Optimizing amino acid and protein supply and utilization in the newborn.

As has been pointed out already (Casey, 1989) homologous milk appears to promote optimal growth and well-being in the infant, although it is not .entirely clear why this should necessarily be so. The difficulty in fully understanding the basis of the relations is particularly well illustrated for protein and amino acids. Within the framework of our general appreciation of nitrogen and protein requirements (Food and Agriculture OrganizatiodWorld Health Organizatioflnited Nations University, 1985), the N content of human milk is remarkably low, whether expressed in relation to the total energy content, or the amount ingested daily by the infant. It would appear that all the protein in the milk is not digested and absorbed. This may be particularly true for certain classes of proteins such as immunoglobulins, although we do not have any precise, quantitative information on the extent of this malabsorption. On the other hand, about 25% of the N in human milk is not present as protein at all. A portion can be identified as free amino acids, but by far the largest contribution, about 60%, comes from urea-N (Harzer et af. 1984). The urea-N has generally been considered to be metabolically unavailable. If this is so, the available protein would appear to be exceptionally low at a time when the demands for infant growth, development and elaboration are at their highest (Fomon & Macy, 1958). With our present concepts of protein and amino acid metabolism it is not possible to rationalize the apparent contradiction between the N requirements for growth and that available from breast milk. In order to make sense of the observed reality, we have to be prepared to consider alternative frameworks of understanding. In order to usefully approach this problem I have to start from a base of assumptions founded on experimental observations. There are four propositions I think it necessary to accept in order to be able to proceed. 1. The classic approach to the study of N metabolism by the balance technique is able to determine that change has taken place, but not necessarily the mechanisms whereby that change was brought about. The introduction of methods that enable us to study dynamic aspects of protein metabolism (Waterlow, 1967), and the application of stable isotope techniques to their application in vivo have enabled us to advance our understanding significantly (Waterlow, 1984). The simplest model for whole body protein turnover assumes that a single metabolic pool of amino acids acts as the precursor for protein synthesis in the whole body (Mehta, 1989). The model has to be a simplification, but it serves to demonstrate that protein turnover is very intense, and at least four to five times greater than implied by the intake of protein (Rcou & Taylor-Roberts, 1969). The stool N is equivalent to 10-15% of the dietary intake. Although it has generally been assumed that this represents malabsorbed N, it is more likely that it is the result of a far more intense metabolic activity in the lower bowel (Jackson, 1986). More recent evidence suggests that any refinement of the model for protein turnover has to accommodate an extensive exchange of protein and N metabolism within the gastrointestinal tract, at least as great as the dietary intake of protein (Fig. 1) (Jackson et af. 1987~). It is likely that this exchange is not simply a movement of amino acids in two directions across a mucosal banier, but also represents modulation of the pattern of N compounds by the gastrointestinal microflora. The N in the lower bowel