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close this bookProtein-Energy Interactions (International Dietary Energy Consultative Group - IDECG, 1991, 437 pages)
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View the documentIntroduction
close this folderSome basic aspects of protein-energy interrelationships
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View the document1. Introduction
close this folder2. Energy dependency of protein and amino acid metabolism
View the document2.1. Qualitative aspects
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View the document2.3. Correlations between energy and protein metabolism
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close this folderAmino acid oxidation and food intake
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View the document2. Nitrogen balance and amino acid oxidation
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View the document4. Interactions between energy and protein metabolism
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close this folderThe metabolic basis of amino acid requirements
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View the document1. Introduction: The nature of the problem
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close this folder4. The variable extrinsic component of the maintenance requirement
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View the document4.1. Indispensable amino acids as toxic metabolites
View the document4.2. Diurnal cycling
View the document5. The anabolic drive
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View the document7. Protein requirements: Formal statement
close this folder8. The issue of protein quality
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View the document8.1. Accretion: Both net and transient
View the document8.2. Minimum obligatory needs: Theoretical predictions
View the document9. Stable isotope studies
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View the document11. Urea salvage
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close this folderCommentary on paper by D.J. Millward
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close this folderCritique of protein-energy interactions in vivo: Urea kinetics
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close this folder2. General considerations
View the document2.1. Functional metabolic demand
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View the document2.3. Functional metabolic mass of protein
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View the document2.6. Amino acids: Essential, non-essential and conditionally essential
close this folder3. The Millward model
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View the document3.1. Present perception of nitrogen disposal
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View the document3.5. The 'effective dietary intake' of nitrogen
View the document3.6. Limits of adaptation to low-protein diets
View the document3.7. Implications of salvaged urea nitrogen
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close this folderThe effects of different levels of energy intake on protein metabolism and of different levels of protein intake on energy metabolism: A statistical evaluation from the published literature
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close this folder2. The effects of different levels of energy intake on protein metabolism
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close this folderEffect of different levels of carbohydrate, fat and protein intake on protein metabolism and thermogenesis
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close this folder3. Effect of energy intake on nitrogen retention
View the document3.1. Fasting and very low caloric intake
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close this folder4. Effect of protein intake on nitrogen retention
View the document4.1. Normal and obese subjects
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close this folder5. The role of glucose and lipid in nitrogen sparing
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close this folder6. Mechanisms of the sparing effect of dietary carbohydrate and fat
View the document6.1. Effect of dietary glucose on leucine oxidation
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View the document8. Practical considerations: Role of the thermic effect of nutrients
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close this folderRespiratory quotients and substrate oxidation rates in the fasted and fed state in chronic energy deficiency
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View the document1. Respiratory quotients in semi-starvation
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View the document5. Effects of refeeding or supplementation on respiratory quotients and substrate oxidation rates of CED subjects
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close this folderEffects of protein-energy interactions on growth
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close this folder2. Mechanisms for effects of protein and energy on growth
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View the document2.1. Insulin and insulin-like growth factors
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View the document3. The determinants of catch-up growth
View the document4. Effect of the protein/energy ratio on growth of premature infants
View the document5. Effect of protein and energy on growth of children with primary malnutrition
View the document6. Effect of the P/E ratio on growth of children with malnutrition secondary to chronic renal insufficiency
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close this folderProtein-energy interrelationships during rapid growth
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View the document1. Efficiency of protein deposition
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close this folderQuantitative relationships between protein and energy metabolism: Influence of body composition
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close this folderProtein-energy relationships in pregnancy and lactation
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View the document1. Influence of gestational weight gain on pregnancy outcomes
close this folder2. Protein needs during pregnancy
View the document2.1. Influence of gestational weight gain on protein needs
View the document2.2. Efficiency of protein utilization during pregnancy
View the document2.3. Influence of dietary energy on protein utilization
View the document2.4. Summary of protein requirements during pregnancy
close this folder3. Energy requirements during pregnancy
View the document3.1. Influence of gestational weight gains on energy needs
View the document3.2. Physical activity and pregnancy
View the document3.3. Summary of energy requirements during pregnancy
close this folder4. Protein needs during lactation
View the document4.1. Estimation of protein needs
View the document4.2. Influence of protein intake on milk composition
View the document4.3. Studies of whole-body protein turnover
View the document4.4. Effects of protein intake on milk production
View the document4.5. Summary of protein needs during lactation
close this folder5. Energy needs during lactation
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View the document5.1. Summary of energy needs for lactation
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close this folderEffects of physical activity on protein-energy interactions: Metabolic and nutritional considerations
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View the document1. Energy metabolism in exercise
View the document2. Are protein requirements affected by exercise when energy requirements are met?
View the document3. Muscle protein breakdown and amino acid oxidation
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close this folderInfluence of physical activity on energy and protein metabolism
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View the document1. Exercise and efficiency of dietary energy and protein utilization
View the document2. Effects of reduced physical activity on energy and protein metabolism
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close this folderExercise, aging and protein metabolism
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View the document1. Body composition changes with age and their consequences
View the document2. Fuels used to meet various components of energy requirements
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View the document4. Exercise-induced muscle damage and acute phase response
View the document5. Exercise and protein metabolism
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close this folderEffect of starvation and very low calorie diets on protein-energy interrelationships in lean and obese subjects
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close this folder2. Early total starvation
View the document2.1. Energy metabolism
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close this folder3. Prolonged total starvation
View the document3.1. Body fat
View the document3.2. Implications of initial body weight and fat stores on protein-energy interrelationships
View the document3.3. Evidence for the first postulate of the model: Survival time in relation to body composition
View the document3.4. Evidence for second postulate of the model: During prolonged starvation the contribution of protein oxidation to energy expenditure is less in obese than lean subjects
View the document3.5. Starvation in man and other species
View the document4.1. Duration of dieting
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View the document4.3. Body composition
View the document4.4. Exercise
View the document5. Some other issues, conclusions and recommendations
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close this folderImpact of gastrointestinal function on protein-energy interactions and nutritional needs
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View the document1. Gastrointestinal function in protein-energy malnutrition
View the document2. Diarrheal diseases
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close this folderRole of the gastrointestinal tract in energy and protein metabolism
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View the document1. Introduction
View the document2. Cell and protein turnover
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View the document5. Restriction of energy and protein intake
View the document6. Fat absorption and exocytosis
View the document7. Chronic environmental enteropathy
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close this folderEffect of protein-energy interaction with reference to immune function and response to disease
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View the document2. Outlining the issues
View the document3. Host metabolism and host defense
View the document4. The metabolic profile of the infected host
View the document5. The role of cytokines
View the document6. Cytokine regulation: Natural antagonists and biological modulators
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close this folderNutrition of immune cells: The implications for whole body metabolism
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close this folder1. Introduction
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View the document1.1. Lymphocytes
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close this folder2. An introduction to metabolic-control logic and its application to the structure of a biochemical pathway
View the document2.1. Near-equilibrium and non-equilibrium reactions
View the document2.2. The flux-generating reaction
View the document3. Use of maximum activities of enzymes as quantitative indices of maximum flux through metabolic pathways
View the document4. Enzyme activities as indication of the capacity of major energy providing pathways in immune cells
View the document5. Glutamine and the immune cells
close this folder6. Glutamine - A link between muscle and the immune system
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View the document6.1. Glutamine synthesis in skeletal muscle
View the document6.2. The transport of glutamine across the muscle membrane: Glutamine uptake and release
View the document7. Large decreases in the concentration of glutamine in plasma
View the document8. The clinical significance of the role of glutamine in immune cells
View the document9. The effects of glutamine provision for the patient
View the document10. Branched-point sensitivity, substrate cycles and thermogenesis
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close this folderMetabolic and nutritional interrelationships between energy and protein in sepsis, trauma and depletion
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View the document2. History 1900-1960
View the document3. Indirect calorimetry and N balance in surgical patients
close this folder4. Nitrogen balance: The role of energy balance and N intake
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View the document4.1. Normal subjects
View the document4.2. Depleted patients
View the document4.3. Injured patients
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close this folderProtein and energy requirements following burn injury
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close this folder2. Resting energy expenditure
View the document2.1. Mechanism of hypermetabolism
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View the document3. Relationship of total energy expenditure (TEE) to REE
View the document4. Sources of energy
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close this folderProtein-energy relationships: Experience with parenteral nutrition
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close this folderModifications of parenteral nutrition support for critical surgical illness
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close this folderDietary protein/energy ratios for various ages and physiological states
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View the document1. Definition, interpretation and uses
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close this folderEffects of disease on desirable protein/energy ratios
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close this folder1. Effects of infections on nutritional status
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View the document1.1. Anorexia
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View the document1.3. Malabsorption
View the document1.4. Catabolic losses
View the document1.5. Anabolic losses
View the document1.6. Fever
View the document1.7. Additional intestinal losses
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close this folder5. Possible role of specific amino acids
View the document5.1. Branched-chain amino acids
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View the document7. Recommendations
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close this folderAmino acid scoring in health and disease
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View the document1. Introduction
close this folder2. Amino acid scoring in health
View the document2.1. Protein quality evaluation: The protein digestibility-corrected amino acid score method
View the document2.2. Protein digestibility
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close this folder3. Amino acid scoring in special cases and disease
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View the document3.1. Amino acid essentiality
View the document3.2. Glycine
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View the document3.4. Arginine
View the document3.5. Cysteine/taurine
View the document3.6. Branched-chain amino acids (BCAAs)
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close this folderResearch needs
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close this folder1. Energy expenditure and metabolism
View the document1.1. Energy expenditure of free-living populations
View the document1.2. More measurements of activity patterns in free-living populations
View the document1.3. Effects of carbohydrates in the diet on fat deposition
close this folder2. Protein metabolism and requirements
View the document2.1. Amino acid oxidation
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View the document2.3. Protein requirements during pregnancy and lactation
View the document2.4. Control of urea recycling from the gut
View the document2.5. Limits to the de novo synthesis of 'conditionally essential' amino acids
View the document2.6. Special roles of particular amino acids
close this folder3. Body composition
View the document3.1. Methods of measurement
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close this folder4. Weight gain in children
View the document4.1. Variability of weight gain and its effect on protein requirements
View the document4.2. Factors limiting protein deposition
View the document4.3. Effects of frequent versus intermittent feeding on growth
View the document4.4. Quantitative and qualitative requirements for catch-up growth
close this folder5. Linear growth
View the document5.1. Potential causes of stunting
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close this folder6. Physical activity
View the document6.1. Effects of physical activity on metabolism and body composition
View the document6.2. Energy intake and physical activity
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close this folder7. Infection
View the document7.1. Interactions between energy, protein and amino acid intakes and cytokine responses
View the document7.2. Methods of quantifying losses imposed by infection
View the document7.3. Development of field methods for assessing the severity and intensity of infection
View the document7.4. Interaction of protein-energy status, immunizations and immune status
View the document8. Functional consequences
View the document9. Variation
View the documentList of participants

2.2. Children

The foregoing has dealt with studies performed on adults. Brief consideration will now be given to protein-energy needs of children. First, however, an overview of assessment methods will be presented. During the first year of life, the protein content of the body increases rapidly. The average increase in body protein is about 3.5 g/d during the first 4 months of life and 3.1 g/d during the next 8 months. By 4 years of age, body protein concentration reaches the adult value of 18 to 19% of body weight. As the growth rate drops rapidly after the first year of life, the maintenance requirement represents a gradually increasing and major proportion of the total protein requirement (FAO/WHO/UNU, 1985).

For the first months of life, requirements are based on intake data because of the difficulties in estimating accurate allowances for growth and maturation. Infants breast-fed by healthy, well-nourished mothers can grow at a satisfactory rate for 4 to 6 months. Measurements of human milk consumption (FAO/WHO/UNU, 1985) demonstrated that protein intakes ranged from 2.43 g/kg/d in the first month to 1.51 g/kg/d in the fourth month. A rounded value of 2.00 g/kg/d was selected as an allowance for this age group, but it was recommended that protein requirements should be considered in relation to energy needs. The protein needs of an infant up to 4 months of age will be met if the energy needs are met, provided the food contains protein of quality and quantity equivalent to that of breast milk. This implies that at least 6°10 of the food-energy in the form of high-quality protein is desirable.

A modified factorial procedure was used to estimate needs for older children, and the FAO/WHO/UNU (1985) group also recognized the need for continuous provision of protein in anticipation of extra, unpredictable demands from the daily variations in growth rate, since protein provided on a day of no growth is probably not held in reserve for later growth. There were no data on which to base reliable estimates for the extra protein needed for this purpose, but a value 50°70 higher than the estimated daily nitrogen increment was considered realistic.

Tabulated values for daily protein and energy allowances for the various age and sex groupings are shown in Table 5 and are initially expressed as high-quality, highly digestible proteins such as meat, milk, fish and eggs. These would need to be corrected for amino acid composition and digestibility to be converted to protein as consumed in ordinary dietaries. Final recommended allowances for dietary protein, as provided by a diet typical of an industrialized country, would thus range from somewhat over 2 g/kg/d in the first year of life to approximately 1 g/kg/d for adolescents. The protein/energy ratios for the various age and sex recommendations will be discussed in a subsequent section.

Table 5. Recommended Allowances for Protein and Energy (NAS-NRC 1989) and calculated values for PCal%

Age and Sex years

Weight kg

Height cm

Protein gm

Energy kcal

APCal%1

B

Infants

Breast Milk2



11

720

6.1

6.1

0 - 0.5

6

60

13

650

8.0

5.2

0.5 - 1.0

9

71

14

850

6.6

5.1

Children

1 - 3

13

90

16

1300

4.9

4.0

4 - 6

20

112

24

1800

5.3

3.6

7 - 10

28

132

28

2000

5.6

4.5

Males

11 - 14

45

157

45

2500

7.2

4.3

15 - 18

66

176

59

3000

7.9

5.3

19 - 24

72

177

58

2900

8.0

6.0

25 - 50

79

176

63

2900

8.7

6.5

51+

77

173

63

2300

11.0

8.0

Females

11 - 14

46

157

46

2200

8.4

5.0

15 - 18

55

163

44

2200

8.0

6.0

19 - 24

58

164

46

2200

8.4

6.3

25 - 50

63

163

50

2200

9.1

6.9

51+ 65

160

50

1900

10.5

8.2


Pregnancy3



60

2500

9.6

7.8

Lactation 1st

6m


65

2700

9.6

7.9

2nd

6m


62

2700

9.2

7.5

1 PCal% = Protein g per 100g x 400/kcal per 100g. Since energy allowances are averages and protein allowances are safe levels (means + 2SD) the direct ratios of allowances (A) are misleading. The ratios (B) are calculated using average protein needs and are, thus, lower.
2 Mature milk composition.
3 Second and third trimesters.

Protein-energy interactions in diets for children have been reviewed by ZLOTKIN (1986). Although recommended intakes of nutrients are listed according to population norms for age and size on an individual basis, protein and energy intakes are generally adjusted to meet specific outcome goals. Recommended intakes for protein and energy for the full-term infant are based on the composition and volume intake of mature human milk, defined as milk produced sometime after 30 days post partum. For infants born prior to term, oral nutrient intake recommendations have been established either from:

(a) analysis of body composition
(b) direct clinical studies of various feeding regimens, or
(c) analysis of the nutrient content of mature human milk.

The establishment of an appropriate outcome for the newborn infant, who is parenterally fed, is even more complicated, since there are potential differences in the body's handling of intravenously versus orally ingested nutrients. As reviewed by ZLOTKIN (1986), the literature describes intravenous formulations delivering 1.5 to 4 g/kg/d of amino acids and 50 to 140 kcal/kg/d for energy, depending on clinical circumstances and whether the infusion is via the central or peripheral vein.

For children, the energy intake necessary to minimize nitrogen loss associated with an amino acid free diet has not been established but is likely to be in the range of 70 kcal/kg/d (ZLOTKIN 1986). For infants who are receiving an energy intake that is adequate to maintain good health, daily nitrogen retention can be shown to increase with increasing nitrogen intake. Even at the highest nitrogen intake level (640 mg/kg/d), there was no decrease in the linear increase in nitrogen retention.

This response is in marked contrast to that seen in the adult where nitrogen retention is assumed, by current theory, to plateau at or slightly above the zero balance line, when excess dietary nitrogen is provided. It should be noted, however, that infants receiving the highest nitrogen intakes also had the highest plasma amino acid levels, with these levels reflecting the composition and quantity of the amino acid solutions infused. Thus, achieving even higher nitrogen retention in infants is possible, though probably undesirable, because of the concomitant metabolic consequences (ZLOTKIN, 1986).

When both nitrogen and energy are taken concurrently both interact to affect nitrogen retention. If energy intake is inadequate to meet maintenance requirements, then protein may be used as an energy source. Similarly, if protein intake is inadequate to meet maintenance needs, then increasing energy intakes will spare protein for protein synthesis. This holds true also for infants and it has been demonstrated (ZLOTKIN, 1986) that, for an energy intake just below maintenance requirements (50-60 non-protein kcal/kg/d), increasing nitrogen intake from 400 to 500 mg/kg/d results in a significant increase in nitrogen retention.

At this same low energy intake, however, a further increase in nitrogen intake to 655 mg/kg/d did not result in any further increase in nitrogen retention. The clinical consequences suggest that, when infants are maintained on a hypocaloric intake, nitrogen should be provided at no more than 480 mg/kg/d, since the administration of excess nitrogen will not contribute to nitrogen retention and may lead to increasing plasma urea and amino acid levels.

Milk formula will meet the protein needs of an infant up to about 4 months, if energy needs are met, since the protein and energy content of infant formulas, at least quantitatively, reflects mature human milk (ZLOTKIN, 1986). Therefore, once again, if the energy needs of the infant are met, so too will be the protein needs. It is generally accepted that the value of 1.5 g of crude protein per 100 kcal (Pcal% = 6) approaches the ideal protein/energy ratio for infant foods (FAO/WHO/UNU, 1985).

For the premature infant fed orally, the situation is much more complicated, since it is not universally accepted that mature human milk is the ideal food for the premature infant. The nutrient content of the milk produced by mothers giving birth to premature infants is different from mature human milk (ATKINSON et al., 1978). The estimated protein needs of the premature infant are 3 g/kg/d and energy needs at 120 kcal/kg/d. Thus, the protein/energy ratio for these infants would be 2.5 g of protein per 100 kcal or Pcal% = 10).

Although the actual requirements for growth and development are independent of the route of feeding, the latter has a significant effect on recommended intakes because bioavailability and absorption considerations are of less consequence and activity levels may differ. ZLOTKIN (1986) has calculated that a energy intake of 80 to 100 kcal/kg/d should be adequate to meet requirements of intravenously fed infants. This value is some 20% lower than the recommended oral intake. It has been estimated also that, for the pre-term infant, as long as adequate energy is provided, a nitrogen intake of about 480 mg/kg/d will safely achieve the goal of duplication of the rates of intrauterine nitrogen accretion. This corresponds to about 13% calories from protein.

The relative effect of glucose and lipids on whole-body protein-metabolism kinetics was assessed in seven infants undergoing parenteral feeding by BRESSON et al. (1991). Protein intake was kept constant, and non-protein energy was either provided as glucose alone or as an isoenergetic glucose-lipid mixture. Protein metabolism and energy-substrate utilization were assessed by a primed, constant L-[13C]leucine infusion, combined with indirect calorimetry. There was a significant difference in the pattern of energy-substrate utilization according to regime. Protein turnover, protein breakdown, and amino acid oxidation rates were higher for the glucose than the glucose-lipid treatment, whereas protein-synthesis rates did not significantly differ. The nature of energy substrates delivered to parenterally fed infants may thus affect protein metabolism.

For requirements of children living in developing countries, the studies that we have considered are those from Thailand, Guatemala and Jamaica. Protein-energy relationships have been reported for children in Thailand by TONTISIRIN et al. (1984b). Nine children, aged 9 to 36 months, weighing 8.1 to 11.1 kg and living in a metabolic unit were given normal local weaning diets at three levels of energy intake, varying from 87 to 118 kcal/kg/d. The diets consisted of rice, fish and banana, and the protein intake was fixed at the safe level of 1.7 g/kg/d. Each level of energy was fed for 7 days and vitamin and mineral supplements were given daily. At the lowest level of energy intake, 87 kcal/kg/d, apparent nitrogen retention and weight gain were quite low being 44 mg N/kg and 3.5 g/d, respectively. At the two higher levels of energy intake (100 and 118 kcal/kg), apparent nitrogen retention was greater than 60 mg/kg per day, and weight gain was 20 g per day or more. The results from this study suggested that at the safe level of protein intake, as recommended by FAO/WHO in 1973, the usual Thai weaning food provided adequate protein for the needs of young children, if energy intake was supplied at 100 kcal/kg/d or more. A longer-term study, lasting 4 months for six normal, healthy young male children, aged 8 to 12 months, that had been rehabilitated for 8 weeks or longer following protein-energy malnutrition and had reached normal weights for height, confirmed the earlier observations that 1.7 g/kg protein was adequate for one-year-old children, provided that the energy intake was 100 kcal/kg/d or more. This would represent Pcal%. = 6.8. Habitual Guatemalan diets were investigated for their capacity to allow for catch-up growth in children with mild to moderate malnutrition (TORUN et al., 1984). Children were fed diets mainly based on corn and beans, but with some animal foods such that protein contents averaged from 2.1 to 1.8 g/kg, depending on the stage of the recovery. The energy density of the diet was increased by adding oil to the beans and sugar to the beverages. It was observed that needs of children 2-4 years old could be satisfied with 85-90 kcal/kg (Pcal% = 8.5-9.5) while catch-up growth required 95-105 kcal/kg (Pcal% = 8).

Nitrogen balance and whole-body protein turnover were measured in children aged about one year by JACKSON et al. (1983). Diets provided 1.7 or 0.7 g milk protein/kg/d and were fed at three levels of metabolizable energy, 80, 90 and 100 kcal/kg/d. The Pcal% values of the diets thus ranged from 2.8 to 8.5%. All the children were in positive nitrogen balance at all levels of energy intake on 1.7 g protein/kg/d. Nitrogen equilibrium was maintained on 0.7 g protein/kg/d when the energy intake exceeded 90 kcal/kg/d, but on 80 kcal/kg/d nitrogen balance was negative. Whole-body protein turnover was measured from the enrichment in urinary ammonia, following a continuous infusion of 15N-glycine.

It was observed that the variation between individuals on the same diet was significantly greater than the variation within individuals at different levels of energy intake. For the group as a whole, protein synthesis on 1.7 g protein/kg/d was 0.74, 0.75 and 0.87 g N/kg/d on 100, 90 and 80 kcal/kg/d, respectively; whereas on 0.7 g protein/kg/d it was 0.37, 0.38 and 0. 40 g N/kg/d. These results show that, over this range of intakes, protein synthesis decreased as dietary protein fell, but tended to remain unchanged or even increase as energy intake fell.

Physical activity is also a factor in energy-protein interrelationships (YOUNG et al., 1983) and may be especially important in children. A study by TORUN et al. (1976) revealed the beneficial effects of continued mild exercise on the utilization of dietary protein in young children aged 2 to 4 years undergoing treatment for protein-energy malnutrition. These children were stimulated to be more physically active through a daily program of games that required a mild increase in energy expenditure. Measurements were made of growth and of body energy and nitrogen balances, and results were compared with those obtained in a similar group of children treated in the traditional manner at INCAP. The more active children were shown to grow better in height and in lean body mass. Thus, the efficiency of utilization of dietary protein-energy for growth was greater in the more active children. It could be concluded that moderate, systemic exercise has a growth-enhancing affect and a favorable impact on the utilization of dietary protein. Similar relationships for other age groups are described elsewhere in this volume.