Dietary Protein Allowances and Implications of Adaptation

The Estimated Average Requirement (EAR) defines the notional mean requirement for the population group. The Recommended Nutrient Intake (RNI) is defined according to the range of interindividual variability and is two standard deviations above the EAR. The RNI (or Recommended Dietary Allowance) is thus an intake that will meet the requirement of most of the population assuming normal distribution of requirements and is therefore a 'safe allowance.' The Lower Nutrient Reference Intake, which is two standard deviations below the EAR, defines the lowest intake that will meet the requirement of some of the population. It follows from these definitions that in deriving dietary allowances from nitrogen balance studies, the variability in the reported values is very important since this is used to set the RNI. The currently agreed value is based on an EAR of 0.66 g/kg and a SD = 12% (i.e., 0.82 g/kg). Such calculations try to assess true between-subject variation rather than measurement errors. The range of individual values from the reported nitrogen balance meta-analysis is shown in Figure 4. Analysis of individual risk of deficiency (intake < requirement) assumes that the requirement is not correlated with the intake so that for an individual with an intake equal to the mean requirement value, the risk of deficiency is 50%, declining to less than 2.5% at the higher intake equal to the RNI.

The serious implication of lack of complete adaptation in short-term multilevel balance studies is that

□ Requirement

□ Requirement


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□ Requirement RNI?

Adaptive range

80 60 40 20 n0

0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 Reported values for the ONL and protein requirement g protein/kg/d

Figure 4 Distribution of reported values for the protein requirements and obligatory nitrogen loss (ONL) and calculation of risk of deficiency for an individual for current protein requirements model (A) and the adaptive metabolic demands model of protein requirements (B). The bars represent the distribution of reported mean values for the obligatory N loss (solid bars; n = 15 studies on 273 subjects) and individual values of intakes for N equilibrium expressed as protein equivalents (open bars; n=224 subjects from 32 studies, after a 5% trim of outliers) from a meta-analysis of N balance data reported by Rand et al. (A) A normal distribution of requirements is shown (solid line), with the Recommended Nutrient Intake (RNI) and risk of deficiency for an individual (broken line) calculated assuming no correlation between protein intake and requirement. (B) RNI and suggested risk of deficiency (broken line), assuming most of the variation in reported requirement values reflects incomplete adaptation to the test diets with the true minimum requirement at the lower end of the observed range. Risk of deficiency in fully adapted individuals will not become significant until intakes fall below the upper range of the true minimum requirement (value currently unknown).

because of the very wide range of protein intakes in the human diet, mainly through variable meat intake, the apparent requirement indicated in a study may still reflect the prior habitual diet. That is, the apparent metabolic demands are higher than minimum

levels because of an adaptive component of amino acid oxidation set to balance previous intakes. This may explain the very wide range of reported apparent requirements analyzed in the nitrogen balance metaanalysis from approximately 0.4 to more than 1.1 g protein/kg/day. If adaptation does account for the variability, than a quite different analytical model would be implied (Figure 4B). Thus, the RNI would be much lower, with risk of deficiency for fully adapted individuals not increasing until intakes decrease to very low levels—close to values equivalent to the ONL. Such adaptive models pose difficult questions for public health nutrition.

Protein Requirements for Growth and Special Needs

For infants, children, and pregnant and lactating women, protein requirements are derived by a semi-factorial analysis of the components of the metabolic demands shown in Figure 1, with an assumed efficiency of utilization, all adjusted for individual variation to give the RNI. The main components as reported in the recent US Dietary Reference Intake (DRI) report are shown in Figure 5. The maintenance value is derived from nitrogen balance studies on children at 0.69 and 0.66gprotein/kg/day for ages 0.75-13 years and older than 13 years, respectively. The dietary requirements for growth derive from measured rates of protein accretion adjusted for an efficiency of utilization of 58%. To account for interindividual variability, the RNI includes the addition of 2 SDs for maintenance and dietary

9 months 1-3

4-8 9-13 14-18 Adult / elderly

EH 2SD (growth + maintenance)

9 months 1-3

■ Maintenance □ Dietary inefficiency

4-8 9-13 14-18 Adult / elderly

EH 2SD (growth + maintenance)

Figure 5 Factorial estimates of protein requirements throughout the life cycle. Overall values are averages of the separate values for boys and girls.

growth needs, calculated from a critical value (CV) that is the weighted mean of the CVs for maintenance (12%) and growth (43%).

Pregnancy Requirements

These allow for protein retention in the products of conception and in the maternal tissues associated with the birth of an 'ideal' 3.3-kg infant. It is assumed that protein gain occurs in the maternal tissues in the early part of pregnancy and in the fetus mainly in the latter stages so that the metabolic demand is uniform throughout pregnancy. Thus, in the United Kingdom a single daily additional amount of 6 g protein throughout pregnancy is recommended. Lactation requirements of 11 and 8 g/day derive from estimates of the protein content of breast milk of healthy mothers (milk nitrogen x 6.25) assuming that daily breast milk protein content is constant for the first 6 months and declines thereafter. For the elderly, requirements are assumed to be the same as for younger adults since there is no evidence that they are higher than those of younger adults.

Areas of Uncertainty

Requirements of Infants

Definitions of protein requirements have historically been problematic and controversial, and current values are no exception. It has been suggested that values for the protein requirement of infants and children proposed in the 1985 FAO/WHO/UNU report were overestimates, and this problem was not entirely resolved in the US DRI report. The argument derives from a comparison of the requirement values with the protein intake of the breast-fed infant. Thus, the average requirement defined by FAO/WHO/UNU for the 3-month-old infant is the same as the average protein intake of the breast-fed infant. Since infants of healthy, well-nourished mothers consuming habitual amounts of breast milk are assumed to be optimally nourished, average intakes of breast milk protein are assumed to represent the safe level of the requirement, which is higher than the average requirement. Resolution of the problem requires use of a lower value for maintenance and a higher value for the assumed efficiency of dietary protein utilization for growth, giving values for the EAR and RNI at 3 months of 1.06 and 1.37 g protein/kg compared with a mean protein intake of the breast-fed infant of 1.44 g/kg. Such values would be lower than those implied by the factorial model used in the US DRI report. However, at this age of most rapid growth, the nitrogen in breast milk is utilized with unusual efficiency—an indication of the special properties and qualities of breast milk that are poorly understood. Therefore, it may be proposed that formula-fed infants require more protein because of less efficient protein utilization. Indeed, some have questioned whether the breast-fed infant is the ideal model for protein requirements, with breast milk protein levels being a compromise between feeding the infant and minimizing losses of maternal protein stores. However, given the lower rates of morbidity of breast fed compared to formula-fed infants, it is difficult to sustain arguments that breast-fed infants are less than optimally nourished.

Optimal Protein Intakes and Implications of Adaptation for Nutrition Policy

In general, protein requirements serve two purposes. One is as a basis for prescription (i.e., advice on safe diets through recommending appropriate dietary intakes). Adaptation implies a low but difficult to define RNI. Indeed, since natural diets, providing sufficient energy and other nutrients, usually provide more than the minimal amount of protein, the magnitude of the minimal requirement becomes to some extent an issue of scientific curiosity only. Formulation of policy in relation to prescriptive matters will inevitably and correctly be most concerned with satisfying the upper range of demands for protein and, where there is uncertainty, include positive margins of error. In this case, it is arguably unwise to adopt an adaptive model and reduce the RNI, even if agreement could be reached on the likely lower limit of adaptation. Indeed, an adaptive model does not imply that protein is an unimportant nutrient for the maintenance of human health and well-being but that indicators other than balance (nitrogen, protein, or amino acid) need to be identified. Thus, the most relevant measure is an optimal requirement allowing balance and supporting both optimal body function and minimum risk of chronic disease. There is increasing experimental evidence for the potential benefit of protein intakes considerably higher than the current RNI for bone health in the elderly and epidemiological evidence for benefit with respect to hypertension and ischemic heart disease. However, such influences are unproven, with no plausible mechanism identified in the latter cases. In any case, there are no quantifiable indicators. This results in a dilemma for those attempting to frame prescriptive dietary guidelines. From this perspective, it is probably wise to retain current values as an operational expedient until it becomes possible to quantify the benefits (and any risks) of protein intakes within the adaptive range.

The other purpose of requirement recommendations is as a diagnostic indicator of risk, often within an epidemiological context in which population groups rather than individuals are considered. In this case, indicators used to estimate prevalence of disease states or deficit risk are carefully chosen so as to strike an acceptable balance between false positives and false negatives. The main implication of adaptation for estimating risk of deficiency as intakes become less than requirements is a dramatic reduction in the prevalence of risk for most populations compared with that assessed according to the traditional model, which does not account for adaptation. As in the prescriptive context, this low risk of deficiency applies only to that of being unable to maintain nitrogen balance after full adaptation with otherwise nutritionally adequate diets satisfying the energy demands. Whether such populations enjoy optimal protein-related health in terms of immune function, bone health, or any other function is a separate issue and needs to be addressed as such. From this perspective, it follows that maintenance of nitrogen balance can no longer be used as a surrogate of adequate protein-related health, and that current lack of quantifiable alternative indicators is no excuse for ignoring the issue of adaptation.

See also: Amino Acids: Chemistry and Classification; Metabolism; Specific Functions. Breast Feeding. Infants: Nutritional Requirements. Osteoporosis. Pantothenic Acid. Pellagra. Pregnancy: Nutrient Requirements. Protein: Synthesis and Turnover; Digestion and Bioavailability; Quality and Sources; Deficiency.

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