The effect of protein deprivation and starvation on the rate of protein synthesis in tissues of the rat.

1. The fractional rate of protein synthesis was measured in tissues of rats in vivo by continuous infusion of [14C]tyrosine. In growing animals proteins of liver and kidney were renewed at a rate greater than 50% per day, those in skeletal muscle, brain and heart at a rate between 13 and 23% per day. 2. Protein synthesis was also measured in liver, kidney, heart, brain and skeletal muscle of rats either given a protein-free diet for 21 days or starved for 2 days. During the first 2 days no clear differences between the effects of these two regimes could be detected. 3. Gastrocnemius muscle did not lose tissue protein till after 9 days without protein in the diet. The rate of protein synthesis was halved after 1 day and halved again after 21 days without protein. It was deduced that the rate of protein breakdown in muscle had declined also. 4. In liver the loss of protein was immediate without any apparent change in the fractional rate of protein synthesis. Between 2 and 21 days of dietary protein deprivation the liver lost protein slowly but the fractional rate of protein synthesis was increased. It is proposed that lack of protein in the diet also causes an increase in the rate of liver protein breakdown.

Nutritional adaptation in man: general introduction and concepts.

The aim of this paper is to clarify thinking on the subject of nutritional adaptation. A series of concepts and questions are proposed with, as examples, some of the responses that occur to low intakes of energy and protein. The main conclusions are first, that in dealing with human beings value judgements cannot be avoided, but to avoid sterile discussion they must be separated from objective descriptions of adaptive responses. Second, the way ahead lies in examining the shape of the responses of different functions to different degrees and kinds of stress. Objective studies of this kind do not require use of the word adaptation.

Amount and rate of disappearance of liver fat in malnourished infants in Jamaica.

The fat content of the liver has been measured in 163 biopsy specimens taken from 95 malnourished children in Jamaica within a few days of admission to hospital and at various stages of recovery. The fat content was also measured in 38 samples from children who died. Severe degrees of fatty infiltration, up to 50% of the wet weight, were found. Fatty liver of this degree of severity may be a cause of death. The increase in fat was accompanied by an increase in water content. This may be the result of breakdown in the energy-dependent regulation of water content. Repeat biopsies were done within 6 weeks of admission in 26 children. The average rate of clearance of fat expressed as a fraction of the amount present at any time was 5.5% per day. An attempt was made by more frequent biopsies to determine whether the rate of decrease was influenced by the protein content of the diet, but the results were inconclusive.

The in vivo measurement of protein synthesis.

Methods of measuring in vivo protein synthesis are briefly reviewed. Methods involving incorporation of label into protein are more appropriate for mixed proteins. The major difficulty is the definition of the precursor pool for protein synthesis. The only data available on the effect of infection on protein synthesis are open to criticism on the grounds that the precursor pool was not sampled.

The relationship between dietary intake, weight change, nitrogen balance, and protein turnover in man.

We have examined the relationships between protein turnover, protein synthesis, and protein breakdown and dietary intake, weight change, and nitrogen balance in children who were recovering and had recovered from severe protein-energy-malnutrition. Protein metabolism was measured by giving [15N]glycine and measuring the enrichment of urinary urea. The level of dietary protein did not affect protein metabolism. There were highly significant correlations between both protein flux and protein synthesis and the ad libitum dietary intake, nitrogen balance, and weight change. Over the range of dietary intake, 60 to 270 cal/kg per day, the protein synthesis rate increased 5-fold. Large changes in dietary intake resulted in small changes in protein breakdown, with breakdown being least on an inadequate intake. Changes in the rate of protein breakdown did not contribute to changes in nitrogen balance or body weight.

Changes in content and composition of brain phospholipids in malnourished children.

The content and composition of phospholipids were studied in the brain of children who died from severe malnutrition within the first 2 years of life, and compared with those obtained from well-nourished children who died of accidents, or of illnesses not known to affect the central nervous system. Each brain was separated into the constituent major parts--the forebrain, brain stem, and the cerebellum. With the exception of a few marasmic children under 1 year of age whose forebrain and cerebellum had higher phospholipid concentration than normal, the concentration of the lipids on dry weight basis in all brain regions of the malnourished children was the same, regardless of age, as that in the children who were normal nutritionally. However, the phospholipid:DNA ratio in the forebrain and the cerebellum of most of the malnourished children under 1 year of age was higher than normal. The brain stem of only a few malnourished children aged around 1 year also had higher phospholipid:DNA ratio than normal. Among the different phospholipids, sphingomyelin was found to be selectively decreased in each brain part of the malnourished children aged 1 year or more.

Energy balance during recovery from malnutrition.

This report presents an account of energy balance of young Jamaican children recovering from protein-energy malnutrition (PEM). This was done in three steps. Initially the true gross energy of a formula used in the treatment of PEM was determined by bomb calorimetry. Then its metabolizable energy content was determined in a group of nine children recovering from PEM. In a similar but different group of eight children total daily metabolizable energy intake (EI), average rate of weight gain (g/kg/day) (WG), and total daily energy expenditure (TDEE) were determined. TDEE was determined by indirect calorimetry using a heart rate counter and is based on the relationship of heart rate to oxygen consumption. In this group, the mean EI was 122.5 kcal, WG was 8.4 g, and TDEE was 92 kcal. The difference between EI and TDEE was 30.7 kcal/kg, or 3.3 kcal/g of weight gain. This difference is presumed to be the stored energy in new tissue and corresponds to a proposed new tissue composition of 31% fat and 14% protein. A regression curve comparison of WG versus EI showed that at zero weight gain EI was 85.5 kcal and each additional gain. The difference of 1.0 kcal between total energy cost and stored energy reflects the energy required to deposit new tissue. Gram weight gain required 4.4 kcal. The latter figure is felt to reflect the total energy cost of weight. From three independent measurements, an estimate of maintenance energy requirements was estimated to be about 82 kcal/kg/day.

Diurnal pattern of protein and energy metabolism in man.

Rates of synthesis and breakdown of body protein and oxidation of leucine were measured in six obese subjects by constant intravenous infusion of (1 14C)leucine for 24-hr periods. During the night, when no food was given, the rate of whole body protein synthesis was 67% of the rate observed furing the day, when food was given hourly. By contrast the rate of body protein breakdown remained constant over the full 24 hr. This resulted in the immediate deposition of about 30% of the protein intake during the day, whereas the remaining 70% was immediately oxidized. At night the rate of protein oxidation fell to only 38% of its daytime value. The rate of oxygen consumption also decreased at this time so that the contributon of protein oxidation to total energy expenditure fell from 27% during the day to 13% at night. These changes reflect the normal, discontinuous pattern of food intake and the need during feeding to store protein in tissues for use in subsequent periods of fasting.

A model for the measurement of whole-body protein turnover incorporating a protein pool with lifetime kinetics.

The hypothesis is proposed that the body contains a pool of protein turning over by lifetime rather than traditional first-order kinetics. The basis of the hypothesis is the observation of a step in the labelling curve or urinary ammonia during constant infusion of [15N]glycine. A four pool model has been constructed with different values for the rate of uptake of tracer into the lifetime pool; the calculated curves of tracer concentration show a step quite similar to that observed experimentally. It is concluded that it is possible, from an experimental curve, to derive an approximate estimate of the relative flux to the lifetime protein pool. Some suggestions are proposed for the physiological nature of this pool.

Dried skimmed milk, breast-feeding and illness episodes--a controlled trial in young children in Khartoum Province, Sudan.

In a controlled trial mothers and children attending urban maternal and child health (MCH) clinics in Khartoum Province were given a fortnightly take home food supplement of 1 Kilogram of dried skimmed milk (DSM) or an equivalent amount of local beans. There were approximately 300 children aged 6-26 months in each group and each child was followed for 3 to 6 months. A comparison of the two groups showed: a) that the DSM group mothers were more likely to continue breastfeeding; b) there was no evidence to associate DSM with an increased incidence of episodes of diarrhoea, fever or vomiting; c) the utilisation of health institutions was very similar in the two groups; and d) there was no significant difference in the mothers' assessment of the proportion of children with a "poor' appetite in either group. This trial met with considerable methodological problems and the results should therefore be interpreted cautiously. There is a great need for more and better designed trials to assess the possible adverse effects of DSM.

Kwashiorkor revisited: the pathogenesis of oedema in kwashiorkor and its significance.

Cicely Williams, in her original description of kwashiorkor, implied that deficiency of protein in the baby's food could be a main cause of the syndrome. The hallmark of kwashiorkor is oedema. According to the 'classical' theory, an inadequate intake of protein leads to a low plasma albumin concentration, which in turn causes oedema. This theory has been contested from several points of view: that hypoalbuminaemia is not the major factor determining the presence of oedema, and that there is no real evidence of dietary protein deficiency. The resolution of this question is of some importance from the point of view of public health diagnosis and prevention. A crucial point in the argument is the pathogenesis of oedema, which is discussed in some detail. Although it is clearly multifactorial, with electrolyte disturbances--potassium deficiency and sodium retention--playing an important role, it is contended that the classical theory is essentially correct. On the dietary side, recent experimental work supports the earlier view that the development of oedema depends on a relative deficiency of protein with a relative excess of energy. Comparisons of intakes with requirements are unconvincing in view of uncertainty about the validity of the estimates of children's needs for protein.

Protein-energy malnutrition: the nature and extent of the problem.

The paper begins by describing how the names 'protein malnutrition' and 'protein-energy malnutrition' (PEM) developed from the local name 'Kwashiorkor'. The central feature of severe PEM is oedema; the classical theory suggests that the cause is a deficiency of protein, but other factors are also involved. In the community mild-moderate PEM is defined by deficits in growth. A distinction has to be made between low weight for height (wasting) and low height for age (stunting), Stunting in particular affects some 50% of children worldwide. Its causes and consequences are briefly discussed. In adults, severe PEM has essentially the same features as in children and includes the condition'famine oedema' or 'hunger oedema'; there are again controversies about its cause. In the community, chronic malnutrition is assessed by the body mass index (BMI) (Wt/Ht(2)). Grades of deficiency have been defined and examples are given of functional consequences of a low BMI. Secondary malnutrition differs from primary PEM because of the role played by cytokines and other concomitants of illness or injury. The importance is emphasized of chronicity or duration in determining the clinical picture.

The nature and significance of nutritional adaptation.

Possible adaptations to a low protein intake are: a decrease in the obligatory nitrogen loss, which would be too small to detect in short-term studies, but would be significant over a longer term; an increase in the efficiency of protein utilization, which has been demonstrated in depleted subjects; and a decrease in lean body mass, mainly at the expense of muscle. However, we do not know the extent to which this last mechanism may really be an adaptation without significant functional loss. In the case of energy there is controversy about the extent to which the gross efficiency of muscular work can be improved. One mechanism might be an alteration in the distribution of fibre types, with a shift from fast to slow fibres. A possible way of reducing the cost of both muscular work and basal metabolism would be a reduction in the mitochondrial proton leak. Both these mechanisms are at least partially under the control of the thyroid gland, which therefore may play an important role in economizing energy expenditure.

Diet of the classical period of Greece and Rome.

The diet of ordinary people in Greece and Rome was derived from cereals, pulses, vegetables, fruit, olive oil, milk, cheese and a little fish and meat. This pattern fits well with what we would not regard as a healthy diet. In both Greece and Rome the bulk of cereals had to be imported, with a good deal of government control. The available evidence suggests that the official rations, if fairly distributed, would have provided an adequate energy intake. The cost of luxury foods such as meat, in relation to that of flour, was much higher than in modern times. The expectation of life at birth was only 30-35 years, but it was long enough to allow for children to be born and for the populations to expand. No reliable information has been found about infant and child mortality. The reasons for life on average being so short were probably disease and war, rather than malnutrition. It is difficult to conceive how the Greeks and Romans could have achieved such remarkable feats, which involved far more than a small elite, if they had not in general had an adequate and nourishing diet.

Introduction. Causes and mechanisms of linear growth retardation (stunting).

A workshop held 6 years ago examined the epidemiology and natural history of stunting in Third World children. Although this condition is extremely common and is usually regarded as a manifestation of chronic malnutrition, in fact almost nothing is known about its causes and mechanisms in nutritional, biochemical, or metabolic terms. The objective of the present workshop is to fill these gaps and to identify, if possible, critical mechanisms by which environmental factors might affect linear growth. An example is described of a longitudinal study which attempted to examine, in more detail than has been done before, what is happening to children during the process of becoming stunted.

Serum inorganic phosphate in protein-energy malnutrition.

We retrieved a series of measurements made 35 years ago of the concentration of inorganic phosphate (P) in the serum from 56 cases of severe protein-energy malnutrition at the Tropical Metabolism Research Unit, Jamaica. There is no record of whether or not the cases were randomly selected. The samples were obtained within 4 days of admission and except in 3 cases there was no follow-up. The average age was 12 months. The children have been classified retrospectively from the notes as marasmus (11 cases), kwashiorkor (22 cases) and marasmic kwashiorkor (23 cases). In all 11 children died (fatality rate 20%), eight of them from the group with marasmic kwashiorkor. Weight-for-age, length-for-age and weight-for-length have been calculated as Z-scores. Nearly all serum phosphate concentrations were low (mean 1.41 mmol.l-1, SD 0.444, range 0.50-2.45) compared with the normal value at this age of about 2 mmol.l-1. The serum P was significantly less depressed in the marasmic children (P = 0.042), but there was no relation between serum P and any of the anthropometric measurements, nor with outcome (death or survival). There was, however, a significant relationship with the degree of oedema. Death was related to age--the children who died were younger (mean difference 3.8 months; P = 0.01; 95% confidence interval 0.23-6.43). It took about 3 weeks of feeding a milk-based diet for serum phosphate to reach normal levels. There have been few previous measurements of serum P in malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Definition of chronic energy deficiency in adults. Report of a working party of the International Dietary Energy Consultative Group.

New criteria are proposed for classifying chronic energy deficiency (CED) in adults. A progressively more precise approach to identifying affected individuals involves measuring body weight and height, then energy intake (or expenditure) and finally the basal metabolic rate (BMR). Three cut-off points for body mass index (BMI) were identified: 18.5, 17.0 and 16.0. A BMI above 18.5 is classified as normal and below 16.0 as grade III CED. A diagnosis of grades I and II CED depends on finding the combination of a BMI of 16.0-16.9 or 17.0-18.4 with a ratio of energy turnover to predicted BMR of less than 1.4. Measuring the individual BMR avoids misclassification and confirms the diagnosis. In groups of African adults 38-63 per cent of each group had a BMI below 18.5 and the majority require studies of their energy turnover before specifying their degree of CED; 3 per cent of Ethiopian women and 24 per cent of a selected male African group had grade III CED. These guidelines can be used when assessing the input of aid programmes and for clinical and other studies.

Long-stay versus short-stay hospital treatment of children suffering from severe protein-energy malnutrition.

OBJECTIVE: To contrast early discharge versus attempted full nutritional rehabilitation in hospital of children suffering from severe protein-energy malnutrition (PEM). DESIGN: Field experiment, two-way analysis of variance with one between group (short- versus long-stay) and one repeated measures factor (admission, then 12, 18, 24, 30 and 36 months post-admission). Covariates introduced. SETTING: Primary health care, Kingston, Jamaica. SUBJECTS: n = 81; mean age 11 months; 79 contribute longitudinal data; 44 every measurement. INTERVENTIONS: When concurrent illnesses had been treated and normal feeding re-established (weight gain 5 g/kg.day-1), subjects were randomly allocated to short-stay (SS) or long-stay (LS) group. LS retained in hospital for full nutritional rehabilitation mean 40 days). SS discharged immediately (mean 18 days) for standard Health Service care at home for 6 months plus high-energy supplement (3.31 MJ with 20.6 g protein daily) for first 3 months. After discharge LS received 6 months home care, but without supplementation. RESULTS: Significant advantages for LS group on NCHS weight & length for age at discharge, and at 12, 18, 24 and for length also 30 months (P < 0.05 to P < 0.001). Weight advantage peaked at 12 and 18 months, length later at 18 and 24 months. CONCLUSIONS: Contrary to earlier reports, full nutritional rehabilitation can be achieved in hospital for children suffering from PEM. Although in the long-term both groups move towards expected levels in their home community, a significant advantage maintained for approximately 2 years is developmentally advantageous during the critical time after weaning.