Symposium

Assessment of Protein Nutritional Status12

VERHOH R. yOCWYG, J. SERGIO MARCHIHI* AND JOAQUN CORTIELLA Laboratory of Human Nutrition, School of Science and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139; Shriners Burns Institute, Boston, MA, 02014; *Diuision of Nutrition, Medical School of RibeiroPreto, RibeiroPreto, SP, 14049, Brazil fective treatment and, even more importantly, for prevention (4) of malnutrition. Thus, we consider here present knowledge with respect to the evaluation of protein nutritional status. We do not intend to, and for space limitations cannot, be comprehensive in our coverage. Hence, the reader might wish to consult various review papers (e.g., 5-11) for a more detailed exposure to the literature in this area. We begin with a brief account of the major ap proaches that might be taken to assess protein nutri tional status and then follow with our major focus, which will be on the biochemical evaluation of protein nutritional status. We will conclude with some thoughts and suggestions concerning measures that might be developed and evaluated for purposes of im proving on diagnostic tools for assessment of the ad equacy of protein nutrition in individuals and popu lation groups.

ABSTRACT An evaluation of protein status can be approached by use of anthropomtrie, clinical, and bio chemical data, either singly or in combination, and fur ther aided with dietary data. Each of these approaches has advantages and limitations. Biochemical evaluation has the potential of being the most objective and quan titative. Indicators that have been or might be used include plasma hormone responses to reduced protein intake, plasma levels of specific proteins or specific amino acids, urinary excretion of specific amino acids and other nitrogen-containing compounds, anthropo mtrie and physical measurements of body muscle mass, and functional tests of muscle strength. Several measurements can be combined to produce nutritional indices of broader potential value. The importance of concomitant infection and inflammation, with its many effects on protein metabolism, cannot be ignored in making these assessments, unfortunately, no single test or group of tests can be recommended at this time as a routine and reliable indicator of protein status. Nonetheless, our increasing knowledge of the metab olism and functions of proteins, together with the recent use of noninvasive stable isotope techniques and of sophisticated physicochemical measurements, pro vides encouragement that more appropriate indicators are in the offlng. J. Nutr. 120:1496-1502, 1990.
INDEXING KEY WORDS:

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COMMENT ON MAJOR APPROACHES As for assessment of the adequacy of nutritional status in terms of energy and/or specific nutrients, the
1 Presented as part of a conference, "Nutrition Monitoring and Nutrition Status Assessment", at the first fall meeting of the Amer ican Institute of Nutrition, Charleston, SC, December 8-10, 1989. The conference was supported in part by cooperative agreement HPU 880004-02-1 with the DHHS Office of Disease Prevention and Health Promotion, the USDA Human Nutrition Information Service, the DHHS National Center for Health Statistics, and the International Life Sciences Institute-Nutrition Foundation. 1 The Planning Committee for the meeting consisted of Drs. He len A. Guthrie, Roy J. Martin, Linda D. Meyers, James A. Olson, Catherine E. Woteki, and Richard G. Allison (ex-officio). The sym posium papers were edited by a committee consisting of Dr. James Allen Olson (coordinator), Dept. of Biochemistry & Biophysics, Iowa State University, Ames, IA; Dr. Cathy C. Campbell, Division of Nutritional Sciences, Cornell University, Ithaca, NY; Dr. Roy J. Martin, Dept. of Foods & Nutrition, University of Georgia, Athens, GA and Dr. Catherine E. Woteki, Food & Nutrition Board, National Academy of Sciences, Washington, DC.

protein status biochemical indicators an thropomtrieindicators infection and inflamma tion stable isotope techniques

An inadequate status of protein and energy nutri tion continues to be a problem of enormous public health and social significance in large population groups throughout developing regions of the world (1). It also occurs in subpopulations within the United States (e.g., 2), including the kwashiorkor form of pro tein-energy malnutrition (3). While the etiological factors responsible may vary from region to region and also within the different subpopulations, in all cases a satisfactory, quantitative assessment of protein nutritional status is a prerequisite for rational and ef
0022-3166/90 S3.00 1990 American Institute of Nutrition.

Received 14 March 1990. Accepted 11 July 1990.

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PROTEIN
Evaluation of Protein Nutrional Status Example Assessment
Dietary ((InadequateIntake (ii)lnoreased Needs

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Biochemical Assessment of Protein Nutritional Status

'
Process: Amino Acid Transfer Protein Synthesis Tissue, organ Body Protein Mass and Function

I
Breakdowfi
I

24 h recall 7 d weighed record

Protein

End Products
<* Protein &
: aaCatabolism

Laboratory/Metabolic

Physiologic and metabolic alterations Reduced tissue protein (muscle:skin:viscera) Altered growth and body composition Increased morbidity Death

Plasma proteins
Urinary urea

Amino acid oxidation Anthropomtrie and Clinical Mid-arm circumference Total body N Creatinine height index

Some Measures: Plasma amino add patterns

Clinical

1. Plasma Proteina 2. Enzymes ( 3. Muscle protein ) synthesis (

1.CHI 2 Mid-arm circumference/' 3. N*-methyl-S histidine 4. Immune parameters

1. Urea N 2. Nitrogen/Crealinine 3. OH-Proline 4. NT-methylhistidine

FIGURE 1 A schematic outline of a possible sequence of events leading to clinically significant changes in protein nutritional status, with an indication of the general ap proaches used and some possible measurements for evalu ation of nutritional status.

FIGURE 2 Simplified organization of protein and amino acid metabolism, with an indication of the major systems involved and measures used to assess the status of these sys tems. Based on G. Arroyave (personal communication).
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evaluation might be approached by using either di etary, anthropomtrie, clinical, and/or biochemical data. The rationale for these various approaches is that a clinically significant protein deficiency state occurs via a series of successive steps, according to the sim plified scheme presented in Fig. 1. Thus, the dietary intake may either be less than sufficient to meet usual requirements (primary deficiency) or it may be inad equate to meet increased metabolic demands of the host due to infection or other stress, including physical trauma and injury (secondary deficiency). Whether the inadequate nutrient supply to cells and organs is due to a primary or secondary dietary deficiency, it will promote metabolic changes that initially favor con servation of the nutrient in short supply and help reorder the quantitative importance of various meta bolic pathways and functions of the nutrient involved. If the inadequate supply is sustained, the biochemical changes then lead to altered levels of tissue and organ proteins and of physiologically important nitrogencontaining compounds and metabolites. These meta bolic changes are expressed by way of altered body composition parameters, including diminished linear growth and weight gain in the young. Eventually clin ical signs and symptoms develop, with increased mor bidity and risk of death. As indicated in Fig. 1, dietary data relate to an early stage in the sequence of events shown here, at least as far as acute changes in diet are concerned. While as sessment of dietary habits and estimations of nutrient intakes can be useful for various purposes, they are not direct measures of nutritional status. Also, the clinical data apply to a relatively late stage in the se quence. Thus, they may have limited value in that the symptoms observed are often nonspecific and possibly unreliable. Furthermore, clinical signs may not be present in a "mild" degree of nutritional deficiency.

Anthropomtriemeasurements also may be limited in their value for assessing the nutritional status of an individual; the considerable variability in these data make interpretation problematic. However, we will again refer to the clinical and anthropomtrie ap proaches below, since they do, or can, play an impor tant role in nutritional assessment despite these gen eral concerns. The remaining approach, therefore, is the biochem ical evaluation of nutritional status. This has the po tential for being the most objective and quantitative of the approaches mentioned. Thus, to provide a fur ther framework for our brief discussion, we have de picted the general features of the organization of body protein and amino acid metabolism in Fig. 2, as well as indicating some examples of biochemical measure ments in relation to the major biochemical and phys iological systems responsible for protein and amino acid homeostasis.

TABLE 1

A list of various biochemical tests, with examples, that might be used for assessment of nutritional status
1. Measurement of nutrient under study in blood, urine, or other biological sample (e.g., retinol, thiamin, amino acid). 2. Measurement of a metabolite of the nutrient in blood or urine (e.g., N-methylinicotinamide, 4-pyridoxic acid, urea). 3. "Functional" tests (e.g., transketolase, transaminases, erythrocyte hemolvsis). 4. Load or saturation test (e.g., thiamin, transferrin saturation). 5. Product of nutrient under study (e.g., hemoglobin, albumin, coenzymes). 6. Abnormal metabolites (e.g., FIGLU, methylmalonate, xanthurenic acid). 7. Other measurements (e.g., tracer and turnover studies, ^Kcounting).

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As outlined in Table 1, biochemical techniques dif fer in type and in the information that is obtained from their application. Furthermore, these various tech niques vary with respect to their analytical complexity, precision, and capacity to detect different degrees of protein malnutrition. An important question, there fore, is which test or combination of tests might be used to make a satisfactory assessment of the protein nutritional status of individuals. This must be an swered if a reliable diagnosis is to be obtained or if the monitoring information is to be reliable and valu able. Unfortunately, the literature remains limited, inadequate, and often contradictory. Thus, the ques tion is difficult to answer at this time in a satisfy ing way.

ration, severity, and nature of the nutritional defi ciency, among other factors. For example, somatomedin C is reduced in cases of protein-energy mal nutrition. Thus, low plasma levels of this hormone, when present together with normal or raised levels of basal growth hormone, might be highly suggestive of protein-energy malnutrition (11). Although the po tential value of plasma somatomedin C levels has been examined (17, 18), its determination does not yet qualify as a valuable routine biochemical index of pro tein nutritional status.

SERUM PROTEIN MEASUREMENTS The concentrations of specific proteins in serum have been used to evaluate protein nutritional status in a large number of studies. The more commonly measured proteins are listed in Table 2, which includes comments about their use and limitations. Benjamin (11) provides an excellent and constructive review of this technique for evaluating protein nutritional sta tus, from which we draw much of the discussion given below. There is now a large body of data concerning the metabolism of albumin and the measurement of serum albumin as an indicator of protein nutritional status. In summary, the following points might be made: the body pool of albumin is large, with ~60% being in the extravascular space. Its half-life is relatively long, and the plasma albumin concentration is buffered at least acutelyby mobilization of the extravascular pool. Albumin concentration does not appear to be a sensitive or specific indicator of acute protein-energy malnutrition, although low albumin concentrations are associated with increased morbidity and mortality. Proteins, which turn over more rapidly than albu min, also have been examined (e.g., 19): transferrin with a half-life of 8-9 d can be measured relatively

METABOLIC RESPONSES TO REDUCED PROTEIN AND AMINO ACID INTAKES A better idea of what tests might be used, or further developed, to determine protein nutritional status should be gained by knowing what metabolic changes occur, and in what sequence, in response to a reduced or inadequate supply of dietary nitrogen and/or of specific indispensable amino acids. This metabolic topic has been reviewed in some detail by Waterlow and colleagues (e.g., 12, 13) as well as by us (14). Briefly, the four major biochemical systems respon sible for maintaining body protein and amino acid homeostasis are 1) amino acid transport and uptake, 2) amino acid oxidation and catabolism, 3) protein syn thesis, and 4) protein breakdown. It is now quite clear that the initial response to an inadequate amino acid or nitrogen intake is a reduction in the rate of amino acid oxidation. This is followed by or simultaneously associated with a decline in the rate of specific organ and tissue protein synthesis. Protein and amino acid metabolism in both muscle and liver is profoundly af fected by a restricted dietary protein (amino acid) in take, with reduced rates of muscle protein synthesis and of the synthesis of export proteins from liver oc curring at a relatively early period (14). These changes lead to an altered pattern of body protein distribution, with skeletal muscle being affected to a greater extent than body weight or total body protein mass (13, 15). Hence, an assessment of muscle mass and/or its met abolic and functional status would be a logical focus of attention, as also would be the measurement of blood proteins that are synthesized within the liver. Further, the responses of organ protein metabolism to altered protein and amino acid intake are associated with and/or due to a variety of hormonal changes (16). Thus, measurement of specific hormone levels might add usefully to the biochemical evaluation of protein nutritional status. It appears, however, that changes in hormones are quite variable and depend on the du

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TABLE 2 Serum proteins and protein nutritional

status1

Limitations"Severe"malnutritionLimited: use

AlbuminTransferrinPre-albuminRetinol-bindingproteinFibronectinAmino variouspathophysiologicvariables by Chronicdeficiency?Acute e.g.,liver disease,infection, depletionAcute othernutrients, (e.g.,Fe, h4-24 depletionAcute A).'11). Vitamin hBenjamin depletionMonitoring ofprognosisAffected acidprofiles1 Based onHalf-life18d8-9 (Clinical d2d12

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easily. The evidence, however, does not generally point to its being a highly useful measure of protein nutri tional status, at least not as a single diagnostic index (e.g., 20). Pre-albumin (transthyretin) and retinol binding protein (RBP),which turn over with half-lives of ~2 d and 12 h, respectively, therefore may be more useful indices. Furthermore, a close correlation often exists between pre-albumin and RBP in response to protein-energy deprivation (e.g., 21) and nutritional therapy. Finally, fibronectin, a glycoprotein synthe sized by many cell types, serves multiple physiological functions, including cell-matrix interactions and the binding of macrophages and fibroblasts. Fibronectin is reduced in acute nutritional deprivation and returns to normal on early nutritional rehabilitation (e.g., 22). Precise determination of fibronectin requires special attention to specimen handling. Nonetheless, its po tential value as an index of protein status deserves fur ther study, especially because it changes in response to various non-nutritional factors, including sepsis and trauma. Indeed, Benjamin (11) has suggested that it would be advisable to include a measure of an acutephase reactant, such as C-reactive protein, to further assist the interpretation of blood protein measure ments, because they are affected by inflammation and infection in addition to nutritional status per se. This point is supported by a number of investigations (e.g., 23-25), and we discuss this matter further below.

regulated and how they relate to the metabolism and turnover of proteins and amino acids in tissues and organs. Hence, although plasma amino acid determi nations can serve a valuable purpose in metabolic studies concerned with the regulation of body protein and amino acid metabolism, they cannot be recom mended at this time for inclusion in the routine lab oratory.

MEASUREMENTS ON URINE In view of the sensitivity of muscle protein metab olism to inadequate intakes of nitrogen and amino ac ids, attempts have been made to develop biochemical tests that assess the size and metabolic status of this tissue, which accounts for ~45% of body protein (15). Since urinary creatinine is derived essentially from the spontaneous conversion of muscle creatine to creati nine, which occurs at a relatively constant rate, the measurement of urinary creatinine excretion relative to height of the individual was proposed as an estimate of muscle protein mass (29). Thus, a creatinine/height index (CHI) is calculated according to the following equation: _ 24-h urine creatinine excretion (mg) X 100 24-h creatine excretion (mg) by a normal subject of same height Guidelines have been proposed to assist the inter pretation of CHI values, with a value of 60-80% being taken as mild protein depletion and a value < 40% as evidence of severe protein depletion. This approach, however, is limited in its application because of the major difficulties involved in making accurate 24-h urine collections, even under the highly controlled conditions of the metabolic research ward. Measurement of the urinary output of 3-methylhistidine (3MH) offers, in theory, another approach for assessing the size and turnover of the skeletal pro tein mass (30). The rational is that 3MH is derived from the breakdown of myosin and actin in skeletal muscle (31) [although perhaps not exclusively; see (32)] and excreted largely unaltered via the kidneys. Fur thermore, the urinary 3MH output is reduced in mal nourished children (30). However, this approach is limited by many of the same problems that apply to the use of creatinine measurements. Furthermore, be cause the status of muscle protein turnover is sensitive to stressful conditions, 3MH may well be increased in depleted patients due to increased rates of muscle pro tein breakdown. Thus, stress would complicate inter pretation of the measured level of 3MH output. Ad ditionally, there are limited data on the excretion of this amino acid in various normal populations, making it difficult to establish suitable guidelines. To date, therefore, determinations of 3MH excretion have

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PLASMA AMINO ACID CONCENTRATIONS Plasma free amino acids change with acute altera tions in the level of protein and amino acid intake. Thus, determination of their profiles in blood has found useful application in the evaluation of amino acid needs (e.g., 26), as well as in the design of amino acid mixtures for use in parenteral nutrition under various clinical states. Some years ago, it was shown that pronounced abnormalities occurred in the plasma amino acid profile of children with frank kwashiorkor, with the nonessential amino acidssuch as alanine, glycine, serine, and prolinebeing raised and the es sential (indispensable) amino acids being lowered (5, 27). In contrast, the changes in plasma amino acid lev els and profiles were less pronounced in the marasmic form of protein-energy malnutrition. Similarly, the urinary amino acid pattern in marasmus differs from that in kwashiorkor (28). Although these earlier find ings suggested that measurement of plasma amino acid levels might offer a practical tool for assessing protein nutritional status, the promise of a useful measure based on amino acid concentrations has not yet been fulfilled. Before it is possible to fully evaluate the potential value of plasma amino acid concentrations, much more must be learned about how their concentrations are

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ET AL. TABLE 3 Techniques for in vivo measurement of muscle mass1

Method Anthropometry Radiographie Isotopie methods 15N-creatinine In vivo neutron activation analysis Nuclear magnetic resonance Urinary markers 24-h creatinine 3-methylhistidine Comment Measures individual muscle groups Computerized tomography Requires biopsy; based on isotope dilution Limited number of facilities Can visualize limb muscle crosssectional area Generally good. Collection demanding. Not applicable in states where turnover is altered.

largely been restricted to detailed metabolic studies, where they have contributed significantly to a better understanding of the regulation and mechanisms of muscle protein turnover under various physiological and pathologic states. Determination of the urinary output of the major end products of nitrogen catabolism (urea, ammonia) also would appear, in theory, to provide an index of the status of protein nutriture. However, there are major problems associated with making accurate de terminations of output (and of intake if body N bal ance is to be determined). Furthermore, nitrogen ex cretion and balance provide information only about the net status of protein metabolism and not much about nutritional state or the size of the protein stores. Finally, the urinary output of hydroxyproline is re duced in nutritional dwarfism. Thus, measurement of this amino acid has also been examined as a possible index of nutritional status. Whitehead (5) proposed a hydroxyproline index (HOP) = hydroxyproline/mL itmol creatinine/kg body wt

Partial summary from Heymsfield et al. (33).

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but this index has not found much application, perhaps because it is complicated by intercurrent infection (5).

PHYSICAL MEASUREMENTS As indicated above, it is of interest to know the size of the body protein mass and its distribution. In re lation to the muscle protein mass, several methods have been suggested, as reviewed by Heymsfield et al. (33). These are summarized in Table 3. Mid-upper arm circumference and cross-sectional muscle area at the mid-upper arm have been used or proposed as measures of muscle mass, but validation and variation appear to remain difficult problems. Durnin & Fidanza (9) are of the opinion that these procedures are unlikely candidates for assessing ab normality, other than in extreme cases. Newer tech niques (34, 35) for measurement of body and tissue composition, including electrical conductivity and impedance, in vivo neutron activation analysis, and magnetic resonance imaging, might help in the further development of approaches for estimation of the pro tein content of specific tissues and body regions. However, their application for assessment of nutri tional status is, in any case, currently limited to spe cialized research and medical centers. "FUNCTIONAL" TESTS AND DISCRIMINANT ANALYSES The majority of measurements and procedures briefly discussed above do not necessarily reveal the

functional status of the various body systems. Hence, attempts have been made to correlate nutritional status with estimates of system functions (e.g., see 8-11), including muscle function such as hand-grip strength (36, 37) and electrical stimulation of skeletal muscle (38-40). Additionally, immune system abnormalities occur with specific nutrient deficiency (41) and in pro tein-energy malnutrition (42). Also, for example, nu tritional support of depleted patients improves T-cellrelated immune function (43). However, in spite of the considerable interest and perhaps potential of such tests, the value of particular tests of immune function for assessment of protein nutritional status remains to be clarified. It is possible that useful tests, which measure with adequate sensitivity the integration of specific physiologic and metabolic systems, might be developed. Such tests, however, would be nonspecific in identifying the specific nature of the nutritional in adequacy. Some workers have advocated making several mea surements of nutritional status for purposes of devel oping a prognostic nutritional index (e.g., 44, 45). It does seem clear to us that it is important to consider several biochemical markers for assessment of protein nutritional status. Discriminant analysis may be used to help choose the best combination of these markers (e.g., 46), including measures of inflammation. Thus, Ingenbleek & Carpentier (47) proposed measurement of a-acidic glycoprotein, C-reactive protein, albumin, and thyroxine-binding pre-albumin, which were then aggregated within a prognostic inflammatory and nu tritional index. This type of approach for the bio chemical assessment of protein nutritional status would appear to be promising and deserves further exploration. We also recognize that a number of in vestigators have emphasized both the importance of the clinical approach for evaluation of nutritional sta-

'fi.1 'tief'** \*\

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tus, as well as the danger of excessive reliance on lab oratory data (e.g., 48-50).

SUMMARY AND CONCLUSIONS From the foregoing, it should be apparent that no single test or group of tests can be recommended at this time as a routine and reliable basis for assessing protein nutritional status. Factors other than the nu tritional variables of interest affect essentially all of the available biochemical measures. Among these are particularly those involving inflammation and, in agreement with Benjamin (11), it would seem wise to include an assessment of inflammation for the critical determination of protein nutritional status. Biochemical tests can, however, be a useful com plement to the clinical and anthropomtrie approaches for nutritional status evaluation. Indeed, we recom mend that they be used for monitoring of hospitalized patients who are at risk of inadequate nutritional sta tus. The choice of a particular group of biochemical tests remains very much a decision for the informed investigator, dictated particularly by the unique sit uation under which the assessment is being made. In our view, this is an unsatisfactory state of affairs. It is clear that research is needed on the metabolic, phys iologic, and pathologic responses to altered protein (amino acid and energy) intakes in humans, with the specific objective of developing and validating tests of nutritional status for use in either field, institutional, and/or clinical settings. Unfortunately, much meta bolic and biochemical research is conducted without this strategic focus, which limits rather than enhances its value, at least in the context of nutritional assess ment. We propose that it is crucial both to characterize more completely the quantitative aspects of human whole body and organ protein and amino acid metab olism under various nutritional conditions and to in clude in this characterization the superimposed effects of stressful stimuli, such as infection or physical trauma. This can be achieved, in part, with the aid of relatively noninvasive stable isotope tracer techniques (e.g., 51). Until this research is undertaken, however, complemented by the knowledge emerging from mo lecular and cell biology, further significant advances in the evaluation of protein nutritional status are un likely to occur.

3. Rossouw, J. E. |1989) Kwashiorkor in North America. Am. /. Clin. ut-. 49: 588-592. 4. SCRIMSHAW, N. S. (1988) Integrating nutrition into pro grammes of primary health care. Food Nutr. Bull. 10: 19-28. 5. WHITEHEAD,R. G. (1969) The assessment of nutritional status in protein-malnourished children. Proc. Nutr. Soc. 28: 1-16.

6. COMMITTEE ON PROCEDURES FOR APPRAISAL OFPROTEIN-CALORIE MALNUTRITION OFTHEINTERNATIONAL UNIONOFNUTRITIONAL SCIENCES. (1970) Assessment of protein nutritional status: a committee report. Am. J. Clin, ut-. 23: 807-819.
7. BURRITT,M. P. & ANDERSON,C. F. (1984) Laboratory assess ment of nutritional status. Hum. Pathol. 15: 130-133. 8. SOLOMONS,N. W. (1985) Assessment of nutritional status: functional indicators of pdiatrienutriture. Pediati. Clin. North Am. 32: 319-334. 9. DURNIN, J. V. G. A. & FIDANZA, F. (1985) Evaluation of nu tritional status. Bibl Nutr. Dieta. 35: 20-30. 10. SOLOMONS,N. W. & ALLEN, L. H. (1983) The functional as sessment of nutritional status: principles, practice and potential. Nutr. Rev. 41:33-50. 11. BENJAMIN,D. R. (1989) Laboratory tests and nutritional as sessment. Protein-energy status. Pediatr. Clin. North Am. 36: 139-161. 12. WATERLOW,J. C. (1986) Metabolic adaptation to low intakes of energy and protein. Annu. Rev. Nutr. 6: 495-526. 13. WATERLOW,J. C., GARLICK, P. J. &. MILLWARD,D. J. (1978) Protein Turnover in Mammalian Tissues and in the Whole Body. North-Holland Publishing, Amsterdam. 14. YOUNG, V. R. & MARCHINI, J. S. (1990) Mechanisms and nu tritional significance of metabolic responses to altered intakes of protein and amino acids, with reference to nutritional ad aptation in humans. Am. /. C-in.Nutr. 51: 270-289. 15. YOUNG, V. R. (1970) The role of skeletal and cardiac muscle in the regulation of protein metabolism. In: Mammalian Protein Metabolism, Vol IV, pp. 585-674, (H. N. Munro, ed.), Academic Press, New York. l.MILLWARD,D. J. (1989) The endocrine response to dietary protein: the anabolic drive on growth. In: Milk Proteins in Hu man Nutrition, pp. 49-61 (C. A. Earth & E. Schlimme, eds.), Steinkopff, Darmstadt. 17. UNTERMAN,T. G., VASQUEZ,R. M., SLAS,A. J., MARTYN,P. A. & PHILLIPS,L. S. (1985) Nutrition and somatomedin. XIII. Usefulness of somatomedin C in nutritional assessment. Am. /. Med. 78: 228-234. 18. BAXTER,R. C. (1986) The somatomedins: insulin-like growth factors. Adv. Clin. Chem. 25: 49-115. 19. SHETTY, P. S., JUNG, R. T., WATRASIEWICZ, K. E. &. JAMES, W. P. T. (1979) Rapid-turnover transport proteins: an index of subclinical protein-energy malnutrition. Lancet ii: 230-232. 20. GALLINA,D. L., AUSMAN,L. M., KRIAUCIUNAS, K. & HEGSTED, D. M. (1987) Dissociated response of plasma albumin and transferrin to protein-calorie restriction in squirrel monkeys (Saimir-sciureus). Am. /. Clin. Nutr. 46: 941-948. 21. SACHS,E. & BERNSTEIN,L. H. (1986) Protein markers of nu trition status as related to sex and age. Clin. Chem. 32: 339341. 22. BUONPANE,E. A., BROWN,R. O., BOUCHER,B. A., FABIAN,T. C. & LUTHER,R. W. (1989) Use of fibronectin and somatomedinC as nutritional markers in the enterai nutrition support of traumatized patients. Crit Care. Med. 17: 126-132.
23. BONDESTAM, M., FOUCARD, T. & GEBRE-MEDHIN, M.

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LITERATURE

CITED

1. FAO. (198/1 The Fifth World Food Survey, Food and Agricul ture Organization of the United Nations, Rome, Italy. 2. BISTRIAN,B. R., BLACKBURN, G. L., HALLOWELL, E. & HEDDLE, R. (1974) Protein status of general surgical patients. /.Am. Med. Assoc. 230: 858-860.

(1988) Serum albumin, retinol binding protein, thyroxin-binding pre-albumin and acute phase reactants as indicators of undernutrition in children with undue susceptibility to acute in fections. Acta. Paediatr. Scand. 77: 94-98.

24. LEICHSENRING, M., DOEHRING-SCHWERDTFEGER, E., BREMER,

H. J., DlAMOUANGANA, J., SCHROEDER, U. &. WAHN,

V. (1988) Investigation of the nutritional state of children in a Congolese village. I. Anthropometrical data, plasma pre-al-

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38. LOPES, J., RSSEL, D. McR., WHITWELL, J. & JEEJEEBHOY, K. N. (1982) Skeletal muscle function in malnutrition. Am. J. Clin. Nutr. 36: 602-610. 39. RSSEL, D. McR., LEITER,L. A., WHITWELL,J., MARLISS,E. B. & JEEJEEBHOY, K. N. (1983) Skeletal muscle function during hypocaloric diets and fasting: a comparison with standard nutri tional assessment parameters. Am. /. Clin. Nutr. 37: 133-138. 40. RUSSELL, D. McR., PRENDERGAST, P. J., DORBY,P. L., GARFINKEL, P. E., WHITWELL,J. & JEEJEEBHOY, K. N. (1983) A comparison between muscle function and body composition in anorexia nervosa: the effect of refeeding. Am. ]. Clin. Nutr. 38: 229-237. 41. BEISEL, W. R. (1982) Single nutrients and immunity. Am. /. Clin. Nutr. 35:417-468. 42. CHANDRA, R. K. (1981) Immunodeficiency in undernutrition and overnutrition. Nutr. Rev. 39: 225-231. 43. DALY,J. M., REYNOLDS, J., SIGAL,R. K., SHOW, J. &. LIBERMAN, M. D. (1990) Effect of dietary protein and amino acids on im mune function. Grit. Care Med. 18: S86-S93. 44. BUZBY,G. P., MULLEN,J. L., MATTHEWS,D. C., HOBBS,C. L. & ROSATO,E. F. (1980) Prognostic nutritional index in gastroin testinal surgery. Am. /. Surg. 139: 160-167.
45. RAINEY-MACDONALD, C. G., HOLLIDAY, R. L., WELLS, G. A. &

25.

26.

27.

28.

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