17032013-Assessment of Protein Status

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SymposiumAssessment of Protein Nutritional Status12

VERHOH R. yOCW YG, J. SERGIO MARCHIHI* AND JOAQUN CORTIELLAL ab ora to ry o f H um an N utritio n, S ch oo l o f S cien ce a nd C lin ica l R esea rc h C en te r, M assa ch usettsIn stitu te of T ec hn olo gy , C am brid ge , M A 0 21 39 ; S hrin ers B urn s In stitu te, B osto n, M A, 02 01 4;*Diu is ion o f Nu tr ition, Medical Schoo l o f R ibeir oPre to , R ibeir oPre to , SP, 14049 , B ra zi l

A BSTRAC T An evaluation of protein status can beapp roached by use o f anthr opomtr ie ,c li ni ca l, and b ioc hemic al d ata , e ith er sin gly o r in c ombin atio n, a nd fu rth er a id ed w ith d ie ta ry d ata . E ac h o f th ese a pp ro ac he shas advan tages and l im i ta ti on s. B iochemica l eva lu at ionh as th e p ote ntia l o f b ein g th e mos t o bje ctiv e a nd q ua ntitative. Indicators that have been or m ight be usedin clu de p la sm a h ormon e re sp on se s to re du ce d p ro te inintake, plasm a lev els of specific proteins or spe cificam in o a cid s, u rin ary exc re tio n o f s pe ci fic am in o a cid sa nd o th er n itro gen-c on ta in in g compound s, a nth ro pom trieand ph ysical m easurem ents of body m usc lem ass, a nd fu nc tio na l te sts o f m usc le stre ng th . S ev era lmeas uremen ts c an b e comb in ed to p ro du ce n utritio na lin dic es o f b ro ad er p ote ntia l v alu e. T he im po rta nc e o fc on com ita nt in fe cti on and in flammatio n, w ith its manyeffects on protein m etabolism , cannot be ignored inm aking these assessm ents, unfortu nately, no singletest or g roup of tests can be reco mm ended at this tim eas a routine and reliable indicator of protein status.N on eth ele ss, o ur in cre asin g k nowle dg e o f th e m eta bo li sm and f unc ti on s o f p ro te in s, t ogethe r w i th the r ecen tuse of noninvasive stable isotope techniques and ofsophisticated physicochem ic al m easurem ents, prov id es e ncou ra gemen t th at mo re app ro pria te in dic ato rsare in the offlng. J. N utr. 120:1496-1502, 1990.INDEXING KEY W ORDS:protein statu s biochem ical indica tors ant hr op om tr ie in dic ato rs n fe ctio n a nd in fla m mat io n ta ble is oto pe te ch niq ue s

A n inadequate status of protein and energy nutrition continues to be a problem of enormous publichealth and social significance in large populationgroups throughout developing regions of the w orld( 1). I t a lso o ccurs in su bpopula tio ns w ith in th e Un ite dS ta te s (e .g ., 2 ), in clu din g th e kwash io rk or fo rm o f p rotein-energy m alnutrition (3). W hile the etiologicalfactors responsible m ay vary from region to regionand also within the different subpopulations, in allc as es a s atis fa cto ry , quantita tiv e a ss es sment o f p ro te innutritional status is a prerequisite for rational and ef

fective treatm ent and, even m ore im portantly, forp re ventio n (4 ) o f maln utritio n. T hu s, we con sid er h erepresent know ledge w ith respect to the evaluation ofprotein nutritional status. W e do not intend to, andfo r spa ce lim itation s can no t, b e comp reh en sive in o urcoverage. Hence, the reader m ight w ish to consultv ario us rev iew pa pers (e .g ., 5 -1 1) for a more de tailedexposure to the literature in this area.We begin with a brief account of the major approaches that m ight be taken to assess protein nutritional status and then follow with our m ajor focus,wh ic h w ill b e on th e b io ch em ic al e va lu atio n o f p ro te innutritional status. W e will conclude with somethoughts and suggestions concerning m easures thatm ight be developed and evaluated for purposes of improving on diagnostic tools for assessm ent of the adequacy of protein nutrition in individuals and popul ation g roups.

COMMENT ON MAJOR APPROACHESA s for assessm ent of the adequacy of nutritionalsta tu s in te rm s o f e ne rg y an d/o r sp ecific n utrien ts, th e1 Presented as part of a conference, "N utrition M onitoring andN utrition S tatus A ssessm ent", at the first fall m eeting of the A merican Institute of N utrition, C harleston, S C, D ecem ber 8-10, 1989.The conference w as supported in part by cooperative agreem entHPU 880004-02-1 with the DHHS Office of Disease Preventionand H ealth Prom otion, the U SD A H um an N utrition Inform ationService, the D HH S N ational C enter for H ealth Statistics, and theIn te rn at io na l L ife S cie nc es I ns ti tu te -N utr iti on Fou nd at io n.1 The Planning C om mittee for the m eeting consisted of D rs. H e

len A. Guthrie, Roy J. M artin, Linda D. M eyers, Jam es A. Olson,C atherine E . W o teki, and R ichard G . A llison (ex-officio). T he symposium papers w ere edited by a com mittee consisting of D r. Jam esA lle n O lso n (co ordin ato r), D ep t. o f B io ch em istry & B io ph ysics , Io waState University, A mes, IA; Dr. Cathy C. Campbell, D ivision ofN utritional Sciences, C ornell U niversity, Ithaca, N Y; D r. R oy J.M artin, D ept. of F oods & N utrition, U niversity of G eorgia, A thens,G A nd D r. C ath erin e E . W o te ki, F oo d & N utrition B oard , N ation alA cadem y of S ciences, W ashington, D C.0022-3166/90 S3.00 1990 A merican Institute of N utrition. Received 14 M arch 1990. A ccepted 11 July 1990.

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PROTEIN STA TUS EV A LUA TION 1497E va lu a tio n o f P ro te in Nu tr io n a l S ta tu s

A s s e s s m e n tDietary ((InadequateIntake( ii )lnoreased Needs

Phys io log ic and metabol icLaboratory/Metabolic alterations

Reduced t is sue p rotein(muscle:skin:viscera)nthropomtriean dClinicalClinical

A lt er ed g row th andbody composi tionIncreased morbid i ty

Death

E x am p l e2 4 h re ca ll7 d w eig he d r ec or d

Plasma prote insU rin a ry u r eaAm ino aci doxidation

M id-arm c ir cum fe renceT ot al b od y NCrea t in ine he igh t i ndex

F IGURE 1 A schematic outline of a possible sequenceof ev ents leading to clinically signif icant changes in proteinnutritional status, w ith an indication of the general approaches used and som e possible m easurem ents for ev aluatio n o f n utritio nal status.

B io c h e m ic a l As s e s s m e n t o f P r o te in Nu t r it io n a l S t a tu s' IP ro ce ss : Am in o Ac idT r a n s f e r

S o m eM e a s u r e s :P l a s m a

a m in o a ddp a t t e r n s

P r o t e i nS y n t h e s i s

Tis s u e , o rg a nB o d y P r o te in

Ma ss a ndF u n c t i o n

P r o t e i n E n d P r o d uc tsB re akd ow fi


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1498 YOUNG ET AL.As ou tlin ed in T ab le 1 , b io ch em ica l tech niq ue s d iffe r in ty pe an d in th e in fo rm atio n th at is o bta in ed fromtheir application. Furtherm ore, these various techn iques var y with r es pect to t he ir ana ly tic al comp lexity ,precision, and capacity to detect different degrees ofprotein m alnutrition. A n im portant question, therefore, is w hich test or com bination of tests m ight beused to m ake a satisfactory assessm ent of the proteinnutritional status of individuals. This must be answ ered if a reliable diagnosis is to be obtained or ifthe m onitoring inform ation is to be reliable and valuable. U nfortunately, the literature rem ains lim ited,inadequate, and often contradictory. Thus, the question is difficult to answer at this time in a satisfyin g way .

METABOLIC RESPONSES TO REDUCEDPROTEIN AND AMINO ACID INTAKESA better idea of w hat tests m ight be used, or furtherdeveloped, to determ ine protein nutritional statussho uld b e g ain ed by k nowin g what m etab olic ch an ge soccur, and in w hat sequence, in response to a reducedor inadequate supply of dietary nitrogen and/or ofspecific indispensable am ino acids. T his m etabolictopic has been review ed in som e detail by W aterlowand colleagues (e.g., 12, 13) as w ell as by us (14).B rie fly , th e fo ur ma jo r b io ch em ic al sy stems re sponsible for m aintaining body protein and am ino acid ho-m eostasis are 1) am ino acid transport and uptake, 2)am ino acid oxidation and catabolism , 3) protein syn

thesis, and 4) protein breakdow n. It is now quite clearthat the initial response to an inadequate am ino acidor nitrogen intake is a reduction in the rate of am inoa cid oxid atio n. T his is fo llowed by o r simu lta neou slyassociated w ith a decline in the rate of specific organand tissue protein synthesis. P rotein and am ino acidm etabolism in both m uscle and liver is profoundly affected by a restricted dietary protein (am ino acid) intake, w ith reduced rates of m uscle protein synthesisand of the synthesis of export proteins from liver occurrin g a t a re la tiv ely e arly p erio d (1 4). T he se chang esle ad to an a lte re d p atte rn o f b ody p ro te in d istrib utio n,w ith sk ele ta l musc le b ein g affe cte d to a g rea ter e xten tthan body w eight or total body protein m ass (13, 15).H ence, an assessm ent of m uscle m ass and/or its m etabolic and functional status w ould be a logical focusof attention, as also would be the measurement ofblood proteins that are synthesized w ithin the liver.F urth er, th e resp on se s o f o rg an p ro tein m eta bo lism toaltered protein and am ino acid intake are associatedw ith and/or due to a variety of horm onal changes (16).T hu s, m easu rem ent of sp ec ific ho rmon e lev els m ig hta dd u se fu lly to th e b io chemic al ev alu atio n o f p ro te innutritional status. It appears, how ever, that changesin horm ones are quite variable and depend on the du

ration, severity, and nature of the nutritional deficiency, am ong other factors. For exam ple, som ato-m edin C is reduced in cases of protein-energy m alnutrition. Thus, low plasm a levels of this horm one,w hen present together w ith norm al or raised levels ofbasal grow th horm one, m ight be highly suggestive ofprotein-energy m alnutrition (11). A lthough the poten tial v alu e o f p la sm a somatome din C lev els ha s b eenexam ined (17, 18), its determ ination does not yetq ua lify as a v alu ab le ro utin e b io ch em ic al in dex o f p rote in nutritio na l sta tu s.

SERU M PRO TEIN M EA SU REM EN TSThe concentrations of specific proteins in serumhave been used to evaluate protein nutritional statusin a large number of studies. The m ore commonlymea su re d p ro te in s a re liste d in T ab le 2 ,wh ic h in clu de s

com ments about their use and lim itations. B enjam in(1 1) p ro vid es a n e xce llen t an d c on stru ctiv e re view o fthis technique for evaluating protein nutritional status, from w hich w e draw m uch of the discussion givenbelow.There is now a large body of data concerning themeta bo lism o f a lb um in a nd th e measu rem en t o f se rumalbum in as an indicator of protein nutritional status.In sum mary, the follow ing points m ight be m ade: thebody pool of album in is large, w ith ~60% being inth e extra va sc ula r sp ac e. Its h alf-life is re la tiv ely lo ng ,and the plasm a album in concentration is buffereda t le as t a cu te lyby mobil iz ation o f t he extrava scula rpool. A lbum in concentration does not appear to be as en sitiv e o r s pecif ic indicato r o f acu te p ro te in -ene rgymaln utritio n, a lth ou gh low a lb um in co nce ntratio nsa re a ss oc ia ted with i nc reas ed morb id ity and morta li ty .Proteins, w hich turn over m ore rapidly than album in, also have been exam ined (e.g., 19): transferrinw ith a half-life of 8-9 d can be m easured relatively

T ABL E 2S er um p rotein s an d p rotein n utr it ion al statu s1

AlbuminTransferrinPre-albuminRetinol-bindingproteinFibronectinAmino

acidprofiles1Based onHalf- l ife18d8-9

d2d12

h4-24hBenjamin

(Clinical

us eimitations"Severe"malnutritionLimited:Chronicdeficiency?AcutedepletionAcutedepletionAcutedepletionMonitoringofprognosisAffected

byariouspathophysioloe.g.,liverdisease,infection,othernutrients,(e.g.,Fe,Vitamin).'11).


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PROTEIN STA TUS EV A LUA TION 1499eas ily . The ev idence , however, doe s not general ly poin tto its being a highly useful m easure of protein nutritional status, at least not as a single diagnostic index(e.g., 20). Pre-album in (transthy retin) and retinolb in din g p ro te in (RBP ),w h ic h tu rn o v er w i th half -liv e sof ~2 d and 12 h, respectiv ely , therefore m ay be m oreu se fu l in dic es. Fu rth ermo re , a c lo se c orre latio n o fte nex ists betw een pre-album in and R B P in response top ro te in -e ne rg y d ep riv atio n (e .g ., 2 1) and nutritio nalth erap y. Fin ally , f ib ro ne ctin , a g ly co pro tein sy nth esiz ed b y many c ell ty p es, se rv e s mu ltip le p hy sio lo gic alf un ctio ns, in clu din g ce ll-m atrix in te ractio ns an d th eb in din g o f macrophag es and f ib ro blasts. Fib ro ne ctinis re du ced in acute n utritio nal d ep riv atio n and re tu rn sto norma l o n early n utritio nal re hab ilitatio n (e .g ., 2 2).Pre cise d ete rm i natio n o f f ib ro ne ctin re qu ire s sp ec ialattention to specim en handling. N onetheless, its poten tial v alu e as an in dex o f p ro tein statu s d eserv es f urth er stu dy , e sp ecially b ecau se it c han ges in resp on seto various non -nut rit ional f ac to rs , i nc luding s ep sis andtraum a. Indeed, B enjam in (11) has suggested that itw ould be adv isable to include a m easure of an acute-p hase reactan t, su ch as C -re ac tiv e p ro tein , to f urth erassist the interpretation of blood protein m easurem e nts, b ec au se th ey are af fec ted b y inf lammatio n an din fe ctio n in ad ditio n to n utritio nal statu s p er se. T h isp oin t is sup po rted by a n umb er o f in ve stig atio ns (e.g .,23-25), and w e discuss this m atter f urther below .

PL A SM A A M IN O A CID CON CEN TR A TION SPlasm a f ree am ino acids change w ith acute alterations in the lev el of protein and am ino acid intak e.T hus, determ ination of their prof iles in blood hasf ound useful application in the ev aluation of am inoacid needs (e.g., 26), as w ell as in the design of am inoacid m ix tures f or use in parenteral nutrition underv arious clinical states. S om e y ears ago, it w as show nth at p ro noun ced abno rma litie s o cc urre d in th e p lasmaam i no ac id p ro file o f c hild re n w i th f ran k kwash io rk o r,w i th th e non esse ntial am i no ac id ssu ch as alan in e,g ly c in e, se rin e, and p ro lin eb ein g raise d and th e e sse ntial (in disp en sab le) am in o ac id s b ein g low ere d (5 ,2 7). In co ntrast, th e ch an ges in p lasma am in o ac id le ve ls an d p ro files w e re less p ro no un ced in th e marasm icf orm of protein-energy m alnutrition. S im ilarly , theurinary am ino acid pattern in m arasm u s dif fers f romth at in kw ash iork or (2 8). A l th ou gh th ese e arlier f in din gs su gg este d th at measu remen t o f p lasma am i no ac idle vels m ight o f fe r a p rac tical tool f o r as se ss ing pro te innutritional status, the prom ise of a usef ul m easurebased on am ino acid concentrations has not y et beenfulfilled.B ef ore it is p ossib le to f ully ev alu ate th e p ote ntialv alu e o f p lasma am i no ac id c on centratio ns, much mo rem ust be learned about how their concentrations are

regulated and how they relate to the m etabolism andturnov er of proteins and am ino acids in tissues ando rg an s. H en ce, alth ou gh p lasma am i no ac id d eterm inations can serv e a v aluable purpose in m etabolicstu die s co nc ern ed w ith th e reg ulatio n o f b ody p ro te inand am ino acid m etabolism , they cannot be recomm ended at this tim e for inclusion in the routine laboratory.

M EA SUREM EN TS ON UR IN EIn v iew of the sensitiv ity of m uscle protein m etabolism to inadequate intak es of nitrogen and am ino acid s, attempts h av e b een made to d ev elop b ioc hem i caltests that assess the siz e and m etabolic status of thistissue, w hich accounts f or ~45% of body protein (15).S in ce u rin ary c re atin in e is d eriv e d e sse ntially f rom th esp on tan eo us co nv ersio n of mu scle creatin e to creatinine, w hich occurs at a relativ ely constant rate, themeasu remen t o f u rin ary c re atin in e e x cre tio n re lativ eto h eig ht o f th e in div id ual was p ropo se d as an e stima teo f mus cle p ro te in mass ( 29 ). Thus, a c reati ni ne /heightindex (CHI) is calculated according to the f ollow ingequation:

_ 24-h urine creatinine ex cretion (m g ) X 10024-h creatine ex cretion (m g ) b y an ormal su bje ct o f sam e he ig htG uidelines hav e been proposed to assist the interpretation of CHI v alues, w ith a v alue of 60-80% beingtak en as m ild protein depletion and a v alue < 40% as

ev id enc e o f sev ere p ro tein d ep letio n. T h is ap pro ac h,how ev er, is lim ited in its application because of them ajor dif ficulties inv olv ed in m ak ing accurate 24-hurine collections, ev en under the highly controlledco nd itio ns o f th e m e tab olic rese arch w ard .M easurem ent of the urinary output of 3-m ethy l-histidine (3MH ) of fers, in theory , another approachf or asse ssin g th e siz e and tu rn ov er o f th e sk eletal p rotein m ass (30). T he rational is that 3M H is deriv edfrom the break dow n of m y osin and actin in sk eletalmus cle ( 31 ) [although perhaps not exclu siv e ly ; s ee (32) ]and ex creted largely unaltered v ia the k idney s. Furtherm ore, the urinary 3MH output is reduced in m alnourished children (30). H ow ev er, this approach islim ited by m any of the sam e problem s that apply tothe u se o f c re atin in e m e asu rem en ts. Fu rth ermo re , b ec au se th e statu s o f mu sc le p ro te in tu rn ov e r is se nsitiv eto stressf ul conditions, 3MH may w ell be increased ind ep le te d patie nts d ue to in cre ase d rate s o f mu sc le p rotein b reak dow n. T h us, stress w o uld complicate interpretation of the m easured lev el of 3M H output. A dditionally , there are lim ited data on the ex cretion ofth is am i no ac id in v ario us normal p opulatio ns, mak in git dif ficult to establish suitable guidelines. T o date,therefore, determ inations of 3M H ex cretion hav e


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1500 Y OUNG ET A L .large ly b een restric ted to d etailed m e tab olic stu dies,w here they hav e contributed signif icantly to a betterunderstanding of the regulation and m echanism s ofmu sc le p ro te in tu rn ov e r und er v ario us phy sio lo gic aland pathologic s tate s.Determ ination of the urinary output of the m ajoren d p ro du cts o f n itro gen c atab olism (u rea, ammonia)also w ould appear, in theory , to prov ide an index ofthe status of protein nutriture. How ev er, there arem ajor problem s associated w ith m ak ing accurate determ inations of output (and of intak e if body N balance is to be determ ined). Furtherm o re, nitrogen excretion and balance prov ide inf orm ation only aboutthe net status of protein m etabolism and not m uchabou t n utritio nal state o r th e siz e o f th e p ro te in sto re s.Finally , the urinary output of hy drox yproline is red uced in n utritio nal dw arf ism . T h us, m e asu rem e nt o fthis am ino acid has also been ex am ined as a possibleindex of nutritional status. W hitehead (5) proposed ahydroxypro li ne index

TABL E 3Techn iques f or i n vi vo measu remen t of muscle mass1

(HOP) = hydroxyproline/mLitm o l creatinine/k g body w tbut th is in de x has not f ou nd much applic atio n, p erh ap sb ecau se it is c omp lic ate d b y in te rc urre nt in fe ctio n (5 ).

PH Y S ICA L ME A SUR EMENT SA s indicated abov e, it is of interest to k now the siz eof the body protein m ass and its distribution. In relation to the m uscle protein m ass, sev eral m ethods

hav e been suggested, as rev iew ed by H eym sf ield et al.(33). T hese are summ ariz ed in T able 3.M i d-u pp er arm c irc um f e re nc e and c ro ss-se ctio nalm uscle area at the m id-upper arm hav e been used orp rop ose d as m e asu re s of mu sc le mass, b ut v alid atio nand v ariation appear to rem ain dif f icult problem s.Durnin & Fidanza (9) are of the opinion that thesep roc ed ures are u nlik ely can did ate s f or assessing abnorm ality , other than in ex trem e cases. N ew er techniques (34, 35) for m easurem ent of body and tissuecom p osition, including electrical conductiv ity andim p edance, in v iv o neutron activ ation analy sis, andmagn etic re so nan ce imag in g, m i gh t h elp in th e f urth erdev elopm ent of approaches f or estim ation of the protein content of specif ic tissues and body regions.H ow ev er, their application f or assessm e nt of nutritional status is, in any case, currently lim ited to spec ializ ed re search and med ical cen te rs .

"FUNCT IONA L" TESTS A NDDIS CR IM IN A N T A N A L Y S ES

T he m ajority of m easurem ents and proceduresbrief ly discussed abov e do not necessarily rev eal the

Method CommentAnthropometryRadiographieI so topi e me thods15N-creatinineIn v iv o n eu tron ac tiv atio nanalysisNu cl ear mag ne ti c re so nan ceUrinary mark e rs24-h creatinine3-methylhistidine

M e asu res in div id ual m u sc legroupsComput eri ze d tomog rap hyR eq uires b iop sy ; b ase d o n iso to pedilutionL im ite d n um b er o f f ac ilitiesC an v isualiz e lim b m uscle cross-s ec ti onal area

Gene ral ly good. Co ll ec ti ondemanding.N ot applicable in states w heretu rn ov er i s alt ere d.Partial summ ary f rom H ey m sf ield et al. (33).

f un ctio nal statu s o f th e v ario us b od y sy stem s . H en ce,at temp ts have been made to corre late nutri tional s tatu sw ith estim ates of sy stem f unctions (e.g., see 8-11),in clu din g mu sc le f un ctio n su ch as hand-g rip stre ng th(3 6, 3 7) an d ele ctric al stim u latio n o f sk ele tal m u scle(3 8-4 0). A dd itio nally , imm une sy stem abno rmalitie so cc ur w i th sp ec if ic n utrie nt d ef ic ie nc y (4 1 ) and in p rote in -e nerg y maln utritio n (4 2). A l so, f or ex amp le, n utritio nal su pport o f d ep le te d patie nts imp ro v es T - ce ll-related im m une function (43). H ow ev er, in spite ofth e c on sid erab le in te re st and p erhap s pote ntial o f su chte sts, th e v alu e o f p articu lar tests o f immune f un ctio nf or asse ssm e nt o f pro te in n utritio nal statu s remain sto be clarif ied. It is possible that useful tests, w hichm easure w ith adequate sensitiv ity the integration ofsp ec if ic p hy sio lo gic and me tabo lic sy stem s , m i gh t b ed ev e lo ped. S u ch te sts, h ow ev er, w ould b e non sp ec if icin id en tif y in g th e sp ec if ic n atu re o f th e nu tritio nal inadequacy.S om e w o rk ers h av e ad vo cated mak in g sev eral m e asu rem en ts o f n utrition al statu s f or p urp oses of d ev eloping a prognostic nutritional index (e.g., 44, 45). Itdoes seem clear to us that it is im portant to considers eve ral b iochemi cal marke rs f o r as se ssment o f p ro te innutritio nal statu s. D isc rim i nan t analy sis may b e u se dto help choose the best com b ination of these m ark ers(e .g ., 4 6), in clu din g measu re s o f in flamm atio n. T hus,In genb le ek & Carp en tie r (4 7) p ropo se d measu remen to f a-ac id ic g lycopro te in , C -reac tiv e p ro te in , albumin ,an d th yro xin e-b in din g p re -alb um in , w h ich w e re th enag greg ated w ith in a pro gn ostic in flammatory an d n utritional index . T his ty pe of approach for the biochem ical assessm ent of protein nutritional statusw ould appear to be prom ising and deserv es f urtherex ploration. W e also recognize that a num ber of inv estigators hav e em p hasiz ed both the im p ortance ofth e c lin ic al approach f or e v alu atio n o f n utritio nal sta-


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'fi.1tief'***\

PRO TEIN STA TUS EVA LUATION 1501tus, as w ell as the danger of excessive reliance on labo ra to ry data (e .g ., 48- 50 ).

SU MM AR Y A ND C ON CLU SIO NSFrom the foregoing, it should be apparent that no

single test or group of tests can be recom mended atthis tim e as a routine and reliable basis for assessingprotein nutritional status. F actors other than the nutritio nal v aria bles o f in tere st a ffec t e ssen tially all o fth e a vaila ble b io ch em ica l m ea su re s. Amon g th ese a reparticularly those involving inflam mation and, inagreem ent w ith B enjam in (11), it w ould seem w ise toin clu de an a sse ssment o f in flamma tio n fo r th e c ritic ald ete rm in atio n o f p ro te in nutritio na l sta tu s.Biochem ical tests can, how ever, be a useful complement to the c linica l and an thropomtrieapproachesfor nutritional status evaluation. Indeed, w e recommen d th at th ey b e u sed fo r mon ito rin g o f h osp italize dpatients w ho are at risk of inadequate nutritional status. The choice of a particular group of biochem icaltests rem ains very m uch a decision for the inform edinvestigator, dictated particularly by the unique situation under w hich the assessm ent is being m ade. Inour view , this is an unsatisfactory state of affairs. Itis cle ar th at re sea rc h is n eed ed o n th e metab olic , p hy siologic, and pathologic responses to altered protein(am ino acid and energy) intakes in hum ans, w ith thesp ec ific o bje ctiv e o f d ev elo pin g and v alid atin g te sts o fn utritio na l sta tu s fo r u se in e ith er fie ld , in stitu tio na l,and/or clinical settings. U nfortunately, m uch m etab olic an d b ioc hem ical resea rc h is co nd ucte d w ith ou tth is stra te gic fo cu s, wh ic h lim its ra th er th an enh an ce sits value, at least in the context of nutritional assessment.W e propose that it is crucial both to characterizem ore com pletely the quantitative aspects of hum anw hole body and organ protein and am ino acid m etabolism under various nutritional conditions and to inc lu de in th is c ha ra cte riz atio n th e supe rimposed e ffe ctsof stressful stimuli, such as infection or physicaltraum a. This can be achieved, in part, w ith the aid ofre la ti ve ly non invasi ve s table is otope trace r te chniques(e .g ., 5 1). Until th is re se arc h is u nd erta ken, h oweve r,com plem ented by the know ledge em erging from m olec ular a nd c ell b io lo gy , fu rthe r sig nific an t ad van cesin the evaluation of protein nutritional status are unlik ely to o ccur.

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17032013-Assessment of Protein Status