Protein-energy malnutrition

Introduction

The plasma amino acid pattern has been studied in healthy patients of different ages [1-7], but few studies provide information about very elderly people [8-11]. Protein energy malnutrition (PEM) occurs in about 50% of hospitalized old people. Both qualitative and quantitative changes in circulating amino acid concentrations have been reported in PEM. Factors affecting the concentration and the pattern of plasma amino acids include the amount and composition of dietary protein, muscle protein metabolism and the labile protein reserve in various tissues, particularly in the liver.

PEM has two main causes: a decrease in nutrient intake and an increase in catabolic reactions (i.e. a hypermetabolic state). In old patients both may be present at the same time or they may occur successively in a short time as a consequence of multiple pathology.

Decrease in food intake leads to a rise in gluconeogenesis. Hypermetabolic states, associated with infections and inflammatory diseases, turn protein anabolism towards acute phase protein synthesis in the liver, while anabolism of the whole organism is disturbed. Increases in catabolic reactions affect muscle protein [12] and provide phenylalanine, tyrosine and methionine -- the branched-chain amino acids [13-15], which are released without muscle metabolism -- glutamine (a regulator of muscle protein turnover [16] and an essential nutrient for cells of the immune [17] and intestinal systems [18]) and alanine, an important amino acid in gluconeogenesis.

We report an investigation into the plasma free amino acid pattern of healthy normal weight aged controls (80-100 years old) and elderly underweight people with PEM (80-100 years old).

Subjects and methods

Subjects

The 68 subjects investigated form two groups.

The first group comprises 44 control patients (20 men 84.5 [+ or -] 2.7 years old, 24 women 85.4 [+ or -] 3.2 years old), admitted to the geriatric unit of the Montpellier-Nimes University Hospital Centre. Selection was on the basis of benign disease without renal, hepatic or metabolic disorder, presenting symptoms being falls, loss of consciousness, immobility and psychiatric problems. Their clinical state and nutritional status were good. Nutritional status was determined using a food intake questionnaire. (Protein intake was in line with the recommendations of the NAS-NRC [19] and Young's published data [20].)

The second group comprises 24 elderly patients with PEM (10 men 86 [+ or -] 5 years old, 14 women 88.4 [+ or -] 5 years old) hospitalized in the same unit. Nine of these patients had anorexia with pure weight loss. Fifteen had anorexia and weight loss associated with underlying illness (e.g. cancer, pneumonia, Parkinsonism, dementia and the stress of recent surgery). Anthropometric and biological data were collected on admission, before beginning parenteral feeding.

Anthropometric measurements

The following anthropometric measurements were performed on all 68 subjects.

Weight and height/body mass index (BMI)

BMI was expressed as weight (kg)/height ([m.sup.2]) [21]. In bed-ridden patients, height is determined using Chumlea's formula [22] from knee height. (Men with malnutrition have BMI [is less than] 19.5 kg/[m.sup.2], women with malnutrition have BMI [is less than] 18.7 kg/[m.sup.2].)

Mid-arm circumference (MAC) [21]

Patients with malnutrition have MAC [is less than] 24.4 cm (men) and [is less than] 23.1 cm (women).

Body weight as a percentage of ideal weight (IBW)

This is determined using the weight table of Metropolitan Life Insurance Company [23]. (PEM is associated with percentage IBW [is less than] 90%.)

Biological data

Serum albumin and prealbumin, total lymphocyte count (TLC) and serum acute phase protein (C reactive protein, [[Alpha].sub.1]-glycoprotein acid) were measured in all patients. TLC is calculated as the percentage of lymphocytes multiplied by the total white blood cell count. PEM is associated with serum albumin [is less than] 32 g/l, serum prealbumin [is less than] 0.24 g/l and TLC [is less than] 1500 cells/[mm.sup.3].

Plasma amino acid profiles were performed on venous blood samples obtained in heparin-treated tubes, early in the morning, after an overnight fast. Plasma samples were determined using cation-exchange columns with ninhydrin detection in an high performance liquid chromatography system (model 6300, Beckman Instruments) with glucosaminic acid as internal standard.

Clinical data

Clinical features were extracted from medical files. Weight and information about the patients' functional abilities (mobility, continence, communication and appetite) were assessed and recorded by the nursing staff using a specially designed form. Assessment of malnutrition risk was recorded.

Statistical analysis

Statistical analysis was performed by means of the PC Statistical Analysis System (SAS Institute Inc.). For a comparison of quantitative variables (such as anthropometric and biological data) between the two groups (patients with PEM and control patients), Student's t-test was used when the distribution variable was normal. Otherwise, the Kruskal-Wallis test was used.

Log transformation normalized the distribution of all serum amino acid variables except for citrulline, hemicystine, histidine and arginine. Untransformed data were used for arginine and hemicystine. Square root transformation normalized the distribution of citrulline and histidine.

Quantitative variables were evaluated by use of analysis of variance on both factors (2 x 2 factorial design), with a hypothesis of no interaction between gender and malnutrition. When a significant gender/ malnutrition interaction was observed, sex effects were examined separately from malnutrition.

Correlations between serum amino acid concentrations and anthropometric or biological data were examined using Spearman's correlation coefficient. Significance levels were set when P [is less than] 0.05.

Results

Table 1 summarizes the nutritional status of the 68 elderly patients. Weight, BMI, MAC, IBW, albumin and prealbumin in plasma and lymphocyte total in blood are significantly decreased in patients with PEM compared with healthy aged patients.

Table 1. Characteristics -- age, anthropometric and biological parameters--of subjects with and without protein energy malnutrition (PEM)

BMI, body mass index; MAC, mid-arm circumference; IBW, ideal body weight; TLC, total lymphocyte count; NS, not significant.

(a) Student's t-test. (b) Kruskal-Wallis test.

The median and range values for the 5th and 95th percentiles of all measured amino acids in each group are presented in Table 2.

[TABULAR DATA 2 NOT REPRODUCIBLE IN ASCII]

Data showed intergender differences only for serine, proline, citrulline and ornithine. For these four amino acids a significant gender/malnutrition interaction was observed and gender effects were examined separately from malnutrition. There was a significant decrease in plasma serine, proline, citrulline and ornithine concentrations in men with PEM. No sex-related patterns could be identified for the other amino acids, hence data for male and female subjects are pooled in Table 3. Statistically significant differences were observed in many amino acids in patients with PEM (Table 3). These patients had significantly lower plasma concentrations of most essential amino acids (isoleucine, leucine, lysine, threonine and valine); the exceptions being methionine and phenylalanine.

(a) In males only.

A similar decreasing trend was observed for non-essential amino acids alanine, arginine, citrulline, glutamine + glutamic acid, histidine, ornithine, proline, serine and taurine, whereas other non-essential amino acids displayed no significant decrease.

In addition, branched-chain amino acids such as leucine, isoleucine, valine and urea cycle amino acids (ornithine, citrulline, arginine) showed a significant decrease (P [is less than] 0.001).

There was no correlation between the concentrations of amino acids and anthropometric parameters.

Discussion

To determine whether our observations are due primarily to malnutrition or to concurrent illnesses, we have subdivided our patients with PEM into two groups: those with pure weight loss and anorexia and those with weight loss and anorexia associated with concurrent illnesses. No difference was found (Kruskal-Wallis test) between the two groups for any anthropometric and biological variable. Even in those with concurrent illnesses, the prominent clinical picture was of severe PEM. All anthropometric parameters and further amino acid concentrations confirm the chronic and severe state of malnutrition in our patients. Such undernutrition may lead to death if not rapidly corrected [20]. In our study, five out of 24 patients died in spite of parenteral feeding. Despite severe malnutrition, 19 patients were capable of taking food if they were given it by either nasogastric or parenteral feeding: two patients went home and 17 to old people's homes.

Our data on plasma amino acid concentrations reflect previous data obtained in malnutrition [24-27].

There is a decreased plasma concentration of most essential amino acids. A reduced food intake and prolonged protein deprivation affect essential amino acid profiles and particularly branched-chain amino acid levels, since those amino acids are ingested with food intake.

There are variable plasma levels of non-essential amino acids. Patients with PEM showed low concentrations of ornithine, histidine, glutanine and glutamic acid (which have intricate pathways), urea cycle amino acids and alanine. The decrease in plasma alanine concentration (33%) may be because alanine, which is a transamination product of pyruvate, is released by muscle before being processed by the liver into gluconeogenesis. This suggests that in elderly patients with PEM, decreases in urea cycle amino acids are of prime importance. Arginine is the precursor of urea and an important factor in albumin synthesis. This relationship between urea cycle amino acids and albumin synthesis may explain the positive correlation found between urea cycle amino acids and albumin concentrations in elderly patients with PEM (r = 0.55, P [is less than] 0.001, n = 53).

We did not find any significant decrease in plasma concentrations of aromatic amino acids. This is in agreement with the results observed in kwashiorkor [28, 29]. Some authors have suggested that phenylalanine hydroxylase activity is reduced in PEM, resulting in decrease in plasma tyrosine relative to plasma phenylalanine [27,30-32]. Our data show no evidence of this. These amino acids are involved in brain neurotransmitter systems, including the synthesis of dopamine, adrenaline and noradrenaline. Plasma precursors of biogenic amines in the central nervous system may be unaffected by PEM. We agree with Martinez [10] that there is no increase in aromatic amino acid plasma concentrations in elderly patients with idiopathic anorexia.

Levels of nearly all essential amino acids and some non-essential amino acids are very low. In a previous study [33], we have shown that some amino acid plasma concentrations (citrulline, hemicystine, histidine, glutamine + glutamic acid, lysine, ornithine and phenylalanine) are higher in elderly patients (80-100 years old) than in younger healthy subjects (20-45 years old). With ageing, especially when associated with PEM, the ability to respond successfully to an inadequate diet or other stressful conditions is reduced. This may explain why mobilization of amino acids from peripheral tissues is decreased.

This study illustrates the effect of ageing and PEM on plasma amino acid concentrations. Interpretation of plasma amino acid concentrations in PEM is not easy. Amino acids are in constant state of flux between the body protein pools. Approximately 2-3% of the total body protein pool turns over daily [34], and circulating free amino acids represent only 0.01% [25-35]. Also, measurements of plasma amino acid concentrations are one point in a dynamic process and cannot be used to draw conclusions about the dynamics of protein metabolism. Furthermore, cellular levels may differ from plasma concentrations. The ratio between intracellular and extracellular amino acid concentrations may vary among individuals, according to age, sex, hormones [4-20-28] and diet. The adaptation to chronic low protein intake in elderly patients with PEM merits further investigation.

Acknowledgements

The authors are grateful for the technical assistance of Claudine Hastings.

Key points

* Little is known about plasma or tissue amino acid concentrations in older people.

* We have obtained an amino acid profile in malnourished patients over 80 and an age-matched control group of ideal body weight.

* Plasma amino acid concentrations are affected by intercurrent illness as well as malnutrition.

* In protein energy malnutrition, concentrations of both essential and non-essential amino acids are low and reflect the severity of the metabolic disturbance.

References

[1.] Ackerman PG, Kheim T. Plasma amino acids in young and older adult human subjects. Clin Chem 1964; 10: 32-40.

[2.] Armstrong MD, Stave U. A study of plasma amino acid levels. U: Normal values for children and adults. Metabolism 1973; 22: 561-70.

[3.] Armstrong MD, Stave U. A study of plasma amino acid levels. m: Variations during growth and aging. Metabolism 1973; 22: 571-8.

[4.] Galante A, Angelico F, Crocchioni G, Penneth V. Intersexual differences in the serum free amino acid pattern of young adults, normal and obese aged subjects. Nutr Metab 1978; 22: 119-26.

[5.] Koh ET, Cha CJ. Comparison of plasma amino acids by race, sex and age. Nutr Rep Int 1983; 28: 8-22.

[6.] Milsom JP, Morgan MY, Sherlock S. Factors affecting plasma amino acid concentration in control subjects. Metabolism 1979; 28: 313-9.

[7.] Scriver CR, Gregory DN, Sovetts D, Tissenbaum G. Normal plasma free amino acid values in adults: the influence of some common physiological variables. Metabolism 1985; 34: 868-73.

[8.] Rudman D, Mattson DE, Feller AG, Cotter R, Johnson RC. Fasting free amino acids in elderly men. Am J Clin Nutr 1%7; 49: 559-66.

[9.] Berthel M, Galeyrand JP, Mark J, Kuntzmann E Amino-acidemie chez le sujet age. Med Hyg 1979; 37: 1881-5.

[10.] Martinez M, Arnalich F, Vasquez JJ, Hernanz A. Altered cerebrospinal fluid amino acid pattern in the anorexia of aging: relationship with biogenic amine metabolism. Life Sci 1993; 53: 1643-50.

[11.] Young VR. Amino acids and proteins in relation to nutrition of elderly people. Age Ageing 1990; 19: 510-24.

[12.] Long CL, Birkhan RH, Geiger JW, Blackemore WS. Contribution of skeletal muscle protein in elevated rates of whole body protein catabolism in septic man. Am J Clin Nutr 1981; 34: 1087-93.

[13.] Harper AK, Miller RH, Block KP. Branched chain amino acid metabolism. Annu Rev Nutr 1984; 4: 409-54.

[14.] Kinney JM, Elwyn DH. Protein metabolism and injury. Annu Rev Nutr 1983; 3: 433-66.

[15.] Smith R, Williamson DH. Biochemical effects of human injury. Trends Biochem Sci 1983; 198: 142-6.

[16.] Watford M. Does glutamine regulate skeletal muscle protein turnover? Trends Biochem Sci 1989; 14: 1-2.

[17.] Newsholme EA, Crabtree B, Ardawi MSM. Glutamine metabolism in lymphocyte: its biochemical, physiological and clinical importance. QJ Exp Physiol 1985; 70: 473-89.

[18.] Winomueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 1974; 249: 5070-9.

[19.] NAS-NRC. Recommanded dietary allowances. Ninth edition. Washington DC: National Academy Sciences-National Research Council, 1980.

[20.] Young VR. Protein and amino acid metabolism with reference to aging and the elderly. Nutr Aging 1990; 279-300.

[21.] Alix A, Papin A, Vetel JM. Les methodologies de l'evaluation de l'etat nutritionnel de la personne agee. Revue de la litterature et analyse critique. Med Hyg 1988; 46: 1507-12.

[22.] Chumlea WC, Vellas B, Roche AF, Guo S, Steinbaug H. Particularites et interet des mesures anthropometriques du status nutritionnel des personnel agees. Age Nutrition 1990; 1: 7-13.

[23.] Metropolitan Life Insurance Company. New weight standards for men and women. Stat Bull Metropol Life Insur Com 1959; 40: 1-4.

[24.] Saunders SM, Truswell SJ, Barbezat-Wittman W, Mansen JDL. Plasma free amino acid pattern in protein caloric malnutrition. Lancet 1967; 14: 795-7.

[25.] Smith SR, Pozefsky T, Chhetri MK. Nitrogen and amino acid metabolism in adults with protein-caloric malnutrition. Metabolism 1974; 23: 603-18.

[26.] Soliman AT, Abd El Hadi IH, Rogol AD. Endocrine and amino acid changes in protein energy malnutrition (PEM). J Trop Pediatr 1991; 37: 331-2.

[27.] Ingenbleek Y, Barclay D, Dirren H. Nutritional significance of alterations in serum amino acid patterns in goitrous patients. Am J Clin Nutr 1986; 43: 310-9.

[28.] Holt LE, Snyderman SE, Norton PM, Roitman E. The plasma aminogram is affected by protein intake. In: Leathen JM, ed. Protein Nutrition and Free Amino Acid Patterns. New Brunswick: Rutgers University Press, 1968; 32.

[29.] Waterlow JC. Assessment of protein nutrition and metabolism in the whole animal with special reference to man. In: Munro HN, ed. Mammalian Protein Metabolism, Vol. 3. New York: Academic Press, 1969; 325.

[30.] Fukagawa NK, Minaker KL, Young VR, Rowe JW. Insulin dose-dependent reductions in plasma amino acids in men. Am J Physiol 1986; 250: 13-7.

[31.] Lesourd B. La denutrition proteique: principale cause de deficit immunitaire chez le sujet age. Age Nutrition 1990; 1: 132-8.

[32.] Viteri F, Behar M, Arroyave G, Scrimshaw NS. Clinical aspects of protein malnutrition. In: Munro HN, Allison JB, eds. Mammalian Protein Metabolism, Vol. 2. New York: Academic Press, 1964; 523.

[33.] Bancel E, Strubel D, Bellet H, Polge A, Peray P, Magnan de Bornier B. Effet de l'age et du sexe sur les concentrations des acides amines plasmatiques. Ann Biol Clin 1994; 52: 667-70.

[34.] Heyman MB. General and specialized parenteral amino-acid formulafions for nutrition support. Perspectives in Practice 1990; 90: 401-11.

[35.] Tweedle DEF. Intravenous amino acid requirements: a review. In: Karran SJ, Alberti KGMM, eds. Practical Nutritional Support. Canterbury: Pitman Medical, 1980; 126-137.

Received 20 December 1996

Christine Carlett, Geriatric Care `Serre-Cavalier'

Denise Strubel, Geriatric Care `Serre-Cavalier'

Pascale Peray, Department of Biostatistics, Montpellier-Nimes University Hospital Centre, Nimes, France

Address correspondence to: A. Polge. Fax: (+33) 466 68 32 05

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