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This report has been stimulated by Young's
production of the MIT pattern of IAA requirements and the very large difference between it
and the FAO pattern. There is said to be a conflict between his views and those of
Millward. My reading of their publications suggests that this is not so. Both are
concerned, to an extent that has not been discussed before, with the meaning of
'requirement'. Both seem to feel that the traditional minimum requirement, as measured by
balances, is not an adequate measure of human needs in a real environment. Millward with
his model has tried to translate this idea into metabolic terms, with his experiments on
diurnal cycling and his concept of the anabolic drive: that an intake above the minimum is
necessary to keep the machinery of protein turnover operating in a flexible way and with
some reserve capacity; but he has not produced alternative figures. His criticisms of
Young's experiments are at the technical level and have for the most part been met in the
more recent studies of the MIT group.
Young's application of tracer methods to amino acid kinetics for the determination of individual amino acid balances is a new departure and should in principle provide a more precise scoring pattern for the assessment of protein quality. However, it involves more assumptions and more technical difficulties than the traditional N balance.
The point at which the results are most vulnerable is the extrapolation to 24 h from shorter periods of observation, for two reasons. Figure 4 shows that neither in the fed nor in the fasted state is the output of labelled CO2 constant. The pattern may vary under different conditions; thus the times chosen from which to extrapolate, determined by the experimental protocol, may not always be appropriate, although they happen to be in the present case (El Khoury et al, 1994a,b). For example, the pattern of 13CO2 production may be different when food is given in a normal meal rather than in small amounts every hour.
The second problem is how, in the extrapolation, to allow for the periods when the tracer is not being infused. The choice of method can make a significant difference. In my calculations I have taken the view that of the two methods proposed by Marchini et al (1993), the first is preferable (see section 7.5).
As far as I am aware there has been no previous detailed comparison of the various studies that have been done at MIT. The results are consistent in supporting an increased requirement for leucine, according to the MIT pattern. There is much less information about the other IAAs, but to the extent that the pattern of their requirements resembles that of body protein (section 4), if the estimate for leucine has to be increased, so must that for all the others.
The main technical problem with the tracer balance studies is that at the level of the whole body, which is a mixture of tissues, to identify a single value for enrichment of the precursor at all the sites of oxidation is impossible. In my opinion the use of KIC is a reasonable compromise, and it is difficult to imagine that any error introduced by it could be large enough to account for the difference between the new and the old estimates of requirements.
The results of all the studies show a rather large amount of variation between individuals, with coefficients of variation for the rate of oxidation, which is the ultimate measurement, that are often of the order of 25% (e.g. Marchini et al, 1993). This is somewhat greater than the variability of N excretion in traditional balances. It would be interesting to know how far the results in an individual are reproducible, and if they are, whether any characteristic can be identified that is accompanied by high or low rates of flux and protein synthesis. This might help us in the debate about the validity of using the rate of protein turnover as a criterion of adequacy.
The criticism that the meals and their pattern are artificial could in principle be investigated by the single dose method in a subject taking a normal meal. Mathematically this is equivalent to a constant infusion if the analysis is based on the areas under the curves for precursor and product (Waterlow et al, 1978), but a larger number of blood and breath samples would have to be collected. Although an oral dose would avoid the invasiveness of an infusion, the problem of extending these studies to developing countries remains very difficult.
Since I have failed to find any source of error large enough to account for the 2-3-fold difference from Rose's estimates, it is logical to look for sources of error in the old rather than the new figures. The shortcomings of nitrogen balances are well recognized (Table 2). The three main points made by Young in his McCollum Award Lecture (1987) are as follows:
(i) 'Body N equilibrium does not necessarily reflect an adequate state of organ protein metabolism or of nutritional status'. Agreed: but cannot exactly the same thing be said about amino acid equilibrium, as measured in the tracer balance studies? Admittedly those studies give us, as a bonus, information on protein turnover and deposition, but, as discussed in section 12, we cannot with any confidence translate these findings into quantitative estimates.
(ii) The second problem, for which no explanation has been found, is that, at intakes above maintenance, N balances tend to be unrealistically positive. Exactly the same applies to the tracer balance studies; for example, with intakes of leucine of 80 mg/kg/d, positive leucine balances were found ranging from 13 to 25 mg/kg/d (Marchini et al, 1993). Presumably it can at least be concluded that these positive balances are not due to collection errors, because what is collected and how it is collected are completely different in the two systems.
(iii) 'The high energy intakes would be expected to lead to an underestimation of the actual requirement where energy intakes were just sufficient to maintain energy balance'. This is probably the most important point. The energy intakes of Rose's subjects were about 55 kcal/kg/d, compared with about 45 kcal/kg in the MIT subjects. On the basis of the classical figure of 2 mg N retained per extra kcal (Calloway & Spector, 1954), this extra energy should spare 20 mg N, and it is by this substantial amount that Rose's balances could have been underestimates. If we accept for the moment Young's thesis that the IAAs contribute to the obligatory loss according to their pattern in body protein, these 10 kcal would correspond to an underestimate of leucine requirement of 10 mg/kg/d (20 × 6.25 × 8/100). This is a maximum figure, since the contribution of leucine to obligatory loss may be less than its contribution to body protein (section 4), but it brings us closer to the mark. If in addition an allowance is made for inefficiency of utilization at 60%, the extra requirement for leucine comes to some 17 mg over and above that proposed by Rose. It is not clear, however, that the same explanation would apply to Leverton's findings in young women (1959), which led to much the same estimates of requirements as those of Rose, because she had lower energy intakes.
Finally, if the IAAs are lost intact, i.e. without first being metabolized, in the faeces and through the skin or in the urine, the tracer balances will be underestimating the total requirement.
I have not attempted to draw any conclusions about the practical action that should result from this body of work, although Young & Pellett (1990) have done so in no uncertain terms. It is an occupational hazard of scientists to say that more research is needed, but I think that it is so in this case. Anyone who has worked in this field for some time will remember how in the 1970s the emphasis on high protein feeds led to mistaken policy decisions and exaggerated reactions. I suggest that there is a need for more balance studies, such as those of Atinmo et al (1988) in Nigeria, where habitual diets in which lysine is likely to be inadequate are fed at the usual level, linked to such measures of functional performance as we are able to develop. Many interesting examples in relation to physical activity in different African populations are given in the book 'Capacity for work in the tropics' (Collins & Roberts, 1988), but these are not related to intakes of protein or IAAs. Children are outside the scope of this report, but I believe that the importance of protein quality for their growth and development still needs further investigation.
It is interesting that whereas up to about 1980 protein requirements dominated our thinking, ever since the Rome meeting more and more attention has been given to energy metabolism, and our colleagues in the energy field are making good progress in defining chronic energy deficiency and in research on its functional effects. It seems strange that in reports, for example about seasonal energy deficiency, a great deal of information is given about changes in energy intake but little or nothing about intake or quality of dietary protein. There to be an opportunity here for promising collaboration.
Meanwhile practical decisions have
to be taken. Even to do nothing is a policy decision. Young & Pellet (1990) have given
their views about the implications of the MIT results. They suggest that diets based on
cereals are :likely to be deficient in lysine and that there is a need for more animal
protein and legumes. The inexorable logic of the increase in the world's population means
that there is no future in diverting cultivable land and resources, already stretched
nearly to their limit (Blaxter, 1987), to the inefficient production of animal protein,
and the stocks in the sea are already dwindling. The development of legumes with a higher
yield and a higher biological value is another matter altogether, and it is to be hoped
that it will be stimulated by the MIT studies. These questions, however, are outside my
brief; they will no doubt be taken up in due course by the international agencies and
other bodies.