Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-19T06:13:25.177Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of long-term refeeding on protein metabolism in patients with cirrhosis of the liver

Published online by Cambridge University Press:  09 March 2007

Jens Kondrup ,
Klaus Nielsen  and
Anders Juul
Jens Kondrup
Affiliation:
The Clinical Nutrition Unit and Division of Hepatology, Department of Medicine A & Department of Growth and Reproduction, Rigshospitalet, 9 Blegdamsvej, DK-2100 Ø, Copenhagen, Denmark
Klaus Nielsen
Affiliation:
The Clinical Nutrition Unit and Division of Hepatology, Department of Medicine A & Department of Growth and Reproduction, Rigshospitalet, 9 Blegdamsvej, DK-2100 Ø, Copenhagen, Denmark
Anders Juul
Affiliation:
The Clinical Nutrition Unit and Division of Hepatology, Department of Medicine A & Department of Growth and Reproduction, Rigshospitalet, 9 Blegdamsvej, DK-2100 Ø, Copenhagen, Denmark
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance. However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen et al. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25% of control values and remained low during refeeding.

Keywords

Nitrogen retentionProtein metabolismAlcoholic cirrhosis
Type
Human and Clinical Nutrition
Information
British Journal of Nutrition , Volume 77 , Issue 2 , February 1997 , pp. 197 - 212
Copyright
Copyright © The Nutrition Society 1997

References

REFERENCES

Bang, P., Eriksson, U., Sara, V., Wivall, I.-L. & Hall, K. (1991). Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays: Improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand. Acta Endocrinologica 124, 620–629.Google ScholarPubMed
Bingham, S. & Cummings, J. H. (1983). The use of 4-aminobenzoiC acid as a marker to validate the completeness of 24h urine collection in man. Clinical Science 64, 629–635.CrossRefGoogle Scholar
Bingham, S. & Cummings, J. H. (1985). Urine nitrogen as an independent validatory measure of dietary intake: a study of nitrogen balance in individuals consuming their normal diet. American Journal of Clinical Nutrition 42, 1276–1289.CrossRefGoogle ScholarPubMed
Blum, W. F., Ranke, M. B., Kietzmann, K., Gauggel, E., Zeisel, H. J. & Bierich, J. R. (1990). A specific radioimmunoassay for the growth hormone(GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. Journal of Clinical Endocrinology and Metabolism 70, 1292–1298.CrossRefGoogle ScholarPubMed
Bonkovsky, H. L., Singh, R. H., Jafri, I. H., Fiellin, D. A., Smith, G. S., Simon, D., Cotsonis, G. A. & Slaker, D. P. (1991). A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition. American Journal of Gastroenterology 86, 1209–1218.Google ScholarPubMed
Castellino, P., Luzi, L., Simonsen, D. C., Haymond, M & DeFronzo, R. A. (1987). Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. Journal of Clinical Investigation 80, 1784–1793.CrossRefGoogle ScholarPubMed
Clemmons, D. R., Smith-Banks, A. & Underwood, L. E. (1992). Reversal of diet-induced catabolism by infusion of recombinant insulin-like growth factor-I in humans. Journal of Clinical Endocrinology and Metabolism 75, 234–238.Google ScholarPubMed
Clemmons, D. R. & Underwood, L. E. (1991). Nutritional regulation of IGF-I and IGF binding. Annual Reviews of Nurition 11, 393–412.CrossRefGoogle ScholarPubMed
Couet, C., Fukagawa, N. K., Matthews, D. E., Bier, D. M. & Young, V. R. (1990). Plasma amino acid kinetics during acute states of glucagon deficiency and excess in healthy adults. American Journal of Physiology 258, E78–E85.Google ScholarPubMed
Elahi, D., McAloon-Dyke, M., Fukagawa, N. K., Sclater, A. L., Wong, G. A., Shannon, R. P., Minaker, K. L., Miles, J. M., Rubenstein, A. H., Vandepol, C. J., Guler, H.-P., Good, W. R., Swaman, J. J. & Wolfe, R. R. (1993). Effect of recombinant human IGF-I on glucose and leucine kinetics in men. American Journal of Physiology 265, E831–E838.Google ScholarPubMed
Fern, E. B., Garlick, P. J. & Waterlow, J. C. (1985). The concept of the single body pool of metabolic nitrogen in determining the rate of whole-body nitrogen turnover. Human Nutrition: Clinical Nutrition 39C, 85–99.Google Scholar
Fulks, R. M., Li, J. B. & Goldberg, A. L. (1975). Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. Journal of Biological Chemistry 250, 290–298.CrossRefGoogle ScholarPubMed
Garlick, P. J. & Grant, I. (1988). Amino acid infusion increase the sensitivity of muscle protein synthesis in vivo to insulin. Journal of Biochemistry 254, 579–584.CrossRefGoogle ScholarPubMed
Giordana, M., Castellino, P., Carroll, C. A. & DeFronzo, R. A. (1995). Comparison of the effects of human recombinant insulin-like growth factor I and insulin on plasma amino acid concentrations and leucine kinetics in humans, Diabetologia 38, 732–738.CrossRefGoogle Scholar
Golden, M. H. N. & Jackson, A. A. (1981). Assumptions and errors in the use of 15N-excretion data to estimate whole body protein turnover. In Nitrogen Metabolism in Man pp. 323–343 [Waterlow, J. C. and Stephen, J. M. L., editors]. London: Applied Science Publisher.Google Scholar
Golden, M. H. N. & Waterlow, J. C. (1977). Total protein synthesis in elderly people: a comparison of results with 15N glycine and 14C leucine. Clinical Science and Molecular Medicine 53, 277–288.Google ScholarPubMed
Goodwin, J. F. (1970). Spectrophotometric quantitation of plasma and urinary amino nitrogen with fluorodinitrobenzene. Standard Methods of Clinical Chemistty 6, 89–98.CrossRefGoogle Scholar
Hamberg, O. & Vilstrup, H. (1994). Effects of glucose on hepatic conversion of amino-nitrogen to urea in patients with cirrhosis: Relationship to glucagon. Hepatology 19, 45–54.CrossRefGoogle Scholar
Hirsch, S., Maza, P. M., Petermann, M., Iturriaga, H., Ugarte, G. & Bunout, D. (1995). Protein turnover in abstinent and non-abstinent patients with alcoholic cirrhosis. Journal of the American College of Nutrition 14, 99–104.CrossRefGoogle ScholarPubMed
Jeevanandam, M., Lowry, S. F., Horowitz, G. D., Legaspi, A. & Brennan, M. F. (1986). Iduence of increasing dietary intake on whole body protein kinetics in normal man. Clinical Nutrition 5, 41–48.CrossRefGoogle ScholarPubMed
Juul, A., Dalgaard, P., Blum, W. F., Bang, P., Hall, K., Michaelsen, K. F., Müller, J. & Skakkebaek, N. E. (1995). Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children and adolescents: The relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. Journal of Clinical Endocrinology and Metabolism 80, 2534–2542.Google ScholarPubMed
Kohno, M., Fujii, T. & Hirayama, C. (1990). 15N Glycine metabolism in normal and cirrhotic subjects. Biochemical Medicine and Metabolic Biology 43, 201–213.CrossRefGoogle ScholarPubMed
Kondrup, J., Nielsen, K. & Hamberg, O. (1992). Nutritional therapy in patients with liver cirrhosis. European Journal of Clinical Nutrition 46, 239–246.Google ScholarPubMed
Lautz, H. U., Selberg, O., Küber, J., Bürger, M. & Müller, M. J. (1992). Forms of malnutrition in patients with liver cirrhosis. Clinical Investigator 70, 478–486.CrossRefGoogle Scholar
McCullough, A. & Glamour, T. (1993). Differences in amino acid kinetics in cirrhosis. Gastroenterology 104, 1858–1864.CrossRefGoogle ScholarPubMed
Martin, M., Ward, K., Slavin, G., Levi, J. & Peters, T. J. (1985). Alcoholic skeletal myopathy, a clinical and pathological study. Quarterly Journal of Medicine 55, 233–251.Google ScholarPubMed
Milikan, W. J., Henderson, J. M., Galloway, J. R., Warren, W. D., Matthews, D. E., McGhee, A. & Kutner, M.H. (1985). In vivo measurement of leucine metabolism with stable isotopes in normal subjects and in those with cirrhosis fed conventional and branched-chain amino acid-enriched diets. Surgery 98, 405–413.Google Scholar
Millward, D. J. (1990). The hormonal control of protein turnover. Clinical Nutrition 9, 115–126.CrossRefGoogle ScholarPubMed
Millward, D. J., Brown, J. G. & van Bueren, J. (1988). The influence of plasma concentrations of triiodothyronine on the acute increases in insulin and muscle protein synthesis in the refed fasted rat. Journal of Endocrinology 118, 417–422.CrossRefGoogle ScholarPubMed
Nielsen, K., Kondrup, J., Elsener, P., Juul, A. & Jensen, E. S. (1994). Casein and soya-bean protein have different effects on whole-body protein turnover at the same nitrogen balance. British Journal of Nutrition 72, 69–81.CrossRefGoogle ScholarPubMed
Nielsen, K., Kondrup, J., Martinsen, L., Døssing, H., Larsson, B., Stilling, B. & Jensen, M. G. (1995). Long-term oral refeeding of patients with cirrhosis of the liver. British Journal of Nutrition 74, 557–567.CrossRefGoogle ScholarPubMed
Nielsen, K., Kondrup, J., Martinsen, L., Stilling, B. & Wikman, B. (1993). Nutritional assessment and adequacy of dietary intake in hospitalized patients with alcoholic liver cirrhosis. British Journal of Nutrition 69, 665–679.CrossRefGoogle ScholarPubMed
Pacy, P. J., Cheng, K. N., Ford, G. C. & Halliday, D. (1990). Influence of glucagon on protein and leucine metabolism: a study in fasting man with induced insulin resistance. British Journal of Surgery 77, 791–794.CrossRefGoogle ScholarPubMed
Pacy, P. J., Price, G. M., Halliday, D., Quevedo, M.-R. & Millward, D. J. (1994). Nitrogen homeostasis in man: the diurnal responses of protein synthesis and degradation and amino acid oxidation to diets with increasing protein intakes. Clinical Science 86, 103–118.CrossRefGoogle ScholarPubMed
Perez-Sala, D., Parrilla, R. & Ayuso, M. S. (1987). Key role of L-alanine in the control of hepatic protein synthesis. Biochemical Journal 241, 491–498.CrossRefGoogle ScholarPubMed
Picou, D. & Taylor-Roberts, T. (1969). Measurement of total protein synthesis and catabolism and nitrogen turnover in infants in different nutritional states and receiving different amounts of dietary protein. Clinical Science 36, 283–296.Google ScholarPubMed
Preedy, V. R., Peters, T. J., Patel, V. B. & Miell, J. P. (1994). Chronic alcoholic myopathy: transcription and translational alterations. FASEB Journal 8, 1146–1151.Google ScholarPubMed
Pugh, R. N. H., Murray-Lyon, I. M., Dawson, J. L., Pietroni, M. C. & Williams, R. (1973). Transection of the oesophagus for bleeding oesophageal varices. British Journal of Surgery 60, 646–649.CrossRefGoogle ScholarPubMed
Swart, G. R., van den Berg, J. W. O., van Vuure, J. K., Tietveld, T., Wattimena, D. L. & Frenkel, M. (1989). Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clinical Nutrition 8, 329–336.CrossRefGoogle ScholarPubMed
Swart, G. R., van den Berg, J. W. O., Wattimena, J. L. D., Rietveld, T., Van Vuure, J. K. & Frenkel, M. (1988). Elevated protein requirement in cirrhosis of the liver investigated by whole body protein turnover studies. Clinical Science 75, 101–107.CrossRefGoogle ScholarPubMed
Tessari, P., Inchiostro, S., Biolo, G., Trevisan, R., Fantin, G., Marescotti, M. C., Iori, E., Tiengo, A. & Crepaldi, C. (1987). Differential effects of hyperinsulinemia and hyperaminoacidemia on leucine-carbon metabolism in vivo. Journal of Clinical Investigation 79, 1062–1069.CrossRefGoogle ScholarPubMed
Tessari, P., Inchiostro, S., Barazzoni, R., Zanetti, M., Orlando, R., Biolo, G., Sergi, G., Pino, A. & Tiengo, A. (1994). Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis. American Journal of Physiology 267, E140–E149.Google ScholarPubMed
Thompson, J. L., Butterfield, G. E., Marcus, R., Hintz, R. L., van Loan, M., Ghiron, L. & Hoffman, A. R. (1995). The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. Journal of Clinical Endocrinology and Metabolism 80, 1845–1852.Google ScholarPubMed
Tygstrup, N. (1966). Determination of the hepatic elimination capacity (Lm) of galactose by single injection. Scandinavian Journal of Clinical and Laboratory Investigation 18, 118–125.Google ScholarPubMed
Yoshizawa, F., Endo, M., Ide, H., Yagasaki, K. & Funabiki, R. (1995). Translational regulation of protein synthesis in the liver and skeletal muscle of mice in response to refeeding. Journal of Nutritional Biochemisty 6, 130–136.CrossRefGoogle Scholar