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close this bookEnergy and Protein requirements, Proceedings of an IDECG workshop, November 1994, London, UK, Supplement of the European Journal of Clinical Nutrition (International Dietary Energy Consultative Group - IDECG, 1994, 198 pages)
close this folderThe requirements of adult man for indispensable amino acids
View the document(introductory text...)
View the document1. Introduction
View the document2. The problem in defining requirements
View the document3. Protein quality
View the document4. The maintenance requirement (MR)
View the document5.Diurnal cycling: the Millward-Rivers model
View the document6. Theoretical basis of the MIT tracer balance studies
View the document7. Technical problems of tracer balance studies
View the document8. Results of the MIT tracer balance studies
View the document9. Relation between leucine oxidation and nitrogen excretion
View the document10. Factors relating to the design of tracer balance experiments
View the document11. Breakpoint analysis
View the document12. Effect of protein/amino acid intake on protein synthesis and breakdown
View the document13. The colon: losses or gains?
View the document14. Conclusion
View the documentReferences
View the documentDiscussion
View the documentReferences

2. The problem in defining requirements

At the meeting of the FAO/WHO Expert Committee on Protein Requirements in 1963 (FAO/WHO, 1965) I maintained that there was only one level of requirement worth talking about - the minimal requirement. I am now persuaded that that view is too restricted because it was confined to results obtained by nitrogen balance. Further, it was suggested that the requirements of all men are more or less equal, to which a committee member from former Czechoslovakia replied 'I am not so sure'. Nicol & Phillips wrote in 1976: 'The protein requirements of all apparently healthy men can only be established in the context of their ecological, socioeconomic and nutritional backgrounds'. Thus as long as 30 years ago doubts were being expressed about the way in which protein requirements should be formulated.

Millward said 'The established perception of the nature of protein requirements is inadequate' (Millward et al, 1990). For him there are three levels of requirement: the optimal, the operational and the minimal. The optimal requirement would be determined by functional criteria such as good health, growth, resistance to disease. These criteria are hard to define, although studies of immune status could be used at the population level. Chittenden lived a healthy and active life for many years on a protein intake of about 30 g per day. He maintained that the high protein intakes recommended by Voit (about 120 g per day) constituted 'individual and racial suicide'. This is the only example I know of in which health has been the criterion for recommending a specific level of protein intake.* It is an important task for the future to search for correlations between protein intake and functional criteria that can be stated in quantitative terms. For example, there is increasing evidence that linear growth in children may be influenced by diets that provide good quality protein (Allen, 1994; Golden, 1994), although we do not know whether the effect is due to vitamins, minerals or amino acids. Golden (1994) has put forward a convincing hypothesis for the role of sulphur amino acids.

* Chittenden observed that in soldiers and athletes who had been living on a generally high protein diet, change to a mainly vegetarian diet providing 0.75 g protein/kg/d for 5 months led to an increase of 38% in strength and work performance by 15 tests (Millward, 1994).

The operational requirement, a term introduced by Millward, although it has overtones of the NPUop of Miller & Payne (1961), will be discussed below in relation to the Millward-Rivers model. It takes account of the fact that nitrogen balance can be achieved over a wide range of protein intakes. This has long been recognized, at least since the time of Folin (1905), but I think it is fair to say that we still do not know how this balance is achieved (Waterlow, 1994).

The minimal requirement, which has been the object of innumerable measurements, is, as its name implies, the lowest level of protein or amino acid intake at which N balance can be achieved and maintained. The work of Sukhatme & Margen (1978), which at one time had a good deal of influence, seemed to imply that this minimal level could be variable in an individual. Millward et al (1989) have said that their work implies 'a regulatory mechanism which adjusts daily N balance over a period of several days ... adaptive mechanisms exist which adjust output to balance intake and limit the extent of any loss or gain of body protein. This is an alternative model defining the requirement as a range of intakes over which equilibrium can occur. In contrast, the conventional model is based on an intrinsic requirement which is a fixed function of body weight'.

It is necessary to comment on this statement. The range of intakes over which balance can be achieved is well recognized and the description of an 'alternative model' is unjustified. Sukhatme & Margen's theory of regulation is based on the finding of auto-correlation in urinary N output. This means that if the output on day 2 is lower than on day 1, it will be lower on day 3 than on day 2, and so on. This process would, if continued, lead to zero output (negative correlation) or infinite output (positive correlation). Obviously this does not Occur; after a few days the cycle is reversed. This reversal appears to be caused by random variation (Sukhatme, personal communication). Healy (1989) has criticized the concept of autocorrelation on theoretical grounds; Rand et al (1979) looked for it in a large series of long-term balance studies and found evidence of it in only a small minority. In any case, autocorrelation, if it relies on random variation to maintain a long-term steady state, would seem to be the reverse of a regulatory mechanism. A regulatory mechanism is one which, like a thermostat, manages to maintain a steady state by opposing or reducing the effect of random variations or imposed fluctuations (Waterlow, 1985).

In the statement that 'the conventional model is based on an intrinsic requirement which is a fixed function of body weight', the key words are 'intrinsic' and 'fixed'. All balance studies are conducted on a particular individual at a particular point in time with a particular body weight and total body nitrogen. It seems reasonable to suppose on physiological grounds that the nitrogen losses, which have to be balanced by the requirement, should depend on the body weight, or better, the lean body mass or total body N. However, I know of no studies that have attempted to establish how strong the correlation is, in the way that we have studies relating the BMR to body weight or lean body mass. I find it difficult to believe that such a correlation does not exist, but that in no way rules out the influence of other factors, such as body composition, age, sex and possibly height in relation to weight. For example, Egun & Atinmo (1993) showed that on a Nigerian diet women had a lower protein requirement per kg than men, but it was the same when related to lean body mass. If the measurement of nitrogen balance was as easy as that of BMR, we would be far further.

We have no information about whether the minimum requirement per unit body nitrogen is in fact fixed. Studies in third world countries, where people might be supposed to be existing on low protein intakes, have so far shown no significant differences in obligatory N losses from those found in industrialized countries (Torun et al, 1981; FAO/WHO/UNU, 1985). However, even if there is a strict physiological relationship between the daily obligatory losses and the amount of body N. there is still a possibility for adaptation in the efficiency with which amino acids are used (Nicol & Phillips, 1976). Millward (1992) contends that in the adult there is a set-point for the upper limit of body protein, which is determined by height and frame size. This idea of a set-point seems very reasonable. For example, in the normal adult neither plasma albumin nor haemoglobin concentration can be raised above a certain level by an increase in dietary protein. In experiments with rats, Henry et al (1953) showed that with increasing protein intake total liver protein rose towards an asymptote, with ever diminishing returns on the increased intake.

It is also well recognized that on moving from a higher to a lower protein intake there is a small loss of body protein, about 1% in the human adult (Young et al, 1968). This small loss can apparently be tolerated without harmful effects (Waterlow, 1985). It has been regarded as drawing on 'labile protein stores', but the concept of a store is inappropriate. It is probably better to regard it as a kinetic adjustment that allows constancy of body protein to be maintained at a new setting, the processes of protein synthesis and breakdown needing a little time to adjust to the new level of intake (Waterlow et al, 1978).

There is a further stage of adaptation. If the intake is too low there will be an exponential loss of body protein until balance is achieved at a new level of body weight (Waterlow, 1985). For example, if the requirement for maintenance is taken as 0.1 g N per kg per day, and a 70 kg man is on a diet that provides 5 g N, or 0.07 g per kg, other things being equal he will lose body N until his weight has fallen to 50 kg, when he will again be in balance. Of course, other things may not be equal; nitrogen may be used more efficiently, as suggested by Allison's work on dogs (Allison, 1951). One may ask, what degree of loss of body N is acceptable? If the subject initially had a height of 1.75 m and at 70 kg a body mass index (BMI) of 22.8, at the end of this second stage the BMI would be 16.3, which, according to current thinking, would be inacceptable (James et al, 1988). Moreover, it appears that such a loss would not be uniform, but would involve a disproportionate amount of muscle mass, visceral mass being well maintained (Soares et al, 1991). This is a further reason why the nitrogen balance at a given point in time cannot be regarded as giving a complete answer to the question of the protein requirement. If we regard the requirement per unit body weight as fixed, what is the ideal body weight at which it should be fixed, or is anything short of Millward's setpoint suboptimal?