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Supplement: Nutrient Composition for Fortified Complementary Foods

Protein and Amino Acid Requirements and the Composition of Complementary Foods¹

Peter J. Reeds^*,2 and Peter J. Garlick^,3

^* Department of Animal Sciences, University of Illinois at Urbana-Champaign, IL, and Department of Surgery, Stony Brook University, Stony Brook, NY

³To whom correspondence should be addressed. E-mail: pgarlick{at}notes.cc.sunysb.edu.

	ABSTRACT

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

 
In this paper, factorial models of the dietary requirements for protein, nitrogen and individual indispensable amino acids are developed from published information on the relationship between age and protein deposition and between protein (amino acid) intake and nitrogen balance. The results are used to develop recommendations on the protein–energy ratio and the amino acid pattern of the diet. As part of the development of the models, factors affecting dietary protein digestibility, bioavailability and efficiency of utilization are discussed. Over the age range of 6–24 mo the models predict a fall in the weight-specific protein and amino acid requirement that results almost entirely from the changes in the growth rate of the children. It is also concluded that the requirement for the maintenance of body protein equilibrium (so-called maintenance) changes little with age. This contrasts markedly with the relationship between age and energy requirements. The amino acid modeling implies that the optimum pattern of individual essential amino acids also changes only marginally across the age range considered in the report. The calculations of the dietary requirement for whole protein imply that achieving a minimum protein–energy ratio of 6.3% is desirable. The amount of protein needed from complementary foods for breast-fed children is discussed.

KEY WORDS: • protein • amino acids • dietary requirements • complementary foods

The period of life with which this paper is concerned is a time of substantial development. At or around age 1 y, most children become ambulant with an attendant increase in total energy expenditure. Children also become progressively more independent of their mother and other caregivers, are exposed to new antigens and pathogens and undergo profound behavioral and intellectual changes. In the ideal situation, these aspects of functional development would be highly desirable endpoints for the development of dietary recommendations. However, quantitative aspects of the nutrient requirements for cognitive and behavioral development, as opposed to protein deposition and linear growth, are so poorly developed that they are of little use as a basis for the accurate definition of nutrient requirements. Thus, at the present stage of our understanding, surrogate measurements such as weight gain and protein accretion are the only endpoints for which sufficient useful data are available. In the discussion that follows, protein deposition and nitrogen balance will be the primary endpoints for the development of factorial models of the protein and amino acid requirements of children.

	Definition of terms

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

 
The topic of protein and amino acid requirements has generated substantial controversy over the past 10 y. Although some consensus is now emerging, a portion of the controversy has resulted from confusion over the meaning of the generic term requirement. The use of three separate terms—biological need, dietary requirement or Estimated Average Requirement (EAR)³ and Recommended Dietary Allowance (RDA) or Recommended Dietary Intake (RDI)—would eliminate this confusion (1).

Biological need defines the quantities of the nutrient in question that are consumed in its various metabolic pathways. From the perspective of protein and amino acid requirements, the biological need can be usefully divided into the needs for protein deposition and the needs for the maintenance of amino acid equilibrium. The latter category includes functions, such as immune and neuromuscular, that are not necessarily directly related to protein metabolism and turnover but are nonetheless of critical importance to adequate health. It is important to recognize that the biological need is not fixed and depends on developmental stage, reproductive state and environmental factors, such as injury and infection.

Dietary requirement or EAR defines the quantity of the nutrient that must be supplied in the diet to satisfy the biological need. The dietary requirement is, by definition, higher than the biological need because diets are not 100% bioavailable and once absorbed into the body are not used with 100% efficiency. Thus, the relationship between biological need and dietary requirement is a function of the diet. For example, in considering these matters expert committees have used statements such as "the requirement for a protein of high quality." This, of course, presumes that we understand what aspects of a protein render it of high quality.

RDA and RDI are the practical expression of the dietary requirement. It is critical to recognize that both are recommendations for populations and that they attempt to account for variability in both biological need and dietary requirement. The convention is to define the RDA and RDI as being 2 SD above the EAR. Thus they define the level of intake that should satisfy the dietary requirement of 97.5% of the population and focus on the prevention of deficiency. Therefore, the RDA (RDI) may be very close if not identical to the lower limit of the range of intakes that provides an excess of the nutrient in question.

	Factors affecting the biological need and its relationship to dietary requirement

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

 
Growth and protein deposition.

At the most simple level, an individual’s requirement for amino acids can be divided into those necessary for growth itself and those that must be supplied to maintain the status quo (i.e., body protein equilibrium and optimum physiological functions). Linear growth and protein deposition are excellent markers for physiological well-being. Both have been defined to a high degree of accuracy and both are also sensitive to the adequacy of amino acid supply. If children are gaining weight and protein as well as increasing in length at an appropriate rate, then there is every likelihood that other aspects of their function are also being adequately supported by the diet.

The factorial calculation of the protein and amino acid needs for growth requires consideration of two factors. First, the age-specific rate and the amino acid composition of body protein deposition define the minimum needs for the process of protein deposition itself. Excellent body compositional data now available allow accurate estimates of the average rate and the variability of protein deposition from birth to age 2 y (2,3). These measurements demonstrate that there is a marked and biexponential fall in the daily rate of protein deposition from birth to age 2 y (Fig. 1). In addition to this, measurements of the amino acid composition of mixed whole-body protein (4) (Table 1) are available, so that good estimates of daily rates of both protein and individual amino acid deposition can be made. The second factor is the efficiency with which children use available amino acids for the support of protein deposition. In contrast to data on the average rate and amino acid composition of protein deposition, good quantitative information on the efficiency with which available amino acids are utilized is not available. In part this lack of information reflects the fact that the efficiency term also involves three separate factors: the amino acid composition (biological value) of the dietary protein, its digestibility and the efficiency with which systemically available amino acids are used to support protein accretion.

View larger version (14K): [in this window] [in a new window]   FIGURE 1 Protein deposition from birth to age 2 y.

Digestibility.

Digestibility can be quantified in different ways, the most common being the measurement of the relationship between nitrogen intake and fecal nitrogen output. This measurement is less than satisfactory and gives little useful information about the digestive process and the true bioavailability of dietary amino acids. First, fecal nitrogen consists largely of bacterial protein and nucleic acids, so that measurements of fecal amino acid output bear little or no relationship to the composition of the dietary protein (7). Second, variations in dietary protein intake have disproportionately small effects on fecal nitrogen output, and the apparent fecal digestibility commonly increases with an increase in protein. This leads to the implausible conclusion that protein digestion rises as dietary protein intake increases. Third, data obtained in both animals and humans [e.g., Shulman et al. (8)] show that at least 50% of fecal nitrogen originates from nitrogen that has been secreted into the intestinal lumen. Recent work involving the ingestion of ¹⁵N-labeled dietary proteins [e.g., Gaudichon et al. (9,10) and Mariotti et al. (11,12)] showed that the true ileal digestibility of a number of protein sources, including milk, cereals and legumes, is >90% and that it varies only minimally among the common sources of dietary protein.

It follows from this that a considerable portion of the intestinal nitrogen loss should be counted as part of the protein needs of the individual and that differences in apparent nitrogen digestibility actually represent variations in endogenous protein outflow. Because other components of the diet, notably dietary fiber, influence endogenous protein losses, the nature of the dietary matrix rather than the source of protein itself is the main influence on apparent digestibility. For example, research in animals has shown that the endogenous protein outflow from the ileum (and hence apparent nitrogen digestibility) is only poorly related to dietary protein intake but is positively related to dry matter intake and negatively related to the energy density, itself a semiquantitative measure of the dietary fiber content.

Two other factors that may ultimately have a substantial effect on our views of the dietary requirements for amino acid have emerged. The first is the realization that the tissues of the gastrointestinal tract can have a major influence on the pattern of amino acids that emerge into the portal vein (13,14). The second is the evidence that amino acids synthesized by lumenal bacteria are available to the host (15,16). In other words, estimates of available amino acids from measurements of their intake could either be significant overestimates because of the negative influence of intestinal metabolism or underestimates because of the availability of amino acids from bacterial synthesis.

Stress, infection and catch-up growth.

Although the data used in this report were obtained in ostensibly healthy children, it must be recognized that a potentially crucial influence on growth in general and protein requirements in particular is intercurrent disease and stress. It has been known for many years that a uniform response to stress is a loss of body nitrogen, and abundant data demonstrate growth faltering during infection (17,18). Studies in Nigeria demonstrated enhanced nitrogen loss and accelerated protein turnover in infected infants (19) whereas investigations in India demonstrated acute increases in leucine oxidation and whole-body proteolysis in response to immunization (20). Work with infected malnourished children in Jamaica demonstrated complex interactions among nutritional status, infection and the synthesis of positive and negative acute-phase protein synthesis (21,22).

Whether infection alters the requirements for specific amino acids is not known, although it has been speculated that infection might specifically influence both aromatic amino acid (23) and sulfur amino acid (24) nutrition. In this context, it must be emphasized that an equally common response to infection is anorexia, so that a significant portion of the growth suppression is simply a natural response to a lower protein intake. Brown et al. (25) showed that diarrheal disease and upper respiratory infections affect the intake of nonhuman-milk components of the diet and have little influence on the suckling’s intake of human milk.

There is a good case for considering the use of nutritional supplements to aid in the subsequent regrowth after infective stress, but this is difficult to implement. It is well documented that as long as sufficient food is provided, infants can achieve weight-specific rates of weight gain well in excess of that expected for their age. Thus, to some extent it can be argued that dietary recommendations for children in disadvantaged communities could usefully contain a factor for the support of catch-up growth in that portion of the population that is recovering from an infection. However, the implementation of such a recommendation is difficult. First, no studies have been done on the appropriate amount or composition of such supplements, although current work in Malawi is exploring the efficacy of tryptophan supplements in this respect (26,27). Second, it is not certain whether catch-up weight gain is of normal composition [e.g., Patrick et al. (28)]. Third, whether children undergoing catch-up growth use dietary protein at a higher than normal efficiency is not known with certainty (29,30). Thus, the accuracy of any recommendation regarding supplements aimed at promoting catch-up growth is questionable.

	Factorial model of dietary protein requirements

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

 
Components of the model.

The ideal factorial model should contain three main components: the rates of the pathways that consume amino acids (and hence protein); the factors, dietary and physiological, that regulate the bioavailability of the amino acids; and the source, magnitude and regulation of the inefficiency of the utilization of bioavailable amino acids.

No data that allow the quantification of these factors are available in anything approaching sufficient extent or accuracy. As a result, definitions of dietary requirements for either protein or amino acids must be based on empirical information on the two main components of the overall need—protein deposition and maintenance. The only extensive data on protein are based on nitrogen balance and age-specific rates of protein deposition. Thus, the factorial model of the protein requirement of infants is based on the following: 1) Regression analysis of the relationship between nitrogen intake and nitrogen balance: This is used to define the maintenance nitrogen requirement and the partial efficiency with which ingested protein is deposited. 2) The age-specific rate of protein deposition as derived from body compositional analysis: Figure 1, which shows the age-related changes in protein deposition, enables the derivation of a very precise (R² = 0.998) prediction equation for the relationship between age (months) and protein deposition [mg protein/(kg · d)]:

3) Unaccounted losses: In the analysis of maintenance nitrogen intake (requirement), an important problem is the estimation of unaccounted nitrogen losses, usually assumed to be due to nitrogen loss in desquamation, hair loss and sweat. The literature on this point is limited (31–34) but indicates that the average value for unaccounted losses is about 6.5 mg at intakes close to maintenance. 4) Efficiency of dietary protein utilization: The estimates of the efficiency of protein utilization derived from the analysis of published values (Fig. 2) include the effect of protein quality (i.e., chemical score), the relationship between the source of dietary protein and the bioavailability as well as variations related to the genotype and physiological state of the subjects. The amalgamation of these three sources of inefficiency is unsatisfactory from a biological point of view, but at present no way exists to separate their respective influences. Although there is no basis for the idea that the three contributors are correlated with one another in a biological sense, it should be noted that closer examination of the results (Fig. 3) reveals a highly significant (R² = 0.75; P < 0.0001) relationship between basal nitrogen balance (i.e., losses at zero protein intake) and the incremental efficiency of protein utilization. Whether this relationship is statistical or has a biological basis is not known.

View larger version (17K): [in this window] [in a new window]   FIGURE 2 The relationship between nitrogen intake and balance in infants and children from 0.5–12 y of postnatal age.

View larger version (18K): [in this window] [in a new window]   FIGURE 3 Relationship between the rate of nitrogen excretion at zero protein intake and the incremental efficiency of protein use.

Ten studies have been published on the relationship between protein intake and nitrogen balance in infants and children aged 4 mo to 12 y (Fig. 2). The studies fall into two groups: 57 subjects who were studied specifically to determine the nitrogen losses at very low or zero protein intakes and 111 subjects who were studied to examine the relationship between protein intake and nitrogen balance both above and below maintenance. The latter group included studies where each subject received at least three intake levels and other studies where multiple data on each individual were not available. These data have recently been subject to analysis of variance (DRI), with unaccounted losses assumed to be 6.5 mg/(kg · d). The overall equation relating nitrogen intake and retention (n = 166) is

The average nitrogen intake for nitrogen equilibrium was 108 mg N/(kg · d) and the slope (efficiency of dietary protein utilization) was 0.56. A number of comments are apposite. Although the difference between diets containing animal or vegetable protein is not significant, the intake for equilibrium was 102 mg N/(kg · d) for animal and 111 mg N/(kg · d) for vegetable and the slope was 0.66 for animal and 0.56 for vegetable. Subanalyses of these data reveal no gender or ethnic effects nor any significant differences in the slope of the line below and above maintenance. This justifies the use of a constant slope in the factorial calculation of protein requirement.

In Table 2, the rates of protein deposition are combined with the relationship between protein intake and nitrogen retention for the two main protein sources. This is then used to calculate the average dietary protein requirement. It is not possible to calculate the 97.5^th centile directly from the regression data because no repeat measurements in the same subject, which would enable SD to be evaluated, were reported. However, in a similar analysis of data from adults, the SD of the maintenance nitrogen requirement was estimated to be about 12% (35). The SD of the rate of growth of body protein can be estimated from longitudinal measurements of whole-body potassium-40 in babies from age 2 wk to 2 y (3). The mean SD is about 43%.

	Amino acid requirements

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

 
For young children, the only available data on the relationship between the intake of specific essential amino acids and nitrogen retention are those reported by Pineda et al. (36) for children aged 1.75–2.25 y. These studies present the most extensive set of data on the amino acid requirements of immature humans and the studies were particularly carefully designed. Notable aspects were that measurements were made in individuals whose intakes were either increasing from an inadequate level or decreasing from a surfeit, at least four and generally five levels of the test amino acid were studied in each subject and amino acid requirements were estimated with three end points: nitrogen balance, plasma concentration of the test amino acid and ratio of urea to creatinine in the urine. The latter two measurements have the advantage that they do not rely on an absolute value for their interpretation. This is critical because in the nitrogen balance measurements, nitrogen retention exhibited a good plateau, but the plateau or asymptotic value [70–110 mg N/(kg · d)] was substantially higher than would be expected from the rates of protein deposition predicted by body composition studies [12 mg N/(kg · d)].

Pineda et al. (36) provide estimates of safe levels (i.e., levels at which all subjects achieved maximum nitrogen retention and amino acid concentration and minimum urea-creatinine ratio). However, because these experimentally derived values relate only to infants aged 2 y and average requirements rather than safe levels were not provided, it is necessary to use the factorial approach for infants in general.

	Factorial estimate of amino acid requirements

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

 
Dietary amino acid requirements for protein deposition.

The estimation of the obligatory amino acid needs for protein deposition can be simply calculated as the product of the amino acid composition of mixed whole-body protein (Table 1) and the estimated rate of protein deposition (Table 2). The conversion of these values to dietary requirements requires an estimate of the efficiency with which dietary amino acids are retained in body protein. No direct data are available to address this point. Thus, in the derivation of the factorial estimates of amino acid requirements, the efficiency of total nitrogen utilization has been used. In order to err on the side of caution, the efficiency of utilization of vegetable proteins (0.56) was used in the calculation. The values in Table 3 are estimates of the 97.5^th centile using the SD for growth of body protein of 43%, derived from longitudinal measurements of total body potassium by Butte et al. (3).

The most difficult problem in the factorial calculation of amino acid dietary requirements is the definition of the quantities used in the maintenance of body protein equilibrium. This is particularly regrettable, because after about age 9 mo, most dietary amino acids are used to maintain the physiological well-being of the individual. The magnitude of maintenance amino acid requirements (i.e., the essential amino acid requirements of adults) has been the subject of intense disagreement over the past 10 y. The arguments arose because the application of ¹³C-amino acid balance measurements to the determination of maintenance amino acid requirements by Young and colleagues (37) developed estimates that greatly exceeded the current recommendations that arose from the nitrogen balance work of Rose and Leverton (see FAO-WHO (38,39) for summary). Recent work from the Toronto group (40,41) and joint research from the Massachusetts Institute of Technology group and the group at Bangalore (42) using the indicator amino acid oxidation method (43) has generally, although not exactly, confirmed Young’s conclusions, and a consensus on the indispensable amino acid requirements for adults has emerged (44).

Unfortunately, except for some results for children with inborn errors of amino acid metabolism (45) and data that have, as yet, appeared only in abstract form (46), no analogous information for infants and children are available. Table 4 shows the estimates of children’s maintenance requirements for amino acids calculated on the assumption that they can be predicted on the basis of the total protein requirement and the composition of body protein (compare with values for adults in Table 1). In all cases, the children’s requirement is greater than that of adults. However, because the total protein requirement for maintenance appears to be the same in adults [0.66 g/(kg · d)] and children [0.67 g/(kg · d)], it seems reasonable to assume that the same applies to individual amino acids, and that the estimates for children derived from the total protein requirement are actually too high (35). Therefore, in the derivation of the current estimates, it is assumed that the maintenance essential amino acid requirements of children over ages 6 mo to 2 y are the same as those obtained in adults (Table 4).

	Implications for complementary feeding

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

View larger version (19K): [in this window] [in a new window]   FIGURE 4 The relationship between age and dietary energy requirement. Recalculated from Butte (47) and Torun et al. (48).

The estimates of total protein requirements for milk and egg or vegetable proteins (Table 2) have been combined with the estimated essential amino acid requirement (Table 5) to calculate an amino acid–scoring pattern (Table 7). When this pattern is used to calculate the intakes of specific single protein sources necessary to support the RDA for individual amino acids, it is clear that some single protein sources are not desirable (Table 8). The problem now becomes one of defining the gap to be filled by complementary foods in the context of continuing but falling human milk intake.

	FOOTNOTES

 
¹ Presented as part of the technical consultation "Nutrient Composition for Fortified Complementary Foods" held at the Pan American Health Organization, Washington, D.C., October 4–5, 2001. This conference was sponsored by the Pan American Health Organization and the World Health Organization. Guest editors for the supplement publication were Chessa K. Lutter, Pan American Health Organization, Washington, D.C.; Kathryn G. Dewey, University of California, Davis; and Jorge L. Rosado, School of Natural Sciences, University of Queretaro, Mexico.

² Deceased; author of the initial draft.

⁴ Abbreviations used: EAR, Estimated Average Requirement; RDA, Recommended Dietary Allowance; RDI, Recommended Dietary Intake.

	LITERATURE CITED

TOP ABSTRACT Definition of terms Factors affecting the biological... Factorial model of dietary... Amino acid requirements Factorial estimate of amino... Implications for complementary... LITERATURE CITED

 

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