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DIETARY REFERENCE INTAKES (DRIs): DRIs): 10 Years Later Korean Nutrition Society November, 2004 Allison A. Yates DRIs Dietary Reference Intakes 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 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 Recommended Dietary Allowances 1989 Energy Protein 7 minerals (Ca, Fe, P, Mg, Zn, I, Se) vitamins (A, C, D, thiamin, riboflavin, niacin, E, K, B6, B12, folate) Safe and adequate daily dietary intakes (biotin, pantothenate, Cu, Mn, F, Cr, Mo) 11 160-02 402-01 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 126-01 401-01 Dietary Reference Intakes Process for Setting DRIs Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Committee of experts Literature review Solicitation of advice Panels Ca, Vitamin D, Phosphorus, Mg, F —Workshops —Scientific Meetings —Correspondence NRC Folate, B12, B Vitamins, Choline Upper Reference Levels Subcommittee Vitamins C and E, Se, ß-carotene and Other Carotenoids Vitamins A and K, As, B, Cr, Cu, Fe, I2, Mn, Mo, Ni, Si, V, Zn Risk Assessment Model Energy, CHO, Lipids, Amino Acids, Protein, Fiber, Physical Activity Uses of DRIs Subcommittee Assessment Planning Electrolytes, Water review Other Food Components? 147-01 Alcohol? 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 Top 10 DRI Questions Should 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) 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? DRIs? Conceptual Approach Criteria for Establishing RDAs Scientific Database Quantitative dietary recommendations need to address multiple users and meet multiple needs Observed intakes in healthy populations observations Balance studies Depletion/repletion studies Animal experiments Biochemical measurements Epidemiological —Labeling —Limits for fortification adequacy of diets of population groups —Assessing One number can’t do it all 142-02 130-01 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 Dietary Reference Intakes EAR UL RDA AI 0.5 0.5 Risk of excess Risk of inadequacy Frequency Distribution of Individual Requirements 2 s.d. Observed level of intake EAR 2 s.d. Increasing Intake Increase 196-02 194-01 Probability That Specified Usual Iron Intake Would Be Inadequate to Meet the Needs of a Randomly Selected Menstruating Woman1 Model for Dietary Reference Values Frequency Distribution of Individual Requirements 1 0.9 Probability of Inadequacy 0.8 Maintain Stores 0.7 0.6 0.5 Maintain Biochemical Function 0.4 0.3 0.2 0.1 Increasing Intake 3 ab 6 ay 9 10 EAR - Based on Indicator of Adequacy RDA Hb > 11.0 g/dl 0 6 195-02 G. Beaton, 1994 It Depends on the Criterion Chosen 0.5 0.5 RDA1 RDA2 Increasing Intake 217-03 10 12 14 16 Usual level of iron intake (mg/day) 18 20 216-03 Why an EAR? To UL Risk of excess Risk of inadequacy EAR1 EAR2 8 establish the recommendation for an individual To assess adequacy of population intakes Dietary Reference Intakes (DRIs) Relationship of EAR and RDA Estimated Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) 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) 199-01 205-02 Dietary Reference Intakes (DRIs) Model for Dietary Reference Values Frequency Distribution of Individual Requirements 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 Dietary Reference Intakes Based EAR UL RDA AI 0.5 0.5 Risk of excess 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 Risk of inadequacy Average Requirement (EAR) = requirement for 50% of the population Observed level of intake 207-01 Increase 196-02 UL Tolerable Upper Intake Level Dietary Reference Intakes (DRIs) 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 Unique Characteristics of Nutrients vs. Food Contaminants Why a UL? Absence To identify when it’ it’s possible to have adverse effects or toxicity when consuming too much of a nutrient of dose-response data 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 Few Effect of Uncertainty Assessment on UL Risk Assessment for Nutrients Risk of Adverse Effects Hazard Identification Dose-Response Assessment Exposure Assessment Risk Characterization (UF) Risk of Adverse Effects Risk Management (FDA) 231-01 RDA UL NOAEL LOAEL 100% 50% 100% RDA NOAEL UL LOAEL 50% Increasing Intake 230-03 Population Prevalence of Inadequate Intakes Why an EAR? To EAR Frequency establish the recommendation for an individual To assess adequacy of population intakes Intakes Area estimates prevalence of inadequacy Usual Intake (amount/day) 246-03 Vitamin C Intake for Men and Women Who Don’ Don’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 Vitamin Folate “Folate” Dietary Folate Equivalents E α - Tocopherol is generic term that includes food folates (pteroylpolyglutamates) and synthetic folic acid (pteroylmonoglutamic acid). Food Vitamin A Retinol Activity Equivalents folates must be hydrolyzed in the intestine prior to absorption, and are therefore less bioavailable than synthetic folic acid. Folate in Foods, Supplements Dietary Folate Equivalents: Serving Size Food Folate: 50% 1 µg DFE = 1.0 µg naturally present folate (DFE = 1 x weight) Folate from Fortified Food: 1 µg DFE = 0.6 µg added to foods 85% (DFE = 1.7 x weight) Folate from Supplements w/ water: >90% 1 µg DFE = 0.5 µg from supplements (DFE = 2 x weight) DFE µg 100 100 400 100 667 167 60 20 400 100 33 800 364-02 B12 RDA for Adults Ages 51+ Years 10-30% Orange juice 120 g Ready-to-eat cereals Highly fortified 30 g Mod. Fortified 1/2 cup Noodles, rice, pasta (cooked) 1 cup Bread 25 g Supplement 1 pill Folate µg Vitamin A 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 Comparison of 1989 and 2001 Interconversion of Vitamin A and Carotenoid Units NRC, 1989 IOM, 2001 1 retinol equivalent (RE) 1 retinol activity equivalent (RAE) = 1 µg all-trans-retinol = 1 µg all-trans-retinol = 2 µg all-trans-β-carotene = 2 µg all-trans- β-carotene in in oil oil = 6 µg all-trans-β= 12 µg all-trans-β- carotene carotene = 12 µg other dietary = 24 µg other dietary provit. A carotenoids provitamin A carotenoids 1 µg all-trans-retinol = 3.33 IU vitamin A activity from retinol (WHO, 1966) Required for normal vision, reproduction, gene expression, embryonic development, growth, and immune function Provitamin A carotenoids: β-carotene β-cryptoxanthin α-carotene Derivation of Retinol Equivalents NRC, 1989 Old RE for dietary β-carotene: supplemental βcarotene 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 αcarotene 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 αcarotene still 1/2 relative to β-carotene ∴ 1/24 Adverse Effects Considered in Setting the Upper Level for Vitamin A Bone mineral density Liver toxicity Teratogenicity 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 Upper Levels for Vitamin A Women of reproductive age NOAEL (teratogenicity) = 4,500 μg/day = 3,000 μg/day* UF 1.5 (women of reproductive All other adults age) Bulging LOAEL (liver toxicity) = 14,000 μg/day = 3,000 μg/day* UF 5 fontanel (infants) * From pre-formed vitamin A sources only Tolerable Upper Intake Levels for Vitamin A (µg/day) Life Stage UL 0–6 mo 7–12 mo 1–3 y 4–8 y 9–13 y 14–18 y ≥ 19 y 600 600 600 900 1,700 2,800 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 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 Vitamin K – vitamin E interaction 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 Setting the EAR for Iron for Infants and Children (1– (1–8 years) Factorial modeling Obligatory fecal, urinary, and dermal (basal) losses Increase in hemoglobin mass Increase in tissue (nonstorage) iron Increase in storage iron Indicators Considered for Estimating the Average Requirement for Iron Serum ferritin concentration total iron binding capacity Serum transferrin saturation Erythrocyte protoporphyrin Soluble serum transferrin receptor Hemoglobin concentration and hematocrit Erythrocyte indexes Balance studies Factorial modeling Plasma Setting the EAR for Iron for Children and Adolescents (9– (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* Zinc Gastrointestinal distress Impaired zinc absorption Cardiovascular disease Cancer Major roles: Catalytic Structural Regulatory UL = LOAEL (gastrointestinal = 70 mg/day ≈ 45 mg/day* UF distress) 1.5 *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 NUTRIENT INTAKES PLANNING DIETS Group Indiv. ASSESSING DIETS Group Indiv. From: Beaton, 1994 What are the Goals of Dietary Planning? 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 “Optimize prevalence of diets that are nutritionally adequate without being excessive” Meet nutrient requirements/recommendations — for — for individuals, low risk groups, low prevalence Avoid potential risks of excessive intakes — for — for individuals, low risk groups, low prevalence Planning for Individuals Planning for Individuals Are there special considerations? No Plan to meet RDA/AI Remain below UL Meet EER Stay within AMDR Pyramid not yet assessed to determine whether it requires revision to DRI recommended intakes Still the most useful way to begin planning individual diets Yes (e.g., smoker - Vitamin C) other nutrients Plan appropriate intakes based on special considerations 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 2: Estimate Target Usual Intake Distribution Step 1: Selecting Goals Acceptable prevalence of adequacy/inadequacy — No conventions; judgement is involved adequate (“almost everyone”), or 2-3% inadequate — 97-98% 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 Acceptable prevalence of potential risk of excess Step 3: Planning Menus Percent of Individuals Baseline Usual Intake Distribution EAR UL RDA For nutrients with EAR: select initial goal based on target usual intake distribution — Median of the distribution is a useful tool intakes are usually less than amounts offered; planning goal may need to be slightly higher than the median — But Usual intake of nutrient (amount /day) For nutrients with an AI: AI can serve as a goal for intakes 247-02 Step 4: Assess Results Percent of Individuals Target Usual Intake Distribution EAR RDA UL Usual intake of nutrient (amount /day) 247-02 Amounts “offered” may not equal amounts consumed Baseline intake distribution may have been obtained from another group Shape of intake distribution may change DRIs Macronutrients: New Concepts Adverse Effects Reviewed for Carbohydrate Behavior Dental Caries Blood Lipid Concentrations Coronary Heart Disease Diabetes Obesity Cancer No UL set for Carbohydrate 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 Added Sugars Glycemic Index Insufficient evidence in healthy people for setting a UL for carbohydrate -containing foods based on Glycemic Index 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 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 Food Composition Tables Dietary Fiber ≈ Total Fiber Based on few novel fibers in foods at the present time Physical Activity Levels (PAL) Criteria and AIs* AIs* for Total Fiber (g/day) AI Life Stage Criterion 0-6 m 7-12 m 1-3 y Prevent CHD 4-8 y Prevent CHD 9-13 y Prevent CHD 14-18 y Prevent CHD 19 - 50 y Prevent CHD > 50 y Prevent CHD Pregnancy Prevent CHD Lactation Prevent CHD Male ND ND 19 25 31 38 38 30 Female ND ND 19 25 26 26 26 21 28 29 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 200-01 (kcal/d) 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? — — — 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 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 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 Pattern1 Amino Acid mg/g protein Histidine Isoleucine Leucine Lysine Methionine + cysteine Phenylalanine + tyrosine Threonine Tryptophan Valine 1Based Dietary Fat 18 25 55 51 25 47 27 7 32 Total Fat Saturated Fat Monounsaturated fatty acids n-6 Polyunsaturated fatty acids n-3 Polyunsaturated fatty acids Trans fatty acids Cholesterol on reqts for 1-3 y for indispensable amino acids 200-01 Dietary Reference Intakes No ULs Set for EAR UL RDA 0.5 0.5 WHY? Risk of excess Total Fat Saturated Fat Monounsaturated Fat n-6 Polyunsaturated Fats n-3 Polyunsaturated Fats Trans Fat Cholesterol Risk of inadequacy Observed level of intake Increase 200-01 Increasing Intake of Cholesterol on Serum Total Cholesterol 3 Defined Diets (Data from Table 1) Self-Selected Diets (Data from Table 2) 2.5 Change in Serum TC (mmol/L) Trans Fatty Acid and Saturated Fat Intake and LDL:HDL Cholesterol Ratio 196-03 Linear (Defined Diets (Data from Table 1)) Linear (Self-Selected Diets (Data from Table 2)) 2 1.5 y = 0.0008x + 0.1737 R2 = 0.1844 1 y = 0.0004x + 0.0108 R2 = 0.1942 0.5 0 -0.5 -1 0 200 400 600 800 Change in Dietary Cholesterol (mg/d) 1000 1200 Dietary Reference Intakes (DRIs) Primary Fat Recommendations DRI is a collective term that includes nutrientbased dietary reference values: Minimize consumption of Saturated Fatty Acid Trans Fatty Acid Cholesterol while consuming a nutritionally adequate diet 200-01 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 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 Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL) Acceptable Macronutrient Distribution Range (AMDR) 199-01 Macronutrients with an AMDR For adults: Protein Fat Carbohydrate 10 - 35% 20 - 35% 45 - 65% n-6 polyunsaturated fatty acids 5 - 10% n-3 α-linolenic acid 0.6 – 1.2% 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