Protein-Energy Interactions


On behalf of the UN ACC-Subcommittee on Nutrition, the International Dietary Energy Consultancy Group (I/D/E/C/G) has been established for the study of dietary energy intake in relation to the health and welfare of individuals and societies by the United Nations University. Its specific objectives are:

1. The compilation and interpretation of research data on functional and other consequences of deficiency, change or excess of dietary energy.

2. The identification of related research needs and priorities, and the promotion of needed research.

3. The publication of scientific and policy statements and other information on the significance of chronic deficiencies and excesses of dietary energy.

4. The identification and promotion of appropriate and practical means of corrective action.

I/D/E/C/G Steering Committee:

- Dr. N.S. Scrimshaw, UNU, Chairman

- Dr. J.G.A.J. Hautvast, IUNS

- Dr. B. Schürch, Executive Secretary

I/D/E/C/G Advisory Group (1991/92)

One-year term:

- Dr. G. Beaton, Toronto, Canada

- Dr. A. Ferro-Luzzi, Rome, Italy

- Dr. G. Pelto, Storrs, USA

Two-year term:

- Dr. W.P.T. James, Aberdeen, Scotland, U.K.

- Dr. E. Pollitt, Davis, USA

- Dr. P.S. Shetty, Bangalore, India

Three-year term:

- Dr. E. Jéquier, Lausanne, Switzerland

- Dr. J.S. Ju, Seoul, Korea

- Dr. R. Uauy, Santiago, Chile

The digitalization of this publication was made possible by a grant from the Nestlé Foundation



Some basic aspects of protein-energy interrelationships

1. Introduction
2. Energy dependency of protein and amino acid metabolism

2.1. Qualitative aspects
2.2. Quantitative aspects
2.3. Correlations between energy and protein metabolism

3. Summary and conclusions

Amino acid oxidation and food intake

1. Introduction
2. Nitrogen balance and amino acid oxidation
3. Amino acid oxidation during periods of positive or negative energy balance
4. Interactions between energy and protein metabolism
5. Amino acid degradation and gluconeogenesis
6. Summary

The metabolic basis of amino acid requirements

1. Introduction: The nature of the problem
2. Nutrient requirement models
3. The Millward & Rivers requirement model: Qualitative aspects
4. The variable extrinsic component of the maintenance requirement

4.1. Indispensable amino acids as toxic metabolites
4.2. Diurnal cycling

5. The anabolic drive
6. Hormonal components of the anabolic drive
7. Protein requirements: Formal statement
8. The issue of protein quality

8.1. Accretion: Both net and transient
8.2. Minimum obligatory needs: Theoretical predictions

9. Stable isotope studies
10. Practical experience of biological values of dietary protein
11. Urea salvage
12. Indispensable amino acid requirements for the anabolic drive
13. Conclusions

Commentary on paper by D.J. Millward


Critique of protein-energy interactions in vivo: Urea kinetics

1. Introduction
2. General considerations

2.1. Functional metabolic demand
2.2. Carbon flux and nitrogen flux
2.3. Functional metabolic mass of protein
2.4. Specific limiting nutrients
2.5. Limitations imposed by protein quality
2.6. Amino acids: Essential, non-essential and conditionally essential

3. The Millward model

3.1. Present perception of nitrogen disposal
3.2. Urea production
3.3. Urea excretion
3.4. Salvaged urea nitrogen
3.5. The 'effective dietary intake' of nitrogen
3.6. Limits of adaptation to low-protein diets
3.7. Implications of salvaged urea nitrogen

4. Conclusions

The 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

1. Introduction
2. The effects of different levels of energy intake on protein metabolism

2.1. Adults
2.2. Children

3. The effects of different levels of protein intake on energy metabolism
4. Protein/energy ratios
5. Summary and conclusions

Effect of different levels of carbohydrate, fat and protein intake on protein metabolism and thersmogenesis

1. Introduction
2. Influence of nutrient intake on nutrient oxidation
3. Effect of energy intake on nitrogen retention

3.1. Fasting and very low caloric intake
3.2. Moderately hypocaloric diets
3.3. Maintenance diets
3.4. Energy intake in excess of maintenance

4. Effect of protein intake on nitrogen retention

4.1. Normal and obese subjects
4.2. Severely depleted subjects
4.3. Moderately depleted subjects

5. The role of glucose and lipid in nitrogen sparing

5.1. Healthy young subjects
5.2. Patients receiving total parenteral nutrition

6. Mechanisms of the sparing effect of dietary carbohydrate and fat

6.1. Effect of dietary glucose on leucine oxidation

7. Effect of amino acid plasma levels on protein synthesis
8. Practical considerations: Role of the thermic effect of nutrients
9. Conclusions

Respiratory quotients and substrate oxidation rates in the fasted and fed state in chronic energy deficiency

1. Respiratory quotients in semi-starvation
2. Respiratory quotients in experimental semi-starvation
3. Respiratory quotients and substrate oxidation rates in chronically energy deficient subjects
4. Substrate oxidation rates during dietary thermogenesis in chronic energy deficiency
5. Effects of refeeding or supplementation on respiratory quotients and substrate oxidation rates of CED subjects

Effects of protein-energy interactions on growth

1. Introduction
2. Mechanisms for effects of protein and energy on growth

2.1. Insulin and insulin-like growth factors
2.2. Growth hormone
2.3. Epidermal growth factor
2.4. Corticosteroids

3. The determinants of catch-up growth
4. Effect of the protein/energy ratio on growth of premature infants
5. Effect of protein and energy on growth of children with primary malnutrition
6. Effect of the P/E ratio on growth of children with malnutrition secondary to chronic renal insufficiency
7. Conclusions and speculations


Protein-energy interrelationships during rapid growth

1. Efficiency of protein deposition
2. Protein turnover during rapid growth
3. Energy cost of protein synthesis

Quantitative relationships between protein and energy metabolism: Influence of body composition

1. Introduction
2. Theoretical basis
3. Constancy of tissue mobilisation
4. Tissue mobilisation in the obese
5. Allometric analysis
6. Conclusions

Protein-energy relationships in pregnancy and lactation

1. Influence of gestational weight gain on pregnancy outcomes
2. Protein needs during pregnancy

2.1. Influence of gestational weight gain on protein needs
2.2. Efficiency of protein utilization during pregnancy
2.3. Influence of dietary energy on protein utilization
2.4. Summary of protein requirements during pregnancy

3. Energy requirements during pregnancy

3.1. Influence of gestational weight gains on energy needs
3.2. Physical activity and pregnancy
3.3. Summary of energy requirements during pregnancy

4. Protein needs during lactation

4.1. Estimation of protein needs
4.2. Influence of protein intake on milk composition
4.3. Studies of whole-body protein turnover
4.4. Effects of protein intake on milk production§

4.5. Summary of protein needs during lactation§

5. Energy needs during lactation

5.1. Summary of energy needs for lactation

6. Conclusions

Effects of physical activity on protein-energy interactions: Metabolic and nutritional considerations

1. Energy metabolism in exercise
2. Are protein requirements affected by exercise when energy requirements are met?
3. Muscle protein breakdown and amino acid oxidation
4. Substrate metabolism in exercise
5. Effect of exercise on protein synthesis
6. Summary and dietary recommendations

Influence of physical activity on energy and protein metabolism

1. Exercise and efficiency of dietary energy and protein utilization
2. Effects of reduced physical activity on energy and protein metabolism
3. Energy substrates and changes in exercise pattern

Exercise, aging and protein metabolism

1. Body composition changes with age and their consequences
2. Fuels used to meet various components of energy requirements
3. Age and dietary protein needs
4. Exercise-induced muscle damage and acute phase response
5. Exercise and protein metabolism
6. Summary

Effect of starvation and very low calorie diets on protein-energy interrelationships in lean and obese subjects

1. Introduction
2. Early total starvation

2.1. Energy metabolism
2.2. Protein metabolism
2.3. Protein/energy ratios

3. Prolonged total starvation

3.1. Body fat
3.2. Implications of initial body weight and fat stores on protein-energy interrelationships
3.3. Evidence for the first postulate of the model: Survival time in relation to body composition
3.4. 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
3.5. Starvation in man and other species

4. Hypocaloric dieting

4.1. Duration of dieting
4.2. Protein and energy intake
4.3. Body composition
4.4. Exercise

5. Some other issues, conclusions and recommendations

Impact of gastrointestinal function on protein-energy interactions and nutritional needs

1. Gastrointestinal function in protein-energy malnutrition
2. Diarrheal diseases
3. Nutritional recommendations

Role of the gastrointestinal tract in energy and protein metabolism

1. Introduction
2. Cell and protein turnover
3. Nutrient absorption
4. Protein synthesis
5. Restriction of energy and protein intake
6. Fat absorption and exocytosis
7. Chronic environmental enteropathy

Effect of protein-energy interaction with reference to immune function and response to disease

1. Introduction
2. Outlining the issues
3. Host metabolism and host defense
4. The metabolic profile of the infected host
5. The role of cytokines
6. Cytokine regulation: Natural antagonists and biological modulators
7. The future

Nutrition of immune cells: The implications for whole body metabolism

1. Introduction

1.1. Lymphocytes
1.2. Macrophages

2. An introduction to metabolic-control logic and its application to the structure of a biochemical pathway

2.1. Near-equilibrium and non-equilibrium reactions
2.2. The flux-generating reaction

3. Use of maximum activities of enzymes as quantitative indices of maximum flux through metabolic pathways
4. Enzyme activities as indication of the capacity of major energy providing pathways in immune cells
5. Glutamine and the immune cells
6. Glutamine - A link between muscle and the immune system

6.1. Glutamine synthesis in skeletal muscle
6.2. The transport of glutamine across the muscle membrane: Glutamine uptake and release

7. Large decreases in the concentration of glutamine in plasma
8. The clinical significance of the role of glutamine in immune cells
9. The effects of glutamine provision for the patient
10. Branched-point sensitivity, substrate cycles and thermogenesis

Metabolic and nutritional interrelationships between energy and protein in sepsis, trauma and depletion

1. Introduction
2. History 1900-1960
3. Indirect calorimetry and N balance in surgical patients
4. Nitrogen balance: The role of energy balance and N intake

4.1. Normal subjects
4.2. Depleted patients
4.3. Injured patients

5. Summary

Protein and energy requirements following burn injury

1. Introduction
2. Resting energy expenditure

2.1. Mechanism of hypermetabolism
2.2. Prediction of resting energy expenditure in burned patients

3. Relationship of total energy expenditure (TEE) to REE
4. Sources of energy
5. Protein requirements

Protein-energy relationships: Experience with parenteral nutrition

1. Introduction
2. Metabolic response to starvation
3. Metabolic response to stress

Modifications of parenteral nutrition support for critical surgical illness


Dietary protein/energy ratios for various ages and physiological states

1. Definition, interpretation and uses
2. Calculation of recommended P/E ratios
3. Recommended P/E ratios
4. Food sources of energy and proteins

Effects of disease on desirable protein/energy ratios

1. Effects of infections on nutritional status

1.1. Anorexia
1.2. Cultural and therapeutic practices
1.3. Malabsorption
1.4. Catabolic losses
1.5. Anabolic losses
1.6. Fever
1.7. Additional intestinal losses

2. Environmental ('tropical') enteritis
3. Other chronic infections
4. Energy vs protein requirements
5. Possible role of specific amino acids

5.1. Branched-chain amino acids
5.2. Glutamine
5.3. Cancer

6. Summary
7. Recommendations

Amino acid scoring in health and disease

1. Introduction
2. Amino acid scoring in health

2.1. Protein quality evaluation: The protein digestibility-corrected amino acid score method
2.2. Protein digestibility
2.3. Amino acid scoring patterns

3. Amino acid scoring in special cases and disease

3.1. Amino acid essentiality
3.2. Glycine
3.3. Glutamine
3.4. Arginine
3.5. Cysteine/taurine
3.6. Branched-chain amino acids (BCAAs)


Research needs

1. Energy expenditure and metabolism

1.1. Energy expenditure of free-living populations
1.2. More measurements of activity patterns in free-living populations
1.3. Effects of carbohydrates in the diet on fat deposition

2. Protein metabolism and requirements

2.1. Amino acid oxidation
2.2. Amino acid requirements
2.3. Protein requirements during pregnancy and lactation
2.4. Control of urea recycling from the gut
2.5. Limits to the de novo synthesis of 'conditionally essential' amino acids
2.6. Special roles of particular amino acids

3. Body composition

3.1. Methods of measurement
3.2. Composition of lean body mass
3.3. Composition of weight gain during pregnancy

4. Weight gain in children

4.1. Variability of weight gain and its effect on protein requirements
4.2. Factors limiting protein deposition
4.3. Effects of frequent versus intermittent feeding on growth
4.4. Quantitative and qualitative requirements for catch-up growth

5. Linear growth

5.1. Potential causes of stunting
5.2. Reversibility of stunting

6. Physical activity

6.1. Effects of physical activity on metabolism and body composition
6.2. Energy intake and physical activity
6.3. Changes in life-style

7. Infection

7.1. Interactions between energy, protein and amino acid intakes and cytokine responses
7.2. Methods of quantifying losses imposed by infection
7.3. Development of field methods for assessing the severity and intensity of infection
7.4. Interaction of protein-energy status, immunizations and immune status

8. Functional consequences
9. Variation
List of participants