Protein Recommendations: Time for an Update?
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1 Protein Recommendations: Time for an Update? Rajavel Elango Ph.D. Assistant Professor Department of Pediatrics, School of Population and Public Health University of British Columbia Scientist Level 1 Nutrition and Metabolism Research Program Child & Family Research Institute BC Children s Hospital
2 Protein Proteos which means primary or taking first place Function as enzymes, transport carriers, and as hormones Nutritional importance of protein is because of their constituent 20 amino acids
3 Amino Acids Essential Lysine, Methionine, Threonine Tryptophan, Phenylalanine, Histidine Leucine, Isoleucine, Valine Conditionally Essential Tyrosine, Cysteine, Arginine Glycine, Proline, Glutamine Non Essential Alanine, Asparagine, Serine Aspartate, Glutamate
4 Overview of Protein Metabolism Dietary Protein (amino acids) CHO, Fat C C Converted to + NH 3 CHO, Fat C Oxidized to CO 2 Synthesis Gut Free Amino Acid Pool Degradation Tissue Protein Stool (C and N) Urine (N) Non Protein Pathways
5 Overview of Protein Metabolism In: Protein intake 90g Gut Secreted Protein 70 g Absorbed Protein +150g Liver Kidney WBC RBC: Hemoglobin Muscle Viscera Brain, lung Plasma Proteins (Albumin etc) Out: Fecal Protein 10g (1.6g N) Urinary Nitrogen 75g (12g N) Other Losses 5g (0.8g N)
6 Number of People Number of People Nutrient Intake Recommendations Dietary Reference Intakes (DRI) Recommendations - North Americans FAO/WHO Recommendations worldwide/global Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) EAR RDA Nutrient Intake Level Nutrient Intake Level Dietary Reference Intakes (DRI) 2005
7 We can put a man on the moon, but.. Cannot come to a consensus on how much protein to give him on Earth! Adult Protein Recommendations (g Pr/kg/d) Year Organization RDA/Safe 1936 League of Nations Intake 1957 FAO FAO/WHO FAO/WHO FAO/WHO/UNU DRI FAO/WHO/UNU
8 Traditional Method to Define Requirements Nitrogen metabolism synonymous with protein metabolism Assumption is Nitrogen Balance = body needs for protein Nitrogen Balance = Nitrogen Intake - Excretion Dietary Reference Intakes (DRI) 2005
9 Traditional Method to Define Requirements Body Nitrogen Balance B = N balance I = Total N intake U = Urine N loss F = Fecal N loss S = Dermal N loss B = I (U + F + S)
10 Urinary Nitrogen Excretion -Low Protein Test Intakes Scrimshaw et al, J Nutr 1972
11 Limitations of Nitrogen Balance Method The rate of urea turnover to test protein is slow (3-7d) Accurate measurement of N balance is difficult: Overestimate intake, Underestimate excretion Therefore falsely positive nitrogen balances may be obtained Unethical to apply in children, elderly and in disease. Dietary Reference Intakes (DRI) 2005
12 New Method to Define Requirements Indicator Amino Acid Oxidation (IAAO) Rapid and quick and ethical to apply in vulnerable populations such as pregnancy, childhood
13 Dietary Protein End Product of Protein Metabolism (amino acids) 13 C Oxidized to 13 CO 2 Gut Free Amino Acid Pool Synthesis Tissue Protein Degradation H 2 O * * Phe Hydroxylase *CO 2 Homogentisate
14 Indicator Amino Acid Oxidation: Concept Decreasing IAAO represents increasing utilization of limiting amino acid for protein synthesis EAR RDA No change in IAAO as requirement for limiting amino acid has been met +2SD Amino Acid / Protein Intake Elango et al. J Nutr 138: , 2008
15 Minimally Invasive Technique Indicator Amino Acid Oxidation (IAAO) Single study day adaptation Elango et al. J Nutr 139: , 2009 Oral Stable Isotope delivery Kriengsinyos et al J Nutr 132:2251-7, 2002 Measurement of 13 CO 2 in breath and urine Bross et al J Nutr 128:1913-9, 1998
16 Typical Study Day Protocol Hour Test Meal Isotopes NaH 13 CO 3 L-[1-13 C]phe Samples Breath Urine VCO 2
17 Method: Pre-study assessment Indirect Calorimetry Calipers Bioelectric Impedance Analysis Medical and diet history, anthropometrics
18 Diet, Sample Collection Breath and Urine Sampling
19 Sample Analysis Multi-flow Continuous Isotope Ratio Mass Spectrometer Urine analysis by LC Tandem Mass Spectrometry
20 Summary of Adult Human Amino Acid Requirements ( ) Requirement estimates in mg/kg/d Amino Acid FAO 1985 IAAO FAO 2007 IAAO Reference Histidine Kriengsinyos et al (2002) Isoleucine Riazi et al (2003) Leucine Riazi et al (2003) Lysine Kriengsinyos et al (2002), Zello et al(1993) Methionine Di Buono et al (2001) Phenylalanine Hsu et al (2006) Threonine Wilson et al (2000) Tryptophan Lazaris-Brunner et al (1998) Valine Riazi et al (2003) Total BCAA Riazi et al (2003) Elango et al. Curr Opin Clin Nutr Metab Care 11:34-39, 2008
21 Current Recommendations for Protein Intake in Humans ADULTS EAR = 0.66 g/kg/d RDA = 0.80 g/kg/d Results based on Nitrogen Balance Dietary Reference Intakes (DRI) 2005; FAO/WHO/UNU 2007
22 Nitrogen Balance (mg N/kg/d) N Balance Studies in Young Men 'Zero' N Balance = 106 mg N/kg/d or 0.66 g Pr/kg/d Nitrogen Intake (mg N/kg/d ) Rand et al AJCN;73:109-27, 2003; Dietary Reference Intakes (DRI) 2005
23 Breath 13 CO2 excretion after L-[1-13 C]phenylalanine oxidation ( mol kg -1 h -1 ) Protein Requirements Adult Men 2.0 Breakpoint = 0.93 g kg -1 d -1 Upper 95% CI = 1.24 g kg -1 d Current DRI (2005) 1.0 EAR = 0.66 g/kg/d RDA = 0.8 g/kg/d Protein Intake (g.kg -1.d -1 ) Current recommendations are ~30% underestimated Humayun, Elango, et al Am J Clin Nutr;86: , 2007
24 Nitrogen Balance (mg N/kg/d) Reanalysis of N Balance Studies in Young Men Breakpoint = 146 mg N/kg/d or 0.91g Pr/kg/d Upper 95 % CI = 158 mg N/kg/d or 0.99 g Pr/kg/d Nitrogen Intake (mg N/kg/d ) Rand et al AJCN;73:109-27, 2003; Humayun, Elango et al AJCN;86: , 2007
25 Current Recommendations for Protein Intake in Children (6-10y) CHILDREN EAR = 0.76 g/kg/d RDA = 0.95 g/kg/d Results based on a Factorial Method Maintenance + Growth (Deposition/Efficiency) Where maintenance = Adult Nitrogen Balance values Dietary Reference Intakes (DRI) 2005; FAO/WHO/UNU 2007
26 Protein Requirements y Children F 13 CO 2 ( mol kg -1 h -1 ) 2.5 Breakpoint = 1.3 g/kg/d Upper 95% CI = 1.55 g/kg/d Current DRI (2005) EAR = 0.76 g/kg/d RDA = 0.95 g/kg/d Protein Intake (g kg -1 d -1 ) Current recommendations are ~70% underestimated Elango et al Am J Clin Nutr, 94: , 2011
27 Summary I Protein Requirements Protein Requirements (g Pr/kg/d) Adults DRI 2005 IAAO Increase In Req Children (6-10y) DRI 2005 IAAO Increase In Req EAR % EAR % RDA % RDA % Protein requirements are significantly underestimated
28 Elderly Protein Intakes 71y+ avg intake = 66 g/d Clear decline with aging Elderly women have lowest protein intake Fulgoni et al, AJCN 2008; 87:1554s-7s
29 Muscle Protein Synthesis (%/h) Muscle Mass and Function Loss with Age Age (years) Muscle mass and muscle protein synthesis decreases with age Sheen et al, AJCN 2001; 83:1554-7; Short et al AJP 2004; 286, E92-101
30 Protein Requirements 80y Women EAR = 0.85 g/kg/d RDA = 1.15 g/kg/d Current recommendations are ~30% underestimated Tang, Elango, Campbell WW et al Faseb J 2012
31 Protein Requirements 65-85y Women Current recommendations are ~30% underestimated Rafii, Courtney-Martin, Elango, Pencharz et al Faseb J 2013
32 Summary II Protein Requirements Protein Requirements (g Pr/kg/d) Elderly Women (80+y) DRI 2005 IAAO Increase In Req EAR % RDA % Currently follow up studies in men 65+y are ongoing
33 Quote: You are what you eat Perhaps: You are what your mother ate
34 Role of Protein in Infant Birthweight Duggleby and Jackson 2001 A 1g increase in protein intake preconception, 10 th, 28 th and 36 th wk of pregnancy leads to 8-11 g increase in birthweight
35 Maternal Fetal Nutrition Maternal Nutritional Cues Growth and Development
36 Pregnancy Recommendations vs Requirement DRI 2005 Recommendation g/kg/d For a 60 kg Pregnant Woman g/d EAR RDA Non-Pregnant adult protein needs + protein deposition Increasing protein intake (68 g/d to 101 g/d) improved birth weight of siblings - Montreal Diet Dispensary ( )
37 Protein Deposition in Pregnancy Protein synthesized per day: T1 T2 T3 1.2 g/d 6.1 g/d 10.7 g/d Pitkin (1976) Clinical Obstetrics and Gynecology 19(3):
38 F 13 CO 2 (umol/kg/h) Early Gestation wks Early gestation: n=34; Age=23-34y; singleton pregnancies EAR = 1.2 g/kg/d r 2 = Protein Intake (g/kg/d) Stephens, Elango et al Faseb J 2012
39 F 13 CO 2 (umol/kg/h) Late Gestation wks Late gestation: n=43; Age=24-35y; singleton pregnancies EAR = 1.52 g/kg/d r 2 = Protein Intake (g/kg/d) Stephens, Elango et al Faseb J 2012
40 Summary II Protein Requirements Protein Requirements (g Pr/kg/d) Pregnant Women DRI 2005 IAAO Early Gestation IAAO Late Gestation EAR RDA 1.1 Currently Lysine requirement studies are ongoing
41 Children Living in Developing Countries Sets Recommendations Grain & Cereal based diet Limiting in Lysine, an essential amino acid General Hypothesis: body has undergone adaptation and accommodation to survive on lower protein and energy Collaboration with St. John s Research Institute, Bangalore, India [2005 current] Malnourished school-aged children
42 F 13 CO 2 ( mol kg -1 h -1 ) F 13 CO 2 ( mol kg -1 h -1 ) Lysine Requirements: Canadian Vs. Indian Children Breakpoint = 35 mg kg -1 d -1 Upper 95% CI = 58 mg kg -1 d Breakpoint = 33.5 mg kg -1 d -1 Upper 95% CI = 46.6 mg kg -1 d Lysine Intake (mg kg -1 d -1 ) Lysine Intake (mg kg -1 d -1 ) EAR = 35 mg/kg/d EAR = 33.5 mg/kg/d Elango et al. AJCN 86:360-5, 2007 Pillai, Elango et al. J Nutr. 140:
43 Lysine Requirements: Malnourished Children EAR = 42.8 mg/kg/d EAR = 35.5 mg/kg/d Pillai, Elango et al. Dietary Protein for Human Health, Proceedings, 2011
44 Summary III Protein and Amino Acid Requirements Global lysine children requirements could be similar Earlier studies by Young & Kurpad in adult Indian men confirmed the same Protein requirements must be considered in the context of Amino acid composition Dietary energy Parasite infestation
45 Conclusions Current protein intake recommendations inadequate Optimal protein and amino intakes could have health benefits Local implications Elderly Care Homes, Hospital Nutrition Services Meals on Wheels Global implications -
46 Acknowledgements Study participants Canadian Institutes for Health Research (CIHR) Grant Support Mead Johnson Nutritionals (Canada) Ajinomoto Co Inc., Japan St. John s Research Institute, Bangalore
47 Questions?
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