prevalence of adequacy/inadequacy No conventions; judgement is involved 97-98% adequate ( almost everyone ), or 2-3% inadequate Acceptable prevalence of potential risk of excess Step 2: Estimate Target Usual Intake Distribution For nutrients with EAR build directly on approach used in assessment When certain assumptions are met: The proportion of a group with usual intakes < EAR approximates the proportion with Intakes < Requirements Baseline Usual Intake Distribution Step 3: Planning Menus Percent of Individuals EAR RDA Usual intake of nutrient (amount /day) UL For nutrients with EAR: select initial goal based on target usual intake distribution Median of the distribution is a useful tool But intakes are usually less than amounts offered; planning goal may need to be slightly higher than the median For nutrients with an AI: AI can serve as a goal for intakes 247-02 Target Usual Intake Distribution Step 4: Assess Results Percent of Individuals EAR RDA UL Amounts offered may not equal amounts consumed Baseline intake distribution may have been obtained from another group Shape of intake distribution may change Usual intake of nutrient (amount /day) 247-02

DRIs Macronutrients: New Concepts Minimum amount of CHO = 130 g/d Limitation on added sugars = < 25% of kcal Quantitative recommendations for fiber in the diet Ranges for energy sources Acceptable Macronutrient Distribution Ranges (AMDR) Physical activity levels to decrease risk of chronic disease & maintain weight Recommendations for indispensable amino acids Protein scoring pattern Adverse Effects Reviewed for Carbohydrate Behavior Dental Caries Blood Lipid Concentrations Coronary Heart Disease Diabetes Obesity Cancer No UL set for Carbohydrate Glycemic Index Insufficient evidence in healthy people for setting a UL for carbohydrate -containing foods based on Glycemic Index Added Sugars Maximal intake of no more than 25 percent of energy from Added Sugars is suggested based on ensuring sufficient intakes of other micronutrients found in low amounts in food and beverages that are major sources of added sugars in the U.S. diet Definition of Fiber in the Diet Dietary Fiber consists of nondigestible carbohydrates and lignin that are intrinsic and intact in plants Functional Fiber consists of isolated, nondigestible carbohydrates that have beneficial physiological effects in humans Total Fiber is the sum of Dietary Fiber and Functional Fiber Food Composition Tables Dietary Fiber Total Fiber Based on few novel fibers in foods at the present time

Criteria and AIs* * for Total Fiber (g/day) AI Life Stage Criterion Male Female 0-6 m ND ND 7-12 m ND ND 1-3 y Prevent CHD 19 19 4-8 y Prevent CHD 25 25 9-13 y Prevent CHD 31 26 14-18 y Prevent CHD 38 26 19-50 y Prevent CHD 38 26 > 50 y Prevent CHD 30 21 Pregnancy Prevent CHD 28 Lactation Prevent CHD 29 Physical Activity Levels (PAL) Physical Activity Level (PAL) = total energy expenditure basal energy expenditure PA = 1.0 if PAL 1.0 < 1.4 (sedentary) PA = 1.12 if PAL 1.4 < 1.6 (low active) PA = 1.27 if PAL 1.6 < 1.9 (active) PA = 1.45 if PAL 1.9 < 2.5 (very active) *AI =14 g/1000 kcal x median energy intake for age group (kcal/d) 200-01 200-01 Physical Activity Recommended physical activity level (PAL) = > 1.6-1.9 Why? To decrease risk of chronic disease (CVD) To maintain ideal body weight (BMI = 18.5 to 25) For lower weight people to meet micronutrient & fiber intake recommendations What is a PAL > 1.6? Maintaining PAL of > 1.6 total activity equivalent to walking at 4 mph for 60 minutes gardening for 60 minutes climbing hill for 30 minutes All activities contribute to increasing the PAL How Activities Compare Metabolic equivalents (METS) Walking ~4 mph 4.5 Golf (with cart) 2.5 Cycling (leisurely) 3.5 Golf (without cart) 4.4 Aerobics 6.0 Jogging (10-min miles) 10.2 Swimming 7.0 Gardening 4.4 Household tasks, moderate effort 3.5 Climbing hills 6.9 Protein Recommendations RDA = 0.8 g/kg body weight/day using meta-analysis of nitrogen balance studies Same for men and women based on body weight No differentiation for animal versus vegetable protein, assumes complementary protein consumption No differentiation for age based on body weight (thus declining LBM) 200-01

Protein Digestibility Corrected Amino Acid Scoring Pattern 1 Amino Acid mg/g protein Histidine 18 Isoleucine 25 Leucine 55 Lysine 51 Methionine + cysteine 25 Phenylalanine + tyrosine 47 Threonine 27 Tryptophan 7 Valine 32 Total Fat Dietary Fat Saturated Fat Monounsaturated fatty acids n-6 Polyunsaturated fatty acids n-3 Polyunsaturated fatty acids Trans fatty acids Cholesterol 1 Based on reqts for 1-3 y for indispensable amino acids 200-01 No ULs Set for Total Fat Saturated Fat Monounsaturated Fat n-6 Polyunsaturated Fats n-3 Polyunsaturated Fats Trans Fat Cholesterol WHY? 200-01 Risk of inadequacy Dietary Reference Intakes EAR RDA 0.5 0.5 UL Observed level of intake Risk of excess Increase 196-03 Trans Fatty Acid and Saturated Fat Intake and LDL:HDL Cholesterol Ratio Increasing Intake of Cholesterol on Serum Total Cholesterol 3 Defined Diets (Data from Table 1) Self-Selected Diets (Data from Table 2) 2.5 Linear (Defined Diets (Data from Table 1)) Change in Serum TC (mmol/l) 2 1.5 1 0.5 0 Linear (Self-Selected Diets (Data from Table 2)) y = 0.0008x + 0.1737 R 2 = 0.1844 y = 0.0004x + 0.0108 R 2 = 0.1942-0.5-1 0 200 400 600 800 1000 1200 Change in Dietary Cholesterol (mg/d)

Primary Fat Recommendations Minimize consumption of Saturated Fatty Acid Trans Fatty Acid Cholesterol while consuming a nutritionally adequate diet 200-01 Dietary Reference Intakes (DRIs) DRI is a collective term that includes nutrientbased dietary reference values: Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) Acceptable Macronutrient Distribution Range (AMDR) 199-01 AMDR Acceptable Macronutrient Distribution Range Recommended range of macronutrient intakes in a healthy diet Associated with reduced risk of chronic disease while providing adequate intakes of essential nutrients Given as a percent of energy intake Macronutrients with an AMDR For adults: Protein 10-35% Fat 20-35% Carbohydrate 45-65% n-6 polyunsaturated fatty acids 5-10% n-3 α-linolenic acid 0.6 1.2% Example of Amount by Weight of Macronutrients in a 2,000 kcal Diet Nutrient AMDR Selected Amount Amount for 2,000 kcal Fat 20 35% 30% 67 g Linoleic acid* 5 10% 7% 16 g α-linolenic acid* 0.6 1.2% 0.8% 1.8 g Protein* 10 35% 15% 75 g Carbohydrate* 45 65% 55% 275 g *More than the AI or RDA for most individuals To Obtain Publications and Tables National Academies Press 1-800-624-6242 http://www.nap.edu download pdf files at FNB website: www.iom.edu/fnb JADA November 2002 vol. 102, pp. 1621-1630 JADA March 2001 vol.101, pp. 294-301 JADA June 2000 vol.98, pp. 699-706