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Fereday A, Gibson NR, Cox M et al. (1998) Variation in amino acid mediated, insulin activated inhibition of proteolysis determines the efficiency of protein utilization. Clinical Science 95: 725-733. Gibson NR, Fereday A, Cox M et al. (1996) Influences of dietary energy and protein on leucine kinetics during feeding in healthy adults. American Journal of Physiology 33: 282-291.

Haussinger D and Lang F (1992) Cell volume and hormone action. Trends in Pharmacological Science 13: 371-373.

Jagoe RT and Goldberg AL (2001) What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? Current Opinion in Clinical Nutrition and Metabolic Care 4: 183-190.

Millward DJ (1995) Insulin and the regulation of amino acid catabolism and protein turnover. In Cynober L (ed.) Amino Acid Metabolism in Health and Disease, pp. 127-136. Boca Raton, FL: CRC Press.

Millward DJ (1995) A protein-stat mechanism for regulation of growth and maintenance of the lean-body mass. Nutrition Research Reviews 8: 93-120.

Millward DJ, Fereday A, Gibson NR et al. (1996) Postprandial protein metabolism. Baillier's Clinical Endocrinology and Metabolism 10: 533-549.

Millward DJ, Fereday A, Gibson NR et al. (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. American Journal of Clinical Nutrition 72: 112-121.

Millward DJ and Rivers JPW (1989) The need for indispensable amino acids: The concept of the anabolic drive. Diabetes Metabolism Reviews 5: 191-212.

Miotto G, Venerando R, Marin O et al. (1994) Inhibition of macroautophagy and proteolysis in the isolated rat hepatocyte by a non-transportable derivative of the multiple antigen peptide Leu8-Lys4-Lys2-Lys-betaAla. Journal of Biological Chemistry 269: 25348-25353.

Pacy PJ, Price GM, Halliday D et al. (1994) Nitrogen homeostasis in man: 2. The diurnal responses of protein synthesis, degradation and amino acid oxidation to diets with increasing protein intakes. Clinical Science 86: 103-118.

Waterlow JC, Garlick PJ, and Millward DJ (1978) Protein Turnover in Mammalian Tissues and in the Whole Body Amsterdam: Elsevier/North-Holland Biomedical Press.

Requirements and Role in Diet

D J Millward, University of Surrey, Guildford, UK

© 2005 Elsevier Ltd. All rights reserved.

Defining minimum amino acid and protein requirements is inherently difficult. Humans are exposed to a wide range of protein intakes, which enable full expression of their genotypical lean body mass throughout the range, and identifying the lower limits of this range has proved intractable. Without unequivocal symptoms of deficiency, the adequacy of an intake can only be assessed in terms of nitrogen or amino acid balance, which is unsatisfactory for several reasons. In particular, adaptation causes major difficulties in designing balance studies and interpreting results. Furthermore, balance methods are inherently imprecise and logistically extremely difficult. It is therefore not surprising that there is much debate about both the nature and the extent of protein requirements.


Protein requirements are best discussed in terms of metabolic demand, dietary requirement, and dietary allowances. Metabolic demand concerns amino acids and is determined by the nature and extent of those metabolic pathways (e.g., net protein synthesis) that consume amino acids and that vary with the phenotype and the developmental and physiological state of the individual. The dietary requirement is the amount of protein and/or its constituent amino acids that must be supplied in the diet in order to satisfy the metabolic demand. The requirement will usually be greater than the metabolic demand. Thus, factors associated with digestion and absorption may limit digestibility (i.e., dietary nitrogen lost in the feces) and biological value (i.e., the availability of the absorbed amino acid pattern in relation to cellular needs, which influences urinary nitrogen excretion). Dietary allowances are a range of intakes derived from estimates of individual requirements taking into account variability between individuals. They are designed to meet the dietary requirements of the population. In the United Kingdom, these allowances are described in terms of Dietary Reference Values (DRVs) and in the United States as Dietary Reference Intakes (DRIs).

Metabolic Demands for Amino Acids

Current evidence supports the representation of the metabolic demands as in Figure 1. The metabolic demand for amino acids is to maintain tissue protein at appropriate levels and to provide for all amino acid-derived metabolites and any additional needs during growth, rehabilitation, pregnancy, and lactation. Tissue proteins are diverse, including structural or fibrous insoluble types and soluble globular

Protein intake

Protein intake


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