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Aat iscy srteevmieawt.i c review. internatioinnatel rgnraotuiopnsa ol fg eroxuppesrt so ft heaxtp perrotsv itdhea tW pHroOvi dweit hW tHheO lawtieths tt hsec ielantteifis ct sacniedn tifi c and technical teacdhvnicicea lo na dav icber ooand ara nbgroea do f ramnegdeic oafl amnedd ipcaulb laicn dh epaultbhl ics uhbejeacltths . subjects. 2002, ISB2N00 927, 8I S9B2 N4 917589 59624 43 ,1 5509 5p6ag4e3s, 50 pages MembersM oefm sbuecrhs eoxfp seurct hg reoxuppesr ts egrrvoeu pwsi tsheoruvte r ewmituhnoeurt arteiomnu inne rtahteioirn p ienr sthoeni-r person- al capaciatile cs arpaathceitrie tsh arant haesr rtehparne saesn traetpivreess eonft agtoivveesr nomf egnotvse ornr moethnetsr boor doitehse;r bodies; The ManTahgeem Meannt aogf eNmuetnritt oiofn N iunt Mritaiojonr i nE mMearjgoern Ecimesergencies their viewthse dir ov ineowt sn decoe nssoat rnilye creesfl seacrti lyth ree fld eecct istihoen sd eocr isthioen ss taotre dth ep osltiactye do f policy of 2000, ISB2N00 907, 8I S9B2 N4 917584 59220 4 4 1, 5244592 p0a g4e, s249 pages WHO. AnW HaOnn. uAaln saunbnsucarilp tsiounb stcor ipthtiiosn steor ieths,is csoemripersis, incgo mapbroisuint gs ixa bsouuct h six such reports, rceopsotsrt sC, HcFo s1ts6 8C.–H Fo r 1U68S.$– 1o5r 1U.–S $(C 1H5F1 .–1 2(8C.4H0F o1r 28 .U4S0 $ or1 1 5U.–S $in 115.– in ComplemCeonmtaprlye mfeeendtianrgy o ffe yeoduinngg ocfh yilodurneng cinh idlderveenlo ipni ndge vceoluonptirnige sc:o Au nrterviieesw: Ao fr eview of developindge vceoloupnitnrige sc).o uFnotrr iefusr)t.h eFro ri nffuorrtmheart ioinnf,o rpmleaatisoen ,c ponletaascet WcoHnOta cPtr eWssH,O Press, World HeWalothrl dO Hrgeaanltizha Otiorng,a n2i0z aativoenn, u2e0 Aapvpeinau, e1 2A1p1p iGa,e n1e2v1a1 2G7e, nSewvait z2e7rl,a nSdw itzerland current sccuiernrtein tc skcnieonwtile cd gkenowledge (tel.: +41( t2e2l. :7 +914 13 22624 7; 9fa1x 3: 2+6441; f2a2x :7 +914 14 82527 7; 9e1- m4a8i5l:7 b; oeo-mkoaridl:e [email protected];@ owr ho.int; or 1998, WH1O99/N8,U WTH/9O8./1N, U22T8/9 p8a.g1e, s228 pages order onlionred eart hotntlpin:/e/w awt wht.twph:/o/w.inwtw/b.owohkoo.irndte/brso)o.korders). WHO InforWmHaOtio Inn fPorromdautciotsn cParno dbuec otsb ctaainn ebde boyb ctaoinnetadc tbinyg c WonHtaOc tPinrges Ws,H O Press, WHO, 121W1 HGOen, e1v2a1 12 7G, eSnweivtzae 2rl7a,n Sdw, Eitzmearlial: nbdo,o Ekmoradile: [email protected], @Fawxh +o4.in1t ,2 F2a 7x9 +1 4418 2527 7o9r1 48 57 or by orderinbgy o onrldineer:i nwgw own.lwinheo: .winwt/bwo.wokhoor.dinet/rbsookorders cvr 15.5mm spine.indd 2 11/13/07 8:20:54 AM 92-4-120935-6_FM_i This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the World Health Organization, the Food and Agriculture Organization of the United Nations, or the United Nations University WHO Technical Report Series 935 PROTEIN AND AMINO ACID REQUIREMENTS IN HUMAN NUTRITION Report of a Joint WHO/FAO/UNU Expert Consultation 92-4-120935-6_FM_ii WHO Library Cataloguing-in-Publication Data Joint FAO/WHO/UNU Expert Consultation on Protein and Amino Acid Requirements in Human Nutrition (2002 : Geneva, Switzerland) Protein and amino acid requirements in human nutrition : report of a joint FAO/WHO/UNU expert consultation. (WHO technical report series ; no. 935) 1. Proteins. 2. Amino acids. 3. Nutritional requirements. I. World Health Organization. II. Food and Agriculture Organization of the United Nations. III. United Nations University. IV. Title. V. Series. ISBN 92 4 120935 6 (NLM classification: QU 145) ISSN 0512-3054 © World Health Organization 2007 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 3264; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the World Health Organization. Typeset in India Printed in Singapore 92-4-120935-6_FM_iii Contents 1. Introduction 1 References 6 2. Conceptual framework for estimating protein and amino acid requirements 9 2.1 Basic concepts 9 2.1.1 Metabolic demand 10 2.1.2 Growth 11 2.2 Dietary influences on demand 12 2.2.1 Energy 12 2.2.2 Micronutrients 12 2.2.3 Lifestyle and environmental influences 13 2.3 Achieving nitrogen balance 13 2.3.1 Maintenance amino acid catabolism and obligatory nitrogen losses 15 2.3.2 Digestibility of dietary proteins 16 2.3.3 Protein quality: matching the supply to the demand 18 2.3.4 Protein utilization and nitrogen balance 19 2.4 Response to variation in protein intake 20 2.4.1 Changes in body composition 21 2.4.2 Labile protein reserves 21 2.4.3 Protein turnover and amino acid recycling 22 2.5 Definition of requirement 24 2.6 Adaptive mechanisms 24 2.6.1 Adaptation of amino acid oxidation 25 2.6.2 Adaptation of urea metabolism: nitrogen metabolism in the lower gut 26 2.7 Summary metabolic model 27 References 30 3. Statistical concepts and procedures involved in deriving recommendations for protein and amino acid requirements 35 3.1 Overview 35 3.2 Phases of requirement estimation 36 3.2.1 Gathering and screening the data 36 3.2.2 Estimating the requirements of individuals 37 3.2.3 Examining influential factors 37 3.2.4 Estimating the distribution of requirements within a population 38 3.3 Reference requirements and intakes 39 3.3.1 Reference intakes and risk of dietary inadequacy for individuals 39 3.3.2 Reference intakes and risk of dietary inadequacy for a population 41 3.4 The cost of protein deficiency 45 References 47 iii 92-4-120935-6_FM_iv 4. General methods used for determining protein and amino acid requirements 49 4.1 Nitrogen balance 49 4.1.1 Practical aspects 50 4.1.2 Data interpretation 51 4.1.3 Other factors 54 4.1.4 General conclusion on nitrogen balance 55 4.2 Carbon balance 55 4.2.1 Practical aspects 55 4.2.2 Specific protocols 57 4.2.3 The 24-hour protocol 58 4.2.4 The fed-only protocol 61 4.2.5 Short-term fasting/feeding protocol 62 4.2.6 Data interpretation 63 4.2.7 General conclusion on carbon balance method 65 4.3 Indicator amino acid method 65 4.3.1 General approach 65 4.3.2 Summary of indicator amino acid method 70 4.4 Predictions from the obligatory nitrogen loss 71 4.5 Indirect estimates through measurement of protein utilization 71 4.6 Conclusions 72 References 73 5. Protein–energy interactions 79 5.1 Energy intakes and protein requirements 79 5.1.1 Nitrogen retention and variable energy balance 79 5.1.2 Nitrogen retention and variable energy turnover 80 5.1.3 Energy intakes and the interpretation of requirement studies 81 5.1.4 Protein–energy interactions in children 81 5.1.5 Protein-sparing effect of non-protein energy substrates 82 5.2 The protein:energy ratio 83 5.2.1 Protein:energy ratios as a measure of dietary protein quality 83 5.2.2 Protein:energy ratio of requirements and dietary assessment 84 5.2.3 Derivation of reference protein:energy ratios 85 References 89 6. Protein quality evaluation 93 6.1 Prediction of protein quality: using the protein digestibility corrected amino acid score (PDCAAS) approach 94 6.1.1 Protein digestibility 94 6.1.2 Biological value 95 6.1.3 Amino acid score 95 6.2 Current concerns about the protein digestibility corrected amino acid score (PDCAAS) approach 96 6.3 Conclusions 99 References 101 iv 92-4-120935-6_FM_v 7. Protein requirements of adults, including older people, and women during pregnancy and lactation 103 7.1 Evaluation of published nitrogen balance studies 104 7.1.1 Adjustment for dermal and miscellaneous nitrogen losses 104 7.1.2 Statistical analysis of nitrogen balance data 105 7.2 Population distribution of protein requirement and determination of the median 107 7.3 Estimation of the variability and population reference intakes 108 7.4 Basal metabolic demands: the obligatory nitrogen loss 109 7.5 Potentially important influential factors identified in the meta-analysis 110 7.5.1 Dietary source of protein 111 7.5.2 Climate 112 7.5.3 Age 112 7.5.4 Sex 112 7.6 Comparison with previous reports and other information 112 7.6.1 Dietary source of protein 113 7.6.2 Protein requirement of elderly people 114 7.6.3 Protein requirement of women 116 7.7 Protein requirements during pregnancy 116 7.7.1 Factorial approach 117 7.7.2 Nitrogen balance 119 7.7.3 Recommendations for protein intake during pregnancy 120 7.7.4 Diet interventions during pregnancy 121 7.7.5 Twin pregnancy 121 7.7.6 Adolescent pregnancy 121 7.8 Protein requirements during lactation 122 7.9 Areas of uncertainty 123 7.10 Summary of protein requirement values for adults, including women during pregnancy and lactation 125 References 126 8. Amino acid requirements of adults 135 8.1 Requirements for indispensable amino acids 136 8.1.1 Lysine 136 8.1.2 Leucine 138 8.1.3 Isoleucine and valine 139 8.1.4 Threonine 140 8.1.5 Aromatic amino acids 141 8.1.6 Tryptophan 143 8.1.7 Sulfur amino acids 144 8.1.8 Histidine 146 8.2 Dispensable amino acids 148 8.3 Summary of amino acid requirements in adults 149 8.4 Safe intakes of indispensable amino acids 150 8.5 Indispensable amino acid requirements in elderly people 150 v 92-4-120935-6_FM_vi 8.6 Requirement values compared with the amino acid content of food proteins and diets 151 References 152 9. Protein and amino acid requirements of infants and children 161 9.1 Maintenance requirement for protein 163 9.1.1 Interpretation of experimental information 163 9.1.2 Variability of maintenance 167 9.2 Protein deposition 167 9.2.1 Infants and young children, age 0–2 years 167 9.2.2 Children, age 4–18 years 168 9.2.3 Variability of protein deposition 170 9.2.4 Growth rates compared with previous estimates 171 9.3 Factorial estimates of protein requirements 171 9.3.1 Comparison with protein intakes of the breastfed infant 172 9.3.2 Implications of the estimated protein requirements for formula-fed infants 174 9.3.3 Average protein requirements and safe levels for infants and children from 6 months to 18 years 175 9.4 Amino acid requirements from infancy to 18 years 177 9.4.1 Infants up to 6 months 177 9.4.2 Older infants and children 178 References 182 10. Catch-up growth 185 10.1 Protein requirements for rapid weight gain in the wasted child 186 10.2 Catch-up in height in stunted children 189 References 191 11. Influence of infection on protein and amino acid requirements 195 11.1 Pattern of the protein and amino acid response to infection 196 11.2 Implications of HIV/AIDS 198 11.3 Recommendations for a protein allowance in infection 199 References 203 12. Implications of the protein and amino acid requirements for populations in developed and developing countries 207 12.1 Protein intakes of infants associated with adequate growth rates 208 12.2 Population intakes and the new requirement values 212 12.3 Implications of the apparent inadequacy of the diets in developing countries 218 References 221 13. Protein intake and health 223 13.1 Renal function 224 13.2 Bone health 224 13.3 Kidney stones 226 vi 92-4-120935-6_FM_vii 13.4 Cardiovascular disease 227 13.5 Cancer 229 13.6 Is there a maximum limit of dietary protein intake? 230 13.7 Conclusions 232 References 233 14. Summary of requirements 241 14.1 Derivation of requirements 241 14.1.1 Safe intake for individuals and populations 241 14.1.2 Precision of estimates 241 14.1.3 Age ranges 242 14.1.4 Relation to body weight 242 14.1.5 Corrections for characteristics of the diet 242 14.2 Protein requirements of adults 242 14.3 Protein requirements of infants, children and adolescents 243 14.4 Protein requirements of women during pregnancy and lactation 244 14.5 Amino acid requirements and scoring pattern of adults 245 14.6 Amino acid requirements and scoring pattern of infants, children and adolescents 245 14.7 Corrections for protein quality of the diet 245 14.8 Protein density of foods and the protein:energy ratio of the requirements 246 References 247 15. Research needs 249 15.1 Recommendations for future research 250 15.2 Regulatory issues 254 References 255 Acknowledgements 257 Annex. Statistical procedures 259 Derivation of reference protein:energy ratio, individual diets 259 Estimation of distribution parameters 260 Regression 260 Analysis of variance 264 References 265 vii 92-4-120935-6_FM_viii

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General methods used for determining protein and amino acid requirements. 4.1 Nitrogen balance. 4.1.1 Practical aspects. 4.1.2 Data interpretation. 4.1.3 Other
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