Hostname: page-component-84b7d79bbc-g7rbq Total loading time: 0 Render date: 2024-08-01T19:38:04.986Z Has data issue: false hasContentIssue false

An adaptive metabolic demand model for protein and amino acid requirements

Published online by Cambridge University Press:  09 March 2007

D. J. Millward*
Affiliation:
Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK
*
Corresponding author: Professor D. J. Millward, fax +44 1483 689297, email D.Millward@surrey.ac.uk
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.

The shortcomings of the metabolic implications of the current protein requirements model are reviewed, and an alternative model, validated with [1-13C]leucine balance results in human adults, is presented and evaluated in the context of defining protein requirements. The model identifies metabolic demands for amino acids as comprising a small fixed component and a variable adaptive component that is relatively insensitive to acute food or protein intake, but which changes slowly with a sustained change in intake, enabling N equilibrium to be achieved. The model accounts for the apparent low efficiency of utilisation of animal proteins in N balance studies and enables more realistic efficiency values to be measured within an experimental framework that takes account of the adaptive metabolic demand. However, the complex relationship between the adaptive metabolic demand and habitual level and quality of protein intake prevents prediction of protein quality by amino acid scoring, which can markedly underestimate actual values. In contrast to the current model, for fully adapted individuals risk of deficiency (i.e. negative N balance after complete adaptation) will only start to increase when intakes fall below the range of the true minimum requirements, i.e. a value that is currently unknown, but likely to be between 0·40 and 0·50 g/kg per d at the lower end of the reported distribution of requirements. At intakes greater than this with additional metabolic demands varying directly with intake, deficiency is only likely as a short-term response to a change to a lower intake within the adaptive range. Thus, for adults satisfying energy needs on most mixed human diets, intakes will be within the adaptive range, and N equilibrium ceases to be a useful indicator of nutritional adequacy of protein. In the context of prescriptive dietary guidelines it may be expedient to retain current values until the benefits (and any risks) of protein intakes within the adaptive range can be quantified. However, from a diagnostic perspective, indicators other than N balance need to be identified, since maintenance of N balance can no longer be used as a surrogate of adequate protein-related health.

Type
Horizons in Nutritional Sciences
Copyright
Copyright © The Nutrition Society 2003

References

Atinmo, T, Mbofung, CMF, Egun, G & Osotimehin, B (1988) Nitrogen balance study in young Nigerian adult males using four levels of protein intake. Br J Nutr 60, 451458.CrossRefGoogle ScholarPubMed
Beaton, GH (1994) Criteria of an adequate diet. In Modern Nutrition in Health and Disease, 8th ed., pp. 14911505. [Shils, ME, Olson, JA & Shike, M, editors]. Philadelpia, PA: Lea & Febiger.Google Scholar
Beaton, GH (1999) Recommended dietary intakes: individuals and populations. In Modern Nutrition in Health and Disease, 9th ed., pp. 17051725. [Shils, ME, Olson, JA, Shike, M & Ross, AC, editors]. Baltimore, MD: Williams & Wilkins.Google Scholar
Calloway, DM & Chenowweth, WL (1973) Utilization of nutrients in milk- and wheat-based diets by men with adequate and reduced abilities to absorb lactose. I. Energy and nitrogen. Am J Clin Nutr 26, 939951.Google ScholarPubMed
Department of Health (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. Report on Health and Social Subjects. no. 41. London: H M Stationery Office.Google Scholar
Durkin, N, Ogar, DA, Tilve, SG & Margen, S (1981) Human Protein Requirements. Autocorrelation and Adaptation to a Low-protein Diet Containing 0.356 gm Protein/kg or 57 mg N/Kg Body Weight. FAO/WHO/UNU Inf. Paper no. 7. Geneva: WHO.Google Scholar
El Khoury, AE, Fukagawa, NK & Sanchez, M et al. (1994 a) Validation of the tracer–balance concept with reference to leucine: 24-h intravenous tracer studies with L-[1-13C] leucine and [15N-15N] urea. Am J Clin Nutr 59, 10001011.CrossRefGoogle Scholar
El Khoury, AE, Fukagawa, NK & Sanchez, M (1994 b) The 24-h pattern and rate of leucine oxidation, with particular reference to tracer estimates of leucine requirements in healthy adults. Am J Clin Nutr 59, 10121020.CrossRefGoogle ScholarPubMed
Fereday, A, Gibson, NR, Cox, M, Pacy, PJ & Millward, DJ (1997) Protein requirements and ageing: metabolic demand and efficiency of utilization. Brit J Nutr 77, 685702.CrossRefGoogle ScholarPubMed
Fereday, A, Gibson, NR, Cox, M, Pacey, PJ & Millward, DJ (1998) Variation in the apparent sensitivity of the insulin-mediated inhibition of proteolysis to amino acid supply determines the efficiency of protein utilization. Clin Sci 95, 725733.CrossRefGoogle ScholarPubMed
Food and Agriculture Organization (1968) Food Composition Table for Use in Africa. FAO: Rome. http://www.fao.org/docrep/003/x6877e/X6877E00.htm#TOCGoogle Scholar
Food and Agriculture Organization/World Health Organization (1973) Energy and Protein Requirements. Report of a Joint FAO/WHO ad hoc Expert Committee. Technical Report Series no. 522. Geneva: WHO.Google Scholar
Food and Agriculture Organization/World Health Organization (1991) In Protein Quality Evaluation. Report of a Joint FAO/WHO Expert Consultation. Rome: FAO.Google Scholar
Food and Agriculture Organization/World Health Organization/United Nations University (1985) In Energy and Protein Requirements. 15. Report of a Joint FAO/WHO/UNU Expert Consultation. Technical Report Series. Geneva: WHO.Google Scholar
Garlick, PJ, McNurlan, MA & Patlak, CS (1999) Adaptation of protein metabolism in relation to limits to high dietary protein intake. Eur J Clin Nutr 53, Suppl 1, S34S43.CrossRefGoogle ScholarPubMed
Garza, C, Scrimshaw, NS & Young, VR (1977 a) Human protein requirements: a long-term metabolic nitrogen balance study in young men to evaluate the 1973 FAO/WHO safe level of egg protein intake. J Nutr 107, 335352.CrossRefGoogle Scholar
Garza, C, Scrimshaw, NS & Young, VR (1977 b) Human protein requirements: evaluation of the 1973 FAO/WHO safe level of protein intake for young men at high energy intakes. Br J Nutr 37, 403420.CrossRefGoogle ScholarPubMed
Garza, C, Scrimshaw, NS & Young, VR (1978) Human protein requirements: interrelationships between energy intake and nitrogen balance in young men consuming the 1973 FAO/WHO safe level of egg protein, with added non-essential amino acids. J Nutr 108, 9096.CrossRefGoogle ScholarPubMed
Gibson, NR, Fereday, A, Cox, M, Halliday, D, Pacy, PJ & Millward, DJ (1996) Influences of dietary energy and protein on leucine kinetics during feeding in healthy adults. Am J Physiol 33, 282291.Google Scholar
Hegsted, DM (2000) From chick nutrition to nutrition policy. Ann Rev Nutr 20, 119.CrossRefGoogle ScholarPubMed
Institute of Medicine (2000) Dietary Reference Intakes: Application in Dietary Assessment. Washington, DC: National Academies Press.Google Scholar
Institute of Medicine (2002) Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press.Google Scholar
Kurpad, AV & Vaz, M (2000) Protein and amino acid requirements in the elderly European. Am J Clin Nutr 54, Suppl. 3, S131S142.CrossRefGoogle Scholar
Marchini, JS, Cortiella, J, Hiramatsu, T, Chapman, TE & Young, VR (1993) Requirements for indispensable amino acids in adult humans: longer term amino acid kinetic study with support for the adequacy of the Massachusetts Institute of Technology amino acid requirement pattern. Am J Clin Nutr 58, 670683.CrossRefGoogle ScholarPubMed
Millward, DJ (1995) A protein-stat mechanism for the regulation of growth and maintenance of the lean-body mass. Nutr Res Rev 8, 93120.CrossRefGoogle ScholarPubMed
Millward, DJ (1998) Metabolic demands for amino acids and the human dietary requirement: Millward & Rivers (1988) revisited. J Nutr 128, 2563S2576S.CrossRefGoogle ScholarPubMed
Millward, DJ (1999 a) The nutritional value of plant based diets in relation to human amino acid and protein requirements. 1999. Proc Nutr Soc 58, 249260.CrossRefGoogle Scholar
Millward, DJ (1999 b) Optimal intakes of dietary protein. Proc Nutr Soc 58, 403413.CrossRefGoogle Scholar
Millward, DJ, Fereday, A, Gibson, NR & Pacy, PJ (1997) Ageing, protein requirements and protein turnover. Am J Clin Nutr 66, 774786.CrossRefGoogle ScholarPubMed
Millward, DJ, Fereday, A, Gibson, NR & Pacy, PJ (2000) Human adult protein and amino acid requirements: [13C-1] leucine balance evaluation of the efficiency of utilization and apparent requirements for wheat protein and lysine compared with milk protein in healthy adults. Am J Clin Nutr 72, 112121.CrossRefGoogle ScholarPubMed
Millward, DJ, Fereday, A, Gibson, NR & Pacy, PJ (2002) Efficiency of utilization and apparent requirements for wheat protein and lysine determined by a single meal [13C-1] leucine balance comparison with milk protein in healthy adults. Am J Clin Nutr 76, 13261334.CrossRefGoogle Scholar
Millward, DJ, Jackson, AA, Price, G & Rivers, JPW (1989) Human amino acid and protein requirements: Current dilemmas and uncertainties. Nutr Res Rev 2, 109132.CrossRefGoogle ScholarPubMed
Millward, DJ & Pacy, PJ (1995) Postprandial protein utilisation and protein quality assessment in man. Clin Sci 88, 597606.CrossRefGoogle ScholarPubMed
Millward, DJ & Rivers, JPW (1988) The nutritional role of indispensible amino acids and the metabolic basis for their requirements. Eur J Clin Nutr 42, 367393.Google ScholarPubMed
Millward, DJ & Roberts, SR (1996) Protein requirement of older individuals. Nutr Res Rev 9, 6788.CrossRefGoogle ScholarPubMed
New, SA & Millward, DJ (2003) Calcium, protein, and fruit and vegetables as dietary determinants of bone health. Am J Clin Nutr 77, 13401341.CrossRefGoogle ScholarPubMed
Oddoye, EA & Margen, S (1979) Nitrogen balance studies in humans: long-term effect of high nitrogen intake on nitrogen accretion. J Nutr 109, 363377.CrossRefGoogle ScholarPubMed
Pellett, PL & Young, VR (1992) The effects of different levels of energy intake on protein metabolism and of different levels of protein intake on energy metabolism: a statistical evaluation from the published literature. In Protein Energy Interactions, pp. 81136. [Scrimshaw, NS and Schurch, B, editors]. Waterville Valley, NH: IDECG, http://www.unu.edu/unupress/food2/UID07E/UID07E00.HTMGoogle Scholar
Platt, BS, Miller, DS & Payne, PR (1961) Protein values of human food. In Recent Advances in Human Nutrition, pp. 351374. [Brock, JF, editor]. Boston, MA: Little, Brown.Google Scholar
Price, GM, Halliday, D, Pacy, PJ, Quevedo, MR & Millward, DJ (1994) Nitrogen homeostasis in man: 1. Influence of protein intake on the amplitude of diurnal cycling of body nitrogen. Clin Sci 86, 91102.CrossRefGoogle ScholarPubMed
Pacy, PJ, Price, GM, Halliday, D, Quevedo, MR & Millward, DJ (1994) Nitrogen homeostasis in man: 2. The diurnal responses of protein synthesis and degradation and amino acid oxidation to diets with increasing protein intakes. Clin Sci 86, 103116.CrossRefGoogle ScholarPubMed
Quevedo, MR, Price, GM, Halliday, D, Pacy, PJ & Millward, DJ (1994) Nitrogen homeostasis in man: 3. Diurnal changes in nitrogen excretion, leucine oxidation and whole body leucine kinetics during a reduction from a high to a moderate protein intake. Clin Sci 86, 185193.CrossRefGoogle ScholarPubMed
Raguso, CA, Perreira, P & Young, VR (1999) A tracer investigation of obligatory oxidative amino acid losses in healthy young adults. Am J Clin Nutr 70, 474483.CrossRefGoogle ScholarPubMed
Rand, WM, Pellett, PL & Young, VR (2003) Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Am J Clin Nutr 77, 109127.CrossRefGoogle ScholarPubMed
Rand, WM, Scrimshaw, NS & Young, VR (1979) Analysis of temporal patterns in urinary nitrogen excretion of young adults receiving constant diets at two nitrogen intakes for 8–11 weeks. Am J Clin Nutr 32, 14081414.CrossRefGoogle Scholar
Reeds, PJ (2000) Dispensable and indispensable amino acids for humans. J Nutr 130, 1835S1840S.CrossRefGoogle ScholarPubMed
Scrimshaw, NS, Hussein, MA, Murray, E, Rand, WM & Young, VR (1972) Protein requirements of man. Variations in obligatory urinary fecal losses in men. J Nutr 102, 15951604.CrossRefGoogle Scholar
Sukhatme, PV & Margen, S (1978) Models of protein deficiency. Am J Clin Nutr 31, 12371256.CrossRefGoogle ScholarPubMed
Tomé, D & Bos, C (2000) Dietary protein and nitrogen utilization. J Nutr 130, 1868S1873S.Google ScholarPubMed
Waterlow, JC (1996) The requirements of adult man for indispensable amino acids. Eur J Clin Nutr 50, Suppl. 1, S151S179.Google ScholarPubMed
Waterlow, JC (1999) The mysteries of nitrogen balance. Nutr Res Rev 12, 2554.CrossRefGoogle ScholarPubMed
Waterlow, JC, Garlick, PJ & Millward, DJ (1978) In Protein Turnover in Mammalian Tissues and in the Whole Body. Amsterdam: Elsevier/North-Holland Biomedical Press.Google Scholar
Yoshimura, H (1972) Physiological effect of protein deficiency with special reference to evaluation of protein nutrition and protein requirement. World Rev Nutr Diet 14, 100133.CrossRefGoogle ScholarPubMed
Young, VR & Borgonha, S (1998) Nutritional adaptation (genetic, physiological and behavioural): Implications for requirements. In From Nutritional Science to Nutrition Policy for Better Global Health, pp. 57160. [Fitzpatrick, DW, Anderson, JE & L'Abbe, ML, editors]. Ottowa: Canadian Federation of Biological Societies.Google Scholar
Young, VR & El-Khoury, AE (1995) Can amino acid requirements for nutritional maintenance in adult humans be approximated from the amino acid composition of body mixed proteins? Proc Natl Acad Sci USA 92, 300304.CrossRefGoogle ScholarPubMed