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FoodandAgricultureorganizationoftheunitedNations

y

IAEA

InternationalAtomicEnergyAgencyAtomsforpeaceandDevelopment

Developmentofaproteindatabaseandthewayforwardforreviewingproteinrequirements

ReportofajointFAO/IAEAtechnicalmeetinginVienna,10–13October2022

Developmentofaproteindatabaseandthewayforwardforreviewingproteinrequirements

ReportofajointFAO/IAEAtechnicalmeetinginVienna,10–13October2022

InternationalAtomicEnergyAgency

FoodandAgricultureOrganizationoftheUnitedNationsRome,2024

Requiredcitation:

FAO&IAEA.2024.Developmentofaproteindatabaseandthewayforwardforreviewingproteinrequirements–ReportofajointFAO/IAEAtechnicalmeetinginVienna,10–13October2022.Rome.

/10.4060/cd1021en

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©FAO/PedroCostaGomes,©FAO/MaximZmeyev,©FAO/SeyllouDialloand©FAO/GiulioNapolitano

iii

Contents

Abbreviations v

Participants vii

1.Introduction 1

Openingremarks 1

Rationaleforaproteindatabaseandpurposeofthetechnicalmeeting 2

Evolutionofexpertdiscussionsonproteinquality 2

2.Overviewofproteininfoodandproteinrequirementissues 4

2.1.Proteininfoods:traditional,alternativeandsustainablefoodproteinsources 4

2.2.Proteinrequirementsthroughoutthelifecourse 5

2.3.IAArequirementsthroughoutthelifecourse 8

2.4.ScoringmethodsandtheIAAreferencepattern 9

3.Proteindigestionintheintestineanddigestibilityissues 11

3.1.Overviewofproteindigestionandmetabolicutilization 11

3.2.Apparentversustruedigestibility 12

3.3.Faecalversusilealdigestibility 13

3.4.NitrogenversusindividualAAdigestibility 15

3.5.Foodfactorsimpactingdigestibility 15

4.ProteinandIAAilealdigestibilityassessedbydifferentmodelsandmethods 17

4.1.Intrinsicstableisotopelabellingofdietaryprotein 17

4.2.Ilealdigestibility–oro-ilealbalancemethodsinhumans 18

4.3.Ilealdigestibility–oro-ilealbalancemethodsinpigs 20

4.4.Ilealdigestibility–oro-ilealbalancemethodsinrats 20

4.5.Truedigestibility–thedualisotopemethodinhumans 22

4.6.Metabolicbioavailability–theIAAOmethodinhumans 26

4.7.Invitrodigestibility 28

5.Principleforthedevelopmentofadatabaseonproteinandaminoaciddigestibility 31

5.1.Initialconsiderations 31

5.2.Identificationofareferencemethodandvalidationissuesofothermethods 31

5.3.Thecriteriatobeused 31

5.4.Initialagreementsregardingthedatabase 33

6.Concludingremarksandfuturedirections 34

7.Recommendationsforthefuture 36

Notes 37

ANNEX:Openingremarks 53

iv

Tables

1.Proteinrequirementandproteintoenergyratiofordifferentagegroups 7

2.WHO/FAO/UNU(2007)indispensableaminoacidrequirements(mg/kg/d)inadultsandchildren.

1985FAO/WHO/UNUvaluesforadultsaregivenforcomparison 8

3.Referenceindispensableaminoacid(IAA)profilecalculatedfromtherequirementsforproteinand

foreachofthenineIAAs 9

4.Aminoacidscoreforlysinebasedon1985and2007IAArequirementpattern 10

5.Ilealandfaecaldigestibilityinadulthumansreceivingameat/cereal/dairy-baseddiet 14

6.IlealproteinandmeanAAdigestibility(inpercentage)inhumansequipped

withanilealtubeandwithileostomies 19

7.Meantrueilealaminoaciddigestibilitydeterminedinhumanvolunteersandrats 22

8.Trueilealdigestibilityofavarietyoffoodproteinsindifferentagegroups 25

9.Metabolicavailabilityoflimitingaminoacidsacrossvariousfoods 27

10.Thestrategiesforstudyingprotein/AAdigestibility 32

Figures

1.Proteinrequirementsofchildrenandyoungpeople(aged18yearsandbelow) 6

2.Meantrueilealaminoaciddigestibilityvaluesdeterminedinhumanvolunteersandrats 23

3.ComparisonbetweeninvivoandinvitromethodsforAAdigestibility 29

v

Abbreviations

AA

aminoacid

AAA

aromaticaminoacids

APE

atompercentexcess

BCAA

branched-chainaminoacids

Cas

casein

CHO

carbohydrate

CO2

carbondioxide

COST

EuropeanCooperationinScienceandTechnology

Digref

digestibilityofthestandardprotein

Digtest

digestibilityofthetestprotein

DIAAR

digestibleindispensableaminoacidratio

DIAAS

digestibleindispensableaminoacidscore

EAR

estimatedaveragerequirement

EED

environmntalentericdysfunction

FAM

FoodandAgricultureMicrodataCatalogue

FAO

FoodandAgricultureOrganizationoftheUnitedNations

GWG

gestationalweightgain

HIC

higher-incomecountry

2H2O

deuteratedwater

H2S

hydrogensulphide

IAA

indispensableaminoacid

IAAO

indicatoraminoacidoxidation

IAEA

InternationalAtomicEnergyAgency

INFOGEST

internationalnetworkofexcellenceonthefateoffoodinthegastrointestinaltract

INFOODS

InternationalNetworkofFoodDataSystems

kcal

kilocalorie

kdn

kidneybeanorblackbean

K15NO3

potassiumnitrate

vi

LMICslower-middle-incomecountries

Nnitrogen

15HN315NO3ammoniumnitrate(15NH4)2SO4ammoniumsulfate

NPPUnetpostprandialproteinutilization

PALphysicalactivitylevel

PDCAASproteindigestibility-correctedaminoacidscore

ppipeaproteinisolate

PPUpostprandialproteinutilizationPRIpopulationreferenceintake

RDArecommendeddietaryallowanceSAAsulphuraminoacids

SDGsSustainableDevelopmentGoals

SOFIStateofFoodSecurityandNutritionintheWorld

spisoyproteinisolate

sunsunflowerproteinisolate

TIMTNOGastro-IntestinalModel

tmptotalmilkprotein

UHTultra-hightemperature

UNUUnitedNationsUniversity

whbranwheatbran,wheat,wholewheat/wheatbran

WHOWorldHealthOrganization

wpiwheyproteinisolate

vii

Participants

•InternationalAtomicEnergyAgency(IAEA)

–MsCorneliaLOECHL

IAEA,NutritionalandHealth-RelatedEnvironmentalStudiesSection,DivisionofHumanHealth,P.O.Box100,1400Vienna,Austria.

–MrVictorOWINO

IAEA,NutritionalandHealth-RelatedEnvironmentalStudiesSection,DivisionofHumanHealth,P.O.Box100,1400Vienna,Austria.

–MsShrutiP.SHERTUKDE

IAEA,NutritionalandHealth-RelatedEnvironmentalStudiesSection,DivisionofHumanHealth,P.O.Box100,1400Vienna,Austria.

•FoodandAgricultureOrganizationoftheUnitedNations(FAO)

–MsMeganHARRISON(Virtual)

FAO,NutritionandFoodSystemsDivision(ESN),VialedelleTermediCaracalla1-00153,Rome,Italy.

–MrTakKeung(Warren)LEE(Virtual)

FAO,RegionalOfficeforAsiaandthePacific,39PhraAthitRoad10200.Bangkok,Thailand.

–MsDafniVASILOPOULOU

FAO,NutritionandFoodSystemsDivision(ESN),VialedelleTermediCaracalla1-00153,Rome,Italy.

–MsRamaniWIJESINHA-BETTONI

FAO,NutritionandFoodSystemsDivision(ESN),VialedelleTermediCaracalla1-00153,Rome,Italy.

–MsMariaXIPSITI(Virtual)

FAO,NutritionandFoodSystemsDivision(ESN),VialedelleTermediCaracalla1-00153,Rome,Italy.

•WorldHealthOrganization(WHO)

–MrJasonMONTEZ(Virtual)

WHO,DepartmentofNutritionandFoodSafety(NFS),20,AvenueAppiaCH-1211,Geneva24,Switzerland.

•BRAZIL

–MrEduardoFERRIOLLI

FaculdadedeMedicinadaUSP,Av.Dr.Arnaldo,455,01246-903SaoPaulo,SP,Brazil.

viii

•CANADA

–MsGlendaCOURTNEY-MARTIN

ResearchInstituteHospitalforSickChildren555UniversityAvenue,Toronto,OntarioM5G1X8,Canada.

–MrRajavelELANGO

ResearchInstituteBritishColumbiaChildren’sHospitalUniversityofBritishColumbia,938West28thAvenue,Vancouver,BritishColumbiaV5Z4H4,Canada.

–MrJamesHOUSE(Virtual)

UniversityofManitoba,FacultyofAgriculturalandFoodSciences,204RichardsonCentreforFunctionalFoodsandNutraceuticals,196InnovationDrive,Winnipeg,ManitobaR3T2N2,Canada.

•CHINA

–MsFeiHAN(Virtual)

AcademyofNationalFoodandStrategicReservesAdministration,Beijing100037,China.

•FRANCE

–MsJulianeCALVEZ

UMR914INRAE/AgroParisTech,PhysiologiedelaNutritionetduComportementAlimentaire(PNCA),

22placedeI’Agronomie,91123Palaiseau,France.

–MsClaireGAUDICHON

UMR914INRAE/AgroParisTech,PhysiologiedelaNutritionetduComportementAlimentaire(PNCA),

22placedeI’Agronomie,91123Palaiseau,France.

–MrDanielTOME

AgroParisTech,Paris,France.

•INDIA

–MrAnuraVKURPAD

DepartmentofPhysiology,StJohn'sMedicalCollege,Bengaluru,Karnataka,India.

•IRELAND

–MsMariaHAYES(Virtual)

FoodBioSciencesDepartmentTeagascFoodResearchCentre,D15KN3K,Dublin,Ireland.

•MEXICO

–MsAnaMaríaCALDERÓNDELABARCA

CentrodeInvestigaciónenAlimentacionyDesarollo,A.C.CarreteraalaVictoria,Km0.6ApartadoPostal173583304Hermosillo,Sonora,Mexico.

•MOROCCO

–MrMohammedELMZIBRI

DivisionSciencesduvivantCentrenationaldel’energie,dessciencesetdestechniquesnucleaires(CNESTEN)BP1382RP.10001Rabat,Morocco.

ix

•NETHERLANDS(KINGDOMOFTHE)

–MrJurriaanJ.MES(Virtual)

WageningenFoodandBiobasedResearchBornseWeilanden,9NL-6708WGWageningen,Netherlands.

•NEWZEALAND

–MsSuzanneHODGKINSON

RiddetInstitute,MasseyUniversity,PrivateBag11222PalmerstonNorth,NewZealand.

–MrPaulMOUGHAN(Virtual)

RiddetInstitute,MasseyUniversity,PrivateBag11222,PalmerstonNorth,NewZealand.

•SPAIN

–MsIsidraRECIO

InstitutodeInvestigacionenCienciasdelaAlimentacion,CIAL(CSIC-UAM)NicolasCabrera,9E-28049,Madrid,Spain.

•THAILAND

–MsWantaneeKRIENGSINYOS

InstituteofNutritionMahidolUniversitySalaya,NakhonPathom,73170,Thailand.

•UNITEDKINGDOMOFGREATBRITAINANDNORTHERNIRELAND

–MrThomasPRESTON

UniversityofGlasgow,ScottishUniversitiesEnvironmentalResearchCentre(SUERC),RankineAvenue,ScottishEnterpriseTechnologyPark,EastKilbride,G750QF,UnitedKingdom.

•UNITEDSTATESOFAMERICA

–MrHansH.STEIN

UniversityofIllinois,DivisionofNutritionalSciences,1207WestGregoryDr.Urbana,IL61801,UnitedStatesofAmerica.

1.Introduction

Forthefirsttime,theFoodandNutritionDivision(FormerlyNutritionandFoodSystemsDivision)oftheFoodandAgricultureOrganizationoftheUnitedNations(FAO)andtheDivisionofHumanHealthoftheInternationalAtomicEnergyAgency(IAEA)jointlyorganizedatechnicalmeetingheldinhybridformatinViennafrom10to13October2022.Duringthemeeting,aframeworkforthedevelopmentofaproteindatabaseandthewayforwardforreviewingproteinrequirementswasdiscussedandagreedupon.ThemeetingwasopenedbythedirectorofIAEA’sDivisionofHumanHealth,thedirectorofIAEAandthedirectorofFAO’sFoodandNutritionDivision.ItwasalsoattendedbyaWorldHealthOrganization(WHO)representativeandworldexpertsintheareasofnutritionandproteinqualityassessmentdrawnfrom16countries.Themeetingagreedontheneedtocreateadatabaseonproteinqualitywithinformationonproteindigestibilityandaminoacidabsorption,tobejointlymanagedbyFAOandIAEA,anddefinedaframeworkforestablishingthedatabase,includingasetofcriteriatobeusedfordatainclusion.Themeetingalsorecognizedthedearthofdataonproteinqualityfromlower-middle-incomecountries(LMICs)andrecommendedthatresourcesbemobilizedtomakethispossiblesothatthedatabase,whenestablished,canincludediversedata,includingthoseonclimate-smartfoodssuchasthoseconsumedinLMICs.Togeneratemoreproteinqualitydata,themeetingidentifiedstableisotopetechniquesasthebest-suitedtooltomeasureproteinqualityinhumansaccuratelyandinaminimallyinvasiveway.AnIAEA-coordinatedresearchprojectbringingtogethermultiplestakeholderstousestableisotopetechniquestogeneratemoredataonproteinqualitywasrecommended.Further,themeetingreviewedandmadesuggestionsonindispensableaminoacid(IAA)referencevaluestobeusedincombinationwithaminoacid(AA)absorptiondatatoaiddialogueonindividualproteinrequirementsacrossagegroups.

Openingremarks

TheopeningsessionwasmoderatedbyMsCorneliaLoechl,HeadoftheNutritionalandHealth-RelatedEnvironmentalStudiesSectionofIAEA’sDivisionofHumanHealth.Themeetingwasjointlyopenedby

MsMayAbdel-Wahab,DirectorofIAEA’sDivisionofHumanHealth,andMsLynnetteNeufeld,DirectorofFAO’sFoodandNutritionDivision.MsAbdel-Wahabnotedthetimelinessandsignificanceofthisuniquemulti-agencyandcross-disciplinaryconvergenceonatopicofgreatimportanceandobservedthatthiswasonesteptowardsaddressingthenumerousfactorsthatundermineourabilitytocombatmalnutritioninallitsformsby2030,especiallyinlightofarapidlygrowingglobalpopulationandmoreawarenessoftheenvironmentalfootprintoffoodconsumption.Shestatedthatthiscomplexityhasledtorecommendationsforashifttomoresustainableproteinsources,especiallywithmoreproteinofplantorigin.Butthiscomeswithtrade-offsrelatedtohowmuchoftheproteinconsumedbecomesavailabletothehumanbody,shenoted.Paradoxically,highatmosphericcarbondioxideemissionsarelinkedtoreducednutrientconcentrationsandbioavailabilityinmajorfoodcropssuchasrice,wheatandbarley,withprotein,ironandzincbeinggreatlyimpacted.Pandemicsandotheremergingchallengessuchasrampantglobalinflationalsocontinuetodrasticallylimitouraccesstofoodsrichinhigh-qualityprotein.MsAbdel-WahabhighlightedthatinthecourseoftimeIAEAhasjoinedhandswithotherplayerssuchasFAOindiscussionsandactivitiestogeneratemuch-neededdataonproteinquality.Sheemphasizedthatstableisotopetechniqueswillcontinuetobecentraltoourabilitytoprovideanevidencebaseuponwhicheffortstoensuresupplyofadequateandhigh-qualityproteintomeetrequirementsacrossvariousagesandphysiologicalstatescanbeanchored.Moreover,allproteinqualitydata,whethercollectedbyisotopictechniquesorotherapproaches,mustbeproperlyandsustainablycuratedandstoredinsecuredatabases.Inclosing,MsAbdel-Wahabremindedtheparticipantsthattheirdiscussionsoncreatingaframeworkfortheproteinqualitydatabasewereveryimportant.

MsNeufeldfurtherwelcomedtheparticipantstothetechnicalmeetingandnotedtheimportanceoftwoagenciescomingtogethertoco-organizeameetingofthissignificance.SheemphasizedthatUnitedNationsagencieshaveauniqueroleinachievingtheSustainableDevelopmentGoals(SDGs)andthealignedglobalnutritiontargetsby2030.Referringtothe2022StateofFoodSecurityandNutritioninthe

2

World(SOFI)report,shesaidthattheworldismovingbackwardsinitseffortstoendhunger,foodinsecurityandmalnutrition;hence,themeetingwasofcriticaltimelyimportancebecauseprovidinganadequate,

sustainableandnutritioussupplyofproteinremains

anincreasingchallenge.Inthisregard,plant-basedproteinsandnovelproteinsourcessuchasinsectshavebeensuggestedtohavegreaternutritionalvalue,aswellaslessenvironmentalimpact,than“traditional”

proteinsources.Understandingthepotentialrole

ofdifferentproteinsourcesbybeingabletoassessproteinqualityisthereforealsoparamountinthelightofchangingfoodsystems,MsNeufeldcontinued.

BetternutritionisoneofthefourfundamentalaspirationssetoutinFAO’sstrategicframework,alongsidebetterproduction,abetterenvironmentandabetterlife.Therighttoadequatefoodandatransitiontowardshealthydietsfornationalpopulationsisatthecoreofbetternutrition.Inthisregard,accuratelydefiningtheamountandqualityofproteinrequiredtomeetnutritionalneedsandappropriatelydescribingtheproteinsuppliedbyfoodsanddietsisofcriticalimportance.MsNeufeldremindedtheparticipantsthatFAO,alongsideIAEA,WHOandothers,hasalonghistoryspanningover50yearsinleadingtheworkonestablishingglobalnutrientrequirementsandcoordinatingdiscussionsonaccuratelymeasuringproteinqualityinfoodsanddiets.

MsNeufeldsaidthatsince2013,followingFAOrecommendationsonbettermethodstoassessproteinquality,sufficientdatahavebecomeavailableonilealAAdigestibilityoffoodsanddietsfromvariousregionsmeasuredindifferentpopulationsanddifferentphysiologicalstatesthroughoutthelifecycle.FAO,withfundingprovidedbytheGovernmentofCanada,recentlyinitiatedaprojectincollaborationwithIAEAtoinformfuturedevelopmentsofaproteindigestibilitydatabasetoaiddialogueontheevaluationofproteinqualityandproteinsufficiencyindifferentpopulations.MsNeufeldthankedtheparticipantsandremindedthemoftheimportanceofthetaskathand.

Rationaleforaproteindatabaseandpurposeofthetechnicalmeeting

Accuratelydefiningtheproteinamountandqualityrequiredtomeethumannutritionalneedsandappropriatelydescribingtheproteinsuppliedbyfoodsanddietsiscriticalformeetingglobalnutritiontargets.ScientificadviceonproteinqualityevaluationisalsorelevantforthedevelopmentofCodexAlimentariusfoodstandardsandguidelines.

Standardizeddataonfoodproteinqualityinhumanshasapotentialtoinformdialogueonrecommendationsforproteinrequirementsforallagegroups,especiallyinthefirst3yearsoflife.

Evolutionofexpertdiscussionsonproteinquality

Manyscientificdevelopmentsrelatedtoproteinqualityhavebeenachievedoverthepastdecades.Aminoacidmetabolicavailability,theproteindigestibility-correctedaminoacidscore(PDCAAS),andthedigestibleindispensableaminoacidscore(DIAAS),whichisbasedonthemeasurementofmetabolicavailabilityandthetruespecificoro-ilealdigestibilityofeachindividualAA,havebeendiscussedinvariousexpertconsultations.1,2In2014,anFAOexpertworkinggroupmeetingheldinBengaluru,India,discussedthemostappropriatemethodologiesformeasuringproteindigestibilityandutilizationinhumans.FiveresearchprotocolscurrentlyinuseorwithpotentialforfurtherdevelopmentforstudyingtrueilealAAdigestibilityinhumans,pigsandratswererecommendedformeasuringtheDIAAS,namely:

i.trueilealaminoaciddigestibility;

ii.thedualisotopetracerapproach;

iii.indicatoraminoacidoxidation;

iv.postprandialproteinutilization;andv.netpostprandialproteinutilization.

TheFAOexpertworkinggroupmeetingfurtherrecommendedestablishingarobustdatabaseofproteindigestibilityoffoodscommonlyconsumedworldwide,includingthoseconsumedinLMICs.Sincethen,datahaveprogressivelyaccumulatedonilealAAdigestibilityoffoods,measuredusingdifferentmethodsbothinanimalmodels(pigsandrats)andinhumans,includingpopulationsfromdifferentregionsandindifferentphysiologicalstatesthroughoutthelifecourse.Anew,non-invasiveindirectdualisotopetracermethodwasdevelopedaspartoftheIAEA-supportedCoordinatedResearchProject“Bioavailabilityofproteinsfromplant-baseddiets”(E4.30.31.)involvingthelabellingofthetargetfoodwithdeuteriumandadditionofa13C-labelledproteinorcrystallineAAmixtureatthepointofconsumption.ThismethodwasusedtoevaluateindividualAAdigestibilityoflegumeproteinsinhealthyadultsinBrazil,India,Jamaica,Mexico,Morocco,PakistanandThailandandto

3

determinetheproteinqualityofcomplementaryfoodsusedforyoungchildreninIndia.

Purposeofthetechnicalmeeting:Toreviewandupdateevidenceandrelatedmethodsonproteinrequirementsandproteinqualityassessmentandtodesignaframeworkfordevelopmentofaproteindigestibilitydatabasetoaiddialogueontheevaluationofproteinqualityandproteinsufficiencyindifferentpopulations.

Specificobjectives

1.Tocriticallyreviewandevaluaterat,pigandhumanmodelsandmethodsusedtoassessilealAAdigestibilityandthedataobtainedwiththemodelsandmethodsrelatedtofoodcommoditiescurrentlyavailableforhumanpopulationsandanimalmodels.

2.ToreviewdataobtainedforhumanpopulationsindifferentphysiologicalorpathologicalstatesandenvironmentsthroughoutthelifecourseonproteinqualitybasedontheDIAASfromproteinsourcesincludingtraditionalfoods,alternativeproteinsourcesandproteiningredients.

3.Toproposeaconcreteframeworkforharnessingtheknowledgeintoafuture,fullyaccessible,robustdatabaseonproteindigestibilityoffoodsanddietsfromdifferentregionsoftheworld.

4.Todiscussandproposemechanismsforutilizinginformationonproteindigestionthatoccursalongtheentiretyofthegastrointestinaltracttoinformdialogueonproteinrequirementsthroughoutthelifecourse.

5.Toproposeadditionalresearchthatisneeded,includingvalidationofmethods.

Reportstructure

Thisreportisasynthesisoftechnicalbackgroundpresentationsanddiscussionsbyparticipantsduringthetechnicalmeeting.Itcoversaglobalpresentationoftheconceptofproteinqualityandrequirementsthroughoutthelifecourse,touchingonhistoricalaspectsoftherecommendationssetvariouslybyFAO/WHO/UnitedNationsUniversity(UNU).Itdiscussestheimportantelementsneededtosetproteinrequirements,suchasIAAscoresandIAAreferencepatternsandtheassociatedmethods.Thereportthennarrowsdownonassessmentofproteindigestionandmetabolicutilizationandrelatedassessmentmethods,includingstableisotopetracertechniques.Lastly,thereportsummarizestheframeworkforanewproteinqualitydatabasejointlymanagedbyFAOandIAEA,whichwasagreedonbyexpertsatthetechnicalmeeting.

4

2.Overviewofproteininfoodandproteinrequirement

issues

Proteinsaccountforasignificantpartofanimalandplanttissuesandmicroorganismsandarethemainnitrogenousconstituents,withapproximately16percentnitrogen(N)byweight.3ThebasicstructuralunitsofproteinsaretheAAs,whicharecharacterizedbyanitrogen-containingaminefunction,anacidcarboxylgroupandaspecificlateralchain.Proteinsareconstitutedby20AAs,whicharelinkedtogetherbypeptidebonds.

2.1.Proteininfoods:traditional,alternativeandsustainablefoodproteinsources

Proteinsareavita

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