Transport proteins as indices of protein status

Abstract

The terms protein status and protein deficiency have been used to denote several quite different concepts. Before beginning to consider how best to measure protein status, and the place of transport protein concentration in this measurement, we must be precise about what we are trying to measure. Laboratory animal investigators clearly refer to the condition resulting from an insufficiency of protein in the diet when they use these terms, irrespective of the clinical or biochemical findings that these diets produce. Clinicians on the other hand refer to a variety of clinical or biochemical findings in the patient, irrespective of the antecedent diet. Thus protein deficiency has been used synonymously with kwashiorkor, nutritional edema, and also for reduced levels of the transport proteins-albumin, transferrin (1), retinolbinding protein, and prealbumin (2). Field workers use the terms in a totally different way-to indicate a lack of body protein in the body compositional sense. It is clear that the very concept of protein deficiency enshrines a whole chain of events. Any particular investigator tacitly assumes the whole chain to exist if he observes a single link in the chain. In essence the thesis is that a protein-deficient diet leads to a loss of body protein, the loss being identified as due to protein deficiency, and not energy deficiency or some other condition, though a coincident reduction in the circulating transport proteins. This in turn leads to edema, skin sores, fatty liver, and the other features of “pure” kwashiorkor. Developing a body protein deficit is synonymous with being in negative nitrogen balance. Consideration of the numerous causes of a negative nitrogen balance indicates the totally nonspecific nature of a protein deficit with respect to various dietary components, trauma and disease. There is no constant relationship between any transport protein and the total amount of protein in the body relative to an appropriate standard; it is only when a body protein deficit arising from a specific cause is considered that a relationship is to be expected. Transport proteins have assumed a special place in the chain of events because they are thought to identify whether a body protein deficit is due to a dietary protein deficiency or not. Because of this the level of circulating transport protein, traditionally albumin, has been used to define protein deficiency in clinical practice; indeed many people hold the view that the degree of hypoalbuminaemia indicates the relative importance of a dietary protein deficiency with respect to energy, or other deficiency, in a malnourished individual. Because of the relatively long half-life of albumin, other transport proteins that respond more rapidly to alterations in the diet have been suggested as more sensitive indices of the degree of dietary protein deficiency (1, 2). For those who define protein status on the basis of the levels of these transport proteins an appraisal of their use in the evaluation of protein status is impossible: this immediately leads to a circular and self-fulfilling argument. Without an independent and true estimate it is not possible to evaluate the reliability with which any particular measurement reflects protein status. The independent measurement of protein status has to be an accurate measurement of protein intake, relative to an estimate of protein requirement, that has itself been derived without recourse to transport protein measurement. In order for a transport protein measurement to be a useful measurement of protein status it is not sufficient for it to respond precisely when a protein-deficient diet is